Fibroblast Growth Factor 23 and Kidney Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

Science.gov (United States)

Chonchol, Michel; Gitomer, Berenice; Isakova, Tamara; Cai, Xuan; Salusky, Isidro; Pereira, Renata; Abebe, Kaleab; Torres, Vicente; Steinman, Theodor I; Grantham, Jared J; Chapman, Arlene B; Schrier, Robert W; Wolf, Myles

2017-09-07

Increases in fibroblast growth factor 23 precede kidney function decline in autosomal dominant polycystic kidney disease; however, the role of fibroblast growth factor 23 in autosomal dominant polycystic kidney disease has not been well characterized. We measured intact fibroblast growth factor 23 levels in baseline serum samples from 1002 participants in the HALT-PKD Study A ( n =540; mean eGFR =91±17 ml/min per 1.73 m 2 ) and B ( n =462; mean eGFR =48±12 ml/min per 1.73 m 2 ). We used linear mixed and Cox proportional hazards models to test associations between fibroblast growth factor 23 and eGFR decline, percentage change in height-adjusted total kidney volume, and composite of time to 50% reduction in eGFR, onset of ESRD, or death. Median (interquartile range) intact fibroblast growth factor 23 was 44 (33-56) pg/ml in HALT-PKD Study A and 69 (50-93) pg/ml in Study B. In adjusted models, annualized eGFR decline was significantly faster in the upper fibroblast growth factor 23 quartile (Study A: quartile 4, -3.62; 95% confidence interval, -4.12 to -3.12 versus quartile 1, -2.51; 95% confidence interval, -2.71 to -2.30 ml/min per 1.73 m 2 ; P for trend kidney volume in adjusted models (quartile 4, 6.76; 95% confidence interval, 5.57 to 7.96 versus quartile 1, 6.04; 95% confidence interval, 5.55 to 6.54; P for trend =0.03). In Study B, compared with the lowest quartile, the highest fibroblast growth factor 23 quartile was associated with elevated risk for the composite outcome (hazard ratio, 3.11; 95% confidence interval, 1.84 to 5.25). Addition of fibroblast growth factor 23 to a model of annualized decline in eGFR≥3.0 ml/min per 1.73 m 2 did not improve risk prediction. Higher serum fibroblast growth factor 23 concentration was associated with kidney function decline, height-adjusted total kidney volume percentage increase, and death in patients with autosomal dominant polycystic kidney disease. However, fibroblast growth factor 23 did not substantially

Very large polycystic kidneys presenting with end stage renal failure ...

African Journals Online (AJOL)

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited cause of renal impairment and End Stage Renal Disease (ESRD). Apart from cysts in the kidneys and other organs such as the liver, pancreas and other organs, patients also develop abdominal hernia thought to be as a result of ...

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease.

NARCIS (Netherlands)

Gevers, T.J.G.; Chrispijn, M.; Wetzels, J.F.M.; Drenth, J.P.H.

2012-01-01

BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease.

Polycystic kidney disease in a patient with achondroplasia ...

African Journals Online (AJOL)

Autosomal dominant polycystic kidney disease is a multisystem disease involving many organs. An association with other diseases such as tuberous sclerosis, von Hippel-Lindau disease and Marfan syndrome have been previously described. We describe a 35 year old female with achondroplasia who developed ...

Outcome of renal transplantation from a donor with polycystic kidney disease.

Science.gov (United States)

Migone, Silvia Regina da Cruz; Bentes, Camila Guerreiro; Nunes, Débora Bacellar Cruz; Nunes, Juliana Bacellar Cruz; Pinon, Rodolfo Marcial da Silva; Silva, Thales Xavit Souza E

2016-01-01

Faced with the long waiting list for a kidney transplant, the use of donors with expanded criteria, like polycystic kidneys, is an option that aims to increase in a short time the supply of kidneys for transplant. This report of two cases of transplants performed from a donor with polycystic kidneys showed promising results, and the receptors evolved with good renal function, serum creatinine measurements within the normal range and with adequate glomerular filtration rate, evaluated over a period of four years post transplant. This fact confirms that the option of using donors with polycystic kidneys is safe and gives good results. Resumo Diante da longa fila de espera por um transplante renal, a utilização de doadores com critério expandido, a exemplo de rins policísticos, torna-se uma opção que visa aumentar a oferta de rins para transplante a curto prazo. O presente relato de dois casos de transplantes realizados a partir de um doador com rins policísticos apresentou resultado promissor, tendo os receptores evoluído com boa função renal, dosagens de creatinina sérica dentro da faixa de normalidade e com taxa de filtração glomerular adequada, avaliados num período de quatro anos pós-transplante. Isto confirma que a opção da utilização de doadores com rins policísticos é segura e apresenta bons resultados.

Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Directory of Open Access Journals (Sweden)

Gevers Tom JG

2012-04-01

Full Text Available Abstract Background A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD. The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. Methods/design This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, α1-microglobulin, KIM-1, H-FABP, MCP-1 and serum (fibroblast growth factor 23 biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. Discussion We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. Trial registration number Clinical trials.gov NCT01354405

Epithelial hyperplasia in human polycystic kidney diseases. Its role in pathogenesis and risk of neoplasia.

OpenAIRE

Bernstein, J.; Evan, A. P.; Gardner, K. D.

1987-01-01

The importance of tubular epithelial hyperplasia in polycystic kidney diseases has become apparent during the last decade. Micropapillary hyperplasia occurs in autosomal dominant polycystic kidney disease, in localized cystic disease, and in acquired cystic disease. Neoplastic or severely dysplastic epithelial hyperplasia occurs in von Hippel-Lindau disease. A histopathologically distinctive epithelial hyperplasia occurs in tuberous sclerosis. In each of these conditions, epithelial hyperplas...

Tolvaptan and Kidney Pain in Patients With Autosomal Dominant Polycystic Kidney Disease : Secondary Analysis From a Randomized Controlled Trial

NARCIS (Netherlands)

Casteleijn, Niek F.; Blais, Jaime D.; Chapman, Arlene B.; Czerwiec, Frank S.; Devuyst, Olivier; Higashihara, Eiji; Leliveld, Anna M.; Ouyang, John; Perrone, Ronald D.; Torres, Vicente E.; Gansevoort, Ron T.

Background: Kidney pain is a common complication in patients with autosomal dominant polycystic kidney disease (ADPKD), and data from the TEMPO 3: 4 trial suggested that tolvaptan, a vasopressin V2 receptor antagonist, may have a positive effect on kidney pain in this patient group. Because pain is

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

International Nuclear Information System (INIS)

Back, Susan J.; Andronikou, Savvas; Kilborn, Tracy; Kaplan, Bernard S.; Darge, Kassa

2015-01-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

Imaging features of tuberous sclerosis complex with autosomal-dominant polycystic kidney disease: a contiguous gene syndrome

Energy Technology Data Exchange (ETDEWEB)

Back, Susan J. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Andronikou, Savvas [University of the Witwatersrand, Radiology Department, Faculty of Health Sciences, Johannesburg (South Africa); Kilborn, Tracy [University of Cape Town, Red Cross War Memorial Children' s Hospital, Cape Town (South Africa); Kaplan, Bernard S. [The Children' s Hospital of Philadelphia, Division of Nephrology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Darge, Kassa [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States)

2015-03-01

Genes for tuberous sclerosis complex (TSC) type 2 and autosomal-dominant polycystic kidney disease (ADPKD) type 1 are both encoded over a short segment of chromosome 16. When deletions involve both genes, an entity known as the TSC2/ADPKD1 contiguous gene syndrome, variable phenotypes of TSC and ADPKD are exhibited. This syndrome has not been reviewed in the radiology literature. Unlike renal cysts in TSC, cystic disease in TSC2/ADPKD1 contiguous gene syndrome results in hypertension and renal failure. A radiologist might demonstrate polycystic kidney disease before the patient develops other stigmata of TSC. Conversely, in patients with known TSC, enlarged and polycystic kidneys should signal the possibility of the TSC2/ADPKD1 contiguous gene syndrome and not simply TSC. Distinguishing these diagnoses has implications in prognosis, treatment and genetic counseling. To describe the clinical and imaging findings of tuberous sclerosis complex and polycystic kidney disease in seven pediatric patients. We retrospectively reviewed renal and brain imaging of children and young adults with genetically proven or high clinical suspicion for TSC2/ADPKD1 contiguous gene syndrome. We included seven pediatric patients from two referral institutions. Ages ranged from birth to 21 years over the course of imaging. The mean follow-up period was 9 years 8 months (4 years 6 months to 20 years 6 months). No child progressed to end-stage renal disease during this period. Three patients were initially imaged for stigmata of TSC, three for abdominal distension and one for elevated serum creatinine concentration. All patients developed enlarged, polycystic kidneys. The latest available imaging studies demonstrated that in 12 of the 14 kidneys 50% or more of the parenchyma was ultimately replaced by >15 cysts, resulting in significant cortical thinning. The largest cysts in each kidney ranged from 2.4 cm to 9.3 cm. Echogenic lesions were present in 13 of the 14 kidneys, in keeping with

An 11-Year-Old Child with Autosomal Dominant Polycystic Kidney Disease Who Presented with Nephrolithiasis

Directory of Open Access Journals (Sweden)

Fatih Firinci

2012-01-01

Full Text Available Patients with autosomal dominant polycystic kidney disease become symptomatic and are diagnosed usually at adulthood. The rate of nephrolithiasis in these patients is 5–10 times the rate in the general population, and both anatomic and metabolic abnormalities play role in the formation of renal stones. However, nephrolithiasis is rare in childhood age group. In this paper, an 11-year-old child with autosomal dominant polycystic kidney disease presenting with nephrolithiasis is discussed.

Should a paediatrician perform abdominal ultrasonography inchildren of parents with polycystic kidney disease?

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Krzysztof Wróblewski

2016-09-01

Full Text Available Autosomal dominant polycystic kidney disease produces symptoms mainly in adulthood. Renal cysts and/or elevated blood pressure can be the first signs of the disease in children. Because of the lack of a targeted therapy, early diagnosis and implementation of actions to slow its progression are the essence of treatment. Aim: The aim of the study was to assess the clinical course of autosomal dominant polycystic kidney disease in children. Material and methods: The study involved the assessment of 28 patients with autosomal dominant polycystic kidney disease diagnosed before the age of 18. The disease was diagnosed during a routine abdominal ultrasound scan in 24 patients and during a scan conducted due to abdominal pain reported by patients in 4 cases. Two patients had the disease diagnosed based on the Ravine criteria, whereas an ultrasound image and family history helped establish the diagnosis in 26 cases. The children enrolled had blood pressure measured, serum creatinine concentration determined and general urinalysis performed. Results: The median age at the diagnosis was 5 years. The family history was positive in 89.3% (25 of patients. Siblings had the disease in 46.43% (13 of cases. None of the children presented with abnormalities in urinalysis or creatinine levels. Two patients were diagnosed with arterial hypertension and in 1 child blood pressure was elevated above the 97th percentile. Urine albumin-to-creatinine ratio exceeding 30 mg/g was observed in 20.8% of children. Conclusions: Autosomal dominant polycystic kidney disease in children is asymptomatic. There are no irregularities either in urinalysis or renal function parameters. An abdominal ultrasound examination, which is inexpensive and non-invasive, is worth considering in all children of parents with autosomal dominant polycystic kidney disease in order to implement early nephroprotection.

Pathogenesis and potential therapy of autosomal dominant polycystic kidney disease

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O.O. Melnyk

2017-10-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is a hereditary disease characterized by progressive growth of the cyst and an increase in the total volume of the kidneys which leads to kidney failure. The main causes of ADPKD are mutations in the genes PKD1 and PKD2 which encode the formation of polycystin-1 and polycystin-2 proteins. There is a connection between structural and functional defects in the primary cilia with the ADPKD. The most promising drugs for the treatment of ADPKD today are vasopressin-2 receptor antagonists, m-TOR and c-AMP inhibitors.

Clinical and radiographic findings of focally infected polycystic kidneys

International Nuclear Information System (INIS)

Rothermel, F.J.; Miller, F.J. Jr.; Sanford, E.; Drago, J.; Rohner, T.J.

1977-01-01

Three patients with localized polycystic kidney infections are presented with the pertinent clinical, laboratory, and radiographic findings. Gallium-67 citrate and angiography play an important role in evaluation of these patients. Angiography in particular is valuable in the diagnosis and the exact localization of the inflammatory disease. Localization is extremely important in planning surgical treatment should conservative therapy fail

Vasopressin, Copeptin, and Renal Concentrating Capacity in Patients with Autosomal Dominant Polycystic Kidney Disease without Renal Impairment

NARCIS (Netherlands)

Zittema, Debbie; Boertien, Wendy E.; van Beek, Andre P.; Dullaart, Robin P. F.; Franssen, Casper F. M.; de Jong, Paul E.; Meijer, Esther; Gansevoort, Ron T.

Background and objectives Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary renal disease, characterized by cyst formation in the kidneys leading to end stage kidney failure. It is clinically acknowledged that ADPKD patients have impaired urine concentrating

Hyperdiagnostic of renal tumor by intravenous urography in patient with adult polycystic disease

International Nuclear Information System (INIS)

Djerassi, R.; Lubomirova, M.; Mutafova, I.; Bogov, B.; Gavrikova, V.; Garvanska, G.

2005-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is one of the often seen (from 1:400 to 1:1000) inherited renal diseases with serious prognosis. The exact diagnosis, earlier treatment of the urinary tract infections and hypertension were the steps for prevention of the renal disease progression. The abdominal ultrasound is method used for screening. The frequency of the renal tumors in general population was not higher compared to those in patients with ADPKD. We described and discussed the results obtained by different imaging techniques in 23 years old female with family history for ADPKD. She was admitted to the 'Alexandrovska' University Hospital Nephrology Clinic because of the recurrence of the urinary tract infection. The diagnosis of renal tumor was suspected by renal intravenous pyelography (IVP). All the others imaging techniques - Triplex sonography-B-mode, Color, Pulse, Power Doppler, Tissue Doppler as well as contrast computer tomography showed the polycystic kidney disease, without focal changes, with several small cysts based in the medulla near distal calyces. This was probably the reason for the false-positive image made by IVP. The diagnostic values of the different imaging techniques in making the exact diagnosis in patients with polycystic kidney disease were comment, as well as a peculiar ultrasound image of the polycystic kidney in young patients, aged less then 30 years. To make the correct diagnosis of ADPKD the combination of all known imaging techniques was needed. The small kidney tumors were better visualized by tissue-harmonic ultrasound

Acute abdomen and ascites as presenting features of autosomal dominant polycystic kidney disease

OpenAIRE

Chaudhary, Sanjay; Qian, Qi

2012-01-01

We describe a patient with sudden onset of abdominal pain and ascites, leading to the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Her presentation was consistent with acute liver cyst rupture as the cause of her acute illness. A review of literature on polycystic liver disease in patients with ADPKD and current management strategies are presented. This case alerts physicians that ADPKD could occasionally present as an acute abdomen; cyst rupture related to ADPKD may be ...

Molecular and cellular pathogenesis of autosomal dominant polycystic kidney disease

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A.P. Bastos

2011-07-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most common human life-threatening monogenic disorders. The disease is characterized by bilateral, progressive renal cystogenesis and cyst and kidney enlargement, often leading to end-stage renal disease, and may include extrarenal manifestations. ADPKD is caused by mutation in one of two genes, PKD1 and PKD2, which encode polycystin-1 (PC1 and polycystin-2 (PC2, respectively. PC2 is a non-selective cation channel permeable to Ca2+, while PC1 is thought to function as a membrane receptor. The cyst cell phenotype includes increased proliferation and apoptosis, dedifferentiation, defective planar polarity, and a secretory pattern associated with extracellular matrix remodeling. The two-hit model for cyst formation has been recently extended by the demonstration that early gene inactivation leads to rapid and diffuse development of renal cysts, while inactivation in adult life is followed by focal and late cyst formation. Renal ischemia/reperfusion, however, can function as a third hit, triggering rapid cyst development in kidneys with Pkd1 inactivation induced in adult life. The PC1-PC2 complex behaves as a sensor in the primary cilium, mediating signal transduction via Ca2+ signaling. The intracellular Ca2+ homeostasis is impaired in ADPKD, being apparently responsible for the cAMP accumulation and abnormal cell proliferative response to cAMP. Activated mammalian target for rapamycin (mTOR and cell cycle dysregulation are also significant features of PKD. Based on the identification of pathways altered in PKD, a large number of preclinical studies have been performed and are underway, providing a basis for clinical trials in ADPKD and helping the design of future trials.

Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model

NARCIS (Netherlands)

Hassane, S.; Claij, N.; Lantinga-van Leeuwen, I.S.; Munsteren, J.C. van; Lent, N. van; Hanemaaijer, R.; Breuning, M.H.; Peters, D.J.M.; Ruiter, M.C. de

2007-01-01

OBJECTIVE - Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multi-system disorder characterized by progressive cyst formation in the kidneys. Serious complications of ADPKD are intracranial and aortic aneurysms. The condition is mainly caused by mutations in the PKD1 or PKD2 gene. We have

A rare cardiac manifestation in autosomal-dominant polycystic kidney disease

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Meriam Hajji

2017-01-01

Full Text Available Autosomal-dominant polycystic kidney disease (ADPKD is a systemic disorder associated with various extrarenal complications. There is little information regarding the occurrence and distribution of cardiovascular abnormalities during the course of ADPKD. The major cardiovascular complications of ADPKD include valvulopathies and vascular ectasia. Aneurysm of the atrial septum (ASA is a very rare manifestation in ADPKD. A 37-year-old woman who was diagnosed with ADPKD was admitted to our hospital for advanced renal failure. Pelvic computed tomography revealed multiple variable-sized cysts in both kidneys. Trans-thoracic echocardiography showed ASA while the patient was completely asymptomatic.

Polycystic Kidney Disease: Pathogenesis and Potential Therapies

Science.gov (United States)

Takiar, Vinita; Caplan, Michael J.

2011-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. PMID:21146605

Performance of an Artificial Multi-observer Deep Neural Network for Fully Automated Segmentation of Polycystic Kidneys.

Science.gov (United States)

Kline, Timothy L; Korfiatis, Panagiotis; Edwards, Marie E; Blais, Jaime D; Czerwiec, Frank S; Harris, Peter C; King, Bernard F; Torres, Vicente E; Erickson, Bradley J

2017-08-01

Deep learning techniques are being rapidly applied to medical imaging tasks-from organ and lesion segmentation to tissue and tumor classification. These techniques are becoming the leading algorithmic approaches to solve inherently difficult image processing tasks. Currently, the most critical requirement for successful implementation lies in the need for relatively large datasets that can be used for training the deep learning networks. Based on our initial studies of MR imaging examinations of the kidneys of patients affected by polycystic kidney disease (PKD), we have generated a unique database of imaging data and corresponding reference standard segmentations of polycystic kidneys. In the study of PKD, segmentation of the kidneys is needed in order to measure total kidney volume (TKV). Automated methods to segment the kidneys and measure TKV are needed to increase measurement throughput and alleviate the inherent variability of human-derived measurements. We hypothesize that deep learning techniques can be leveraged to perform fast, accurate, reproducible, and fully automated segmentation of polycystic kidneys. Here, we describe a fully automated approach for segmenting PKD kidneys within MR images that simulates a multi-observer approach in order to create an accurate and robust method for the task of segmentation and computation of TKV for PKD patients. A total of 2000 cases were used for training and validation, and 400 cases were used for testing. The multi-observer ensemble method had mean ± SD percent volume difference of 0.68 ± 2.2% compared with the reference standard segmentations. The complete framework performs fully automated segmentation at a level comparable with interobserver variability and could be considered as a replacement for the task of segmentation of PKD kidneys by a human.

Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses

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Carsten Bergmann

2018-02-01

Full Text Available Autosomal recessive polycystic kidney disease (ARPKD is a hepatorenal fibrocystic disorder that is characterized by enlarged kidneys with progressive loss of renal function and biliary duct dilatation and congenital hepatic fibrosis that leads to portal hypertension in some patients. Mutations in the PKHD1 gene are the primary cause of ARPKD; however, the disease is genetically not as homogeneous as long thought and mutations in several other cystogenes can phenocopy ARPKD. The family history usually is negative, both for recessive, but also often for dominant disease genes due to de novo arisen mutations or recessive inheritance of variants in genes that usually follow dominant patterns such as the main ADPKD genes PKD1 and PKD2. Considerable progress has been made in the understanding of polycystic kidney disease (PKD. A reduced dosage of disease proteins leads to the disruption of signaling pathways underlying key mechanisms involved in cellular homeostasis, which may help to explain the accelerated and severe clinical progression of disease course in some PKD patients. A comprehensive knowledge of disease-causing genes is essential for counseling and to avoid genetic misdiagnosis, which is particularly important in the prenatal setting (e.g., preimplantation genetic diagnosis/PGD. For ARPKD, there is a strong demand for early and reliable prenatal diagnosis, which is only feasible by molecular genetic analysis. A clear genetic diagnosis is helpful for many families and improves the clinical management of patients. Unnecessary and invasive measures can be avoided and renal and extrarenal comorbidities early be detected in the clinical course. The increasing number of genes that have to be considered benefit from the advances of next-generation sequencing (NGS which allows simultaneous analysis of a large group of genes in a single test at relatively low cost and has become the mainstay for genetic diagnosis. The broad phenotypic and genetic

Autosomal-dominant polycystic kidney disease (ADPKD) : executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

NARCIS (Netherlands)

Chapman, Arlene B.; Devuyst, Olivier; Eckardt, Kai-Uwe; Gansevoort, Ron T.; Harris, Tess; Horie, Shigeo; Kasiske, Bertram L.; Odland, Dwight; Pei, York; Perrone, Ronald D.; Pirson, Yves; Schrier, Robert W.; Torra, Roser; Torres, Vicente E.; Watnick, Terry; Wheeler, David C.

Autosomal-dominant polycystic kidney disease (ADPKD) affects up to 12 million individuals and is the fourth most common cause for renal replacement therapy worldwide. There have been many recent advances in the understanding of its molecular genetics and biology, and in the diagnosis and management

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry

NARCIS (Netherlands)

Mekahli, Djalila; van Stralen, Karlijn J.; Bonthuis, Marjolein; Jager, Kitty J.; Balat, Ayşe; Benetti, Elisa; Godefroid, Nathalie; Edvardsson, Vidar O.; Heaf, James G.; Jankauskiene, Augustina; Kerecuk, Larissa; Marinova, Svetlana; Puteo, Flora; Seeman, Tomas; Zurowska, Aleksandra; Pirenne, Jacques; Schaefer, Franz; Groothoff, Jaap W.; Levtchenko, E.; Haffner, D.; Bjerre, A.; Massy, Z.; Shtiza, D.; Kramar, R.; Oberbauer, R.; Baiko, S.; Sukalo, A.; van Hoeck, K.; Collart, F.; des Grottes, J. M.; Pokrajac, D.; Roussinov, D.; Batinić , D.; Lemac, M.; Slavicek, J.; Seeman, T.; Vondrak, K.; Heaf, J. G.; Toots, U.; Finne, P.; Grö nhagen-Riska, C.; Couchoud, C.; Lasalle, M.; Sahpazova, E.; Abazi, N.; Ristoka Bojkovska, N.; von Gersdorff, G.; Scholz, C.; Tö nshoff, B.; Krupka, K.

2016-01-01

The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry

NARCIS (Netherlands)

Mekahli, D.; Stralen, K.J. van; Bonthuis, M.; Jager, K.J.; Balat, A.; Benetti, E.; Godefroid, N.; Edvardsson, V.O.; Heaf, J.G.; Jankauskiene, A.; Kerecuk, L.; Marinova, S.; Puteo, F.; Seeman, T.; Zurowska, A.; Pirenne, J.; Schaefer, F.; Groothoff, J.W.; Hoitsma, A.J.; et al.,

2016-01-01

BACKGROUND: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in

Rationale and Design of a Clinical Trial Investigating Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease

NARCIS (Netherlands)

Torres, Vicente E.; Devuyst, Olivier; Chapman, Arlene B.; Gansevoort, Ron T.; Perrone, Ronald D.; Ouyang, John; Blais, Jaime D.; Czerwiec, Frank S.; Sergeyeva, Olga

Background: In TEMPO 3: 4, the vasopressin V2-receptor antagonist tolvaptan slowed kidney growth and function decline in autosomal dominant polycystic kidney disease (ADPKD) patients with relatively preserved kidney function. Methods: Prospective, phase 3b, multi-center, randomized-withdrawal,

Autosomal dominant polycystic kidney disease and pain - a review of the disease from aetiology, evaluation, past surgical treatment options to current practice.

Science.gov (United States)

Badani, K K; Hemal, A K; Menon, M

2004-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD), often referred to as "adult" polycystic kidney disease, is one of the commonest hereditary disorders. It affects approximately 4 to 6 million individuals worldwide. The disease progresses to end-stage renal disease and it accounts for 10-15% of patients requiring dialysis in the United States. A comprehensive Medline search for aetiology, evaluation, screening, cellular biology, and treatment was utilized to locate, extract, and synthesize relevant data with respect to this topic. Special attention was focused on urologic literature and surgical textbooks regarding operative treatment of pain associated with ADPKD. Now, patients with ADPKD have more treatment options. More specifically, several therapeutic alternatives are now available for the management of pain in these patients. A recent review of literature supports the performance of open or laparoscopic cyst decortication procedures for control of pain and infection without the worry of causing further renal impairment in those with preserved renal function.

Is Autosomal Dominant Polycystic Kidney Disease Becoming a Pediatric Disorder?

Directory of Open Access Journals (Sweden)

Stéphanie De Rechter

2017-12-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD affects 1 in 400 to 1,000 live births, making it the most common monogenic cause of renal failure. Although no definite cure is available yet, it is important to affect disease progression by influencing modifiable factors such as hypertension and proteinuria. Besides this symptomatic management, the only drug currently recommended in Europe for selected adult patients with rapid disease progression, is the vasopressin receptor antagonist tolvaptan. However, the question remains whether these preventive interventions should be initiated before extensive renal damage has occurred. As renal cyst formation and expansion begins early in life, frequently in utero, ADPKD should no longer be considered an adult-onset disease. Moreover, the presence of hypertension and proteinuria in affected children has been reported to correlate well with disease severity. Until now, it is controversial whether children at-risk for ADPKD should be tested for the presence of the disease, and if so, how this should be done. Herein, we review the spectrum of pediatric ADPKD and discuss the pro and contra of testing at-risk children and the challenges and unmet needs in pediatric ADPKD care.

Polycystic kidney disease and cancer after renal transplantation.

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Wetmore, James B; Calvet, James P; Yu, Alan S L; Lynch, Charles F; Wang, Connie J; Kasiske, Bertram L; Engels, Eric A

2014-10-01

Autosomal dominant polycystic kidney disease (ADPKD), the most common form of polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia. However, it is not known whether renal transplant recipients with PKD have an increased risk of cancer. Data from the Scientific Registry of Transplant Recipients, which contains information on all solid organ transplant recipients in the United States, were linked to 15 population-based cancer registries in the United States. For PKD recipients, we compared overall cancer risk with that in the general population. We also compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poisson regression, and we determined incidence rate ratios (IRRs) adjusted for age, sex, race/ethnicity, dialysis duration, and time since transplantation. The study included 10,166 kidney recipients with PKD and 107,339 without PKD. Cancer incidence in PKD recipients was 1233.6 per 100,000 person-years, 48% higher than expected in the general population (standardized incidence ratio, 1.48; 95% confidence interval [95% CI], 1.37 to 1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000 person-years. The unadjusted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01 to 1.20). However, PKD recipients were older (median age at transplantation, 51 years versus 45 years for non-PKD recipients), and after multivariable adjustment, cancer incidence was lower in PKD recipients than in others (IRR, 0.84; 95% CI, 0.77 to 0.91). The reason for the lower cancer risk in PKD recipients is not known but may relate to biologic characteristics of ADPKD or to cancer risk behaviors associated with ADPKD. Copyright © 2014 by the American Society of Nephrology.

Acute abdomen and ascites as presenting features of autosomal dominant polycystic kidney disease.

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Chaudhary, Sanjay; Qian, Qi

2012-12-27

We describe a patient with sudden onset of abdominal pain and ascites, leading to the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Her presentation was consistent with acute liver cyst rupture as the cause of her acute illness. A review of literature on polycystic liver disease in patients with ADPKD and current management strategies are presented. This case alerts physicians that ADPKD could occasionally present as an acute abdomen; cyst rupture related to ADPKD may be considered in the differential diagnoses of acute abdomen.

Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside

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Hyun-Jung Kim

2012-09-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common life-threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tubular epithelial cells, which plays a crucial role in cyst development and/or growth in PKD. Activation of the proliferative mammalian target of rapamycin (mTOR signaling pathway has been demonstrated in polycystic kidneys from rodents and humans. mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. On the basis of animal studies, human studies were undertaken. Two large randomized clinical trials published in the New England Journal of Medicine of everolimus or sirolimus in ADPKD patients were very unimpressive and associated with a high side-effect profile. Possible reasons for the unimpressive nature of the human studies include their short duration, the high drop-out rate, suboptimal dosing, lack of randomization of “fast” and “slow progressors” and the lack of correlation between kidney size and kidney function in ADPKD. The future of mTOR inhibition in ADPKD is discussed.

Association between Nephrolithiasis, Hypertension and Obesity in Polycystic Kidney Disease

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Valbona Bajrami

2015-12-01

Full Text Available AIM: We aim to define the correlations between nephrolithiasis, hypertension, age and obesity in patients with autosomal dominant polycystic kidney disease (ADPKD in Albania. MATERIAL AND METHODS: We included 100 patients with autosomal dominant polycystic kidney from 2011 to 2014. The patients underwent X-ray and renal ultrasonography. We performed the metabolic evaluation of blood and urine. RESULTS: The patients with renal stones had a higher level of mean systolic and diastolic blood pressure compared with patients without stones (155 ± 12 mmHg vs. 145 ± 8 mmHg, and 105 ± 0.9 mmHg vs. 92 ± 1.28 mmHg, respectively. Patients with renal stones were older (47 ± 15 vs. 38 ± 5 years, had a higher prevalence of obesity [body mass index (BMI: 28 ± 2.4 vs. 25.7 ± 0.6], had higher levels of total cholesterol level (220 ± 5 mg/dl vs. 203 ± 4 mg/dl as well as triglyceride levels (160 ± 9 mg/dl vs. 126 ± 4 mg/dl, compared with no renal stone individuals. CONCLUSION: ADPKD patients with renal stones in our study had a higher mean level of systolic and diastolic blood pressure, BMI and cholesterol and triglycerides levels compared with individuals without renal stones.

An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

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Tobias Eisenberger

Full Text Available Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs. Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease.

Science.gov (United States)

Eisenberger, Tobias; Decker, Christian; Hiersche, Milan; Hamann, Ruben C; Decker, Eva; Neuber, Steffen; Frank, Valeska; Bolz, Hanno J; Fehrenbach, Henry; Pape, Lars; Toenshoff, Burkhard; Mache, Christoph; Latta, Kay; Bergmann, Carsten

2015-01-01

Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furthermore it is becoming obvious that clinical manifestations can be mimicked by mutations in a number of other genes with the necessity for broader genetic testing. We established and validated a sequence capture based NGS testing approach for all genes known for cystic and polycystic kidney disease including PKD1. Thereby, we demonstrate that the applied standard mapping algorithm specifically aligns reads to the PKD1 locus and overcomes the complication of unspecific capture of pseudogenes. Employing careful and experienced assessment of NGS data, the method is shown to be very specific and equally sensitive as established methods. An additional advantage over conventional Sanger sequencing is the detection of copy number variations (CNVs). Sophisticated bioinformatic read simulation increased the high analytical depth of the validation study and further demonstrated the strength of the approach. We further raise some awareness of limitations and pitfalls of common NGS workflows when applied in complex regions like PKD1 demonstrating that quality of NGS needs more than high coverage of the target region. By this, we propose a time- and cost-efficient diagnostic strategy for comprehensive molecular genetic testing of polycystic kidney disease which is highly automatable and will be of particular value when therapeutic options for PKD emerge and genetic testing is needed for larger numbers of patients.

The Oak Ridge Polycystic Kidney mouse: modeling ciliopathies of mice and men.

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Lehman, J M [University of Alabama, Birmingham; Michaud III, Edward J [ORNL; Schoeb, T [University of Alabama, Birmingham; Aydin Son, Yesim [University of Tennessee, Knoxville (UTK); Miller, M [University of Alabama, Birmingham; Yoder, Bradley [University of Alabama, Birmingham

2008-08-01

The Oak Ridge Polycystic Kidney (ORPK) mouse was described nearly 14 years ago as a model for human recessive polycystic kidney disease. The ORPK mouse arose through integration of a transgene into an intron of the Ift88 gene resulting in a hypomorphic allele (Ift88Tg737Rpw). The Ift88Tg737Rpw mutation impairs intraflagellar transport (IFT), a process required for assembly of motile and immotile cilia. Historically, the primary immotile cilium was thought to have minimal importance for human health; however, a rapidly expanding number of human disorders have now been attributed to ciliary defects. Importantly, many of these phenotypes are present and can be analyzed using the ORPK mouse. In this review, we highlight the research conducted using the OPRK mouse and the phenotypes shared with human cilia disorders. Furthermore, we describe an additional follicular dysplasia phenotype in the ORPK mouse, which alongside the ectodermal dysplasias seen in human Ellis-van Creveld and Sensenbrenner's syndromes, suggests an unappreciated role for primary cilia in the skin and hair follicle.

Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease

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Taimur Dad

2018-05-01

Full Text Available Introduction: The high burden of cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD is related to development of hypertension and left ventricular hypertrophy. Blood pressure reduction has been shown to reduce left ventricular mass in ADPKD; however, moderators and predictors of response to lower blood pressure are unknown. Methods: This was a post hoc cohort analysis of HALT PKD study A, a randomized placebo controlled trial examining the effect of low blood pressure and single versus dual renin−angiotensin blockade in early ADPKD. Participants were hypertensive ADPKD patients 15 to 49 years of age with estimated glomerular filtration rate (eGFR > 60 ml/min per 1.73 m2 across 7 centers in the United States. Predictors included age, sex, baseline eGFR, systolic blood pressure, total kidney volume, serum potassium, and urine sodium, potassium, albumin, and aldosterone. Outcome was left ventricular mass index (LVMI measured using 1.5-T magnetic resonance imaging at months 0, 24, 48, and 60. Results: Reduction in LVMI was associated with higher baseline systolic blood pressure and larger kidney volume regardless of blood pressure control group assignment (P < 0.001 for both. Male sex and baseline eGFR were associated with a positive annual slope in LVMI (P < 0.001 and P = 0.07, respectively. Conclusion: Characteristics associated with higher risk of progression in ADPKD, including higher systolic blood pressure, larger kidney volume, and lower eGFR are associated with improvement in LVMI with intensive blood pressure control, whereas male sex is associated with a smaller slope of reduction in LVMI. Keywords: autosomal dominant polycystic kidney disease, hypertension, left ventricular hypertrophy, left ventricular mass index

A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease.

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Xiong, Huaqi; Chen, Yongxiong; Yi, Yajun; Tsuchiya, Karen; Moeckel, Gilbert; Cheung, Joseph; Liang, Dan; Tham, Kyi; Xu, Xiaohu; Chen, Xing-Zhen; Pei, York; Zhao, Zhizhuang Jeo; Wu, Guanqing

2002-07-01

Autosomal recessive polycystic kidney disease (ARPKD) is a common hereditary renal cystic disease in infants and children. By genetic linkage analyses, the gene responsible for this disease, termed polycystic kidney and hepatic disease 1 (PKHD1), was mapped on human chromosome 6p21.1-p12, and has been further localized to a 1-cM genetic interval flanked by the D6S1714/D6S243 (telomeric) and D6S1024 (centromeric) markers. We recently identified a novel gene in this genetic interval from kidney cDNA, using cloning strategies. The gene PKHD1 (PKHD1-tentative) encodes a novel 3396-amino-acid protein with no apparent homology with any known proteins. We named its gene product "tigmin" because it contains multiple TIG domains, which usually are seen in proteins containing immunoglobulin-like folds. PKHD1 encodes an 11.6-kb transcript and is composed of 61 exons spanning an approximately 365-kb genomic region on chromosome 6p12-p11.2 adjacent to the marker D6S1714. Northern blot analyses demonstrated that the gene has discrete bands with one peak signal at approximately 11 kb, indicating that PKHD1 is likely to have multiple alternative transcripts. PKHD1 is highly expressed in adult and infant kidneys and weakly expressed in liver in northern blot analysis. This expression pattern parallels the tissue involvement observed in ARPKD. In situ hybridization analysis further revealed that the expression of PKHD1 in the kidney is mainly localized to the epithelial cells of the collecting duct, the specific tubular segment involved in cyst formation in ARPKD. These features of PKHD1 make it a strong positional candidate gene for ARPKD.

Chronic Kidney Pain in Autosomal Dominant Polycystic Kidney Disease : A Case Report of Successful Treatment by Catheter-Based Renal Denervation

NARCIS (Netherlands)

Casteleijn, Niek F.; de Jager, Rosa L.; Neeleman, M. Peer; Blankestijn, Peter J.; Gansevoort, Ron T.

Chronic pain is a common concern in patients with autosomal dominant polycystic kidney disease (ADPKD). We report what to our knowledge is the first catheter-based renal denervation procedure in a patient with ADPKD resulting in successful management of chronic pain. The patient was a 43-year-old

Weight loss in a patient with polycystic kidney disease: when liver cysts are no longer innocent bystanders.

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Cecere, N; Hakem, S; Demoulin, N; Hubert, C; Jabbour, N; Goffette, P; Pirson, Y; Morelle, J

2015-10-01

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disorder, and liver involvement represents one of its major extra-renal manifestations. Although asymptomatic in most patients, polycystic liver disease (PLD) can lead to organ compression, severe disability and even become life-threatening, thereby warranting early recognition and appropriate management. We report the case of a 56-year-old woman with ADPKD and severe weight loss secondary to a giant hepatic cyst compressing the pylorus. Partial hepatectomy was required after failure of cyst aspiration and sclerotherapy, and patient's condition improved rapidly. We discuss the presentation and classification of compressing liver cysts, and the available therapeutic alternatives for this potentially severe complication of ADPKD.

Prenatal MRI Findings of Polycystic Kidney Disease Associated with Holoprosencephaly

International Nuclear Information System (INIS)

Koplay, Mustafa; Onbas, Omer; Alper, Fatih; Borekci, Bunyamin

2009-01-01

Holoprosencephaly (HPE) and polycystic kidney disease (PKD) are genetically heterogeneous anomalies which can make up part of various syndromes or chromosomal anomalies. Due to the rapid lethality prognosis, early and precise prenatal diagnosis would be of great value. This case report describes extensive PKD involvement, already present in utero, in a patient with HPE and subdural effusion visible by MR imaging. The detailed anatomic information obtained by the MR imaging can guide the surgical planning and can aid antenatal counseling

Prenatal MRI Findings of Polycystic Kidney Disease Associated with Holoprosencephaly

Energy Technology Data Exchange (ETDEWEB)

Koplay, Mustafa [Ergani Status Hospital, Diyarbakir (Turkmenistan); Onbas, Omer; Alper, Fatih; Borekci, Bunyamin [Ataturk University, Erzurum (Turkmenistan)

2009-06-15

Holoprosencephaly (HPE) and polycystic kidney disease (PKD) are genetically heterogeneous anomalies which can make up part of various syndromes or chromosomal anomalies. Due to the rapid lethality prognosis, early and precise prenatal diagnosis would be of great value. This case report describes extensive PKD involvement, already present in utero, in a patient with HPE and subdural effusion visible by MR imaging. The detailed anatomic information obtained by the MR imaging can guide the surgical planning and can aid antenatal counseling.

Autosomal dominant polycystic kidney disease: Study of clinical characteristics in an Indian population

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Sanjay Vikrant

2017-01-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common hereditary form of kidney disease. Clinical data on this multisystem disorder are scarce from developing countries. We conducted a prospective observational study of the clinical profile of ADPKD patients at a single center over a period of six years. A total of 208 patients were studied. Majority were male (60.6% and the mean age was 45.8 ± 14.5 years. About 61.5% had early stage (Stages 1-3 of chronic kidney disease (CKD and 38.5% had advanced CKD (Stages 4 and 5. Clinical features observed included pain abdomen (46.2%, nocturia (65.9%, hematuria (21.6%, nephrolithiasis (38.9%, urinary tract infection (UTI (38.9%, hypertension (69.5%, and raised serum creatinine (54.3%. The prevalence of nocturia, hypertension, and renal dysfunction showed a significant increase with age (P = 0.001. Extrarenal manifestations were polycystic liver disease in 77 patients (37%, cysts in pancreas in two (1%, and stroke in three (1.5% (hemorrhage in 2 and infarct in 1. There was significantly higher prevalence of hypertension (P = 0.027 and nephrolithiasis (P = 0.044 in males compared to females. Ninety-two patients (44.2% had a positive family history for ADPKD. Fifteen (7.2% had kidney failure at the diagnosis of ADPKD, were hospitalized, and underwent emergency dialysis. A total of 20 patients (9.6% developed end-stage kidney disease during the study period. The age at diagnosis was higher, and there was a high prevalence of hypertension, nocturia, abdominal pain, nephrolithiasis, UTI, and renal dysfunction in Indian ADPKD patients.

Preimplantation Genetic Diagnosis Counseling in Autosomal Dominant Polycystic Kidney Disease.

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Murphy, Erin L; Droher, Madeline L; DiMaio, Miriam S; Dahl, Neera K

2018-03-30

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary forms of chronic kidney disease. Mutations within PKD1 or PKD2 lead to innumerable fluid-filled cysts in the kidneys and in some instances, end-stage renal disease (ESRD). Affected individuals have a 50% chance of passing the mutation to each of their offspring. Assisted reproductive technology using preimplantation genetic diagnosis (PGD) allows these individuals to reduce this risk to 1% to 2%. We assess the disease burden of 8 individuals with ADPKD who have undergone genetic testing in preparation for PGD. Clinical features that predict high risk for progression to ESRD in patients with ADPKD include genotype, early onset of hypertension, a urologic event before age 35 years, and a large height-adjusted total kidney volume. Patients may have a family history of intracranial aneurysms or complications involving hepatic cysts, which may further influence the decision to pursue PGD. We also explore the cost, risks, and benefits of using PGD. All patients with ADPKD of childbearing potential, regardless of risk for progression to ESRD or risk for a significant disease burden, will likely benefit from genetic counseling. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

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2017-09-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most prevalent genetic disease, affecting at least 600,000 Americans . It is characterized...Pennathur, Michigan Metabolomics and Obesity Center (MMOC) at U. Michigan and statistical consultation from Dr. K. Abebe at U. Pittsburgh. Cell

The Role of G-Protein-Coupled Receptor Proteolysis Site Cleavage of Polycystin-1 in Renal Physiology and Polycystic Kidney Disease

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Marie Trudel

2016-01-01

Full Text Available Polycystin-1 (PC1 plays an essential role in renal tubular morphogenesis, and PC1 dysfunction causes human autosomal dominant polycystic kidney disease. A fundamental characteristic of PC1 is post-translational modification via cleavage at the juxtamembrane GPCR proteolysis site (GPS motif that is part of the larger GAIN domain. Given the considerable biochemical complexity of PC1 molecules generated in vivo by this process, GPS cleavage has several profound implications on the intracellular trafficking and localization in association with their particular function. The critical nature of GPS cleavage is further emphasized by the increasing numbers of PKD1 mutations that significantly affect this cleavage process. The GAIN domain with the GPS motif therefore represents the key structural element with fundamental importance for PC1 and might be polycystic kidney disease’s (PKD Achilles’ heel in a large spectrum of PKD1 missense mutations. We highlight the central roles of PC1 cleavage for the regulation of its biogenesis, intracellular trafficking and function, as well as its significance in polycystic kidney disease.

An autopsy case of vertebrobasilar dolichoectasia under hemodialysis due to autosomal dominant polycystic kidney disease

OpenAIRE

Nakagawa, Shiori; Furuichi, Kengo; Sagara, Akihiro; Shinozaki, Yasuyuki; Kitajima, Shinji; Toyama, Tadashi; Hara, Akinori; Iwata, Yasunori; Sakai, Norihiko; Shimizu, Miho; Matsui, Kazuhiro; Kaneko, Shuichi; Toyama, Tatsuhiko; Wada, Takashi

2015-01-01

A 60-year-old male with end-stage kidney disease due to autosomal polycystic kidney disease began maintenance hemodialysis in 2005. A brain CT scan showed dilatation of left vertebral artery, basilar artery, bilateral post cerebral artery, and middle cerebral artery. At the time, he was diagnosed as vertebrobasilar dolichoectasia. He was once admitted to our hospital for ischemic stroke. After discharge, he was treated with anticoagulant agent from 2010 to 2012 without any new stroke events. ...

Bilateral perinephric pseudocysts and polycystic kidneys in a ferret

International Nuclear Information System (INIS)

Puerto, D.A.; Walker, L.M.; Saunders, H.M.

1998-01-01

A 3-year-old castrated male domestic ferret was evaluated for abdominal distention. Survey lateral and dorsoventral abdominal radiographs were made. There were two soft tissue radiopacities consistent with grossly enlarged kidneys displacing small bowel and colon cranially, ventrally and caudally. Abdominal ultrasound was performed and revealed bilateral perinephric pseudocysts and polycystic kidneys. The perinephric pseudocysts were found to be dilated renal capsules on exploratory surgery and were drained. On follow up examinations, the pseudocysts were drained by ultrasound-guided paracentesis. The perinephric cyst fluid was distinguished from urine by measuring creatinine concentration and plans were made to resect the renal capsules due to rapid re-accumulation of pseudocyst fluid. The ferret's condition deteriorated and euthanasia was performed. Post-mortem examination was declined by the owner. Perinephric pseudocysts are rare and this is the first published report in a ferret. Ultrasound examination is the most rapid, accurate and non-invasive method for diagnosis of perinephric pseudocysts

The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease

DEFF Research Database (Denmark)

Jafar, Tazeen H; Stark, Paul C; Schmid, Christopher H

2005-01-01

BACKGROUND: It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors...... of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine......%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P

Overview of autosomal dominant polycystic kidney disease in the south of Spain

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Ana Isabel Morales García

2018-03-01

Full Text Available Introduction: Although autosomal dominant polycystic kidney disease is the most common hereditary kidney disease, available data tend to be limited to after initiation of renal replacement therapy. Objective: To ascertain an overview of autosomal dominant polycystic kidney disease within the health area of Granada in southern Spain. Materials and methods: From January 2007 to December 2016, we collected clinical, family and demographic information about all patients with autosomal dominant polycystic kidney disease, irrespective of whether or not they were treated with RRT, in the Granada health area. The computer software SPSS 15.0 and GenoPro were used. Results: 50.6% of the 1107 diagnosed patients were men. 99.1% were Caucasian and 4–6 generations/family were studied. The geographical distribution was heterogeneous. There was no family history in 2.43%. The mean age of diagnosis was 34.0 ± 17.80 years and the diagnosis was made after having offspring in 57.7% of cases. The main reason for diagnosis was family history (46.4%. The mean age of initiation of renal replacement therapy was 54.2 ± 11.05 years. 96.3% of the deceased had some degree of renal failure at the time of death. The mean age of death was 60.9 ± 14.10 years, the main cause of death being unknown in 33.5% of cases, followed by cardiovascular (27.8%. Conclusions: Cases and families were concentrated in certain geographical areas and a significant number of individuals were undiagnosed prior to cardiovascular death or diagnosed late after reproduction. Given that there is currently no curative treatment, the primary prevention strategy of preimplantation genetic diagnosis should play a leading role. Resumen: Introducción: La poliquistosis renal autosómica dominante es la enfermedad renal hereditaria más frecuente aunque los datos disponibles generalmente son tras el inicio del tratamiento renal sustitutivo. Objetivo: Conocer la situaci

Novel three-dimensional imaging volumetry in autosomal dominant polycystic kidney disease: comparison with 2D volumetry.

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Shin, Dongsuk; Lee, Kyu-Beck; Hyun, Young Youl; Lee, Young Rae; Hwang, Young-Hwan; Park, Hayne Cho; Ahn, Curie

2014-08-01

Autosomal dominant polycystic kidney disease (ADPKD) volumetry is an important marker for evaluating the progression of disease. Three-dimensional (3D) volumetry is generally more timesaving than 2D volumetry, but its reliability and accuracy are uncertain. Small and large phantoms simulating polycystic kidneys and 20 patients with ADPKD underwent magnetic resonance imaging (MRI) volumetry. We evaluated the total kidney volume (TKV) and total cyst volume (TCV) using a novel 3D volumetry program (XelisTM) and compared 3D volumetry data with the conventional 2D method (the reference volume values). After upload and threshold setting, the other organs surrounding the kidney were removed by picking and sculpting. The novel method involves drawing of the kidney or cyst and automatic measurement of kidney volume and cyst volume in 3D images. The 3D volume estimation of the small and large phantoms differed from the actual values by 6.9% and -8.2%, respectively, for TKV and by 2.1% and 1.4% for TCV. In ADPKD patients, the intra-reader reliability of 3D volumetry was 30 ± 180 mL (1.3 ± 10.3%) and 25 ± 113 mL (1.2 ± 9.4%), respectively, for TKV and TCV. Correlation between 3D volumetry and 2D volumetry of TKV and TCV resulted in a high correlation coefficient and a regression slope approaching 1.00 (r = 0.97 - 0.98). The mean of the volume percentage differences for 3D vs. 2D for TKV : TCV were -6.0 ± 8.9% : 2.0 ± 11.8% in large ADPKD and -16.1 ± 10.4% : 13.2 ± 21.9% in small ADPKD. Our study showed that 3D volumetry has reliability and accuracy compared with 2D volumetry in ADPKD. 3D volumetry is more accurate for TCV and large ADPKD.

[Massive increase of foetal abdominal circumference due to hereditary polycystic kidney disease].

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Dukic, L; Schaffelder, R; Schaible, T; Sütterlin, M; Siemer, J

2010-06-01

Autosomal recessive polycystic kidney disease (ARPKD) is a rare condition with a poor prognosis. We report on a 30-year-old primagravid woman in the 34th) week of gestation who was admitted to our hospital. ARPKD of the foetus had been sonographically suspected since the 26th week of gestation. Ultrasound examination showed big polycystic kidneys on both sides. The non-consanguineous parents wanted a maximum therapy for the infant. Foetal digitalisation because of heart insufficiency and prophylactic lung maturation was started. In the further course, Doppler sonographic values worsened and a Caesarean section was performed in the 34th week of gestation at the demand of the parents and due to the expected problems in case of a vaginal delivery. The weight of the newborn was 3,780 g and the abdominal circumference was 50 cm. The newborn was intubated immediately after birth and artificial ventilation was performed. Extracorporeal membrane oxygenation was not possible due to the bad cardial condition. The boy died 16 h after delivery. The parents refused genetic examination and autopsy of the newborn. ARPKD is a severe disease that may have obstetric relevance, due to the massively increased abdominal circumference. Therefore, termination of pregnancy or preterm induction of labor should be considered in order to avoid Caesarean section. Additionally, early prenatal diagnosis with genetic analysis of PRKD1 in cases of suspected ARPKD can be helpful. Georg Thieme Verlag KG Stuttgart, New York.

Aberrant Regulation of Notch3 Signaling Pathway in Polycystic Kidney Disease.

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Idowu, Jessica; Home, Trisha; Patel, Nisha; Magenheimer, Brenda; Tran, Pamela V; Maser, Robin L; Ward, Christopher J; Calvet, James P; Wallace, Darren P; Sharma, Madhulika

2018-02-20

Polycystic kidney disease (PKD) is a genetic disorder characterized by fluid-filled cysts in the kidney and liver that ultimately leads to end-stage renal disease. Currently there is no globally approved therapy for PKD. The Notch signaling pathway regulates cellular processes such as proliferation and de-differentiation, which are cellular hallmarks of PKD. Thus we hypothesized that the Notch pathway plays a critical role in PKD. Evaluation of protein expression of Notch signaling components in kidneys of Autosomal Recessive PKD (ARPKD) and Autosomal Dominant PKD (ADPKD) mouse models and of ADPKD patients revealed that Notch pathway members, particularly Notch3, were consistently upregulated or activated in cyst-lining epithelial cells. Notch3 expression correlated with rapidly growing cysts and co-localized with the proliferation marker, PCNA. Importantly, Notch inhibition significantly decreased forskolin-induced Notch3 activation and proliferation of primary human ADPKD cells, and significantly reduced cyst formation and growth of human ADPKD cells cultured in collagen gels. Thus our data indicate that Notch3 is aberrantly activated and facilitates epithelial cell proliferation in PKD, and that inhibition of Notch signaling may prevent cyst formation and growth.

Cux1 promotes cell proliferation and polycystic kidney disease progression in an ADPKD mouse model.

Science.gov (United States)

Porath, Binu; Livingston, Safia; Andres, Erica L; Petrie, Alexandra M; Wright, Joshua C; Woo, Anna E; Carlton, Carol G; Baybutt, Richard; Vanden Heuvel, Gregory B

2017-10-01

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common monogenic hereditary disorders in humans characterized by fluid-filled cysts, primarily in the kidneys. Cux1, a cell cycle regulatory gene highly expressed during kidney development, is elevated in the cyst-lining cells of Pkd1 mutant mice, and in human ADPKD cells. However, forced expression of Cux1 is insufficient to induce cystic disease in transgenic mice or to induce rapid cyst formation after cilia disruption in the kidneys of adult mice. Here we report a double mutant mouse model that has a conditional deletion of the Pkd1 gene in the renal collecting ducts together with a targeted mutation in the Cux1 gene (Pkd1 CD ;Cux1 tm2Ejn ). While kidneys isolated from newborn Pkd1 CD mice exhibit cortical and medullary cysts, kidneys isolated from newborn Pkd1 CD ;Cux1 tm2Ejn-/- mice did not show any cysts. Because Cux1 tm2Ejn-/- are perinatal lethal, we evaluated Pkd1 CD mice that were heterozygote for the Cux1 mutation. Similar to the newborn Pkd1 CD ;Cux1 tm2Ejn-/- mice, newborn Pkd1 CD ;Cux1 tm2Ejn+/- mice did not show any cysts. Comparison of Pkd1 CD and Pkd1 CD ;Cux1 tm2Ejn+/- mice at later stages of development showed a reduction in the severity of PKD in the Pkd1 CD ;Cux1 tm2Ejn+/- mice. Moreover, we observed an increase in expression of the cyclin kinase inhibitor p27, a target of Cux1 repression, in the rescued collecting ducts. Taken together, our results suggest that Cux1 expression in PKD is not directly involved in cystogenesis but promotes cell proliferation required for expansion of existing cysts, primarily by repression of p27. Copyright © 2017 the American Physiological Society.

Enhanced Autophagy in Polycystic Kidneys of AQP11 Null Mice

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Yasuko Tanaka

2016-11-01

Full Text Available Aquaporin-11 (AQP11 is an intracellular water channel expressed at the endoplasmic reticulum (ER of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(−/− kidneys. PCR analysis showed the increased expression of the transcript encoding LC3 (Map1lc3b as well as other autophagy-related genes in AQP11(−/− mice. Using green fluorescent protein (GFP-LC3 transgenic mice and AQP11(−/− mice, we found that the number of GFP-LC3–positive puncta was increased in the proximal tubule of AQP11(−/− mice before the cyst formation. Interestingly, they were also observed in the cyst-lining epithelial cell. Further PCR analyses revealed the enhanced expression of apoptosis-related and ER stress–related caspase genes before and after the cyst formation, which may cause the enhanced autophagy. These results suggest the involvement of autophagy in the development and maintenance of kidney cysts in AQP11(−/− mice.

Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0419 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...COVERED 1 Sep 2016 - 31 Aug 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal...inappropriate cell growth, fluid secretion, and dysregulation of cellular energy metabolism. The enzyme AMPK regulates a number of cellular pathways, including

Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease

Science.gov (United States)

2016-09-01

pathways that are involved in cyst development and expansion. These experiments will make use of cultured ADPKD cells and a mouse model of ADPKD to...AWARD NUMBER: W81XWH-15-1-0420 TITLE: Cellular Energy Pathways as Novel Targets for the Therapy of Autosomal Dominant Polycystic Kidney Disease...PRINCIPAL INVESTIGATOR: Kenneth R. Hallows, MD, PhD, FASN CONTRACTING ORGANIZATION: University of Southern California Los Angeles, CA 90089-0701

Birth weight and polycystic ovary syndrome in adult life

DEFF Research Database (Denmark)

Mumm, Hanne; Kamper-Jørgensen, Mads; Nybo Andersen, Anne-Marie

2013-01-01

OBJECTIVE: To study the association between birth weight and polycystic ovary syndrome (PCOS) in adult life in Danish women born 1973-1991. DESIGN: Register study. SETTING: Data were extracted from the Danish Medical Birth Register and the Danish National Patient Register (NPR). PATIENT(S): All...

Blood Pressure and Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease

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Mariusz Niemczyk

2014-12-01

Full Text Available Background/Aims: Autosomal dominant polycystic kidney disease (ADPKD is correlated with an increased frequency of both intracranial aneurysms (ICANs, and arterial hypertension (AH. The aim of our study was to search for the association between blood pressure (BP and ICANs in ADPKD patients. Methods: Sixty-eight adult, pre-dialysis phase ADPKD patients underwent both screening for ICANs with magnetic resonance angiography of the brain, and ambulatory blood pressure monitoring (ABPM. Results: ICANs were diagnosed in 10 patients (ICAN(+ group, while in 58 were not (ICAN(- group. The nighttime maximum diastolic blood pressure (DBP, maximum increase in DBP from measurement to measurement (positive delta of DBP at night, and the standard deviation of the daytime mean arterial pressure were significantly higher in ICAN(+ compared to ICAN(- patients. Additionally, in a subgroup of patients after 45 years-of-age, ICAN(+ patients had significantly higher maximum 24-hour and daytime systolic blood pressure, maximum 24-hour, daytime, nighttime DBP, maximum daytime and nighttime positive delta of DBP compared to ICAN(- cases. Conclusions: Development of ICANs in hypertensive ADPKD patients is accompanied with higher values of some BP parameters measured by ABPM. Hypertensive ADPKD patients with substantial fluctuations in BP assessed by ABPM, especially those after 45 years-of-age, should become candidates for screening for ICANs.

Caffeine intake by patients with autosomal dominant polycystic kidney disease

International Nuclear Information System (INIS)

Vendramini, L.C.; Nishiura, J.L.; Baxmann, A.C.; Heilberg, I.P.

2012-01-01

Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake

Caffeine intake by patients with autosomal dominant polycystic kidney disease

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Vendramini, L.C.; Nishiura, J.L.; Baxmann, A.C.; Heilberg, I.P. [Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

2012-07-20

Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

NARCIS (Netherlands)

Spithoven, Edwin M.; Meijer, E.; Borns, C.; Boertien, W. E.; Gaillard, C. A. J. M.; Kappert, P.; Greuter, Marcel J W; van der Jagt, E.; Vart, P.; de Jong, P. E.; Gansevoort, Ron T.

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR)

Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3

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Bryda, E.C.; Ling, H.; Rathbun, D.E. [New York State Department of Health, Albany, NY (United States)] [and others

1996-08-01

A chlorambucil (CHL)-induced mutation of the jcpk (juvenile congenital polycystic kidney disease) gene causes a severe early onset polycystic kidney disease. In an intercross involving Mus musculus castaneus, jcpk was precisely mapped 0.2 cM distal to D10Mit115 and 0.8 cM proximal to D10Mit173. In addition, five genes, Cdc2a, Col6al, Col6a2, Bcr, and Ank3 were mapped in both this jcpk intercross and a (BALB/c X CAST/Ei)F{sub 1} x BALB/c backcross. All five genes were eliminated as possible candidates for jcpk based on the mapping data. The jcpk intercross allowed the orientation of the Ank3 gene relative to the centromere to be determined. D10Mit115, D10Mit173, D10Mit199, and D10Mit200 were separated genetically in this cross. The order and genetic distances of all markers and gene loci mapped in the jcpk intercross were consistent with those derived from the BALB/c backcross, indicating that the CHL-induced lesion has not generated any gross chromosomal abnormalities detectable in these studies. 39 refs., 3 figs.

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

NARCIS (Netherlands)

Spithoven, E. M.; Meijer, E.; Borns, C.; Boertien, W. E.; Gaillard, C. A. J. M.; Kappert, P.; Greuter, M. J. W.; van der Jagt, E.; Vart, P.; de Jong, P. E.; Gansevoort, R. T.

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values.

Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data

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Knight T

2015-02-01

Full Text Available Tyler Knight,1 Caroline Schaefer,1 Holly Krasa,2 Dorothee Oberdhan,2 Arlene Chapman,3 Ronald D Perrone4 1Covance Market Access Services Inc., Gaithersburg, MD, 2Otsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD, 3Emory University, Atlanta, GA, 4Tufts Medical Center and Tufts University School of Medicine, Boston, MA, USA Background: Autosomal dominant polycystic kidney disease (ADPKD results in kidney cyst development and enlargement, resulting in chronic kidney disease (CKD leading to renal failure. This study sought to determine if ADPKD patients in the early stages of CKD contribute to a sizable economic burden for the US health care system. Methods: This was a retrospective, matched cohort study, reviewing medical resource utilization (MRU and costs for adults in a US private-payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13. ADPKD patients were matched by age grouping (0–17, 18–34, 35–44, 45–54, 55–64, and 65+ years and sex to controls to understand the burden of ADPKD. Descriptive statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or previous renal transplant. Results: The analysis included ADPKD patients in CKD stages 1–5 (n=316 to n=860, dialysis (n=586, and post-transplant (n=615. Mean ages did not differ across CKD stages (range 43–56 years. Men were the majority in the later stages but the minority in the early stages. The proportion of patients with at least one hospitalization increased with CKD stage, (12% to >40% CKD stage 2 to stage 5, dialysis or post-transplant. The majority had at least one hospital outpatient visit and at least one pharmacy claim. Total 6-month per-patient costs were greater among ADPKD patients than in age-matched and sex-matched healthy non-ADPKD controls (P<0.001 for all comparisons. Conclusion: ADPKD patients with normal kidney function are associated with a significant economic burden to the health care system

Health-related quality of life across all stages of autosomal dominant polycystic kidney disease

DEFF Research Database (Denmark)

Eriksson, Daniel; Karlsson, Linda; Eklund, Oskar

2017-01-01

BACKGROUND: A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess...... stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5. CONCLUSIONS: Later stages...

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease.

Science.gov (United States)

Kocyigit, Ismail; Yilmaz, Mahmut Ilker; Gungor, Ozkan; Eroglu, Eray; Unal, Aydin; Orscelik, Ozcan; Tokgoz, Bulent; Sipahioglu, Murat; Sen, Ahmet; Carrero, Juan Jesús; Oymak, Oktay; Axelsson, Jonas

2016-11-30

In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease. We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up. At baseline, median eGFR was 69 mL/min./1.73 m 2 , mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44-75) mL/min./1.73 m 2 , 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p 0.76], and ΔPWV [cut-off:≤7.80]. Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.

Emergence of hepatic fibrosis and portal hypertension in infants and children with autosomal recessive polycystic kidney disease. Initial and follow-up sonographic and radiographic findings

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Premkumar, A; Berdon, W E; Abramson, S J; Newhouse, J H; Levy, J

1988-02-01

Long-term imaging and clinical findings are reported in six children whose polycystic kidney disease was detected in infancy or early childhood. Over time (2 years to 20 years) all patients developed portal hypertension from hepatic fibrosis, a problem primarily noted in recessive pattern polycystic kidney disease. Mild renal failure (two patients) was accompanied by serious systemic hypertension in the same patients. In one family, one of the babies also showed dilated right hepatic ducts. Imaging studies included urography and CT although recently ultrasonography was the method of choice. The relative renal and hepatic manifestations in these patients so changed with time that it would seem fallacious to attempt to use rigid classifications based on findings at initial diagnosis.

Inhibition of Aerobic Glycolysis Attenuates Disease Progression in Polycystic Kidney Disease.

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Meliana Riwanto

Full Text Available Dysregulated signaling cascades alter energy metabolism and promote cell proliferation and cyst expansion in polycystic kidney disease (PKD. Here we tested whether metabolic reprogramming towards aerobic glycolysis ("Warburg effect" plays a pathogenic role in male heterozygous Han:SPRD rats (Cy/+, a chronic progressive model of PKD. Using microarray analysis and qPCR, we found an upregulation of genes involved in glycolysis (Hk1, Hk2, Ldha and a downregulation of genes involved in gluconeogenesis (G6pc, Lbp1 in cystic kidneys of Cy/+ rats compared with wild-type (+/+ rats. We then tested the effect of inhibiting glycolysis with 2-deoxyglucose (2DG on renal functional loss and cyst progression in 5-week-old male Cy/+ rats. Treatment with 2DG (500 mg/kg/day for 5 weeks resulted in significantly lower kidney weights (-27% and 2-kidney/total-body-weight ratios (-20% and decreased renal cyst index (-48% compared with vehicle treatment. Cy/+ rats treated with 2DG also showed higher clearances of creatinine (1.98±0.67 vs 1.41±0.37 ml/min, BUN (0.69±0.26 vs 0.40±0.10 ml/min and uric acid (0.38±0.20 vs 0.21±0.10 ml/min, and reduced albuminuria. Immunoblotting analysis of kidney tissues harvested from 2DG-treated Cy/+ rats showed increased phosphorylation of AMPK-α, a negative regulator of mTOR, and restoration of ERK signaling. Assessment of Ki-67 staining indicated that 2DG limits cyst progression through inhibition of epithelial cell proliferation. Taken together, our results show that targeting the glycolytic pathway may represent a promising therapeutic strategy to control cyst growth in PKD.

A Challenging Case of Hepatoblastoma Concomitant with Autosomal Recessive Polycystic Kidney Disease and Caroli Syndrome—Review of the Literature

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Nevil Kadakia

2017-06-01

Full Text Available We report a rare case of an 18-month-old female with autosomal recessive polycystic kidney disease, Caroli syndrome, and pure fetal type hepatoblastoma. The liver tumor was surgically resected with no chemotherapy given. Now 9 years post resection she demonstrates no local or distant recurrence and stable renal function.

Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

Science.gov (United States)

Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

2017-11-01

Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

Pregnancy in autosomal recessive polycystic kidney disease.

Science.gov (United States)

Banks, Nicole; Bryant, Joy; Fischer, Roxanne; Huizing, Marjan; Gahl, William A; Gunay-Aygun, Meral

2015-03-01

Autosomal recessive polycystic kidney disease (ARPKD) is the most common childhood-onset ciliopathy. As treatments improve, more women are reaching reproductive age, but little is known about ARPKD and pregnancy. In our ongoing study on ARPKD and other ciliopathies, 12 females over 18 years of age were identified and systematically evaluated. Six had children; four carried pregnancies and delivered, one used assisted reproductive technology and had a surrogate carry the pregnancy, and one adopted. We report the outcomes of four pregnancies with live birth deliveries and two women who chose alternate family building options. Patient one was diagnosed at 6 months, and at age 21 had a pregnancy complicated by transient worsening of renal function (creatinine increase from 1.15 to 1.78 mg/dL). Patient two was diagnosed with ARPKD at age seven and had an uncomplicated pregnancy at age 23. Patient three was diagnosed incidentally with ARPKD at age 23, 3 months after completion of an uncomplicated pregnancy. Patient four who had an uncomplicated pregnancy at age 33 was diagnosed with ARPKD at age 46. Women with ARPKD face reproductive decisions largely bereft of information about the pregnancies of other ARPKD patients. We report four cases of pregnancy and ARPKD to expand current knowledge and encourage further research.

An overview of experimental and early investigational therapies for the treatment of polycystic kidney disease.

Science.gov (United States)

Santoro, Domenico; Pellicanò, Vincenzo; Visconti, Luca; Trifirò, Gianluca; Buemi, Michele; Cernaro, Valeria

2015-01-01

At present, treatment of autosomal dominant polycystic kidney disease (ADPKD) is essentially supportive as there is still no specific therapy. However, recent advances with ADPKD pathophysiology have stimulated research for new therapeutic strategies. The aim of this systematic review is to analyze the experimental and early investigational therapies currently under evaluation in this field. Data from completed clinical trials were retrieved from the currently available scientific literature and from the ClinicalTrials.gov website. Among the drugs currently being explored, mammalian target of rapamycin inhibitors reduce kidney volume enlargement but their role remains uncertain. The most promising drug is the V2 receptor antagonist tolvaptan, which reduces the increased rate of total kidney volume and slows down glomerular filtration rate decline. The main candidates for the treatment of cysts growth, both in the kidney and in the liver whenever present, are the somatostatin analogues, such as lanreotide and octreotide and more recently pasireotide. As for other therapies, some favorable results have been achieved but data are still not sufficient to establish if these approaches may be beneficial in slowing ADPKD progression in the future.

The 10 sea urchin receptor for egg jelly proteins (SpREJ are members of the polycystic kidney disease-1 (PKD1 family

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Miyata Shinji

2007-07-01

Full Text Available Abstract Background Mutations in the human polycystic kidney disease-1 (hPKD1 gene result in ~85% of cases of autosomal dominant polycystic kidney disease, the most frequent human monogenic disease. PKD1 proteins are large multidomain proteins involved in a variety of signal transduction mechanisms. Obtaining more information about members of the PKD1 family will help to clarify their functions. Humans have five hPKD1 proteins, whereas sea urchins have 10. The PKD1 proteins of the sea urchin, Strongylocentrotus purpuratus, are referred to as the Receptor for Egg Jelly, or SpREJ proteins. The SpREJ proteins form a subfamily within the PKD1 family. They frequently contain C-type lectin domains, PKD repeats, a REJ domain, a GPS domain, a PLAT/LH2 domain, 1–11 transmembrane segments and a C-terminal coiled-coil domain. Results The 10 full-length SpREJ cDNA sequences were determined. The secondary structures of their deduced proteins were predicted and compared to the five human hPKD1 proteins. The genomic structures of the 10 SpREJs show low similarity to each other. All 10 SpREJs are transcribed in either embryos or adult tissues. SpREJs show distinct patterns of expression during embryogenesis. Adult tissues show tissue-specific patterns of SpREJ expression. Conclusion Possession of a REJ domain of about 600 residues defines this family. Except for SpREJ1 and 3, that are thought to be associated with the sperm acrosome reaction, the functions of the other SpREJ proteins remain unknown. The sea urchin genome is one-fourth the size of the human genome, but sea urchins have 10 SpREJ proteins, whereas humans have five. Determination of the tissue specific function of each of these proteins will be of interest to those studying echinoderm development. Sea urchins are basal deuterostomes, the line of evolution leading to the vertebrates. The study of individual PKD1 proteins will increase our knowledge of the importance of this gene family.

The Therapeutic Effect of the Antitumor Drug 11beta and Related Molecules on Polycystic Kidney Disease

Science.gov (United States)

2016-10-01

shown that two parent compounds, 11B-dichloro and 11B- dipropyl, are effective in preventing and delaying cyst growth in two different orthologous mouse...polycystic kidney disease (PKD). In collaboration with the Essigmann lab at MIT, we have shown that two parent compounds, 11B-dichloro and 11B-dipropyl, are...cultured at the permissible temperature (33 °C), then re-plated at 37 °C, in the absence of interferon gamma, conditions in which turn off the large T

Generation of an induced pluripotent stem cell line, IBMS-iPSC-014-05, from a female autosomal dominant polycystic kidney disease patient carrying a common mutation of R803X in PKD2

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Ming-Ching Ho

2017-12-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC line from the peripheral blood mononuclear cells (PBMCs of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers.

Branched-chain amino acids enhance cyst development in autosomal dominant polycystic kidney disease.

Science.gov (United States)

Yamamoto, Junya; Nishio, Saori; Hattanda, Fumihiko; Nakazawa, Daigo; Kimura, Toru; Sata, Michio; Makita, Minoru; Ishikawa, Yasunobu; Atsumi, Tatsuya

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1 flox/flox :Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age. The BCAA group showed significantly greater kidney/body weight ratio and higher cystic index in both the kidney and liver compared to the placebo-treated mice. We found that the L-type amino acid transporter 1 that facilitates BCAA entry into cells is strongly expressed in cells lining the cysts. We also found increased cyst-lining cell proliferation and upregulation of mTOR and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways in the BCAA group. In vitro, we cultured renal epithelial cell lines from Pkd1 null mice with or without leucine. Leucine was found to stimulate cell proliferation, as well as activate mTOR and MAPK/ERK pathways in these cells. Thus, BCAA accelerated disease progression by mTOR and MAPK/ERK pathways. Hence, BCAA may be harmful to patients with ADPKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Imaging features of ductal plate malformations in adults

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Venkatanarasimha, N., E-mail: nandashettykv@yahoo.com [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom); Thomas, R.; Armstrong, E.M.; Shirley, J.F.; Fox, B.M.; Jackson, S.A. [Department of Radiology, Derriford Hospital, Plymouth (United Kingdom)

2011-11-15

Ductal plate malformations, also known as fibrocystic liver diseases, are a group of congenital disorders resulting from abnormal embryogenesis of the biliary ductal system. The abnormalities include choledochal cyst, Caroli's disease and Caroli's syndrome, adult autosomal dominant polycystic liver disease, and biliary hamartoma. The hepatic lesions can be associated with renal anomalies such as autosomal recessive polycystic kidney disease (ARPKD), medullary sponge kidney, and nephronophthisis. A clear knowledge of the embryology and pathogenesis of the ductal plate is central to the understanding of the characteristic imaging appearances of these complex disorders. Accurate diagnosis of ductal plate malformations is important to direct appropriate clinical management and prevent misdiagnosis.

A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8

Directory of Open Access Journals (Sweden)

McCooke John K

2012-08-01

Full Text Available Abstract Background Nephronophthisis (NPHP as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK rat. Results In this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a- related kinase 8 ( Nek8 gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation. Conclusions When assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.

Clinical characteristics and disease predictors of a large Chinese cohort of patients with autosomal dominant polycystic kidney disease.

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Dongping Chen

Full Text Available OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD is a relentlessly progressing form of chronic kidney disease for which there is no cure. The aim of this study was to characterize Chinese patients with ADPKD and to identify the factors which predict cyst growth and renal functional deterioration. METHODS: To analyze disease predicting factors we performed a prospective longitudinal observational study in a cohort of 541 Chinese patients with ADPKD and an eGFR ≥ 30 ml/min/1.73 m(2. Patients were followed clinically and radiologically with sequential abdominal magnetic resonance imaging (MRI. Clinical characteristics and laboratory data were related to changes in estimated glomerular filtration rate (eGFR and total kidney volume (TKV. A linear regression model was developed to analyze the factors which determine eGFR and TKV changes. RESULTS: The age range of this unselected cohort ranged from 4 to 77 years. Median follow-up time was 14.3 ± 10.6 months. Although inter-individual differences in eGFR and TKV were large, there was a consistent link between these two parameters. Baseline log10-transformed TKV and urinary protein/creatinine ratio were identified as the major predictors for a faster eGFR decline and were associated with a higher TKV growth rate. Interestingly, a lower thrombocyte count correlated significantly with lower eGFR (r = 0.222 and higher TKV (r = 0.134. CONCLUSIONS: This large cohort of Chinese patients with ADPKD provides unique epidemiological data for comparison with other cohorts of different ethnicity. In Chinese patients we identified a lower thrombocyte count as a significant predictor of disease progression. These results are important for the design of future clinical trials to retard polycystic kidney disease progression.

Mutational analysis in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Identification of five mutations in the PKD1 gene.

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Abdelwahed, Mayssa; Hilbert, Pascale; Ahmed, Asma; Mahfoudh, Hichem; Bouomrani, Salem; Dey, Mouna; Hachicha, Jamil; Kamoun, Hassen; Keskes-Ammar, Leila; Belguith, Neïla

2018-05-31

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia. Copyright © 2017. Published by Elsevier B.V.

Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease

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Cruz, Nelly M.; Song, Xuewen; Czerniecki, Stefan M.; Gulieva, Ramila E.; Churchill, Angela J.; Kim, Yong Kyun; Winston, Kosuke; Tran, Linh M.; Diaz, Marco A.; Fu, Hongxia; Finn, Laura S.; Pei, York; Himmelfarb, Jonathan; Freedman, Benjamin S.

2017-11-01

Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD. Removal of adherent cues increases cystogenesis 10-fold, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters. Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression and collagen compaction. Cyclic adenosine monophosphate (cAMP), when added, induces cysts in both PKD organoids and controls. These biomaterials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvironment at the earliest stages of the disease.

Relationship between intracranial aneurysms and the severity of autosomal dominant polycystic kidney disease.

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Yoshida, Hiroki; Higashihara, Eiji; Maruyama, Keisuke; Nutahara, Kikuo; Nitatori, Toshiaki; Miyazaki, Isao; Shiokawa, Yoshiaki

2017-12-01

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disease characterized by the progressive enlargement of innumerable renal cysts. Although the association of intracranial aneurysms (ICANs) with ADPKD is well known, the relationship between the ICAN and the disease severity including total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) is poorly understood. We screened 265 patients with ADPKD (mean age, 48.8 years; range, 14.9-88.3 years) with MR angiography. The patients with a past history related to ICANs were excluded from the study. The incidence and characteristics of ICAN in patients with ADPKD were evaluated. TKV was measured by volumetric analyses of MR imaging. We detected 65 ICANs in 49 patients (37 women and 12 men, mean age, 52.7 years; range, 20.4-86 years). The incidence of ICANs was 18.5% and female patients had was higher incidence (23.1%) than male patients (11.4%) (p = 0.02). An age of those with ICANs was significantly higher than those without (p = 0.006), and the cumulative risk of diagnosis of ICANs increased with age. TKV was significantly larger in those with ICANs than those without (p = 0.001), but eGFR was not different between two groups (p = 0.07). By multivariate analyses, only TKV was significantly related to the development of ICANs (p = 0.02). The incidence of ICANs increased with age, was higher in females, and correlated with kidney enlargement in patients with ADPKD. Necessity of screening ICANs would be particularly high in elderly women with large kidneys.

Advances in cell proliferation and apoptosis signal pathway and therapies of polycystic kidney disease

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Xiao-ying LIAN

2016-12-01

Full Text Available Polycystic kidney disease (PKD is one of the monogenic inherited diseases. In PKD, excessive cell proliferation and fluid secretion, and disruption of the mechanisms controlling tubular diameter may all lead to cyst formation. Current evidence has demonstrated that intracellular calcium ion and cAMP imbalance drive both abnormal cell proliferation and apoptosis signal pathway. The present paper summarized the evidence implicating calcium ion and cAMP as central players in the signaling pathway of cell proliferation and apoptosis in PKD, and considered the potential therapeutic approaches targeted to slow cyst growth in PKD. DOI: 10.11855/j.issn.0577-7402.2016.11.13

A stepwise approach for effective management of chronic pain in autosomal-dominant polycystic kidney disease.

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Casteleijn, Niek F; Visser, Folkert W; Drenth, Joost P H; Gevers, Tom J G; Groen, Gerbrand J; Hogan, Marie C; Gansevoort, Ron T

2014-09-01

Chronic pain, defined as pain existing for >4-6 weeks, affects >60% of patients with autosomal-dominant polycystic disease (ADPKD). It can have various causes, indirectly or directly related to the increase in kidney and liver volume in these patients. Chronic pain in ADPKD patients is often severe, impacting physical activity and social relationships, and frequently difficult to manage. This review provides an overview of pathophysiological mechanisms that can lead to pain and discusses the sensory innervation of the kidneys and the upper abdominal organs, including the liver. In addition, the results of a systematic literature search of ADPKD-specific treatment options are presented. Based on pathophysiological knowledge and evidence derived from the literature an argumentative stepwise approach for effective management of chronic pain in ADPKD is proposed. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Glycogen synthase kinase-3β promotes cyst expansion in polycystic kidney disease.

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Tao, Shixin; Kakade, Vijayakumar R; Woodgett, James R; Pandey, Pankaj; Suderman, Erin D; Rajagopal, Madhumitha; Rao, Reena

2015-06-01

Polycystic kidney diseases (PKDs) are inherited disorders characterized by the formation of fluid filled renal cysts. Elevated cAMP levels in PKDs stimulate progressive cyst enlargement involving cell proliferation and transepithelial fluid secretion often leading to end-stage renal disease. The glycogen synthase kinase-3 (GSK3) family of protein kinases consists of GSK3α and GSK3β isoforms and has a crucial role in multiple cellular signaling pathways. We previously found that GSK3β, a regulator of cell proliferation, is also crucial for cAMP generation and vasopressin-mediated urine concentration by the kidneys. However, the role of GSK3β in the pathogenesis of PKDs is not known. Here we found that GSK3β expression and activity were markedly upregulated and associated with cyst-lining epithelia in the kidneys of mice and humans with PKD. Renal collecting duct-specific gene knockout of GSK3β or pharmacological inhibition of GSK3 effectively slowed down the progression of PKD in mouse models of autosomal recessive or autosomal dominant PKD. GSK3 inactivation inhibited cAMP generation and cell proliferation resulting in reduced cyst expansion, improved renal function, and extended life span. GSK3β inhibition also reduced pERK, c-Myc, and cyclin-D1, known mitogens in proliferation of cystic epithelial cells. Thus, GSK3β has a novel functional role in PKD pathophysiology, and its inhibition may be therapeutically useful to slow down cyst expansion and progression of PKD.

Radiologic and clinical bronchiectasis associated with autosomal dominant polycystic kidney disease.

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Teng Moua

Full Text Available BACKGROUND: Polycystin 1 and 2, the protein abnormalities associated with autosomal dominant polycystic kidney disease (ADPKD, are also found in airway cilia and smooth muscle cells. There is evidence of increased radiologic bronchiectasis associated with ADPKD, though the clinical and functional implications of this association are unknown. We hypothesized an increased prevalence of both radiologic and clinical bronchiectasis is associated with APDKD as compared to non-ADPKD chronic kidney disease (CKD controls. MATERIALS AND METHODS: A retrospective case-control study was performed at our institution involving consecutive ADPKD and non-ADPKD chronic kidney disease (CKD patients seen over a 13 year period with both chest CT and PFT. CTs were independently reviewed by two blinded thoracic radiologists. Manually collected clinical data included symptoms, smoker status, transplant history, and PFT findings. RESULTS: Ninety-two ADPKD and 95 non-ADPKD CKD control patients were compared. Increased prevalence of radiologic bronchiectasis, predominantly mild lower lobe disease, was found in ADPKD patients compared to CKD control (19 vs. 9%, P = 0.032, OR 2.49 (CI 1.1-5.8. After adjustment for covariates, ADPKD was associated with increased risk of radiologic bronchiectasis (OR 2.78 (CI 1.16-7.12. Symptomatic bronchiectasis occurred in approximately a third of ADPKD patients with radiologic disease. Smoking was associated with increased radiologic bronchiectasis in ADPKD patients (OR 3.59, CI 1.23-12.1. CONCLUSIONS: Radiological bronchiectasis is increased in patients with ADPKD particularly those with smoking history as compared to non-ADPKD CKD controls. A third of such patients have symptomatic disease. Bronchiectasis should be considered in the differential in ADPKD patients with respiratory symptoms and smoking history.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

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Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

2015-08-07

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

International Nuclear Information System (INIS)

Webb, Carol F.; Ratliff, Michelle L.; Powell, Rebecca; Wirsig-Wiechmann, Celeste R.; Lakiza, Olga; Obara, Tomoko

2015-01-01

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

Automatic total kidney volume measurement on follow-up magnetic resonance images to facilitate monitoring of autosomal dominant polycystic kidney disease progression.

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Kline, Timothy L; Korfiatis, Panagiotis; Edwards, Marie E; Warner, Joshua D; Irazabal, Maria V; King, Bernard F; Torres, Vicente E; Erickson, Bradley J

2016-02-01

Renal imaging examinations provide high-resolution information about the anatomic structure of the kidneys and are used to measure total kidney volume (TKV) in autosomal dominant polycystic kidney disease (ADPKD) patients. TKV has become the gold-standard image biomarker for ADPKD progression at early stages of the disease and is used in clinical trials to characterize treatment efficacy. Automated methods to segment the kidneys and measure TKV are desirable because of the long time requirement for manual approaches such as stereology or planimetry tracings. However, ADPKD kidney segmentation is complicated by a number of factors, including irregular kidney shapes and variable tissue signal at the kidney borders. We describe an image processing approach that overcomes these problems by using a baseline segmentation initialization to provide automatic segmentation of follow-up scans obtained years apart. We validated our approach using 20 patients with complete baseline and follow-up T1-weighted magnetic resonance images. Both manual tracing and stereology were used to calculate TKV, with two observers performing manual tracings and one observer performing repeat tracings. Linear correlation and Bland-Altman analysis were performed to compare the different approaches. Our automated approach measured TKV at a level of accuracy (mean difference ± standard error = 0.99 ± 0.79%) on par with both intraobserver (0.77 ± 0.46%) and interobserver variability (1.34 ± 0.70%) of manual tracings. All approaches had excellent agreement and compared favorably with ground-truth manual tracing with interobserver, stereological and automated approaches having 95% confidence intervals ∼ ± 100 mL. Our method enables fast, cost-effective and reproducible quantification of ADPKD progression that will facilitate and lower the costs of clinical trials in ADPKD and other disorders requiring accurate, longitudinal kidney quantification. In addition, it will hasten the routine use of

Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

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Balbo, B.E.P. [Divisão de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Sapienza, M.T.; Ono, C.R. [Divisão de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Jayanthi, S.K. [Divisão de Radiologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Dettoni, J.B. [Divisão de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Castro, I.; Onuchic, L.F. [Divisão de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-06-13

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.

Recurrent acute pancreatitis and cholangitis in a patient with autosomal dominant polycystic kidney disease

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Kambiz Yazdanpanah

2013-01-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is an inherited disorder associated with multiple cyst formation in the different organs. Development of pancreatic cyst in ADPKD is often asymptomatic and is associated with no complication. A 38-year-old man with ADPKD was presented with six episodes of acute pancreatitis and two episodes of cholangitis in a period of 12 months. Various imaging studies revealed multiple renal, hepatic and pancreatic cysts, mild ectasia of pancreatic duct, dilation of biliary system and absence of biliary stone. He was managed with conservative treatment for each attack. ADPKD should be considered as a potential risk factor for recurrent acute and/or chronic pancreatitis and cholangitis.

Live Donor Renal Transplant With Simultaneous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease Is Feasible and Satisfactory at Long-term Follow-up.

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Ahmad, Sarwat B; Inouye, Brian; Phelan, Michael S; Kramer, Andrew C; Sulek, Jay; Weir, Matthew R; Barth, Rolf N; LaMattina, John C; Schweitzer, Eugene J; Leeser, David B; Niederhaus, Silke V; Bartlett, Stephen T; Bromberg, Jonathan S

2016-02-01

Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant. Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys. Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously. Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.

Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

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Zhiguo Mao

2016-08-01

Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

[Rare case of congenital cystic adenomatoid malformation associated with polycystic kidney disease].

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Jabłoński, Janusz; Jankowski, Zbigniew; Sitkiewicz, Anna; Lewandowska, Małgorzata; Andrzejewska, Ewa

2011-01-01

Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary abnormality that results from aberrant fetal lung development. It about 4-26% of cases it can be associated with other congenital abnormalities. We describe a case of congenital cystic adenomatoid malformation 2 associated with polycystic kidney disease. The association of these two congenital malformations is exceptional. Only four similar cases have been reported in the literature. A 2-year-old girl was referred to the Department of Paediatric Surgery and Oncology Medical University of Lodz with pneumonia and left pneumothorax. For three weeks prior to referral the patient was treated with antibiotics. Chest x-ray revealed hyperinflation of left upper lobe with mediastinal shift to right. Computer tomographic scan of the lung revealed multiple cyst in the left upper lobe, left-site pneumothorax and mediastinal shift to the right. The patient underwent thoracotomy. Intraoperatively, multiple cysts in the left upper lobe were found and left upper lobectomy was performed. Histologic study was compatible with type 2 congenital cystic adenomatoid malformation. Ultrasound examination showed multilocular cysts in both kidneys. The dimensions of the cysts were: MWR4. 54x45x45 mm and 25x21x24 mm on the left and right sides, respectively. Significant increase in cyst size on the left side was observed. Ten months after first hospitalization resection of the cystic lower pole of the left kidney was performed. The presence of even a single renal cyst in a child with CCAM is an indication for further follow up examinations.

Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice.

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Gansevoort, Ron T; Arici, Mustafa; Benzing, Thomas; Birn, Henrik; Capasso, Giovambattista; Covic, Adrian; Devuyst, Olivier; Drechsler, Christiane; Eckardt, Kai-Uwe; Emma, Francesco; Knebelmann, Bertrand; Le Meur, Yannick; Massy, Ziad A; Ong, Albert C M; Ortiz, Alberto; Schaefer, Franz; Torra, Roser; Vanholder, Raymond; Więcek, Andrzej; Zoccali, Carmine; Van Biesen, Wim

2016-03-01

Recently, the European Medicines Agency approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease. In this paper, on behalf of the ERA-EDTA Working Groups of Inherited Kidney Disorders and European Renal Best Practice, we aim to provide guidance for making the decision as to which ADPKD patients to treat with tolvaptan. The present position statement includes a series of recommendations resulting in a hierarchical decision algorithm that encompasses a sequence of risk-factor assessments in a descending order of reliability. By examining the best-validated markers first, we aim to identify ADPKD patients who have documented rapid disease progression or are likely to have rapid disease progression. We believe that this procedure offers the best opportunity to select patients who are most likely to benefit from tolvaptan, thus improving the benefit-to-risk ratio and cost-effectiveness of this treatment. It is important to emphasize that the decision to initiate treatment requires the consideration of many factors besides eligibility, such as contraindications, potential adverse events, as well as patient motivation and lifestyle factors, and requires shared decision-making with the patient. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Liver cysts associated with polycystic kidney disease: Role of Tc-99m hepatobiliary imaging

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Salam, M.; Keeffe, E.B.

1989-01-01

A 42-year-old woman with multiple hepatic cysts associated with autosomal polycystic kidney disease was evaluated for abdominal discomfort and new liver test abnormalities following blind aspirations of her liver cysts. Tc-99m mebrofenin hepatobiliary imaging revealed a markedly enlarged liver with multiple photon deficient areas, focal retention of isotope in the left hepatic ductal system, no accumulation of radionuclide in cysts, and an unusual medial gallbladder position. Endoscopic retrograde cholangiography confirmed all of these findings. Abdominal discomfort and liver biochemical abnormalities were attributed to cyst compression of nearby structures, including bile ducts. Hepatobiliary imaging is useful to exclude communication of bile ducts with hepatic cysts, to detect incidental abnormalities such as partial bile duct obstruction, and to distinguish the gallbladder from nearby hepatic cysts

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

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Wüthrich Rudolf P

2007-09-01

Full Text Available Abstract Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD. Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune® in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918

Polycystic kidney disease

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... don't have other diseases may be good candidates for a kidney transplant. Possible Complications Health problems ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

Autosomal dominant polycystic kidney disease in a family with mosaicism and hypomorphic allele.

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Reiterová, Jana; Štekrová, Jitka; Merta, Miroslav; Kotlas, Jaroslav; Elišáková, Veronika; Lněnička, Petr; Korabečná, Marie; Kohoutová, Milada; Tesař, Vladimír

2013-03-15

Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of inherited kidney disease that results in renal failure. ADPKD is a systemic disorder with cysts and connective tissue abnormalities involving many organs. ADPKD caused by mutations in PKD1 gene is significantly more severe than the cases caused by PKD2 gene mutations. The large intra-familial variability of ADPKD highlights a role for genetic background. Here we report a case of ADPKD family initially appearing unlinked to the PKD1 or PKD2 loci and the influence of mosaicism and hypomorphic allele on the variability of the clinical course of the disease. A grandmother with the PKD1 gene mutation in mosaicism (p.Val1105ArgfsX4) and with mild clinical course of ADPKD (end stage renal failure at the age of 77) seemed to have ADPKD because of PKD2 gene mutation. On the other hand, her grandson had a severe clinical course (end stage renal disease at the age of 45) in spite of the early treatment of mild hypertension. There was found by mutational analysis of PKD genes that the severe clinical course was caused by PKD1 gene frameshifting mutation inherited from his father and mildly affected grandmother in combination with inherited hypomorphic PKD1 allele with described missense mutation (p.Thr2250Met) from his clinically healthy mother. The sister with two cysts and with PKD1 hypomorphic allele became the kidney donor to her severely affected brother. We present the first case of ADPKD with the influence of mosaicism and hypomorphic allele of the PKD1 gene on clinical course of ADPKD in one family. Moreover, this report illustrates the role of molecular genetic testing in assessing young related kidney donors for patients with ADPKD.

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

NARCIS (Netherlands)

Lantinga, M.A. (Marten A.); D’Agnolo, H.M.A. (Hedwig M. A.); E. Casteleijn (Eric); de Fijter, J.W. (Johan W.); E. Meijer (Esther); A.L. Messchendorp (A. Lianne); D. Peters (Dorien); M. Salih (Mahdi); E.M. Spithoven (Edwin); D. Soonawala (Darius); F.W. Visser (Folkert); Wetzels, J.F.M. (Jack F. M.); R. Zietse (Bob); J.P.H. Drenth (Joost); R.T. Gansevoort (Ron); Drenth, J.P.H.; J.W. de Fijter (Johan); Gansevoort, R.T.; D.J.M. Peters (Dorien J.M.); J.F.M. Wetzels (Jack); Zietse, R.

2017-01-01

textabstractIntroduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several

Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease.

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Li, Linda Xiaoyan; Fan, Lucy X; Zhou, Julie Xia; Grantham, Jared J; Calvet, James P; Sage, Julien; Li, Xiaogang

2017-06-30

Autosomal dominant polycystic kidney disease (ADPKD) is driven by mutations in PKD1 and PKD2 genes. Recent work suggests that epigenetic modulation of gene expression and protein function may play a role in ADPKD pathogenesis. In this study, we identified SMYD2, a SET and MYND domain protein with lysine methyltransferase activity, as a regulator of renal cyst growth. SMYD2 was upregulated in renal epithelial cells and tissues from Pkd1-knockout mice as well as in ADPKD patients. SMYD2 deficiency delayed renal cyst growth in postnatal kidneys from Pkd1 mutant mice. Pkd1 and Smyd2 double-knockout mice lived longer than Pkd1-knockout mice. Targeting SMYD2 with its specific inhibitor, AZ505, delayed cyst growth in both early- and later-stage Pkd1 conditional knockout mouse models. SMYD2 carried out its function via methylation and activation of STAT3 and the p65 subunit of NF-κB, leading to increased cystic renal epithelial cell proliferation and survival. We further identified two positive feedback loops that integrate epigenetic regulation and renal inflammation in cyst development: SMYD2/IL-6/STAT3/SMYD2 and SMYD2/TNF-α/NF-κB/SMYD2. These pathways provide mechanisms by which SMYD2 might be induced by cyst fluid IL-6 and TNF-α in ADPKD kidneys. The SMYD2 transcriptional target gene Ptpn13 also linked SMYD2 to other PKD-associated signaling pathways, including ERK, mTOR, and Akt signaling, via PTPN13-mediated phosphorylation.

Rare co-occurrence of osteogenesis imperfecta type I and autosomal dominant polycystic kidney disease.

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Hoefele, Julia; Mayer, Karin; Marschall, Christoph; Alberer, Martin; Klein, Hanns-Georg; Kirschstein, Martin

2016-11-01

There are several clinical reports about the co-occurrence of autosomal dominant polycystic kidney disease (ADPKD) and connective tissue disorders. A simultaneous occurrence of osteogenesis imperfecta (OI) type I and ADPKD has not been observed so far. This report presents the first patient with OI type I and ADPKD. Mutational analysis of PKD1 and COL1A1 in the index patient revealed a heterozygous mutation in each of the two genes. Mutational analysis of the parents indicated the mother as a carrier of the PKD1 mutation and the father as a carrier of the COL1A1 mutation. The simultaneous occurrence of both disorders has an estimated frequency of 3.5:100 000 000. In singular cases, ADPKD can occur in combination with other rare disorders, e.g. connective tissue disorders.

Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients

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Annapareddy Shiva Nagendra Reddy

2016-01-01

Full Text Available Introduction: Autosomal dominant polycystic kidney disease (ADPKD is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD in ADPKD. In the present study we investigated six genes coding for endothelin 1 (EDN1 tagging-single nucleotide polymorphisms (tag-SNPs to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.

Post transplant urinary tract infection in Autosomal dominant polycystic kidney disease a perpetual diagnostic dilema - 18-fluorodeoxyglucose - Positron emission computerized tomography - A valuable tool

International Nuclear Information System (INIS)

Sainaresh, VV; Jain, SH; Patel, HV; Shah, PR; Vanikar, AV; Trivedi, HL

2011-01-01

Urinary tract infection (UTI) is the most common infection contracted by renal allograft recipients. In patients of autosomal dominant polycystic kidney disease (ADPKD), cyst infection presents a complex diagnostic and therapeutic challenge especially in the post transplant period. Accurate diagnosis forms the cornerstone in salvaging the graft from potentially catastrophic outcome. We describe a case of xanthogranulomatous pyelonephritis (XPN) in the native kidney in a patient of post transplant ADPKD which presented as frequently relapsing UTI with graft dysfunction where in accurate diagnosis was made possible with the aid of 18-fluorodeoxyglucose (FDG) - Positron emission computerized tomography (PET/CT)

A comparison of pediatric and adult kidney donors for adult recipients.

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Pugliese, M R; Ridolfi, L; Nanni Costa, A; Taddei, S; Venturoli, N; Petrini, F

1999-01-01

The high demand for organs for transplantation has made it necessary to consider using even the oldest and youngest of potential donors in order to increase the organ supply. In this retrospective study, the outcome of kidney transplantation using cadaveric pediatric donors was compared with that of an adult control series. Graft procurement took place in two regions of Italy (Emilia-Romagna and Piemonte) over an 11-year period. A group of pediatric donors (Actuarial patient and graft survival rates did not differ significantly between the two groups (patient survival 96% and 96% for pediatric donors versus 98% and 92% for adult donors at 1 and 5 years post-transplantation; graft survival 76% and 68% for pediatric donors versus 88% and 74% for adult donors 1 and 5 y post-transplantation). Complications were also evaluated, but no difference was found (the only exception being the creatinine level in the 5th year). Renal transplantation with cadaveric donors starting at 4 years of age gave results comparable to kidneys coming from adults. These data show that cadaveric pediatric donor kidneys may be used in adult recipients with good results. The ethical implications of the subject are extensively reviewed.

Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

International Nuclear Information System (INIS)

Bonon, Anna; Mangolini, Alessandra; Pinton, Paolo; Senno, Laura del; Aguiari, Gianluca

2013-01-01

Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G 0 /G 1 phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new opportunities

Berberine slows cell growth in autosomal dominant polycystic kidney disease cells

Energy Technology Data Exchange (ETDEWEB)

Bonon, Anna; Mangolini, Alessandra [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Pinton, Paolo [Department of Morphology, Surgery and Experimental Medicine, Section of General Pathology, University of Ferrara, 44121 Ferrara (Italy); Senno, Laura del [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy); Aguiari, Gianluca, E-mail: dsn@unife.it [Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, 44121 Ferrara (Italy)

2013-11-22

Highlights: •Berberine at appropriate doses slows cell proliferation in ADPKD cystic cells. •Reduction of cell growth by berberine occurs by inhibition of ERK and p70-S6 kinase. •Higher doses of berberine cause an overall cytotoxic effect. •Berberine overdose induces apoptotic bodies formation and DNA fragmentation. •Antiproliferative properties of this drug make it a new candidate for ADPKD therapy. -- Abstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary monogenic disorder characterized by development and enlargement of kidney cysts that lead to loss of renal function. It is caused by mutations in two genes (PKD1 and PKD2) encoding for polycystin-1 and polycystin-2 proteins which regulate different signals including cAMP, mTOR and EGFR pathways. Abnormal activation of these signals following PC1 or PC2 loss of function causes an increased cell proliferation which is a typical hallmark of this disease. Despite the promising findings obtained in animal models with targeted inhibitors able to reduce cystic cell growth, currently, no specific approved therapy for ADPKD is available. Therefore, the research of new more effective molecules could be crucial for the treatment of this severe pathology. In this regard, we have studied the effect of berberine, an isoquinoline quaternary alkaloid, on cell proliferation and apoptosis in human and mouse ADPKD cystic cell lines. Berberine treatment slows cell proliferation of ADPKD cystic cells in a dose-dependent manner and at high doses (100 μg/mL) it induces cell death in cystic cells as well as in normal kidney tubule cells. However, at 10 μg/mL, berberine reduces cell growth in ADPKD cystic cells only enhancing G{sub 0}/G{sub 1} phase of cell cycle and inhibiting ERK and p70-S6 kinases. Our results indicate that berberine shows a selected antiproliferative activity in cellular models for ADPKD, suggesting that this molecule and similar natural compounds could open new

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease

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Gnanasambandan Ramanathan

2017-01-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544 were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Gender hormones and the progression of experimental polycystic kidney disease.

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Stringer, Kenneth D; Komers, Radko; Osman, Shukri A; Oyama, Terry T; Lindsley, Jessie N; Anderson, Sharon

2005-10-01

Male gender is a risk factor for progression of autosomal-dominant polycystic kidney disease (ADPKD), clinically and in the Han:SPRD rat model. Orchiectomy limits progression, but mechanisms of the detrimental effect of androgen, and/or beneficial effects of estrogen, are not known. This protocol tested the hypothesis that male gender (intact androgen status) promotes progression, while female gender (intact estrogen status) is protective; and that these disease-modifying effects are due to changes in expression of known fibrotic mediators. Studies were performed in male and female noncystic control (+/+) and cystic (+/-) rats subjected to orchiectomy, ovariectomy, or sham operation. At 12 weeks of age, renal function was measured. Blood and kidneys were taken for measurement of plasma and renal renin, endothelin (ET-1), endothelial nitric oxide synthase (eNOS), and vascular endothelial growth factor (VEGF), using biochemical, protein expression, and immunohistochemical methods. Cystic male rats exhibited significantly reduced glomerular filtration (GFR) and effective renal plasma flow (ERPF) rates, with suppression of plasma and renal renin, up-regulation of renal ET-1 and eNOS, and down-regulation of renal VEGF expression. Orchiectomy attenuated the fall in GFR and ERPF, while numerically limiting changes in eNOS and VEGF. Female rats exhibited less cystic growth, with normal renin status, lesser elevation of renal ET-1, and proportionately lesser changes in VEGF and eNOS. Ovariectomy led to higher blood pressure and reduced GFR and ERPF, with a trend toward upregulation of ET-1, and significant down-regulation of VEGF and eNOS. Female gender is protective, but ovariectomy attenuates the protective effect of female gender, in association with changes in renal expression of ET-1, VEGF, and eNOS. The accelerated disease in male rats can be attenuated by orchiectomy and consequent changes in expression of disease mediators.

Expression of Nek1 during kidney development and cyst formation in multiple nephron segments in the Nek1-deficient kat2J mouse model of polycystic kidney disease.

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Chen, Yumay; Chiang, Huai-Chin; Litchfield, Patricia; Pena, Michelle; Juang, Charity; Riley, Daniel J

2014-07-17

Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. Among them, Nek1 is the primary protein inactivated in kat2J mouse models of PKD. We report the expression pattern of Nek1 and characterize the renal cysts that develop in kat2J mice. Nek1 is detectable in all murine tissues but its expression in wild type and kat2J heterozygous kidneys decrease as the kidneys mature, especially in tubular epithelial cells. In the embryonic kidney, Nek1 expression is most prominent in cells that will become podocytes and proximal tubules. Kidney development in kat2J homozygous mice is aberrant early, before the appearance of gross cysts: developing cortical zones are thin, populated by immature glomeruli, and characterized by excessive apoptosis of several cell types. Cysts in kat2J homozygous mice form postnatally in Bowman's space as well as different tubular subtypes. Late in life, kat2J heterozygous mice form renal cysts and the cells lining these cysts lack staining for Nek1. The primary cilia of cells lining cysts in kat2J homozygous mice are morphologically diverse: in some cells they are unusually long and in others there are multiple cilia of varying lengths. Our studies indicate that Nek1 deficiency leads to disordered kidney maturation, and cysts throughout the nephron.

Unexpected relevance of the hallmarks of cancer to the pathogenesis of polycystic kidney disease

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Seeger-Nukpezah, Tamina; Geynisman, Daniel M.; Nikonova, Anna S.; Benzing, Thomas; Golemis, Erica A.

2018-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited disorder in which renal tissue is gradually replaced with fluid-filled cysts, giving rise to chronic kidney disease (CKD) and progressive loss of renal function. ADPKD is also associated with liver ductal cysts, hypertension, chronic pain and extrarenal problems such as cerebral aneurysms. Intriguingly, improved understanding of the signalling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of solid tumours, even though the gross presentation of tumours and the greater morbidity and mortality associated with tumour invasion and metastasis would initially suggest an entirely different disease processes. The commonalities between ADPKD and cancer are provocative, particularly in the context of recent preclinical and clinical studies of ADPKD that have shown promise with drugs that were originally developed for cancer. The potential therapeutic benefit of such repurposing has led us to review in detail the pathological features of ADPKD through the lens of the defined, classic hallmarks of cancer. In addition, we have evaluated features typical of ADPKD, and determined whether evidence supports the presence of such features in cancer cells. This analysis, which places pathological processes in the context of defined signalling pathways and approved signalling inhibitors, highlights potential avenues for further research and therapeutic exploitation in both diseases. PMID:25870008

Quantitative MRI of kidneys in renal disease.

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Kline, Timothy L; Edwards, Marie E; Garg, Ishan; Irazabal, Maria V; Korfiatis, Panagiotis; Harris, Peter C; King, Bernard F; Torres, Vicente E; Venkatesh, Sudhakar K; Erickson, Bradley J

2018-03-01

To evaluate the reproducibility and utility of quantitative magnetic resonance imaging (MRI) sequences for the assessment of kidneys in young adults with normal renal function (eGFR ranged from 90 to 130 mL/min/1.73 m 2 ) and patients with early renal disease (autosomal dominant polycystic kidney disease). This prospective case-control study was performed on ten normal young adults (18-30 years old) and ten age- and sex-matched patients with early renal parenchymal disease (autosomal dominant polycystic kidney disease). All subjects underwent a comprehensive kidney MRI protocol, including qualitative imaging: T1w, T2w, FIESTA, and quantitative imaging: 2D cine phase contrast of the renal arteries, and parenchymal diffusion weighted imaging (DWI), magnetization transfer imaging (MTI), blood oxygen level dependent (BOLD) imaging, and magnetic resonance elastography (MRE). The normal controls were imaged on two separate occasions ≥24 h apart (range 24-210 h) to assess reproducibility of the measurements. Quantitative MR imaging sequences were found to be reproducible. The mean ± SD absolute percent difference between quantitative parameters measured ≥24 h apart were: MTI-derived ratio = 4.5 ± 3.6%, DWI-derived apparent diffusion coefficient (ADC) = 6.5 ± 3.4%, BOLD-derived R2* = 7.4 ± 5.9%, and MRE-derived tissue stiffness = 7.6 ± 3.3%. Compared with controls, the ADPKD patient's non-cystic renal parenchyma (NCRP) had statistically significant differences with regard to quantitative parenchymal measures: lower MTI percent ratios (16.3 ± 4.4 vs. 23.8 ± 1.2, p quantitative measurements was obtained in all cases. Significantly different quantitative MR parenchymal measurement parameters between ADPKD patients and normal controls were obtained by MT, DWI, BOLD, and MRE indicating the potential for detecting and following renal disease at an earlier stage than the conventional qualitative imaging techniques.

Leprecan distribution in the developing and adult kidney.

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Lauer, M; Scruggs, B; Chen, S; Wassenhove-McCarthy, D; McCarthy, K J

2007-07-01

The temporal and spatial deposition of extracellular matrix proteins is critical for nephrogenesis and glomerular maturation. We previously characterized leprecan as a novel chondroitin sulfate proteoglycan which has been recently shown to have prolyl hydroxylase activity. In this study, we examine the distribution of leprecan during nephrogenesis and after a hypertrophic stimulus to the adult kidney. During development, leprecan was localized to mesenchymal aggregates, early comma- and S-phase structures as determined by immunohistochemistry and in situ hybridization. Leprecan mRNA was increased in cells around the vascular cleft of the S- and comma-phase glomeruli. Expression was found in podocytes, mesangial cells, and parietal epithelial cells of loop-phase glomeruli. Leprecan mRNA was substantially decreased in the glomeruli of the adult kidney compared to the developing kidney with a uniform distribution between the glomeruli and the tubules. Within adult glomeruli, leprecan was found in the mesangium mesangial matrix, podocytes, and in Bowman's capsule. In response to glomerular hypertrophy, produced by unilateral nephrectomy, leprecan synthesis was increased in the adult kidney. We suggest that the regulated expression of leprecan during glomerular development or hypertrophy coupled with its reported prolyl hydroxylase activity plays a role during basement membrane assembly.

Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease.

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Liu, Bin; Li, Chenghai; Liu, Zijuan; Dai, Zonghan; Tao, Yunxia

2012-09-11

Polycystic Kidney Disease (PKD) kidneys exhibit increased extracellular matrix (ECM) collagen expression and metalloproteinases (MMPs) activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. We examined the role of type I collagen (collagen I) and membrane bound type 1 MMP (MT1-MMP) on cyst development using both in vitro 3 dimensional (3D) collagen gel culture and in vivo PCK rat model of PKD. We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease

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Liu Bin

2012-09-01

Full Text Available Abstract Background Polycystic Kidney Disease (PKD kidneys exhibit increased extracellular matrix (ECM collagen expression and metalloproteinases (MMPs activity. We investigated the role of these increases on cystic disease progression in PKD kidneys. Methods We examined the role of type I collagen (collagen I and membrane bound type 1 MMP (MT1-MMP on cyst development using both in vitro 3 dimensional (3D collagen gel culture and in vivo PCK rat model of PKD. Results We found that collagen concentration is critical in controlling the morphogenesis of MDCK cells cultured in 3D gels. MDCK cells did not form 3D structures at collagen I concentrations lower than 1 mg/ml but began forming tubules when the concentration reaches 1 mg/ml. Significantly, these cells began to form cyst when collagen I concentration reached to 1.2 mg/ml, and the ratios of cyst to tubule structures increased as the collagen I concentration increased. These cells exclusively formed cyst structures at a collagen I concentration of 1.8 mg/ml or higher. Overexpression of MT1-MMP in MDCK cells significantly induced cyst growth in 3D collagen gel culture. Conversely, inhibition of MMPs activity with doxycycline, a FDA approved pan-MMPs inhibitor, dramatically slowed cyst growth. More importantly, the treatment of PCK rats with doxycycline significantly decreased renal tubule cell proliferation and markedly inhibited the cystic disease progression. Conclusions Our data suggest that increased collagen expression and MMP activity in PKD kidneys may induce cyst formation and expansion. Our findings also suggest that MMPs may serve as a therapeutic target for the treatment of human PKD.

Exon sequencing of PKD1 gene in an Iranian patient with autosomal-dominant polycystic kidney disease.

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Hafizi, Atousa; Khatami, Saeid Reza; Galehdari, Hamid; Shariati, Gholamreza; Saberi, Ali Hossein; Hamid, Mohammad

2014-07-01

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 (16p13.3, 46 exons) and PKD2 (4q21, 15 exons). Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel missense mutations were reported just in the 7-year-old boy: ACA>GCA found in exon 15 at codon 2241 and CAC>AAC found in exon 38 at codon 3710. For checking the pathogenicity of these mutations, exons 15, 25, and 38 of 50 unrelated normal cases were sequenced. our findings suggested that GTG>ATG is a polymorphism with high frequency (60%) as well as ACA>GCA and CAC>AAC are polymorphisms with frequencies of 14% and 22%, respectively in the population of Southwest Iran.

Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).

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Grieben, Mariana; Pike, Ashley C W; Shintre, Chitra A; Venturi, Elisa; El-Ajouz, Sam; Tessitore, Annamaria; Shrestha, Leela; Mukhopadhyay, Shubhashish; Mahajan, Pravin; Chalk, Rod; Burgess-Brown, Nicola A; Sitsapesan, Rebecca; Huiskonen, Juha T; Carpenter, Elisabeth P

2017-02-01

Mutations in either polycystin-1 (PC1 or PKD1) or polycystin-2 (PC2, PKD2 or TRPP1) cause autosomal-dominant polycystic kidney disease (ADPKD) through unknown mechanisms. Here we present the structure of human PC2 in a closed conformation, solved by electron cryomicroscopy at 4.2-Å resolution. The structure reveals a novel polycystin-specific 'tetragonal opening for polycystins' (TOP) domain tightly bound to the top of a classic transient receptor potential (TRP) channel structure. The TOP domain is formed from two extensions to the voltage-sensor-like domain (VSLD); it covers the channel's endoplasmic reticulum lumen or extracellular surface and encloses an upper vestibule, above the pore filter, without blocking the ion-conduction pathway. The TOP-domain fold is conserved among the polycystins, including the homologous channel-like region of PC1, and is the site of a cluster of ADPKD-associated missense variants. Extensive contacts among the TOP-domain subunits, the pore and the VSLD provide ample scope for regulation through physical and chemical stimuli.

Percutaneous Nephrolithotomy in Autosomal Dominant Polycystic Kidney Disease: Is it Different from Percutaneous Nephrolithotomy in Normal Kidney?

Science.gov (United States)

Singh, Vishwajeet; Sinha, Rahul Janak; Gupta, Dheeraj Kumar

2013-08-01

Nephrolithiasis has been reported in 20-28% of patients, of whom 50% are symptomatic for stone disease and 20% require definite urologic intervention. The management of nephrolithiasis includes oral alkali dissolution therapy, extracorporeal shock wave lithotripsy and surgical treatment. In such patients, percutaneous nephrolithotomy (PNL) as a method of stone treatment has been reported in few cases with limited experience. The aim of this study is to present our experience of PNL in autosomal dominant polycystic kidney disease (ADPKD) and assessing the outcome results. From 2002 to 2011, 22 patients (26 renal units) suffering from ADPKD with stone were managed by PNL. Demographic characteristics, operative parameters and postoperative complications were recorded and analysed. The overall success rate of PNL was 82.1% and PNL with extracorporeal shock wave lithotripsy for clinically significant residual fragments was 92.85% respectively. The hematuria required blood transfusion (n = 9), postoperative fever due to cyst infection (n = 4) and paralytic ileus (n = 3) were recorded. The PNL in ADPKD PNL is safe and effective but have more postoperative complications such as bleeding requiring transfusions, fever due to cyst infection and paralytic ileus.

Medical resource utilization and costs associated with autosomal dominant polycystic kidney disease in the USA: a retrospective matched cohort analysis of private insurer data

Science.gov (United States)

Knight, Tyler; Schaefer, Caroline; Krasa, Holly; Oberdhan, Dorothee; Chapman, Arlene; Perrone, Ronald D

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) results in kidney cyst development and enlargement, resulting in chronic kidney disease (CKD) leading to renal failure. This study sought to determine if ADPKD patients in the early stages of CKD contribute to a sizable economic burden for the US health care system. Methods This was a retrospective, matched cohort study, reviewing medical resource utilization (MRU) and costs for adults in a US private-payer claims database with a diagnosis code of ADPKD (ICD-9-CM 753.13). ADPKD patients were matched by age grouping (0–17, 18–34, 35–44, 45–54, 55–64, and 65+ years) and sex to controls to understand the burden of ADPKD. Descriptive statistics on 6-month MRU and costs were assessed by CKD stages, dialysis use, or previous renal transplant. Results The analysis included ADPKD patients in CKD stages 1–5 (n=316 to n=860), dialysis (n=586), and post-transplant (n=615). Mean ages did not differ across CKD stages (range 43–56 years). Men were the majority in the later stages but the minority in the early stages. The proportion of patients with at least one hospitalization increased with CKD stage, (12% to >40% CKD stage 2 to stage 5, dialysis or post-transplant). The majority had at least one hospital outpatient visit and at least one pharmacy claim. Total 6-month per-patient costs were greater among ADPKD patients than in age-matched and sex-matched healthy non-ADPKD controls (P<0.001 for all comparisons). Conclusion ADPKD patients with normal kidney function are associated with a significant economic burden to the health care system relative to the general population. Any treatments that delay progression to later stages of CKD may provide potential health care cost offsets. PMID:25759590

Health-related quality of life across all stages of autosomal dominant polycystic kidney disease.

Science.gov (United States)

Eriksson, Daniel; Karlsson, Linda; Eklund, Oskar; Dieperink, Hans; Honkanen, Eero; Melin, Jan; Selvig, Kristian; Lundberg, Johan

2017-12-01

A limited number of studies have assessed health-related quality of life (HRQoL) in autosomal dominant polycystic kidney disease (ADPKD). Results to date have been conflicting and studies have generally focused on patients with later stages of the disease. This study aimed to assess HRQoL in ADPKD across all stages of the disease, from patients with early chronic kidney disease (CKD) to patients with end-stage renal disease. A study involving cross-sectional patient-reported outcomes and retrospective clinical data was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Patients were enrolled into four mutually exclusive stages of the disease: CKD stages 1-3; CKD stages 4-5; transplant recipients; and dialysis patients. Overall HRQoL was generally highest in patients with CKD stages 1-3, followed by transplant recipients, patients with CKD stages 4-5 and patients on dialysis. Progressive disease predominately had an impact on physical health, whereas mental health showed less variation between stages of the disease. A substantial loss in quality of life was observed as patients progressed to CKD stages 4-5. Later stages of ADPKD are associated with reduced physical health. The value of early treatment interventions that can delay progression of the disease should be considered. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE AND CONGENITAL HEPATIC FIBROSIS: SUMMARY STATEMENT OF A FIRST NATIONAL INSTITUTES OF HEALTH/OFFICE OF RARE DISEASES CONFERENCE

Science.gov (United States)

Gunay-Aygun, Meral; Avner, Ellis D.; Bacallo, Robert L.; Choyke, Peter L.; Flynn, Joseph T.; Germino, Gregory G.; Guay-Woodford, Lisa; Harris, Peter; Heller, Theo; Ingelfinger, Julie; Kaskel, Frederick; Kleta, Robert; LaRusso, Nicholas F.; Mohan, Parvathi; Pazour, Gregory J.; Shneider, Benjamin L.; Torres, Vicente E.; Wilson, Patricia; Zak, Colleen; Zhou, Jing; Gahl, William A.

2010-01-01

Researchers and clinicians with expertise in autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF) and related fields met on May 5-6, 2005, on the National Institutes of Health (NIH) campus for a 1.5-day symposium sponsored by the NIH Office of Rare Diseases, the National Human Genome Research Institute (NHGRI), and in part by the ARPKD/CHF Alliance. The meeting addressed the present status and the future of ARPKD/CHF research. PMID:16887426

Embolization of renal arteries before transplantation in patients with polycystic kidney disease: a single institution long-term experience

Energy Technology Data Exchange (ETDEWEB)

Petitpierre, F.; Cornelis, F.; Lasserre, A.S.; Tricaud, E.; Le Bras, Y.; Grenier, N. [Pellegrin Hospital, Department of Radiology, Bordeaux (France); Couzi, L.; Merville, P. [Pellegrin Hospital, Department of Nephrology, Bordeaux (France); Combe, C.; Ferriere, J.M. [Pellegrin Hospital, Department of Urology, Bordeaux (France)

2015-11-15

We aimed to retrospectively assess the long-term safety and efficacy of embolization of renal arteries (ERA) in patients with polycystic kidney disease (PKD) before renal transplantation. Between January 2008 and November 2013, 82 ERA procedures were performed on 76 kidneys in 73 patients (mean age 53 years, range: 34-72). All patients had terminal-stage PKD and were under dialysis and on the renal transplant waiting list with a temporary contraindication due to excessive renal volume. ERA was considered successful in 89.5 % (68/76) of embolized kidneys, meaning that the temporary contraindication for transplantation could be withdrawn for 65 patients (on average 5.6 months, range: 2.8-24.3, after ERA). Mean volume reduction was 40 (range: 2-69) at 3 months and 59 % (35-86) thereafter (both p < 0.001). Post-embolization syndrome occurred after 15 of 82 procedures (18.3 %). The severe complication rate was 4.9 %. Forty-three (67.7 %) transplantations were successfully conducted after ERA, with a mean follow-up of 26.2 months (range: 1.8-59.5), and the estimated 5-year graft survival rate was 95.3 % [95 % CI: 82.7-98.8]. ERA is a safe and effective alternative to nephrectomy before renal transplantation in patients with PKD. (orig.)

Embolization of renal arteries before transplantation in patients with polycystic kidney disease: a single institution long-term experience

International Nuclear Information System (INIS)

Petitpierre, F.; Cornelis, F.; Lasserre, A.S.; Tricaud, E.; Le Bras, Y.; Grenier, N.; Couzi, L.; Merville, P.; Combe, C.; Ferriere, J.M.

2015-01-01

We aimed to retrospectively assess the long-term safety and efficacy of embolization of renal arteries (ERA) in patients with polycystic kidney disease (PKD) before renal transplantation. Between January 2008 and November 2013, 82 ERA procedures were performed on 76 kidneys in 73 patients (mean age 53 years, range: 34-72). All patients had terminal-stage PKD and were under dialysis and on the renal transplant waiting list with a temporary contraindication due to excessive renal volume. ERA was considered successful in 89.5 % (68/76) of embolized kidneys, meaning that the temporary contraindication for transplantation could be withdrawn for 65 patients (on average 5.6 months, range: 2.8-24.3, after ERA). Mean volume reduction was 40 (range: 2-69) at 3 months and 59 % (35-86) thereafter (both p < 0.001). Post-embolization syndrome occurred after 15 of 82 procedures (18.3 %). The severe complication rate was 4.9 %. Forty-three (67.7 %) transplantations were successfully conducted after ERA, with a mean follow-up of 26.2 months (range: 1.8-59.5), and the estimated 5-year graft survival rate was 95.3 % [95 % CI: 82.7-98.8]. ERA is a safe and effective alternative to nephrectomy before renal transplantation in patients with PKD. (orig.)

A Case of New Familiar Genetic Variant of Autosomal Dominant Polycystic Kidney Disease-2: A Case Study.

Science.gov (United States)

Litvinchuk, Tetiana; Tao, Yunxia; Singh, Ruchi; Vasylyeva, Tetyana L

2015-01-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal cyst formation due to mutations in genes coding for polycystin-1 [PKD1 (85-90% of cases), on ch 16p13.3] and polycystin-2 [PKD2 (10-15% of cases), on ch 4q13-23] and PKD3 gene (gene unmapped). It is also associated with TSC2/PKD1 contiguous gene syndrome. ADPKD is usually inherited, but new mutations without a family history occur in approximately 10% of the cases. A 17-year-old boy was followed up for bilateral cystic kidney disease, hypertension, and obesity since he was 13 years old. The diagnosis was an accidental finding during abdominal CT at age 13 to rule out appendicitis. A renal ultrasonogram also demonstrated a multiple bilateral cysts. Because of parental history of bilateral renal cysts, PKD1 and PKD2, genetic testing was ordered. Results showed, PKD2 variant 1:3 bp deletion of TGT; nucleotide position: 1602-1604; codon position: 512-513; mRNA reading frame maintained. The same mutation was later identified in his father. A smaller number of patients have a defect in the PKD2 locus on chromosome 4 (resulting in PKD2 disease). There are no known published cases on this familiar genetic variant of ADPKD-2 cystic kidney disease. In this case, the disease is present unusually early in life.

Polycystin-1 C terminus cleavage and its relation with polycystin-2, two proteins involved in polycystic kidney disease

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Claudia A. Bertuccio

2013-04-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD, a most common genetic cause of chronic renal failure, is characterized by the progressive development and enlargement of cysts in kidneys and other organs. The cystogenic process is highly complex and involves a high proliferative rate, increased apoptosis, altered protein sorting, changed secretory characteristics, and disorganization of the extracellular matrix. ADPKD is caused by mutations in the genes encoding polycystin-1 (PC-1 or polycystin-2 (PC-2. PC-1 undergoes multiple cleavages that intervene in several signaling pathways involved in cellular proliferation and differentiation mechanisms. One of these cleavages releases the cytoplasmic C-terminal tail of PC-1. In addition, the C-terminal cytoplasmic tails of PC-1 and PC-2 interact in vitro and in vivo. The purpose of this review is to summarize recent literature that suggests that PC-1 and PC-2 may function through a common signaling pathway necessary for normal tubulogenesis. We hope that a better understanding of PC-1 and PC-2 protein function will lead to progress in diagnosis and treatment for ADPKD.

The value of intrarenal resistive index in autosomal dominant polycystic kidney disease

International Nuclear Information System (INIS)

Lee, Young Rae; Lee, Kyu Beck; Park, Hae Won

1998-01-01

The purpose of this study was to determine the value of the intrarenal resistive index(RI), measured by Doppler sonography, in order to assess intrarenal vascular resistance in autosomal dominant polycystic kidney disease (ADPKD) patients. In 26 patients with ADPKD, RI was measured by Doppler sonography and correlated with the presence of hypertension, renal function (creatinine clearance) and anatomical renal severity index (RSI), thus indicating renal morphologic abnormalities during Bmode sonography. RI was significantly higher in 18 hypertensive ADPKD patients (0.64±0.65) (Mean±1SD;range:0.52-0.74) than in eight normotensive patients (0.59± 0.50) (0.48-0.64) (p<0.05). Statistically significant inverse correlation was found between RI values and creatinine clearance (r=3D-0.45, p<0.05), and statistically significant correlation was found between RI values and RSI, indicating the degree of renal parenchymal involvement. RI correlates with the development of hypertension, renal function and renal morphologic abnormality scoring by RSI during B-mode Doppler sonography, and measured in this way may thus be used to assess renal vascular resistance in ADPKD patients.=20

Localized Cystic Disease of the Kidney: A Rare Cause of Hypertension in a Young Adult

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Aynur Solak

2013-01-01

Full Text Available Localized cystic disease of kidney (LCDK is a rare, non-familial, non-progressive renal disorder that is not associated with cysts or disorders in other organs. Only a few cases have been reported in the literature. While this condition is morphologically identical to the autosomal dominant form of polycystic kidney disease, it is not inherited and is not associated with significant deterioration of renal function. We present a case of a 16-year-old male patient who suffered from hypertension for over two years. On imaging we found several, variable-sized cysts in the upper half of the right kidney. The left kidney and lower segment of the right kidney were normal. Selective renal vein catheterization and sampling showed markedly elevated renin level in the right upper segmental vein (92 pg/ml, normal value: 11-33 pg/ml. The patient underwent a right upper heminephrectomy and histopathology was suggestive of LCDK. After surgery, the patient′s blood pressure returned to normal levels without any need of antihypertensive medication and he is under follow-up on outpatient basis for the past two years.

Disorders of fatty acid oxidation and autosomal recessive polycystic kidney disease-different clinical entities and comparable perinatal renal abnormalities.

Science.gov (United States)

Hackl, Agnes; Mehler, Katrin; Gottschalk, Ingo; Vierzig, Anne; Eydam, Marcus; Hauke, Jan; Beck, Bodo B; Liebau, Max C; Ensenauer, Regina; Weber, Lutz T; Habbig, Sandra

2017-05-01

Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early

MR imaging of adult glomerulocystic kidney disease

International Nuclear Information System (INIS)

Egashira, K.; Nakata, H.; Hashimoto, O.; Kaizu, K.; University of Occupational and Environmental Health School of Medicine, Kitakyushu

1991-01-01

A 59-year-old man with hypertension and severe renal dysfunction was diagnosed as having adult glomerulocystic kidney disease. MR imaging of the kidney showed a diffuse reduction of the intensity of the renal cortex with a loss of normal cortico-medullary differentiation of T1-weighted images. Numerous small cortical cysts were also demonstrated. These MR findings complemented the results of the biopsy and were useful for making a definitive diagnosis. (orig.)

Diagnostic approach to chronic kidney disease

African Journals Online (AJOL)

syndrome may suggest disorders such as polycystic kidney disease,. Alport syndrome, focal ... metabolic syndrome assists with the evaluation of the patient's cardiovascular risk .... found during heavy exercise, fever and stress. • Common ...

Autosomal dominant polycystic kidney disease caused by somatic and germline mosaicism.

Science.gov (United States)

Tan, A Y; Blumenfeld, J; Michaeel, A; Donahue, S; Bobb, W; Parker, T; Levine, D; Rennert, H

2015-04-01

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder caused by loss of function mutations of PKD1 or PKD2 genes. Although PKD1 is highly polymorphic and the new mutation rate is relatively high, the role of mosaicism is incompletely defined. Herein, we describe the molecular analysis of ADPKD in a 19-year-old female proband and her father. The proband had a PKD1 truncation mutation c.10745dupC (p.Val3584ArgfsX43), which was absent in paternal peripheral blood lymphocytes (PBL). However, very low quantities of this mutation were detected in the father's sperm DNA, but not in DNA from his buccal cells or urine sediment. Next generation sequencing (NGS) analysis determined the level of this mutation in the father's PBL, buccal cells and sperm to be ∼3%, 4.5% and 10%, respectively, consistent with somatic and germline mosaicism. The PKD1 mutation in ∼10% of her father's sperm indicates that it probably occurred early in embryogenesis. In ADPKD cases where a de novo mutation is suspected because of negative PKD gene testing of PBL, additional evaluation with more sensitive methods (e.g. NGS) of the proband PBL and paternal sperm can enhance detection of mosaicism and facilitate genetic counseling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Positive Predictive Values of International Classification of Diseases, 10th Revision Coding Algorithms to Identify Patients With Autosomal Dominant Polycystic Kidney Disease

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Vinusha Kalatharan

2016-12-01

Full Text Available Background: International Classification of Diseases, 10th Revision codes (ICD-10 for autosomal dominant polycystic kidney disease (ADPKD is used within several administrative health care databases. It is unknown whether these codes identify patients who meet strict clinical criteria for ADPKD. Objective: The objective of this study is (1 to determine whether different ICD-10 coding algorithms identify adult patients who meet strict clinical criteria for ADPKD as assessed through medical chart review and (2 to assess the number of patients identified with different ADPKD coding algorithms in Ontario. Design: Validation study of health care database codes, and prevalence. Setting: Ontario, Canada. Patients: For the chart review, 201 adult patients with hospital encounters between April 1, 2002, and March 31, 2014, assigned either ICD-10 codes Q61.2 or Q61.3. Measurements: This study measured positive predictive value of the ICD-10 coding algorithms and the number of Ontarians identified with different coding algorithms. Methods: We manually reviewed a random sample of medical charts in London, Ontario, Canada, and determined whether or not ADPKD was present according to strict clinical criteria. Results: The presence of either ICD-10 code Q61.2 or Q61.3 in a hospital encounter had a positive predictive value of 85% (95% confidence interval [CI], 79%-89% and identified 2981 Ontarians (0.02% of the Ontario adult population. The presence of ICD-10 code Q61.2 in a hospital encounter had a positive predictive value of 97% (95% CI, 86%-100% and identified 394 adults in Ontario (0.003% of the Ontario adult population. Limitations: (1 We could not calculate other measures of validity; (2 the coding algorithms do not identify patients without hospital encounters; and (3 coding practices may differ between hospitals. Conclusions: Most patients with ICD-10 code Q61.2 or Q61.3 assigned during their hospital encounters have ADPKD according to the clinical

9. The Contribution of Animal Experiments to Kidney Transplantation

OpenAIRE

Botting, Jack Howard

2016-01-01

Haemodialysis is life-saving and curative in acute renal failure. By reversing the build-up of metabolic products normally excreted by a functioning kidney, dialysis enables the temporarily affected kidneys to heal and resume normal function. In chronic renal failure however, the burden of regular dialysis is necessary unless a healthy kidney from a donor can be grafted. Chronic Renal Failure Chronic renal failure (CRF) due to glomerulonephritis, pyelonephritis or polycystic kidney disease is...

EFFICACY AND SAFETY OF SIROLIMUS IN REDUCING CYST VOLUME IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

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Sreelatha Melemadathil

2016-11-01

Full Text Available BACKGROUND Autosomal-Dominant Polycystic Kidney Disease is by far the most frequent inherited kidney disease. In White populations, its prevalence ranges from one in 400 to one in 1000 (Gabow 1993. Though the corresponding figure in Blacks is not yet available, the incidence of ESRD due to ADPKD is similar in American Blacks and Whites (Yium et al, 1994. Renoprotective interventions in ADPKD are maximal reduction of blood pressure and proteinuria and limit the effects of additional potential promoters of disease progression such as dyslipidaemia, chronic hyperglycaemia or smoking. At present, there is no definitive treatment for reducing cyst volume and hence disease progression. Sirolimus (Rapamycin is an immunosuppressant mostly used for the management of kidney transplant recipients. This drug by specifically and effectively inhibiting mTOR, exerts antiproliferative and growth inhibiting effects and could be important for the inhibition of cyst progression in ADPKD. MATERIALS AND METHODS It is an interventional randomised open label, active control study for six months. ADPKD type 1 patients between the age of 18 to 60 years with a GFR > 40 mL/min/1.73 m2 were included in the study. RESULTS Total number of subjects enrolled – 60. Patients enrolled in sirolimus arm – 40. Patients enrolled in conventional treatment arm - 20. Patients dropped out due to sirolimus side effects - 5. Patients lost to followup - 1. Patients completed treatment in conventional treatment arm - 20. CONCLUSION Treatment with mTOR inhibitor sirolimus for 6 months was effective in reducing total kidney volume, total renal cyst volume and volume of the largest cyst in patients with ADPKD. There was a small, but significant increase in renal parenchymal volume on treatment with sirolimus. Extending the duration of treatment to one year caused further significant reduction in total kidney volume and cyst volume. Major side effect of sirolimus in our patients was

Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease

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Boehn Susanne NE

2008-12-01

Full Text Available Abstract Background MicroRNAs (miRNAs play key roles in mammalian gene expression and several cellular processes, including differentiation, development, apoptosis and cancer pathomechanisms. Recently the biological importance of primary cilia has been recognized in a number of human genetic diseases. Numerous disorders are related to cilia dysfunction, including polycystic kidney disease (PKD. Although involvement of certain genes and transcriptional networks in PKD development has been shown, not much is known how they are regulated molecularly. Results Given the emerging role of miRNAs in gene expression, we explored the possibilities of miRNA-based regulations in PKD. Here, we analyzed the simultaneous expression changes of miRNAs and mRNAs by microarrays. 935 genes, classified into 24 functional categories, were differentially regulated between PKD and control animals. In parallel, 30 miRNAs were differentially regulated in PKD rats: our results suggest that several miRNAs might be involved in regulating genetic switches in PKD. Furthermore, we describe some newly detected miRNAs, miR-31 and miR-217, in the kidney which have not been reported previously. We determine functionally related gene sets, or pathways to reveal the functional correlation between differentially expressed mRNAs and miRNAs. Conclusion We find that the functional patterns of predicted miRNA targets and differentially expressed mRNAs are similar. Our results suggest an important role of miRNAs in specific pathways underlying PKD.

Vasopressin in chronic kidney disease, in particular ADPKD : Causal factor or innocent bystander?

NARCIS (Netherlands)

Zittema, Debbie

2016-01-01

Vasopressin is an important hormone for water regulation of the body. When dehydration occurs, vasopressin secretion leads to water reabsorption in the kidney to prevent water loss. However, vasopressin seems to have deleterious effects on the kidney as well. In autosomal dominant polycystic kidney

Normal kidney size and renal cortical thickness of the Korean adults

International Nuclear Information System (INIS)

Chung, Hee Kyung; Hahm, Chang Kok

1974-01-01

1. The kidney size and cortical thickness were measured from intravenous pyelograms of healthy Korean adults of 250 males and 250 females. 2. The measured size and cortical thickness of kidney were following figure (mm). 3. The size of kidney of male is a little larger than female both in vertical length and horizontal width. 4. The renal cortical thickness were not significant in differences between male and female, right and left, in each poles. 5. In the study of distribution of length differences between pairs of kidneys in our series, the length of right kidney is larger in 18.6%, and width in 27.2%. 6. Comparative study is carried out measuring the length of first lumbar vertebral bodies including 4 intervertebral spaces. 7. The site of kidney is larger in the group of greater length of vertebral height. 8. The renal cortical thickness have no significant differences in according to the differences of length of vertebral height, in each poles. 9. Comparing with the western authors, the kidney size of the Korean adult is not smaller than western

Benefits of a transfer clinic in adolescent and young adult kidney transplant patients.

Science.gov (United States)

McQuillan, Rory F; Toulany, Alene; Kaufman, Miriam; Schiff, Jeffrey R

2015-01-01

Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer

Benefits of a Transfer Clinic in Adolescent and Young Adult Kidney Transplant Patients

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Rory F. McQuillan

2015-12-01

Full Text Available Background: Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services. Objective: The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer. Methods: We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer. Results: The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03. The median change in estimated glomerular

Hypertension after bilateral kidney irradiation in young and adult rats

International Nuclear Information System (INIS)

Jongejan, H.T.; van der Kogel, A.J.; Provoost, A.P.; Molenaar, J.C.

1987-01-01

The mechanism of a rise in blood pressure after kidney irradiation is unclear but most likely of renal origin. We have investigated the role of the renin-angiotensin system and dietary salt restriction in the development of systolic hypertension after bilateral kidney irradiation in young and adult rats. Three to 12 months after a single X-ray dose of 7.5 or 12.5 Gy to both kidneys of young and adult rats, the systolic blood pressure (SBP) and plasma renin concentration (PRC) were measured regularly. A single X-ray dose of 12.5 Gy caused a moderate rise in SBP and a slight reduction in PRC in both young and adult rats. A dose of 7.5 Gy did not significantly alter the SBP or PRC during the follow-up period of 1 year. In a second experiment, the kidneys of young rats received an X-ray dose of 20 Gy. Subsequently, rats were kept on a standard diet (110 mmol sodium/kg) or a sodium-poor diet (10 mmol sodium/kg). On both diets, SBP started to rise rapidly 3 months after kidney irradiation. Sodium balance studies carried out at that time revealed an increased sodium retention in the irradiated rats compared to controls on the same diet. In rats on a low sodium intake, there was neither a delay nor an alleviation in the development of hypertension. Compared to controls, the PRC tended to be lower in irradiated rats up to 4 months after irradiation. Subsequently, malignant hypertension developed in all 20 Gy rats, resulting in pressure natriuresis, stimulating the renin-angiotensin system. Our findings indicated that hypertension after bilateral kidney irradiation was not primarily the result of an activation of the renin-angiotensin system. Although there were some indications that sodium retention played a role, dietary sodium restriction did not influence the development of hypertension

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

Science.gov (United States)

Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V K S

2016-06-01

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Fetal polycystic renal disease: prenatal sonographic findings with pathologic correlation

International Nuclear Information System (INIS)

Jun, Soon Ae; Park, Yong Hyun; Cha, Sun Hee; Kay, Jung Woong; Cho, Joo Yeon; Cha, Kwang Yul; Cha, Kyung Sub; Chi, Je G.

1990-01-01

Polycystic renal disease are congenital disorders, most of which are fatal in the postnatal period. A series of ten cases of polycystic renal disease diagnosed prenatally by ultrasonography is presented. Diagnostic criteria of ultrasonography for cystic renal disease are; 1. enlarge kidney (4 cases) 2. echogenic density of kidney (3 cases) 3. 0.4 - 0.9cm sized multiple cysts within the renal cortex (3 cases) 4. decreased amount of amniotic fluid (4 cases) 5. hydronephrosis (4 cases) 6. distended bladder (2 cases) 7. absence of bladder (2 cases) Eight of ten cases were confirmed by autopsy. Seven cases had other associated congenital anomalies, i.e. pulmonary hypoplasia (5), hepatic fibrosis (3), congenital heart disease (3), tracheoesophageal fistula with imperforate anus (1), caudal regression syndrome (1), Meckel-Gruber syndrome (1) and ambiguous genitalia (2). Additional cytogenetic study of the fetus and the careful family history taking followed by prenatal diagnosis of cystic renal disease. Precise prenatal diagnosis may allow patients the option of elective abortion or may prevent unnecessary obstetric intervention

Mutational screening of PKD2 gene in the north Indian polycystic ...

Indian Academy of Sciences (India)

Sonam Raj

2017-09-27

Sep 27, 2017 ... Polycystic kidney disease (PKD) is a systemic disorder which adds majority of renal patients to end stage renal disease. ... This study was performed using PCR and automated DNA sequencing in 84 cases and .... protein is expressed in all segments of nephron except .... patient cohort from northern India.

Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study.

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Andreas D Kistler

Full Text Available Treatment options for autosomal dominant polycystic kidney disease (ADPKD will likely become available in the near future, hence reliable diagnostic and prognostic biomarkers for the disease are strongly needed. Here, we aimed to define urinary proteomic patterns in ADPKD patients, which aid diagnosis and risk stratification. By capillary electrophoresis online coupled to mass spectrometry (CE-MS, we compared the urinary peptidome of 41 ADPKD patients to 189 healthy controls and identified 657 peptides with significantly altered excretion, of which 209 could be sequenced using tandem mass spectrometry. A support-vector-machine based diagnostic biomarker model based on the 142 most consistent peptide markers achieved a diagnostic sensitivity of 84.5% and specificity of 94.2% in an independent validation cohort, consisting of 251 ADPKD patients from five different centers and 86 healthy controls. The proteomic alterations in ADPKD included, but were not limited to markers previously associated with acute kidney injury (AKI. The diagnostic biomarker model was highly specific for ADPKD when tested in a cohort consisting of 481 patients with a variety of renal and extrarenal diseases, including AKI. Similar to ultrasound, sensitivity and specificity of the diagnostic score depended on patient age and genotype. We were furthermore able to identify biomarkers for disease severity and progression. A proteomic severity score was developed to predict height adjusted total kidney volume (htTKV based on proteomic analysis of 134 ADPKD patients and showed a correlation of r = 0.415 (p<0.0001 with htTKV in an independent validation cohort consisting of 158 ADPKD patients. In conclusion, the performance of peptidomic biomarker scores is superior to any other biochemical markers of ADPKD and the proteomic biomarker patterns are a promising tool for prognostic evaluation of ADPKD.

"An evil heritage": interview study of pain and autosomal dominant polycystic kidney disease.

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Heiwe, Susanne; Bjuke, Monica

2009-09-01

Pain is a common problem for patients with autosomal dominant polycystic kidney disease (ADPKD). Knowledge about patients' experience of the pain, pain management, and pain's effect on everyday life is, however, limited. In clinical practice there is a need to improve the care of these patients. To be able to do so, information about how the disease and its pain affect the patients is required. This study explores patients' experience of living with ADPKD and its pain. The findings are based on in-depth semistructured interviews. The participants were 22 patients with ADPKD. The data were transcribed and analyzed by using phenomenology. Findings showed that the patients experienced limitations in their everyday life due to inexplicable and unpredictable pain and fatigue. Also, pain management was experienced as suboptimal and pain was seldom discussed at health care appointments. Emotional distress concerning the hereditary nature of the disease was also present. Health care providers need to increase their focus on pain and pain management to reduce the disease's intrusion in patients' everyday life. Also, patients and people in the patients' immediate surroundings need to be given information and education about the disease and its pain as well as the opportunity to talk about their worries concerning heredity. By implementing the findings of the present study when meeting a patient with ADPKD, improved patient satisfaction and health-related quality of life could be accomplished.

Positron-emission computed tomography in cyst infection diagnosis in patients with autosomal dominant polycystic kidney disease.

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Jouret, François; Lhommel, Renaud; Beguin, Claire; Devuyst, Olivier; Pirson, Yves; Hassoun, Ziad; Kanaan, Nada

2011-07-01

Cyst infection remains a challenging issue in patients with autosomal dominant polycystic kidney disease (ADPKD). In most patients, conventional imaging techniques are inconclusive. Isolated observations suggest that (18)fluorodeoxyglucose (¹⁸FDG) positron-emission computed tomography (PET/CT) might help detect cyst infection in ADPKD patients. Comparative assessment of administrative databases from January 2005 to December 2009 identified 27 PET/CT scans performed in 24 ADPKD patients for suspicion of abdominal infection. Cyst infection was definite if confirmed by cyst fluid analysis. Cyst infection was probable if all four of the following criteria were met: temperature of >38°C for >3 days, loin or liver tenderness, C-reactive protein plasma level of >5 mg/dl, and no CT evidence for intracystic bleeding. Episodes with only two or three criteria were grouped as "fever of unknown origin". Thirteen infectious events in 11 patients met all criteria for kidney (n = 3) or liver (n = 10) cyst infection. CT was contributive in only one patient, whereas PET/CT proved cyst infection in 11 patients (84.6%). In addition, 14 episodes of "fever of unknown origin" in 13 patients were recorded. PET/CT identified the source of infection in nine patients (64.3%), including 2 renal cyst infections. Conversely, PET/CT showed no abnormal ¹⁸FDG uptake in 5 patients, including 2 intracystic bleeding. The median delay between the onset of symptoms and PET/CT procedure was 9 days. This retrospective series underscores the usefulness of PET/CT to confirm and locate cyst infection and identify alternative sources of abdominal infection in ADPKD patients.

Mutations in DZIP1L, which encodes a ciliary transition zone protein, cause autosomal recessive polycystic kidney disease

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Lu, Hao; Galeano, Maria C. Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P. Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D.; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H.; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C.; Wright, Graham D.; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A.; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten

2017-01-01

Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in the DAZ interacting protein 1-like (DZIP1L) gene in patients with ARPKD, findings we have further validated by loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and at the distal end of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. Consistent with a defect in the diffusion barrier, we found that the ciliary membrane translocation of the PKD proteins, polycystin-1 and −2, is compromised in DZIP1L mutant cells. Together, these data provide the first conclusive evidence that ARPKD is not a homogeneous disorder, and establishes DZIP1L as a second gene involved in its pathogenesis. PMID:28530676

Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.

Science.gov (United States)

Lu, Hao; Galeano, Maria C Rondón; Ott, Elisabeth; Kaeslin, Geraldine; Kausalya, P Jaya; Kramer, Carina; Ortiz-Brüchle, Nadina; Hilger, Nadescha; Metzis, Vicki; Hiersche, Milan; Tay, Shang Yew; Tunningley, Robert; Vij, Shubha; Courtney, Andrew D; Whittle, Belinda; Wühl, Elke; Vester, Udo; Hartleben, Björn; Neuber, Steffen; Frank, Valeska; Little, Melissa H; Epting, Daniel; Papathanasiou, Peter; Perkins, Andrew C; Wright, Graham D; Hunziker, Walter; Gee, Heon Yung; Otto, Edgar A; Zerres, Klaus; Hildebrandt, Friedhelm; Roy, Sudipto; Wicking, Carol; Bergmann, Carsten

2017-07-01

Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish. DZIP1L localizes to centrioles and to the distal ends of basal bodies, and interacts with septin2, a protein implicated in maintenance of the periciliary diffusion barrier at the ciliary transition zone. In agreement with a defect in the diffusion barrier, we found that the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromised in DZIP1L-mutant cells. Together, these data provide what is, to our knowledge, the first conclusive evidence that ARPKD is not a homogeneous disorder and further establish DZIP1L as a second gene involved in ARPKD pathogenesis.

Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease.

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Munoz-Garrido, Patricia; Marin, José J G; Perugorria, María J; Urribarri, Aura D; Erice, Oihane; Sáez, Elena; Úriz, Miriam; Sarvide, Sarai; Portu, Ainhoa; Concepcion, Axel R; Romero, Marta R; Monte, María J; Santos-Laso, Álvaro; Hijona, Elizabeth; Jimenez-Agüero, Raúl; Marzioni, Marco; Beuers, Ulrich; Masyuk, Tatyana V; LaRusso, Nicholas F; Prieto, Jesús; Bujanda, Luis; Drenth, Joost P H; Banales, Jesús M

2015-10-01

Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels ([Ca(2+)]i). Here, the therapeutic value of ursodeoxycholic acid (UDCA) was investigated. Effect of UDCA was examined in vitro and in polycystic (PCK) rats. Hepatic cystogenesis and fibrosis, and the bile acid (BA) content were evaluated from the liver, bile, serum, and kidneys by HPLC-MS/MS. Chronic treatment of PCK rats with UDCA inhibits hepatic cystogenesis and fibrosis, and improves their motor behaviour. As compared to wild-type animals, PCK rats show increased BA concentration ([BA]) in liver, similar hepatic Cyp7a1 mRNA levels, and diminished [BA] in bile. Likewise, [BA] is increased in cystic fluid of PLD patients compared to their matched serum levels. In PCK rats, UDCA decreases the intrahepatic accumulation of cytotoxic BA, normalizes their diminished [BA] in bile, increases the BA secretion in bile and diminishes the increased [BA] in kidneys. In vitro, UDCA inhibits the hyperproliferation of polycystic human cholangiocytes via a PI3K/AKT/MEK/ERK1/2-dependent mechanism without affecting apoptosis. Finally, the presence of glycodeoxycholic acid promotes the proliferation of polycystic human cholangiocytes, which is inhibited by both UDCA and tauro-UDCA. UDCA was able to halt the liver disease of a rat model of PLD through inhibiting cystic cholangiocyte hyperproliferation and decreasing the levels of cytotoxic BA species in the liver, which suggests the use of UDCA as a potential therapeutic tool for PLD patients. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

Science.gov (United States)

Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

2013-01-20

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

Autosomal recessive polycystic kidney disorder due to two novel compound heterozygote mutations in PKHD1 gene: case report

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Mohammad Miryounesi

2017-01-01

Full Text Available Background: Autosomal recessive polycystic kidney disorder (ARPCKD is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC. It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys. Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A. Bioinformatics tools predicted these variants to be pathogenic. Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.

CT findings in adult Wilms' tumor involving both kidneys

International Nuclear Information System (INIS)

Feijoo, R.; Lasierra, R.; Pina, J.I.; Benito, J.L.

1998-01-01

Wilms' tumor is the most common renal neoplasm during childhood, but it rarely presents in adults and even less frequently involves both kidneys at onset. The preoperative diagnosis is difficult, although it should be suspected (despite the low incidence) in cases of renal masses that contain necrotic tissue, calcification or fat. We report the case of a 32-year-old woman who presented with bilateral kidney mass and lung metastases. The patient had never complained of urinary symptoms prior to this finding. (Author) 12 refs

Enfermedad poliquística autosómica recesiva Recessive autosomal polycystic disease

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Sandalio Durán Álvarez

2007-06-01

Full Text Available Como enfermedades renales poliquísticas hereditarias se describen clásicamente la autosómica recesiva y la autosómica dominante, mal llamadas enfermedad poliquística de tipo infantily de;tipo adulto, respectivamente, pues ambas pueden verse tanto en una como en otra edad. Los conceptos cambiantes en cuanto a la enfermedad autosómica recesiva, dados por los progresos en el tratamiento de los recién nacidos con la enfermedad, y la localización del gen, que por su mutación la produce, nos motivan hacer esta breve revisión con la finalidad de contribuir a la comprensión de la enfermedad por los estudiantes de medicina y el médico general básico.Recessive autosomal and dominant autosomal polycystic kidney diseases are classically described as hereditary illnesses; they are also called polycystic disease of child type” and of adult typerespectively since both may be seen in any of these two life stages. The changing concepts of recessive autosomal disease, given the advances made in the treatment of newborns with this disease, and the location of the gen, the mutation of which causes it, encouraged us to make a brief literature review to help medical students and general practitioners to understand this disease.

Treatment of Persistent Gross Hematuria with Tranexamic Acid in Autosomal Dominant Polycystic Kidney Disease

Directory of Open Access Journals (Sweden)

Qing Yao

2017-04-01

Full Text Available Background/Aims: In this retrospective study we aimed to compare the effect of tranexamic acid (TXA vs etamsylate, two hemostatic agents, on hematuria duration in autosomal dominant polycystic kidney disease (ADPKD patients with persistent gross hematuria. Methods: This is a retrospective study of 40 patients with ADPKD and macroscopic hematuria. 20 patients receiving TXA and snake venom blood clotting enzyme injection were compared with 20 matched patients receiving etamsylate and snake venom blood clotting enzyme injection. The primary outcome was hematuria duration and the secondary outcomes were blood transfusion requirements and adverse events. Results: The hematuria duration was shorter in the TXA group compared with the etamsylate group (4[3-5] d vs 7[6-10] d, P<0.001. The volume of blood transfusion tended to be less in the TXA group than in the etamsylate group (300±115 ml vs 486±195 ml, P=0.12, and the number of patients needing a blood transfusion also tended to be lower [20% (4/20 vs 35% (7/20, P=0.29]. TXA and etamsylate were equally well tolerated and no serious adverse events were observed in both groups. Conclusions: Our study indicates that TXA treatment was more effective than etamsylate in stopping bleeding in ADPKD patients with persistent gross hematuria.

Prevalence of autosomal dominant polycystic kidney disease in the European Union.

Science.gov (United States)

Willey, Cynthia J; Blais, Jaime D; Hall, Anthony K; Krasa, Holly B; Makin, Andrew J; Czerwiec, Frank S

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease, but estimates of its prevalence vary by >10-fold. The objective of this study was to examine the public health impact of ADPKD in the European Union (EU) by estimating minimum prevalence (point prevalence of known cases) and screening prevalence (minimum prevalence plus cases expected after population-based screening). A review of the epidemiology literature from January 1980 to February 2015 identified population-based studies that met criteria for methodological quality. These examined large German and British populations, providing direct estimates of minimum prevalence and screening prevalence. In a second approach, patients from the 2012 European Renal Association‒European Dialysis and Transplant Association (ERA-EDTA) Registry and literature-based inflation factors that adjust for disease severity and screening yield were used to estimate prevalence across 19 EU countries (N = 407 million). Population-based studies yielded minimum prevalences of 2.41 and 3.89/10 000, respectively, and corresponding estimates of screening prevalences of 3.3 and 4.6/10 000. A close correspondence existed between estimates in countries where both direct and registry-derived methods were compared, which supports the validity of the registry-based approach. Using the registry-derived method, the minimum prevalence was 3.29/10 000 (95% confidence interval 3.27-3.30), and if ADPKD screening was implemented in all countries, the expected prevalence was 3.96/10 000 (3.94-3.98). ERA-EDTA-based prevalence estimates and application of a uniform definition of prevalence to population-based studies consistently indicate that the ADPKD point prevalence is <5/10 000, the threshold for rare disease in the EU. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.

Long-term effect of coffee consumption on autosomal dominant polycystic kidneys disease progression: results from the Suisse ADPKD, a Prospective Longitudinal Cohort Study.

Science.gov (United States)

Girardat-Rotar, Laura; Puhan, Milo A; Braun, Julia; Serra, Andreas L

2018-02-01

Previous in vitro experiments of human polycystic kidney disease (PKD) cells reported that caffeine is a risk factor for the promotion of cyst enlargement in patients with autosomal dominant PKD (ADPKD). The relentless progression of ADPKD inclines the majority of physicians to advocate minimization of caffeine consumption despite the absence of clinical data supporting such a recommendation so far. This is the first clinical study to assess prospectively the association between coffee consumption and disease progression in a longitudinal ADPKD cohort. Information on coffee consumption and disease progression was collected at each follow-up visit using standardized measurement methods. The main model for the outcomes, kidney size (height-adjusted total kidney volume, htTKV) and kidney function (estimated glomerular filtration rate, eGFR), was a linear mixed model. Patients entered the on-going Swiss ADPKD study between 2006 and June 2014 and had at least 1 visit every year. The sample size of the study population was 151 with a median follow-up of 4 visits per patient and a median follow-up time of 4.38 years. After multivariate adjustment for age, smoking, hypertension, sex, body mass index and an interaction term (coffee*visit), coffee drinkers did not have a statistically significantly different kidney size compared to non-coffee drinkers (difference of -33.03 cm 3 height adjusted TKV, 95% confidence interval (CI) from -72.41 to 6.34, p = 0.10). After the same adjustment, there was no statistically significant difference in eGFR between coffee and non-coffee drinkers (2.03 ml/min/1.73 m 2 , 95% CI from -0.31 to 4.31, p = 0.089). Data derived from our prospective longitudinal study do not confirm that drinking coffee is a risk factor for ADPKD progression.

Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary.

Science.gov (United States)

Pereira, Virginia M; Honorato-Sampaio, Kinulpe; Martins, Almir S; Reis, Fernando M; Reis, Adelina M

2014-10-01

Atrial natriuretic peptide (ANP) is known to regulate ovarian functions, such as follicular growth and steroid hormone production. The aim of the present study was to investigate the natriuretic peptide system in a rat model of chronic anovulation, the rat polycystic ovary. Adult female Wistar rats received a single subcutaneous injection of 2mg estradiol valerate to induce polycystic ovaries, while the control group received vehicle injection. Two months later, their ovaries were quickly removed and analyzed. Polycystic ovaries exhibited marked elevation of testosterone and estradiol levels compared to control ovaries. The levels of ANP and the expression of ANP mRNA were highly reduced in the polycystic ovaries compared to controls. By immunohistochemistry, polycystic ovaries showed weaker ANP staining in stroma, theca cells and oocytes compared to controls. Polycystic ovaries also had increased activity of neutral endopeptidase, the main proteolytic enzyme that degrades natriuretic peptides. ANP receptor C mRNA was reduced and ANP binding to this receptor was absent in polycystic ovaries. Collectively, these results indicate a downregulation of the natriuretic peptide system in rat polycystic ovary, an established experimental model of anovulation with high ovarian testosterone and estradiol levels. Together with previous evidence demonstrating that ANP inhibits ovarian steroidogenesis, these findings suggest that low ovarian ANP levels may contribute to the abnormal steroid hormone balance in polycystic ovaries. Copyright © 2014 Elsevier Inc. All rights reserved.

The Jeremiah Metzger Lecture. Polycystic kidney disease: old disease in a new context.

Science.gov (United States)

Grantham, Jared J

2002-01-01

I want to thank the organizers for inviting me to present the Jeremiah Metzger Lecture at this, the 114th meeting of the ACCA. It is a high honor, indeed, to join a list of very distinguished predecessors. And for this opportunity to tell you about my passion in medicine and science, I am most grateful. Most of you in this room have passing knowledge of polycystic kidney disease, probably hearing about it in your medical school Pathology course where you were shown an especially grotesque, enormously enlarged kidney either encased in transparent plastic or submerged in a bucket of formaldehyde. In that minute or two when PKD was discussed in lecture, you may have been told that this is a rare, hereditary disorder that causes kidney failure and that nothing can be done to alter that course. Unless you chose to specialize in General Internal Medicine or Nephrology, you may not have encountered PKD again until today, despite the fact there are approximately 600,000 PKD patients in the USA and over 10,000,000 worldwide, and it accounts for approximately 5% of non-diabetic dialysis and renal transplant patients (Table 1). I might have overlooked PKD as well had it not been for a close friend that I grew up with who had inherited the disease from his mother. He was very open about the fact that he had cysts in his kidneys that caused bleeding into the urine from time to time, especially after a solid hit during a game of tackle football. We remained friends long after I left home for college and medical school. At an early stage of my research career in medicine, while wondering how nephron segments processed glomerular filtrate, I inadvertently discovered that renal tubules could secrete as well as reabsorb salt and water. This was quite an unexpected finding at the time (1). But it occurred to [table: see text] me that this might be a means to fill renal cysts with fluid and so I decided to learn more about the pathology and pathogenesis of PKD. This didn't take long

Attitudes in Patients with Autosomal Dominant Polycystic Kidney Disease Toward Prenatal Diagnosis and Preimplantation Genetic Diagnosis.

Science.gov (United States)

Swift, Oscar; Vilar, Enric; Rahman, Belinda; Side, Lucy; Gale, Daniel P

2016-12-01

No recommendations currently exist regarding implementation of both prenatal diagnosis and preimplantation genetic diagnosis (PGD) for autosomal dominant polycystic kidney disease (ADPKD). This study evaluated attitudes in ADPKD patients with either chronic kidney disease (CKD) stages I-IV or end-stage renal failure (ESRF) toward prenatal diagnosis and PGD. Ninety-six ADPKD patients were recruited from an outpatient clinic, wards, and dialysis units. Thirty-eight patients had ESRF and 58 had CKD stages I-IV. Participants were given an information sheet on prenatal diagnosis and PGD and subsequently completed a questionnaire. The median age of participants was 51.5 years. Seventeen percent of ADPKD patients with CKD and 18% of ADPKD patients with ESRF would consider prenatal diagnosis and termination of pregnancy for ADPKD. Fifty percent with CKD would have opted for PGD (or might consider it in the future) were it available and funded by the UK National Health Service, compared to 63% in the ESRF group (p = 0.33). Sixty-nine percent in the CKD group and 68% in the ESRF group believed that PGD should be offered to other patients. There was a spectrum of attitudes among this cohort. A proportion of patients believe that PGD should be made available to prospective parents with this disease. The discrepancy between the low proportion (17% CKD, 18% ESRF) who would consider prenatal diagnosis and termination of pregnancy and the higher number who hypothetically express an intention or wish to access PGD (50% CKD and 63% ESRF) indicates far greater acceptability for diagnostic methods that occur before embryo implantation. It is not known how the development of methods to identify patients whose renal function is likely to decline rapidly and treatments altering the natural history of ADPKD will affect these attitudes.

Ursodeoxycholic acid in advanced polycystic liver disease: A phase 2 multicenter randomized controlled trial.

Science.gov (United States)

D'Agnolo, Hedwig M A; Kievit, Wietske; Takkenberg, R Bart; Riaño, Ioana; Bujanda, Luis; Neijenhuis, Myrte K; Brunenberg, Ellen J L; Beuers, Ulrich; Banales, Jesus M; Drenth, Joost P H

2016-09-01

Ursodeoxycholic acid (UDCA) inhibits proliferation of polycystic human cholangiocytes in vitro and hepatic cystogenesis in a rat model of polycystic liver disease (PLD) in vivo. Our aim was to test whether UDCA may beneficially affect liver volume in patients with advanced PLD. We conducted an international, multicenter, randomized controlled trial in symptomatic PLD patients from three tertiary referral centers. Patients with PLD and total liver volume (TLV) ⩾2500ml were randomly assigned to UDCA treatment (15-20mg/kg/day) for 24weeks, or to no treatment. Primary endpoint was proportional change in TLV. Secondary endpoints were change in symptoms and health-related quality of life. We performed a post-hoc analysis of the effect of UDCA on liver cyst volume (LCV). We included 34 patients and were able to assess primary endpoint in 32 patients, 16 with autosomal dominant polycystic kidney disease (ADPKD) and 16 with autosomal dominant polycystic liver disease (ADPLD). Proportional TLV increased by 4.6±7.7% (mean TLV increased from 6697ml to 6954ml) after 24weeks of UDCA treatment compared to 3.1±3.8% (mean TLV increased from 5512ml to 5724ml) in the control group (p=0.493). LCV was not different after 24weeks between controls and UDCA treated patients (p=0.848). However, UDCA inhibited LCV growth in ADPKD patients compared to ADPKD controls (p=0.049). UDCA administration for 24weeks did not reduce TLV in advanced PLD, but UDCA reduced LCV growth in ADPKD patients. Future studies might explore whether ADPKD and ADPLD patients respond differently to UDCA treatment. Current therapies for polycystic liver disease are invasive and have high recurrence risks. Our trial showed that the drug, ursodeoxycholic acid, was not able to reduce liver volume in patients with polycystic liver disease. However, a subgroup analysis in patients that have kidney cysts as well showed that liver cyst volume growth was reduced in patients who received ursodeoxycholic acid in comparison

Recent important strategies in the management of chronic kidney ...

African Journals Online (AJOL)

The following are discussed: the possible use of metformin in patients with type 2 diabetes-related CKD; recent inexpensive important developments in the treatment of autosomal-dominant polycystic kidney disease; prevention of acidosis and the early dietary reduction of red meat consumption; and the therapeutic lowering ...

Dioxin (TCDD induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

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Mohan Manikkam

Full Text Available Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

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Peces, Ramón; Martínez-Ara, Jorge; Peces, Carlos; Picazo, Mariluz; Cuesta-López, Emilio; Vega, Cristina; Azorín, Sebastián; Selgas, Rafael

2011-01-01

We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function. PMID:21552769

Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

Directory of Open Access Journals (Sweden)

Ramón Peces

2011-01-01

Full Text Available We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD and concomitant nephrotic syndrome secondary to membranous nephropathy (MN. A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI and an angiotensin II receptor blocker (ARB for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

Birth of a healthy infant following preimplantation PKHD1 haplotyping for autosomal recessive polycystic kidney disease using multiple displacement amplification

Science.gov (United States)

Janson, Marleen M.; Roesler, Mark R.; Avner, Ellis D.; Strawn, Estil Y.; Bick, David P.

2010-01-01

Purpose To develop a reliable preimplantation genetic diagnosis protocol for couples who both carry a mutant PKHD1 gene wishing to conceive children unaffected with autosomal recessive polycystic kidney disease (ARPKD). Methods Development of a unique protocol for preimplantation genetic testing using whole genome amplification of single blastomeres by multiple displacement amplification (MDA), and haplotype analysis with novel short tandem repeat (STR) markers from the PKHD1 gene and flanking sequences, and a case report of successful utilization of the protocol followed by successful IVF resulting in the birth of an infant unaffected with ARPKD. Results We have developed 20 polymorphic STR markers suitable for linkage analysis of ARPKD. These linked STR markers have enabled unambiguous identification of the PKHD1 haplotypes of embryos produced by at-risk couples. Conclusions We have developed a reliable protocol for preimplantation genetic diagnosis of ARPKD using single-cell MDA products for PKHD1 haplotyping. PMID:20490649

Premature aging of cardiovascular/platelet function in polycystic ovarian syndrome.

Science.gov (United States)

Chan, Wai Ping A; Ngo, Doan T; Sverdlov, Aaron L; Rajendran, Sharmalar; Stafford, Irene; Heresztyn, Tamila; Chirkov, Yuliy Y; Horowitz, John D

2013-07-01

The objective of this study was to compare the impact of aging on nitric oxide (NO) modulation of platelet and vascular function in healthy women and women with polycystic ovary syndrome. A case-control study of women ages 18 to 60 years, comparing women with polycystic ovarian syndrome against age-matched healthy controls, was performed. A total of 242 women, of whom 109 had polycystic ovarian syndrome (based on Rotterdam criteria), participated in the study. Women who were pregnant or on clopidogrel were excluded from the study. Inhibition of platelet aggregation by nitric oxide (primary outcome measure), vascular endothelial function, plasma concentrations of N(G), N(G)-dimethyl-L-arginine (ADMA), endothelial progenitor cell count, and high-sensitivity C-reactive protein (markers of endothelial dysfunction and inflammation) were assessed. With increasing age in control women, there was progressive attenuation of platelet responses to NO, impairment of endothelial function, and elevation of ADMA levels (P ≤.001). Irrespective of age, women with polycystic ovarian syndrome exhibited greater impairment of all these parameters (all P polycystic ovarian syndrome, these changes are present from early adult life and may contribute to premature atherogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

European ADPKD Forum multidisciplinary position statement on autosomal dominant polycystic kidney disease care: European ADPKD Forum and Multispecialist Roundtable participants.

Science.gov (United States)

Harris, Tess; Sandford, Richard; de Coninck, Brenda; Devuyst, Olivier; Drenth, Joost P H; Ecder, Tevfik; Kent, Alastair; Gansevoort, Ron T; Górriz, José Luis; Ong, Albert C M; Pirson, Yves; Torres, Vicente E; Budde, Klemens; Clément, Denis; Derchi, Lorenzo E; Eleftheroudi, Marianna; Levtchenko, Elena; Peters, Dorien; Van Poppel, Hendrik; Vanholder, Raymond

2017-12-22

Autosomal dominant polycystic kidney disease (ADPKD) is a chronic, progressive condition characterized by the development and growth of cysts in the kidneys and other organs and by additional systemic manifestations. Individuals with ADPKD should have access to lifelong, multidisciplinary, specialist and patient-centred care involving: (i) a holistic and comprehensive assessment of the manifestations, complications, prognosis and impact of the disease (in physical, psychological and social terms) on the patient and their family; (ii) access to treatment to relieve symptoms, manage complications, preserve kidney function, lower the risk of cardiovascular disease and maintain quality of life; and (iii) information and support to help patients and their families act as fully informed and active partners in care, i.e. to maintain self-management approaches, deal with the impact of the condition and participate in decision-making regarding healthcare policies, services and research. Building on discussions at an international roundtable of specialists and patient advocates involved in ADPKD care, this article sets out (i) the principles for a patient-centred, holistic approach to the organization and delivery of ADPKD care in practice, with a focus on multispecialist collaboration and shared-decision making, and (ii) the rationale and knowledge base for a route map for ADPKD care intended to help patients navigate the services available to them and to help stakeholders and decision-makers take practical steps to ensure that all patients with ADPKD can access the comprehensive multispecialist care to which they are entitled. Further multispecialty collaboration is encouraged to design and implement these services, and to work with patient organizations to promote awareness building, education and research. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.

Quality of life and body mass index in overweight adult women with polycystic ovary syndrome during a lifestyle modification program

OpenAIRE

De Frène, Veerle; Verhofstadt, Lesley; Lammertyn, Jan; Stuyver, Isabelle; Buysse, Ann; De Sutter, Petra

2015-01-01

Objective: To evaluate changes in body mass index (BMI) and health-related quality of life (HRQoL), including an acne parameter, of overweight adult women with polycystic ovary syndrome (PCOS) during a lifestyle modification program. Design: Prospective longitudinal within-patient study. Setting: Department of Reproductive Medicine of the Ghent University Hospital (Belgium). Participants: Thirty-three overweight (BMI >= 25 kg/m(2)) women with PCOS between age 18 and 43 years. ...

CT examination of the kidneys

International Nuclear Information System (INIS)

Handa, Youji; Ishida, Ken; Arita, Takeshi; Ishine, Kenji; Tezen, Takashi; Ohta, Nobuhiro

1985-01-01

Plain CT scanning of the kidney was performed in 16 patients with renal failure whose basic renal disorder had been not necessarily known beforehand. The findings of the CT examination were composed of renal atrophy of various degree (12 cases), cystic lesions (8 cases), polycystic renal disease (one case), nephrosclerosis (2 cases), hydronephrosis (2 cases), ureter and renal stones (one case), and normal CT profile (2 cases). Being based on these CT findings and other clinical informations, basic renal disorders could be either presumed or confirmed. It was concluded that plain CT scanning of the kidney was useful to decide a method of treatment and to estimate prognosis in patients with renal failure. (author)

Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans.

Science.gov (United States)

Magistroni, Riccardo; Boletta, Alessandra

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

DEFF Research Database (Denmark)

Ørskov, Bjarne; Feldt-Rasmussen, Bo Friis; Strandgaard, Svend Valdemar

2012-01-01

Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular......, cerebrovascular, infection, other and unknown. Results. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios...

Autosomal Dominant Polycystic Kidney Disease, incidental finding ...

African Journals Online (AJOL)

N.J. Gildenhuys

2016-06-30

Jun 30, 2016 ... This case study serves as a learning opportunity and future reference in the cases and management of ... sentation, special investigations, and treatment. The table ... trauma to an abnormal kidney is still a controversial topic. .... running into fence. AP ... He does not have any prior medical or surgical history.

Progression of autosomal dominant kidney disease: measurement of the stage transitions of chronic kidney disease

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Christopher M Blanchette

2015-04-01

Full Text Available Background: Autosomal dominant polycystic kidney disease (ADPKD is a progressive genetic disorder characterized by the development of numerous kidney cysts that result in kidney failure. Little is known regarding the key patient characteristics and utilization of healthcare resources for ADPKD patients along the continuum of disease progression. This observational study was designed to describe the characteristics of ADPKD patients and compare them with those of patients with other chronic kidney diseases. Methods: This retrospective cohort study involved patients with a claim for ADPKD or PKD unspecified from 1/1/2000–2/28/2013 and ≥6 months of previous continuous enrollment (baseline within a large database of administrative claims in the USA. A random sample of chronic kidney disease (CKD patients served as comparators. For a subset of ADPKD patients who had only a diagnosis code of unspecified PKD, abstraction of medical records was undertaken to estimate the proportion of patients who had medical chart-confirmed ADPKD. In patients with linked electronic laboratory data, the estimated glomerular filtration rate was calculated via serum creatinine values to determine CKD stage at baseline and during follow-up. Proportions of patients transitioning to another stage and the mean age at transition were calculated. Results: ADPKD patients were, in general, younger and had fewer physician visits, but had more specific comorbidities at observation start compared with CKD patients. ADPKD patients had a longer time in the milder stages and longer duration before recorded transition to a more severe stage compared with CKD patients. Patients with ADPKD at risk of rapid progression had a shorter time-to-end-stage renal disease than patients with CKD and ADPKD patients not at risk, but stage duration was similar between ADPKD patients at risk and those not at risk. Conclusions: These results suggest that distribution of patients by age at transition

Polycystic kidney disease among 4,436 intracranial aneurysm patients from a defined population.

Science.gov (United States)

Nurmonen, Heidi J; Huttunen, Terhi; Huttunen, Jukka; Kurki, Mitja I; Helin, Katariina; Koivisto, Timo; von Und Zu Fraunberg, Mikael; Jääskeläinen, Juha E; Lindgren, Antti E

2017-10-31

To define the association of autosomal dominant polycystic kidney disease (ADPKD) with the characteristics of aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (IA) disease. We fused data from the Kuopio Intracranial Aneurysm database (n = 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation. In total, there were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31% vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD (Cox regression hazard ratio 7.7, 95% confidence interval 2.8-20; p IAs in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs. © 2017 American Academy of Neurology.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

Science.gov (United States)

Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

2016-04-01

The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from adult DD to DKT recipients was 77% compared to 56% for

Functional Budd-Chiari Syndrome Associated With Severe Polycystic Liver Disease

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Precil Diego Miranda de Menezes Neves

2017-06-01

Full Text Available A 50-year-old woman with end-stage renal disease secondary to autosomal dominant polycystic kidney disease was referred to a quaternary care center due to significantly increased abdominal girth. Her physical examination revealed tense ascites and abdominal collateral veins. A 10-L paracentesis improved abdominal discomfort and disclosed a transudate, suggestive of portal hypertension. A computed tomographic scan revealed massive hepatomegaly caused by multiple cysts of variable sizes, distributed throughout all hepatic segments. Contrast-enhanced imaging uncovered extrinsic compression of hepatic and portal veins, resulting in functional Budd-Chiari syndrome and portal hypertension. Although image-guided drainage followed by sclerosis of dominant cysts could potentially lead to alleviation of the extrinsic compression, the associated significant risk of cyst hemorrhage and infection precluded this procedure. In this scenario, the decision was to submit the patient to a liver-kidney transplantation. After 1 year of this procedure, the patient maintains normal liver and kidney function and refers significant improvement in quality of life.

Src family kinases in chronic kidney disease.

Science.gov (United States)

Wang, Jun; Zhuang, Shougang

2017-09-01

Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved. Copyright © 2017 the American Physiological Society.

Affected parent sex and severity of autosomal dominant polycystic kidney disease: a retrospective cohort study
.

Science.gov (United States)

Nowak, Kristen L; Chonchol, Michel; You, Zhiying; Gupta, Malika; Gitomer, Berenice

2018-03-01

Parental inheritance may differentially affect autosomal dominant polycystic kidney disease (-ADPKD) severity via genetic imprinting or in utero epigenetic modifications; however, evidence is inconsistent. We conducted a longitudinal retrospective cohort study to assess the association between sex of the affected parent and time to hypertension diagnosis, end-stage renal disease (ESRD), and death in patients with the PKD1 genotype. 814 individuals who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was parental sex, and outcomes were diagnosis of hypertension, progression to ESRD, and death. We also examined associations in four strata according to affected parent and participant sex, as previous studies have reported earlier onset of ESRD in males compared to females. The median follow-up for each outcome was as follows: hypertension, 30 (interquartile range (IQR): 18, 37); ESRD, 43 (IQR: 31, 52), death 39 (IQR: 25, 52) years of age. Among affected offspring in the entire cohort, there was no difference in hypertension diagnosis (p = 0.97) or progression to ESRD (p = 0.79) according to affected parent sex; however, participants with an affected mother were more likely to die than participants with an affected father (p father (p < 0.01) but not when the affected parent was the mother (p ≥ 0.11). Our results are largely in contrast to the hypothesis that severity of ADPKD is worse with maternal inheritance of disease.
.

Insulin sensitizers in adolescents with polycystic ovary syndrome.

Science.gov (United States)

LE, Trang N; Wickham, Edmond P; Nestler, John E

2017-10-01

Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess in women of reproductive age. The diagnosis of PCOS can be more challenging in adolescents than in adult women given significant overlap between normal puberty and the signs of PCOS, including acne, menstrual irregularity, and polycystic ovarian morphology. Optimal treatments for adult women with PCOS vary depending on patient risk factors and reproductive goals, but mainly include hormonal contraception and insulin sensitizers. There is continued interest in targeting the intrinsic insulin resistance that contributes to metabolic and hormonal derangements associated with PCOS. The vast majority of published data on insulin sensitizing PCOS treatments are reported in adult women; these have included weight loss, metformin, thiazolidinediones, and the inositols. Furthermore, there is also a small but growing body of evidence in support of the use of insulin sensitizers in adolescents, with or without oral contraceptives. Discussion of the available treatments, including benefits, potential side effects, and incorporation of patient and family preferences is critical in developing a plan of care aimed at achieving patient-important improvements in PCOS signs and symptoms while addressing the longer-term cardiometabolic risks associated with the syndrome.

Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists.

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Adrien Flahault

Full Text Available Despite a high prevalence of intracranial aneurysm (ICA in autosomal dominant polycystic kidney disease (ADPKD, rupture events are rare. The current recommendations for ICA screening are based on expert opinions and studies with low levels of evidence.The aim of our study was to describe the attitudes of practicing nephrologists in Europe towards screening for ICA using magnetic resonance angiography (MRA.We conducted a web-based survey among 1315 European French-speaking nephrologists and nephrology residents. An anonymous, electronic questionnaire including 24 independent questions related to ICA screening modalities, indications and participant profiles was sent by email between September and December 2014. Four hundred and twenty nephrologists (mostly from France participated, including 31 nephrology residents; the response rate was 32%.Systematic screening for ICA was advocated by 28% of the nephrologists. A family history of ICA rupture, sudden death, stroke and migraine were consensual indications for screening (> 90% of the panel. In other clinical situations largely not covered by the recommendations (pregnancy, nephrectomy, kidney transplantation, cardiac or hepatic surgery, uncontrolled hypertension, lack of familial ADPKD history, at-risk activity, tobacco use, the attitudes towards screening were highly divergent. ICA screening was influenced by nephrologists experience with ADPKD and by their practice setting. The majority of participants (57% would not repeat a normal ICA screening. Only a few participants (22% knew that non-contrast MRA was the reference diagnostic tool for ICA screening, whereas most participants thought that contrast enhancement was necessary to screen for ICA. The results from the nephrology residents were analyzed separately and yielded similar results.This practice survey revealed that most nephrologists follow the current recommendations for the initial screening of ICAs. However, more than a quarter of the

Potential Deleterious Effects of Vasopressin in Chronic Kidney Disease and Particularly Autosomal Dominant Polycystic Kidney Disease

NARCIS (Netherlands)

Meijer, E.; Boertien, W. E.; Zietse, R.; Gansevoort, R. T.

2011-01-01

The antidiuretic hormone vasopressin is crucial for regulating free water clearance in normal physiology. However, it has also been hypothesized that vasopressin has deleterious effects on the kidney. Vasopressin is elevated in animals and patients with chronic kidney disease. Suppression of

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

DEFF Research Database (Denmark)

Ørskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo Friis

2012-01-01

Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular...... (HR) 0.65, P = 0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P = 0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval...

Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease

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Yu Chaowen

2011-12-01

Full Text Available Abstract Background Autosomal dominant polycystic kidney disease (ADPKD is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 (16p13.3 and PKD2 (4q21. Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC. Methods Both PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources. Results A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65. About 69% (20/29 of the mutations are first reported with a recurrent mutation rate of 31%. Conclusions Mutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.

Self-management interventions for adults with chronic kidney disease: a scoping review.

Science.gov (United States)

Donald, Maoliosa; Kahlon, Bhavneet Kaur; Beanlands, Heather; Straus, Sharon; Ronksley, Paul; Herrington, Gwen; Tong, Allison; Grill, Allan; Waldvogel, Blair; Large, Chantel A; Large, Claire L; Harwood, Lori; Novak, Marta; James, Matthew T; Elliott, Meghan; Fernandez, Nicolas; Brimble, Scott; Samuel, Susan; Hemmelgarn, Brenda R

2018-03-22

To systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD). Community-based. Adults with CKD stages 1-5 (not requiring kidney replacement therapy). Self-management strategies for adults with CKD. Using a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1-5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare. Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework. There was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence. © Article author(s) (or their employer(s) unless otherwise stated in the

Low birth weight may increase body fat mass in adult women with polycystic ovarian syndrome

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Sonia Minooee

2016-05-01

Full Text Available Background: Women engaged with polycystic ovarian syndrome (PCOS, as the commonest endocrine disorder, are known to have a specific type of adiposity. Birth weight is among different contributors reported to be responsible for this diversity. Objective: We aimed to compare the relation between birth weight and body fat mass (BFM/ body lean mass (BLM in PCOS and their age and body mass index (BMI matched normal controls. Materials and Methods: In this case-control study, a total number of 70 reproductive aged women, diagnosed with PCOS and 70 age- BMI matched healthy women without hirsutism and/or ovulatory dysfunction were recruited., control group had no polycystic ovaries in ultrasonographic scans. A detailed history of birth weight was taken and was divided into the following categories: <2,500 (low birth weight, LBW and 2,500-4,000 (normal birth weight; NBW. Results: Results showed that LBW prevalence was higher in women with PCOS than in controls (19.3% (27 vs. 15.7% (22. Also body fat and lean mass (BFM, BLM have increased in adult women with PCOS who were born underweight compared to their normal (19.8±9.05 vs. 12.9±4.5, p=0.001 and 48.9±6.9 vs. 43.2±5.8, p=0.004 respectively. Conclusion: Fetal birth weight influences on the adulthood obesity, BFM and BLM. This impact is different among women with and without PCOS

Renal cancer in kidney transplanted patients.

Science.gov (United States)

Frascà, Giovanni M; Sandrini, Silvio; Cosmai, Laura; Porta, Camillo; Asch, William; Santoni, Matteo; Salviani, Chiara; D'Errico, Antonia; Malvi, Deborah; Balestra, Emilio; Gallieni, Maurizio

2015-12-01

Renal cancer occurs more frequently in renal transplanted patients than in the general population, affecting native kidneys in 90% of cases and the graft in 10 %. In addition to general risk factors, malignancy susceptibility may be influenced by immunosuppressive therapy, the use of calcineurin inhibitors (CNI) as compared with mammalian target of rapamycin inhibitors, and the length of dialysis treatment. Acquired cystic kidney disease may increase the risk for renal cancer after transplantation, while autosomal dominant polycystic kidney disease does not seem to predispose to cancer development. Annual ultrasound evaluation seems appropriate in patients with congenital or acquired cystic disease or even a single cyst in native kidneys, and every 2 years in patients older than 60 years if they were on dialysis for more than 5 years before transplantation. Immunosuppression should be lowered in patients who develop renal cancer, by reduction or withdrawal of CNI. Although more evidence is still needed, it seems reasonable to shift patients from CNI to everolimus or sirolimus if not already treated with one of these drugs, with due caution in subjects with chronic allograft nephropathy.

In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis

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Connolly, Fiona; Rae, Michael T.; Späth, Katharina; Boswell, Lyndsey; McNeilly, Alan S.; Duncan, W. Colin

2015-01-01

Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development. PMID:26148093

Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF)

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Turkbey, Baris; Choyke, Peter L. [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); Ocak, Iclal [National Institutes of Health, Molecular Imaging Program, National Cancer Institute, Bethesda, MD (United States); University of Pittsburgh Medical Center, Department of Radiology, Pittsburgh, PA (United States); Daryanani, Kailash [National Institutes of Health, Clinical Center, Department of Radiology, Bethesda, MD (United States); Font-Montgomery, Esperanza; Lukose, Linda; Bryant, Joy; Tuchman, Maya; Gahl, William A. [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); Mohan, Parvathi [George Washington University, Department of Pediatric Gastroenterology, Washington, DC (United States); Heller, Theo [National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States); Gunay-Aygun, Meral [National Institutes of Health, National Human Genome Research Institute, Medical Genetics Branch, Bethesda, MD (United States); National Institutes of Health, Intramural Program, Office of Rare Diseases, Office of the Directors, Bethesda, MD (United States)

2009-02-15

ARPKD/CHF is an inherited disease characterized by non-obstructive fusiform dilatation of the renal collecting ducts leading to enlarged spongiform kidneys and ductal plate malformation of the liver resulting in congenital hepatic fibrosis. ARPKD/CHF has a broad spectrum of clinical presentations involving the kidney and liver. Imaging plays an important role in the diagnosis and follow-up of ARPKD/CHF. Combined use of conventional and high-resolution US with MR cholangiography in ARPKD/CHF patients allows detailed definition of the extent of kidney and hepatobiliary manifestations without requiring ionizing radiation and contrast agents. (orig.)

NCBI nr-aa BLAST: CBRC-FCAT-01-1153 [SEVENS

Lifescience Database Archive (English)

Full Text Available 1| polycystic kidney and hepatic disease 1 [Homo sapiens] emb|CAH73867.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAH72781.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI16676.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI20324.1| polycystic kidney and hepatic disease 1 (autosomal r...ecessive) [Homo sapiens] emb|CAI20233.1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_619639.3 0.0 76% ...

NCBI nr-aa BLAST: CBRC-CJAC-01-1207 [SEVENS

Lifescience Database Archive (English)

Full Text Available 1| polycystic kidney and hepatic disease 1 [Homo sapiens] emb|CAH73867.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAH72781.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI16676.1| polycystic kidney and hepatic disease 1 (autos...omal recessive) [Homo sapiens] emb|CAI20324.1| polycystic kidney and hepatic disease 1 (autosomal r...ecessive) [Homo sapiens] emb|CAI20233.1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_619639.3 0.0 87% ...

Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

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Sotiria Palimeri

2016-06-01

Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen exposure, exert a more profound negative impact on the kidney of an androgenized female rat model that mimics the metabolic characteristics of polycystic ovary syndrome.

Awareness level of kidney functions and diseases among adults in a Nigerian population

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Okwuonu, C. G.; Chukwuonye, I. I.; Ogah, S. O.; Abali, C.; Adejumo, O. A.; Oviasu, E.

2015-01-01

The prevalence of kidney diseases is on the increase in Nigeria. The cost of its management is far beyond the reach of an average patient. Prevention is thus of paramount importance and awareness of kidney diseases will help in its prevention. The aim of this study is to assess the level of awareness of kidney functions and diseases among adults in a Nigerian population. A semi-structured, researcher – administered questionnaire was the tool for data collection. Four hundred and thirty-five questionnaires were analyzed. There were 160 males (36.8%) and 275 females (63.2%). The mean age was 42.8 ± 14 years with a range of 18–78 years. Among these, 82.1% were aware of the kidneys' involvement in waste removal from the body through urine while 36% and 29% were aware of kidneys' role in blood pressure regulation and blood production, respectively. Only 26.6% correctly identified at least two basic functions of the kidneys. Also, 32.6% of the respondents were aware of at least three common causes of kidney diseases in our environment. Majority of the respondents (70.7%) did not know that kidney diseases could be inherited. Furthermore, belief in alternative therapy for kidney disease was documented in 83.2%, while unawareness of dialysis as a treatment modality was recorded in 68% of the respondents. The awareness of kidney functions and diseases among the population is poor. Measures are needed to improve this to stem the rising prevalence of chronic kidney disease in Nigeria. PMID:26060365

Outcomes of acute kidney injury in children and adults in sub-Saharan Africa: a systematic review.

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Olowu, Wasiu A; Niang, Abdou; Osafo, Charlotte; Ashuntantang, Gloria; Arogundade, Fatiu A; Porter, John; Naicker, Saraladevi; Luyckx, Valerie A

2016-04-01

Access to diagnosis and dialysis for acute kidney injury can be life-saving, but can be prohibitively expensive in low-income settings. The burden of acute kidney injury in sub-Saharan Africa is presumably high but remains unknown. We did a systematic review to assess outcomes of acute kidney injury in sub-Saharan Africa and identify barriers to care. We searched PubMed, African Journals Online, WHO Global Health Library, and Web of Science for articles published between Jan 1, 1990, and Nov 30, 2014. We scored studies, and all were of medium-to-low quality. We made a pragmatic decision to include all studies to best reflect reality, and did a descriptive analysis of extracted data. This study is registered with PROSPERO, number CRD42015015690. We identified 3881 records, of which 41 met inclusion criteria, including 1403 adult patients and 1937 paediatric patients. Acute kidney injury in sub-Saharan Africa is severe, with 1042 (66%) of 1572 children and 178 (70%) 253 of adults needing dialysis in studies reporting dialysis need. Only 666 (64%) of 1042 children (across 11 studies) and 58 (33%) of 178 adults (across four studies) received dialysis when needed. Overall mortality was 34% in children and 32% in adults, but rose to 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were out-of-pocket costs, erratic hospital resources, late presentation, and female sex. Patients in these studies are those with resources to access care. In view of overall study quality, data interpretation should be cautious, but high mortality and poor access to dialysis are concerning. The global scarcity of resources among patients and health centres highlights the need for a health-system-wide approach to prevention and management of acute kidney injury in sub-Saharan Africa. None. Copyright © 2016 Olowu et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

The diagnosis and lived experience of polycystic ovary syndrome: A qualitative study.

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Tomlinson, Julie; Pinkney, Jonathan; Adams, Linda; Stenhouse, Elizabeth; Bendall, Alison; Corrigan, Oonagh; Letherby, Gayle

2017-10-01

To explore the impact of the diagnosis of polycystic ovary syndrome on health/ill health identity, how women experience this diagnosis and their health beliefs. Polycystic ovary syndrome is a common and heterogeneous condition, giving rise to a wide range of different health concerns. Previous research on polycystic ovary syndrome has been dominated by the medical perspective and less is known about the experiences and needs of women. A qualitative study of 32 premenopausal adult women with polycystic ovary syndrome (diagnosis confirmed by Rotterdam criteria), aged between 18 and 45 years, recruited from a primary and secondary care setting. Thematic analysis of transcripts from 11 focus groups conducted between 2013-2015. Women identified a range of concerns affecting personal and reproductive identity, health knowledge and beliefs: (1) delays and barriers to diagnosis; (2) general lack of empathy by the medical profession; (3) difficulty in accessing specialist referral; (4) lack of information from professionals; (5) inconsistent and sometimes unsatisfactory experiences with medications; (6) insufficient help and advice regarding in/fertility; (7) relative lack of awareness or concern about longer term risks such as diabetes; and (8) significant discrepancies between the beliefs of women with polycystic ovary syndrome and how they experienced the attitudes of healthcare professionals. There appears to be a divergence between women's experience and attitudes of healthcare professionals. The diagnosis, support and lived experience of women with polycystic ovary syndrome could be enhanced by better professional recognition of these concerns, improved knowledge and communication about polycystic ovary syndrome and better access to support and specialist advice. © 2017 John Wiley & Sons Ltd.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide.

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Williams, Robert C; Opelz, Gerhard; Weil, E Jennifer; McGarvey, Chelsea J; Chakkera, Harini A

2017-05-01

Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets. There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation. These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

Outcomes of adult dual kidney transplants by KDRI in the United States.

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Klair, T; Gregg, A; Phair, J; Kayler, L K

2013-09-01

UNOS guidelines provide inadequate discriminatory criteria for kidneys that should be transplanted as single (SKT) versus dual (DKT). We evaluated the utility of the kidney donor risk index (KDRI) to define kidneys with better outcomes when transplanted as dual. Using SRTR data from 1995 to 2010 of de novo KTX recipients of adult deceased-donor kidneys, we examined outcomes of SKT and DKT stratified by KDRI group ≤1.4 (n = 49 294), 1.41-1.8 (n = 15 674), 1.81-2.2 (n = 6523) and >2.2 (n = 2791). DKT of kidneys with KDRI >2.2 was associated with significantly better overall graft survival [adjusted hazard ratio (aHR) 0.83, 95% confidence interval (CI) 0.72-0.96] compared to single kidneys with KDRI >2.2. DKT was associated with significantly decreased odds of delayed graft function (top 2 KDRI categories) and significantly decreased odds of 1-year serum creatinine level >2 mg/dL (top 3 KDRI categories). Among SKT and DKT from KDRI >2.2 there were 16.1 and 13.9 graft losses per 100 patient follow-up years, respectively. KDRI >2.2 is a useful discriminatory cut-off for the determination of graft survival benefit with the use of DKT; however, the benefit of increased graft years was less than half of single kidneys from donors in the same KDRI range. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Polycystic ovarian disease: animal models.

Science.gov (United States)

Mahajan, D K

1988-12-01

The reproductive systems of human beings and other vertebrates are grossly similar. In the ovary particularly, the biochemical and physiologic processes are identical not only in the formation of germ cells, the development of primordial follicles and their subsequent growth to Graafian follicles, and eventual ovulation but also in anatomic structure. In a noncarcinogenic human ovary, hypersecretion of androgen causes PCOD. Such hypersecretion may result from a nonpulsatile, constant elevated level of circulating LH or a disturbance in the action of neurotransmitters in the hypothalamus. In studying the pathophysiology of PCOD in humans, one must be aware of the limitations for manipulating the hypothalamic-pituitary axis. Although the rat is a polytocous rodent, the female has a regular ovarian cyclicity of 4 or 5 days, with distinct proestrus, estrus, and diestrus phases. Inasmuch as PCOD can be experimentally produced in the rat, that species is a good model for studying the pathophysiology of human PCOD. These PCOD models and their validity have been described: (1) estradiol-valerate, (2) DHA, (3) constant-light (LL), and (4) neonatally androgenized. Among these, the LL model is noninvasive and seems superior to the others for study of the pathophysiology of PCOD. The production of the polycystic ovarian condition in the rat by the injection of estrogens or androgens in neonate animals, or estradiol or DHA in adult rats, or the administration of antigonadotropins to these animals all cause a sudden appearance of the persistent estrus state by disturbing the metabolic and physiologic processes, whereas exposure of the adult rat to LL causes polycystic ovaries gradually, similar to what is seen in human idiopathic PCOD. After about 50 days of LL, the rat becomes anovulatory and the ovaries contain thickened tunica albuginea and many atretic follicles, and the tertiary follicles are considerably distended and cystic. The granulosa and theca cells appear normal

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

OpenAIRE

Williams, Robert C.; Opelz, Gerhard; Weil, E. Jennifer; McGarvey, Chelsea J.; Chakkera, Harini A.

2017-01-01

Background Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years. Methods Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. ...

Percutaneous Nephrolithotomy under Ultrasound Guidance in Patients with Renal Calculi and Autosomal Dominant Polycystic Kidney Disease: A Report of 11 Cases

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Xiao Wang

2017-01-01

Full Text Available Nephrolithiasis accelerates the renal failure in the patients with ADPKD. In order to evaluate the role of percutaneous nephrolithotomy in management of calculus in these patients, 11 patients with autosomal dominant polycystic kidney disease and renal stones were included in the study. Two patients had bilateral renal stones. All patients were treated by percutaneous nephrolithotomy under ultrasound guidance. 13 percutaneous nephrolithotomy procedures were performed in 1 stage by the urology team under ultrasound guidance. 5 people received second operation with flexible nephroscopy in lateral position. The success rate and morbidity and mortality of the technique and hospital stay were recorded. Results. The puncture procedure was fully successful in all cases. The renal function improved in these patients. 5 patients had moderate fever after the surgery. 5 patients received flexible nephroscopy to take out the residual calculi. 2 persons had ESWL therapy after the surgery. Conclusion. PCNL is an ideal, safe, and effective method to remove the stones from those patients with no definite increase in the risk of complication. The outcome and stone-free rate are satisfactory comparable to the PCNL in the patients without ADPKD.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

Science.gov (United States)

Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

2016-05-01

Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

Polycystic kidney disease in the medaka (Oryzias latipes pc mutant caused by a mutation in the Gli-Similar3 (glis3 gene.

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Hisashi Hashimoto

Full Text Available Polycystic kidney disease (PKD is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3 gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients.

Mini-percutaneous nephrolithotomy for stones in anomalous-kidneys: a prospective study.

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Khadgi, Sanjay; Shrestha, Babu; Ibrahim, Hamdy; Shrestha, Sunil; ElSheemy, Mohammed S; Al-Kandari, Ahmed M

2017-08-01

To evaluate safety and efficacy of minipercutaneous nephrolithotomy (Mini-PNL) in management of stones in different types of renal anomalies. Patients with stones ≥2 cm or SWL-resistant stones in anomalous-kidneys treated by Mini-PNL between March 2010 and September 2012 were included prospectively. Mini-PNL was done under regional anesthesia in prone position with fluoroscopic guidance through 18 Fr sheath using semirigid ureteroscope (8.5/11.5 Fr) and pneumatic lithotripter. All patients were followed-up for 2-3 years. Stone-free rate was defined as absence of residual fragments ≥2 mm. Student-T, Mann-Whitney, Chi square (χ 2 ), Fisher-exact, one way ANOVA or Kruskal-Wallis test were used for analysis. Mini-PNL was performed for 59 patients (20 horseshoe, 15 malrotated, 7 polycystic, 13 duplex and 4 ectopic pelvic-kidneys). Mean age was 40.18 ± 12.75 (14-78) years. Mean stone burden was 31.72 ± 21.43 (7.85-141.3) mm 2 . Two tracts were required in 7 (11.9 %) patients. Tubeless Mini-PNL with double-J insertion was performed in all patients except two. Operative time was 50.17 ± 18.73 (15-105) min. Hemoglobin loss was 0.44 ± 0.30 (0-1.4) g/dL. Complications were reported in 15 (25.4 %) patients. No pleural injury, sepsis, perinephric-collection or renal-pelvis perforation were reported. Stone-free rate was 89.8 % (converted to open-surgery in one patient, second-look PNL in two patients, auxiliary SWL in three patients). Stone-free rate improved to 98.3 % after retreatment and auxiliary SWL. Site of puncture was mostly upper calyceal in horseshoe-kidney (80 %), mid calyceal in polycystic-kidney (85.7 %) and lower calyceal in duplex-kidney (46.2 %). Punctures were also significantly infracostal in horseshoe-kidney (100 %) and supracostal in both duplex (53.8 %) and malrotated-kidneys (66.7 %). Mini-PNL is safe for management of stones in anomalous-kidney with SFR comparable to standard-PNL but with less complications.

Congenital giant megaureter associated with ipsilateral multicystic dysplastic kidney in newborn

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Rajendran Ramaswamy

2016-01-01

Full Text Available Congenital giant megaureter presents as abdominal mass and impose diagnostic difficulties. It can be associated with other upper urinary tract anomalies. A female newborn with antenatal diagnosis of polycystic kidneys was admitted at birth due to lower abdominal mass. Ultrasound and CT scans diagnosed a multiloculated cystic lesion in the mid and lower abdomen along with right side multicystic kidney. At laparotomy, an extaperitoneal, lobulated cystic swelling was found due to rightside giant megaureter. Its lower end was of normal caliber and orthotopic. End cutaneous ureterostomy was done. Intravenous urogram and isotope renograms showed nonfunctioning right kidney. She also had grade II vesicoureteral reflux on left side. Child suffered urinary infection twice. At 9m age, right nephroureterectomy was done. Histopathologic examination was consistent with cystic renal dysplasia and dilated ureter. This is the first case report of giant megaureter associated with ipsilateral multicystic dysplastic kidney in newborn.

Modeling Kidney Disease with iPS Cells

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Freedman, Benjamin S.

2015-01-01

Induced pluripotent stem cells (iPSCs) are somatic cells that have been transcriptionally reprogrammed to an embryonic stem cell (ESC)-like state. iPSCs are a renewable source of diverse somatic cell types and tissues matching the original patient, including nephron-like kidney organoids. iPSCs have been derived representing several kidney disorders, such as ADPKD, ARPKD, Alport syndrome, and lupus nephritis, with the goals of generating replacement tissue and ‘disease in a dish’ laboratory models. Cellular defects in iPSCs and derived kidney organoids provide functional, personalized biomarkers, which can be correlated with genetic and clinical information. In proof of principle, disease-specific phenotypes have been described in iPSCs and ESCs with mutations linked to polycystic kidney disease or focal segmental glomerulosclerosis. In addition, these cells can be used to model nephrotoxic chemical injury. Recent advances in directed differentiation and CRISPR genome editing enable more specific iPSC models and present new possibilities for diagnostics, disease modeling, therapeutic screens, and tissue regeneration using human cells. This review outlines growth opportunities and design strategies for this rapidly expanding and evolving field. PMID:26740740

Implications of the 2014 Androgen Excess and Polycystic Ovary Syndrome Society guidelines on polycystic ovarian morphology for polycystic ovary syndrome diagnosis

NARCIS (Netherlands)

Christ, J. P.; Gunning, M. N.; Fauser, B. C.J.M.

2017-01-01

The Androgen Excess and Polycystic Ovary Syndrome Society (AEPCOS) has recommended an updated threshold for polycystic ovarian morphology (PCOM) of 25 follicles or more, 10 ml or more of ovarian volume, or both. We describe the effect of these guidelines on reproductive and metabolic characteristics

Relationship between chronic kidney disease with diabetes or hypertension and frailty in community-dwelling Japanese older adults.

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Lee, Sungchul; Lee, Sangyoon; Harada, Kazuhiro; Bae, Seongryu; Makizako, Hyuma; Doi, Takehiko; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao; Shimada, Hiroyuki

2017-10-01

The aim of the present study was to evaluate the relationship between kidney function with concomitant diabetes or hypertension and frailty in community-dwelling Japanese older adults. The participants were 9606 residents (community-dwelling Japanese older adults) who completed baseline assessments. The estimated glomerular filtration rate (mL/min/1.73 m 2 ) was determined according to the serum creatinine level, and participants were classified into four mutually exclusive categories: ≥60.0 (normal range), 45.0-59.9, 30.0-44.9 and who met three, four or five criteria satisfied the definition of having frailty. Multivariate logistic regression was used to examine the relationships between estimated glomerular filtration rate and frailty. After multivariate adjustment, participants with lower kidney function (estimated glomerular filtration rate hypertension (OR 2.53, 95% CI 1.45-5.12) showed a significantly increased risk of frailty in the lower kidney function group, regardless of multivariate controls. Furthermore, the analyses showed an even greater increase in the risk of frailty in patients with a history of both diabetes and hypertension (OR 3.67, 95% CI 1.13-14.1) CONCLUSIONS: A lower level of kidney function was associated with a higher risk of frailty in community-dwelling Japanese older adults. Geriatr Gerontol Int 2017; 17: 1527-1533. © 2016 Japan Geriatrics Society.

Coping with missing data in phase III pivotal registration trials: Tolvaptan in subjects with kidney disease, a case study.

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Ouyang, John; Carroll, Kevin J; Koch, Gary; Li, Junfang

2017-07-01

Missing data cause challenging issues, particularly in phase III registration trials, as highlighted by the European Medicines Agency (EMA) and the US National Research Council. We explore, as a case study, how the issues from missing data were tackled in a double-blind phase III trial in subjects with autosomal dominant polycystic kidney disease. A total of 1445 subjects were randomized in a 2:1 ratio to receive active treatment (tolvaptan), or placebo. The primary outcome, the rate of change in total kidney volume, favored tolvaptan (P outline the analyses undertaken to address the issue of missing data thoroughly. "Tipping point analyses" were performed to explore how extreme and detrimental outcomes among subjects with missing data must be to overturn the positive treatment effect attained in those subjects who had complete data. Nonparametric rank-based analyses were also performed accounting for missing data. In conclusion, straightforward and transparent analyses directly taking into account missing data convincingly support the robustness of the preplanned analyses on the primary and secondary endpoints. Tolvaptan was confirmed to be effective in slowing total kidney volume growth, which is considered an efficacy endpoint by EMA, and in lessening the decline in renal function in patients with autosomal dominant polycystic kidney disease. Copyright © 2017 John Wiley & Sons, Ltd.

Quality of Life and Body Mass Index in Overweight Adult Women with Polycystic Ovary Syndrome During a Lifestyle Modification Program.

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De Frène, Veerle; Verhofstadt, Lesley; Lammertyn, Jan; Stuyver, Isabelle; Buysse, Ann; De Sutter, Petra

2015-01-01

To evaluate changes in body mass index (BMI) and health-related quality of life (HRQoL), including an acne parameter, of overweight adult women with polycystic ovary syndrome (PCOS) during a lifestyle modification program. Prospective longitudinal within-patient study. Department of Reproductive Medicine of the Ghent University Hospital (Belgium). Thirty-three overweight (BMI ≥ 25 kg/m²) women with PCOS between age 18 and 43 years. Participants followed a 24-week lifestyle modification program consisting of a diet, exercise, and psychological subprogram. BMI was assessed at Weeks 0, 8, 16, and 24 of the program. The HRQoL was measured at Week 0, 12, and 24 of the program using the PolyCystic Ovary Syndrome Questionnaire (PCOSQ) and a Visual Analogue Scale (VAS) to evaluate the influence of acne on HRQoL. During a 24-week period no significant decrease in BMI occurred (mean difference = 1.71, 95% confidence interval [CI] [-1.38, 4.81]. During that period, there was a significant positive evolution of the total PCOSQ score, F(2, 37.5) = 23.7, the emotions, F(2, 37.9) = 4.2, weight, F(2, 42.1) = 24.8, body hair, F(2, 35.6) = 3.3, and infertility problems domain scores, F(2, 43.1) = 15.64, of the PCOSQ, as well as of the acne VAS score, F(2, 29.3) = 4.2. These effects primarily occurred during the first 12 weeks. In spite of no significant changes in BMI, the HRQoL of overweight adult women with PCOS significantly improved during a 24-week lifestyle modification program. © 2015 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Sonographic analysis of adult polycystic kidney disease ...

African Journals Online (AJOL)

2014-03-24

Mar 24, 2014 ... local incidence and peculiarities in clinical and sonographic characteristics are unknown. ... Click here to download free Android application for this journal ..... as well as in the authors' country[15,16,58] must be a source.

Radiology of the kidneys in patients under maintenance hemodialysis

International Nuclear Information System (INIS)

Bahner, M.L.; Kaick, G. van; Bommer, J.; Sommerer, C.

1999-01-01

The kidneys of patients with chronic renal failure undergoing maintenance hemodialysis may show different variances or complications. Most common are secondarily acquired renal cysts, which my be found in as many as 92% of patients after 8 years of hemodialysis. Single (in 12.5% of patients) or multiple (8.3%) cysts with bleeding are common; additionally, hematuria or ruptured cysts may be found. Bleeding into cysts is more common in patients with autosomal dominant polycystic kidney disease. Due to the decreasing urinary production development of kidney stones is very uncommon, but calcification in or around cysts can be found in 71% of patients. Kidney tumors occur 41 times more often in patients with chronic renal failure than in patients without kidney disease. We detected tumors in 4.2% of our patients on long-term dialysis. Diagnostic differentiation of the relatively slow growing and fairly late metastasizing malignant tumors from adenomas is not possible. Nevertheless, we screen our patients every 3-4 years. Computed tomography is superior to ultrasonography for this purpose, because ultrasonography lacks the necessary sensitivity in this group of patients. (orig.) [de

Results of simultaneous and sequential pediatric liver and kidney transplantation.

Science.gov (United States)

Rogers, J; Bueno, J; Shapiro, R; Scantlebury, V; Mazariegos, G; Fung, J; Reyes, J

2001-11-27

The indications for simultaneous and sequential pediatric liver (LTx) and kidney (KTx) transplantation have not been well defined. We herein report the results of our experience with these procedures in children with end-stage liver disease and/or subsequent end-stage renal disease. Between 1984 and 1995, 12 LTx recipients received 15 kidney allografts. Eight simultaneous and seven sequential LTx/KTx were performed. There were six males and six females, with a mean age of 10.9 years (1.5-23.7). One of the eight simultaneous LTx/KTx was part of a multivisceral allograft. Five KTx were performed at varied intervals after successful LTx, one KTx was performed after a previous simultaneous LTx/KTx, and one KTx was performed after previous sequential LTx/KTx. Immunosuppression was with tacrolimus or cyclosporine and steroids. Indications for LTx were oxalosis (four), congenital hepatic fibrosis (two), cystinosis (one), polycystic liver disease (one), A-1-A deficiency (one), Total Parenteral Nutrition (TPN)-related (one), cryptogenic cirrhosis (one), and hepatoblastoma (one). Indications for KTx were oxalosis (four), drug-induced (four), polycystic kidney disease (three), cystinosis (one), and glomerulonephritis (1). With a mean follow-up of 58 months (0.9-130), the overall patient survival rate was 58% (7/12). One-year and 5-year actuarial patient survival rates were 66% and 58%, respectively. Patient survival rates at 1 year after KTx according to United Network of Organ Sharing (liver) status were 100% for status 3, 50% for status 2, and 0% for status 1. The overall renal allograft survival rate was 47%. Actuarial renal allograft survival rates were 53% at 1 and 5 years. The overall hepatic allograft survival rate was equivalent to the overall patient survival rate (58%). Six of seven surviving patients have normal renal allograft function, and one patient has moderate chronic allograft nephropathy. All surviving patients have normal hepatic allograft function. Six

Diabetes and Kidney Disease

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... et.al. Clinical manifestations of kidney disease among US adults with diabetes. Journal of the American Medical Association. 2016;316( ... of Washington, Associate Director, Kidney Research Institute ... The National Institute of Diabetes and Digestive and Kidney Diseases Health Information Center ...

Polycystic Ovary Syndrome FAQ

Science.gov (United States)

... Ovary Syndrome (PCOS) • What are common signs and symptoms of polycystic ovary syndrome (PCOS)? • What causes PCOS? • What is insulin resistance? • ... with PCOS? •Glossary What are common signs and symptoms of polycystic ovary syndrome (PCOS)? Common PCOS signs and symptoms include the ...

FDG-PET/CT in autosomal dominant polycystic kidney disease patients with suspected cyst infection.

Science.gov (United States)

Pijl, Jordy Pieter; Glaudemans, Andor W J M; Slart, Riemer H J A; Kwee, Thomas Christian

2018-04-13

Purpose: To determine the value of 18 F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) for diagnosing renal or hepatic cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: This retrospective single-center study included all patients with ADPKD who underwent FDG-PET/CT because of suspected cyst infection between 2010 and 2017. Results: Thirty FDG-PET/CT scans of thirty individual patients were included, of which 19 were positive for cyst infection. According to a previously established clinical and biochemical reference standard, FDG-PET/CT achieved sensitivity of 88.9%, specificity of 75.0%, positive predictive value of 84.2%, and negative predictive value of 81.8% for the diagnosis of cyst infection. In 5 cases, FDG-PET/CT suggested a different pathologic process that explained the symptoms, including pneumonia ( n = 1), generalized peritonitis ( n = 1), pancreatitis ( n = 1), colitis ( n = 1), and cholangitis ( n = 1). Total duration of hospital stay and duration between FDG-PET/CT scan and hospital discharge of patients with an FDG-PET/CT scan positive for cyst infection were significantly longer than those with a negative scan ( P = 0.005 and P = 0.009, respectively). Creatinine levels were significantly higher in patients with an FDG-PET/CT scan positive for cyst infection than in patients with a negative scan ( P = 0.015). Other comparisons of clinical parameters (age, gender, presence of fever (>38.5°C) for more than 3 days, abdominal pain, history of solid organ transplantation and nephrectomy, immune status), laboratory values (C-reactive protein level (CRP), leukocyte count, estimated glomerular filtration rate), and microbiologic results (blood and urine cultures) were not significantly different ( P = 0.13-1.00) between FDG-PET/CT-positive and -negative patients. Conclusion: FDG-PET/CT is a useful and recommendable (upfront) imaging modality for the evaluation of

The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum.

Science.gov (United States)

Rosenfield, Robert L

2015-12-01

Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities. The objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM. Adolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state. There is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.

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Lata, Sneh; Marasa, Maddalena; Li, Yifu; Fasel, David A; Groopman, Emily; Jobanputra, Vaidehi; Rasouly, Hila; Mitrotti, Adele; Westland, Rik; Verbitsky, Miguel; Nestor, Jordan; Slater, Lindsey M; D'Agati, Vivette; Zaniew, Marcin; Materna-Kiryluk, Anna; Lugani, Francesca; Caridi, Gianluca; Rampoldi, Luca; Mattoo, Aditya; Newton, Chad A; Rao, Maya K; Radhakrishnan, Jai; Ahn, Wooin; Canetta, Pietro A; Bomback, Andrew S; Appel, Gerald B; Antignac, Corinne; Markowitz, Glen S; Garcia, Christine K; Kiryluk, Krzysztof; Sanna-Cherchi, Simone; Gharavi, Ali G

2018-01-16

The utility of whole-exome sequencing (WES) for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Genetic diagnostics may be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remains unknown. To study the diagnostic utility of WES in a selected referral population of adults with CKD. Observational cohort. A major academic medical center. 92 adults with CKD of unknown cause or familial nephropathy or hypertension. The diagnostic yield of WES and its potential effect on clinical management. Whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including 9 probands with CKD of unknown cause and encompassing 13 distinct genetic disorders. Among these, loss-of-function mutations were identified in PARN in 2 probands with tubulointerstitial fibrosis. PARN mutations have been implicated in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; these findings extend the phenotype of PARN mutations to renal fibrosis. In addition, review of the American College of Medical Genetics actionable genes identified a pathogenic BRCA2 mutation in a proband who was diagnosed with breast cancer on follow-up. The results affected clinical management in most identified cases, including initiation of targeted surveillance, familial screening to guide donor selection for transplantation, and changes in therapy. The small sample size and recruitment at a tertiary care academic center limit generalizability of findings among the broader CKD population. Whole-exome sequencing identified diagnostic mutations in a substantial number of adults with CKD of many causes. Further study of the utility of WES in the evaluation and care of patients with CKD in additional settings is warranted. New York State Empire Clinical Research Investigator Program, Renal Research Institute, and National Human Genome Research Institute of the National Institutes of

Intergenerational Associations of Chronic Disease and Polycystic Ovary Syndrome

OpenAIRE

Davies, Michael J.; Marino, Jennifer L.; Willson, Kristyn J.; March, Wendy A.; Moore, Vivienne M.

2011-01-01

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. OBJECTIVE: To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. DESIGN, S...

Histological changes in kidneys of adult rats treated with Monosodium glutamate: A light microscopic study

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Singh BR, Ujwal Gajbe, Anil Kumar Reddy, Vandana Kumbhare

2015-01-01

Full Text Available Introduction: Monosodium Glutamate (MSG, which is chemically known as AJI-NO-MOTO also familiar as MSG in routine life. MSG is always considered to be a controversial food additive used in the world. It is a natural excitatory neurotransmitter, helps in transmitting the fast synaptic signals in one third of CNS. Liver and kidney play a crucial role in metabolism as well as elimination of MSG from the body. Present study is to detect structural changes in adult rat kidney tissue treated with MSG; observations are done with a light microscope. Materials & Methods: The study was conducted in the department of Anatomy, J.N.M.C, Sawangi (M Wardha. Thirty (30 adult Wistar rats (2-3 months old weighing about (200 ± 20g were used in the current study, animals were divided into three groups (Group – A, B, C. Group A: Control, Group B: 3 mg /gm body weight, Group C: 6 mg /gm body weight, MSG were administered orally daily for 45 days along with the regular diet. Observations & Results: The Mean values of animals weight at the end of experiment (46th day respectively were 251.2 ± 13, 244.4 ± 19.9 and 320 ± 31.1. Early degenerative changes like, Glomerular shrinkage (GSr, loss of brush border in proximal convoluted tubules and Cloudy degeneration was observed in sections of kidney treated with 3 mg/gm body weight of MSG. Animals treated with 6 mg/gm body weight of MSG showed rare changes like interstitial chronic inflammatory infiltrate with vacuolation in some of the glomeruli, and much glomerular shrinkage invaginated by fatty lobules. Conclusion: The effects of MSG on kidney tissues of adult rats revealed that the revelatory changes are directly proportional to the doses of MSG.

Polycystic Ovary Syndrome in Adolescents.

Science.gov (United States)

Witchel, Selma Feldman; Roumimper, Hailey; Oberfield, Sharon

2016-06-01

Polycystic ovary syndrome (PCOS) is a familial heterogeneous disorder affecting 6% to 10% of reproductive-age women. The use of criteria developed for adult women is problematic for the adolescent girl because the clinical features associated with PCOS are normal pubertal events. The recent consensus statement on PCOS in adolescents stated that hyperandrogenism and oligomenorrhea need to persist for at least 2 years to consider the diagnosis of PCOS. Although insulin resistance, hyperinsulinism, and obesity are often associated with PCOS, these features are not considered valid diagnostic criteria. Recent genomewide association studies implicate genetic loci involved in the hypothalamic-pituitary-ovarian axis. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of long-term label-retaining cells in the regeneration of adult mouse kidney after ischemia/reperfusion injury.

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Liu, Xiangchun; Liu, Haiying; Sun, Lina; Chen, Zhixin; Nie, Huibin; Sun, Aili; Liu, Gang; Guan, Guangju

2016-04-30

Label-retaining cells (LRCs) have been recognized as rare stem and progenitor-like cells, but their complex biological features in renal repair at the cellular level have never been reported. This study was conducted to evaluate whether LRCs in kidney are indeed renal stem/progenitor cells and to delineate their potential role in kidney regeneration. We utilized a long-term pulse chase of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in C57BL/6J mice to identify renal LRCs. We tracked the precise morphological characteristics and locations of BrdU(+)LRCs by both immunohistochemistry and immunofluorescence. To examine whether these BrdU(+)LRCs contribute to the repair of acute kidney injury, we analyzed biological characteristics of BrdU(+)LRCs in mice after ischemia/reperfusion (I/R) injury. The findings revealed that the nuclei of BrdU(+) LRCs exhibited different morphological characteristics in normal adult kidneys, including nuclei in pairs or scattered, fragmented or intact, strongly or weakly positive. Only 24.3 ± 1.5 % of BrdU(+) LRCs co-expressed with Ki67 and 9.1 ± 1.4 % of BrdU(+) LRCs were positive for TUNEL following renal I/R injury. Interestingly, we found that newly regenerated cells formed a niche-like structure and LRCs in pairs tended to locate in this structure, but the number of those LRCs was very low. We found a few scattered LRCs co-expressed Lotus tetragonolobus agglutinin (LTA) in the early phase of injury, suggesting differentiation of those LRCs in mouse kidney. Our findings suggest that LRCs are not a simple type of slow-cycling cells in adult kidneys, indicating a limited role of these cells in the regeneration of I/R injured kidney. Thus, LRCs cannot reliably be considered stem/progenitor cells in the regeneration of adult mouse kidney. When researchers use this technique to study the cellular basis of renal repair, these complex features of renal LRCs and the purity of real stem cells among renal LRCs should be considered.

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

Energy Technology Data Exchange (ETDEWEB)

Spithoven, E.M.; Meijer, E.; Boertien, W.E.; Gaillard, C.A.J.M.; Jong, P.E. de; Gansevoort, R.T. [University of Groningen, Department of Nephrology, Community and Occupational Medicine, University Medical Center Groningen, PO Box 30.001, RB Groningen (Netherlands); Borns, C.; Kappert, P.; Greuter, M.J.W.; Jagt, E. van der [University of Groningen, Department of Radiology, Community and Occupational Medicine, University Medical Center Groningen, Groningen (Netherlands); Vart, P. [University of Groningen, Department of Health Sciences, Community and Occupational Medicine, University Medical Center Groningen, Groningen (Netherlands)

2016-03-15

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBF{sub MRI}) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBF{sub MRI} measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBF{sub MRI}. After validation, we measured RBF{sub MRI} in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBF{sub MRI} and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBF{sub MRI} measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBF{sub MRI} compared to RBF{sub Hip,} whereas in subjects with lower eGFRs, this was significantly less for RBF{sub MRI}. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. (orig.)

Hypertension in Adults: Part 1. Prevalence, types, causes and effects

African Journals Online (AJOL)

Siegal_D

Hyper / Hypothyroidism. ▫ Acromegaly. ▫ Hyperparathyroidism. ▫ Exogenous hormones, e.g. contraceptive pills, glucocorticoids. 2. Renal causes: ▫ Glomerulonephritis. ▫ Diabetic nephropathy. ▫ Polycystic kidney disease. ▫ Renal artery stenosis. 3. Other causes: ▫ Coarctation of the aorta. ▫ Pregnancy associated hypertension.

Effec Of Low Protein Diet On Chronic Renal Failure Due To Autosomal Dominant Polycystic Kidney Disease

Directory of Open Access Journals (Sweden)

Terukuni Ideura

2012-06-01

Full Text Available There are few reports about therapeutic effects of low protein diet on the progression of chronic renal failure due to autosomal dominant polycystic kidney disease (ADPKD, although the disease is common.The annual incidence rate for end-stage renal disease caused by ADPKD is around 6 per million.In this retrospective study in one center, ten chronic renal failure patients due to ADPKD with creatinine clearnce of 17.0±3.3 mL/min /1.73 m2 and serum creatinine (Cr level of 4.4±0.7 mg/dL were studied for 40 months after the introduction of severe low protein diet (SLPD (0.48±0.03 g/kgBW/day without supplementation of essential amino acids or keto-analogues. Dietary protein intake was estimated by urea appearance rate from 24hr urine sample according to Mitch-Maroni's formula. The results clearly showed that ▵1/Cr/month(×10−3 was significantly suppressed from 5.8±0.9 to 2.0±0.6 following the introduction of SLPD (p<0.02. Furthermore, BUN/Cr ratio decreased from 10.4±0.02 to 7.3±0.02 (p<0.01. Mean blood pressure (mmHg remained unchanged; 92±3 vs 89±3 (ns, and urinary protein excretion (g/day did not change; 0.6±0.2 vs 0.6±0.1 (ns. There were no significant differences between body mass index, serum albumin, transferrin and hemoglobin levels as the indices of nutritional state before and after the introduction of SLPD.In conclusion, SLPD was effective in suppressing the progression of further decline in renal function due to ADPKD under nutritionally safety condition in this cohort.

Graded Association Between Kidney Function and Impaired Orthostatic Blood Pressure Stabilization in Older Adults.

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Canney, Mark; O'Connell, Matthew D L; Sexton, Donal J; O'Leary, Neil; Kenny, Rose Anne; Little, Mark A; O'Seaghdha, Conall M

2017-05-04

Impaired orthostatic blood pressure (BP) stabilization is highly prevalent in older adults and is a predictor of end-organ injury, falls, and mortality. We sought to characterize the relationship between postural BP responses and the kidney. We performed a cross-sectional analysis of 4204 participants from The Irish Longitudinal Study on Ageing, a national cohort of community-dwelling adults aged ≥50 years. Beat-to-beat systolic and diastolic BP were measured during a 2-minute active stand test. The primary predictor was cystatin C estimated glomerular filtration rate (eGFR) categorized as follows (mL/min per 1.73 m 2 ): ≥90 (reference, n=1414); 75 to 89 (n=1379); 60 to 74 (n=942); 45 to 59 (n=337); postural BP response merits further study in kidney disease as a potential means of identifying those at risk of hypotension-related events. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Kidney transplant survival in pediatric and young adults

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Acott Phil

2011-10-01

Full Text Available Abstract Background There is a perception that kidney transplant recipients transferred from pediatric centers to adult care have an increased risk of graft loss. It is not clear whether young adults transplanted in adult centers also suffer from high graft loss rates. Methods We examined death censored graft survival in 3 cohorts of young patients transplanted at a single center. Pediatric (PED patients transplanted at the pediatric center were compared to a cohort of young adults (YAD; age 18- Results In a multivariate Cox model for death-censored graft survival, PED survival was statistically similar to the YAD (HR 0.86, 95% CI 0.44, 1.7, p = 0.66, however the ADL cohort (HR 0.45, 95% CI 0.25, 0.82, p = 0.009 demonstrated better survival. Admitted non-adherence rates were not different among cohorts. Patients were transferred within a narrow age window (18.6 ± 1.0 age in years but at a wide range of times from the date of transplantation (5.1 ± 3.5 years and with a wide range of graft function (serum creatinine 182 ± 81 μmol/L. Conclusions The perception that pediatric transfers do poorly reflects advanced graft dysfunction in some at the time of transfer. The evidence also suggests that it is not the transfer of care that is the critical issue but rather recipients, somewhere between the ages of 11-14 and 25, are a unique and vulnerable cohort. Effective strategies to improve outcomes across this age group need to be identified and applied consistently.

The Content and Quality of Health Information on the Internet for Patients and Families on Adult Kidney Cancer.

Science.gov (United States)

Alsaiari, Ahmed; Joury, Abdulaziz; Aljuaid, Mossab; Wazzan, Mohammed; Pines, Jesse M

2017-12-01

The Internet is one of the major sources for health information for patients and their families, particularly when patients face serious life-threatening conditions such as kidney cancer in adults. In this study, we evaluate the content and quality of health information on adult kidney cancer using several validated instruments. We accessed the three most popular search engines (Google, Yahoo, Bing), using two terms: "kidney cancer" and "renal cell carcinoma," and reviewed the top 30 hits. After exclusion of duplicated websites, websites targeting health care professionals, and unrelated websites, 35 websites were included. Content was assessed using a 22-item checklist adapted from the American Cancer Society. We assessed website quality using the DISCERN questionnaire, HONcode and JAMA benchmark criteria, readability using three readability scores, and ALEXA for global traffic ranking systems. The average website had 16 of 22 content items while 6 websites fulfilled all 22 items. Among all websites, the average DISCERN quality score was 42 out of 80, 15 (42.8 %) of websites had HONcode certification, and only 3 (8.5 %) fulfilled all JAMA benchmark criteria. The average website readability was at the ninth grade reading level. The content and quality of health-related information on the Internet for adult kidney cancer are variable in comprehensiveness and quality. Many websites are difficult to read without a high school education. A standardized approach to presenting cancer information on the Internet for patients and families may be warranted.

Role of Integrin-Beta1 in Polycystic Kidney Disease

Science.gov (United States)

2012-04-01

interactions affect proliferation and cell differentiation2. We previously showed an increase of integrin-!2ŕ expression in polycystin-1 (PC1) deficient...that since the Cre activity in TgAqp2-Cre transgenic mouse was observed also in testes, our breeding scheme was devised to ensure maternal ...inheritance of the transgene, as paternal transmission would lead to gene recombination not only in the kidneys, but also in sperm and the resulting

Kidney (Renal Cell) Cancer—Patient Version

Science.gov (United States)

Kidney cancer can develop in adults and children. The main types of kidney cancer are renal cell cancer, transitional cell cancer, and Wilms tumor. Certain inherited conditions increase the risk of kidney cancer. Start here to find information on kidney cancer treatment, research, and statistics.

Averting the Legacy of Kidney Disease—Focus on Childhood

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Julie R. Ingelfinger

2016-02-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. “For in every adult there dwells the child that was, and in every child there lies the adult that will be.”—John Connolly, The Book of Lost Things.

Aberrant Smad3 phosphoisoforms in cyst-lining epithelial cells in the cpk mouse, a model of autosomal recessive polycystic kidney disease.

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Hama, Taketsugu; Nakanishi, Koichi; Sato, Masashi; Mukaiyama, Hironobu; Togawa, Hiroko; Shima, Yuko; Miyajima, Masayasu; Nozu, Kandai; Nagao, Shizuko; Takahashi, Hisahide; Sako, Mayumi; Iijima, Kazumoto; Yoshikawa, Norishige; Suzuki, Hiroyuki

2017-12-01

Cystic epithelia acquire mesenchymal-like features in polycystic kidney disease (PKD). In this phenotypic alteration, it is well known that transforming growth factor (TGF)-β/Smad3 signaling is involved; however, there is emerging new data on Smad3 phosphoisoforms: Smad3 phosphorylated at linker regions (pSmad3L), COOH-terminal regions (pSmad3C), and both (pSmad3L/C). pSmad3L/C has a pathological role in colorectal cancer. Mesenchymal phenotype-specific cell responses in the TGF-β/Smad3 pathway are implicated in carcinomas. In this study, we confirmed mesenchymal features and examined Smad3 phosphoisoforms in the cpk mouse, a model of autosomal recessive PKD. Kidney sections were stained with antibodies against mesenchymal markers and domain-specific phospho-Smad3. TGF-β, pSmad3L, pSmad3C, JNK, cyclin-dependent kinase (CDK) 4, and c-Myc were evaluated by Western blotting. Cophosphorylation of pSmad3L/C was assessed by immunoprecipitation. α-Smooth muscle actin, which indicates mesenchymal features, was expressed higher in cpk mice. pSmad3L expression was increased in cpk mice and was predominantly localized in the nuclei of tubular epithelial cells in cysts; however, pSmad3C was equally expressed in both cpk and control mice. Levels of pSmad3L, JNK, CDK4, and c-Myc protein in nuclei were significantly higher in cpk mice than in controls. Immunoprecipitation showed that Smad3 was cophosphorylated (pSmad3L/C) in cpk mice. Smad3 knockout/ cpk double-mutant mice revealed amelioration of cpk abnormalities. These findings suggest that upregulating c-Myc through the JNK/CDK4-dependent pSmad3L pathway may be key to the pathophysiology in cpk mice. In conclusion, a qualitative rather than a quantitative abnormality of the TGF-β/Smad3 pathway is involved in PKD and may be a target for disease-specific intervention. Copyright © 2017 the American Physiological Society.

Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

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Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

2012-12-01

The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Resistive index for kidney evaluation in normal and diseased cats.

Science.gov (United States)

Tipisca, Vlad; Murino, Carla; Cortese, Laura; Mennonna, Giuseppina; Auletta, Luigi; Vulpe, Vasile; Meomartino, Leonardo

2016-06-01

The objectives were to determine the resistive index (RI) in normal cats and in cats with various renal diseases, and to evaluate the effect of age on RI. The subjects were cats that had ultrasonography (US) of the urinary tract and RI measurement at our centre between January 2003 and April 2014. Based on clinical evaluation, biochemical and haematological tests, urinalysis and US, the cats were classified as healthy or diseased. RI measurements were made from the interlobar or arcuate arteries. Data were analysed for differences between the right and the left kidney, the two sexes, different age groups in healthy cats, and between healthy and diseased cats. A total of 116 cats (68 males, 48 females) were included: 24 healthy and 92 diseased. In the healthy cats, RI (mean ± SD) differed significantly (P = 0.02) between the right kidney (0.54 ± 0.07) and the left kidney (0.59 ± 0.08). For the left kidney, RI was significantly higher in cats with chronic kidney disease (0.73 ± 0.12) and acute kidney injury (0.72 ± 0.08) (P = 0.0008). For the right kidney, RI was significantly higher in cats with chronic kidney disease (0.72 ± 0.11), acute kidney injury (0.74 ± 0.08), polycystic kidney disease (0.77 ± 0.11) and renal tumour (0.74 ± 0.001) (P cats, useful in the differential diagnosis of diffuse renal diseases. While it does not change with the age of the cat, ultrasonographers should be aware that RI may differ between the two kidneys. © ISFM and AAFP 2015.

Higher protein intake is not associated with decreased kidney function in pre-diabetic older adults following a one-year intervention

DEFF Research Database (Denmark)

Møller, Grith; Andersen, Jens Rikardt; Ritz, Christian

2018-01-01

Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic...... intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults....

An observational study of health literacy and medication adherence in adult kidney transplant recipients.

Science.gov (United States)

Demian, Maryam N; Shapiro, R Jean; Thornton, Wendy Loken

2016-12-01

There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Kidney recipients who were at least 6 months post-transplant and outpatients of Vancouver General Hospital in B.C., Canada were recruited through invitation letters. A total of 96 recipients completed the Health Literacy Questionnaire, which provides a multifactorial profile of self-reported health literacy and the Transplant Effects Questionnaire-Adherence subscale measuring self-reported immunosuppressant adherence. Hierarchical linear regression was used to analyze the association between health literacy and adherence after controlling for identified risk factors of non-adherence. Our sample was on average 53 years old, 56% male and 9 years post-transplant. Kidney recipients reported low levels of health literacy on scales measuring active health management and critical appraisal of information and 75% reported non-perfect adherence. Worse adherence was associated with poorer overall health literacy (Δ R 2 = 0.08, P = 0.004) and lower scores on six of nine of the health literacy factors. Poorer health literacy is associated with lower immunosuppressant adherence in adult kidney transplant recipients suggesting the importance of considering a recipient's level of health literacy in research and clinical contexts. Medication adherence interventions can target the six factors of health literacy identified as being risk factors for lower medication adherence.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands

NARCIS (Netherlands)

Dobrowolski, Linn C; van Huis, Maike; van der Lee, Johanna H; Peters Sengers, Hessel; Liliën, Marc R; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H; de Fijter, Johan W; Berger, Stefan P; van Zuilen, Arjan; Nurmohamed, Shaikh A; Betjes, Michiel H G; Hilbrands, Luuk; Hoitsma, Andries J; Bemelman, Frederike J; Krediet, C T Paul; Groothoff, Jaap W

2016-01-01

INTRODUCTION: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the

NCBI nr-aa BLAST: CBRC-FCAT-01-1153 [SEVENS

Lifescience Database Archive (English)

Full Text Available .1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAH72782.1| polycystic ...kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAI16677.1| polycystic kidney and hepatic disease 1 (autos...ney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_733842.2 0.0 76% ...

NCBI nr-aa BLAST: CBRC-CJAC-01-1207 [SEVENS

Lifescience Database Archive (English)

Full Text Available .1| polycystic kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAH72782.1| polycystic ...kidney and hepatic disease 1 (autosomal recessive) [Homo sapiens] emb|CAI16677.1| polycystic kidney and hepatic disease 1 (autos...ney and hepatic disease 1 (autosomal recessive) [Homo sapiens] NP_733842.2 0.0 87% ...

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

Science.gov (United States)

Sarathy, Harini; Henriquez, Gabriela; Abramowitz, Matthew K; Kramer, Holly; Rosas, Sylvia E; Johns, Tanya; Kumar, Juhi; Skversky, Amy; Kaskel, Frederick; Melamed, Michal L

2016-01-01

Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity. We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria. Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4%) versus Mexican-Americans (40.6%) or non-Hispanic whites (37.4%) (P-value = 0.004). Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2), p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease. Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.

Abdominal Obesity, Race and Chronic Kidney Disease in Young Adults: Results from NHANES 1999-2010.

Directory of Open Access Journals (Sweden)

Harini Sarathy

Full Text Available Kidney dysfunction in obesity may be independent of and may precede the development of hypertension and/or diabetes mellitus. We aimed to examine if abdominal obesity is associated with early markers of CKD in a young healthy population and whether these associations differ by race and/or ethnicity.We analyzed data from the NHANES 1999-2010 for 6918 young adults ages 20-40 years. Abdominal obesity was defined by gender criteria of waist circumference. CKD markers included estimated glomerular filtration rate and albuminuria ≥30 mg/g. Race stratified analyses were done overall and in subgroups with normal blood pressures, normoglycemia and normal insulin sensitivity. Awareness of CKD was assessed in participants with albuminuria.Abdominal obesity was present in over one-third of all young adults and was more prevalent among non-Hispanic blacks (45.4% versus Mexican-Americans (40.6% or non-Hispanic whites (37.4% (P-value = 0.004. Mexican-American young adults with abdominal obesity had a higher odds of albuminuria even among those with normal blood pressure, normal glucose, and normal insulin sensitivity [adjusted odds ratio 4.5; 95% confidence interval (1.6-12.2, p = 0.004]. Less than 5% of young adults with albuminuria of all races and ethnicities had been told they had kidney disease.Abdominal obesity in young adults, especially in Mexican-Americans, is independently associated with albuminuria even with normal blood pressures, normoglycemia and normal insulin levels. Greater awareness of CKD is needed to protect this young population from long-standing exposure to abdominal obesity and early progressive renal disease.

Averting the legacy of kidney disease – focus on childhood

Directory of Open Access Journals (Sweden)

Julie R. Ingelfinger

2016-03-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Averting the legacy of kidney disease: focus on childhood

Science.gov (United States)

Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

2016-01-01

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:28031959

Averting the legacy of kidney disease - focus on childhood

Directory of Open Access Journals (Sweden)

J.R. Ingelfinger

2016-01-01

Full Text Available World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Community-acquired acute kidney injury in adults in Africa.

Science.gov (United States)

Adu, Dwomoa; Okyere, Perditer; Boima, Vincent; Matekole, Michael; Osafo, Charlotte

We review recent published data on demographics, causes, diagnoses, treatment, and outcome of acute kidney injury (AKI) in Africa. A review of the incidence, etiology, diagnoses, and treatment of AKI in adults in Africa from studies published between the years 2000 and 2015. The incidence of AKI in hospitalized patients in Africa ranges from 0.3 to 1.9% in adults. Between 70 and 90% of cases of AKI are community acquired. Most patients with AKI are young with a weighted mean age of 41.3 standard deviation (SD) 9.3 years, and a male to female ratio of 1.2 : 1.0. Medical causes account for between 65 and 80% of causes of AKI. This is followed by obstetric causes in 5 - 27% of cases and surgical causes in 2 - 24% of cases. In the reported studies, between 17 and 94% of patients who needed dialysis received this. The mortality of AKI in adults in Africa ranged from 11.5 to 43.5%. Most reported cases of AKI in Africa originate in the community. The low incidence of hospital-acquired AKI is likely to be due to under ascertainment. Most patients with AKI in Africa are young and have a single precipitating cause. Prominent among these are infection, pregnancy complications and nephrotoxins. Early treatment can improve clinical outcomes.

Prediction of polycystic ovarian syndrome based on ultrasound findings and clinical parameters.

Science.gov (United States)

Moschos, Elysia; Twickler, Diane M

2015-03-01

To determine the accuracy of sonographic-diagnosed polycystic ovaries and clinical parameters in predicting polycystic ovarian syndrome. Medical records and ultrasounds of 151 women with sonographically diagnosed polycystic ovaries were reviewed. Sonographic criteria for polycystic ovaries were based on 2003 Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine guidelines: at least one ovary with 12 or more follicles measuring 2-9 mm and/or increased ovarian volume >10 cm(3) . Clinical variables of age, gravidity, ethnicity, body mass index, and sonographic indication were collected. One hundred thirty-five patients had final outcomes (presence/absence of polycystic ovarian syndrome). Polycystic ovarian syndrome was diagnosed if a patient had at least one other of the following two criteria: oligo/chronic anovulation and/or clinical/biochemical hyperandrogenism. A logistic regression model was constructed using stepwise selection to identify variables significantly associated with polycystic ovarian syndrome (p polycystic ovaries and 115 (89.8%) had polycystic ovarian syndrome (p = .009). Lower gravidity, abnormal bleeding, and body mass index >33 were significant in predicting polycystic ovarian syndrome (receiver operating characteristics curve, c = 0.86). Pain decreased the likelihood of polycystic ovarian syndrome. Polycystic ovaries on ultrasound were sensitive in predicting polycystic ovarian syndrome. Ultrasound, combined with clinical parameters, can be used to generate a predictive index for polycystic ovarian syndrome. © 2014 Wiley Periodicals, Inc.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands

NARCIS (Netherlands)

Dobrowolski, Linn C.; van Huis, Maike; van der Lee, Johanna H.; Sengers, Hessel Peters; Lilien, Marc R.; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H.; de Fijter, Johan W.; Berger, Stefan P.; van Zuilen, Arjan; Nurmohamed, Shaikh A.; Betjes, Michiel H. G.; Hilbrands, Luuk; Hoitsma, Andries J.; Bemelman, Frederike J.; Krediet, Paul; Groothoff, Jaap W.

2016-01-01

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from

Impact of end-stage kidney disease on academic achievement and employment in young adults: a mixed methods study.

Science.gov (United States)

Murray, Peter D; Dobbels, Fabienne; Lonsdale, Daniel C; Harden, Paul N

2014-10-01

Young adult kidney patients are at an important stage of development when end-stage kidney disease (ESKD) may adversely influence progress in education and employment. This study is designed to assess the impact of ESKD on education and employment outcomes in young adults. This cross-sectional study was a mixed methods design. Education and career achievements in young adults with ESKD were recorded quantitatively using a questionnaire survey (n = 57): 14 of 57 representative participants were subsequently selected for semistructured interview. Questionnaire survey was conducted in 57 young adults (median age 25): 8.8% (n = 5) were predialysis; 14.0% (n = 8) dialysis; and 78.9% (n = 45) were kidney transplant recipients. Median school-leaving age was 16 (interquartile range = 15-19). Of 57 young adults, 10 (17.5%) were still studying, 43 (75.4%) had completed education, 34 (59.7%) were employed (23 full time and 11 part time), and 19 (33.3%) were unemployed. Twenty-seven of 45 transplanted patients were employed (60.0%). Of these 27, 21 were full time (77.8%). Five of eight dialysis patients were employed: only one of eight was full-time employed (12.5%). Themes impacting on education and employment included low energy levels, time missed, loss of self-esteem, and feelings of loneliness and isolation, which may progress to depression and recreational drug use. Lack of understanding from educators and employers resulting in lost work, and career ambitions changed or limited because of dialysis. Dialysis has a major negative impact on education and reduced employment rates of young adults. There is a general lack of understanding among educators and employers of the impact of ESKD. Low energy levels, lack of self-esteem, and depression are key factors. There is a need for health care providers to recognize this issue and invest in supporting young adults with ESKD. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights

Polycystic ovary syndrome and metformin in pregnancy

DEFF Research Database (Denmark)

Lilja, Anna E; Mathiesen, Elisabeth R

2006-01-01

UNLABELLED: The diagnostic criteria of polycystic ovary syndrome incorporate hyperandrogenism, polycystic ovaries, anovulation and irregular menstrual bleeding and the syndrome is a recognized reason behind infertility. The biguanide metformin has encouraging effects on several metabolic aspects...... of the syndrome, including insulin sensitivity, plasma glucose concentration and lipid profile. Moreover, metformin improves the ovarian function in women diagnosed with polycystic ovary syndrome. Hence, metformin is considered an agent for ovulation induction among these patients. However, even higher ovulation...

9-Hydroxyprostaglandin dehydrogenase activity in the adult rat kidney. Regional distribution and sub-fractionation.

Science.gov (United States)

Asciak, C P; Domazet, Z

1975-02-20

1. Catabolism of prostaglandin F2alpha in the adult rat kidney takes place by the following sequence of enzymatic steps: (1) 15-hydroxyprostaglandin dehydrogenase; (2) prostaglandin delta13-reductase; and (3) 9-hydroxyprostaglandin dehydrogenase. 2. 9-Hydroxyprostaglandin dehydrogenase activity was highest in the cortex with lesser amounts in the medulla and negligible activity detected in the papilla. A similar distribution was observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 3. Most of the 9-hydroxyprostaglandin dehydrogenase activity in the homogenate was found in the high-speed supernatant as also observed for 15-hydroxyprostaglandin dehydrogenase and prostaglandin delta13-reductase. 4. These observations indicate that the rat kidney contains an abundance of prostaglandin-catabolising enzymes which favour formation of metabolites of the E-type.

MAGIC Study: Aims, Design and Methods using SystemCHANGE™ to Improve Immunosuppressive Medication Adherence in Adult Kidney Transplant Recipients.

Science.gov (United States)

Russell, Cynthia L; Moore, Shirley; Hathaway, Donna; Cheng, An-Lin; Chen, Guoqing; Goggin, Kathy

2016-07-16

Among adult kidney transplant recipients, non-adherence to immunosuppressive medications is the leading predictor of poor outcomes, including rejection, kidney loss, and death. An alarming one-third of kidney transplant patients experience medication non-adherence even though the problem is preventable. Existing adherence interventions have proven marginally effective for those with acute and chronic illnesses and ineffective for adult kidney transplant recipients. Our purpose is to describe the design and methods of the MAGIC (Medication Adherence Given Individual SystemCHANGE™) trial We report the design of a randomized controlled trial with an attention-control group to test an innovative 6-month SystemCHANGE™ intervention designed to enhance immunosuppressive medication adherence in adult non-adherent kidney transplant recipients from two transplant centers. Grounded in the Socio-Ecological Model, SystemCHANGE™ seeks to systematically improve medication adherence behaviors by identifying and shaping routines, involving supportive others in routines, and using medication taking feedback through small patient-led experiments to change and maintain behavior. After a 3-month screening phase of 190 eligible adult kidney transplant recipients, those who are adherent as measured by electronic monitoring, will be randomized into a 6-month SystemCHANGE™ intervention or attention-control phase, followed by a 6-month maintenance phase without intervention or attention. Differences in adherence between the two groups will be assessed at baseline, 6 months (intervention phase) and 12 months (maintenance phase). Adherence mediators (social support, systems-thinking) and moderators (ethnicity, perceived health) are examined. Patient outcomes (creatinine/blood urea nitrogen, infection, acute/chronic rejection, graft loss, death) and cost effectiveness are to be examined. Based on the large effect size of 1.4 found in our pilot study, intervention shows great promise

Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and hospitalization in older adults receiving hemodialysis.

Science.gov (United States)

Hall, Rasheeda K; Luciano, Alison; Pieper, Carl; Colón-Emeric, Cathleen S

2018-01-15

For older adults receiving dialysis, health-related quality of life is not often considered in prognostication of death or future hospitalizations. To determine if routine health-related quality of life measures may be useful for prognostication, the objective of this study is to determine the extent of association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse outcomes in older adults receiving dialysis. This is a longitudinal study of 3500 adults aged ≥75 years receiving dialysis in the United States in 2012 and 2013. We used Cox and Fine and Gray models to evaluate the association of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for sociodemographic variables, hemodialysis access type, laboratory values, and Charlson index. Three thousand one hundred thirty-two hemodialysis patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880 (28.1%) died and 2023 (64.6%) had at least one hospitalization over a median follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical component summary (PCS) in the lowest quintile had an increased adjusted risk of death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in the highest quintile. Cohort members with a SF-12 mental component summary in the lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17-1.65) compared with those in the highest quintile. In adjusted analyses, there was no association between the symptoms of kidney disease, effects of kidney disease, and burden of kidney disease subscales with time to death or first hospitalization. Competing risk models showed similar HRs. Among the KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with both death and future hospitalizations in older adults receiving hemodialysis Further research is needed to assess the value this subscale may add

Nuclear magnetic resonance imaging of the kidney

International Nuclear Information System (INIS)

Hricak, H.; Crooks, L.; Sheldon, P.; Kaufman, L.

1983-01-01

The role of nuclear magnetic resonance (NMR) imaging of the kidney was analyzed in 18 persons (6 normal volunteers, 3 patients with pelvocaliectasis, 2 with peripelvic cysts, 1 with renal sinus lipomatosis, 3 with renal failure, 1 with glycogen storage disease, and 2 with polycystic kidney disease). Ultrasound and/or computed tomography (CT) studies were available for comparison in every case. In the normal kidney distinct anatomical structures were clearly differentiated by NMR. The best anatomical detail ws obtained with spin echo (SE) imaging, using a pulse sequence interval of 1,000 msec and an echo delay time of 28 msec. However, in the evaluation of normal and pathological conditions, all four intensity images (SE 500/28, SE 500/56, SE 1,000/28, and SE 1,000/56) have to be analyzed. No definite advantage was found in using SE imaging with a pulse sequence interval of 1,500 msec. Inversion recovery imaging enhanced the differences between the cortex and medulla, but it had a low signal-to-noise level and, therefore, a suboptimal overall resolution. The advantages of NMR compared with CT and ultrasound are discussed, and it is concluded that NMR imaging will prove to be a useful modality in the evaluation of renal disease

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

Science.gov (United States)

Schrem, Harald; Schneider, Valentin; Kurok, Marlene; Goldis, Alon; Dreier, Maren; Kaltenborn, Alexander; Gwinner, Wilfried; Barthold, Marc; Liebeneiner, Jan; Winny, Markus; Klempnauer, Jürgen; Kleine, Moritz

2016-01-01

The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers. 1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs) of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences. Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21). Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46), post-transplant lymphoproliferative disorder (SIR = 8.36), prostate cancer (SIR = 2.22), bladder cancer (SIR = 3.24), thyroid cancer (SIR = 10.13) and melanoma (SIR = 3.08). Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29), polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD) (p = 0.001, HR: 0.68), high body mass index in kg/m2 (pKaizen events and audits for root-cause analysis of relevant detection rate changes. Further, comparative G-chart analysis would enable benchmarking of cancer surveillance processes between centers.

Hypertension after kidney transplantation

NARCIS (Netherlands)

Dobrowolski, L.C.

2016-01-01

Hypertension increases the cardiovascular risk in kidney transplant recipients (KTRs). In chapter 2 we found that hypertension was highly prevalent in adult (77.2%), paediatric (62.7%) and young adult (86.4%) KTRs. Transition from the paediatric to adult care did not affect hypertension and there

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease.

Science.gov (United States)

Spithoven, E M; Meijer, E; Borns, C; Boertien, W E; Gaillard, C A J M; Kappert, P; Greuter, M J W; van der Jagt, E; Vart, P; de Jong, P E; Gansevoort, R T

2016-03-01

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. Renal blood flow (RBF) can be accurately measured by phase-contrast MRI in ADPKD patients. RBF measured by phase-contrast is associated with ADPKD disease severity. RBF measurement by phase-contrast MRI may be less feasible in patients with an impaired eGFR.

Optimal management of subfertility in polycystic ovary syndrome

OpenAIRE

Berger, Joshua J; Bates, G Wright

2014-01-01

Joshua J Berger, G Wright Bates JrUniversity of Alabama at Birmingham, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Birmingham, AL, USAAbstract: The purpose of this paper is to provide a stepwise approach to treating the infertility/subfertility associated with polycystic ovary syndrome. Defining polycystic ovary syndrome in a patient requires first investigating other possible causes for polycystic ovary morphology, acne, hirsutism, obesity...

Epidemiology, diagnosis, and management of polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Sirmans SM

2013-12-01

Full Text Available Susan M Sirmans, Kristen A PateDepartment of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USAAbstract: Polycystic ovary syndrome (PCOS is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.Keywords: polycystic ovary syndrome

Optimal management of subfertility in polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Berger JJ

2014-06-01

Full Text Available Joshua J Berger, G Wright Bates JrUniversity of Alabama at Birmingham, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Birmingham, AL, USAAbstract: The purpose of this paper is to provide a stepwise approach to treating the infertility/subfertility associated with polycystic ovary syndrome. Defining polycystic ovary syndrome in a patient requires first investigating other possible causes for polycystic ovary morphology, acne, hirsutism, obesity, and the metabolic derangements that often accompany polycystic ovary syndrome. Beginning with lifestyle modification and use of metformin, the progressive inclusion of more intensive therapies for induction of ovulation is described. Second-line treatments are discussed and the new findings from a large multicenter trial are discussed in the context of evidence-based treatment strategies for first-line agents. Finally, monofollicular development as a treatment goal and in vitro fertilization are discussed for those with recalcitrant disease.Keywords: polycystic ovary syndrome, infertility, metformin, ovarian drilling, ovulation induction, subfertility

Polycystic Ovary Induction in Mouse by Testosterone Enanthate

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Zahra Kalhori

2014-03-01

Full Text Available Background &Objective: Polycystic ovary is the most common cause of infertility in Women. Animal models are required for understanding the pathogenesis of polycystic ovary. The objective of this study then was to develop an animal model for inducing the polycystic ovaries using testosterone enanthate.Materials & Methods: In this study, for inducing the polycystic ovary phenotype, female rats about12-14 days-old were injected daily with testosterone enanthate for 2 and 4 weeks (experiment groups: 1 and 2, while the control groups (1 and 2 were injected only with vehicle.The ovaries from both groups were fixed and then were used for histological studies.Results: Testosterone enanthate treatment causes the histological changes in mouse ovary and significantly increased the percentage of preantral and cystic follicles and decreased the percentage of antral follicles in the experiment group, comparing with the control group (P<0.05.Conclusion: It concluded that testosterone enanthate can induces polycystic ovary in mouse.

Prevalence of Hypertension in Children with Early-Stage ADPKD.

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Massella, Laura; Mekahli, Djalila; Paripović, Dušan; Prikhodina, Larisa; Godefroid, Nathalie; Niemirska, Anna; Ağbaş, Ayşe; Kalicka, Karolina; Jankauskiene, Augustina; Mizerska-Wasiak, Malgorzata; Afonso, Alberto Caldas; Salomon, Rémi; Deschênes, Georges; Ariceta, Gema; Özçakar, Z Birsin; Teixeira, Ana; Duzova, Ali; Harambat, Jérôme; Seeman, Tomáš; Hrčková, Gabriela; Lungu, Adrian Catalin; Papizh, Svetlana; Peco-Antic, Amira; De Rechter, Stéphanie; Giordano, Ugo; Kirchner, Marietta; Lutz, Teresa; Schaefer, Franz; Devuyst, Olivier; Wühl, Elke; Emma, Francesco

2018-04-19

Autosomal dominant polycystic kidney disease is the most common inheritable kidney disease, frequently thought to become symptomatic in adulthood. However, patients with autosomal dominant polycystic kidney disease may develop signs or symptoms during childhood, in particular hypertension. Although ambulatory BP monitoring is the preferred method to diagnose hypertension in pediatrics, data in children with autosomal dominant polycystic kidney disease are limited. Our retrospective multicenter study was conducted to collect ambulatory BP monitoring recordings from patients with autosomal dominant polycystic kidney disease age 1 cm per kidney and daytime hypertension (odds ratio, 1.70; 95% confidence interval, 1.21 to 2.4; P =0.002), nighttime hypertension (odds ratio, 1.31; 95% confidence interval, 1.05 to 1.63; P =0.02), or 24-hour hypertension (odds ratio, 1.39; 95% confidence interval, 1.08 to 1.81; P =0.01). Kidney length, expressed as SD score, was also significantly associated with nighttime hypertension (odds ratio, 1.23; 95% confidence interval, 1.06 to 1.42; P =0.10). These data indicate high prevalence of hypertension in children with autosomal dominant polycystic kidney disease starting at young ages. Copyright © 2018 by the American Society of Nephrology.

The Role of Follicular Fluid Thiol/Disulphide Homeostasis in Polycystic Ovary Syndrome.

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Tola, Esra Nur; Köroğlu, Nadiye; Ergin, Merve; Oral, Hilmi Baha; Turgut, Abdülkadir; Erel, Özcan

2018-04-04

Oxidative stress is suggested as a potential triggering factor in the etiopathogenesis of Polycystic ovary syndrome related infertility. Thiol/disulphide homeostasis, a recently oxidative stress marker, is one of the antioxidant mechanism in human which have critical roles in folliculogenesis and ovulation. The aim of our study is to investigate follicular fluid thiol/disulphide homeostasis in the etiopathogenesis of Polycystic ovary syndrome and to determine its' association with in vitro fertilization outcome. The study procedures were approved by local ethic committee. Cross sectional design Methods: Follicular fluid of twenty-two Polycystic ovary syndrome women and twenty ovulatory controls undergoing in vitro fertilization treatment were recruited. Thiol/disulphide homeostasis was analyzed via a novel spectrophotometric method. Follicular native thiol levels were found to be lower in Polycystic ovary syndrome group than non- Polycystic ovary syndrome group (p=0.041) as well as native thiol/total thiol ratio (pPolycystic ovary syndrome group (pPolycystic ovary syndrome patients was found. A positive predictive effect of native thiol on fertilization rate among Polycystic ovary syndrome group was also found (p=0.03, β=0.45, 95% CI=0.031-0.643). Deterioration in thiol/disulphide homeostasis, especially elevated disulphide levels could be one of the etiopathogenetic mechanism in Polycystic ovary syndrome. Increased native thiol levels is related to fertilization rate among Polycystic ovary syndrome patients and also positive predictor marker of fertilization rate among Polycystic ovary syndrome patients. Improvement of thiol/disulphide homeostasis could be of importance in the treatment of Polycystic ovary syndrome to increase in vitro fertilization success in Polycystic ovary syndrome.

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation.

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Jean-François Gautier

Full Text Available Fetal exposure to hyperglycemia impacts negatively kidney development and function.Our objective was to determine whether fetal exposure to moderate hyperglycemia is associated with epigenetic alterations in DNA methylation in peripheral blood cells and whether those alterations are related to impaired kidney function in adult offspring.Twenty nine adult, non-diabetic offspring of mothers with type 1 diabetes (T1D (case group were matched with 28 offspring of T1D fathers (control group for the study of their leukocyte genome-wide DNA methylation profile (27,578 CpG sites, Human Methylation 27 BeadChip, Illumina Infinium. In a subset of 19 cases and 18 controls, we assessed renal vascular development by measuring Glomerular Filtration Rate (GFR and Effective Renal Plasma Flow (ERPF at baseline and during vasodilatation produced by amino acid infusion.Globally, DNA was under-methylated in cases vs. controls. Among the 87 CpG sites differently methylated, 74 sites were less methylated and 13 sites more methylated in cases vs. controls. None of these CpG sites were located on a gene known to be directly involved in kidney development and/or function. However, the gene encoding DNA methyltransferase 1 (DNMT1--a key enzyme involved in gene expression during early development--was under-methylated in cases. The average methylation of the 74 under-methylated sites differently correlated with GFR in cases and controls.Alterations in methylation profile imprinted by the hyperglycemic milieu of T1D mothers during fetal development may impact kidney function in adult offspring. The involved pathways seem to be a nonspecific imprinting process rather than specific to kidney development or function.

Asymmetric dimethylarginine and lipid peroxidation products in early autosomal dominant polycystic kidney disease

DEFF Research Database (Denmark)

Wang, Dan; Strandgaard, S.; Borresen, M.L.

2008-01-01

academic medical center. Factor: Patients with ADPKD versus controls. Outcomes & Measurement: Plasma (P) levels, urinary (U) excretion, and urinary clearance (C) of ADMA and HODE. Because of multiple comparisons, P for significance is considered less than 0.0167. Results: Patients with ADPKD had......-sectional nature of study, and limited number of markers of oxidative stress. Conclusions: P-ADMA and P-HODE levels are increased in patients with early ADPKD. Increased P-ADMA level is related to decreased CADMA and is accompanied by oxidative stress. Am J Kidney Dis 51:184-191. (c) 2008 by the National Kidney...

Acute Kidney Injury in the Elderly

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Abdel-Kader, Khaled; Palevsky, Paul

2009-01-01

Synopsis The aging kidney undergoes a number of important anatomic and physiologic changes that increase the risk of acute kidney injury (formerly acute renal failure) in the elderly. This article reviews these changes and discusses the diagnoses frequently encountered in the elderly patient with acute kidney injury. The incidence, staging, evaluation, management, and prognosis of acute kidney injury are also examined with special focus given to older adults. PMID:19765485

Vesicoureteral Reflux, a Scarred kidney, and Minimal Proteinuria: An Unusual Cause of Adult Secondary Hypertension

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Shaifali Sandal

2011-01-01

Full Text Available Hypertension affects about 65 million individuals in the United States. In adult patients, primary aldosteronism and renovascular causes are described as most prevalent. Vesicoureteral reflux as a cause of hypertension, while commonly described in pediatric populations, is less prevalent in the adult population especially in the absence of proteinuria. We present the case of a 31-year-old female presenting with early onset hypertension. Workup for renovascular hypertension was unrevealing. She was found to have right-sided vesicoureteral reflux with a unilateral scarred kidney. Patient underwent a nephrectomy with marked improvement in blood pressure control.

Kidney stem cells in development, regeneration and cancer.

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Dziedzic, Klaudyna; Pleniceanu, Oren; Dekel, Benjamin

2014-12-01

The generation of nephrons during development depends on differentiation via a mesenchymal to epithelial transition (MET) of self-renewing, tissue-specific stem cells confined to a specific anatomic niche of the nephrogenic cortex. These cells may transform to generate oncogenic stem cells and drive pediatric renal cancer. Once nephron epithelia are formed the view of post-MET tissue renal growth and maintenance by adult tissue-specific epithelial stem cells becomes controversial. Recently, genetic lineage tracing that followed clonal evolution of single kidney cells showed that the need for new cells is constantly driven by fate-restricted unipotent clonal expansions in varying kidney segments arguing against a multipotent adult stem cell model. Lineage-restriction was similarly maintained in kidney organoids grown in culture. Importantly, kidney cells in which Wnt was activated were traced to give significant clonal progeny indicating a clonogenic hierarchy. In vivo nephron epithelia may be endowed with the capacity akin to that of unipotent epithelial stem/progenitor such that under specific stimuli can clonally expand/self renew by local proliferation of mature differentiated cells. Finding ways to ex vivo preserve and expand the observed in vivo kidney-forming capacity inherent to both the fetal and adult kidneys is crucial for taking renal regenerative medicine forward. Some of the strategies used to achieve this are sorting human fetal nephron stem/progenitor cells, growing adult nephrospheres or reprogramming differentiated kidney cells toward expandable renal progenitors. Copyright © 2014. Published by Elsevier Ltd.

Investigation of Demodex folliculorum frequency in patients with polycystic ovary syndrome.

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Eser, Ayla; Erpolat, Seval; Kaygusuz, Ikbal; Balci, Hatice; Kosus, Aydin

2017-01-01

Background: Demodex mites are acari that reside in the pilosebaceous unit of the skin and have been associated with skin disorders. The objective of this study was to investigate the prevalence of Demodex folliculorum (D. folliculorum) mites in polycystic ovary syndrome patients as well as to examine the relationship between Demodex infestation and the presence of acne and oily or dry skin types in polycystic ovary syndrome patients. 41 polycystic ovary syndrome patients and 47 non-polycystic ovary syndrome control subjects were enrolled in the study. polycystic ovary syndrome was diagnosed according to the revised 2003 ESHRE/ASRM polycystic ovary syndrome Consensus Workshop Group diagnostic criteria. Microscopic examination of D. folliculorum mites was carried out by standardized skin surface biopsy. The result was considered positive when there were more than 5 mites per cm2. D. folliculorum was positive in 53.7% of the polycystic ovary syndrome patients and 31.9% of the non-polycystic ovary syndrome group (p=0.052). Demodex positivity was significantly associated with acne (p=0.003) and oily skin (p=0.005) in the polycystic ovary syndrome patients but not in the controls. Our study is limited by the relatively small number of subjects and the observational nature of the study design. Demodex mites might have a role in acne pathogenesis in patients with polycystic ovary syndrome. Anti-Demodex treatment may increase the response to treatment of acne. Further studies are indicated.

Clinical and Biochemical Characteristics of Polycystic Ovary ...

African Journals Online (AJOL)

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting women of reproductive age and characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. There are no published data on this syndrome in Libyan patients. Aims and objectives: To assess the frequency of ...

Borderline personality disorder and polycystic ovary syndrome: A review of the literature.

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Tan, Raelene Ym; Grigg, Jasmin; Kulkarni, Jayashri

2018-02-01

This review examines the existing evidence for the relationship between borderline personality disorder and polycystic ovary syndrome, and to identify commonalities in etiological mechanisms of borderline personality disorder and polycystic ovary syndrome that might explain the relationship between these seemingly disparate disorders. A search of Medline, EMBASE and Cochrane Central was undertaken on 5 December 2016 to identify studies investigating women with borderline personality disorder and polycystic ovary syndrome (or symptoms and markers specific to polycystic ovary syndrome). Nine studies were identified, including three cross-sectional studies investigating symptoms of polycystic ovary syndrome in women with borderline personality disorder, two cross-sectional and one cohort study examining the prevalence of psychiatric diagnoses in women with polycystic ovary syndrome and three case reports of comorbid borderline personality disorder and polycystic ovary syndrome. Overall, the literature shows women with borderline personality disorder to have higher than expected serum androgen levels and incidence of polycystic ovaries, which can be key features of polycystic ovary syndrome. However, this research is still in its infancy, which limits our understanding of this potential comorbid phenomenon. Given the emerging anecdotal and empirical evidence to date, a theoretical discussion of the potential psychoneuroendocrinological mechanism underlying the borderline personality disorder and polycystic ovary syndrome comorbidity is provided. Further rigorous studies using standardized diagnostic criteria for polycystic ovary syndrome are warranted. Specifically, the use of prospective controlled cohort studies may be able to determine the causality and temporality of observed comorbid borderline personality disorder and polycystic ovary syndrome.

Diagnostic Algorithm in the Management of Acute Febrile Abdomen in Patients with Autosomal Dominant Polycystic Kidney Disease.

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Neuville, Marie; Hustinx, Roland; Jacques, Jessica; Krzesinski, Jean-Marie; Jouret, François

2016-01-01

Acute febrile abdomen represents a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD). Although criteria have been proposed for cyst infection (CyI) and hemorrhage (CyH), there is a lack of comparative assessments. Furthermore, distinguishing cystic from non-cystic complications remains problematic. ADPKD patients presenting with abdominal pain and/or fever between 01/2005 and 06/2015 were retrospectively identified in a systematic computerized billing database. CyH was defined as spontaneous intracystic density above 50 Hounsfield units on computed tomography (CT). CyI was definite if confirmed by cyst puncture, and probable if 4 criteria were met: 3-day fever, loin/liver tenderness, C-reactive protein (CRP) plasma levels >50mg/L and no CT evidence for CyH. Other episodes were grouped as inflammation of unknown origin (IUO). Among a cohort of 173 ADPKD patients, 101 presented with 205 episodes of abdominal pain (n = 172) and/or fever (n = 33). 20 patients experienced 30 CyH, whereas 16 presented 23 episodes of definite (n = 11) or probable (n = 12) CyI. 35 IUO were observed in 31 patients. Clinically, fever was observed in 7% vs. 100% vs. 66% of CyH, CyI and IUO, respectively. Biologically, CRP cut-off at 70 mg/dl showed 92% sensitivity and 81% specificity in CyI diagnosis. Urine or blood cultures remained sterile in >90% of CyH, but were contributive in 53.4% of CyI and IUO, with a 74.2% prevalence for E. coli. Radiologically, ultrasounds, CT and magnetic resonance diagnosed CyI in 2.6%, 20% and 16.7% of cases, respectively. 18F-FDG positron-emission tomography (PET)/CT was done within a median period of 7 days post antibiotics, and significantly changed patient management in 71.4%. This retrospective single-center series underscores the usefulness of clinical-fever-and biological-CRP-parameters, but emphasizes the limitations of bacteriological and radiological investigations in cases of acute febrile abdomen in ADPKD

VALPROATE, BIPOLAR DISORDER AND POLYCYSTIC OVARIAN SYNDROME.

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Okanović, Milana; Zivanović, Olga

2016-01-01

Polycystic ovarian syndrome is a syndrome of ovarian dysfunction with the principal features of hyperandrogenism and polycystic ovary morphology. A large number of studies conducted on this topic have suggested a possible role of anticonvulsants, particularly valproate, in the pathogenesis or risk factors associated with polycystic ovarian syndrome. Bipolar treatment guidelines from Canada and the United States of America recommend valproate as the first line strategy in the acute treatment of bipolar disorder. Most persons with bipolar disorder require maintenance treatment. Long-term administration of valproate in women with bipolar disorder or epilepsy is believed to result in the increased risk of hyperandrogenism, menstrual abnormalities and polycystic ovaries. Valproate may also increase the risk of infertility and other associated symptoms of polycystic ovarian syndrome. Therefore, particular caution is indicated in the use of valproate in women of reproductive age. The treatment of the female patients with bipolar disorder presents various challenges for the clinician. Every woman of reproductive age needs to know the risk and benefits of her pharmacologic treatment options. Bipolar disorder should be considered chronic disorder, whose development is largely affected by hormonal changes and reproductive cycle in women. These issues should be researched more thoroughly in order to opt for the most appropriate treatment in women with bipolar disorder.

Diagnosis of adolescent polycystic ovary syndrome.

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Hardy, Tristan S E; Norman, Robert J

2013-08-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age and is increasingly recognized as a disorder manifesting in the peripubertal and adolescent period. Diagnosis in the adolescent is difficult due to the high background rate of menstrual irregularity, the high prevalence of polycystic ovarian morphology and hyperandrogenic features in this population. Recent guidelines suggest that menstrual irregularity for over two years, reduced reliance on ultrasound diagnosis of polycystic ovarian morphology, and accurate assessment of hyperandrogenic and metabolic features are suitable strategies for the diagnosis of PCOS in the adolescent. Accurate diagnosis is important given the long-term implications of the disorder, with increasing emphasis on metabolic sequelae. Copyright © 2013 Elsevier Inc. All rights reserved.

Near-adult height in male kidney transplant recipients started on growth hormone treatment in late puberty.

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Gil, Silvia; Aziz, Mariana; Adragna, Marta; Monteverde, Marta; Belgorosky, Alicia

2018-01-01

Growth retardation and its impact on adult height is considered to be one of the most common complications in patients with chronic kidney disease (CKD). Treatment with recombinant human growth hormone (rhGH) has been effective in improving growth in kidney transplantation (KTx) patients, but little data are available on adult height in patients who began rhGh treatment in late puberty. Near-adult height was evaluated in 13 KTx patients treated with rhGH [growth hormone group (GHGr); dose 9.33 mg/m 2 per week] for a period of at least 18 months. At initiation of rhGH treatment, testicular volume was >8 ml and serum testosterone was >1 ng/ml compared with the control group (CGr) of ten KTx patients who did not receive rHGH. All subjects were of similar chronological age and bone age and had similar creatinine clearance (CrCl) levels, cumulative corticoid dose, height standard deviation score (SDS), target height SDS, and target height:initial height at the beginning of the study. Near-adult height was significantly greater in the GHGr than in the CGr (-1.8 ± 0.8 vs. -2.9 ± 1.1; p = 0.018). The difference between initial height and near-adult height in the GHGr revealed a significant height gain (initial height -3.1 ± 1.1; near-adult height -1.8 ± 0.8 SDS, respectively; delta 1.2 ± 0.3; p = 0.021). The CrCl level was not significantly different between the GHGr and CGr at either at study initiation or when attaining near-adult height (p = 0.74 and p = 0.23, respectively). Treatment with rhGH was effective in improving adult height in KTx patients who began treatment in late puberty, without any effect on renal function.

Associated cutaneous diseases in obese adult patients: a prospective study from a skin referral care center.

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Al-Mutairi, Nawaf

2011-01-01

The aim of the present study was to determine the spectrum of skin diseases seen among adult obese patients referred to Farwaniya Hospital. A total of 437 overweight/obese subjects (200 men and 237 women) aged 18-74 years were enrolled in the study, which was conducted from October 2008 to November 2009. Demographic details such as age, sex, occupation, personal and family history of diabetes mellitus, hypertension, and obesity were recorded. A thorough examination was performed by an experienced dermatologist (N.A.M.). Blood investigations such as complete blood count, fasting and postprandial blood sugar levels, liver function tests, kidney function tests, lipid profile, and thyroid function tests were done for all patients in addition to hormonal assay and abdominal sonar to exclude polycystic ovary disease for indicated patients. Common skin diseases found among these patients were plantar hyperkeratosis: n = 197; acanthosis nigricans: n = 144; skin tags: n = 131; striae cutis distensae: n = 102; intertrigo: n = 97; acne vulgaris: n = 94. Diabetes mellitus was diagnosed in 87 patients, polycystic ovary syndrome/hyperandrogenism in 74 female patients, and hyperlipidemia in 209 patients. This study shows that certain dermatoses such as plantar hyperkeratosis, acanthosis nigricans, skin tags, striae cutis distensae, and intertrigo are more common among obese persons. Some, such as plantar hyperkeratosis, could serve as markers of obesity and its severity, while the presence of acanthosis nigricans and skin tags may point to underlying internal disease such as diabetes and polycystic ovary syndrome. Copyright © 2011 S. Karger AG, Basel.

Polycystic ovary syndrome | Maharaj | Journal of Endocrinology ...

African Journals Online (AJOL)

Polycystic ovary syndrome. ... Journal of Endocrinology, Metabolism and Diabetes of South Africa ... the disorder, that we now know as the polycystic ovary (or ovarian) syndrome (PCOS), in seven women with amenorrhoea, enlarged ovaries with multiple cysts and hirsutism.2 These patients were treated with ovarian wedge ...

Polycystic liver disease with right pleural effusion

Science.gov (United States)

Anggreini, A. Y.; Dairi, L. B.

2018-03-01

Polycystic liver disease (PCLD) is a condition in which multiple cysts form in the hepatic parenchyma. The polycystic liver disease is also an autosomal dominant disorder (ADPLD) caused by a mutation in a gene that encodes a protein hepatocystin. PCLD has a prevalence count of 1:200,000 people in the people of America. PCLD occurs ± 24% of patients in the third decade of age to 80% by the sixth decade. Women tend to get larger cysts and more and correlated with the number of pregnancies. The following case report of a woman, 51-years-old who was treated at Haji Adam Malik hospital Medan with a diagnosis of polycystic liver disease with right pleural effusion. Some literature has reported complications of the polycystic liver disease but rarely reported with pleural effusion presentation. The patient had already undergone a puncture of pleural fluid and after three weeks of treatment condition of the patient improved and permitted to be outgoing patient.

Definition and Facts for Kidney Stones in Adults

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... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

Laparoscopic Nephrectomy versus Open Nephrectomy for Patients with Autosomal Dominant Polycystic Kidney Disease: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Pengyu Guo

Full Text Available To compare efficacy and safety of laparoscopicnephrectomy (LN versus open nephrectomy (ON in the management of autosomal dominant polycystic kidney disease (ADPKD, we conducted a systematic review and meta-analysis.A systematic search of the electronic databases PubMed, Scopus, and the Cochrane Library was performed up to October 2014. This systematic review was performed based on observational comparative studies that assessed the two techniques. The weighted mean difference (WMD and risk ratio (RR, with their corresponding 95% confidence interval (CI, were calculated to compare continuous and dichotomous variables, respectively.Seven studies were identified, including 195 cases (118 LN/77 ON. Although LN was associated with longer operative time (WMD 30.236, 95%CI 14.541 -45.932, P<0.001 and the specimen might not have been resected as heavy as the ON group (WMD -986.516, 95%CI -1883.24--89.795, P = 0.031, patients in this group might benefit from a shorter length of hospital stay (WMD -3.576, 95%CI 4.976--2.176, P <0.001, less estimated blood loss (WMD -180.245, 95%CI -317.939--42.556, P = 0.010, and lower need of transfusion (RR 0.345, 95%CI 0.183-0.650, P = 0.001. The LN group also had less overall complications (RR 0.545, 95%CI 0.329-0.903, P = 0.018. The need of narcotic analgesics between the two groups might have no significant difference (WMD -54.66, 95%CI -129.76-20.44, P = 0.154.LN for giant symptomatic ADPKD was feasible, safe and efficacious. Morbidity was significantly reduced compared with the open approach. For an experienced laparoscopist, LN might be a better alternative.

Diagnosis and Treatment of Polycystic Ovary Syndrome.

Science.gov (United States)

Williams, Tracy; Mortada, Rami; Porter, Samuel

2016-07-15

Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations.

Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

Science.gov (United States)

Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

2006-09-01

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

Novel mTORC1 and 2 Signaling Pathways in Polycystic Kidney Disease (PKD)

Science.gov (United States)

2017-09-01

30 27 32 2K (g) 0.35 0.53 0.36 * 2K/TBW (%) 1.1 2.0 1.2 * Cyst volume (%) 0 40.1 14.6 * No of cysts/kidney 0 5.3 0.8 * Heart wt (g) 0.3 0.15 0.17...some delay in the project. There were no other delays in the project Changes that had a significant impact on expenditures Delays in hiring PRA... Heart wt (g) 0.3 0.15 0.17 15 BUN (mg/dL) 24 29 25 SCr (mg/dL) 0.22 0.33 0.2* 2K/TBW (%) Two kidney/total body weight, *pɘ.05 vs. Pkd1

Prevalence of Polycystic Ovary Syndrome Phenotypes Using Updated Criteria for Polycystic Ovarian Morphology: An Assessment of Over 100 Consecutive Women Self-reporting Features of Polycystic Ovary Syndrome

OpenAIRE

Clark, Nina M.; Podolski, Amanda J.; Brooks, Eric D.; Chizen, Donna R.; Pierson, Roger A.; Lehotay, Denis C.; Lujan, Marla E.

2014-01-01

The prevalence of polycystic ovary syndrome (PCOS) and its distinct clinical phenotypes were assessed using 3 sets of international diagnostic criteria in women self-reporting concerns over outward features of PCOS. Revised ultrasonographic criteria for polycystic ovaries (PCO) based on modern ultrasound technology were used. Of the participants, 53%, 62%, and 70% were diagnosed with PCOS using National Institutes of Health, Androgen Excess and PCOS Society, and Rotterdam criteria, respective...

Healthy Kidneys (A Cup of Health with CDC)

Centers for Disease Control (CDC) Podcasts

Kidneys that function properly are critical for maintaining good health, however, more than one in seven American adults have kidney disease and most aren't aware of their condition. In this podcast, Nilka Rios Burrows discusses the importance of maintaining healthy kidneys.

Ion channelopathies of the kidney and adrenal gland

NARCIS (Netherlands)

Beck, B. B.; Wollnik, B.; Koemhoff, M.

2013-01-01

Genetic kidney diseases represent a significant proportion of kidney diseases manifesting in childhood and adolescence, but are also gaining importance in slowly progressive or late-onset adult diseases. A significant portion of kidney diseases particularly in childhood are associated with end stage

Young adults' perspectives on living with kidney failure: a systematic review and thematic synthesis of qualitative studies.

Science.gov (United States)

Bailey, Phillippa K; Hamilton, Alexander J; Clissold, Rhian L; Inward, Carol D; Caskey, Fergus J; Ben-Shlomo, Yoav; Owen-Smith, Amanda

2018-01-10

Young adults fare worse than younger adolescents or older adults on a broad range of health indicators. Those with a chronic illness such as renal failure are a particularly vulnerable group, who experience poor outcomes compared with both children and older adults. Understanding how being in receipt of renal replacement therapy (RRT) affects the lives of young adults might help us to better prepare and support these individuals for and on RRT, and improve outcomes. This study aimed to synthesise research describing young adults' experiences of the psychosocial impact of kidney failure and RRT. A systematic literature review identified qualitative research reporting the perspectives of people aged 16-30 years receiving RRT on the psychosocial impact of renal failure. Electronic databases (including Medline/EMBASE/PsycINFO/ASSIA) were searched to November 2017 for full-text papers. The transparency of reporting of each study was assessed using the Consolidated Criteria for Reporting Qualitative Health Research (COREQ) framework. Quality was assessed using the Critical Appraisal Skills Programme qualitative checklist. An inductive thematic synthesis was undertaken. Seven studies from five different countries were included, comprising 123 young adults receiving RRT. Comprehensiveness of reporting was variable: studies reported 9-22 of the 32 COREQ-checklist items.Three global themes about the impact of kidney failure on young adults were identified: (1) difference desiring normality, (2) thwarted or moderated dreams and ambitions, and (3) uncertainty and liminality. These reflected five organising themes: (1) physical appearance and body image, (2) activity and participation, (3) educational disruption and underachievement, (4) career ambitions and employment difficulties, and (5) social isolation and intimate relationships. Across different countries and different healthcare settings, young adults on RRT experience difference and liminality, even after

Current aspects of polycystic ovary syndrome: A literature review

Directory of Open Access Journals (Sweden)

VICTOR HUGO LOPES DE ANDRADE

Full Text Available SUMMARY Polycystic ovary syndrome (PCOS is a heterogeneous endocrine disorder with variable prevalence, affecting about one in every 15 women worldwide. The diagnosis of polycystic ovary syndrome requires at least two of the following criteria: oligoovulation and/or anovulation, clinical and/or biochemical evidence of hyperandrogenism and morphology of polycystic ovaries. Women with PCOS appear to have a higher risk of developing metabolic disorders, hypertension and cardiovascular disorders. The aim of this article was to present a review of the literature by searching the databases Pubmed and Scielo, focusing on publications related to polycystic ovaries, including its pathogenesis, clinical manifestations, diagnosis and therapeutic aspects, as well as its association with cardiovascular and arterial hypertensive disorders.

Prevalence estimates of chronic kidney disease in Canada: results of a nationally representative survey

Science.gov (United States)

Arora, Paul; Vasa, Priya; Brenner, Darren; Iglar, Karl; McFarlane, Phil; Morrison, Howard; Badawi, Alaa

2013-01-01

Background: Chronic kidney disease is an important risk factor for death and cardiovascular-related morbidity, but estimates to date of its prevalence in Canada have generally been extrapolated from the prevalence of end-stage renal disease. We used direct measures of kidney function collected from a nationally representative survey population to estimate the prevalence of chronic kidney disease among Canadian adults. Methods: We examined data for 3689 adult participants of cycle 1 of the Canadian Health Measures Survey (2007–2009) for the presence of chronic kidney disease. We also calculated the age-standardized prevalence of cardiovascular risk factors by chronic kidney disease group. We cross-tabulated the estimated glomerular filtration rate (eGFR) with albuminuria status. Results: The prevalence of chronic kidney disease during the period 2007–2009 was 12.5%, representing about 3 million Canadian adults. The estimated prevalence of stage 3–5 disease was 3.1% (0.73 million adults) and albuminuria 10.3% (2.4 million adults). The prevalence of diabetes, hypertension and hypertriglyceridemia were all significantly higher among adults with chronic kidney disease than among those without it. The prevalence of albuminuria was high, even among those whose eGFR was 90 mL/min per 1.73 m2 or greater (10.1%) and those without diabetes or hypertension (9.3%). Awareness of kidney dysfunction among adults with stage 3–5 chronic kidney disease was low (12.0%). Interpretation: The prevalence of kidney dysfunction was substantial in the survey population, including individuals without hypertension or diabetes, conditions most likely to prompt screening for kidney dysfunction. These findings highlight the potential for missed opportunities for early intervention and secondary prevention of chronic kidney disease. PMID:23649413

Polycystic ovary syndrome

African Journals Online (AJOL)

excess ... Polycystic ovarian morphology (PCOM) on ultrasonography. JEMDSA ..... have rapid onset of virilisation with clitoromegaly and breast atrophy, features .... endometrial cancer.89,90 Thus one of the aims of therapy is to improve the ...

Polycystic Ovary Syndrome - diagnosis and treatment

OpenAIRE

Hussain, Amna

2015-01-01

Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder, and a major cause of infertility in women. An excessive amount of androgen hormones are produced by polycystic ovaries in PCOS with irregular menstruation and anovulation as result. The most common early symptoms are infertility, hirsutism and acne. Type 2 diabetes mellitus, metabolic syndrome, and possibly cardiovascular disease and endometrial carcinoma are all associated as lifelong implications with t...

Clinical Variability in Cardiovascular Disease Risk Factor Screening and Management in Adolescent and Young Adult Women with Polycystic Ovary Syndrome.

Science.gov (United States)

Baer, Tamara E; Milliren, Carly E; Walls, Courtney; DiVasta, Amy D

2015-10-01

To review the clinical presentation, evaluation, and management of normal-weight (NW), overweight (OW), and obese (OB) adolescent and young adult women with polycystic ovary syndrome (PCOS) during a 2-year follow-up. Retrospective chart review. One hundred seventy-three adolescent and young adult women, aged 12-22 years, diagnosed with PCOS. Demographic, health data, and laboratory measures were abstracted from 3 clinic visits: baseline and 1- and 2-year follow-up. Subjects were classified as NW, OW, or OB. Longitudinal data were analyzed using repeated-measures analysis of variance. Body mass index, self-reported concerns, and lifestyle changes. Most patients (73%) were OW or OB. Family history of type 2 diabetes was greater in OW (38%) and OB (53%) patients compared with NW (22%) patients (P = .002). Acanthosis nigricans was identified in OW (62%) and OB (21%) patients but not in NW patients (0%; P insulin (P PCOS were OW or OB. Substantial clinical variability existed in cardiovascular disease (CVD) screening; among those screened, OW and OB patients had greater CVD risk factors. Despite self-reported concerns about weight and diabetes risk among OW and OB patients, no clinically significant change in body mass index percentile occurred. Evidence-based interventions and recommendations for screening tests are needed to address CVD risk in adolescents and young adults with PCOS. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Polycystic Ovary Syndrome : Genetic determinants of the phenotype

NARCIS (Netherlands)

O. Valkenburg (Olivier)

2015-01-01

markdownabstract__Abstract__ The polycystic ovary syndrome (PCOS) was first described in 1935 by Stein and Leventhal as an association of amenorrhoea, obesity and a typical, polycystically enlarged, appearance of the ovaries at laparatomy1. Taking into account the absence of advanced

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Science.gov (United States)

Orskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo; Strandgaard, Svend

2012-04-01

With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31 December 2008. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular, cerebrovascular, infection, other and unknown. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios (HR) 0.65, P=0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P=0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval, the prevalence of cancer increased by 35% (P=0.0002) while the cancer incidence was stable. In Danish patients with ADPKD and ESRD, there was a significant reduction in cardiovascular and cerebrovascular deaths from 1993 to 2008. The prevalence of cancer increased without significant change in cancer incidence or deaths from cancer.

[Evidence-based therapy of polycystic ovarian syndrome].

Science.gov (United States)

Gődény, Sándor; Csenteri, Orsolya Karola

2015-11-08

Polycystic ovary syndrome is recognized as the most common hormonal and metabolic disorder likely to affect women. The heterogeneous endocrinopathy is characterized by clinical and/or biochemical hyperandrogenism, oligo- or amenorrhoea, anovulatory infertility, and polycystic ovarian morphology. The syndrome is often associated with obesity, hyperinsulinemia and adversely affects endocrine, metabolic, and cardiovascular health. The symptoms and complaint of the patients vary with age. To maximise health gain of the syndrome, adequate, evidence based effective, efficient and safe treatment is necessary. This article summarises the highest available evidence provided by studies, meta-analysis and systematic reviews about the therapeutical possibilities for treating obesity, hyperandrogenism, menstrual abnormalities, infertility and psychological problems related to polycystic ovary syndrome.

Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

Science.gov (United States)

Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

2014-06-01

In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

Social participation after successful kidney transplantation

NARCIS (Netherlands)

Van der Mei, Sijrike F.; Van Sonderen, Eric L. P.; Van Son, Willem J.; De Jong, Paul E.; Groothoff, Johan W.; Van den Heuvel, Wim J. A.

2007-01-01

Purpose. To explore and describe the degree of social participation after kidney transplantation and to examine associated factors. Method. A cross-sectional study on 239 adult patients 1-7.3 years after kidney transplantation was performed via in-home interviews on participation in obligatory

Polycystic Ovary Syndrome

Science.gov (United States)

Polycystic ovary syndrome (PCOS) happens when a woman's ovaries or adrenal glands produce more male hormones than normal. PCOS causes cysts ( ... PCOS are at higher risk of diabetes, metabolic syndrome, heart disease, and high blood pressure. PCOS is ...

Polycystin-1 promotes PKCα-mediated NF-κB activation in kidney cells

International Nuclear Information System (INIS)

Banzi, Manuela; Aguiari, Gianluca; Trimi, Viky; Mangolini, Alessandra; Pinton, Paolo; Witzgall, Ralph; Rizzuto, Rosario; Senno, Laura del

2006-01-01

Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-κB signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293 CTT ), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-κB nuclear levels and NF-κB-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-κB promoter activation was mediated by PKCα because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293 CTT cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-κB inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKCα-mediated NF-κB signalling and cell survival

Social participation after successful kidney transplantation

OpenAIRE

Van der Mei, Sijrike F.; Van Sonderen, Eric L. P.; Van Son, Willem J.; De Jong, Paul E.; Groothoff, Johan W.; Van den Heuvel, Wim J. A.

2007-01-01

Purpose. To explore and describe the degree of social participation after kidney transplantation and to examine associated factors. Method. A cross-sectional study on 239 adult patients 1-7.3 years after kidney transplantation was performed via in-home interviews on participation in obligatory activities (i.e., employment, education, household tasks) and leisure activities (avolunteer work, assisting others, recreation, sports, clubs/associations, socializing, going out). Results. Kidney tran...

Young Adult Kidney Transplant Recipients: Nonadherent and Happy.

Science.gov (United States)

Massey, Emma K; Meys, Karlijn; Kerner, Roy; Weimar, Willem; Roodnat, Joke; Cransberg, Karlien

2015-08-01

The aim of this study was to investigate (a) the extent to which age at first renal replacement therapy, achievement of developmental milestones, satisfaction of psychological needs, and coping were related to subjective well-being and medication adherence among young adult kidney transplant recipients; and (b) the relationship between subjective well-being and immunosuppressive medication adherence. A cross-sectional, interview study was conducted among renal transplant patients aged 20 to 30 years. In addition to sociodemographic and medical characteristics, concepts measured were: subjective well-being (Positive And Negative Affect Schedule; Satisfaction With Life Scale), medication adherence (Basel Assessment of Adherence to Immunosuppressive Medication Scale), dispositional coping (Brief COPE), achievement of developmental milestones (Course of Life Questionnaire), and satisfaction of psychological needs (Basic Psychological Needs Scale). Sixty-two patients participated (66% men; mean age, 26 years). Sixty-five percent were classified as nonadherent in the past month. In contrast, subjective self-rated overall adherence was high. None of the variables measured were related to nonadherence. Higher feelings of competence and autonomy, and timely achievement of social and psychosexual developmental milestones were related to higher subjective well-being. Well-being and adherence did not differ according to age at diagnosis or first renal replacement therapy. Two thirds of participants were classified as nonadherent which conflicts with participants' own high rating of medication adherence. This emphasizes the need for continued adherence support among young adult transplant recipients; however, no targets for interventions were found in this study. Potential targets for interventions aimed at improving well-being include competence and autonomy.

Sex steroid receptors and apoptosis-related proteins are differentially expressed in polycystic ovaries of adult dogs.

Science.gov (United States)

Chuffa, Luiz Gustavo de Almeida; Lupi Júnior, Luiz Antonio; da Maia Lima, Alfredo Feio

2016-02-01

In Polycystic Ovaries (PCOs), the dynamics of sex hormone receptors and follicle-related apoptotic signaling remain unknown. In this study, we investigated the expression of androgen receptors (AR), estrogen receptors (ERα and ERβ), and apoptosis-related molecules (BAX, active caspase-3, Bcl-2 and Survivin) on different follicular stages of PCOs in adult dogs. Clinical evidences of high estradiol and testosterone levels, persistent estrus and vaginal discharge were observed. Inhibin B immunolabeling was increased in primary and 2 to 5-mm follicles, and a marked epithelial hyperplasia was common in the ovarian surface. Ovarian epithelia and primary follicles showed low expression of AR, ERα, and ERβ, whereas a moderate immunoexpression of AR was found in theca cells of secondary follicles and cysts. In PCOs, growing follicles displayed ERα expression, and secondary follicles exhibited higher ERβ expression. In addition, while few ERα-positive cells were found in the cysts, ERβ was moderately expressed in growing follicles and cysts. BAX was upregulated in the ovarian epithelium, primary follicles, and in the wall of follicular cysts. Active caspase-3 was significantly downregulated in the epithelium, primary follicles, and follicular cysts, whereas growing follicles had a strong immunoexpression in the granulosa cells. Bcl-2 and survivin were increased in the epithelium and primary follicles, and only survivin was upregulated in secondary and growing follicles. While Bcl-2 had a diffuse immunexpression in the follicular cysts, survivin was overexpressed by these cells. We concluded that sex steroid receptors and apoptotic proteins are differentially expressed in the follicles of adult dogs with PCOs. Copyright © 2015 Elsevier Ltd. All rights reserved.

The risk factors for diabetes mellitus after kidney transplantation

International Nuclear Information System (INIS)

Effat Razeghi; Monireh Amerian; Peimaneh Heydarian

2010-01-01

Post-transplant diabetes mellitus (PTDM) is an adverse complication of kidney transplantation, associated with decreased graft and patient survival. We investigated the risk factors for PTDM and their relation to graft rejection in our kidney transplant recipients. We prospectively included 109 consecutive first kidney transplant recipients transplanted at the Sina Hospital in Tehran from June 2003 to May 2004. Patients were excluded if they had diabetes at the time of transplantation either as the cause of kidney failure or as a comorbidity. PTDM was defined by fasting blood sugar =126 mg/dL or random blood sugar =200 mg/dL on two occasions and the need for insulin therapy and/or oral hypoglycemic drugs for at least two weeks. Thirty non-diabetic transplant recipients were diagnosed as having PTDM during the six month followup period after transplantation. Sixty non-PTDM controls, matched for age, sex and immun suppressive regimen, and transplanted as closely as possible to the PTDM cases, were randomly selected. The risk factors for PTDM were investigated in these 90 transplant recipients. Age older than 50 years (P = 0.04), history of hypertension (P = 0.02), polycystic kidney disease (P = 0.015), duration on dialysis more than one year (P < 0.0001), family history of diabetes mellitus (P < 0.0001), mean daily dose of prednisolone =15 mg/day (P < 0.0001) and cyclosporine =240 mg/day (P < 0.0001) were all more in the PTDM group. Also, the mean serum triglycerides was higher (P = 0.019) and there was an increased risk of graft rejection (P < 0.0001) in the PTDM group (Author).

Physical Activity and Kidney Injury in Pediatric and Young Adult Kidney Transplant Recipients.

Science.gov (United States)

Wolf, Mattie F; George, Roshan P; Warshaw, Barry; Wang, Elizabeth; Greenbaum, Larry A

2016-12-01

To quantify physical activity and grip strength in pediatric kidney transplant recipients and describe attitudes about exercise and exercise counseling given concerns about allograft injury. This was a cross-sectional analysis of 101 kidney transplant recipients (7-21 years old) >6 months post-transplant. Patients completed the Physical Activity Questionnaire (PAQ). Grip strength was measured with a dynamometer. We asked about activity limitations and provider counseling. Univariate analysis and multiple linear regression were used to determine independent predictors of PAQ score and grip strength z score. We enrolled 101 of 122 eligible patients. Median PAQ score was 2.2 (range 0-5) and was lower compared with controls (P < .001). The average grip strength z score was -1.1 and -0.7 in the right and left hand, respectively. Predictors of lower grip strength were younger age (P = .036), non-African American race (P = .029), lower height z score (P = .010), and longer percentage of lifetime with kidney disease (P = .029). Although 49% and 67% limited exercise before and after transplant, respectively, 67% reported increased activity after transplant. By parent report, provider counseling included limiting certain activities (71%) and encouraging regular exercise (45%). Physical activity and grip strength are low after kidney transplant. Patients perceive an emphasis on exercise limitations rather than the benefits of regular exercise. Interventions that encourage physical activity may be beneficial. Copyright © 2016 Elsevier Inc. All rights reserved.

Cyst Ablation Using a Mixture of N-Butyl Cyanoacrylate and Iodized Oil in Patients with Autosomal Dominant Polycystic Kidney Disease: the Long-Term Results

Energy Technology Data Exchange (ETDEWEB)

Kim, See Hyung; Kim, Seung Hyup; Cho, Jeong Yeon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2009-08-15

We wanted to assess the long-term results of cyst ablation with using N-butyl cyanoacrylate (NBCA) and iodized oil in patients with autosomal dominant polycystic kidney disease (ADPKD) and symptomatic cysts. Cyst ablation using a mixture of NBCA and iodized oil was performed in 99 cysts from 21 patients who had such symptoms as abdominal distension and pain. The collapse or reaccumulation of the ablated cysts after the procedure was assessed during the follow-up period of 36 to 90 months. The treatment effects, including symptom relief, and the clinical data such as the blood pressure and serum creatinine levels were also assessed, together with the complications. The procedure was technically successful in all 99 cysts from the 21 patients. Any procedure-related significant complications were not detected. Seventy-seven of 99 cysts (78%) were successfully collapsed on the follow-up CT. Twenty-two cysts showed reaccumulation during long-term follow-up period. The clinical symptoms were relieved in 17 of the 21 patients (76%). Four of 12 patients (33%) with hypertension and two of six patients (33%) with azotemia were improved. End stage renal disease (ESRD) occurred in six of the 21 patients (28%) during the follow-up period. The mean age of ESRD in our patients was 57 years. The mean time interval for the development of ESRD was 19 months. Ablation using a mixture of NBCA and iodized oil may be an effective, safe method for obtaining symptom relief in patients with ADPKD.

Complete Heart Block with Diastolic Heart Failure and Pulmonary Edema Secondary to Enlarging Previously Diagnosed Thrombosed Aneurysm of Sinus of Valsalva in a Patient with History of Autosomal Dominant Polycystic Kidney Disease

Directory of Open Access Journals (Sweden)

Sherif Ali Eltawansy

2015-01-01

Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is associated with vascular aneurysms that can affect any part of the vascular tree, like ascending aorta or coronary arteries. Sinus of Valsalva is known as an anatomical dilation at the root of aorta above the aortic valve and very few cases show aneurysm at that site in patients with ADPKD. Sinus of Valsalva aneurysm (SVA can present with rupture and acute heart failure and infective endocarditis or could be asymptomatic accidentally discovered during cardiac catheterization. We report a case of a 76-year-old male with a unique constellation of cardiovascular anomalies associated with ADPKD. Patient was previously diagnosed with aneurysms affecting ascending aorta, sinus of Valsalva, and coronary arteries. Several years later, he came with complete heart block which was discovered later to be secondary to enlargement of his previously diagnosed thrombosed SVA. His case was complicated with acute heart failure and pulmonary edema. Conclusion. Patients with ADPKD can present with extrarenal manifestations. In our case, aneurysm at sinus of Valsalva was progressively enlarging and presented with complete heart block.

Diagnostic Algorithm in the Management of Acute Febrile Abdomen in Patients with Autosomal Dominant Polycystic Kidney Disease.

Directory of Open Access Journals (Sweden)

Marie Neuville

Full Text Available Acute febrile abdomen represents a diagnostic challenge in patients with autosomal dominant polycystic kidney disease (ADPKD. Although criteria have been proposed for cyst infection (CyI and hemorrhage (CyH, there is a lack of comparative assessments. Furthermore, distinguishing cystic from non-cystic complications remains problematic.ADPKD patients presenting with abdominal pain and/or fever between 01/2005 and 06/2015 were retrospectively identified in a systematic computerized billing database. CyH was defined as spontaneous intracystic density above 50 Hounsfield units on computed tomography (CT. CyI was definite if confirmed by cyst puncture, and probable if 4 criteria were met: 3-day fever, loin/liver tenderness, C-reactive protein (CRP plasma levels >50mg/L and no CT evidence for CyH. Other episodes were grouped as inflammation of unknown origin (IUO.Among a cohort of 173 ADPKD patients, 101 presented with 205 episodes of abdominal pain (n = 172 and/or fever (n = 33. 20 patients experienced 30 CyH, whereas 16 presented 23 episodes of definite (n = 11 or probable (n = 12 CyI. 35 IUO were observed in 31 patients. Clinically, fever was observed in 7% vs. 100% vs. 66% of CyH, CyI and IUO, respectively. Biologically, CRP cut-off at 70 mg/dl showed 92% sensitivity and 81% specificity in CyI diagnosis. Urine or blood cultures remained sterile in >90% of CyH, but were contributive in 53.4% of CyI and IUO, with a 74.2% prevalence for E. coli. Radiologically, ultrasounds, CT and magnetic resonance diagnosed CyI in 2.6%, 20% and 16.7% of cases, respectively. 18F-FDG positron-emission tomography (PET/CT was done within a median period of 7 days post antibiotics, and significantly changed patient management in 71.4%.This retrospective single-center series underscores the usefulness of clinical-fever-and biological-CRP-parameters, but emphasizes the limitations of bacteriological and radiological investigations in cases of acute febrile abdomen in

Genetic investigation into ethnic disparity in polycystic ovarian syndrome

DEFF Research Database (Denmark)

Li, Shuxia; Zhu, Dongyi; Duan, Hongmei

2013-01-01

Polycystic ovarian syndrome is universally the most common endocrinopathy in women of reproductive age. It is characterized by composite clinical phenotypes reflecting the reproductive impact of ovarian dysfunction (androgen excess, oligo-/anovulation, polycystic ovary) and metabolic abnormalities...... more efficient strategies for treatment and prevention of polycystic ovarian syndrome....... to unravel the molecular basis of the interethnic difference in the pathogenesis of the syndrome. It is hoped that identification and characterization of population-specific structural genetic and functional genomic patterns could help to not only deepen our understanding of the aetiology but also develop...

Polycystic ovary syndrome

DEFF Research Database (Denmark)

Aziz, M; Naver, Klara; Wissing, Marie Louise Muff

2012-01-01

Objectives: The primary objective of this multicenter study is to evaluate the relative impact of insulin resistance (IR) and body mass index (BMI) in women with polycystic ovary syndrome (PCOS) on (1) Key hemodynamic/thrombogenic variables, (2) Oocyte quality and early embryo development, (3...

From Placenta to Polycystic Ovarian Syndrome: The Role of Adipokines

Directory of Open Access Journals (Sweden)

Chiara Sartori

2016-01-01

Full Text Available Adipokines are cytokines produced mainly by adipose tissue, besides many other tissues such as placenta, ovaries, peripheral-blood mononuclear cells, liver, muscle, kidney, heart, and bone marrow. Adipokines play a significant role in the metabolic syndrome and in cardiovascular diseases, have implications in regulating insulin sensitivity and inflammation, and have significant effects on growth and reproductive function. The objective of this review was to analyze the functions known today of adiponectin, leptin, resistin, and visfatin from placenta throughout childhood and adolescence. It is well known now that their serum concentrations during pregnancy and lactation have long-term effects beyond the fetus and newborn. With regard to puberty, adipokines are involved in the regulation of the relationship between nutritional status and normal physiology or disorders of puberty and altered gonadal function, as, for example, premature pubarche and polycystic ovarian syndrome (PCOS. Cytokines are involved in the maturation of oocytes and in the regular progression of puberty and pregnancy.

Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights

NARCIS (Netherlands)

Westerveld, H. E.; Hoogendoorn, M.; de Jong, A. W. F.; Goverde, A. J.; Fauser, B. C. J. M.; Dallinga-Thie, G. M.

2008-01-01

The polycystic ovary syndrome (PCOS) affects 5-10% of all premenopausal women. It is diagnosed by a combination of oligo-amenorrhea and hyperandrogenism (NIH criteria) or by the presence of two out of three of: oligo-amenorrhea, hyperandrogenism, polycystic ovaries on ultrasound (Rotterdam

Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

Science.gov (United States)

Platt, Adrienne M

2015-07-01

School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure. © 2015 The Author(s).

Value of ultrasonography in the diagnosis of polycystic ovary syndrome - literature review.

Science.gov (United States)

Bachanek, Michał; Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

2015-12-01

Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2-9 mm and/or ovarian volume ≥10 cm(3). Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms.

Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome

OpenAIRE

Xu Boqun; Dai Xiaonan; Cui YuGui; Gao Lingling; Dai Xue; Chao Gao; Diao Feiyang; Liu Jiayin; Li Gao; Mei Li; Yuan Zhang; Xiang Ma

2013-01-01

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and ...

Medication understanding, non-adherence, and clinical outcomes among adult kidney transplant recipients.

Science.gov (United States)

Patzer, Rachel E; Serper, Marina; Reese, Peter P; Przytula, Kamila; Koval, Rachel; Ladner, Daniela P; Levitsky, Josh M; Abecassis, Michael M; Wolf, Michael S

2016-10-01

We sought to evaluate the prevalence of medication understanding and non-adherence of entire drug regimens among kidney transplantation (KT) recipients and to examine associations of these exposures with clinical outcomes. Structured, in-person interviews were conducted with 99 adult KT recipients between 2011 and 2012 at two transplant centers in Chicago, IL; and Atlanta, GA. Nearly, one-quarter (24%) of participants had limited literacy as measured by the Rapid Estimate of Adult Literacy in Medicine test; patients took a mean of 10 (SD=4) medications and 32% had a medication change within the last month. On average, patients knew what 91% of their medications were for (self-report) and demonstrated proper dosing (via observed demonstration) for 83% of medications. Overall, 35% were non-adherent based on either self-report or tacrolimus level. In multivariable analyses, fewer months since transplant and limited literacy were associated with non-adherence (all Padherence, and hospitalization could help target appropriate self-care interventions. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic kidney disease in lithium-treated older adults: a review of epidemiology, mechanisms, and implications for the treatment of late-life mood disorders.

Science.gov (United States)

Rej, Soham; Elie, Dominique; Mucsi, Istvan; Looper, Karl J; Segal, Marilyn

2015-01-01

Lithium is an important medication in the treatment of mood disorders. However, clinicians are hesitant to use lithium in older adults for fear of its medical effects, particularly kidney disease. This review describes the current understanding of the epidemiology and mechanisms underlying chronic kidney disease (CKD) in older lithium users, with recommendations for using lithium safely in late life. Prevalence estimates of CKD in older lithium users range from 42-50%, which does not differ greatly from the 37.8% rates seen in community-dwelling non-lithium using, non-psychiatric populations. Clinical and pre-clinical data suggest a variety of synergistic mechanisms contributing to CKD in older lithium users, including aging, cardiovascular factors, oxidative stress, inflammation, nephrogenic diabetes insipidus, acute kidney injury, and medication interactions. With regards to CKD, lithium can be used safely in many older adults with mood disorders. Compared to patients with pre-existing CKD, those with an estimated glomerular filtration rate >60 mL/min/1.73 m(2) are probably not as susceptible to lithium-associated renal decline. Using lithium concentrations kidney injury, nephrogenic diabetes insipidus, diabetes mellitus, hypertension, smoking, and coronary artery disease can all help prevent CKD and further renal decline in older lithium users.

The first description of severe anemia associated with acute kidney injury and adult minimal change disease: a case report

Directory of Open Access Journals (Sweden)

Qian Yimei

2009-01-01

Full Text Available Abstract Introduction Acute kidney injury in the setting of adult minimal change disease is associated with proteinuria, hypertension and hyperlipidemia but anemia is usually absent. Renal biopsies exhibit foot process effacement as well as tubular interstitial inflammation, acute tubular necrosis or intratubular obstruction. We recently managed a patient with unique clinical and pathological features of minimal change disease, who presented with severe anemia and acute kidney injury, an association not previously reported in the literature. Case presentation A 60-year-old Indian-American woman with a history of hypertension and diabetes mellitus for 10 years presented with progressive oliguria over 2 days. Laboratory data revealed severe hyperkalemia, azotemia, heavy proteinuria and progressively worsening anemia. Urine eosinophils were not seen. Emergent hemodialysis, erythropoietin and blood transfusion were initiated. Serologic tests for hepatitis B, hepatitis C, anti-nuclear antibodies, anti-glomerular basement membrane antibodies and anti-neutrophil cytoplasmic antibodies were negative. Complement levels (C3, C4 and CH50 were normal. Renal biopsy unexpectedly displayed 100% foot process effacement. A 24-hour urine collection detected 6.38 g of protein. Proteinuria and anemia resolved during six weeks of steroid therapy. Renal function recovered completely. No signs of relapse were observed at 8-month follow-up. Conclusion Adult minimal change disease should be considered when a patient presents with proteinuria and severe acute kidney injury even when accompanied by severe anemia. This report adds to a growing body of literature suggesting that in addition to steroid therapy, prompt initiation of erythropoietin therapy may facilitate full recovery of renal function in acute kidney injury.

Clinical and Molecular Investigations Into Ciliopathies

Science.gov (United States)

2018-03-27

Autosomal Recessive Polycystic Kidney Disease; Congenital Hepatic Fibrosis; Caroli's Disease; Polycystic Kidney Disease; Joubert Syndrome; Cerebro-Oculo-Renal Syndromes; COACH Syndrome; Senior-Loken Syndrome; Dekaban-Arima Syndrome; Cogan Oculomotor Apraxia; Nephronophthisis; Bardet-Biedl Syndrome; Alstrom Syndrome; Oral-Facial-Digital Syndrome

Comprasion of ovarian stromal blood flow measured by color Doppler ultrasonography in polycystic ovary syndrome patients and healthy women with ultrasonographic evidence of polycystic.

Science.gov (United States)

Ozdemir, Ozhan; Sari, Mustafa Erkan; Kalkan, Dilek; Koc, Esra Meltem; Ozdemir, Seyda; Atalay, Cemal Resat

2015-04-01

To compare ovarian stromal artery blood flows measured by Doppler ultrasonography of polycystic ovary syndrome (PCOS) patients and healthy women with polycystic ovarian image in ultrasonography. Forty-two patients diagnosed with PCOS according to the criteria of 2003 Rotterdam Concencus Conferance on PCOS and 38 healthy volunteers with polycystic ovarian image in ultrasonography were included in the study. Ovarian volumes and ovarian stromal artery blood flows were measured by 3-dimensional (3-D) ultrasonography and Doppler ultrasonography in all patients. In patients with PCOS, ovarian stromal artery pulsatility index (PI) and resistivity index (RI) were found significantly different from healthy women with polycystic ovarian image in ultrasonography (p ovarian volumes were found significantly higher in patients with PCOS (p ovarian volumes and ovarian stromal artery resistivity indices. Ovarian stromal artery Doppler examination could have an importance to explain the pathophysiology of PCOS, but there are few publications in the literature about PCOS and the details of ovarian stromal artery Doppler parameters in patients with polycystic ovarian image only. We conclude that Doppler ultrasonography findings of PCOS patients might be helpful in understanding the clinical follow-up and etiology of the disease.

Vitamin D status in kidney transplant patients

DEFF Research Database (Denmark)

Ewers, Bettina; Gasbjerg, Ane; Mølgaard, Christian

2008-01-01

BACKGROUND: A high prevalence of vitamin D insufficiency has been found in the general population and in patients with chronic kidney disease. OBJECTIVE: The aim was to examine vitamin D status and determinants and metabolic correlates of serum 25-hydroxyvitamin D in a population of adult Danish...... kidney transplant patients. DESIGN: This was a cross-sectional study of 173 adult kidney transplant patients with a mean (+/-SD) age of 53.4 +/- 11.7 y and a median graft age of 7.4 y (interquartile range: 3.3-12.7 y). Serum concentrations of intact parathyroid hormone (S-PTH), 25-hydroxyvitamin D [S-25....... Low S-25(OH)D concentrations were associated with 1) increased S-PTH concentrations (P = 0.0002), independently of S-1,25(OH)(2)D concentrations, and 2) decreased S-1,25(OH)(2)D concentrations (P = 0.002), independently of graft function. CONCLUSIONS: Hypovitaminosis D is common among Danish kidney...

Healthy Kidneys (A Cup of Health with CDC)

Centers for Disease Control (CDC) Podcasts

2017-03-02

Kidneys that function properly are critical for maintaining good health, however, more than one in seven American adults have kidney disease and most aren’t aware of their condition. In this podcast, Nilka Rios Burrows discusses the importance of maintaining healthy kidneys.  Created: 3/2/2017 by MMWR.   Date Released: 3/2/2017.

Chronic Kidney Disease Awareness Among Individuals with Clinical Markers of Kidney Dysfunction

Science.gov (United States)

Plantinga, Laura C.; Hsu, Chi-yuan; Jordan, Regina; Burrows, Nilka Ríos; Hedgeman, Elizabeth; Yee, Jerry; Saran, Rajiv; Powe, Neil R.

2011-01-01

Summary Background and objectives Awareness of chronic kidney disease (CKD) among providers and patients is low. Whether clinical cues prompt recognition of CKD is unknown. We examined whether markers of kidney disease that should trigger CKD recognition among providers are associated with higher individual CKD awareness. Design, setting, participants, & measurements CKD awareness was assessed in 1852 adults with an estimated GFR kidneys?” Participants were grouped by distribution of the following abnormal markers of CKD: hyperkalemia, acidosis, hyperphosphatemia, elevated blood urea nitrogen, anemia, albuminuria, and uncontrolled hypertension. Odds of CKD awareness associated with each abnormal marker and groupings of markers were estimated by multivariable logistic regression. Results Among individuals with kidney disease, only those with albuminuria had greater odds of CKD awareness (adjusted odds ratio, 4.0, P disease. Conclusions Although individuals who manifest many markers of kidney dysfunction are more likely to be aware of their CKD, their CKD awareness remains low. A better understanding of mechanisms of awareness is required to facilitate earlier detection of CKD and implement therapy to minimize associated complications. PMID:21784832

Prevalence of chronic kidney disease in adults with metabolic syndrome

Directory of Open Access Journals (Sweden)

P C Emem-Chioma

2011-01-01

Full Text Available The burden of chronic kidney disease (CKD and other non- communicable diseases continues to rise globally, and recent studies suggest that metabolic syndrome (MS may add to this burden by contributing to the development of CKD. Given that reports on the prevalence of CKD in patients with MS in this environment are scanty, this study was undertaken with the sole aim of determining the prevalence of CKD in subjects with MS as defined by the International Diabetes Federation (IDF and the National Cholesterol Education Project Adult Treatment Panel III (NCEP ATP III. A total of 240 consenting adults (18-70 years attending the general out- patient clinic of the General Hospital Okrika for various ailments were studied. Subjects were screened for MS as per the above- mentioned criteria. Estimated GFR (eGFR was determined with Modification of Diet for Renal Disease (MDRD formula and CKD was defined as eGFR less than 60 mL/min/1.73 m2 . Data was analyzed using SPSS version 12.0 and Epi info version 4.06d; P 0.05. CKD was more common in subjects with MS compared with those without, although the difference was not statistically significant. The prevalence of CKD in subjects with MS in our study population did not differ significantly when the different MS definitions were employed.

Clinical and Laboratory Characteristics of Acute Community-Acquired Urinary Tract Infections in Adult Hospitalised Patients

Directory of Open Access Journals (Sweden)

Dilista Piljić

2010-02-01

Full Text Available Urinary tract infections (UTI cause a great number of morbidity and mortality. These infections are serious complications in pregnancy, patients with diabetes, polycystic kidneys disease, sickle cell anaemia, kidney transplant and in patients with functional or structural anomalies of the urinary tract. The aim of this investigation was to determine a dominant causative agents of UTI and some of the clinical and laboratory characteristics of acute community-acquired UTI in adult hospitalised patients. We studied 200 adult patients with acute community-acquired UTI hospitalised in the Clinic for Infectious Diseases Tuzla from January 2006 to December 2007. The patients were divided into two groups: a group of patients with E. coli UTI (147 and a group of patients with non-E. coli UTI (53. In these two groups, the symptoms and signs of illness, blood test and urine analysis results were analysed. Our results have shown that the patients with E. coli UTI frequently had fever higher than 38,5 degrees C (p<0,0001, chills (p=0,0349, headache (p=0,0499, cloudy urine (p<0,0001, proteinuria (p=0,0011 and positive nitrite-test (p=0,0002. The patients with non-E. coli UTI frequently had fever lower than 38,5 degrees C (p<0,0001 and urine specific gravity <1015 (p=0,0012. There was no significant difference in blood test results between patients with E. coli and non-E. coli UTI. These clinical and laboratory findings can lead us to early etiological diagnosis of these UTI before urine culture detection of causative agents, which takes several days. Early etiological diagnosis of the E. coli and non-E. coli UTI is necessary for an urgent administration of appropriate empirical antibiotic treatment. This is very important in prevention of irreversible kidney damage, prolonged treatment, complications, as well as recidives and chronicity of the illness.

Epidemiology, diagnosis, and management of polycystic ovary syndrome

Science.gov (United States)

Sirmans, Susan M; Pate, Kristen A

2014-01-01

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%–70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications. PMID:24379699

Epidemiology, diagnosis, and management of polycystic ovary syndrome.

Science.gov (United States)

Sirmans, Susan M; Pate, Kristen A

2013-12-18

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

The Histological Appearances Of The Adult Kidney In Hiv Infection ...

African Journals Online (AJOL)

SITWALA COMPUTERS

Luchengam@gmail.com. ABSTRACT. Background: Kidney disease in acquired immunodeficiency syndrome is very common. The cause of the various histological appearances include HIV infection of the kidney, immunologic responses to the.

The three-kidney rat

International Nuclear Information System (INIS)

Provoost, A.P.; Van Aken, M.

1984-01-01

In contrast to the numerous research into the adaption of renal function when nephons are lost, much less attention has been paid to the effects of an extra kidney. Through the availability of inbred rat strains, techniques to transplant rat kidneys, and methods to measure total and individual kidney function repeatedly in the same animal, it became possible to study the renal function in rats with three kidneys. Adult male rats of a highly inbred Wistar strain were used. Nine recipients of a third kidney (3-K) were compared with 5 sham operated control (2-K) rats. The total GFR, as measured by the plasma clearance of Cr-5l EDTA, was taken 1,3,6,9, and 15 weeks after operation. The contribution of each kidney to the total renal function was determined by a Tc-99m DTPA scan performed at weeks 10 and 16. After transplantation the total GFR of 3-K rats was, in general, not different from the value before transplantation or from that of 2-K rats. The lack of increase of the GFR of 3-K rats was not the result of a non-functioning graft

Investigation of Demodex folliculorum frequency in patients with polycystic ovary syndrome*

OpenAIRE

Eser, Ayla; Erpolat, Seval; Kaygusuz, Ikbal; Balci, Hatice; Kosus, Aydin

2017-01-01

Abstract: Background: Background: Demodex mites are acari that reside in the pilosebaceous unit of the skin and have been associated with skin disorders. Objective: The objective of this study was to investigate the prevalence of Demodex folliculorum (D. folliculorum) mites in polycystic ovary syndrome patients as well as to examine the relationship between Demodex infestation and the presence of acne and oily or dry skin types in polycystic ovary syndrome patients. Methods: 41 polycystic ...

MicroRNAs related to androgen metabolism and polycystic ovary syndrome

DEFF Research Database (Denmark)

Sørensen, Anja Elaine; Udesen, Pernille Bækgaard; Wissing, Marie Louise

2016-01-01

Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women. PCOS is associated with altered features of androgen metabolism, increased insulin resistance and impaired fertility. Furthermore, PCOS, being a syndrome diagnosis, is heterogeneous and characterized by polycystic ovaries...

Healthy Kidneys (A Minute of Health with CDC)

Centers for Disease Control (CDC) Podcasts

2014-03-13

In the U.S., kidney disease affects about one in 10 adults and is the ninth-leading cause of death. This podcast discusses the dangers of kidney disease.  Created: 3/13/2014 by MMWR.   Date Released: 3/13/2014.

Validation of the Kidney Failure Risk Equation in Manitoba

Directory of Open Access Journals (Sweden)

Reid H. Whitlock

2017-04-01

Full Text Available Background: Patients with chronic kidney disease (CKD are at risk to progress to kidney failure. We previously developed the Kidney Failure Risk Equation (KFRE to predict progression to kidney failure in patients referred to nephrologists. Objective: The objective of this study was to determine the ability of the KFRE to discriminate which patients will progress to kidney failure in an unreferred population. Design: A retrospective cohort study was conducted using administrative databases. Setting: This study took place in Manitoba, Canada. Measurements: Age, sex, estimated glomerular filtration rate (eGFR, and urine albumin-to-creatinine ratio (ACR were measured. Methods: We included patients from the Diagnostic Services of Manitoba database with an eGFR <60 mL/min/1.73 m 2 and ACR measured between October 2006 and March 2007. Five-year kidney failure risk was predicted using the 4-variable KFRE and compared with treated kidney failure events from the Manitoba Renal Program database. Sensitivity and specificity for KFRE risk thresholds (3% and 10% over 5 years were compared with eGFR thresholds (30 and 45 mL/min/1.73 m 2 . Results: Of 1512 included patients, 151 developed kidney failure over the 5-year follow-up period. The 4-variable KFRE showed a superior prognostic discrimination compared with eGFR alone (area under the receiver operating characteristic curve [AUROC] values, 0.90 [95% confidence interval {CI}: 0.88-0.92] for KFRE vs 0.78 [95% CI: 0.74-0.83] for eGFR. At a 3% threshold over 5 years, the KFRE had a sensitivity of 97% and a specificity of 62%. At 10% risk, sensitivity was 86%, and specificity was 80%. Limitations: Only 11.7% of stage 3-5 CKD patients had simultaneous ACR measurement. The KFRE does not account for other indications for referral such as suspected glomerulonephritis, polycystic kidney disease, and recurrent stone disease. Conclusions: The KFRE has been validated in a population with a demographic and referral

Pharmacological management of acute kidney injury and chronic kidney disease in neonates.

Science.gov (United States)

Jetton, Jennifer G; Sorenson, Mark

2017-04-01

Both acute kidney injury (AKI) and chronic kidney disease (CKD) are seen more frequently in the neonatal intensive care unit (NICU) as advances in supportive care improve the survival of critically ill infants as well as those with severe, congenital kidney and urinary tract anomalies. Many aspects of the infant's care, including fluid balance, electrolyte and mineral homeostasis, acid-base balance, and growth and nutrition require close monitoring by and collaboration among neonatologists, nephrologists, dieticians, and pharmacologists. This educational review summarizes the therapies widely used for neonates with AKI and CKD. Use of these therapies is extrapolated from data in older children and adults or based on clinical experience and case series. There is a critical need for more research on the use of therapies in infants with kidney disease as well as for the development of drug delivery systems and preparations scaled more appropriately for these small patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cryo-EM structure of the polycystic kidney disease-like channel PKD2L1.

Science.gov (United States)

Su, Qiang; Hu, Feizhuo; Liu, Yuxia; Ge, Xiaofei; Mei, Changlin; Yu, Shengqiang; Shen, Aiwen; Zhou, Qiang; Yan, Chuangye; Lei, Jianlin; Zhang, Yanqing; Liu, Xiaodong; Wang, Tingliang

2018-03-22

PKD2L1, also termed TRPP3 from the TRPP subfamily (polycystic TRP channels), is involved in the sour sensation and other pH-dependent processes. PKD2L1 is believed to be a nonselective cation channel that can be regulated by voltage, protons, and calcium. Despite its considerable importance, the molecular mechanisms underlying PKD2L1 regulations are largely unknown. Here, we determine the PKD2L1 atomic structure at 3.38 Å resolution by cryo-electron microscopy, whereby side chains of nearly all residues are assigned. Unlike its ortholog PKD2, the pore helix (PH) and transmembrane segment 6 (S6) of PKD2L1, which are involved in upper and lower-gate opening, adopt an open conformation. Structural comparisons of PKD2L1 with a PKD2-based homologous model indicate that the pore domain dilation is coupled to conformational changes of voltage-sensing domains (VSDs) via a series of π-π interactions, suggesting a potential PKD2L1 gating mechanism.

Value of ultrasonography in the diagnosis of polycystic ovary syndrome – literature review

Science.gov (United States)

Abdalla, Nebil; Cendrowski, Krzysztof; Sawicki, Włodzimierz

2015-01-01

Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversified and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003) and Androgen Excess & PCOS Society (2006). This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2–9 mm and/or ovarian volume ≥10 cm3. Such an ultrasound image in one gonad only is sufficient to define polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confirmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted influence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms. PMID:26807298

Polycystic ovary syndrome.

Science.gov (United States)

Azziz, Ricardo; Carmina, Enrico; Chen, ZiJiang; Dunaif, Andrea; Laven, Joop S E; Legro, Richard S; Lizneva, Daria; Natterson-Horowtiz, Barbara; Teede, Helena J; Yildiz, Bulent O

2016-08-11

Polycystic ovary syndrome (PCOS) affects 5-20% of women of reproductive age worldwide. The condition is characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) - with excessive androgen production by the ovaries being a key feature of PCOS. Metabolic dysfunction characterized by insulin resistance and compensatory hyperinsulinaemia is evident in the vast majority of affected individuals. PCOS increases the risk for type 2 diabetes mellitus, gestational diabetes and other pregnancy-related complications, venous thromboembolism, cerebrovascular and cardiovascular events and endometrial cancer. PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM. Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features. This Primer summarizes the current state of knowledge regarding the epidemiology, mechanisms and pathophysiology, diagnosis, screening and prevention, management and future investigational directions of the disorder.

Healthy Kidneys (A Minute of Health with CDC)

Centers for Disease Control (CDC) Podcasts

2017-03-02

More than one in seven American adults are estimated to have kidney disease and most are not aware of their condition. This podcast discusses the importance of maintaining healthy kidneys.  Created: 3/2/2017 by MMWR.   Date Released: 3/2/2017.

Elevation of isoprostanes in polycystic ovary syndrome and its relationship with cardiovascular risk factors.

Science.gov (United States)

Calzada, M; López, N; Noguera, J A; Mendiola, J; Torres, A M

2018-04-23

To evaluate the plasma level of 8-isoprostanes in women with polycystic ovary syndrome. To also investigate whether there is a relationship between 8-isoprostanes and several cardiovascular risk factors. A total of 125 women with polycystic ovary syndrome and 169 healthy women were enrolled in this case-control study. 8-Isoprostanes and different parameters were measured in all subjects. Patients were evaluated for the presence of polycystic ovary syndrome according to the Rotterdam Consensus Conference criteria. 8-Isoprostanes levels were significantly higher in patients with polycystic ovary syndrome (138.4 ± 104.1 pg/mL) compared with control group (68.6 ± 34.3 pg/mL) (p polycystic ovary syndrome patients with high 8-isoprostanes than those with normal 8-isoprostanes (p polycystic ovary syndrome group had a positive correlation with waist circumference, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B, homocysteine, insulin, homeostatic model assessment for insulin resistance. Patients with polycystic ovary syndrome have higher 8-isoprostanes levels and it is associated with several cardiovascular risk factors.

Dual Kidney Allocation Score: A Novel Algorithm Utilizing Expanded Donor Criteria for the Allocation of Dual Kidneys in Adults.

Science.gov (United States)

Johnson, Adam P; Price, Thea P; Lieby, Benjamin; Doria, Cataldo

2016-09-08

BACKGROUND Dual kidney transplantation (DKT) of expanded-criteria donors is a cost-intensive procedure that aims to increase the pool of available deceased organ donors and has demonstrated equivalent outcomes to expanded-criteria single kidney transplantation (eSKT). The objective of this study was to develop an allocation score based on predicted graft survival from historical dual and single kidney donors. MATERIAL AND METHODS We analyzed United Network for Organ Sharing (UNOS) data for 1547 DKT and 26 381 eSKT performed between January 1994 and September 2013. We utilized multivariable Cox regression to identify variables independently associated with graft survival in dual and single kidney transplantations. We then derived a weighted multivariable product score from calculated hazard ratios to model the benefit of transplantation as dual kidneys. RESULTS Of 36 donor variables known at the time of listing, 13 were significantly associated with graft survival. The derived dual allocation score demonstrated good internal validity with strong correlation to improved survival in dual kidney transplants. Donors with scores less than 2.1 transplanted as dual kidneys had a worsened median survival of 594 days (24%, p-value 0.031) and donors with scores greater than 3.9 had improved median survival of 1107 days (71%, p-value 0.002). There were 17 733 eSKT (67%) and 1051 DKT (67%) with scores in between these values and no differences in survival (p-values 0.676 and 0.185). CONCLUSIONS We have derived a dual kidney allocation score (DKAS) with good internal validity. Future prospective studies will be required to demonstrate external validity, but this score may help to standardize organ allocation for dual kidney transplantation.

Sonographic evaluation of polycystic ovaries.

Science.gov (United States)

Zhu, Ruo-Yan; Wong, Yee-Chee; Yong, Eu-Leong

2016-11-01

The morphological features of the ovaries in women with polycystic ovary syndrome (PCOS) have been well described by ultrasound imaging technology. These include enlarged ovary size, multiple small follicles of similar size, increased ovarian stromal volume and echogenicity, peripheral distribution of the follicles, and higher stromal blood flow. Ultrasound identification of the presence of polycystic ovarian morphology (PCOM) has been recognized as a component of PCOS diagnosis. With the advance of ultrasound technology, new definition has been proposed recently. There is, however, a paucity of data for the ovarian morphology in normal and PCOS adolescents. Magnetic resonance imaging has the potential to be an alternative imaging modality for diagnosing PCOM in adolescence. Copyright © 2016. Published by Elsevier Ltd.

Postnatal depression in a community-based study of women with polycystic ovary syndrome.

Science.gov (United States)

March, Wendy A; Whitrow, Melissa J; Davies, Michael J; Fernandez, Renae C; Moore, Vivienne M

2018-02-20

Women with polycystic ovary syndrome are susceptible to depression and anxiety and so may also be at risk for postnatal depression. This study investigates whether women with polycystic ovary syndrome have an elevated risk of postnatal depression. Cross-sectional data for parous women (n = 566) were available from a birth cohort. Polycystic ovary syndrome was diagnosed using the Rotterdam criteria. Details of reproductive history, pregnancy, birth, and postnatal depression were obtained through structured interview. Comparisons were made between women with and without polycystic ovary syndrome using logistic regression analysis, including the investigation of interactions. A positive but statistically non-significant association was found between polycystic ovary syndrome and postnatal depression (odds ratio 1.6, 95% confidence interval 0.9-2.9). Compared with their counterparts, women with polycystic ovary syndrome were substantially more likely: to have difficulty conceiving (odds ratio 5.2, 95% confidence interval 2.9-9.4), to have conceived with medical assistance (odds ratio 11.6, 95% confidence interval 5.5-24.4), and to have pregnancy complications (gestational diabetes, pregnancy-induced hypertension, or preeclampsia; odds ratio 2.0, 95% confidence interval 1.1-3.5). Where women with polycystic ovary syndrome had a history of miscarriage or conceived with medical assistance, the combination interacted (p = 0.06 and p polycystic ovary syndrome may not have an excess risk of postnatal depression overall, those who had suffered a miscarriage or required medical assistance to conceive were at substantially elevated risk. Findings point to vulnerability inherent in polycystic ovary syndrome being amplified, either by stressful experiences on the pathway to pregnancy/childbirth or by specific fertility treatment regimens. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Value of ultrasonography in the diagnosis of polycystic ovary syndrome – literature review

Directory of Open Access Journals (Sweden)

Michał Bachanek

2015-12-01

Full Text Available Polycystic ovary syndrome is a multi-factorial disease. Its etiopathogenesis has not been elucidated in detail. It is the most common endocrine disorder in women of child-bearing age. This disease entity is primarily characterized by disrupted ovulation and hyperandrogenism, but the clinical picture can be diversifi ed and symptom intensity can vary. Currently, the sonographic assessment of ovaries is one of the obligatory criteria for the diagnosis of PCOS according to the Rotterdam consensus (2003 and Androgen Excess & PCOS Society (2006. This criterion is determined by the presence of ≥12 follicles within the ovary with a diameter of 2–9 mm and/or ovarian volume ≥10 cm3. Such an ultrasound image in one gonad only is suffi cient to defi ne polycystic ovaries. The coexistence of polycystic ovaries with polycystic ovary syndrome is confi rmed in over 90% of cases irrespective of ethnic factors or race. However, because of the commonness of ultrasound features of polycystic ovaries in healthy women, the inclusion of this sign to the diagnostic criteria of polycystic ovary syndrome is still questioned. The development of new technologies has an undoubted infl uence on the percentage of diagnosed polycystic ovaries. This process has caused an increase in the percentage of polycystic ovary diagnoses since the Rotterdam criteria were published. It is therefore needed to prepare new commonly accepted diagnostic norms concerning the number of ovarian follicles and the standardization of the technique in which they are counted. The assessment of anti-Müllerian hormone levels as an equivalent of ultrasound features of polycystic ovaries is a promising method. However, analytic methods have to be standardized in order to establish commonly accepted diagnostic norms.

Metabolic implications of menstrual cycle length in non-hyperandrogenic women with polycystic ovarian morphology.

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Alebić, Miro Šimun; Stojanović, Nataša; Baldani, Dinka Pavičić; Duvnjak, Lea Smirčić

2016-12-01

This cross-sectional study aimed to investigate the association between menstrual cycle lenght and metabolic parameters in non-hyperandrogenic women with polycystic ovarian morphology, n = 250. Metabolic profiles of all participants were evaluated using anthropometric parameters (body mass index, waist circumference), parameters of dyslipidemia (total cholesterol, HDL-cholesterol, triglycerides) and markers of insulin resistance (fasting insulin, homeostasis model assessment for insulin resistance index). The associations between menstrual cycle lenght and cardiometabolic risk factors such as insulin resistance, dyslipidemia, and obesity were investigated. In non-hyperandrogenic women with polycystic ovarian morphology, menstrual cycle lenght was associated with hypertriglyceridemia and insulin resistance independently of body mass index. Moreover, menstrual cycle lenght added value to body mass index in predicting hypertriglyceridemia. The optimal menstrual cycle lenght cut-off value for identifying of non-hyperandrogenic women with polycystic ovarian morphology at metabolic risk was found to be 45 days. Metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology (n = 75) with menstrual cycle lenght >45 days was similar to that of hyperandrogenic women with polycystic ovarian morphology (n = 138) while metabolic profile of non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght ≤45 days (n = 112) was similar to that of controls (n = 167). Non-hyperandrogenic women with polycystic ovarian morphology with menstrual cycle lenght >45 days had higher prevalence of cardiometabolic risk factors compared to those with menstrual cycle lenght ≤45 days. Non-hyperandrogenic women with polycystic ovarian morphology are not metabolically homogeneous. Menstrual cycle lenght is an easy-to-obtain clinical parameter positively associated with the probability of unfavorable metabolic status in non

Expression of SET Protein in the Ovaries of Patients with Polycystic Ovary Syndrome.

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Boqun, Xu; Xiaonan, Dai; Yugui, Cui; Lingling, Gao; Xue, Dai; Gao, Chao; Feiyang, Diao; Jiayin, Liu; Gao, Li; Li, Mei; Zhang, Yuan; Ma, Xiang

2013-01-01

Background. We previously found that expression of SET gene was up-regulated in polycystic ovaries by using microarray. It suggested that SET may be an attractive candidate regulator involved in the pathophysiology of polycystic ovary syndrome (PCOS). In this study, expression and cellular localization of SET protein were investigated in human polycystic and normal ovaries. Method. Ovarian tissues, six normal ovaries and six polycystic ovaries, were collected during transsexual operation and surgical treatment with the signed consent form. The cellular localization of SET protein was observed by immunohistochemistry. The expression levels of SET protein were analyzed by Western Blot. Result. SET protein was expressed predominantly in the theca cells and oocytes of human ovarian follicles in both PCOS ovarian tissues and normal ovarian tissues. The level of SET protein expression in polycystic ovaries was triple higher than that in normal ovaries (P polycystic ovaries more than that in normal ovaries. Combined with its localization in theca cells, SET may participate in regulating ovarian androgen biosynthesis and the pathophysiology of hyperandrogenism in PCOS.

Polycystic Ovary Syndrome (PCOS)

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... a type of hormone) or signs of high androgens, such as having excess body or facial hair Cysts (fluid-filled sacs) on one or both ovaries—"polycystic" literally means "having many cysts" Some women diagnosed with PCOS have the first two conditions listed above as ...

Metabolic Syndrome: Polycystic Ovary Syndrome.

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Mortada, Rami; Williams, Tracy

2015-08-01

Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Implications of the 2014 Androgen Excess and Polycystic Ovary Syndrome Society guidelines on polycystic ovarian morphology for polycystic ovary syndrome diagnosis.

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Christ, J P; Gunning, M N; Fauser, B C J M

2017-10-01

The Androgen Excess and Polycystic Ovary Syndrome Society (AEPCOS) has recommended an updated threshold for polycystic ovarian morphology (PCOM) of 25 follicles or more, 10 ml or more of ovarian volume, or both. We describe the effect of these guidelines on reproductive and metabolic characteristics in 404 women. These women were separated into four groups: group A: hyperandrogenism and oligo-amenorrhoea (n = 157); group B: hyperandrogenism or oligo-amenorrhoea and PCOM meeting AEPCOS 2014 criteria (n = 125); group C: hyperandrogenism or oligo-amenorrhoea and PCOM meeting Rotterdam 2003 but not AEPCOS 2014 criteria (n = 72); and group D: non-PCOS not meeting either criteria (n = 50). Groups B, C and D did not differ across any metabolic markers. The AEPCOS 2014 guidelines may have limited utility in distinguishing metabolic risk factors and result in the exclusion of a large group of oligo-anovulatory women. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Calcium Balance in Chronic Kidney Disease.

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Hill Gallant, Kathleen M; Spiegel, David M

2017-06-01

The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

Epidemiology, diagnosis, and management of polycystic ovary syndrome

OpenAIRE

Sirmans SM; Pate KA

2013-01-01

Susan M Sirmans, Kristen A PateDepartment of Clinical and Administrative Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, USAAbstract: Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%–20% when the European Society for Human Reproduction and...

Wilms' Tumor 1 Overexpression in Granulosa Cells Is Associated with Polycystic Ovaries in Polycystic Ovary Syndrome Patients.

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Wang, Qun; Huang, Tao; Shu, Xin; Zhao, Shi-Gang; Liang, Yu; Muhammad, Tahir; Gao, Fei; Zhao, Han; Liu, Hong-Bin

2018-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Wilms' tumor 1 (WT1) encoding a transcription factor involved in the differentiation of granulosa cells (GCs) regulates androgen receptor in the development of male genitalia. However, the expression pattern and possible role of WT1 in ovaries of PCOS patients are still unknown. GCs from 95 PCOS patients (PCOS group) and 62 healthy controls (control group) were isolated. The expression of WT1 in GCs was quantified using the reverse transcription-polymerase chain reaction. The correlation between WT1 expression and clinical characteristics was evaluated in PCOS patients. WT1 expression was increased in PCOS patients compared with the normal controls. The expression of WT1 was moderately correlated with testosterone (r = 0.334, p = 0.001) and luteinizing hormone (r = 0.357, p = 0.001) levels and the antral follicle counts (r = 0.337, p = 0.001). Our study provided novel insights into the relationship between hyperandrogenism and polycystic ovaries of PCOS and WT1. © 2018 S. Karger AG, Basel.

Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences.

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Yau, T Tl; Ng, N Yh; Cheung, L P; Ma, R Cw

2017-12-01

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.

Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries

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Ito, Y.; Fisher, C.R.; Simpson, E.R. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)); Conte, F.A.; Grumbach, M.M. (Univ. of California, San Francisco, CA (United States))

1993-11-15

The authors identified two mutations in the CYP19 gene responsible for aromatase deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from the patient revealed two single-base changes, at bp 1303 (C[yields]T) and bp 1310 (G[yields]A) in exon X, which were newly found missense mutations and resulted in codon changes of R435C and C437Y, respectively. Subcloning followed by sequencing confirmed that the patient is a compound heterozygote. The results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient's mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had [approx]1.1% of the activity of the wild type, whereas C437Y was totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To the authors' knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disease.

Polycystic ovarian syndrome

OpenAIRE

Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

2013-01-01

Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

Protein-energy wasting and uremic failure to thrive in children with chronic kidney disease: they are not small adults.

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Nourbakhsh, Noureddin; Rhee, Connie M; Kalantar-Zadeh, Kamyar

2014-12-01

Protein-energy wasting (PEW), a condition of decreased body protein and fat mass, is highly prevalent in patients with chronic kidney disease (CKD) and a potent predictor of mortality in this population. In adults with CKD, PEW has typically been defined on the basis of (1) deranged biochemical parameters, (2) reduced body mass, (3) reduced muscle mass, and (4) decreased dietary protein intake. Emerging data suggest that PEW may also commonly afflict children with CKD and have a negative impact on growth and development ("uremic failure to thrive"), yet it remains comparatively understudied and less well characterized in these patients. Given the challenges of applying adult-defined PEW criteria to the pediatric population, the authors of a recent study entitled "Protein energy wasting in children with chronic kidney disease" [Abraham et al. (2014) Pediatr Nephrol 29:1231-1238] have sought to develop a scoring system and three alterative definitions for this condition using a combination of biochemical markers, clinical measurements, and subjective reporting in children in the CKiD cohort: (1) minimal PEW definition (≥2 adult-defined PEW criteria); (2) standard PEW definition (≥3 adult-defined PEW criteria); (3) modified PEW definition (≥3 adult-defined PEW criteria, plus short stature or poor growth). These authors observed that meeting the modified PEW definition was associated with a significantly increased risk of hospitalization in unadjusted analyses, i.e., a 2.2-fold higher risk, and trended towards increased risk in multivariable adjusted analyses, i.e., 2.0-fold higher risk. At the present time, future studies validating these findings and developing further refined definitions and/or scoring systems for the detection and management of PEW in children and uremic failure to thrive are urgently needed.

Polycystic echinococcosis in Colombia: the larval cestodes in infected rodents.

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Morales, G A; Guzman, V H; Wells, E A; Angel, D

1979-07-01

Described are the characteristics of the polycystic larval cestodes found in an endemic area of echinococcosis in the Easter Plains of Colombia and the tissue reaction evoked in infected rodents. Of 848 free-ranging animals examined, polycystic hydatids were found in 44/93 Cuniculus paca and 1/369 Proechimys sp. None of 20 Dasyprocta fuliginosa examined was infected, but hunters provided a heart with hydatid cysts and information about two additional animals with infected livers. Recognition of an endemic area of polycystic echinococcosis provides a means to investigate the life cycle of the parasites and to study the histogenesis of the larval cestodes in susceptible laboratory animals.

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

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Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

2017-10-01

Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the

Obesity Differentially Affects Phenotypes of Polycystic Ovary Syndrome

OpenAIRE

Moran, Carlos; Arriaga, Monica; Rodriguez, Gustavo; Moran, Segundo

2012-01-01

Obesity or overweight affect most of patients with polycystic ovary syndrome (PCOS). Phenotypes are the clinical characteristics produced by the interaction of heredity and environment in a disease or syndrome. Phenotypes of PCOS have been described on the presence of clinical hyperandrogenism, oligoovulation and polycystic ovaries. The insulin resistance is present in the majority of patients with obesity and/or PCOS and it is more frequent and of greater magnitude in obese than in non obese...

Interventions to improve medication adherence in adult kidney transplant recipients: a systematic review.

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Low, Jac Kee; Williams, Allison; Manias, Elizabeth; Crawford, Kimberley

2015-05-01

In kidney transplantation, adherence to immunosuppressive therapy is paramount for long-term graft survival. This systematic review aimed to assess the effectiveness of interventions to improve medication adherence in adult kidney transplantation. Eight electronic databases were searched from inception to November 2013. Only primary intervention studies, which reported measurement of adherence to immunosuppressive medications after kidney transplantation, were included. The quality of all studies was assessed using the Consolidated Standards of Reporting Trials and Transparent Reporting of Evaluations with Non-randomized Designs checklists. A synthesis was undertaken to tease out the domains targeted by interventions: (i) educational/cognitive, (ii) counselling/behavioural, (iii) psychologic/affective and (iv) financial support. For each study, key information, such as population, location, methods of measurements, comparison group, type of intervention and outcomes, were extracted and tabulated. Twelve intervention studies were identified. Quality of studies ranged from 16.0 to 80.5%. Effective interventions were implemented for 3, 6 and 12 months. Medication adherence rates were greatly enhanced when multidimensional interventions were implemented whereas one-off feedback from a nurse and financial assistance programmes offered little improvement. Dose administration aids when used in conjunction with self-monitoring also improved adherence. The number of patients who had a drug holiday (at least 1-day interval without a dose) was higher in a once-daily regimen than a twice-daily regimen. The findings of this review suggest an intervention targeting behavioural risk factors or a combination of behavioural, educational and emotional changes is effective in enhancing medication adherence. Effectiveness of an intervention may be further enhanced if patients are encouraged to participate in the development process. © The Author 2014. Published by Oxford University

HIV and chronic kidney disease

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Naicker, Saraladevi; Rahmania, Sadaf; Kopp, Jeffrey B.

2015-01-01

Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 – 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune comple...

Urinary tract infection - adults

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Bladder infection - adults; UTI - adults; Cystitis - bacterial - adults; Pyelonephritis - adults; Kidney infection - adults ... control. Menopause also increases the risk of a UTI. The following also increase your chances of developing ...

Pathomechanisms of polycystic ovary syndrome: Multidimensional approaches.

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Sagvekar, Pooja; Dadachanji, Roshan; Patil, Krutika; Mukherjee, Srabani

2018-03-01

Polycystic ovary syndrome is a complex endocrine disorder affecting numerous women of reproductive age across the globe. Characterized mainly by irregular menses, hirsutism, skewed LH: FSH ratios and bulky polycystic ovaries, this multifactorial endocrinopathy results in unfavorable reproductive and metabolic sequelae, including anovulatory infertility, type 2 diabetes, metabolic syndrome and cardiovascular disease in later years. Increasing evidence has shown that the manifestation of polycystic ovary syndrome (PCOS) is attributable to a cumulative impact of altered genetic, epigenetic and protein profiles which bring about a systemic dysfunction. While genetic approaches help ascertain role of causal variants in its etiology, tissue-specific epigenetic patterns help in deciphering the auxiliary role of environmental, nutritional and behavioral factors. Proteomics is advantageous, linking both genotype and phenotype and contributing to biomarker discovery. Investigating molecular mechanism underlying PCOS is imperative in order to gain insight into the pathophysiology of PCOS and formulate novel diagnostic and treatment strategies. In this review we have summarized these three aspects, which have been successfully utilized to delineate the pathomechanisms of PCOS.

POLYCYSTIC OVARY SYNDROME IN ADOLESCENCE

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Diana Baptista

2017-02-01

Conclusion: Identification of adolescents at risk for Polycystic Ovary Syndrome is critical, not only for an appropriate therapeutic approach, but also to prevent co-morbidities associated with the syndrome, including obesity, insulin resistance, dyslipidemia and infertility.

Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome

OpenAIRE

Montezuma, Thais; Ant?nio, Fl?via Ign?cio; de S? Rosa e Silva, Ana Carolina Japur; de S?, Marcos Felipe Silva; Ferriani, Rui Alberto; Ferreira, Cristine Homsi Jorge

2011-01-01

OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18- to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University...

Occupational risk and chronic kidney disease: a population-based study in the United States adult population.

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Rubinstein, Sofia; Wang, Chengwei; Qu, Wenchun

2013-01-01

Previous studies on occupational risk for chronic kidney disease (CKD) have analyzed a limited range of occupations and focused on nephrotoxins. The primary purpose of this study was to examine the relative risk for the occurrence of CKD between different occupations in the US adult population. This was a population-based survey study of 91,340 participants in the US, who completed the National Health Interview Survey, 2004 through 2008. The outcome variable, CKD, was defined as having weakening/failing kidneys in the past 12 months, as diagnosed by a physician. The predictor variable, occupation, was obtained using the census occupational codes, regrouped according to North American Industrial Classification System. After controlling for age, gender, hypertension, and education, and with the category Life, Physical, and Social Science Occupations as a reference group, the likelihood of developing CKD was 4.3 times higher in respondents working in Building, Grounds Cleaning and Maintenance Occupations, 4.4 times higher in Healthcare Practitioners and Technical Occupations, 4.7 times higher in Transportation and Material Moving Occupations and in Computer and Mathematical Occupations, 4.8 times higher in Production Occupations, 5.3 times higher in Food Preparation and Serving Related Occupations, and 6.1 times higher in Healthcare Support Occupations and in Legal Occupations. This study identified occupation groups in US adult population with increased risk for CKD. Alleviation of workplace stress is suggested as a goal for behavioral intervention in high-risk occupations.

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

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Mazidi, Moshen; Rezaie, Peyman; Covic, Adriac; Malyszko, Jolanta; Rysz, Jacek; Kengne, Andre Pascal; Banach, Maciej

2017-10-06

Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function. We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults. The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights. Of the 10568 eligible participants, 48.0% ( n =5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all p function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, p =0.056). The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.

Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility.

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Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter A; Christman, Gregory M; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Schlaff, William; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2017-08-01

While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed. The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility. A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale. Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility. Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function. Copyright © 2017 Elsevier Inc. All rights reserved.

The cytoplasmic C-terminus of polycystin-1 increases cell proliferation in kidney epithelial cells through serum-activated and Ca2+-dependent pathway(s)

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Manzati, Elisa; Aguiari, Gianluca; Banzi, Manuela; Manzati, Michele; Selvatici, Rita; Falzarano, Sofia; Maestri, Iva; Pinton, Paolo; Rizzuto, Rosario; Senno, Laura del

2005-01-01

Polycystin-1 (PC1) is a large transmembrane protein important in renal differentiation and defective in most cases of autosomal dominant polycystic kidney disease (ADPKD), a common cause of renal failure in adults. Although the genetic basis of ADPKD has been elucidated, molecular and cellular mechanisms responsible for the dysregulation of epithelial cell growth in ADPKD cysts are still not well defined. We approached this issue by investigating the role of the carboxyl cytoplasmic domain of PC1 involved in signal transduction on the control of kidney cell proliferation. Therefore, we generated human HEK293 cells stably expressing the PC1 cytoplasmic tail as a membrane targeted TrkA-PC1 chimeric receptor protein (TrkPC1). We found that TrkPC1 increased cell proliferation through an increase in cytoplasmic Ca 2+ levels and activation of PKCα, thereby upregulating D1 and D3 cyclin, downregulating p21 waf1 and p27 kip1 cyclin inhibitors, and thus inducing cell cycle progression from G0/G1 to the S phase. Interestingly, TrkPC1-dependent Ca 2+ increase and PKCα activation are not constitutive, but require serum factor(s) as parallel component. In agreement with this observation, a significant increase in ERK1/2 phosphorylation was observed. Consistently, inhibitors specifically blocking either PKCα or ERK1/2 prevented the TrkPC1-dependent proliferation increase. NGF, the TrkA ligand, blocked this increase. We propose that in kidney epithelial cells the overexpression of PC1 C-terminus upregulates serum-evoked intracellular Ca 2+ by counteracting the growth-suppression activity of endogenous PC1 and leading to an increase in cell proliferation

Adipose expression of adipocytokines in women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Fog Svendsen, Pernille; Christiansen, Michael; Hedley, Paula Louise

2012-01-01

To investigate the role of adipocytokines in the pathophysiology of polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression and plasma levels of adipocytokines.......To investigate the role of adipocytokines in the pathophysiology of polycystic ovary syndrome (PCOS) by analyzing the messenger RNA (mRNA) expression and plasma levels of adipocytokines....

The Diagnostic Value of Anti-Müllerian Hormone in Early Post Menarche Adolescent Girls with Polycystic Ovarian Syndrome.

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Kocaay, Pınar; Siklar, Zeynep; Buyukfirat, Sema; Berberoglu, Merih

2018-02-17

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism and chronic anovulation, which affects 5%-10% of reproductive-age women. Diagnosis of adult patients with PCOS is made easily with clinical and laboratory methods and the anti-Müllerian hormone (AMH) level are accepted as a good indicator. However, there is still no complete consensus on the diagnosis of PCOS in adolescents. Prospective cohort study, December 2013 to November 2014. The study was conducted on adolescent girls with oligomenorrhea, with at least 2 years since menarche. The study group consisted of adolescent girls with complete PCOS and incomplete PCOS. A control group was formed of healthy adolescent girls. Complete PCOS was diagnosed according to the Rotterdam criteria, as the presence of all the following characteristics: oligomenorrhea, hyperandrogenism, and polycystic ovarian morphology on ultrasound image. Incomplete PCOS was accepted as "oligomenorrhea and polycystic ovarian morphology," or "oligomenorrhea and hyperandrogenism." All patients underwent a physical examination and the anthropometric assessments, insulin resistance, and acanthosis nigricans were recorded. It was also noted whether or not the patient had an acne score. The Ferriman-Gallwey score was applied to evaluate hirsutism. The results of this study showed that no statistically significant difference was found between the PCOS and incomplete PCOS groups and the control group with respect to AMH levels. The use of adult-specific diagnostic methods in adolescence might result in an incomplete diagnosis and inadequate treatment plan. Although the serum AMH level clearly facilitates the diagnosis of PCOS, the use of the AMH level in adolescence in PCOS diagnosis is still controversial and further studies are needed. Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Coronary artery disease risk in young women with polycystic ovary syndrome.

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Ding, Dah-Ching; Tsai, I-Ju; Wang, Jen-Hung; Lin, Shinn-Zong; Sung, Fung-Chang

2018-02-02

Women with polycystic ovary syndrome are characterized by obesity, menstruation irregularity, hirsutism and infertility, and prevalent with cardiometabolic comorbidities, but population-based studies on the risk of developing coronary artery disease are limited. From claims data of the Taiwan National Health Insurance, we identified 8048 women with polycystic ovary syndrome aged 15-49 years newly diagnosed in 1998-2013, and 32192 women without the syndrome and CAD as controls, frequency matched by age and diagnosis date. By the end of 2013, after a mean follow-up period of 5.9 years, the overall incidence of coronary artery disease was 63% higher in women with polycystic ovary syndrome than in controls (2.25 vs. 1.38 per 1000 person-years). The adjusted hazard ratio [aHR] of coronary artery disease was 1.44 (95% confidence interval (CI) = 1.14-1.81) for women with polycystic ovary syndrome, compared with controls. Hazards of coronary artery disease were significant during follow-up periods of 3-4 years (aHR = 1.52, 95% CI = 1.00-2.30) and of 5-9 years (aHR = 1.58, 95% CI = 1.07-2.32). The incidence of coronary artery disease increased further in those with cardiometabolic comorbidities. Among women with polycystic ovary syndrome, those with comorbid diabetes had an incidence of 35.2 per 1000 person-years, 20-fold greater than those without cardiometabolic comorbidities. In conclusion, women with polycystic ovary syndrome are at an elevated risk of coronary artery disease. Preventive interventions should be provided to them, particularly for those with the comorbidity of metabolism symptom.

Comparing effects of metformin and ginger rhizome extract on the pituitary - gonad function in adult female rats with polycystic ovary syndrome

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Mahbobeh Foroozandeh

2017-06-01

Full Text Available Background & aim: Polycystic Ovary Syndrome (PCOS is one of the most common causes of infertility in women. Due to the prevalence of PCOS in worldwide, this study aimed to compare the effect of metformin with ginger on pituitary-gonad function in PCOS adult female rats was performed. Methods: In this experimental study, 72 adult female rats divided to control, sham PCOS and 7 experimental groups PCOS receiving metformin at 500mg/kg, the ginger at doses 100, 200 & 300mg/kg and ginger at doses 100, 200 & 300mg /kg with metformin at 500 mg/kg were used. All injections by gavage and for 28 days were conducted. After phlebotomizing the animals, to measure hormones FSH, LH and estrogen, progesterone and testosterone, their ovaries removed and after preparing tissue sections, follicles were counted. Data obtained by 18-SPSS software and ANOVA and Duncan were analyzed, then the significant difference of data at P> 0.05was considered. Results: The results showed that letrozole by creating PCOS causes to increase atretic follicles, testosterone, estrogen and reduce other follicles and FSH at P<0.01, and metformin and Ginger alone and together cause to reduce atretic follicles, testosterone, estrogen and increase other follicles and FSH at P<0.01. Conclusion: The results showed that metformin and Ginger alone or together cause to improve PCOS, and these improvements in both groups receiving simultaneous ginger with metformin can be seen more.

The kidneys

International Nuclear Information System (INIS)

Freeman, L.M.; Lutzker, L.G.

1984-01-01

It has unfortunately remained true that radionuclide renal imaging studies have not been so widely accepted as other types of scintigraphy, despite improvements in radiopharmaceuticals and imaging techniques. Perhaps this is because of the variety of established radiologic techniques available for the study of the kidneys and the addition of new modalities such as CT scanning and ultrasound. Clinicians may have become confused by the multiplicity of options, which has obscured the distinction between renal scintigraphy and all other methods of imaging the kidney, i.e., that renal scintigraphy provides functional information in an easily quantifiable form. It is interesting that pediatric practitioners have more easily recognized the functional importance of this modality than have the practitioners of adult medicine, who more often prefer anatomic modalities, either traditional or new

Pattern of human chorionic gonadotropin binding in the polycystic ovary

International Nuclear Information System (INIS)

Brawer, J.; Richard, M.; Farookhi, R.

1989-01-01

The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles

Pattern of human chorionic gonadotropin binding in the polycystic ovary

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Brawer, J.; Richard, M.; Farookhi, R. (McGill Univ., Montreal, Quebec (Canada))

1989-08-01

The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

The assessment of cognitive function in older adult patients with chronic kidney disease: an integrative review.

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Hannan, Mary; Steffen, Alana; Quinn, Lauretta; Collins, Eileen G; Phillips, Shane A; Bronas, Ulf G

2018-05-25

Chronic kidney disease (CKD) is a common chronic condition in older adults that is associated with cognitive decline. However, the exact prevalence of cognitive impairment in older adults with CKD is unclear likely due to the variety of methods utilized to assess cognitive function. The purpose of this integrative review is to determine how cognitive function is most frequently assessed in older adult patients with CKD. Five electronic databases were searched to explore relevant literature related to cognitive function assessment in older adult patients with CKD. Inclusion and exclusion criteria were created to focus the search to the assessment of cognitive function with standardized cognitive tests in older adults with CKD, not on renal replacement therapy. Through the search methods, 36 articles were found that fulfilled the purpose of the review. There were 36 different types of cognitive tests utilized in the included articles, with each study utilizing between one and 12 tests. The most commonly utilized cognitive test was the Mini Mental State Exam (MMSE), followed by tests of digit symbol substitution and verbal fluency. The most commonly assessed aspect of cognitive function was global cognition. The assessment of cognitive function in older adults with CKD with standardized tests is completed in various ways. Unfortunately, the common methods of assessment of cognitive function may not be fully examining the domains of impairment commonly found in older adults with CKD. Further research is needed to identify the ideal cognitive test to best assess older adults with CKD for cognitive impairment.

RNA interference mediated pten knock-down inhibit the formation of polycystic ovary.

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Ouyang, Jie-Xiu; Luo, Tao; Sun, Hui-Yun; Huang, Jian; Tang, Dan-Feng; Wu, Lei; Zheng, Yue-Hui; Zheng, Li-Ping

2013-08-01

Pten (phosphatase and tensin homolog deleted on chromosome 10), a kind of tumor suppressor gene, plays important roles in female reproductive system. But its expression and roles in the formation of polycystic ovaries are yet to be known. In this study, we constructed a rat model of PCOS using norethindrone and HCG injections and found the expressions of pten mRNA and PTEN protein increased significantly in the polycystic ovary tissue by immunohistochemistry, RT-PCR, and western blot. Furthermore, the results showed that in vivo ovaries could be effectively transfected by lentiviral vectors through the ovarian microinjection method and indicated that pten shRNA may inhibit the formation of polycystic ovaries by pten down-regulation. Our study provides new information regarding the role of PTEN in female reproductive disorders, such as polycystic ovary syndrome.

Polycystic ovary morphology is associated with insulin resistance in women with polycystic ovary syndrome.

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Hong, So-Hyeon; Sung, Yeon-Ah; Hong, Young Sun; Jeong, Kyungah; Chung, Hyewon; Lee, Hyejin

2017-10-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic anovulation, hyperandrogenism, polycystic ovary morphology (PCOM) and metabolic disturbances including insulin resistance and type 2 diabetes mellitus. Although insulin resistance could be associated with PCOM, recent studies have shown controversial results. The aim of this study was to determine the relationship between PCOM and insulin resistance. This was a cross-sectional clinical study. A total of 679 women with PCOS who were diagnosed using the National Institute of Child Health and Human Disease (NICHD) criteria and 272 control women were analysed. We measured fasting glucose and insulin levels, 75 g oral glucose tolerance test-derived glucose and insulin levels, testosterone levels, ovarian volume and follicle number. Polycystic ovary morphology was described in 543 women (80.0%) with PCOS. Women with PCOS had significantly higher 2 hours postload glucose, fasting and 2 hours postload insulin levels, ovarian volume, ovarian follicle numbers and lower insulin sensitivity compared with those of the controls (all P<.01). In women with PCOS, ovarian volume and ovarian follicle number were negatively associated with the quantitative insulin sensitivity check index after adjusting for age, body mass index and total testosterone; however, this association was not observed in the controls. In the logistic regression analysis, increased ovarian follicle number was associated with decreased insulin sensitivity in women with PCOS. In PCOS, enlarged ovarian volume and follicle excess were associated with insulin resistance, and the number of ovarian follicles could be a predictor of insulin resistance. © 2017 John Wiley & Sons Ltd.

Estimated GFR and Subsequent Higher Left Ventricular Mass in Young and Middle-Aged Adults With Normal Kidney Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

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Bansal, Nisha; Lin, Feng; Vittinghoff, Eric; Peralta, Carmen; Lima, Joao; Kramer, Holly; Shlipak, Michael; Bibbins-Domingo, Kirsten

2016-02-01

Left ventricular hypertrophy is common and is associated with cardiovascular events and death among patients with known chronic kidney disease. However, the link between reduced glomerular filtration rate (GFR) and left ventricular mass index (LVMI) remains poorly explored among young and middle-aged adults with preserved kidney function. In this study, we examined the association of cystatin C-based estimated GFR (eGFRcys) and rapid decline in eGFR with subsequent LVMI. Observational study. We included 2,410 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with eGFRcys > 60mL/min/1.73m(2) at year 15 and who had an echocardiogram obtained at year 25. eGFRcys at year 15 and rapid decline in eGFRcys (defined as >3% per year over 5 years from years 15 to 20). LVMI measured at year 25. We adjusted for age, sex, race, diabetes, body mass index, low- and high-density lipoprotein cholesterol levels, cumulative systolic blood pressure, and albuminuria. Mean age was 40±4 (SD) years, 58% were women, and 43% were black. After 10 years of follow-up, mean LVMI was 39.6±13.4g/m(2.7). Compared with eGFRcys > 90mL/min/1.73m(2) (n = 2,228), eGFRcys of 60 to 75mL/min/1.73m(2) (n = 29) was associated with 5.63 (95% CI, 0.90-10.36) g/m(2.7) greater LVMI (P = 0.02), but there was no association of eGFRcys of 76 to 90mL/min/1.73m(2) (n = 153) with LVMI after adjustment for confounders. Rapid decline in eGFRcys was associated with higher LVMI compared with participants without a rapid eGFRcys decline (β coefficient, 1.48; 95% CI, 0.11-2.83; P = 0.03) after adjustment for confounders. There were a limited number of participants with eGFRcys of 60 to 90mL/min/1.73m(2). Among young and middle-aged adults with preserved kidney function, eGFRcys of 60 to 75mL/min/1.73m(2) and rapid decline in eGFRcys were significantly associated with subsequently higher LVMI. Further studies are needed to understand the mechanisms that contribute to elevated

Technical Evaluation: Identification of Pathogenic Mutations in PKD1 and PKD2 in Patients with Autosomal Dominant Polycystic Kidney Disease by Next-Generation Sequencing and Use of a Comprehensive New Classification System.

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Kinoshita, Moritoshi; Higashihara, Eiji; Kawano, Haruna; Higashiyama, Ryo; Koga, Daisuke; Fukui, Takafumi; Gondo, Nobuhisa; Oka, Takehiko; Kawahara, Kozo; Rigo, Krisztina; Hague, Tim; Katsuragi, Kiyonori; Sudo, Kimiyoshi; Takeshi, Masahiko; Horie, Shigeo; Nutahara, Kikuo

2016-01-01

Genetic testing of PKD1 and PKD2 is expected to play an increasingly important role in determining allelic influences in autosomal dominant polycystic kidney disease (ADPKD) in the near future. However, to date, genetic testing is not commonly employed because it is expensive, complicated because of genetic heterogeneity, and does not easily identify pathogenic variants. In this study, we developed a genetic testing system based on next-generation sequencing (NGS), long-range polymerase chain reaction, and a new software package. The new software package integrated seven databases and provided access to five cloud-based computing systems. The database integrated 241 polymorphic nonpathogenic variants detected in 140 healthy Japanese volunteers aged >35 years, who were confirmed by ultrasonography as having no cysts in either kidney. Using this system, we identified 60 novel and 30 known pathogenic mutations in 101 Japanese patients with ADPKD, with an overall detection rate of 89.1% (90/101) [95% confidence interval (CI), 83.0%-95.2%]. The sensitivity of the system increased to 93.1% (94/101) (95% CI, 88.1%-98.0%) when combined with multiplex ligation-dependent probe amplification analysis, making it sufficient for use in a clinical setting. In 82 (87.2%) of the patients, pathogenic mutations were detected in PKD1 (95% CI, 79.0%-92.5%), whereas in 12 (12.8%) patients pathogenic mutations were detected in PKD2 (95% CI, 7.5%-21.0%); this is consistent with previously reported findings. In addition, we were able to reconfirm our pathogenic mutation identification results using Sanger sequencing. In conclusion, we developed a high-sensitivity NGS-based system and successfully employed it to identify pathogenic mutations in PKD1 and PKD2 in Japanese patients with ADPKD.

MicroRNA-106b-5p regulates cisplatin chemosensitivity by targeting polycystic kidney disease-2 in non-small-cell lung cancer.

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Yu, Shaorong; Qin, Xiaobing; Chen, Tingting; Zhou, Leilei; Xu, Xiaoyue; Feng, Jifeng

2017-09-01

Systemic therapy with cytotoxic agents remains one of the main treatment methods for non-small-cell lung cancer (NSCLC). Cisplatin is a commonly used chemotherapeutic agent, that, when combined with other drugs, is an effective treatment for NSCLC. However, effective cancer therapy is hindered by a patient's resistance to cisplatin. Unfortunately, the potential mechanism underlying such resistance remains unclear. In this study, we explored the mechanism of microRNA-106b-5p (miR-106b-5p), which is involved in the resistance to cisplatin in the A549 cell line of NSCLC. Quantitative real-time PCR was used to test the expression of miR-106-5p in the A549 and the A549/DDP cell line of NSCLC. The cell counting kit-8 assay was used to detect cell viability. Flow cytometry was used to measure cell cycle and cell apoptosis. Luciferase reporter assays and western blot were performed to confirm whether polycystic kidney disease-2 (PKD2) is a direct target gene of miR-106b-5p. Immunohistochemistry was performed to examine the distribution of PKD2 expression in patients who are sensitive and resistant to cisplatin. The experiments indicated that the expression of miR-106b-5p was significantly decreased in A549/DDP compared with that in A549. MiR-106b-5p affected the tolerance of cells to cisplatin by negatively regulating PKD2. Upregulation of miR-106b-5p or downregulation of PKD2 expression can cause A549/DDP cells to become considerably more sensitive to cisplatin. The results showed that miR-106b-5p enhanced the sensitivity of A549/DDP cells to cisplatin by targeting the expression of PKD2. These findings suggest that the use of miR-106b-5p may be a promising clinical strategy in the treatment of NSCLC.

Independent Pre-Transplant Recipient Cancer Risk Factors after Kidney Transplantation and the Utility of G-Chart Analysis for Clinical Process Control.

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Harald Schrem

Full Text Available The aim of this study is to identify independent pre-transplant cancer risk factors after kidney transplantation and to assess the utility of G-chart analysis for clinical process control. This may contribute to the improvement of cancer surveillance processes in individual transplant centers.1655 patients after kidney transplantation at our institution with a total of 9,425 person-years of follow-up were compared retrospectively to the general German population using site-specific standardized-incidence-ratios (SIRs of observed malignancies. Risk-adjusted multivariable Cox regression was used to identify independent pre-transplant cancer risk factors. G-chart analysis was applied to determine relevant differences in the frequency of cancer occurrences.Cancer incidence rates were almost three times higher as compared to the matched general population (SIR = 2.75; 95%-CI: 2.33-3.21. Significantly increased SIRs were observed for renal cell carcinoma (SIR = 22.46, post-transplant lymphoproliferative disorder (SIR = 8.36, prostate cancer (SIR = 2.22, bladder cancer (SIR = 3.24, thyroid cancer (SIR = 10.13 and melanoma (SIR = 3.08. Independent pre-transplant risk factors for cancer-free survival were age 62.6 years (p = 0.001, HR: 1.29, polycystic kidney disease other than autosomal dominant polycystic kidney disease (ADPKD (p = 0.001, HR: 0.68, high body mass index in kg/m2 (p<0.001, HR: 1.04, ADPKD (p = 0.008, HR: 1.26 and diabetic nephropathy (p = 0.004, HR = 1.51. G-chart analysis identified relevant changes in the detection rates of cancer during aftercare with no significant relation to identified risk factors for cancer-free survival (p<0.05.Risk-adapted cancer surveillance combined with prospective G-chart analysis likely improves cancer surveillance schemes by adapting processes to identified risk factors and by using G-chart alarm signals to trigger Kaizen events and audits for root-cause analysis of relevant detection rate changes

Polycystin 1 loss of function is directly linked to an imbalance in G-protein signaling in the kidney.

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Zhang, Bo; Tran, Uyen; Wessely, Oliver

2018-03-22

The development of the kidney relies on the establishment and maintenance of a precise tubular diameter of its functional units, the nephrons. This process is disrupted in polycystic kidney disease (PKD), resulting in dilations of the nephron and renal cyst formation. In the course of exploring G-protein-coupled signaling in the Xenopus pronephric kidney, we discovered that loss of the G-protein α subunit, Gnas, results in a PKD phenotype. Polycystin 1, one of the genes mutated in human PKD, encodes a protein resembling a G-protein-coupled receptor. Furthermore, deletion of the G-protein-binding domain present in the intracellular C terminus of polycystin 1 impacts functionality. A comprehensive analysis of all the G-protein α subunits expressed in the Xenopus pronephric kidney demonstrates that polycystin 1 recruits a select subset of G-protein α subunits and that their knockdown - as in the case of Gnas - results in a PKD phenotype. Mechanistically, the phenotype is caused by increased endogenous G-protein β/γ signaling and can be reversed by pharmacological inhibitors as well as knocking down Gnb1. Together, our data support the hypothesis that G proteins are recruited to the intracellular domain of PKD1 and that this interaction is crucial for its function in the kidney. © 2018. Published by The Company of Biologists Ltd.

Characteristics of intracranial aneurysms in the else kröner-fresenius registry of autosomal dominant polycystic kidney disease.

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Neumann, Hartmut P H; Malinoc, Angelica; Bacher, Janina; Nabulsi, Zinaida; Ivanovas, Vera; Bruechle, Nadine Ortiz; Mader, Irina; Hoffmann, Michael M; Riegler, Peter; Kraemer-Guth, Annette; Burchardi, Christian; Schaeffner, Elke; Martin, Rodolfo S; Azurmendi, Pablo J; Zerres, Klaus; Jilg, Cordula; Eng, Charis; Gläsker, Sven

2012-01-01

Patients who harbor intracranial aneurysms (IAs) run a risk for aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is possible and recommended depending on the size and location of the aneurysm as well as patient age and condition. IAs are major manifestations of autosomal dominant polycystic kidney disease (ADPKD). Current guidelines do not suggest surveillance of IAs in ADPKD except in the setting of family history if IA was known in any relative with ADPKD. Management of IAs in ADPKD is problematic because limited data exist from large studies. We established the Else Kröner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for age at diagnosis of IAs, stage of renal insufficiency, and number, location and size of IAs as well as family history of cerebral events. Patients with symptomatic or asymptomatic IAs were included. All patients with ADPKD-related IAs were offered mutation scanning of the susceptibility genes for ADPKD, the PKD1 and PKD2 genes. Of 463 eligible ADPKD patients from the population base of Germany, 32 (7%) were found to have IAs, diagnosed at the age of 2-71 years, 19 females and 13 males. Twenty (63%) of these 32 patients were symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients. IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%), IAs were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated index cases (93%) had no IAs or cerebral events documented in their relatives with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline mutations. The mutations were randomly distributed across the PKD1 gene in 14 and the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD patients without IAs revealed that only 45/320 (14%) had MR angiography. In ADPKD, rupture of IAs occurs frequently before the start of dialysis

Characteristics of Intracranial Aneurysms in the Else Kröner-Fresenius Registry of Autosomal Dominant Polycystic Kidney Disease

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Neumann, Hartmut P.H.; Malinoc, Angelica; Bacher, Janina; Nabulsi, Zinaida; Ivanovas, Vera; Bruechle, Nadine Ortiz; Mader, Irina; Hoffmann, Michael M.; Riegler, Peter; Kraemer-Guth, Annette; Burchardi, Christian; Schaeffner, Elke; Martin, Rodolfo S.; Azurmendi, Pablo J.; Zerres, Klaus; Jilg, Cordula; Eng, Charis; Gläsker, Sven

2012-01-01

Background Patients who harbor intracranial aneurysms (IAs) run a risk for aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is possible and recommended depending on the size and location of the aneurysm as well as patient age and condition. IAs are major manifestations of autosomal dominant polycystic kidney disease (ADPKD). Current guidelines do not suggest surveillance of IAs in ADPKD except in the setting of family history if IA was known in any relative with ADPKD. Management of IAs in ADPKD is problematic because limited data exist from large studies. Methods We established the Else Kröner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for age at diagnosis of IAs, stage of renal insufficiency, and number, location and size of IAs as well as family history of cerebral events. Patients with symptomatic or asymptomatic IAs were included. All patients with ADPKD-related IAs were offered mutation scanning of the susceptibility genes for ADPKD, the PKD1 and PKD2 genes. Results Of 463 eligible ADPKD patients from the population base of Germany, 32 (7%) were found to have IAs, diagnosed at the age of 2–71 years, 19 females and 13 males. Twenty (63%) of these 32 patients were symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients. IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%), IAs were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated index cases (93%) had no IAs or cerebral events documented in their relatives with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline mutations. The mutations were randomly distributed across the PKD1 gene in 14 and the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD patients without IAs revealed that only 45/320 (14%) had MR angiography. Conclusion In ADPKD, rupture of IAs occurs

Characteristics of Intracranial Aneurysms in the Else Kröner-Fresenius Registry of Autosomal Dominant Polycystic Kidney Disease

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Hartmut P.H. Neumann

2012-10-01

Full Text Available Background: Patients who harbor intracranial aneurysms (IAs run a risk for aneurysm rupture and subsequent subarachnoid hemorrhage which frequently results in permanent deficits or death. Prophylactic treatment of unruptured aneurysms is possible and recommended depending on the size and location of the aneurysm as well as patient age and condition. IAs are major manifestations of autosomal dominant polycystic kidney disease (ADPKD. Current guidelines do not suggest surveillance of IAs in ADPKD except in the setting of family history if IA was known in any relative with ADPKD. Management of IAs in ADPKD is problematic because limited data exist from large studies. Methods: We established the Else Kröner-Fresenius Registry for ADPKD in Germany. Clinical data were assessed for age at diagnosis of IAs, stage of renal insufficiency, and number, location and size of IAs as well as family history of cerebral events. Patients with symptomatic or asymptomatic IAs were included. All patients with ADPKD-related IAs were offered mutation scanning of the susceptibility genes for ADPKD, the PKD1 and PKD2 genes. Results: Of 463 eligible ADPKD patients from the population base of Germany, 32 (7% were found to have IAs, diagnosed at the age of 2–71 years, 19 females and 13 males. Twenty (63% of these 32 patients were symptomatic, whereas IAs were detected in an asymptomatic stage in 12 patients. IAs were multifocal in 12 and unifocal in 20 patients. In 26 patients (81%, IAs were diagnosed before end-stage renal failure. Twenty-five out of 27 unrelated index cases (93% had no IAs or cerebral events documented in their relatives with ADPKD. In 16 unrelated index patients and 3 relatives, we detected germline mutations. The mutations were randomly distributed across the PKD1 gene in 14 and the PKD2 gene in 2 index cases. Questionnaires answered for 320/441 ADPKD patients without IAs revealed that only 45/320 (14% had MR angiography. Conclusion: In ADPKD

Sheep models of polycystic ovary syndrome phenotype

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Veiga-Lopez, Almudena

2012-01-01

Polycystic ovary syndrome (PCOS) is a fertility disorder affecting 5–7% of reproductive-aged women. Women with PCOS manifest both reproductive and metabolic defects. Several animal models have evolved, which implicate excess steroid exposure during fetal life in the development of the PCOS phenotype. This review addresses the fetal and adult reproductive and metabolic consequences of prenatal steroid excess in sheep and the translational relevance of these findings to PCOS. By comparing findings in various breeds of sheep, the review targets the role of genetic susceptibility to fetal insults. Disruptions induced by prenatal testosterone excess are evident at both the reproductive and metabolic level with each influencing the other thus creating a self-perpetuating vicious cycle. The review highlights the need for identifying a common mediator of the dysfunctions at the reproductive and metabolic levels and developing prevention and treatment interventions targeting all sites of disruption in unison for achieving optimal success. PMID:23084976

Prevalence of Reduced Kidney Function by Estimated Glomerular Filtration Rate Using an Equation Based on Creatinine and Cystatin C in Metabolic Syndrome and Its Components in Korean Adults

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Yang Ho Kang

2016-09-01

Full Text Available BackgroundIt is known that metabolic syndrome (MetS is associated with chronic kidney disease. We evaluated and compared the prevalence of reduced kidney function in MetS and its components by estimated glomerular filtration rate (eGFR using an equation based on creatinine (eGFRcr, cystatin C (eGFRcys, and combined creatinine-cystatin C (eGFRcr-cys in Korean adults.MethodsWe analyzed data from 3,649 adults who participated in a comprehensive health examination.ResultsMean values of eGFRcys were higher compared with mean values of eGFRcr (96.1±18.2 mL/min/1.73 m2 vs. 91.2±13.6 mL/min/1.73 m2 in total subjects. The prevalence of reduced kidney function increased with age (9.6% for eGFRcys vs. 5.8% for eGFRcr-cys vs. 4.9% for eGFRcr, in subjects aged ≥60 years, and significantly increased with MetS, abdominal obesity, hypertension, high triglyceride, low high density lipoprotein (HDL, and high insulin resistance. The prevalence of MetS, abdominal obesity, hypertension, high insulin resistance, low HDL, and hepatic steatosis was significantly increased in subjects with reduced kidney function. This increased prevalence and the odds ratio of reduced kidney function for prevalence of MetS was highest for eGFRcys, followed by those of eGFRcr-cys, and eGFRcr.ConclusionThe prevalence of reduced kidney function by eGFR was significantly increased in subjects with MetS and its related components. eGFRcys and eGFRcr-cys were superior to eGFRcr in detecting reduced kidney function.

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

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Orlando, Giuseppe; Khan, Muhammad A; El-Hennawy, Hany; Farney, Alan C; Rogers, Jeffrey; Reeves-Daniel, Amber; Gautreaux, Michael D; Doares, William; Kaczmorski, Scott; Stratta, Robert J

2018-03-01

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) 20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome.

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Montezuma, Thais; Antônio, Flávia Ignácio; Rosa e Silva, Ana Carolina Japur de Sá; Sá, Marcos Felipe Silva de; Ferriani, Rui Alberto; Ferreira, Cristine Homsi Jorge

2011-01-01

The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. One hundred thirteen 18-to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls) were recruited at the University Hospital of School Medicine of São Paulo University at Ribeirão Preto City, Brazil. The subjects were not taking any hormonal medication, had not undergone previous pelvic surgery and did not exercise their pelvic floor muscles. The women were divided into the following four groups: I-polycystic ovary syndrome with normal body mass index (n = 18), II-polycystic ovary syndrome with body mass index >25 (n = 32), III-controls with normal body mass index (n = 29), and IV-controls with Body Mass Index >25 (n = 34). Quality of life was evaluated using the SF-36 questionnaire, and the subjects with urinary complaints also completed the International Consultation on Incontinence Questionnaire Short Form to evaluate the severity of their urinary incontinence. The replies to the International Consultation on Incontinence Questionnaire Short Form revealed a significant difference in urinary function between groups, with 24% of the subjects in group IV reporting urinary incontinence. The mean scores for the SF-36 questionnaire revealed that group II had the lowest quality of life. The control obese group (IV) reported a higher prevalence of urinary incontinence. There was no difference in the reported frequency of urine loss between the polycystic ovary syndrome and control groups with normal body mass index or between the polycystic ovary syndrome and control groups with body mass index >25.

Assessment of symptoms of urinary incontinence in women with polycystic ovary syndrome

Directory of Open Access Journals (Sweden)

Thais Montezuma

2011-01-01

Full Text Available OBJECTIVES: The pelvic floor muscles are sensitive to androgens, and due to hyperandrogenism, women with polycystic ovary syndrome can have increased mass in these muscles compared to controls. The aim of this study is to compare reports of urine leakage and quality of life between women with and without polycystic ovary syndrome. METHODS: One hundred thirteen 18-to 40-year-old nulliparous women with polycystic ovary syndrome or without the disease (controls were recruited at the University Hospital of School Medicine of São Paulo University at Ribeirão Preto City, Brazil. The subjects were not taking any hormonal medication, had not undergone previous pelvic surgery and did not exercise their pelvic floor muscles. The women were divided into the following four groups: I-polycystic ovary syndrome with normal body mass index (n = 18, II-polycystic ovary syndrome with body mass index >25 (n = 32, III-controls with normal body mass index (n = 29, and IV-controls with Body Mass Index >25 (n = 34. Quality of life was evaluated using the SF-36 questionnaire, and the subjects with urinary complaints also completed the International Consultation on Incontinence Questionnaire Short Form to evaluate the severity of their urinary incontinence. RESULTS: The replies to the International Consultation on Incontinence Questionnaire Short Form revealed a significant difference in urinary function between groups, with 24% of the subjects in group IV reporting urinary incontinence. The mean scores for the SF-36 questionnaire revealed that group II had the lowest quality of life. CONCLUSIONS: The control obese group (IV reported a higher prevalence of urinary incontinence. There was no difference in the reported frequency of urine loss between the polycystic ovary syndrome and control groups with normal body mass index or between the polycystic ovary syndrome and control groups with body mass index >25.

Young for young! Mandatory age-matched exchange of paediatric kidneys.

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Pape, Lars; Ehrich, Jochen H H; Offner, Gisela

2007-04-01

Some allocation systems include a mandatory donation of paediatric kidneys to children, others do not. Both approaches have medical and organisational advantages and disadvantages for adults and children. This article discusses why "young for young" is the best allocation system for children. Primary age-matched kidney allocation to children is one important factor leading to: (1) higher long-term glomerular filtration rates (GFRs) and graft survival and, thereby, to lesser need for dialysis; (2) better psychosocial rehabilitation, growth and development of children and, last but not least, (3) likely increase of the donor pool. As a consequence, health care costs will be reduced for children with end-stage renal failure. The chance of adults receiving an adequate kidney would be only minimally reduced by this policy. Therefore, we recommend an age-matched allocation programme giving children with end- stage kidney diseases a better prognosis.

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants

Directory of Open Access Journals (Sweden)

Janina Müller-Deile, MD

2017-10-01

Full Text Available Background. Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. Methods. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1 expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. Results. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Conclusions. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that

Persistent estrus rat models of polycystic ovary disease: an update.

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Singh, Krishna B

2005-10-01

To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. University Health Sciences Center. Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.

The effects of polycystic ovary syndrome on gestational diabetes mellitus.

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Aktun, Hale Lebriz; Yorgunlar, Betul; Acet, Mustafa; Aygun, Banu Kumbak; Karaca, Nilay

2016-01-01

The aim of this study was to explore the inter-relationship between polycystic ovary syndrome and gestational diabetes mellitus, and demonstrate maternal and fetal outcomes. This was a case-control study in 1360 pregnant women who received a diagnosis of gestational diabetes mellitus between 24 and 28 weeks of gestational age. Among all diagnosed with gestational diabetes mellitus, 150 pregnant women had received a polycystic ovary syndrome, and 160 women who did not have polycystic ovary syndrome were designated as controls. The incidence of pregnancy-induced hypertension was 26.3% and 12% in the case and control groups, respectively. Preeclampsia was seen at an incidence of 12% and 6% in case and in control groups, respectively. The difference in neonatal hypoglycemia between the two groups was statistically significant, with an incidence of 17% and 5% in the case and in control groups, respectively. This study demonstrated that the presence of polycystic ovary syndrome along with gestational diabetes mellitus increases the risk of pregnancy induced hypertension by 2.4 fold, preeclampsia by 2 fold and neonatal hypoglycemia by 3.2 fold, compared to gestational diabetes mellitus alone.

A simplified donor risk index for predicting outcome after deceased donor kidney transplantation.

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Watson, Christopher J E; Johnson, Rachel J; Birch, Rhiannon; Collett, Dave; Bradley, J Andrew

2012-02-15

We sought to determine the deceased donor factors associated with outcome after kidney transplantation and to develop a clinically applicable Kidney Donor Risk Index. Data from the UK Transplant Registry on 7620 adult recipients of adult deceased donor kidney transplants between 2000 and 2007 inclusive were analyzed. Donor factors potentially influencing transplant outcome were investigated using Cox regression, adjusting for significant recipient and transplant factors. A United Kingdom Kidney Donor Risk Index was derived from the model and validated. Donor age was the most significant factor predicting poor transplant outcome (hazard ratio for 18-39 and 60+ years relative to 40-59 years was 0.78 and 1.49, respectively, Pinformed consent.

Liraglutide in polycystic ovary syndrome

DEFF Research Database (Denmark)

Nylander, Malin; Frøssing, Signe; Kistorp, Caroline

2017-01-01

Polycystic ovary syndrome (PCOS) is associated with increased risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) in later life. We aimed to study the effect of liraglutide intervention on markers of VTE and CVD risk, in PCOS. In a double-blind, placebo-controlled, randomized...

Gene Expression in the Normal Adult Human Kidney Assessed by Complementary DNA Microarray

OpenAIRE

Higgins, John P.T.; Wang, Lingli; Kambham, Neeraja; Montgomery, Kelli; Mason, Veronica; Vogelmann, Stefanie U.; Lemley, Kevin V.; Brown, Patrick O.; Brooks, James D.; van de Rijn, Matt

2004-01-01

The kidney is a highly specialized organ with a complex, stereotyped architecture and a great diversity of functions and cell types. Because the microscopic organization of the nephron, the functional unit of the kidney, has a consistent relationship to the macroscopic anatomy of the kidney, knowledge of the characteristic patterns of gene expression in different compartments of the kidney could provide insight into the functions and functional organization of the normal nephron. We studied g...

Beyond Income: A Social Justice Approach to Assessing Poverty among Older Adults with Chronic Kidney Disease.

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Caplan, Mary A; Washington, Tiffany R; Swanner, Lauren

2017-01-01

How social workers define and assess poverty is a matter of economic and social justice. Recent conceptual and measurement advances point to a multidimensional definition of poverty which captures material, social, and political deprivations. Using data from a survey, this article describes how nephrology social workers assess poverty among older adults living with a chronic kidney disease (N = 52). Results suggest respondents already conceive of poverty as a multidimensional experience, support awareness-raising about poverty, and primarily assess poverty by employment status, income, access to transportation, and education. Opportunities to expand poverty assessment in future work are promising.

Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome

OpenAIRE

Erol, Nurdan; Karaagac, Aysu Turkmen; Kounis, Nicholas G

2014-01-01

Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female wi...

Nutrition for Early Chronic Kidney Disease in Adults

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... Disease (CKD) Eating Right Related Topics English English French Español Section Navigation Chronic Kidney Disease (CKD) What ... foods, instead of deep frying. Cook with nonstick cooking spray or a small amount of olive oil ...

Polycystic ovarian disease: the adrenal connection.

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Marouliss, George B; Triantafillidis, Ioannis K

2006-01-01

Polycystic ovarian disease (PCOD) is characterized by hyperandrogenemia, ovulatory dysfunction and polycystic ovaries (PCO). The increased androgen production in PCOD comes primarily from the ovaries. However, in about 40% of patients there is excessive adrenal androgen production (DHEA, DHEA-Sulfate, Androstenedione, Testosterone and Dihydrotestosterone). The contribution of the adrenal in the PCOD is suggested by the presence of adrenal androgen excess in PCO, the presence of PCO in women with enzymatic adrenal hyperplasia as well as in women with adrenal tumors. However, the cause of adrenal androgen hypersecretion is not yet fully understood but it may include endogenous hypersecretion of the zona reticularis of unclear cause, hypersecretion of cortical-androgen-stimulating hormone (CASH), stress, hyperprolactinemia, adrenal enzymatic defects etc. This short review covers the aspects of adrenal androgen hypersecretion in PCOD.

Profiling conserved biological pathways in Autosomal Dominant Polycystic Kidney Disorder (ADPKD) to elucidate key transcriptomic alterations regulating cystogenesis: A cross-species meta-analysis approach.

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Chatterjee, Shatakshee; Verma, Srikant Prasad; Pandey, Priyanka

2017-09-05

Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen. Intra-species combined analysis was performed after considering removal of batch effect. Significantly enriched GO biological processes and KEGG pathways were computed and their overlap was observed. For the conserved pathways, biological modules and gene regulatory networks were observed. Additionally, Gene Set Enrichment Analysis (GSEA) using Molecular Signature Database (MSigDB) was performed for genes found in conserved pathways. We obtained 28 modules of significantly enriched GO processes and 5 major functional categories from significantly enriched KEGG pathways conserved in human, mice and rats that in turn suggest a global transcriptomic perturbation affecting cyst - formation, growth and progression. Significantly enriched pathways obtained from up-regulated genes such as Genomic instability, Protein localization in ER and Insulin Resistance were found to regulate cyst formation and growth whereas cyst progression due to increased cell adhesion and inflammation was suggested by perturbations in Angiogenesis, TGF-beta, CAMs, and Infection related pathways. Additionally, networks revealed shared genes among pathways e.g. SMAD2 and SMAD7 in Endocytosis and TGF-beta. Our study suggests cyst formation and progression to be an outcome of interplay between a set of several key deregulated pathways. Thus, further translational research is warranted focusing on developing a combinatorial therapeutic

Polycystic ovary morphology: age-based ultrasound criteria.

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Kim, Hyun-Jun; Adams, Judith M; Gudmundsson, Jens A; Arason, Gudmundur; Pau, Cindy T; Welt, Corrine K

2017-09-01

To determine age-based criteria for polycystic ovary morphology. Cross-sectional, case-control design. Outpatient setting. Women with polycystic ovary syndrome (PCOS) defined by hyperandrogenism and irregular menses (n = 544) and controls with regular menses and no evidence of hyperandrogenism (n = 666) participated. Parameters were tested in a second cohort of women with PCOS (n = 105) and controls (n = 32) meeting the same criteria. Subjects underwent a pelvic ultrasound documenting ovarian volume and maximum follicle number in a single plane. A receiver operating characteristic curve was constructed to determine the ovarian volume and follicle number with the best sensitivity and specificity to define PCOS for age groups at approximately 5-year intervals from age 18 to >44 years. The best sensitivity and specificity were obtained using a threshold volume of 12 mL and 13 follicles for ages ≤24 years, 10 mL and 14 follicles for ages 25-29 years, 9 mL and 10 follicles for ages 30-34 years, 8 mL and 10 follicles for ages 35-39 years, 10 mL and 9 follicles for ages 40-44 years, and 6 mL and 7 follicles for ages >44 years. Data from a second cohort confirmed the need to decrease volume and follicle number with increasing age to diagnose PCOS. Polycystic ovary morphology was most accurate at predicting the PCOS diagnosis for women ages 30-39 years. The ovarian volume and follicle number threshold to define polycystic ovary morphology should be lowered starting at age 30. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Nutritional support and dietary interventions for women with polycystic ovary syndrome

OpenAIRE

Papavasiliou,Kleopatra; Papakonstantinou,Emilia

2017-01-01

Kleopatra Papavasiliou, Emilia Papakonstantinou Unit of Human Nutrition, Department of Food Science and Human Nutrition, Agricultural University of Athens, Athens, Greece Abstract: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, which leads to reproductive, metabolic and hormonal abnormalities. Hyperinsulinemia, insulin resistance, androgen excess, ovulatory dysfunction, polycystic ovaries, gonadotropin abnormalities, obesity, adipose tissu...

Histone deacetylase 6 inhibition reduces cysts by decreasing cAMP and Ca2+ in knock-out mouse models of polycystic kidney disease.

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Yanda, Murali K; Liu, Qiangni; Cebotaru, Valeriu; Guggino, William B; Cebotaru, Liudmila

2017-10-27

Autosomal dominant polycystic kidney disease (ADPKD) is associated with progressive enlargement of multiple renal cysts, often leading to renal failure that cannot be prevented by a current treatment. Two proteins encoded by two genes are associated with ADPKD: PC1 ( pkd1 ), primarily a signaling molecule, and PC2 ( pkd2 ), a Ca 2+ channel. Dysregulation of cAMP signaling is central to ADPKD, but the molecular mechanism is unresolved. Here, we studied the role of histone deacetylase 6 (HDAC6) in regulating cyst growth to test the possibility that inhibiting HDAC6 might help manage ADPKD. Chemical inhibition of HDAC6 reduced cyst growth in PC1-knock-out mice. In proximal tubule-derived, PC1-knock-out cells, adenylyl cyclase 6 and 3 (AC6 and -3) are both expressed. AC6 protein expression was higher in cells lacking PC1, compared with control cells containing PC1. Intracellular Ca 2+ was higher in PC1-knock-out cells than in control cells. HDAC inhibition caused a drop in intracellular Ca 2+ and increased ATP-simulated Ca 2+ release. HDAC6 inhibition reduced the release of Ca 2+ from the endoplasmic reticulum induced by thapsigargin, an inhibitor of endoplasmic reticulum Ca 2+ -ATPase. HDAC6 inhibition and treatment of cells with the intracellular Ca 2+ chelator 1,2-bis(2-aminophenoxy)ethane- N , N , N ', N '-tetraacetic acid tetrakis(acetoxymethyl ester) reduced cAMP levels in PC1-knock-out cells. Finally, the calmodulin inhibitors W-7 and W-13 reduced cAMP levels, and W-7 reduced cyst growth, suggesting that AC3 is involved in cyst growth regulated by HDAC6. We conclude that HDAC6 inhibition reduces cell growth primarily by reducing intracellular cAMP and Ca 2+ levels. Our results provide potential therapeutic targets that may be useful as treatments for ADPKD. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping.

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Czerniecki, Stefan M; Cruz, Nelly M; Harder, Jennifer L; Menon, Rajasree; Annis, James; Otto, Edgar A; Gulieva, Ramila E; Islas, Laura V; Kim, Yong Kyun; Tran, Linh M; Martins, Timothy J; Pippin, Jeffrey W; Fu, Hongxia; Kretzler, Matthias; Shankland, Stuart J; Himmelfarb, Jonathan; Moon, Randall T; Paragas, Neal; Freedman, Benjamin S

2018-05-15

Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting. High-content imaging analysis reveals both dose-dependent and threshold effects during organoid differentiation. Immunofluorescence and single-cell RNA sequencing identify previously undetected parietal, interstitial, and partially differentiated compartments within organoids and define conditions that greatly expand the vascular endothelium. Chemical modulation of toxicity and disease phenotypes can be quantified for safety and efficacy prediction. Screening in gene-edited organoids in this system reveals an unexpected role for myosin in polycystic kidney disease. Organoids in HTS formats thus establish an attractive platform for multidimensional phenotypic screening. Copyright © 2018 Elsevier Inc. All rights reserved.

Polycystic Ovary Syndrome

OpenAIRE

McCartney, Christopher R.; Marshall, John C.

2016-01-01

Polycystic ovary syndrome is a condition in which a woman has an imbalance of female sex hormones. This may lead to menstrual cycle changes, cysts in the ovaries, trouble getting pregnant, and other health changes. In PCOS, mature eggs are not released from the ovaries. Instead, they can form very small cysts in the ovary. These changes can contribute to infertility. Common symptoms of PCOS include Menstrual disorders, Infertility, High levels of testosterone and Metabolic syndrome. Obesity, ...

Does hypertension remain after kidney transplantation?

Directory of Open Access Journals (Sweden)

Gholamreza Pourmand

2015-05-01

Full Text Available Hypertension is a common complication of kidney transplantation with the prevalence of 80%. Studies in adults have shown a high prevalence of hypertension (HTN in the first three months of transplantation while this rate is reduced to 50- 60% at the end of the first year. HTN remains as a major risk factor for cardiovascular diseases, lower graft survival rates and poor function of transplanted kidney in adults and children. In this retrospective study, medical records of 400 kidney transplantation patients of Sina Hospital were evaluated. Patients were followed monthly for the 1st year, every two months in the 2nd year and every three months after that. In this study 244 (61% patients were male. Mean ± SD age of recipients was 39.3 ± 13.8 years. In most patients (40.8% the cause of end-stage renal disease (ESRD was unknown followed by HTN (26.3%. A total of 166 (41.5% patients had been hypertensive before transplantation and 234 (58.5% had normal blood pressure. Among these 234 individuals, 94 (40.2% developed post-transplantation HTN. On the other hand, among 166 pre-transplant hypertensive patients, 86 patients (56.8% remained hypertensive after transplantation. Totally 180 (45% patients had post-transplantation HTN and 220 patients (55% didn't develop HTN. Based on the findings, the incidence of post-transplantation hypertension is high, and kidney transplantation does not lead to remission of hypertension. On the other hand, hypertension is one of the main causes of ESRD. Thus, early screening of hypertension can prevent kidney damage and reduce further problems in renal transplant recipients.

β-endorphins Plasma Level is Higher in Lean Polycystic Ovary Syndrome (PCOS) Women.

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Kiałka, M; Milewicz, T; Spałkowska, M; Krzyczkowska-Sendrakowska, M; Wasyl, B; Pełka, A; Krzysiek, J

2016-01-01

The evaluation the β-endorphin plasma levels in lean women with polycystic ovary syndrome as well as in women without this disorder. The associations between β-endorphins and other laboratory parameters were also investigated. 31 women lean, defined as women with normal range body mass index, 15 with polycystic ovary syndrome and 16 without this disorder were included to the study. In all the patients the level of β-endorphins was measured. Also the diagnostic laboratory profile including hormone assessment was made in all patients. There were significant differences in β-endorphin levels between the 2 groups. The β-endorphin level was higher in the polycystic ovary syndrome group compared to the healthy controls (15.5±4.37 pg/ml vs. 6.9±2.47 pg/ml, ppolycystic ovary syndrome group. Increase in β-endorphin level of 1 pg/ml was associated with an increase of cortisol at 8 am level of 1.134 µg/dl and decrease of sex hormone binding globuline of 0.948 nmol/l in polycystic ovary syndrome group. Our study showed that the levels of β-endorphins were significantly higher in lean patients with polycystic ovary syndrome than in lean controls. Moreover, β-endorphins levels were found to be correlated with other hormonal parameters. In this respect, β-endorphins may play a role in polycystic ovary syndrome pathophysiology. © Georg Thieme Verlag KG Stuttgart · New York.

Dyslipidaemia in woman with polycystic ovarian syndrome: a case control study in tertiary care hospital of Karachi.

Science.gov (United States)

Hussain, Amna; Alam, Junaid Mahmood

2014-09-01

To compare lipid profile in lean and obese women with polycystic ovary syndrome with normal weight and obese controls. The case-control study was conducted at the Department of Chemical Pathology, Liaquat National Hospital, Karachi, from March 2006 to April 2007. It comprised 50 cases of polycystic ovary syndrome along with 50 healthy controls matching for age, gender and weight. SPSS 14 was used for statistical analysis. The mean fasting levels of triglyceride and Low density lipoprotein cholesterol were considerably higher in women with polycystic ovary syndrome than those in the control group (p polycystic ovary syndrome, obesity and triglyceride levels (p Polycystic ovary syndrome is associated with a more pronounced atherogenic lipid profile. Lipid parameters were adversely affected in a subgroup that was obese. As such, women with polycystic ovary syndrome are at high risk of developing cardiovascular disease due to the presence of dyslipidaemia.

Health Literacy of Living Kidney Donors and Kidney Transplant Recipients

Science.gov (United States)

Dageforde, Leigh Anne; Petersen, Alec W.; Feurer, Irene D.; Cavanaugh, Kerri L.; Harms, Kelly A.; Ehrenfeld, Jesse M.; Moore, Derek E.

2015-01-01

Background Health literacy (HL) may be a mediator for known socioeconomic and racial disparities in living kidney donation. Methods We evaluated the associations of patient and demographic characteristics with HL in living kidney donors (LD), living donor kidney transplant recipients (LDR), and deceased donor recipients (DDR) in a single center retrospective review of patients undergoing kidney donation or transplantation from September 2010 to July 2012. HL and demographic data were collected. HL was assessed via the Short Literacy Survey (SLS) comprising three self-reported screening questions scored using the 5-point Likert scale [low (3-8), moderate (9-14), high (15)]. Chi-square and logistic regression were used to test factors associated with lower HL. Results The sample included 360 adults (105 LD, 103 LDR, 152 DDR; 46±14 years; 70% white; 56% male; 14±3 years of education). HL scores were skewed (49% high, 41% moderate, 10% low). The distribution of HL categories differed significantly among groups (p=0.019). After controlling for age, race, gender, education and a race-education interaction term, DDR were more likely to have moderate or low HL than LDR (OR 1.911; 95%CI 1.096, 3.332; p=0.022) Conclusions Overall, living donors had high HL. The distribution of low, moderate and high HL differed significantly between LD, DDR and LDR. DDR had a higher likelihood of having low HL than LDR. Screening kidney transplant candidates and donors for lower HL may identify barriers to living donation. Future interventions addressing HL may be important to increase living donation and reduce disparities. PMID:24573114

Concise Review: Kidney Generation with Human Pluripotent Stem Cells.

Science.gov (United States)

Morizane, Ryuji; Miyoshi, Tomoya; Bonventre, Joseph V

2017-11-01

Chronic kidney disease (CKD) is a worldwide health care problem, resulting in increased cardiovascular mortality and often leading to end-stage kidney disease, where patients require kidney replacement therapies such as hemodialysis or kidney transplantation. Loss of functional nephrons contributes to the progression of CKD, which can be attenuated but not reversed due to inability to generate new nephrons in human adult kidneys. Human pluripotent stem cells (hPSCs), by virtue of their unlimited self-renewal and ability to differentiate into cells of all three embryonic germ layers, are attractive sources for kidney regenerative therapies. Recent advances in stem cell biology have identified key signals necessary to maintain stemness of human nephron progenitor cells (NPCs) in vitro, and led to establishment of protocols to generate NPCs and nephron epithelial cells from human fetal kidneys and hPSCs. Effective production of large amounts of human NPCs and kidney organoids will facilitate elucidation of developmental and pathobiological pathways, kidney disease modeling and drug screening as well as kidney regenerative therapies. We summarize the recent studies to induce NPCs and kidney cells from hPSCs, studies of NPC expansion from mouse and human embryonic kidneys, and discuss possible approaches in vivo to regenerate kidneys with cell therapies and the development of bioengineered kidneys. Stem Cells 2017;35:2209-2217. © 2017 AlphaMed Press.

Genetics Home Reference: polycystic ovary syndrome

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... on PubMed Ünlütürk U, Sezgin E, Yildiz BO. Evolutionary determinants of polycystic ovary syndrome: part 1. Fertil ... genome editing and CRISPR-Cas9? What is precision medicine? What is newborn screening? New Pages Alopecia areata ...

Metabolic screening in patients with polycystic ovary syndrome is largely underutilized among obstetrician-gynecologists.

Science.gov (United States)

Dhesi, Amy S; Murtough, Katie L; Lim, Jonathan K; Schulkin, Jay; McGovern, Peter G; Power, Michael L; Morelli, Sara S

2016-11-01

Women with polycystic ovary syndrome have substantially higher rates of insulin resistance, impaired glucose tolerance, type 2 diabetes, dyslipidemia, and metabolic syndrome when compared with women without the disease. Given the high prevalence of these comorbidities, guidelines issued by the American College of Obstetricians and Gynecologists and the Endocrine Society recommend that all women with polycystic ovary syndrome undergo screening for impaired glucose tolerance and dyslipidemia with a 2 hour 75 g oral glucose tolerance test and fasting lipid profile upon diagnosis and also undergo repeat screening every 2-5 years and every 2 years, respectively. Although a hemoglobin A1C and/or fasting glucose are widely used screening tests for diabetes, both the American College of Obstetricians and Gynecologists and the Endocrine Society preferentially recommend the 2 hour oral glucose tolerance test in women with polycystic ovary syndrome as a superior indicator of impaired glucose tolerance/diabetes mellitus. However, we found that gynecologists underutilize current recommendations for metabolic screening in women with polycystic ovary syndrome. In an online survey study targeting American College of Obstetricians and Gynecologists fellows and junior fellows, 22.3% of respondents would not order any screening test at the initial visit for at least 50% of their patients with polycystic ovary syndrome. The most common tests used to screen for impaired glucose tolerance in women with polycystic ovary syndrome were hemoglobin A1C (51.0%) and fasting glucose (42.7%). Whereas 54.1% would order a fasting lipid profile in at least 50% of their polycystic ovary syndrome patients, only 7% of respondents order a 2 hour oral glucose tolerance test. We therefore call for increased efforts to encourage obstetrician-gynecologists to address metabolic abnormalities in their patients with polycystic ovary syndrome. Such efforts should include education of physicians early in their

Metformin in polycystic ovary syndrome

NARCIS (Netherlands)

Moll, E.

2013-01-01

The main result of this thesis can be summarized as follows: the addition of metformin to clomifene citrate in therapy-naïve women with polycystic ovary syndrome does not increase their chance of pregnancy except for possibly a subgroup of older women with high waist hip ratio, does hardly lead to

Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

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Troy Camarata

Full Text Available New nephron formation (nephrogenesis ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

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Camarata, Troy; Howard, Alexis; Elsey, Ruth M; Raza, Sarah; O'Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

2016-01-01

New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney

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Camarata, Troy; Howard, Alexis; Elsey, Ruth M.; Raza, Sarah; O’Connor, Alice; Beatty, Brian; Conrad, Jack; Solounias, Nikos; Chow, Priscilla; Mukta, Saima; Vasilyev, Aleksandr

2016-01-01

New nephron formation (nephrogenesis) ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds) and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles) may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates) showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population. PMID:27144443

Medication adherence in the transition of adolescent kidney transplant recipients to the adult care.

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Akchurin, Oleh M; Melamed, Michal L; Hashim, Becky L; Kaskel, Frederick J; Del Rio, Marcela

2014-08-01

Non-adherence is common in adolescent and young adult kidney transplant recipients, leading to adverse graft outcomes. The aim of this study was to determine whether adherence to immunosuppressant medications changes during transition from a pediatric to an adult program within the same transplant center. Adherence was assessed for a period of two yr before and two yr after the transfer. Subtherapeutic trough levels of serum tacrolimus and level variability were used as measures of adherence. Twenty-five patients were transitioned between 1996 and 2011 at the median age of 22.3 [IQR 21.6-23.0] yr. Young adults 21-25 yr of age (n = 26) and non-transitioned adolescents 17-21 yr of age (currently followed in the program, n = 24 and those that lost their grafts prior to the transfer, 22) formed the comparison groups. In the transitioned group, adherence prior to the transfer was not significantly different from the adherence after the transfer (p = 0.53). The rate of non-adherence in the group of non-transitioned adolescents who lost their grafts (68%) was significantly higher than in the transitioned group (32%, p = 0.01). In the group of young adults, adherence was not significantly different from the transitioned group (p = 0.27). Thus, transition was not associated with differences in medication adherence in this single-center study. Large-scale studies are needed to evaluate the national data on medication adherence after transfer. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of vitamin D status and obesity on C-reactive protein in kidney-transplant patients

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Ewers, B.; Gasbjerg, A.; Zerahn, B.

2008-01-01

and Patients: Data were collected between December 2005 and April 2006 from 161 adult (aged >18 years) kidney-transplant patients (mean age, 53.1 years; SD, 11.5 years; females/males, 78/83), with a median kidney-graft age of 7.0 years and serum CRP levels :... was found. Fat mass correlated positively with CRP, suggesting that obesity may increase the risk of cardiovascular disease and chronic allograft rejection in kidney-transplant patients. (C) 2008 by the National Kidney Foundation, Inc Udgivelsesdato: 2008/5......Objective: We examined whether vitamin D status and obesity are associated with low-grade systemic inflammation, as assessed by serum concentrations of C-reactive protein (CRP) in an adult population of kidney-transplant patients. Design: This was a single-center, cross-sectional study. Setting...

An observational study of health literacy and medication adherence in adult kidney transplant recipients

OpenAIRE

Demian, Maryam N.; Shapiro, R. Jean; Thornton, Wendy Loken

2016-01-01

Background There is a high prevalence of non-adherence to immunosuppressants in kidney transplant recipients. Although limited health literacy is common in kidney recipients and is linked to adverse outcomes in other medical populations, its effect on medication adherence in kidney transplant recipients remains poorly understood. The objective was to investigate the effect of lower health literacy on immunosuppressant adherence. Methods Kidney recipients who were at least 6 months post-transp...

A follow-up study of autosomal dominant polycystic kidney disease with intracranial aneurysms using 3.0 T three-dimensional time-of-flight magnetic resonance angiography

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Jiang, Tao; Wang, Peng; Qian, Yi [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Zheng, Xuan [Clinical Nutrition Department of Changhai Hospital, Second Military Medical University, Shanghai (China); Xiao, Liaoyuan [Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Yu, Shengqiang, E-mail: yushengqiang_cz@163.com [Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Liu, Shiyuan, E-mail: laijiangtaotao@163.com [Department of Radiology, Changzheng Hospital, Second Military Medical University, Shanghai (China)

2013-11-01

Objective: Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). Our aim was to screen and follow up the unruptured intracranial aneurysms (UIAs) detected by 3.0 T three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) in patients with ADPKD in order to evaluate the growth of UIAs and the value of 3D-TOF MRA. Methods: From 2011 to 2012, we followed up UIAs detected in 40 ADPKD patients who had MRA examinations with an interval of at least 36 months. All MRA examinations were performed on a 3 T system (Achieva X-Series, Philips Medical Systems) with a Sense-Head-8 receiver head coil. The acquired data sets were transferred to a workstation (EWS, Philips Medical) to perform maximum intensity projection (MIP) and volume rendering (VR) with a specialized software package (Philips Medical). The size of UIAs was determined as the longest diameter in transverse or vertical measurement. UIAs that grew more than 20% were considered as enlarged. Results: Fifty UIAs were found in 40 previously examined ADPKD patients who underwent 3.0 T 3D-TOF MRA follow-ups. No patients ever had treatment before the second examination. The longest diameter of all follow-up UIAs was less than 10 mm and mean diameter was 3.64 ± 2.25 mm. UIAs in only 4 patients (10%) were considered as enlarged. None of the 50 IAs in the 40 ADPKD patients ruptured during the MRA follow-up period. Conclusion: 3.0 T 3D-TOF MRA was feasible for UIAs follow-up in ADPKD patients. The chance of enlargement and rupture of UIAs in ADPKD patients was not higher than in the general population.

A follow-up study of autosomal dominant polycystic kidney disease with intracranial aneurysms using 3.0 T three-dimensional time-of-flight magnetic resonance angiography.

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Jiang, Tao; Wang, Peng; Qian, Yi; Zheng, Xuan; Xiao, Liaoyuan; Yu, Shengqiang; Liu, Shiyuan

2013-11-01

Autosomal dominant polycystic kidney disease (ADPKD) patients have an increased risk for intracranial aneurysms (IAs). Our aim was to screen and follow up the unruptured intracranial aneurysms (UIAs) detected by 3.0 T three-dimensional time-of-flight magnetic resonance angiography (3D-TOF MRA) in patients with ADPKD in order to evaluate the growth of UIAs and the value of 3D-TOF MRA. From 2011 to 2012, we followed up UIAs detected in 40 ADPKD patients who had MRA examinations with an interval of at least 36 months. All MRA examinations were performed on a 3T system (Achieva X-Series, Philips Medical Systems) with a Sense-Head-8 receiver head coil. The acquired data sets were transferred to a workstation (EWS, Philips Medical) to perform maximum intensity projection (MIP) and volume rendering (VR) with a specialized software package (Philips Medical). The size of UIAs was determined as the longest diameter in transverse or vertical measurement. UIAs that grew more than 20% were considered as enlarged. Fifty UIAs were found in 40 previously examined ADPKD patients who underwent 3.0 T 3D-TOF MRA follow-ups. No patients ever had treatment before the second examination. The longest diameter of all follow-up UIAs was less than 10mm and mean diameter was 3.64 ± 2.25 mm. UIAs in only 4 patients (10%) were considered as enlarged. None of the 50 IAs in the 40 ADPKD patients ruptured during the MRA follow-up period. 3.0 T 3D-TOF MRA was feasible for UIAs follow-up in ADPKD patients. The chance of enlargement and rupture of UIAs in ADPKD patients was not higher than in the general population. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Attention deficit-hyperactivity disorder symptoms in women with polycystic ovary syndrome.

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Hergüner, Sabri; Harmancı, Hatice; Toy, Harun

2015-01-01

Several studies suggest that androgens are involved in the etiology of attention deficit-hyperactivity disorder (ADHD). In this study, we investigated the ADHD symptoms in women with polycystic ovary syndrome (PCOS), a complex endocrine, hormonal, and metabolic condition associated with hyperandrogenism. Forty women between the ages of 18 and 35 years with PCOS were recruited for the study group. For comparison, 40 healthy women who had regular menses were included. Current and childhood ADHD symptoms were assessed by using the Adult ADHD Self-Report Scale and Wender-Utah Rating Scale, respectively. Women with PCOS had higher total Adult ADHD Self-Report Scale and total Wender-Utah Rating Scale scores than controls. According to the Wender-Utah Rating Scale, the frequency of childhood ADHD was significantly higher in PCOS group than the control. Adult ADHD Self-Report Scale: Hyperactivity-Impulsivity and Wender-Utah Rating Scale: Behavioral Problems/Impulsivity scores were significantly higher in women with PCOS. However, there were no significant differences between groups in both current and childhood inattention scores. We found no correlations between ADHD symptoms and serum hormone levels including testosterone in women with PCOS. These results suggest that women with PCOS have higher ADHD symptoms. Further studies are needed to investigate the association between PCOS and ADHD. © The Author(s) 2015.

Oncological repercussions of polycystic ovary syndrome

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de França Neto, Antônio H; Rogatto, Silvia; Do Amorim, Melania M R

2010-01-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine disorder that has been associated with insulin resistance and metabolic syndrome. Evidence has suggested that PCOS may be associated with the appearance of certain types of cancer, particularly endometrial, ovarian and breast cancer...

Diabetes risk in women with gestational diabetes mellitus and a history of polycystic ovary syndrome: a retrospective cohort study.

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Bond, R; Pace, R; Rahme, E; Dasgupta, K

2017-12-01

To investigate whether polycystic ovary syndrome further increases postpartum diabetes risk in women with gestational diabetes mellitus and to explore relationships between polycystic ovary syndrome and incident diabetes in women who do not develop gestational diabetes. This retrospective cohort study (Quebec Physician Services Claims; Hospitalization Discharge Databases; Birth and Death registries) included 34 686 women with gestational diabetes during pregnancy (live birth), matched 1:1 to women without gestational diabetes by age group, year of delivery and health region. Diagnostic codes were used to define polycystic ovary syndrome and incident diabetes. Cox regression models were used to examine associations between polycystic ovary syndrome and incident diabetes. Polycystic ovary syndrome was present in 1.5% of women with gestational diabetes and 1.2% of women without gestational diabetes. There were more younger mothers and mothers who were not of white European ancestry among those with polycystic ovary syndrome. Those with polycystic ovary syndrome more often had a comorbidity and a lower proportion had a previous pregnancy. Polycystic ovary syndrome was associated with incident diabetes (hazard ratio 1.52; 95% CI 1.27, 1.82) among women with gestational diabetes. No conclusive associations between polycystic ovary syndrome and diabetes were identified (hazard ratio 0.94; 95% CI 0.39, 2.27) in women without gestational diabetes. In women with gestational diabetes, polycystic ovary syndrome confers additional risk for incident diabetes postpartum. In women without gestational diabetes, an association between PCOS and incident diabetes was not observed. Given the already elevated risk of diabetes in women with a history of gestational diabetes, a history of both polycystic ovary syndrome and gestational diabetes signal a critical need for diabetes surveillance and prevention. © 2017 Diabetes UK.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

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Dobrowolski, Linn C; van Huis, Maike; van der Lee, Johanna H; Peters Sengers, Hessel; Liliën, Marc R; Cransberg, Karlien; Cornelissen, Marlies; Bouts, Antonia H; de Fijter, Johan W; Berger, Stefan P; van Zuilen, Arjan; Nurmohamed, Shaikh A; Betjes, Michiel H G; Hilbrands, Luuk; Hoitsma, Andries J; Bemelman, Frederike J; Krediet, C T Paul; Groothoff, Jaap W

2016-11-01

Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The monocyte counts to HDL cholesterol ratio in obese and lean patients with polycystic ovary syndrome.

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Usta, Akin; Avci, Eyup; Bulbul, Cagla Bahar; Kadi, Hasan; Adali, Ertan

2018-04-10

Women with polycystic ovary syndrome are more likely to suffer from obesity, insulin resistance, and chronic low-grade inflammation. In fact, the excessive activation of monocytes exacerbates oxidative stress and inflammation. However, high-density lipoprotein cholesterol neutralizes the pro-inflammatory and pro-oxidant effects of monocytes. The aim of this study is to investigate whether monocyte counts to high-density lipoprotein cholesterol ratio can predict the inflammatory condition in patients with polycystic ovary syndrome. In this cross-sectional study, a total of 124 women (61 of them with polycystic ovary syndrome and 63 age-matched healthy volunteers) were included in the study population. Obese polycystic ovary syndrome patients (n = 30) with a body mass index of ≥25 kg/m 2 and lean polycystic ovary syndrome patients (n = 31) with a body mass index of polycystic ovary syndrome were significantly higher than in control subjects (p = 0.0018). Moreover, a regression analysis revealed that body mass index, the homeostasis model assessment of insulin resistance and the high sensitivity C-reactive protein levels were confounding factors that affected the monocyte counts to high density lipoprotein cholesterol values. Additionally, a univariate and multivariate logistic regression analysis demonstrated that the increased monocyte counts to high density lipoprotein cholesterol values were more sensitive than the other known risk factors (such as increased body mass index, homeostasis model assessment of insulin resistance and high sensitive C-reactive protein levels) in the prediction of the inflammation in patients with polycystic ovary syndrome. The present study demonstrated that the monocyte count to high density lipoprotein cholesterol may be a novel and useful predictor of the presence of polycystic ovary syndrome.

Prevalence of chronic kidney disease among adults in a rural community in South India: Results from the kidney disease screening (KIDS project

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Y J Anupama

2014-01-01

Full Text Available Prevalence of chronic kidney disease (CKD appears to be increasing in India. A few studies have studied the prevalence of CKD in urban populations, but there is a paucity of such studies in the rural populations. This project was undertaken to study the prevalence of CKD among adults in a rural population near Shimoga, Karnataka and to study the risk factor profile. Door-to-door screening of 2091 people aged 18 and above was carried out. Demographic and anthropometric data were obtained, urine was analyzed for protein by dipstick and serum creatinine was measured in all participants. Glomerular filtration rate was estimated (eGFR using the 4-variable modification of diet in renal disease (MDRD equation and Cockcroft-Gault equation corrected to the body surface area (CG-BSA. The total number of subjects studied was 2091. Mean age was 39.88 ± 15.87 years. 45.57% were males. The prevalence of proteinuria was 2.8%. CKD was seen in 131 (6.3% subjects when GFR was estimated by MDRD equation. The prevalence of CKD was 16.54% by the CG-BSA method. There was a statistically significant relationship of CKD with gender, advancing age, abdominal obesity, smoking, presence of diabetes and hypertension. The prevalence of CKD is higher compared to the previous studies from rural India and is comparable to that in the studies from the urban Indian populations. The wide difference between the CKD prevalence between MDRD and CG-BSA equations suggests the need for a better measure of kidney function applicable to Indian population.

Dual Kidney Transplantation Offers a Valuable Source for Kidneys With Good Functional Outcome.

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Khalid, U; Asderakis, A; Rana, T; Szabo, L; Chavez, R; Ilham, M A; Ablorsu, E

2016-01-01

Reasons for declining kidney donors are older age, with or without, hypertension, kidney dysfunction, and diabetes. Implantation of both kidneys into a single recipient from such donors may improve their acceptability and outcome. Patients who underwent dual kidney transplantation (DKT) between June 2010 and May 2014 were identified from a prospectively maintained database. Single kidney transplantations (SKT) with matching donor criteria were also identified. Donors considered for DKT were the following: DBDs >70 years of age with diabetes and/or hypertension; DCDs >65 years of age with diabetes and/or hypertension; and DCDs >70 years of age. Over a 4-year period, 34 patients underwent adult DKT, and 51, with matching donor criteria, underwent SKT. The median estimated glomerular filtration rate (eGFR) at 12 and 36 months of DKT was 49 (range, 5-79) and 42 (range, 15-85) mL/min compared with SKT of 35 (range, 10-65) and 32 (range, 6-65), respectively. The 1-year graft survival for DKT and SKT was 88% and 96% (P = .52), and patient survival was 94% and 98%, respectively (P = .12). Median hospital stay, intensive care unit admission, and wound complications were more frequent in the DKT group. Graft function following DKT is significantly better compared with matched criteria SKT; graft and patient survival are similar. There is an increased rate of complications following DKT, with longer hospital stay and ICU admission. Copyright © 2016 Elsevier Inc. All rights reserved.

Occupational risk and chronic kidney disease: a population-based study in the United States adult population

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Rubinstein S

2013-03-01

Full Text Available Sofia Rubinstein,1 Chengwei Wang,1 Wenchun Qu2 1Department of Medicine, Nassau University Medical Center, East Meadow, NY, USA; 2Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA Objective: Previous studies on occupational risk for chronic kidney disease (CKD have analyzed a limited range of occupations and focused on nephrotoxins. The primary purpose of this study was to examine the relative risk for the occurrence of CKD between different occupations in the US adult population. Materials and methods: This was a population-based survey study of 91,340 participants in the US, who completed the National Health Interview Survey, 2004 through 2008. The outcome variable, CKD, was defined as having weakening/failing kidneys in the past 12 months, as diagnosed by a physician. The predictor variable, occupation, was obtained using the census occupational codes, regrouped according to North American Industrial Classification System. Results: After controlling for age, gender, hypertension, and education, and with the category Life, Physical, and Social Science Occupations as a reference group, the likelihood of developing CKD was 4.3 times higher in respondents working in Building, Grounds Cleaning and Maintenance Occupations, 4.4 times higher in Healthcare Practitioners and Technical Occupations, 4.7 times higher in Transportation and Material Moving Occupations and in Computer and Mathematical Occupations, 4.8 times higher in Production Occupations, 5.3 times higher in Food Preparation and Serving Related Occupations, and 6.1 times higher in Healthcare Support Occupations and in Legal Occupations. Conclusion: This study identified occupation groups in US adult population with increased risk for CKD. Alleviation of workplace stress is suggested as a goal for behavioral intervention in high-risk occupations. Keywords: CKD, risk factors, occupations

Screening for Chronic Kidney Disease: Preventing Harm or Harming the Healthy?

OpenAIRE

Echouffo-Tcheugui, Justin B.; Kengne, Andre P.

2012-01-01

Editors' Summary Background Chronic kidney disease (CKD)—the gradual loss of kidney function—is increasingly common worldwide. In the US, for example, about 26 million adults have CKD, and millions more are at risk of developing the condition. Throughout life, small structures called nephrons inside the kidneys filter waste products and excess water from the blood to make urine. If the nephrons stop working because of injury or disease, the rate of blood filtration decreases, and dangerous am...

Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development

DEFF Research Database (Denmark)

Madsen, Kirsten; Stubbe, Jane; Skøtt, Ole

2004-01-01

COX-2 in these cells. Thus low plasma concentrations of corticosterone allowed for cortical and medullary COX-2 induction during postnatal kidney development. Increased circulating glucocorticoid in the postnatal period may damage late renal development through inhibition of COX-2.......In postnatal weeks 2-4, cyclooxygenase-2 (COX-2) is induced in the rat kidney cortex where it is critically involved in final stages of kidney development. We examined whether changes in circulating gluco- or mineralocorticosteroids or in their renal receptors regulate postnatal COX-2 induction....... Plasma corticosterone concentration peaked at birth, decreased to low levels at days 3-13, and increased to adult levels from day 22. Aldosterone peaked at birth and then stabilized at adult levels. Gluco- and mineralocorticoid receptor (GR and MR) mRNAs were expressed stably in kidney before, during...

Synthetic marijuana and acute kidney injury: an unforeseen association.

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Kazory, Amir; Aiyer, Ravi

2013-06-01

Synthetic cannabinoids (SCs) have emerged as drugs of abuse with increasing popularity among young adults. The potential renal complication related to the abuse of SC was not recognized until recently. Here, we present a case of severe acute kidney injury (AKI) that developed after inhalation of SC in an otherwise healthy young patient. A kidney biopsy revealed severe acute tubular necrosis, and supportive management resulted in the recovery of the kidney function. Herein, we briefly summarize the only two previous reports (a total of 21 cases) on the association between SC abuse and renal dysfunction and identify the common aspects in all observations.

Vitamin D, Phosphate and Fibroblast Growth Factor 23: A role in the pathogenesis and management of Chronic Kidney Disease and Chronic Kidney Disease Mineral and Bone Disorder

OpenAIRE

Damasiewicz, Matthew John

2017-01-01

Chronic kidney disease (CKD) is defined by the presence of proteinuria or decreased kidney function, with a prevalence of 10-15% in the adult population. CKD can progress to end-stage kidney disease (ESKD) and is associated with progressive abnormalities of bone and mineral metabolism, defined as CKD mineral and bone disorder (CKD-MBD). The use of vitamin D in CKD, the optimal level for initiating treatment and the use of current and novel biomarkers in the management of ...

Polycystic ovary syndrome: from phenotype to genetype

NARCIS (Netherlands)

Y.V. Louwers (Yvonne)

2014-01-01

markdownabstract__Abstract__ oligomenorrhea or amenorrhea, hirsutism or hyperandrogenism and polycystic ovarian morphology. Later in life, adverse metabolic implications, such as obesity, insulin resistance, type 2 diabetes and cardiovascular disease, become more prominent. In this thesis, we

Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study.

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Gottschau, Mathilde; Kjaer, Susanne Krüger; Jensen, Allan; Munk, Christian; Mellemkjaer, Lene

2015-01-01

To assess the association between polycystic ovary syndrome (PCOS) and cancer, especially of the endometrium, breast and ovary. The Danish National Patient Register was used to identify 12,070 in- and outpatients in whom PCOS was diagnosed when they were aged 9-49 years during 1977-2012. Using the Danish Cancer Registry, we followed the cohort through 2012 and compared the women's cancer incidence with that of the general Danish female population by means of standardized incidence ratios (SIRs). Cancer was diagnosed in 279 women with PCOS (SIR = 1.19; 95% CI = 1.06-1.34). We found an almost fourfold increased risk for endometrial cancer (numbers observed (N) = 16, SIR = 3.9; 95% CI = 2.2-6.3), the large majority of cases being type 1 (N = 14, SIR = 4.7; 95% CI = 2.6-7.9). We found no association between PCOS and breast (N = 59, SIR = 1.1; 95% CI = 0.8-1.4) or ovarian cancer (N = 10, SIR = 1.8; 95% CI = 0.8-3.2); however, significantly increased risks were found for kidney, colon and brain cancers. The results of this large cohort study support those of case-control studies showing that women with PCOS are at increased risk for endometrial cancer, whereas their risks for breast and ovarian cancer are similar to those of women in the general population. Our finding that women with PCOS also are at increased risk for cancers of the kidney, colon and brain requires further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Lesions in mink (Mustela vison) infected with giant kidney worm (Dioctophyma renale).