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Sample records for acidosis renal tubular

  1. Renal tubular acidosis and nerve deafness.

    Dunger, D B; Brenton, D. P.; Cain, A R

    1980-01-01

    Two brothers are described with renal tubular acidosis and nerve deafness: the elder also had rickets and hypokalaemia. The parents were unaffected. Studies of urinary acidification and bicarbonate excretion were consistent with a distal tubular abnormality. This report strengthens the view previously proposed in similar cases that nerve deafness and renal tubular acidosis constitute a genetic entity. Examination for nerve deafness is indicated in any child with renal tubular acidosis.

  2. Distal renal tubular acidosis in recurrent renal stone formers

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available, this...... (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...

  3. [Hypokalemic pareses secondary to renal tubular acidosis].

    Gøransson, L G; Apeland, T; Omdal, R

    2000-01-30

    A 24 year old woman presented with flaccid paralysis, severe hypokalaemia and hyperchloremia, metabolic acidosis. Immunological tests and labial glandular biopsy indicated primary Sjögren's syndrome as the underlying cause of her distal renal tubular acidosis. The patient recovered after alkali and potassium substitution and was put on oral treatment with potassium citrate. PMID:10827521

  4. Clinical profile of distal renal tubular acidosis

    Ratan Jha; Muthukrishnan, J.; Shekhar Shiradhonkar; Kiran Patro; Harikumar KVS; Modi, K.D.

    2011-01-01

    To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive ...

  5. Renal tubular acidosis complicated with hypokalemic periodic paralysis.

    Chang, Y C; Huang, C C; Chiou, Y Y; Yu, C Y

    1995-07-01

    Three Chinese girls with hypokalemic periodic paralysis secondary to different types of renal tubular acidosis are presented. One girl has primary distal renal tubular acidosis complicated with nephrocalcinosis. Another has primary Sjögren syndrome with distal renal tubular acidosis, which occurs rarely with hypokalemic periodic paralysis in children. The third has an isolated proximal renal tubular acidosis complicated with multiple organ abnormalities, unilateral carotid artery stenosis, respiratory failure, and consciousness disturbance. The diagnostic evaluation and emergent and prophylactic treatment for these three types of renal tubular acidosis are discussed. PMID:7575850

  6. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  7. Type IV renal tubular acidosis associated with Alport's syndrome.

    Tkácová, R.; Roland, R.; Böör, A.; Kovácová, A.; Lazúrová, I.; Tkác, I.; Hildebrand, T.; Sefara, P.

    1993-01-01

    A case of hereditary nephritis with mild reduction of renal function associated with renal tubular acidosis type IV is described. The patient was admitted with life-threatening hyperkalaemia. To our knowledge, type IV renal tubular acidosis has not been reported previously in association with Alport's syndrome in an adult patient.

  8. Clinical profile of distal renal tubular acidosis

    Ratan Jha

    2011-01-01

    Full Text Available To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA, we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA, acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54% patients. Urological defect in children (22/44 and autoimmune disease in adults (11/52 were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR 60 mL/min (P <0.005. In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period.

  9. Clinical profile of distal renal tubular acidosis.

    Jha, Ratan; Muthukrishnan, J; Shiradhonkar, Shekhar; Patro, Kiran; Harikumar, Kvs; Modi, K D

    2011-03-01

    To determine the clinical profile and progression of renal dysfunction in distal renal tubular acidosis (dRTA), we retrospectively studied 96 consecutive cases of dRTA diagnosed at our center. Patients with unexplained metabolic bone disease, short stature, hypokalemia, re-current renal stones, chronic obstructive uropathy or any primary autoimmune condition known to cause dRTA were screened. Distal RTA was diagnosed on the basis of systemic metabolic acidosis with urine pH >5.5 and positive urine anion gap. In those patients who had fasting urine pH >5.5 with normal baseline systemic pH and bicarbonate levels (incomplete RTA), acid load test with ammonium chloride was done. A cause of dRTA could be established in 53 (54%) patients. Urological defect in children (22/44) and autoimmune disease in adults (11/52) were the commonest causes. Hypokalemic paralysis, proximal muscle weakness and voiding difficulty were the common modes of presentation. Doubling of serum creatinine during the study period was noted in 13 out of 27 patients who had GFR 60 mL/min (P <0.005). In conclusion, urological disorders were the commonest cause of dRTA in children while autoimmune disorders were the commonest asso-ciation in adults. Worse baseline renal function, longer duration of disease and greater frequency of nephrolithiasis/nephrocalcinosis and urological disorders were noted in those who had wor-sening of renal dysfunction during the study period. PMID:21422623

  10. Renal tubular acidosis due to the milk-alkali syndrome.

    Rochman, J; Better, O S; Winaver, J; Chaimowitz, C; Barzilai, A; Jacobs, R

    1977-06-01

    A 60-year-old man with a history of excessive ingestion of calcium carbonate presented with azotemia, hypercalcemia and hyperphosphatemia. His acid-base status was initially normal. Following the cessation of calcium carbonate treatment, the hypercalcemia and azotemia disappeared, and the patient was found to be in metabolic acidosis with blunted acid excretion and a urine pH of 6.1. Kidney biopsy showed focal tubular calcification; the tubular damage was apparently caused by hypercalcemia and had resulted in renal tubular acidosis. During the three months of observation since that time there has been a tendecy for spontaneous remission of the renal tubular acidosis. Impaired renal hydrogen ion excretion prevented the development of metabolic alkalosis despite ingestion of alkali initially, and was later responsible for the metabolic acidosis. Renal tubular acidosis occurring as a sequel to the milk-alkali syndrome may aggravate the danger of nephrocalcinosis in this syndrome. PMID:885714

  11. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    C. Ripoli; Pinna, A.; Marras, S.; M.L. Fenu; Nurchi, A M

    2012-01-01

    Introduction: distal renal tubular acidosis (dRTA) presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions...

  12. Screening renal stone formers for distal renal tubular acidosis

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted......; 13 had incomplete and 1 had complete distal RTA. Distal RTA was found particularly in recurrent stone formers (17%), and especially in those with bilateral stone disease, where a distal renal tubular acidification defect was found in 50%. We have been unable to differentiate primary from secondary...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use in...

  13. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...... groups. Fractional loss of bicarbonate in urine was higher in controls than in bypass patients. The renal impairment is classified as distal renal tubular acidosis....

  14. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

    Ravi, P.; Ekambaranath, T. S.; Arasi, S. Ellil; Fernando, E.

    2013-01-01

    Renal tubular acidosis (RTA) is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I) is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI) represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previ...

  15. [Primary distal renal tubular acidosis: a case report].

    Abdallah, Jihene Ben; Charfeddine, Bassem; Braham, Imen; Neffati, Souhir; Othmen, Leila Ben; Letaief, Affef; Smach, Mohamed Ali; Bourfifa, Zoheier; Dridi, Hedi; Limem, Khalifa

    2011-01-01

    The primary distal renal tubular acidosis is characterized biochemically by the inability of the kidney to produce appropriately acid urine in the presence of systemic metabolic acidosis or after acid loading (e.g. ammonium chloride). It is secondary to defective excretion of H(+) by the cells of the collecting duct. We report the observation of the child MC, 4-year-old, for whom the association of polyuria-polydipsia syndrome, a failure to thrive, nephrolithiasis, hypercalciuria, and especially a high urine pH in the presence of metabolic acidosis did evoke diagnosis of distal renal tubular acidosis. An urine acidification test with ammonium chloride was performed, the urinary pH was always higher than 5.5, thus confirming the diagnosis. PMID:21464016

  16. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association.

    Ravi, P; Ekambaranath, T S; Arasi, S Ellil; Fernando, E

    2013-11-01

    Renal tubular acidosis (RTA) is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I) is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI) represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI. PMID:24339526

  17. Type 4 renal tubular acidosis in a kidney transplant recipient.

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. PMID:27105603

  18. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    C. Ripoli

    2012-08-01

    Full Text Available Introduction: distal renal tubular acidosis (dRTA presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA.

  19. Atypical presentation of distal renal tubular acidosis in two siblings.

    Tasic, Velibor; Korneti, Petar; Gucev, Zoran; Hoppe, Bernd; Blau, Nenad; Cheong, Hae Il

    2008-07-01

    Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy. PMID:18386070

  20. Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning.

    Sakai, Norihiro; Hirose, Yasuo; Sato, Nobuhiro; Kondo, Daisuke; Shimada, Yuko; Hori, Yasushi

    2016-01-01

    A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis. PMID:27181539

  1. Hypokalemic quadriparesis and rhabdomyolysis as a rare presentation of distal renal tubular acidosis.

    Ahmad Bhat, Manzoor; Ahmad Laway, Bashir; Mustafa, Farhat; Shafi Kuchay, Mohammad; Mubarik, Idrees; Ahmad Palla, Nazir

    2014-01-01

    Distal renal tubular acidosis is a syndrome of abnormal urine acidification and is characterized by hyperchloremic metabolic acidosis, hypokalemia, hypercalciurea, nephrocalcinosis and nephrolithiasis. Despite the presence of persistent hypokalemia, acute muscular paralysis is rarely encountered in males. Here, we will report an eighteen year old male patient who presented with flaccid quadriparesis and was subsequently found to have rhabdomyolysis, severe short stature, skeletal deformities and primary distal renal tubular acidosis. PMID:25250276

  2. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L. PMID:25193912

  3. Distal renal tubular acidosis with multiorgan autoimmunity: a case report.

    van den Wildenberg, Maria J; Hoorn, Ewout J; Mohebbi, Nilufar; Wagner, Carsten A; Woittiez, Arend-Jan; de Vries, Peter A M; Laverman, Gozewijn D

    2015-04-01

    A 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered autoimmune. However, the patient did not meet criteria for any of the autoimmune disorders classically associated with dRTA. She had very high antibody titers against parietal cells, intrinsic factor, and thyroid peroxidase (despite normal thyroid function). The patient consented to a kidney biopsy, and acid-base transporters, anion exchanger type 1 (AE1), and pendrin were undetectable by immunofluorescence. Indirect immunofluorescence detected diminished abundance of AE1- and pendrin-expressing intercalated cells in the kidney, as well as staining by the patient's serum of normal human intercalated cells and parietal cells expressing the adenosine triphosphatase hydrogen/potassium pump (H(+)/K(+)-ATPase) in normal human gastric mucosa. The dRTA likely is caused by circulating autoantibodies against intercalated cells, with possible cross-reactivity against structures containing gastric H(+)/K(+)-ATPase. This case demonstrates that in patients with dRTA without a classic autoimmune disorder, autoimmunity may still be the underlying cause. The mechanisms involved in autoantibody development and how dRTA can be caused by highly specific autoantibodies against intercalated cells have yet to be determined. PMID:25533600

  4. Type IV renal tubular acidosis and spironolactone therapy in the elderly.

    O'Connell, J. E.; Colledge, N. R.

    1993-01-01

    Spironolactone therapy is a well-known cause of hyperkalaemia, but in susceptible patient, it may also be associated with metabolic acidosis. We report a case of severe renal tubular acidosis (Type IV) with life-threatening hyperkalaemia caused by spironolactone, and discuss the mechanisms by which this may occur.

  5. Hypokalemic quadriparesis and rhabdomyolysis as a rare presentation of distal renal tubular acidosis

    Ahmad Bhat, Manzoor; Ahmad Laway, Bashir; Mustafa, Farhat; Shafi Kuchay, Mohammad; Mubarik, Idrees; Ahmad Palla, Nazir

    2014-01-01

    Distal renal tubular acidosis is a syndrome of abnormal urine acidification and is characterized by hyperchloremic metabolic acidosis, hypokalemia, hypercalciurea, nephrocalcinosis and nephrolithiasis. Despite the presence of persistent hypokalemia, acute muscular paralysis is rarely encountered in males. Here, we will report an eighteen year old male patient who presented with flaccid quadriparesis and was subsequently found to have rhabdomyolysis, severe short stature, skeletal deformities ...

  6. Genetics Home Reference: renal tubular acidosis with deafness

    ... Prevention: Hearing Loss in Children Centre for Genetics Education (Australia): Deafness and Hearing Loss Gallaudet University: Laurent Clerc National Deaf Education Center KidsHealth: What's Hearing Loss? MalaCards: renal tubular ...

  7. Renal tubular acidosis presenting as respiratory paralysis: Report of a case and review of literature

    Kalita J; Nair P; Kumar G; Misra U

    2010-01-01

    Respiratory paralysis due to renal tubular acidosis (RTA) is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L) and hyperchloremic (110 meq/l) acidosis (pH 7.1). She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP) because acetazolamide used...

  8. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism

    Parvaiz Ahmad Koul; Wahid, A.

    2011-01-01

    A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an auto...

  9. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

    Yılmaz, Hakkı; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Yıldırım, İ

    2013-07-01

    We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia. PMID:22212410

  10. A Rare Case of Type I RenalTubular Acidosis with Membranous Nephropathy Presenting as Hypokalemic Paralysis

    Sunder, Sham; Sathi, Satyanand; K Venkataramanan; Verma, Himanshu; Bhardwaj, Minakshi; Rajesh, J.; Mahapatra, Himanshu

    2013-01-01

    Type 1 renal tubular acidosis (RTA), or distal RTA (dRTA), is a disorder of renal tubular acidification, which is generally asymptomatic but may rarely present as hypokalemic paralysis. Here, we report the case of a young male who presented with sudden onset weakness of all 4 limbs and a 2-month history of swelling of the legs. An investigation revealed hypokalemia, metabolic acidosis, and nephrotic syndrome. Additional analyses revealed normal anion gap metabolic acidosis with a positive uri...

  11. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism

    Parvaiz Ahmad Koul

    2011-01-01

    Full Text Available A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery.

  12. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism.

    Koul, Parvaiz Ahmad; Wahid, A

    2011-09-01

    A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery. PMID:21912036

  13. Renal Tubular Acidosis after Jejunoileal Bypass for Morbid Obesity: role of secondary hyperparathyroidism

    Andersen, NN; Ladefoged, NN

    1991-01-01

    The effect of calcium infusion was studied in patients with renal tubular acidosis (RTA) and secondary hyperparathyroidism. Both developed after jejunoileal bypass operation (JIB) for morbid obesity. In three of four cases the acidification defect was abolished, probably due to a decrease of serum...... parathyroid hormone. As we found RTA in 9% (95% confidence limits 2-21%) of our patients, screening for acidosis is recommended in obesity patients after malabsorptive operations. RTA can be verified through an ammonium loading test. Before deciding on re-establishing bowel continuity due to RTA, we suggest...

  14. Renal tubular acidosis presenting as respiratory paralysis: Report of a case and review of literature

    Kalita J

    2010-01-01

    Full Text Available Respiratory paralysis due to renal tubular acidosis (RTA is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L and hyperchloremic (110 meq/l acidosis (pH 7.1. She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

  15. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats

    Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A.; Ramachandran, Anup; Subramani, Sathya

    2010-01-01

    Background and Purpose: A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. Objectives: To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Materials and Methods: Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram ...

  16. Sjögren’s, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series

    Sandhya, Pulukool; Danda, Debashish; Rajaratnam, Simon; Thomas, Nihal

    2014-01-01

    Objective: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjögren's Syndrome (pSS). Methods: The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiologica...

  17. Primary Sjö-gren's syndrome presenting with distal, renal tubular acidosis and rhabdomyolysis.

    Prakash, E B S; Fernando, M E; Sathiyasekaran, Malathi; Bhoopathy, R M; Jayanth, J J; Samuel, J

    2006-12-01

    Primary Sjögren's syndrome (PSS) is rare in India. Clinically manifest renal disease in PSS is uncommon and is usually an autoimmune tubulointerstitial nephritis presenting with distal renal tubular acidosis (dRTA) or a urinary concentrating defect. Hypokalemic paralysis due to dRTA in PSS is rare but well documented in medical literature. Rhabdomyolysis as a consequence of hypokalemia in PSS is exceptional. We report a case of PSS with dRTA and rhabdomyolysis causing prolonged respiratory failure and quadriparesis. PMID:17334013

  18. Hearing impairment in association with distal renal tubular acidosis among Saudi children.

    Zakzouk, S M; Sobki, S H; Mansour, F; al Anazy, F H

    1995-10-01

    A follow-up of seven patients with the autosomal recessive inherited syndrome of distal renal tubular acidosis (RTA) and sensorineural hearing loss is described. Five patients were diagnosed as having primary distal renal tubular acidosis and rickets, four were found to have severe sensorineural hearing loss of over 80 dB: two of which are brothers. Two patients were diagnosed as having secondary distal renal acidosis due to a genetic disorder called osteopetrosis; they are brothers and their audiograms showed a mild conductive hearing loss of an average 35 dB bilaterally. All patients had growth retardation with improvement due to alkaline therapy but their hearing loss was not affected by the medication. The pedigrees of two families with half sibs showed the familial incidence for consanguineous marriage. Consanguinity was found to be positive in five out of the seven patients. The tribal tradition in Saudi Arabia fosters consanguineous marriages for cultural and social reasons and pre-arranged marriages are still seen. PMID:7499943

  19. [Distal renal tubular acidosis: report of 3 cases].

    Guibaud, P; Parchoux, B; Langue, J; Bouissou, F; Barthe, P; Larbre, F

    1979-06-01

    Three observations of R.T.A. with nerve deafness are reported. Case 1 and 2 concern consanguinous brothers whose parents are not affected, which confirm the syndrom as an autosomal recessive entity. The third, sporadic, case relates to a 13-year-old non consanguinous girl. Metabolic abnormalities and renal evolution with nephrocalcinosis was such as in Albright disease. However a progressive nerve deafness makes distinction. The authors underline the importance of this sometimes difficult distinction for genetic counseling. PMID:541679

  20. SYSTEMIC LUPUS ERYTHEMATOSUS PRESENTING AS HYPOKALEMIC PERIODIC PARALYSIS SECONDARY TO DISTAL RENAL TUBULAR ACIDOSIS

    Ranjeet; Gurinder

    2014-01-01

    Systemic lupus erythematosus, referred to as SLE or lupus, is sometimes called the “great imitator.” Why? Because of its wide range of symptoms, people often confuse lupus with other health problems. We report the case of a 22-year-old woman who presented with a flaccid paralysis of limbs due to severe hypokalemia as a consequence of distal renal tubular acidosis (dRTA). A search for the cause of dRTA revealed latent Systemic Lupus Erythematosus (SLE). SLE presenting as dRTA ...

  1. SYSTEMIC LUPUS ERYTHEMATOSUS PRESENTING AS HYPOKALEMIC PERIODIC PARALYSIS SECONDARY TO DISTAL RENAL TUBULAR ACIDOSIS

    Ranjeet

    2014-05-01

    Full Text Available Systemic lupus erythematosus, referred to as SLE or lupus, is sometimes called the “great imitator.” Why? Because of its wide range of symptoms, people often confuse lupus with other health problems. We report the case of a 22-year-old woman who presented with a flaccid paralysis of limbs due to severe hypokalemia as a consequence of distal renal tubular acidosis (dRTA. A search for the cause of dRTA revealed latent Systemic Lupus Erythematosus (SLE. SLE presenting as dRTA is uncommon

  2. Systemic lupus erythematosus with distal renal tubular acidosis presenting as hypokalemic paralysis with respiratory failure.

    Koul, Parvaiz Ahmad; Wahid, Abdul; Shah, Bashir Ahmad

    2003-01-01

    An eighteen-year-old woman presented with hypokalemic respiratory failure. She was found to have distal renal tubular acidosis (dRTA) as the underlying cause for hypokalemia. This was treated successfully, and no apparent etiology for the dRTA was discovered. Three years later she presented with full-blown picture of systemic lupus erythematosus (SLE) together with features of persistent dRTA complicated, this time, with bilateral renal calculi and nephrocalcinosis. It is very likely that the dRTA was an early feature that preceded the other markers of SLE. The moral of this case is that patients with dRTA should be followed-up carefully as a primary cause for the dRTA may show up in-due-course and to monitor the treatment so as to prevent long-term complications of the RTA. PMID:18209445

  3. Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

    Osther, P J; Bollerslev, Jens; Hansen, A B;

    1993-01-01

    Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had......-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA....... significantly increased in iRTA compared with NUA and NC (P <0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism--the same metabolic abnormalities which characterize classic type 1 RTA. Mild non...

  4. An Uncommon Presentation of HDR Syndrome: Distal Renal Tubular Acidosis in a Patient with Sjögren's Syndrome

    Ebru Sevinç OK

    2015-12-01

    Full Text Available HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. Haploinsufficiency of GATA3 on chromosome 10p15 is implicated in the pathogenesis of the syndrome. It may manifest itself with clinical features other than the classical triad. Here we report a case of HDR syndrome with concomitant Sjögren’s syndrome in a 33-year-old who female presented with distal renal tubular acidosis (dRTA.

  5. Sjögren’s, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series

    Sandhya, Pulukool; Danda, Debashish; Rajaratnam, Simon; Thomas, Nihal

    2014-01-01

    Objective: To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjögren's Syndrome (pSS). Methods: The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiological findings were retrieved. RTA was diagnosed in cases of hyperchloremic metabolic acidosis with urinary pH values higher than 5.5. Those with known features suggestive of RTA including hypokalemic paralysis, hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete RTA. Results: Of the 380 patients with clinically suspected pSS, 25 had RTA. The median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at presentation. Sixteen patients (64%) had present or past history of hypokalemic paralysis. Pseudofractures were seen in 7 patients and an additional 2 had subclinical radiological osteomalacia. Majority of the patients (61.2%) had a normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3 levels were not significantly different between patients with osteomalacia and those without. Conclusion: Most patients were asymptomatic for RTA inspite of clinically overt and elicitable features. Skeletal manifestation was a common finding in patients with Sjögren and RTA, despite normal levels of 25 (OH) D3 in a majority. PMID:25584094

  6. Distal renal tubular acidosis as a cause of osteomalacia in a patient with primary Sjögren's syndrome

    Jovelić Aleksandra

    2005-01-01

    Full Text Available Background. One half of the patients with primary Sjögren’s syndrome has extraglandular manifestations, including renal involvement. The most frequent renal lesion is tubulo-interstitial nephritis, which manifests clinically as distal tubular acidosis and may result in the development of osteomalacia. Case report. In a 29 - year-old female patient, with bilateral nephrolithiasis, the diagnosis of primary Sjögren’s syndrome, tubulo-interstitial nephritis, distal renal tubular acidosis, and hypokalemia were established. She was treated for hypokalemia. Two years later she developed bone pains and muscle weakness, she wasn’t able to walk, her proximal muscles and pelvic bones were painful, with radiological signs of pelvic bones osteopenia and pubic bones fractures. The diagnosis of osteomalacia was established and the treatment started with Schol’s solution, vitamin D and calcium. In the following two months, acidosis was corrected, and the patient started walking. Conclusion. In our patient with primary Sjögren’s syndrome and interstitial nephritis, osteomalacia was a result of the long time decompensate acidosis, so the correction of acidosis, and the supplementation of vitamin D and calcium were the integral part of the therapy.

  7. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  8. Hypokalemic paralysis and osteomalacia secondary to renal tubular acidosis in a case with primary Sjögren's syndrome.

    Kawashima, Masanori; Amano, Tetsuki; Morita, Yoshitaka; Yamamura, Masahiro; Makino, Hirofumi

    2006-01-01

    A 39-year-old Japanese woman was admitted to our hospital for severe weakness owing to potassium deficiency caused by type 1 renal tubular acidosis (RTA1). Sicca complex, serological tests, and lip biopsy revealed that she had Sjögren's syndrome (SS). Acidosis was corrected by alkali supplement treatment. She also had an impaired renal function with proteinuria, and high absorbance on Ga scintigram was recognized in both kidneys. She was taking warfarin potassium after aortic valve substitution due to aortic regurgitation, therefore renal biopsy was not performed. Prednisone (20 mg/day) was administered for renal inflammation. One month later, she suffered severe chest wall pains with some local tender points over the costae of both sides, which was presumed to be due to pseudo-fractures based on osteomalacia. Hypokalemic paralysis and osteomalacia should be taken into consideration in the diagnosis of SS with RTA1. PMID:16622725

  9. Distal Renal Tubular Acidosis, Hypokalemic Paralysis, Nephrocalcinosis, Primary Hypothyroidism, Growth Retardation, Osteomalacia and Osteoporosis Leading to Pathological Fracture: A Case Report

    Mayada Mohammad Swar; Mohammad Mizanur Rahman; Khairy Mostafa Sharkawi; Basak, Ramen C.

    2011-01-01

     Renal tubular acidosis (RTA) is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acido...

  10.  Distal Renal Tubular Acidosis, Hypokalemic Paralysis, Nephrocalcinosis, Primary Hypothyroidism, Growth Retardation, Osteomalacia and Osteoporosis Leading to Pathological Fracture: A Case Report

    Mayada Mohammad Swar

    2011-07-01

    Full Text Available  Renal tubular acidosis (RTA is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA, hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA have been reported.

  11. Distal renal tubular acidosis, hypokalemic paralysis, nephrocalcinosis, primary hypothyroidism, growth retardation, osteomalacia and osteoporosis leading to pathological fracture: a case report.

    Basak, Ramen C; Sharkawi, Khairy Mostafa; Rahman, Mohammad Mizanur; Swar, Mayada Mohammad

    2011-07-01

    Renal tubular acidosis (RTA) is a constellation of syndromes arising from different derangements of tubular acid transport. Recent advances in the biology of urinary acidification have allowed us to discern various molecular mechanisms responsible for these syndromes. RTA often presents as renal stone disease with nephrocalcinosis, ricket/osteomalacia and growth retardation in children with ultimate short stature in adulthood. The case reported here has features of distal renal tubular acidosis (dRTA), hypokalemic paralysis, primary hypothyroidism, growth retardation, osteomalacia and osteopenia leading to stress fracture. All these features presenting in a single case (as in our case) is a rare occurrence, so far other cases of distal renal tubular acidosis (dRTA) have been reported. PMID:22043434

  12. Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

    Rink Nikki; Bitzan Martin; O'Gorman Gus; Nagel Mato; Torban Elena; Goodyer Paul

    2012-01-01

    Hereditary distal renal tubular acidosis (dRTA) is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1) expressed in α -intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI) r...

  13. An Unusual Initial Presentation of Sjögren’s Syndrome: Severe Hypokalemic Paralysis Secondary to Distal Renal Tubular Acidosis

    Sengul, Erkan; Bunul, Fatih; Yazici, Ayten; Sengul, Aysun; Dindar, Sevim; Halhalli, Gökçen Selma Kilic; Binnetoglu, Emine

    2013-01-01

    Sjögren’s syndrome is mainly affects the exocrine glands. Patients usually complain of persistent dryness of the mouth and eyes. However, nonexocrine organs such as the kidneys are often affected in these patients. Distal renal tubular acidosis (dRTA) and interstitiel nephritis are common in Sjögren’s syndrome. Nonetheless, severe hypokalemia and paralysis secondary to dRTA are unusual initial manifestation of Sjögren’s syndrome. Here, we describe a case of a 48 year old women admitted to the...

  14. Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

    Menegon L.F.

    1998-01-01

    Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

  15. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient’s Perceptions of Over-the-Counter Medications and Their Adverse Effects

    Mark D. Salter

    2013-01-01

    Full Text Available We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient’s perception of over-the-counter (OTC medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them.

  16. Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

    Rink Nikki

    2012-01-01

    Full Text Available Hereditary distal renal tubular acidosis (dRTA is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1 expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.

  17. Endolymphatic sac enlargement in a girl with a novel mutation for distal renal tubular acidosis and severe deafness.

    Nikki, Rink; Martin, Bitzan; Gus, O'Gorman; Mato, Nagel; Elena, Torban; Paul, Goodyer

    2012-01-01

    Hereditary distal renal tubular acidosis (dRTA) is caused by mutations of genes encoding subunits of the H(+)-ATPase (ATP6V0A4 and ATP6V1B1) expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI) revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation. PMID:22966473

  18. Genetics Home Reference: SLC4A1-associated distal renal tubular acidosis

    ... hemolysis), causing a shortage of red blood cells ( anemia ). Hemolytic anemia can lead to unusually pale skin (pallor), extreme ... these abnormal red blood cells may lead to hemolytic anemia. Some people have nonhereditary forms of distal renal ...

  19. Atp6v0a4 knockout mouse is a model of distal renal tubular acidosis with hearing loss, with additional extrarenal phenotype

    Elizabeth E. Norgett; Golder, Zoe J.; Lorente-Cánovas, Beatriz; Ingham, Neil; Steel, Karen P; Karet Frankl, Fiona E.

    2012-01-01

    Autosomal recessive distal renal tubular acidosis (dRTA) is a severe disorder of acid–base homeostasis, often accompanied by sensorineural deafness. We and others have previously shown that mutations in the tissue-restricted a4 and B1 subunits of the H+-ATPase underlie this syndrome. Here, we describe an Atp6v0a4 knockout mouse, which lacks the a4 subunit. Using β-galactosidase as a reporter for the null gene, developmental a4 expression was detected in developing bone, nose, eye, and skin, i...

  20. PRIMARY SJOGREN’S SYNDROME AND DISTAL RENAL TUBULAR ACIDOSIS: PRESENTING WITH NEPHROGENIC DIABETES INSI PIDUS SECONDARY TO SEVERE HYPOKALEMIA-A CASE REPORT

    Ksh. Achouba

    2013-02-01

    Full Text Available NTRODUCTION: Sjogren’s syndrome is a slowly progressing autoimmun e disease characterized by lymphocytic infiltration of the exo crine glands, mainly the lacrimal and salivary glands, resulting in their impaired secreto ry function. Simultaneously, systemic involvement and symptoms of cutaneous, respiratory, r enal, hepatic, neurologic, and vascular systems often occur.[ 1 ] This syndrome can present either alone (as primary Sjogren’s syndrome or in the context of an underlying connec tive tissue disease (as secondary Sjogren’s syndrome.[ 2 ] Renal involvement is a well recognized extra glan dular manifestation of primary Sjogren’s syndrome (pSS. Most common manifestations are related to tubular dysfunction, resulting from chronic interstitial nephritis, which can manifest as distal renal tubular acidosis (dRTA, proximal RTA(pRTA, tubular proteinuria, or nephrogenic diabetes insipidus.[ 3 , 4 ] Hypokalemic periodic paralysis, urolithiasis, or osteo malacia are uncommon renal manifestations of pSS.[ 1 ] Here, we present a case of primary Sjogren’s syndr ome predominantly presenting as a renal manifestation in the form of nephrogenic Diabetes Insipidus secondary to severe hypokalemia due to dRTA .

  1. Renal Tubular Acidosis

    ... is normal, but too much acid—acidosis—can disturb many bodily functions. Healthy kidneys help maintain acid- ... disseminates research findings through its clearinghouses and education programs to increase knowledge and understanding about health and ...

  2. A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis.

    Imai, Eri; Kaneko, Shuzo; Mori, Takayasu; Okado, Tomokazu; Uchida, Shinichi; Tsukamoto, Yusuke

    2016-06-01

    A 40-year-old Japanese man who had a medical history of hypokalemic periodic paralysis 4 months prior was hospitalized to undergo a cholecystectomy. Hypokalemia, nephrocalcinosis and alkaluria suggesting distal renal tubular acidosis (dRTA) were detected, but metabolic acidosis was not evident. An ammonium chloride/furosemide-fludrocortisone/bicarbonate loading test demonstrated a remarkable disability in urinary H(+) excretion. A novel heterozygous mutation in the ATP6V0A4 gene encoding the vacuolar H(+)-ATPase (V-ATPase) a4 subunit p.S544L was detected. Among cases of V-ATPase a4 mutations, this is the first case in which a heterozygous mutation developed to an incomplete or latent form of dRTA. PMID:27274828

  3. A primary Sjögren's syndrome patient with distal renal tubular acidosis, who presented with symptoms of hypokalemic periodic paralysis: Report of a case study and review of the literature.

    Soy, Mehmet; Pamuk, Omer Nuri; Gerenli, Murat; Celik, Yahya

    2005-11-01

    Although renal tubular acidosis (RTA), secondary to autoimmune interstitial nephritis, develops in a large proportion of patients with Sjögren's syndrome (SS), most of the subjects are asymptomatic. Here, we shall present a 39-year-old female patient who came to us with hypokalemic periodic paralysis (HPP), and who was later diagnosed with distal RTA. The patient, who had xerostomia and xerophthalmia for a long period of time, was diagnosed with primary SS from serologic and histologic findings. The patient recovered by being prescribed potassium replacement therapy. Although renal biopsy was not performed, corticosteroids were administered because HPP indicated severe interstitial nephritis. HPP did not reoccur during a 2-year follow-up period. We also review cases with SS-related distal RTA and HPP. PMID:15690142

  4. 儿童远端肾小管酸中毒1例%1 Case of Children With Distal Renal Tubular Acidosis

    王瑞彬

    2015-01-01

    在儿科临床工作中,如果小儿有烦渴,多饮,多尿,腹泻,乏力,低钾血症,不明原因的代谢性酸中毒,生长发育落后,佝偻病,要考虑到本病,进一步检查血离子,血气,肾功能,尿常规,双肾超声,腕骨 X 线片。注意酸碱度,有无高氯性酸中毒,电解质紊乱,活动性佝偻病,肾结石,肾钙化。%In pediatric clinical work if the child has thirst, polydipsia, polyuria, diarrhea, fatigue, hypokalemia, metabolic acidosis, unexplained, growth retardation, rickets, taking into account the disease, further examination of blood ions, blood gas, kidney function, urine routine, renal ultrasound, Carpale x-ray. Note that the pH is hyperchloremic acidosis, electrolyte disorder, activity of rickets, kidney stones, renal calcification.

  5. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    Berg, van den Else; Engberink, M.F.; Brink, E.J.; Baak, van M.A.; Joosten, M.M.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. Thi

  6. Acidosis and Urinary Calcium Excretion

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine;

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and...... renal tubule and then discuss why not all gene defects that cause renal tubular acidosis are associated with hypercalciuria and nephrocalcinosis....

  7. Differential uptake of Tc-99m DMSA and Tc-99m EC in renal tubular disorders: Report of two cases and review of the literature

    Tc-99m DMSA and Tc-99m EC studies are invaluable functional imaging modalities for renal structural and functional assessment. Normally, the relative renal function estimated by the two methods correlates well with each other. We here present two patients with renal tubular acidosis who showed impaired/altered DMSA uptake with normal EC renal dynamic study depicting the pitfall of DMSA imaging in tubular disorders. The two presented cases also depict distinct pattern of Tc-99m DMSA scintigraphic findings in patients with proximal and distal renal tubular acidosis, thus highlighting the factors affecting DMSA kinetics

  8. 桥本甲状腺炎合并干燥综合征肾小管酸中毒致低钾血症的临诊应对%Approach to the patient with hypokalemia caused by Hashimoto′s thyroiditis associated with primary Sjogren′s syndrome and renal tubular acidosis

    张洪梅; 张伟伟; 李晓永; 陈寒蓓; 杨震; 钮忆欣; 苏青

    2016-01-01

    Hypokalemia is a common clinical symptom. It is quite important to clarify the cause of hypokalemia. Autoimmune thyroid disease and primary Sjogren syndrome ( pSS ) have a common genetic predisposition. The coexistence of both diseases is frequent. Renal tubular acidosis ( RTA) is one of the causes of hypokalemia, which can be primary and secondary to other diseases in etiology. Primary RTA is more common in children. As for adults, RTA is often secondary to pSS. In this paper, we reported a case of hypokalemia caused by Hashimoto’s thyroiditis associated with primary Sjogren’s syndrome and renal tubular acidosis in order to call attention to the special cause and treatment of hypokalemia.%低钾血症临床上较为常见,明确低血钾的原因至关重要。自身免疫性甲状腺疾病及干燥综合征有共同的遗传易感性,往往同时发生,肾小管性酸中毒为低钾血症病因之一,按病因分原发性和继发性,原发性多见于儿童,成人以继发性肾小管酸中毒多见,多继发于原发性干燥综合征。本文详细描述了1例桥本甲状腺炎合并干燥综合征肾小管酸中毒导致低钾血症的诊疗过程,以使临床医生重视低钾血症的病因,及时诊治。

  9. Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells

    Maria José Rodriguez Cabalgante; Liliana Gadola; Leonella Luzardo; María Márquez; José Boggia; Mirian Aparecida Boim

    2012-01-01

    INTRODUCTION: Epithelial-to-mesenchymal transition (EMT) is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF) β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290) were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours): A) Control: pH 7.4, B) Acidosis: pH 7.0 and C) Calcium citrate (0.2 mmol/L) + pH 7.0. Chan...

  10. Inherited renal tubular defects with hypokalemia

    Muthukrishnan J; Modi K; Kumar P; Jha Ratan

    2009-01-01

    Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hy...

  11. Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

    Adeva-Andany, María M.; Carlos Fernández-Fernández; David Mouriño-Bayolo; Elvira Castro-Quintela; Alberto Domínguez-Montero

    2014-01-01

    Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial ...

  12. Luminal nucleotides are tonic inhibitors of renal tubular transport

    Leipziger, Jens Georg

    2011-01-01

    in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal...... necessary for flow-stimulated luminal ATP release. Tubular ATP secretion may occur via nonjunctional connexin-hemichannels (connexin 30), which are strategically placed in the apical membrane of distal tubular intercalated cells and can be activated by tubular flow. SUMMARY: The tubular lumen has been...

  13. Inherited renal tubular defects with hypokalemia

    Muthukrishnan J

    2009-01-01

    Full Text Available Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter′s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman′s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  14. The rebirth of interest in renal tubular function.

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. PMID:26936872

  15. Intrarenal purinergic signaling in the control of renal tubular transport

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all ...... of NaCl at the macula densa. This review describes the relevant aspects of local, intrarenal purinergic signaling and outlines its integrative concepts....

  16. Acidosis láctica por metformina desencadenada por una insuficiencia renal aguda Metformin-induced lactic acidosis due to acute renal failure

    M.D. Macías-Robles

    2011-04-01

    Full Text Available La acidosis láctica es una complicación grave pero infrecuente asociada al empleo de metformina. Se discuten los mecanismos fisiopatológicos implicados en la acidosis láctica, con especial atención al papel potencial del fármaco. Presentamos un caso severo de este efecto secundario de la metformina en una paciente con diabetes tipo 2 que ingresó en el Servicio de Urgencias Hospitalario por un cuadro de insuficiencia renal aguda. El diagnóstico quedó apoyado por unos niveles séricos elevados de la biguanida, procedimiento escasamente utilizado en la práctica clínica. El tratamiento consiste en suspender la administración del fármaco e iniciar de forma inmediata la hemodiálisis con bicarbonato, lo cual proporciona un tratamiento sintomático y etiológico al eliminar del suero tanto el lactato como el antidiabético oral. Los síntomas de la acidosis láctica por metformina son inespecíficos y el comienzo es sutil, lo que hace necesario un alto nivel de sospecha para establecer un diagnostico precoz.Lactic acidosis is a serious but uncommon side effect of metformin use. We discuss the pathophysiological mechanisms of lactic acidosis with particular regard to the role played by the drug as a potential cause of the entity. We report on a severe case of this kind of drug toxicity in a patient with type 2 diabetes mellitus, admitted to the emergency department with acute renal failure symptoms. The diagnosis was supported by elevated serum levels of the biguanide, a procedure scarcely used in clinical practice. The management of this complication consists in drug discontinuation and hemodialysis with bicarbonate that provides symptomatic and ethiological treatment by removing both the lactate and the hypoglycemic agent from the serum. Since the symptoms of metformin-associated lactic acidosis are unspecific and its onset is subtle, a high level of suspicion is needed to establish an early diagnosis.

  17. Recent advances in renal tubular calcium reabsorption.

    Mensenkamp, A.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2006-01-01

    PURPOSE OF REVIEW: Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption. RECENT FINDINGS: The thiazide diuretics are known for their hypocalciuric effect. Recently, it has been demonstr

  18. Management of Metformin-Associated Lactic Acidosis by Continuous Renal Replacement Therapy

    Keller, Geoffray; Cour, Martin; Hernu, Romain; Illinger, Julien; Robert, Dominique; Argaud, Laurent

    2011-01-01

    Background Metformin-associated lactic acidosis (MALA) is a severe metabolic failure with high related mortality. Although its use is controversial, intermittent hemodialysis is reported to be the most frequently used treatment in conjunction with nonspecific supportive measures. Our aim was to report the evolution and outcome of cases managed by continuous renal replacement therapy (CRRT). Methodology and Principal Findings Over a 3-year period, we retrospectively identified patients admitte...

  19. Renal Tubular Functions in Children with Primary Nocturnal Enuresis

    Süleyman Kalman

    2012-03-01

    Full Text Available Introduction: The etiology of primary nocturnal enuresis (PNE is multifactorial. The effects of genetic and hormonal factors, sleep disorders, and bladder dysfunction have been claimed. The other factors include increased urine production at night and impairment of the circadian rhythm of antidiuretic hormone. Aim: To investigate renal tubular functions in children with PNE. Methods: Forty patients with PNE were included in the study. Urine density, FENa, FEK and TRP were analyzed in daytime and nighttime urine. Results: The mean nighttime urine density was 1020.12±7.38 and the mean daytime urine density was 1013.20±7.11 (p0.05. Conclusion: Urine density in children with PNE was lower at night. However, there was no difference in of FENa, FEK and TRP. Further studies are needed in order to investigate renal tubular functions in children with PNE (The Me di cal Bul le tin of Ha se ki 2012; 50: 10-3

  20. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey;

    2012-01-01

    Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuri...

  1. Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H;

    1987-01-01

    Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive...... capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments....

  2. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  3. Renal hücreli karsinom tanılı bir olguda tekrarlayan hiperkalemi atakları

    A. ALP; Akdam, H.; Ünsal, A; Uyanık, Ö; Ayhan, M; Çulhacı, N; Akar, H.; Yeniçerioğlu, Y

    2014-01-01

    Hyperkalemia is one of the most urgent entities in clinical practice. The importance of hyperkalemia arises from its cardiovascular effects that can be mortal. Relapsing hyperkalemia is rare and usually associated with renal disorders. Renal tubular acidosis is one of them. Although Type 4 renal tubular acidosis is generally associated with diabetes mellitus, this entity also may accompanied by other disorders. Renal cell carcinoma is the most common type of kidney cancer in adults and recent...

  4. Lactic Acidosis

    K.Srikanth

    2012-10-01

    Full Text Available Abstract. Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia. Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poisoning or certain malignancies. Underutilization involves removal of lactic acid by oxidation or conversion to glucose. Liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine deficiency, and uncoupling of oxidative phosphorylation are the most common causes. The kidneys also contribute to lactate removal. Concerns have been raised regarding the role of metformin in the production of lactic acidosis, on the basis of individual case reports. The risk appears to be considerably less than with phenformin and involves patients with underlying severe renal and cardiac dysfunction.

  5. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  6. Macrophage Matrix Metalloproteinase-9 Mediates Epithelial-Mesenchymal Transition in Vitro in Murine Renal Tubular Cells

    Tan, Thian Kui; Zheng, Guoping; Hsu, Tzu-Ting; Wang, Ying; Lee, Vincent W.S.; Tian, Xinrui; Wang, Yiping; Cao, Qi; Wang, Ya; Harris, David C H

    2010-01-01

    As a rich source of pro-fibrogenic growth factors and matrix metalloproteinases (MMPs), macrophages are well-placed to play an important role in renal fibrosis. However, the exact underlying mechanisms and the extent of macrophage involvement are unclear. Tubular cell epithelial−mesenchymal transition (EMT) is an important contributor to renal fibrosis and MMPs to induction of tubular cell EMT. The aim of this study was to investigate the contribution of macrophages and MMPs to induction of t...

  7. Prevalence of renal tubular dysfunction in beta thalassemia minor in shiraz

    Ali Moradi Nakhodcheri

    2012-02-01

    Full Text Available  Background & objective: β-Thalassemia minor is an asymptomatic hereditary disease. The first study on the relation of renal tubular dysfunction and β-thalassemia minor was performed in 2002 but those studies seem inadequate.The main goal of this study is through evaluation of renal tubular function in 100 patients with thalassemia minor. Materials & Methods: 100 patients with β- thalassemia which confirmed by hemoglobin electrophoresis and CBC as well as RBC indices were studied.14 out of 100 cases exit because of Urinary Tract Infection, diabetes mellitus or hypertension.Complete chemistry profile was performed on serum and urine of all reminder 86 patients (46 female and 40 male. Patients classified into two groups: β-thalassemia minor with anemia and without anemia. Another control group include 50 healthy individuals also considered.Then data analyzed by proper statistical methods. Results: 20 out of 86 reminder cases e.g. 24% showed at least one index of renal tubular dysfunction.58% of patients was been anemic and 42% non anemic. The most prominent tubular dysfunction was seen in a 29 years old lady with glucosuria and without anemia. conclusion: β-Thalassemia minor is common in Iran specially in Fars province. This study revealed significant renal tubular dysfunction in patient with β-thalassemia minor. So it is necessary to check out thalassemic patients for renal function tests periodically. Key words: β-thalassemia, minor,renal tubular dysfunction

  8. Quantitation of renal function with glomerular and tubular agents

    Quantitative methods to measure the glomerular and tubular function of the kidneys with radionuclides have been available for many years. They have not been widely used because the techniques and the calculations exceeded the scope of routine nuclear medicine practice. Validation of simplified methods and the introduction of computer technology have made measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) simple enough so that they can be performed reproducibly in most nuclear medicine departments. The estimation of ERPF with radioiodinated OIH and GFR with /sup 99m/TcDTPA can be achieved in many ways, all of which yield clinically useful results. How to get the best results using the simplest methods is still unclear. The required accuracy depends on the intended clinical use. Our preference at the present time is to use a single or double plasma sample to calculate global ERPF or GFR, and to use the 1-2 min OIH or 1-3 min Tc-DTPA uptake to calculate relative function of the two kidneys (split function ERPF or GFR). The choice of method will be influenced by local factors, such as the nature of the patient population, the case volume, and the resources available. A desirable goal for future studies is to document carefully the capabilities and limitations of each alternative method, so that the choice can be rational

  9. Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

    Etezadi Farhad

    2012-09-01

    Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  10. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

    Prabahar Murugesan

    2008-01-01

    Full Text Available Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phos-phorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diag-nosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.

  11. Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment.

    Bruijstens, L.A.; Luin, M. van; Buscher-Jungerhans, P.M.; Bosch, F.H.

    2008-01-01

    BACKGROUND: Lactic acidosis in metformin use is a widely recognised but rare side effect. Case reports usually describe elderly patients with conditions which in themselves can cause lactic acidosis or with known contraindications to metformin. We present cases of an elderly woman, a younger woman a

  12. Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.

    Ramkumar, Nirupama; Stuart, Deborah; Mironova, Elena; Bugay, Vladislav; Wang, Shuping; Abraham, Nikita; Ichihara, Atsuhiro; Stockand, James D; Kohan, Donald E

    2016-07-01

    The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 mo of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+) excretion and investigated the signaling mechanisms by which PRR regulates Na(+) balance. No detectable differences in BP were observed between control and PRR KO mice fed normal- or low-Na(+) diets. However, compared with controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+) balance with normal- and low-Na(+) intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+) retention following angiotensin II (ANG II) infusion. Furthermore, PRR KO mice had significantly lower epithelial Na(+) channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT1, ERK1/2, or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+) wasting and reduces the hypertensive response to ANG II. PMID:27053687

  13. p-Cresol mediates autophagic cell death in renal proximal tubular cells.

    Lin, Hsin-Hung; Huang, Chiu-Ching; Lin, Tze-Yi; Lin, Ching-Yuang

    2015-04-01

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases. PMID:25668154

  14. Metabolic acidosis

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  15. Renal tubular dysfunction nephrocalcinosis in a patient with BetaThalassemia Minor

    Thalassemia is a hereditary anemia resulting from defect in hemoglobinproduction. Beta thalassemia is due to impaired production. Beta thalassemiais due to impaired production of beta globin chains, leading to a relativeexcess of alpha globin chains. The term beta thalassemia minor is used todescribe heterozygotes, who carry one normal beta globin and one betathalassemic allele. The vast majority of these patients are asymptomatic.However, a variety of renal tubular abnormalities including hypercaliuria,hypomagnesemia with renal magnesium wasting, decreased tubular absorption ofphosphorous, hypouricemia with renal uric acid wasting, renal glycosuria andtubular proteinuria have been described even in patients with betathalassemia minor. We here in report a 24-year old patient who was found tohave thalassemia minor and nephrocalcinosis with evidence of renal tubulardysfunction. Investigations revealed normal renal function, hypercalciuria,reduced tubular reabsorption of phosphorous, hypomagnesemia and renalmagnesium wasting. Screening for aminoaciduria was found to be negative. Anacid loading test revealed normal urinary acidification. Ultrasonogram of theabdomen revealed nephrocalcinosis and splenomegaly. Detailed work up foranemia showed normal white cell and platelet count while peripheral smearshowed microcytic hypochromic anemia with few target cells. Hemoglobinelectrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% andhemoglobin F of 1.8% consistent with beta thalassemia minor. Her parentalscreening was normal. A diagnosis of beta thalassemia minor with renaltubular dysfunction was made and the patient was started on thiazidediuretics to reduce hypercalciuria and advised regular follow-up. (author)

  16. Study on the assessment of renal tubular function with combined determination of multiple markers

    Objective: To investigate the degree of tubular injury in patients with glomerular diseases by measuring the urinary contents of various tubular function markers (THP, RBP, α1-m, β2-m, NAG, ET-1 ) and IL-6 as well as free water clearance. Methods: Twenty four hour urinary contents of THP, α1-m, β2-m, ET-1, IL-6 (with RIA) RBP (with ELISA) and NAG (with colorimetry) as well as free water clearance were determined in 353 patients with various kinds of primary glomerular diseases and 32 controls. Results: Renal tubular injury was most pronounced in patients with chronic renal failure followed by patients with lupus nephritis. In patients with chronic renal failure (n=36 ), urinary contents of all these markers were significantly different from those in controls (P<0.01). In other patients, urinary contents of at least one or several markers were significantly different from those in controls with the exception of patients with latent nephritis (n=8). Conclusion: Renal tubular function damage could be demonstrated in most of the patients with primary glomerular diseases. (authors)

  17. A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

    GAO Ci-xiu; YANG Lin; WANG Ke-qiang; XU Shi-xiong; DAI Pei-dong

    2009-01-01

    Objective:To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods:A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic response (MR), tubuloglomerular feedback (TGF) and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results:The results predict the dynamics of renal autoregulation on its blood pressure and flow,and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion:The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.

  18. Renal hyperconcentration of /sup 99m/Tc-HEDP in experimental acute tubular necrosis

    The effect of transient renal ischemia on renal concentration and distribution of /sup 99m/Tc-HEDP, /sup 99m/Tc-DMSA, and /sup 99m/Tc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. /sup 99m/Tc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1 to 4 hrs after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. /sup 99m/Tc-HEDP may be useful in evaluation of renal failure secondary to tubular injury

  19. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

    Hao Jia Wu

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF and TNFα-stimulating gene (TSG-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

  20. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  1. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

    Ryuji Morizane

    Full Text Available Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  2. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    Gui, Ting; Gai, Zhibo

    2015-01-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly ...

  3. Ioxaglate-induced light and electron microscopic alterations in the renal proximal tubular epithelium of rats.

    Battenfeld, R; Khater A el-R; Drommer, W; Guenzel, P; Kaup, F J

    1991-01-01

    Vacuolization of the proximal tubular epithelial cells was produced in rats by the intravenous administration of the radiographic contrast medium ioxaglate at high multiples of the human diagnostic dose. Samples of the renal cortex and outer zone of the medulla were examined by light and electron microscopy. We observed enlargement, confluence, and migration of vacuoles containing pleomorphic dense material and distinct inclusion bodies. With time, vacuolization disappeared, though single vacuoles partly engaged in extruding their contents into the tubular lumen were still visible. We concluded that radiographic contrast medium at high dose levels can produce a reversible disturbance in the transport vesicular system of the proximal tubular epithelial cells without affecting the specific cell organelles. PMID:2022451

  4. Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury

    冯娟

    2013-01-01

    Objective To explore the mechanism of protecting cells from hypoxia/reoxygenation(H/R) injury by constructing specific small interference RNA(siRNA) to inhibit NALP3 expression in rat renal tubular epithelial

  5. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  6. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P; Strandgaard, S

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril...... on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 m......L/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and...

  7. Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans

    Olsen, Niels Vidiendal; Hansen, J M; Kanstrup, I L; Richalet, J P; Leyssac, P P

    1993-01-01

    Renal function was investigated in eight normal subjects before and during infusion of dopamine (3 micrograms.kg-1 x min-1) at sea level (SL) and at high altitude (HA, 4,350 m). Lithium clearance (CLi) was used as an index of proximal tubular outflow. HA significantly increased arterial pressure......, heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P <0.05), but glomerular filtration rate (GFR), CLi, sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P <0.001) and 30% (P <0...

  8. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

    Prabahar Murugesan; Jain Manish; Chandrasekaran Venkatraman; Indhumathi Elayaperumal; Soundararajan Periasamy

    2008-01-01

    Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with ...

  9. Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

    Nobuhiko Satoh

    2015-01-01

    Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

  10. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

  11. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD. PMID:27281190

  12. Intracellular calcium ions as regulators of renal tubular sodium transport.

    Windhager, E; Frindt, G; Yang, J M; Lee, C O

    1986-09-15

    This review addresses the putative role of intracellular calcium ions in the regulation of sodium transport by renal tubules. Cytoplasmic calcium-ion activities in proximal tubules of Necturus are less than 10(-7) M and can be increased by lowering the electrochemical potential gradient for sodium ions across the peritubular cell membrane, or by addition of quinidine or ionomycin to peritubular fluid. Whereas lowering of the peritubular Na concentration increases cytosolic [Ca++] and [H+], ionomycin, a calcium ionophore, raises intracellular [Ca++] without decreasing pHi. The intracellular calcium-ion level is maintained by transport processes in the plasma membrane and membranes of intracellular organelles, as well as by calcium-binding proteins. Calcium ions inhibit net transport of sodium by reducing the rate of sodium entry across the luminal cell membrane. In the collecting tubule this inhibition is caused, at least in part, by an indirect reduction in the activity of the amiloride-sensitive sodium channel. PMID:2430134

  13. Fatal Cryocrystalglobulinemia With Intravascular and Renal Tubular Crystalline Deposits.

    DeLyria, Paul A; Avedschmidt, Sarah E; Yamada, Chisa; Farkash, Evan A

    2016-05-01

    Cryocrystalglobulinemia is a rare variant of cryoglobulinemia in which monoclonal immunoglobulins self-assemble into crystalline arrays. We report a case of a 53-year-old man who presented with systemic thrombotic microangiopathy causing multiorgan failure, including decreased kidney, lung, and gastrointestinal function; skin necrosis; and mental status changes. Skin and kidney biopsy specimens showed intravascular thrombi, along with intravascular, intratubular, and periglomerular crystalline deposits. Typical morphologic features of cryoglobulinemia, such as a leukocytoclastic vasculitis and pseudothrombi, were absent. Spindled crystals precipitated in the cryoglobulin assay, and immunofixation showed them to be composed of monoclonal immunoglobulin G κ light chains. Ultrastructural analysis demonstrated deposits to have an array-like substructure. The patient was successfully treated with a combination of plasmapheresis, steroids, and bortezomib, but experienced a relapse and died 12 months after his initial diagnosis. Cryocrystalglobulinemia causes significant morbidity and mortality and should be classified as a monoclonal gammopathy of renal significance when it occurs in patients not meeting diagnostic criteria for multiple myeloma. PMID:26775022

  14. Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

    The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

  15. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Damianovich, Maya; Ziv, Ilan; Aloya, Tali; Grimberg, Hagit; Levin, Galit; Reshef, Ayelet; Bentolila, Alfonso; Cohen, Avi; Shirvan, Anat [NeuroSurvival Technologies (NST) Ltd., Petah Tikva (Israel); Heyman, Samuel N.; Shina, Ahuva [Mt.Scopus and the Hebrew University Medical School, Department of Medicine, Hadassah Hospital, Jerusalem (Israel); Rosen, Seymour [Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Pathology, Boston, MA (United States); Kidron, Dvora [Meir Hospital, Department of Pathology, Kfar-Saba (Israel)

    2006-03-15

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  16. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  17. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  18. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  19. Micropatterning control of tubular commitment in human adult renal stem cells.

    Sciancalepore, Anna G; Portone, Alberto; Moffa, Maria; Persano, Luana; De Luca, Maria; Paiano, Aurora; Sallustio, Fabio; Schena, Francesco P; Bucci, Cecilia; Pisignano, Dario

    2016-07-01

    The treatment of renal injury by autologous, patient-specific adult stem cells is still an unmet need. Unsolved issues remain the spatial integration of stem cells into damaged areas of the organ, the commitment in the required cell type and the development of improved bioengineered devices. In this respect, biomaterials and architectures have to be specialized to control stem cell differentiation. Here, we perform an extensive study on micropatterned extracellular matrix proteins, which constitute a simple and non-invasive approach to drive the differentiation of adult renal progenitor/stem cells (ARPCs) from human donors. ARPCs are interfaced with fibronectin (FN) micropatterns, in the absence of exogenous chemicals or cellular reprogramming. We obtain the differentiation towards tubular cells of ARPCs cultured in basal medium conditions, the tubular commitment thus being specifically induced by micropatterned substrates. We characterize the stability of the tubular differentiation as well as the induction of a polarized phenotype in micropatterned ARPCs. Thus, the developed cues, driving the functional commitment of ARPCs, offer a route to recreate the microenvironment of the stem cell niche in vitro, that may serve, in perspective, for the development of ARPC-based bioengineered devices. PMID:27105437

  20. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  1. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  2. Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.

    Saegusa, S; Shimizu, F; Nagase, M; Kasegawa, A

    1979-08-01

    We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed. PMID:157110

  3. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27Kip1, collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  4. Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

    Bale, P M; Kan, A E; Dorney, S F

    1994-01-01

    We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes. PMID:8066004

  5. Renal tubular dysfunction in pediatric patients with beta-thalassemia major

    Ali Ahmadzadeh

    2011-01-01

    Full Text Available To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca, protein, uric acid (UA, creatinine (Cr, urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN, fasting blood sugar, serum creatinine (SCr, electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16 years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR. The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L and 3.2 IU/L in the control group (P 0.21 (P = 0.006. Nine (6.4% thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2. Sixty-nine (49.3% out of the 140 patients and 45 (65.2% of the patients having UNAG had uricosuria also (UUA/UCr > 0.26. Ten (7% patients had microscopic hematuria and 10 (7% patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

  6. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury.

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-04-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo-induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3(-/-)) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  7. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  8. Prohibitin is associated with antioxidative protection in hypoxia/reoxygenation-induced renal tubular epithelial cell injury

    Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Huang, Wei-Fang; Drummen, Gregor P. C.

    2013-11-01

    Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735 each P mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

  9. Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing.

    Yu, Wenmin; Li, Yiping; Wang, Zhi; Liu, Lei; Liu, Jing; Ding, Fengan; Zhang, Xiaoyi; Cheng, Zhengyuan; Chen, Pingsheng; Dou, Jun

    2016-09-01

    Chronic hypoxia often occurs among patients with chronic kidney disease (CKD). Renal proximal tubular cells may be the primary target of a hypoxic insult. However, the underlying transcriptional mechanisms remain undefined. In this study, we revealed the global changes in gene expression in HK‑2 human renal proximal tubular cells under hypoxic and normoxic conditions. We analyzed the transcriptome of HK‑2 cells exposed to hypoxia for 24 h using RNA sequencing. A total of 279 differentially expressed genes was examined, as these genes could potentially explain the differences in HK‑2 cells between hypoxic and normoxic conditions. Moreover, 17 genes were validated by qPCR, and the results were highly concordant with the RNA seqencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to better understand the functions of these differentially expressed genes. The upregulated genes appeared to be significantly enriched in the pathyway of extracellular matrix (ECM)-receptor interaction, and in paticular, the pathway of renal cell carcinoma was upregulated under hypoxic conditions. The downregulated genes were enriched in the signaling pathway related to antigen processing and presentation; however, the pathway of glutathione metabolism was downregulated. Our analysis revealed numerous novel transcripts and alternative splicing events. Simultaneously, we also identified a large number of single nucleotide polymorphisms, which will be a rich resource for future marker development. On the whole, our data indicate that transcriptome analysis provides valuable information for a more in depth understanding of the molecular mechanisms in CKD and renal cell carcinoma. PMID:27432315

  10. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells.

    Gui, Ting; Gai, Zhibo

    2015-12-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296). PMID:26697325

  11. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    Ting Gui

    2015-12-01

    Full Text Available To assess the effect of farnesoid X receptor (FXR, a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist or DMSO (as controls overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296.

  12. Reduction of high-energy shock-wave-induced renal tubular injury by selenium.

    Strohmaier, W L; Lahme, S; Weidenbach, P M; Bichler, K H

    1999-10-01

    In shock-wave-induced renal injury cavitation-generated free radicals play an important role. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of selenium, a free radical scavenger, in shock-wave-induced tubular cell injury. Suspensions of MDCK cells (33 x 10(6) cells/ml) were placed in small containers (volume 1.1 ml) for shock wave exposure. Two groups of 12 containers each were examined: (1) control (no medication), (2) selenium (0.4 microg/ml nutrient medium). Six containers in each group were exposed to shock waves (impulse rate 256, frequency 60 Hz, generator voltage 18 kV), while the other six containers in each group served as a control. After shock wave exposure, the concentration of cellular enzymes such as lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), glutamate oxaloacetate transaminase (GOT) and glutamate lactate dehydrogenase (GLDH) in the nutrient medium was examined. Following shock wave exposure there was a significant rise in LDH, NAG, GOT and GLDH concentrations. Selenium reduced this enzyme leakage significantly. Thus we conclude that selenium protects renal tubular cells against shock-wave-induced injury. Since selenium is an essential part of glutathione peroxidase, this effect seems to be mediated by a reduction in reactive oxygen species. PMID:10550528

  13. Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats.

    Jenkin, Kayte A; O'Keefe, Lannie; Simcocks, Anna C; Grinfeld, Esther; Mathai, Michael L; McAinch, Andrew J; Hryciw, Deanne H

    2015-05-01

    Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague-Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9). In a different cohort, rats were fed a HFD for 15 weeks. After 9 weeks consuming a HFD, rats were injected daily for 6 weeks with 3 mg/kg AM251 (n=9) or saline via i.p. injection (n=9). After 10 weeks consuming a HFD, CB1 and megalin protein expression were significantly increased in the kidneys of obese rats. Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats. Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinaemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGFA, TGFB1 and collagen IV in the kidney. This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats. PMID:25804605

  14. Renal tubular dysgenesis with hypocalvaria and ileocecal valve agenesis: an autopsy report

    Ariel Barreto Nogueira

    2012-12-01

    Full Text Available Renal tubular dysgenesis (RTD is a rare, lethal, autosomal recessive disorder characterized by non-differentiation of the renal proximal convoluted tubules, resulting in oligohydramnios. It is usually diagnosed in the second trimester of pregnancy, following the oligohydramnios sequence, pulmonary hypoplasia and hypocalvaria. The prognosis is poor, and death usually occurs in utero or within the first few days of life. The pathogenesis of RTD is associated with the perinatal use of drugs, such as angiotensin- converting enzyme inhibitors, angiotensin II receptor antagonists, and anti- inflammatory drugs, as well as with fetal transfusion syndrome, genetic mutations in the pathway of the renin-angiotensin system pathway, cocaine snorting, or other pathological mechanisms that reduce renal blood flow. Here, we report the autopsy of a neonate born to consanguineous parents at 38 weeks of gestation, with RTD, decreased amniotic fluid, oligohydramnios sequence, hypocalvaria, pulmonary hypoplasia, and ileocecal valve agenesis. To our knowledge, the latter has never been reported associated with RTD.

  15. Lactic Acidosis

    K.Srikanth

    2012-01-01

    Abstract. Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poiso...

  16. Regulation of MUTYH, a DNA Repair Enzyme, in Renal Proximal Tubular Epithelial Cells

    Jianping Lu

    2015-01-01

    Full Text Available MUTYH is a DNA repair enzyme that initiates a base excision repair (BER by recognizing and removing 8-Oxoguanine (8-oxoG and its paired adenine. We demonstrated that both TGF-β1 and H2O2 treatment led to an increased 8-oxoG in cultured human proximal tubule epithelial (HK-2 cells, while the former induced epithelial-mesenchymal transition and the latter caused cell apoptosis. Without stimulation, HK-2 cells showed MUTYH expression in mitochondria. TGF-β1 triggered a transient upregulation of mitochondrial MUTYH and induced the expression of nuclear isoforms, while H2O2 showed no role on MUTYH expression. Ureteral obstruction (UUO mice exhibited high 8-oxoG reactivity with tubulointerstitial lesions. After obstruction, the MUTYH expression was increased only in tubules at day 3 and decreased with obvious tubular atrophy at day 10. Particularly, MUTYH was primarily located in normal tubular cytoplasm with a dominant mitochondrial form. A few cells with nuclear MUTYH expression were observed in the fibrotic interstitium. We confirmed that increased MUTYH expression was upregulated and positively correlated with the severity of kidney fibrosis. Thus, renal fibrosis caused a cell-type-specific and time-dependent response of oxidative DNA repairs, even within the same tissues. It suggests that intervention of MUTYH might be effective for therapies.

  17. Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.

    Calpurnia Jayakumar

    Full Text Available BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.

  18. Cadmium activates extracellular signal-regulated kinase 5 in HK-2 human renal proximal tubular cells

    Highlights: ► Cadmium exposure induces ERK5 phosphorylation in HK-2 renal proximal tubular cells. ► BIX02189 treatment suppresses cadmium-induced ERK5 but not ERK1/2 phosphorylation. ► BIX02189 treatment suppresses cadmium-induced CREB and c-Fos phosphorylation. ► ERK5 activation by cadmium exposure may play an anti-apoptotic role in HK-2 cells. -- Abstract: We examined the effects of cadmium chloride (CdCl2) exposure on the phosphorylation and functionality of extracellular signal-regulated kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, in HK-2 human renal proximal tubular cells. Following exposure to CdCl2, ERK5 phosphorylation increased markedly, but the level of total ERK5 was unchanged. ERK5 phosphorylation following CdCl2 exposure was rapid and transient, similar to the time course of ERK1/2 phosphorylation. Treatment of HK-2 cells with the MAPK/ERK kinase 5 inhibitor, BIX02189, suppressed CdCl2-induced ERK5 but not ERK1/2 phosphorylation. The CdCl2-induced increase of phosphorylated cAMP response element-binding protein (CREB) and activating transcription factor-1 (ATF-1), as well as the accumulation of mobility-shifted c-Fos protein, were suppressed by BIX02189 treatment. Furthermore, BIX02189 treatment enhanced cleavage of poly(ADP-ribose) polymerase and increased the level of cytoplasmic nucleosomes in HK-2 cells exposed to CdCl2. These findings suggest that ERK5 pathway activation by CdCl2 exposure might induce the phosphorylation of cell survival-transcription factors, such as CREB, ATF-1, and c-Fos, and may exert a partial anti-apoptotic role in HK-2 cells.

  19. Survey on relation between Major Thalassemia and Desferiexamine with renal tubular damage.

    H.M. Jafari, M.D.

    2007-01-01

    Full Text Available AbstractBackground and Purpose: Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major (TM patients in comparison with control group.Materials and Methods: This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test (t, chi square.Results: the Total of 84 (42 patients and, 42 controls patients were studied. The Mean age of the patients was years. Dose of Deferral was 70±19 mg/kg. The results showed no significant statistical differences in levels of microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups.Conclusion: In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with sever anemia, high dose desferal and Iron over load.

  20. Stem Cell Conditioned Culture Media Attenuated Albumin-Induced Epithelial-Mesenchymal Transition in Renal Tubular Cells

    Junping Hu

    2015-03-01

    Full Text Available Background: Proteinuria-induced epithelial-mesenchymal transition (EMT plays an important role in progressive renal tubulointerstitial fibrosis in chronic renal disease. Stem cell therapy has been used for different diseases. Stem cell conditioned culture media (SCM exhibits similar beneficial effects as stem cell therapy. The present study tested the hypothesis that SCM inhibits albumin-induced EMT in cultured renal tubular cells. Methods: Rat renal tubular cells were treated with/without albumin (20 µmg/ml plus SCM or control cell media (CCM. EMT markers and inflammatory factors were measured by Western blot and fluorescent images. Results: Albumin induced EMT as shown by significant decreases in levels of epithelial marker E-cadherin, increases in mesenchymal markers fibroblast-specific protein 1 and a-smooth muscle actin, and elevations in collagen I. SCM inhibited all these changes. Meanwhile, albumin induced NF-κB translocation from cytosol into nucleus and that SCM blocked the nuclear translocation of NF-κB. Albumin also increased the levels of pro-inflammatory factor monocyte chemoattractant protein-1 (MCP-1 by nearly 30 fold compared with control. SCM almost abolished albumin-induced increase of MCP-1. Conclusion: These results suggest that SCM attenuated albumin-induced EMT in renal tubular cells via inhibiting activation of inflammatory factors, which may serve as a new therapeutic approach for chronic kidney diseases.

  1. Clostridium perfringens epsilon toxin is cytotoxic for human renal tubular epithelial cells.

    Fernandez Miyakawa, Mariano E; Zabal, Osvaldo; Silberstein, Claudia

    2011-04-01

    Clostridium perfringens epsilon toxin (ETX) is responsible for a fatal enterotoxemia in different animal species, producing extensive renal damage, neurological disturbance and edema of lungs, heart and kidneys. However, there is no information about the susceptibility of humans to ETX. Here, we report that primary cultures of human renal tubular epithelial cells (HRTEC) exposed to ETX showed a marked swelling with subsequent large blebs surrounding most cells. The incubation of HRTEC with ETX produced a reduction of cell viability in a dose- and time-dependent manner. The CD(50) after 1-hour and 24-hour incubation were 3 µg/mL and 0.5 µg/mL, respectively. The pulse with ETX for 3 min was enough to produce a significant cytotoxic effect on HRTEC after 1-hour incubation. ETX binds to HRTEC forming a large complex of about 160 kDa similar to what was found in the Madin-Darby canine kidney (MDCK) cell line. The HRTEC could be a useful cell model to improve the understanding of the mechanisms involved on the cell damage mediated by ETX. PMID:20488848

  2. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  3. Renal acidification defects in patients with their first renal stone episode

    Osther, P J; Hansen, A B; Röhl, H F

    1988-01-01

    To rule out renal acidification defects, 40 consecutive patients with their first renal stone episode were evaluated by measurement of fasting morning urine pH levels followed by a short ammonium chloride loading test in cases with high levels. Two patients (5%) exhibited incomplete distal renal...... tubular acidosis, the rest had normal urinary acidification. In view of the short duration of stone disease in the patients studied, the acidification defects were considered to be primary, and the stone formation secondary. The results justify extension of these simple screening procedures for unmasking...... renal acidification defects to include all patients with renal stone disease....

  4. Incomplete renal tubular acidosis as a predisposing factor for calcium phosphate stones in neuropathic bladder: a case report

    Vaidyanathan, Subramanian; Soni, Bakul M.; Watson, Ian D; Singh, Gurpreet; Peter L. Hughes; Mansour, Paul

    2008-01-01

    We present a male tetraplegic patient, who developed stones in neuropathic bladder six times within a span of three years. Unusual features of this case are: (1) This patient started developing stones in urinary bladder thirteen years after sustaining spinal cord injury. (2) He was performing intermittent catheterisation and did not have an indwelling catheter. (3) The presenting symptom of vesical lithiasis was abdominal spasms and not urine infection. (4) The major component of the stones w...

  5. Osteopathy of renal tubular acidosis: Case report%肾小管酸中毒性骨病1例

    李欣欣

    2011-01-01

    @@ 患者男,49岁.因"腰腿疼痛3年,加重1个月"来诊.患者既往有慢性乙型肝炎病史,长期服用多种抗病毒药物.入院查体:腰椎及髋部压痛明显,直腿抬高试验及"4"字征(-).实验室检查:HLA B27(-).尿常规检查:尿蛋白(-),尿糖:(+),尿pH值7.00;电解质:TCO2 17.21 mmol/L,K+ 3.26 mmol/L,Cl- 106.00 mmol/L;肾功能检查:Cr 106.00 μmol/L,Bun 6.90 mmol/L.血钙1.92 mmol/L,血磷1.80 mmol/L.

  6. Role of CDK5/cyclin complexes in ischemia-induced death and survival of renal tubular cells

    Guevara, Tatiana; Sancho, Mónica; Pérez-Payá, Enrique; Orzáez, Mar

    2014-01-01

    Ischemia reperfusion processes induce damage in renal tubules and compromise the viability of kidney transplants. Understanding the molecular events responsible for tubule damage and recovery would help to develop new strategies for organ preservation. CDK5 has been traditionally considered a neuronal kinase with dual roles in cell death and survival. Here, we demonstrate that CDK5 and their regulators p35/p25 and cyclin I are also expressed in renal tubular cells. We show that treatment with CDK inhibitors promotes the formation of pro-survival CDK5/cyclin I complexes and enhances cell survival upon an ischemia reperfusion pro-apoptotic insult. These findings support the benefit of treating with CDK inhibitors for renal preservation, assisting renal tubule protection. PMID:24675881

  7. A simple slide-rule method for the assessment of renal tubular reaborption of phosphate in man.

    Walton, R J; Bijvoet, O L

    1977-12-15

    The activity of renal tubular reabsorption of phosphate in man is best expressed as the ratio of the maximum rate or reabsorption to the glomerular filtration rate (TmP/GFR). A slide-rule method based on existing data is described for the derivation of TmP/GFR from values of phosphate and creatinine concentrations in single samples of plasma and urine. This is a simple method which is suitable both for research and for clinical purposes. PMID:923101

  8. Effects of renal tubular dysfunction on bone in tenofovir-exposed HIV-positive patients

    Campbell, Lucy; Pope, Matthew; Burling, Keith; Fisher, Martin; Gilleece, Yvonne; Walker-Bone, Karen; Post, Frank A.

    2016-01-01

    Objectives Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men. Design and methods We analysed urinary retinol binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross sectional sample of randomly selected HIV positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy x-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD. Results Of 293 men (mean age 48 years, 94% white ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (β -0.2, p=0.002) and hip (total: β -0.1, p=0.02; femoral neck: β -0.1, p=0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by >5 fold elevations in RBPCR was associated with significantly lower BMD of the spine. Conclusions RTD was associated with lower BMD of the spine in HIV-positive men. RBPCR quantification may identify patients at increased risk of TDF-associated BMD reduction. PMID:26372384

  9. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  10. Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function

    Olsen, Niels Vidiendal; Fogh-Andersen, N; Strandgaard, S;

    1996-01-01

    1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo...... or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 micrograms min-1 kg-1 of dopamine. 2. Baseline values of endogenous CLi and...... fractional excretion of lithium (FELi) [27.0 (23.5-30.5) ml/min and 24.2 (20.3-28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9-35.4) ml/min (P <0.05) and 27.4 (25.2-29.6)% (P <0.05); lithium, 600 mg: 33.4 (29.2-37.6)ml/min (P <0.05) and 28.6 (26...

  11. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  12. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

  13. Stimulation of Na+/H+ antiport is an early event in hypertrophy of renal proximal tubular cells

    Renal hypertrophy in vivo is achieved by an increase in protein content per cell and an increase in cell size with minimal hyperplasia. Hypertrophied renal tubular cells remain quiescent and demonstrate an increase in transcellular transport rates. This situation was simulated in vitro by exposing a confluent, quiescent primary culture of rabbit renal proximal tubular cells to either insulin, prostaglandin E1, or hypertonic NaCl for 24 or 48 hr. Protein per cell increased by 20-30% with little or no increase in [3H]thymidine incorporation into DNA. Mean cell volume was also increased in insulin- and hypertonic NaCl-treated but not in prostaglandin E1-treated cells. Two hours of exposure to the growth stimuli increased amiloride-sensitive Na+ uptake, Na-dependent H+ efflux, and ouabain-sensitive Rb+ uptake, indicating that stimulation of Na+/H+ antiport (exchange) occurs as an early event in their action. Hypertrophied cells continued to demonstrate enhanced Na+/H+ antiport after the growth stimuli were removed for 3 hr, by which time their acute effects are reversed

  14. Renal Function in Diabetic Disease Models: The Tubular System in the Pathophysiology of the Diabetic Kidney

    Vallon, Volker; Thomson, Scott C.

    2013-01-01

    Diabetes mellitus affects the kidney in stages. At the onset of diabetes mellitus, in a subset of diabetic patients the kidneys grow large, and glomerular filtration rate (GFR) becomes supranormal, which are risk factors for developing diabetic nephropathy later in life. This review outlines a pathophysiological concept that focuses on the tubular system to explain these changes. The concept includes the tubular hypothesis of glomerular filtration, which states that early tubular growth and sodium-glucose cotransport enhance proximal tubule reabsorption and make the GFR supranormal through the physiology of tubuloglomerular feedback. The diabetic milieu triggers early tubular cell proliferation, but the induction of TGF-β and cyclin-dependent kinase inhibitors causes a cell cycle arrest and a switch to tubular hypertrophy and a senescence-like phenotype. Although this growth phenotype explains unusual responses like the salt paradox of the early diabetic kidney, the activated molecular pathways may set the stage for tubulointerstitial injury and diabetic nephropathy. PMID:22335797

  15. EGCG decreases binding of calcium oxalate monohydrate crystals onto renal tubular cells via decreased surface expression of alpha-enolase.

    Kanlaya, Rattiyaporn; Singhto, Nilubon; Thongboonkerd, Visith

    2016-06-01

    Crystal retention on tubular cell surface inside renal tubules is considered as the earliest and crucial step for kidney stone formation. Therapeutics targeting this step would cease the development of kidney stone. This study thus aimed to investigate the potential role of epigallocatechin-3-gallate (EGCG), a major antioxidant found in green tea leaves, in the reduction of calcium oxalate monohydrate (COM) crystal binding onto renal tubular cells. Pretreatment of the cells with EGCG for up to 6 h significantly diminished crystal-binding capability in a dose-dependent manner. Indirect immunofluorescence assay without and with cell permeabilization followed by laser-scanning confocal microscopy revealed that EGCG significantly reduced surface expression of alpha-enolase, whereas its intracellular level was increased. Western blot analysis confirmed such contradictory changes in membrane and cytosolic fractions of EGCG-treated cells, whereas the total level in whole cell lysate remained unchanged. Moreover, overexpression of surface alpha-enolase and enhancement of cell-crystal adhesion induced by 10 mM sodium oxalate were completely abolished by EGCG. Taken together, these data indicate that EGCG decreases binding of COM crystals onto renal tubular cells by decreasing the surface expression of alpha-enolase via re-localization or inhibition of alpha-enolase shuttling from the cytoplasm to the plasma membrane. These findings may also explain the effects of EGCG in reducing COM crystal deposition in previous animal models of kidney stone disease. Thus, EGCG may be useful for the prevention of new or recurrent stone formation. PMID:26898643

  16. Heat-preconditioning confers protection from Ca2+-mediated cell toxicity in renal tubular epithelial cells (BSC-1)

    Kuhlmann, Martin K.; Betz, Regina; Hanselmann, Rainer; Köhler, Hans

    1997-01-01

    A rise in intracellular calcium may mediate ischemic damage by phospholipid hydrolysis and proteolysis Heat shock proteins have been shown to provide protection from various forms of cell stress, but not from models of Ca2+-mediated injury. The effect of heat preconditioning in a model of ionomycin-induced injury in cultured renal tubular epitheliaal cells (BSC-1) was examined. Hsp70-mRNA expression was induced by hyperthermia (HT) (42°C, 60 min). Hsp70 protein accumulation was maximal after ...

  17. HIV-1 Promotes Renal Tubular Epithelial Cell Protein Synthesis: Role of mTOR Pathway

    Rehman, Shabina; Husain, Mohammad; Yadav, Anju; Kasinath, Balakuntalam S.; Malhotra, Ashwani; Singhal, Pravin C.

    2012-01-01

    Tubular cell HIV-infection has been reported to manifest in the form of cellular hypertrophy and apoptosis. In the present study, we evaluated the role of mammalian target of rapamycin (mTOR) pathway in the HIV induction of tubular cell protein synthesis. Mouse proximal tubular epithelial cells (MPTECs) were transduced with either gag/pol-deleted NL4-3 (HIV/MPTEC) or empty vector (Vector/MPTEC). HIV/MPTEC showed enhanced DNA synthesis when compared with Vector/MPTECs by BRDU labeling studies....

  18. Comparison of Ultrasound Corticomedullary Strain with Doppler Parameters in Assessment of Renal Allograft Interstitial Fibrosis/Tubular Atrophy.

    Gao, Jing; Rubin, Jonathan M; Weitzel, William; Lee, Jun; Dadhania, Darshana; Kapur, Sandip; Min, Robert

    2015-10-01

    To compare the capability of ultrasound strain and Doppler parameters in the assessment of renal allograft interstitial fibrosis/tubular atrophy (IF/TA), we prospectively measured ultrasound corticomedullary strain (strain) and intra-renal artery Doppler end-diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI) in 45 renal transplant recipients before their kidney biopsies. We used 2-D speckle tracking to estimate strain, the deformation ratio of renal cortex to medulla produced by external compression using the ultrasound transducer. We also measured Doppler EDV, PSV and RI at the renal allograft inter-lobar artery. Using the Banff scoring system for renal allograft IF/TA, 45 patients were divided into the following groups: group 1 with ≤5% (n = 12) cortical IF/TA; group 2 with 6%-25% (n = 12); group 3 with 26%-50% (n = 11); and group 4 with >50% (n = 10). We performed receiver operating characteristic curve analysis to test the accuracy of these ultrasound parameters and duration of transplantation in determining >26% cortical IF/TA. In our results, strain was statistically significant in all paired groups (all p EDV was significant only between high-grade (>26%, including 26%-50% and >50%) and low-grade (≤25%, including 0.05). The areas under the receiver operating characteristic curve for strain, EDV, PSV, RI and duration of transplantation in determining >26% cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively. Our results suggest that corticomedullary strain seems to be superior to Doppler parameters and duration of transplantation in assessment of renal allograft cortical IF/TA. PMID:26219696

  19. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B; Fogh-Andersen, N; Jordening, H; Munck, O

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or...

  20. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy. PMID:21689714

  1. Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells

    Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (·O2), nitric oxide (NO·), and peroxynitrite (ONOO-), as well as nuclear factor-kappa B (NF-κB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, ·O2, NO·, ONOO-, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-κB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

  2. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

    Bruun, N E; Ibsen, H; Skøtt, P; Toftdahl, D; Giese, J; Holstein-Rathlou, N H

    1988-01-01

    1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155....../101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates...... reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment...

  3. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Ana B Sanz

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  4. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

    Kohan Donald E; Schmid Douglas I; Hughes Alisa K

    2002-01-01

    Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN), h...

  5. The tubular extraction rate (TER) of 99mTc-MAG3: A new quantitative parameter of renal function

    First clinical results have shown that among the 99mTc-complexes which were synthesized for renal function studies 99mTc-MAG3 revealed the most similar biokinetical characteristics compared with o-I-hippurate (OIH). Totally 90 simultaneous investigations of 12 kidney transplant patients were performed with 99mTc-MAG3 and 131I-OIH during the early post-transplantation period. It could be demonstrated that in case of an acute graft rejection or an acute tubular necrosis the respective renograms were qualitatively identical. Therefore, loss of information caused by using 99mTc-MAG3 instead of 131I-OIH could be excluded (BUBECK et al. 1987 b). During slope-clearance calculations after simultaneous application of both radiopharmaceuticals (n=16), volumes of distribution were revealed to be 11% for Tc-MAG3 and 16% for OIH related to the body weight. By determination of the plasma-protein binding, the glomerular filtered fraction of both substances were estimated to be 5 and 2% of the plasma activity for OIH and Tc-MAG3, respectively. Due to the negligible amount, which is eliminated by glomerular filtration, the clearance of Tc-MAG3 is a measure of its tubular extraction. It therefore may be termed as the 'Tubular Extraction Rate' (TER) of Tc-MAG3. From totally 103 simultaneous clearance-measurements with both 131I-OIH and 99mTc-MAG3 (88 were estimated on steady state conditions) the clearance-ration of Tc-MAG3/OIH was determined to be 0.67 (r=0.94). All these data yielded a 'Tubular Extraction Coefficient' (TEC) of 0.83 for OIH and 0.56 for Tc-MAG3. Derived from the known OIH-clearances in normal subjects an age-dependent formula for Tc-MAG3 was established: TER(MAG3) = 435.8-(3.03xage). Due to the hitherto known characteristics 99mTc-MAG3 can clinically be used as a substitute for radioiodinated OIH in both application areas, renal imaging and quantitative function studies of the kidneys. (orig.)

  6. Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure – A case report

    Bagshaw Sean M

    2004-08-01

    Full Text Available Abstract Background Dialysis disequilibrium syndrome (DDS is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD. We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L. Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L (urea-reduction-ratio 71%. Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

  7. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    Nielsen, Stine; Rossing, Kasper; Hess, Georg;

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid......-binding protein (LFABP)....

  8. Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats

    The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of 14C-tetraethylammonium, 3H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (CLi/CIn) and the distal nephron segments (CNa/CLi). The changes in CLi/CIn became maximal at doses above 0.5 mg/kg, whereas CNa/CLi was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of CNa/CLi. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment. (author)

  9. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    K J Kelly

    Full Text Available Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  10. Topiramate and severe metabolic acidosis: case report Acidose metabólica grave por topiramato: relato de caso

    Jayme E. Burmeister

    2005-06-01

    Full Text Available Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron - a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and should be given careful attention.Topiramato pode produzir raramente uma acidose metabólica através da inibição da anidrase carbônica no túbulo distal do néfron - acidose tubular renal do tipo 2. Relatamos o caso de mulher de 40 anos previamente saudável que desenvolveu quadro de acidose metabólica assintomática grave, sem outra etiologia identificável, durante uso de topiramato na dose de 100mg/dia por três meses. Este efeito colateral, embora infrequente, parece ser imprevisível e requer atenção cuidadosa.

  11. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways.

    Thongnuanjan, Penjai; Soodvilai, Sirima; Chatsudthipong, Varanuj; Soodvilai, Sunhapas

    2016-01-01

    Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment. PMID:27193727

  12. Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

    Altun, Demet; Kurekci, Ahmet Emin; Gursel, Orhan; Hacıhamdioglu, Duygu Ovunc; Kurt, Ismail; Aydın, Ahmet; Ozcan, Okan

    2014-10-01

    We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen. PMID:25099508

  13. Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney

    Abildgaard, U; Amtorp, O; Holstein-Rathlou, N H;

    1988-01-01

    This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance of...... content of adrenaline and noradrenaline. The results suggest that the increase in APR and FPR during RVP elevation is due mainly to local sympathetic reflex mechanisms....

  14. Kidney-specific knockout of Sav1 in the mouse promotes hyperproliferation of renal tubular epithelium through suppression of the Hippo pathway.

    Kai, Tomoki; Tsukamoto, Yoshiyuki; Hijiya, Naoki; Tokunaga, Akinori; Nakada, Chisato; Uchida, Tomohisa; Daa, Tsutomu; Iha, Hidekatsu; Takahashi, Mika; Nomura, Takeo; Sato, Fuminori; Mimata, Hiromitsu; Ikawa, Masahito; Seto, Masao; Matsuura, Keiko; Moriyama, Masatsugu

    2016-05-01

    We have previously reported that Salvador homologue 1 (SAV1), a component of the Hippo pathway, is significantly down-regulated in high-grade clear cell renal cell carcinoma (ccRCC) due to 14q copy number loss, and that this down-regulation contributes to the proliferation and survival of renal tubular epithelial cells through activation of Yes-associated protein 1 (YAP1), a downstream target of the Hippo pathway. However, the impact of SAV1 loss on the proliferation and survival of kidney cells in vivo remained to be determined. To address this issue, we generated kidney-specific Sav1-knockout (Cdh16-Cre;Sav1(fl/fl) ) mice. Sav1 deficiency enhanced the proliferation of renal tubular epithelial cells in Cdh16-Cre;Sav1(fl/fl) mice, accompanied by nuclear localization of Yap1, suggesting suppression of the Hippo pathway. Sav1 deficiency in renal tubules also caused structural and cellular abnormalities of the epithelial cells, including significant enlargement of their nuclei. Furthermore, Cdh16-Cre;Sav1(fl/fl) mice developed both glomerular and tubular cysts. Although lining cells of the glomerular cysts showed no atypia, those of the tubular cysts showed variations in cell size and nuclear shape, which became more severe as the mice aged. In aged Cdh16-Cre;Sav1(fl/fl) mice, we observed focal disruption of proximal tubules and perivascular lymphocytic infiltration. In conclusion, Sav1 is required for the maintenance of growth, nuclear size and structure of renal tubules under physiological conditions, and its deficiency leads to the acquisition of enhanced proliferation of renal epithelial cells through suppression of Hippo signalling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26913567

  15. The role of AT1 and AT2 angiotensin receptors in the mechanism of apoptosis in renal tubular cells after physical exercise.

    Podhorska-Okołów, M; Dziegiel, P; Gomułkiewicz, A; Dolińska-Krajewska, B; Murawska-Ciałowicz, E; Jethon, Z; Zabel, M

    2004-01-01

    Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors. PMID:15638358

  16. Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.

    Chen, Yongwen; Li, Jingyi; Zhang, Jingbo; Zhao, Tingting; Zou, Liyun; Tang, Yan; Zhang, Xiaoping; Wu, Yuzhang

    2005-08-01

    Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells. PMID:15953571

  17. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.

    Shiyo Muratsu-Ikeda

    Full Text Available BACKGROUND: Oxidative stress and endoplasmic reticulum (ER stress play a crucial role in tubular damage in both acute kidney injury (AKI and chronic kidney disease (CKD. While the pathophysiological contribution of microRNAs (miRNA to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. METHODS: We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2 gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. CONCLUSIONS: miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules.

  18. Can we target tubular damage to prevent renal function decline in diabetes?

    Bonventre, Joseph V

    2012-09-01

    The glomerulus has been at the center of attention as the primary site of injury in diabetic nephropathy (DN). Although there is no question that there are changes seen in the glomerulus, it is also well known that tubulointerstitial changes are a prominent component of the disease, especially in patients with type 2 diabetes. The level of albuminuria and DN disease progression best correlate with tubular degeneration and interstitial fibrosis. Nephrotoxicity studies in animals reveal that albuminuria is a highly sensitive marker of early tubular toxicity even in the absence of glomerular pathology. Urinary biomarker data in human beings support the view that proximal tubule injury contributes in a primary way, rather than in a secondary manner, to the development of early DN. I present a model in which very specific injury to the proximal tubule in vivo in the mouse results in severe inflammation, loss of blood vessels, interstitial fibrosis, and glomerulosclerosis. Increased glucose levels, free glycation adducts, reactive oxygen species, and oxidized lipids result in toxicity to tubule epithelia. This results in loss of cells with a stimulus to repair the epithelium. However, because of sublethal injury there is cell-cycle arrest in epithelial cells attempting to replace damaged cells. This leads to epithelial secretion of both profibrogenic growth factors, collagens, and factors that cause pericytes to proliferate and differentiate into myofibroblasts, leading to endothelial destabilization and capillary rarefaction. Local ischemia ensues with further injury to the tubules, more profibrogenic mediators, matrix protein deposition, fibrosis, and glomerulosclerosis. PMID:23062986

  19. Overall renal and tubular function during infusion of amino acids in normal man

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D; Fogh-Andersen, N; Nielsen, S L; Leyssac, P P

    1990-01-01

    infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...

  20. In Situ lactate dehydrogenase activiy-a novel renal cortical imaging biomarker of tubular injury?

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    Renal ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI) in several disease states, including hypovolemic shock, sepsis, surgery. Imbalance in energy metabolism and mitochondrial function is a hallmark in IRI which can be caused by mechanisms like oxidative stress...

  1. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney ston

  2. Renal proximal tubular cell fibronectin accumulation in response to glucose is polyol pathway dependent

    Morrisey; Steadman; Williams; Phillips

    1999-06-01

    Thickening and reduplication of the tubular basement membrane has been reported as an early event in diabetic nephropathy. In the current study we have examined the polar requirements of proximal tubular cells for the D-glucose stimulated accumulation of fibronectin. We also examined the mechanism by which glucose led to accumulation of fibronectin, with particular emphasis on the polyol pathway. Incubation of confluent monolayers of LLC-PK1 cells grown on tissue culture inserts with 25 mM D-glucose on either their apical or basolateral aspect, led to fibronectin accumulation in the basolateral compartment. This reached statistical significance 24 h following apical addition of glucose (2.7 fold increase compared to 5 mM D-glucose, p = 0.007, n = 6), and 12 h after the basolateral addition of glucose (2.54 fold increase compared to 5 mM D-glucose, p = 0.02, n = 6). The increase in fibronectin concentration in response to glucose was inhibited by the aldose reductase inhibitor sorbinil. At a dose of 100&mgr;M sorbinil there was 59% inhibition of fibronectin accumulation in response to glucose, 48 h after the addition of the inhibitor (4.76 +/- 1.4 vs 11.53 +/- 1.41, mean +/- SD, p = 0.01, n = 3). Exposure of cells to glucose at either their apical or basolateral aspect lead to accumulation of intracellular glucose and polyol pathway activation, as assessed by sorbitol accumulation. Accumulation of intracellular glucose and hence subsequent polyol pathway activation occurred independently of transport of glucose by either apical sodium linked glucose transporter (SLGT) or basolateral GLUT 1. The data demonstrate that fibronectin generation in response to glucose was non-polar in terms application of glucose, but polar in terms of fibronectin accumulation. Furthermore modulation of fibronectin was mediated by polyol pathway activation, and more specifically related to the metabolism of sorbitol to fructose. PMID:10354307

  3. Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury

    Li, Dao; Li, Jin; Li, Hui; Wu, Qiong; Li, Qi-Xiong

    2016-01-01

    Objective(s): Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions. Materials and Methods: Fifty male Sprague-Dawley rats weighing 250–300 g were randomly divided into five groups: administrations of olive oil (control, PO), RG (0.4 mg/kg, PO), CsA (30 mg/kg in olive oil, SC), RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil SC) every day for 15 days. Results: SC administration of CsA (30 mg/kg) to rats produced marked elevations in the levels of renal impairment parameters such as urinary protein, N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine (SCr), and blood urea nitrogen (BUN). It also caused histologic injury to the kidneys. Oral administration of RG (0.2 and 0.4 mg/kg) markedly decreased all the aforementioned changes. In addition, CsA caused increases in the levels of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione in kidney homogenate, which were reversed significantly by both doses of RG. Conclusion: The findings of our study indicate that RG may play an important role in protecting the kidney from oxidative insult.

  4. Polar release of pathogenic Old World hantaviruses from renal tubular epithelial cells

    Krautkrämer Ellen

    2012-11-01

    Full Text Available Abstract Background Epithelio- and endotheliotropic viruses often exert polarized entry and release that may be responsible for viral spread and dissemination. Hantaviruses, mostly rodent-borne members of the Bunyaviridae family infect epithelial and endothelial cells of different organs leading to organ dysfunction or even failure. Endothelial and renal epithelial cells belong to the target cells of Old World hantavirus. Therefore, we examined the release of hantaviruses in several renal epithelial cell culture models. We used Vero cells that are commonly used in hantavirus studies and primary human renal epithelial cells (HREpC. In addition, we analyzed MDCKII cells, an epithelial cell line of a dog kidney, which represents a widely accepted in vitro model of polarized monolayers for their permissiveness for hantavirus infection. Results Vero C1008 and primary HREpCs were grown on porous-support filter inserts for polarization. Monolayers were infected with hantavirus Hantaan (HTNV and Puumala (PUUV virus. Supernatants from the apical and basolateral chamber of infected cells were analyzed for the presence of infectious particles by re-infection of Vero cells. Viral antigen and infectious particles of HTNV and PUUV were exclusively detected in supernatants collected from the apical chamber of infected Vero C1008 cells and HREpCs. MDCKII cells were permissive for hantavirus infection and polarized MDCKII cells released infectious hantaviral particles from the apical surface corresponding to the results of Vero and primary human epithelial cells. Conclusions Pathogenic Old World hantaviruses are released from the apical surface of different polarized renal epithelial cells. We characterized MDCKII cells as a suitable polarized cell culture model for hantavirus infection studies.

  5. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

    Kohan Donald E

    2002-08-01

    Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

  6. Effect of dietary calcium and magnesium on experimental renal tubular deposition of calcium oxalate crystal induced by ethylene glycol administration and its prevention with phytin and citrate.

    Ebisuno, S; Morimoto, S; Yoshida, T; Fukatani, T; Yasukawa, S; Ohkawa, T

    1987-01-01

    Oral administration of ethylene glycol to rats, and the resultant intratubular depositions of microcrystals of calcium oxalate were studied investigating the influences of dietary calcium or magnesium and assessing the protective efficacies against the crystallizations by treatment with phytin and sodium citrate. With increase of calcium intake and consequent increase of urinary calcium excretion there was a marked increase in the amount of tubular deposit of calcium oxalate crystal and in the calcium content of renal tissue. Although magnesium deficiency accelerated renal tubular calcium oxalate deposition, the protection against the crystal formation was not observed with excessive dietary magnesium. When rats were fed a high-calcium diet supplemented with phytin, a significant inhibition of the intratubular crystallization was observed. It appeared obvious that a hypocalciuric action of phytin was attributed to the effect of the prevention. There was vigorous protection of crystal formation by treatment with sodium citrate, which correlated with the level of citrate concentration in the drinking water. PMID:3433579

  7. Disruption of E-Cadherin by Matrix Metalloproteinase Directly Mediates Epithelial-Mesenchymal Transition Downstream of Transforming Growth Factor-β1 in Renal Tubular Epithelial Cells

    Zheng, Guoping; Lyons, James Guy; Tan, Thian Kui; Wang, Yiping; Hsu, Tzu-Ting; Min, Danqing; Succar, Lena; Rangan, Gopala K; Hu, Min; Henderson, Beric R.; Alexander, Stephen I; Harris, David C H

    2009-01-01

    Epithelial-mesenchymal transition (EMT) plays an important role in organ fibrosis, including that of the kidney. Loss of E-cadherin expression is a hallmark of EMT; however, whether the loss of E-cadherin is a consequence or a cause of EMT remains unknown, especially in the renal system. In this study, we show that transforming growth factor (TGF)-β1-induced EMT in renal tubular epithelial cells is dependent on proteolysis. Matrix metalloproteinase-mediated E-cadherin disruption led directly ...

  8. HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells.

    Peng, Li; He, Qingnan; Li, Xiaoyan; Shuai, Lanjun; Chen, Haixia; Li, Yongzhen; Yi, Zhuwen

    2016-07-01

    Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. Epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOX‑A13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)‑induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSA‑induced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction in HKC cells, which were co‑incubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose‑ and time‑dependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSA‑induced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway. PMID:27176855

  9. Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro

    Purpose: To evaluate the cytotoxic effects of the iso-osmolar contrast medium iodixanol on renal tubular cell cultures. Materials and Methods: LLC-PK1 cells were incubated with iodixanol and isotonic NaCl (18.75 - 75 mg I/ml, 1 - 24 hours). Cell death was assessed by the trypan blue exclusion test. To assess apoptosis, mononucleosomes and oligonucleosomes of cell lysates were determined. Measurement of BrdU (5-bromo-2'-deoxyuridine) incorporation into the DNA was used for the quantification of cell proliferation. Results: Iodixanol did not induce any significant increase in the number of necrotic cells (8 % and 9 % at 37.5 and 75 mg I/ml vs. 8 % for control, p > 0.05). In contrast, iodixanol significantly increased the number of oligonucleosomes indicating induction of apoptosis (125 ± 4 % of control, p < 0.05). Iodixanol induced a significant, dose- and time-dependent inhibition of BrdU incorporation indicating the inhibition of cell proliferation (92 ± 2 % and 79 ± 2 % of control at 18.75 and 37.5 mg I/ml, p < 0.001). (orig.)

  10. Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro

    Heinrich, M.C.; Scheer, M.; Heckmann, M.; Kuefner, M.A.; Uder, M. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.

    2009-04-15

    Purpose: To evaluate the cytotoxic effects of the iso-osmolar contrast medium iodixanol on renal tubular cell cultures. Materials and Methods: LLC-PK1 cells were incubated with iodixanol and isotonic NaCl (18.75 - 75 mg I/ml, 1 - 24 hours). Cell death was assessed by the trypan blue exclusion test. To assess apoptosis, mononucleosomes and oligonucleosomes of cell lysates were determined. Measurement of BrdU (5-bromo-2'-deoxyuridine) incorporation into the DNA was used for the quantification of cell proliferation. Results: Iodixanol did not induce any significant increase in the number of necrotic cells (8 % and 9 % at 37.5 and 75 mg I/ml vs. 8 % for control, p > 0.05). In contrast, iodixanol significantly increased the number of oligonucleosomes indicating induction of apoptosis (125 {+-} 4 % of control, p < 0.05). Iodixanol induced a significant, dose- and time-dependent inhibition of BrdU incorporation indicating the inhibition of cell proliferation (92 {+-} 2 % and 79 {+-} 2 % of control at 18.75 and 37.5 mg I/ml, p < 0.001). (orig.)

  11. Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response.

    Gu, Li-Li; Zhang, Xin-Yue; Xing, Wen-Min; Xu, Jia-Dong; Lu, Hong

    2016-07-01

    Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0-250μmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress. PMID:27344125

  12. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine.

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J L; Krämer, Bernhard K; Yard, Benito A; Hauske, Sibylle J

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity. PMID:26788523

  13. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    Shiqi Zhang

    2016-01-01

    Full Text Available Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS. Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG exposure makes cultured human umbilical vein endothelial cells (HUVECs and renal proximal tubular epithelial cells (PTECs more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG or HG (30 mM, were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1, ferroportin (IREG, and transferrin receptor protein 1 (TFRC. Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.

  14. Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

    张春; 孟宪芳; 朱忠华; 杨晓; 邓安国

    2004-01-01

    Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.

  15. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H; Leyssac, P P; Amtorp, O; Dikhoff, T G

    1986-01-01

    /min) and fractional lithium clearance (from 0.31 +/- 0.03 to 0.44 +/- 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 +/- 0...... significant increase in urinary flow rate (from 0.39 +/- 0.07 ml/min to 0.73 +/- 0.12 ml/min), sodium clearance (from 0.33 +/- 0.11 ml/min to 0.65 +/- 0.14 ml/min), potassium clearance (from 9.23 +/- 0.48 ml/min to 10.77 +/- 0.95 ml/min), lithium clearance (from 15.55 +/- 2.21 ml/min to 23.76 +/- 4.00 ml...

  16. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

    Zhang, Xiuli; Liang, Dan; Lian, Xu; Jiang, Yan; He, Hui; Liang, Wei; Zhao, Yue; Chi, Zhi-Hong

    2016-06-01

    Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Berberine (BBR) is identified as a potential anti-diabetic herbal medicine due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (Nrf2 and HO-1), which also were blocked by LY294002 (an inhibitor of PI3K) in HG-treated NRK-52E and HK-2 cells. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential. BBR-induced anti-apoptotic function was demonstrated by decreasing apoptotic proteins (cytochrome c, Bax, caspase3 and caspase9). All these findings suggest that BBR exerts the anti-apoptosis effects through activation of PI3K/Akt signal pathways and leads to activation of Nrf2 and induction of Nrf2 target genes, and consequently protecting the renal tubular epithelial cells from HG-induced apoptosis. PMID:26979714

  17. ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

    Jones, Frances E.; Bailey, Matthew A.; Murray, Lydia S.; Lu, Yinhui; McNeilly, Sarah; Schlötzer-Schrehardt, Ursula; Lennon, Rachel; Sado, Yoshikazu; Brownstein, David G.; Mullins, John J.; Kadler, Karl E.; Van Agtmael, Tom

    2016-01-01

    ABSTRACT Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies. PMID:26839400

  18. Proximal tubular efflux transporters involved in renal excretion of p-cresyl sulfate and p-cresyl glucuronide: Implications for chronic kidney disease pathophysiology.

    Mutsaers, Henricus A M; Caetano-Pinto, Pedro; Seegers, Andries E M; Dankers, Anita C A; van den Broek, Petra H H; Wetzels, Jack F M; van den Brand, Jan A J G; van den Heuvel, Lambertus P; Hoenderop, Joost G; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2015-10-01

    The uremic solutes p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) accumulate in patients with chronic kidney disease (CKD), and might contribute to disease progression. Moreover, retention of these solutes may directly be related to renal tubular function. Here, we investigated the role of the efflux transporters Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance Protein (BCRP) in pCS and pCG excretion, and studied the impact of both solutes on the phenotype of human conditionally immortalized renal proximal tubule epithelial cells (ciPTEC). Our results show that p-cresol metabolites accumulate during CKD, with a shift from sulfation to glucuronidation upon progression. Moreover, pCS inhibited the activity of MRP4 by 40% and BCRP by 25%, whereas pCG only reduced MRP4 activity by 75%. Moreover, BCRP-mediated transport of both solutes was demonstrated. Exposure of ciPTEC to pCG caused epithelial-to-mesenchymal transition, indicated by increased expression of vimentin and Bcl-2, and diminished E-cadherin. This was associated with altered expression of key tubular transporters. In conclusion, BCRP is likely involved in the renal excretion of both solutes, and pCG promotes phenotypical changes in ciPTEC, supporting the notion that uremic toxins may be involved in CKD progression by negatively affecting renal tubule cell phenotype and functionality. PMID:26216510

  19. Disruption of E-Cadherin by Matrix Metalloproteinase Directly Mediates Epithelial-Mesenchymal Transition Downstream of Transforming Growth Factor-β1 in Renal Tubular Epithelial Cells

    Zheng, Guoping; Lyons, James Guy; Tan, Thian Kui; Wang, Yiping; Hsu, Tzu-Ting; Min, Danqing; Succar, Lena; Rangan, Gopala K.; Hu, Min; Henderson, Beric R.; Alexander, Stephen I.; Harris, David C.H.

    2009-01-01

    Epithelial-mesenchymal transition (EMT) plays an important role in organ fibrosis, including that of the kidney. Loss of E-cadherin expression is a hallmark of EMT; however, whether the loss of E-cadherin is a consequence or a cause of EMT remains unknown, especially in the renal system. In this study, we show that transforming growth factor (TGF)-β1-induced EMT in renal tubular epithelial cells is dependent on proteolysis. Matrix metalloproteinase-mediated E-cadherin disruption led directly to tubular epithelial cell EMT via Slug. TGF-β1 induced the proteolytic shedding of E-cadherin, which caused the nuclear translocation of β-catenin, the transcriptional induction of Slug, and the repression of E-cadherin transcription in tubular epithelial cells. These findings reveal a direct role for E-cadherin and for matrix metalloproteinases in causing EMT downstream of TGF-β1 in fibrotic disease. Specific inhibition rather than activation of matrix metalloproteinases may offer a novel approach for treatment of fibrotic disease. PMID:19590041

  20. Clinical Spectrum of Acute Renal Failure in Dammam Central Hospital, Dammam, Saudi Arabia

    Ghacha Reda

    2000-01-01

    Full Text Available Fifty consecutive patients of acute renal failure (ARF seen over a period of two years at the Dammam Central Hospital, Dammam were studied. The mean age of the patients was 39.3 years ranging from 14 to 90 years. The main etiological factors for ARF were acute tubular necrosis (67.5% and obstructive uropathy (30%. The mortality rate was 26% and the poor prognostic factors included sepsis, acidosis, shock and the need for emergency hemodialysis.

  1. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  2. Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method

    Abildgaard, U; Holstein-Rathlou, N H; Leyssac, P P

    1986-01-01

    reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional......The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium...... lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during...

  3. Study on Effect of Baoyuan Qiangshen (保元强肾) Capsule No. Ⅱ on Tubular Interstitial Injury in Chronic Renal Failure Patients

    2001-01-01

    Objective: To explore the protective effect of Baoyuan Qiangshen Capsule No. Ⅱ (BYQS) and its mechanism in treating chronic renal failure (CRF). Methods: Sixty CRF patients were divided into 2 groups randomly, the treated group used BYQS combined with Lotensin and the control group administered with essential amino acid combined with Lotensin. Changes of renal functions and tubular labelled proteins were observed. Results: The markedly effective rate and total effective rate of the treated group were 63.3% and 93.3% respectively, and those of the control group were 30.0% and 56.7% respectively, the effect of the treated group was obviously better than that of the control group (P<0.01). In the treated group after medication, blood urea nitrogen, serum creatinine and clearance rate of creatinine were improved significantly (P<0.01), while Tamm-Horfau protein increased significantly (P<0.01). Conclusion: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF.

  4. PRIMARY SJOGREN’S SYNDROME AND DISTAL RENAL TUBULAR ACIDOSIS: PRESENTING WITH NEPHROGENIC DIABETES INSI PIDUS SECONDARY TO SEVERE HYPOKALEMIA-A CASE REPORT

    Ksh. Achouba; Banashree Devi; Kh. Lokeshwar; Ram

    2013-01-01

    NTRODUCTION: Sjogren’s syndrome is a slowly progressing autoimmun e disease characterized by lymphocytic infiltration of the exo crine glands, mainly the lacrimal and salivary glands, resulting in their impaired secreto ry function. Simultaneously, systemic involvement and symptoms of cutaneous, respiratory, r enal, hepatic, neurologic, and vascular systems often occur.[ 1 ] This syndrome can present either alone (as primary Sjogren’s syndrome) or in the...

  5. Parathyroid hormone-mitogen-activated protein kinase axis exerts fibrogenic effect of connective tissue growth factor on human renal proximal tubular cells

    GUO Yun-shan; YUAN Wei-jie; ZHANG Ai-ping; DING Yao-hai; WANG Yan-xia

    2010-01-01

    Background Enhanced and prolonged expression of connective tissue growth factor (CTGF) is associated with kidney fibrosis. Parathyroid hormone (PTH) is involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa in renal failure. PTH activated mitogen-activated protein kinase (MAPK) signaling pathway is present in renal tubular cells. The aim of this study was to identify the mechanism how the signal is transduced to result in extracellular signal-regulated protein kinase (ERK) activation, leading to upregulation of CTGF.Methods The levels of CTGF mRNA and protein in human kidney proximal tubular cells (HK-2) treated with PTH in the presence or absence of the MAPK inhibitor PD98059 were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and immunoblotting assay. The activation of the CTGF promoter in HK-2 cells was determined by the dual-luciferase assay. The effects of the protein kinase A (PKA) activator 8-Br-cAMP and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) on MAPK phosphorylation, and the effects of the PKA inhibitor H89 and PKC inhibitor calphostin C on MAPK phosphorylation and CTGF expression were detected by immunoblotting assay.Results PD98059 inhibited the PTH stimulated expression of CTGF, which strongly suggested that the MAPK signaling pathway plays an important role in the PTH-induced CTGF upregulation in renal tubular cells. A PKA activator as well as PKC activators induced MAPK phosphorylation, and both PKA and PKC inhibitors antagonized PTH-induced MAPK phosphorylation and CTGF expression.Conclusion CTGF expression is upregulated by PTH through a PKC/PKA-ERK-dependent pathway.

  6. Attenuation of Tubular Injury and Renal Fibrosis by TI-HU-YIN via Reduction in Transforming Growth Factor-β1 Expression in Unilateral Ureteral Obstruction Mice.

    Tarng, Der-Cherng; Liu, I-Shan; Lin, Lie-Chwen; Chen, Nien-Jung

    2015-12-31

    TI-HU-YIN (JCKD), a compound composed of many Chinese herbs, is hypothesized to attenuate renal tubular injury and interstitial fibrosis. Moreover, its renoprotective effects were assessed in animal and in vitro studies. First, male C57BL/6 mice were under sham operation or unilateral ureteral obstruction (UUO) surgery, and then treated with phosphate buffer solution (PBS), aliskirin and valsartan (A+V), and JCKD for 14 days. At 7 and 14 days, mice were sacrificed and the kidney tissues were assessed for histopathological changes and transforming growth factor (TGF)-β1 expression. As compared to sham group, UUO-PBS group had more serious tubular dilatation and injury, α-smooth muscle actin-positive areas, F4/80-positive macrophages, and interstitial fibrosis. Impressively, these pathologic changes were significantly attenuated in UUO mice both treated with JCKD and A+V as compared to UUO-PBS group. At 14 days, TGF-β1 expression was significantly suppressed in kidney tissues of UUO-JCKD group as well as in UUO-A+V group. Second, TGF-β1 production was increased in macrophage J774 cells and NRK-52E proximal tubular cells stimulated by angiotensin (Ang)-II at 10 nM for 24 h and at 1 nM for 48 h, respectively. JCKD (≥ 400 μg/ml) inhibited the TGF-β1 production at baseline and stimulated by Ang II in both cell lines. Our study showed that JCKD reduced renal injury, macrophage infiltration and interstitial fibrosis possibly through suppressing the TGF-β1 expression in UUO mice. Accordingly, JCKD is potential to retard the progression of chronic kidney disease. Further studies are needed to validate its renoprotective effects in the inhibition of TGF-β1 expression and the amelioration of renal fibrosis. PMID:26717915

  7. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  8. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  9. Effects of 1,25-dihydroxyvitamin D3 on high glucose-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells

    郭汉城

    2013-01-01

    Objective To study the effects of 1,25-dihydroxyvitamin D3on high-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells.Methods The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ;high glucose group (HG group,30 mmol/L D-glucose) ;mannitol group (MG group,5.5 mmol/L D-glucose+24.5 mmol/L manni-

  10. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

    Ueda, Kohei [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Fujiki, Katsunori; Shirahige, Katsuhiko [Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo (Japan); Gomez-Sanchez, Celso E. [Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS (United States); Endocrinology, University of Mississippi Medical Center, MS (United States); Fujita, Toshiro [Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Nangaku, Masaomi [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Nagase, Miki, E-mail: mnagase-tky@umin.ac.jp [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Department of Anatomy and Life Structure, School of Medicine Juntendo University, Tokyo (Japan)

    2014-02-28

    Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10{sup −7} M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10{sup −7} M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10{sup −9} M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

  11. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

    Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10−7 M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7 M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9 M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases

  12. Kidney Specific Protein-Positive Cells Derived from Embryonic Stem Cells Reproduce Tubular Structures In Vitro and Differentiate into Renal Tubular Cells

    Ryuji Morizane; Toshiaki Monkawa; Shizuka Fujii; Shintaro Yamaguchi; Koichiro Homma; Yumi Matsuzaki; Hideyuki Okano; Hiroshi Itoh

    2013-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be...

  13. Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model.

    Jennings, Paul; Weiland, Christina; Limonciel, Alice; Bloch, Katarzyna M; Radford, Robert; Aschauer, Lydia; McMorrow, Tara; Wilmes, Anja; Pfaller, Walter; Ahr, Hans J; Slattery, Craig; Lock, Edward A; Ryan, Michael P; Ellinger-Ziegelbauer, Heidrun

    2012-04-01

    Ochratoxin A (OTA) is a widely studied compound due to its role in renal toxicity and carcinogenicity. However, there is still no consensus on the exact mechanisms of toxicity or carcinogenicity. In the current study, we analysed the effect of OTA on three human renal proximal tubular models (human primary, RPTEC/TERT1 and HK-2 cells) and two rat renal proximal tubular models (rat primary and NRK-52E cells). Global transcriptomics analysis at two exposure times was performed to generate a set of 756 OTA sensitive genes. This gene set was then compared in more detail across all models and additionally to a rat in vivo renal cortex model. The results demonstrate a well-conserved response across all models. OTA resulted in deregulation of a number of pathways including cytoskeleton, nucleosome regulation, translation, transcription, ubiquitination and cell cycle pathways. Interestingly, the oxidative stress activated Nrf2 pathway was not enriched. These results point to an epigenetic action of OTA, perhaps initiated by actin binding as the actin remodelling gene, advillin was the highest up-regulated in all models. The largest model differences were observed between the human and the rat in vitro models. However, since the human in vitro models were more similar to the rat in vivo model, it is more likely that these differences are model-specific rather than species-specific per se. This study demonstrates the usefulness of in vitro cell culture models combined with transcriptomic analysis for the investigation of mechanisms of toxicity and carcinogenicity. In addition, these results provide further evidence supporting a non-genotoxic mechanism of OTA-induced carcinogenicity. PMID:22124623

  14. Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

    Drug-induced renal tubular injury is one of the major concerns in preclinical safety evaluations. Toxicogenomics is becoming a generally accepted approach for identifying chemicals with potential safety problems. In the present study, we analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. The compounds were administered orally or intravenously once daily to male Sprague-Dawley rats. The animals were exposed to four different doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and 29. Gene expression profiles were generated from kidney RNA by using Affymetrix GeneChips and analyzed in conjunction with the histopathological changes. We used the filter-type gene selection algorithm based on t-statistics conjugated with the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%. Then, 92 genes were extracted as the genomic biomarker candidates that were used to construct the classifier. The gene list contains well-known biomarkers, such as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of metallopeptidase 1, and also novel biomarker candidates. Most of the genes involved in tissue remodeling, the immune/inflammatory response, cell adhesion/proliferation/migration, and metabolism were predominantly up-regulated. Down-regulated genes participated in cell adhesion/proliferation/migration, membrane transport, and signal transduction. Our classifier has better prediction accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics approach would be useful for concurrent diagnosis of renal tubular injury.

  15. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  16. Changes in Renal Function and Blood Pressure in Patients with Stone Disease

    Worcester, Elaine M.

    2007-04-01

    Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

  17. Renal β-intercalated cells maintain body fluid and electrolyte balance

    Gueutin, Victor; Vallet, Marion; Jayat, Maximilien; Peti-Peterdi, Janos; Cornière, Nicolas; Leviel, Françoise; Sohet, Fabien; Wagner, Carsten A.; Eladari, Dominique; Chambrey, Régine

    2013-01-01

    Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt- and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1–/– mice) displayed renal loss of NaCl, K+, and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) a...

  18. Ochratoxin A induces karyomegaly and cell cycle aberrations in renal tubular cells without relation to induction of oxidative stress responses in rats.

    Taniai, Eriko; Yafune, Atsunori; Nakajima, Masahiro; Hayashi, Shim-Mo; Nakane, Fumiyuki; Itahashi, Megu; Shibutani, Makoto

    2014-01-01

    Ochratoxin A (OTA) is a renal carcinogen that induces karyomegaly in target renal tubular cells of the outer stripe of the outer medulla (OSOM). This study was performed to clarify the relationship between oxidative stress and the karyomegaly-inducing potential involving cell cycle aberration of OTA in the OSOM. Rats were treated with OTA for 28 days in combination with enzymatically modified isoquercitrin (EMIQ) or α-lipoic acid (ALA) as antioxidants. OTA increased the mRNA levels of the antioxidant enzyme-related genes Gpx1, Gpx2, Gstm1 and Nfe2l2, but did not increase the levels of Gsta5, Keap1, Nqo1, Hmox1, Aldh1a1, Por, Prdx1 and Txn1. OTA also did not change the levels of thiobarbituric acid-reactive substances, glutathione disulfide/reduced glutathione, and the immunoreactive tubular cell distribution of nuclear factor erythroid 2-related factor 2 in the OSOM. Co-treatment with EMIQ or ALA did not cause any changes in these parameters. As previously reported, OTA increased cell proliferation activity, apoptosis and immunohistochemical cellular distributions of molecules suggestive of induction of DNA damage and cell cycle aberrations involving spindle checkpoint disruption and cell cycle arrest. However, co-treatment with EMIQ or ALA did not suppress these changes, and ALA co-treatment increased the cell proliferation activity induced by OTA. These results suggest that OTA facilitates cell cycling involving cell cycle aberrations and apoptosis as a basis of the mechanism behind the development of karyomegaly and subsequent carcinogenicity targeting the OSOM, without relation to induction of oxidative stress. On the other hand, ALA may promote the OTA-induced proliferation of carcinogenic target cells. PMID:24120684

  19. Curcumin inhibits transforming growth factor-β1-induced EMT via PPARγ pathway, not Smad pathway in renal tubular epithelial cells.

    Rui Li

    Full Text Available Tubulointerstitial fibrosis (TIF is the final common pathway in the end-stage renal disease. Epithelial-to-mesenchymal transition (EMT is considered a major contributor to the TIF by increasing the number of myofibroblasts. Curcumin, a polyphenolic compound derived from rhizomes of Curcuma, has been shown to possess potent anti-fibrotic properties but the mechanism remains elusive. We found that curcumin inhibited the EMT as assessed by reduced expression of α-SMA and PAI-1, and increased E-cadherin in TGF-β1 treated proximal tubular epithelial cell HK-2 cells. Both of the conventional TGF-β1/Smad pathway and non-Smad pathway were investigated. Curcumin reduced TGF-β receptor type I (TβR-I and TGF-β receptor type II (TβR II, but had no effect on phosphorylation of Smad2 and Smad3. On the other hand, in non-Smad pathway curcumin reduced TGF-β1-induced ERK phosphorylation and PPARγ phosphorylation, and promoted nuclear translocation of PPARγ. Further, the effect of curcumin on α-SMA, PAI-1, E-cadherin, TβR I and TβR II were reversed by ERK inhibitor U0126 or PPARγ inhibitor BADGE, or PPARγ shRNA. Blocking PPARγ signaling pathway by inhibitor BADGE or shRNA had no effect on the phosphorylation of ERK whereas the suppression of ERK signaling pathway inhibited the phosphorylation of PPARγ. We conclude that curcumin counteracted TGF-β1-induced EMT in renal tubular epithelial cells via ERK-dependent and then PPARγ-dependent pathway.

  20. Surface heat shock protein 90 serves as a potential receptor for calcium oxalate crystal on apical membrane of renal tubular epithelial cells.

    Fong-Ngern, Kedsarin; Sueksakit, Kanyarat; Thongboonkerd, Visith

    2016-07-01

    Adhesion of calcium oxalate monohydrate (COM) crystals on renal tubular epithelial cells is a crucial step in kidney stone formation. Finding potential crystal receptors on the apical membrane of the cells may lead to a novel approach to prevent kidney stone disease. Our previous study identified a large number of crystal-binding proteins on the apical membrane of MDCK cells. However, their functional role as potential crystal receptors had not been validated. The present study aimed to address the potential role of heat shock protein 90 (HSP90) as a COM crystal receptor. The apical membrane was isolated from polarized MDCK cells by the peeling method and recovered proteins were incubated with COM crystals. Western blot analysis confirmed the presence of HSP90 in the apical membrane and the crystal-bound fraction. Immunofluorescence staining without permeabilization and laser-scanning confocal microscopy confirmed the surface HSP90 expression on the apical membrane of the intact cells. Crystal adhesion assay showed that blocking surface HSP90 by specific anti-HSP90 antibody and knockdown of HSP90 by small interfering RNA (siRNA) dramatically reduced crystal binding on the apical surface of MDCK cells (by approximately 1/2 and 2/3, respectively). Additionally, crystal internalization assay revealed the presence of HSP90 on the membrane of endocytic vesicle containing the internalized COM crystal. Moreover, pretreatment of MDCK cells with anti-HSP90 antibody significantly reduced crystal internalization (by approximately 1/3). Taken together, our data indicate that HSP90 serves as a potential receptor for COM crystals on the apical membrane of renal tubular epithelial cells and is involved in endocytosis/internalization of the crystals into the cells. PMID:27115409

  1. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Svensson, Kristoffer; Schnyder, Svenia; Cardel, Bettina; Handschin, Christoph

    2016-01-01

    The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction. PMID:27463191

  2. Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

    Rodriguez, Stéphane; Rudloff, Stefan; Koenig, Katrin Franziska; Karthik, Swapna; Hoogewijs, David; Huynh-Do, Uyen

    2016-08-01

    Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis. Three distinct zones were observed: tubular necrosis, infarction border zone and preserved normal tissue. EphA2 is a receptor tyrosine kinase with pivotal roles in cell architecture, migration and survival, upon juxtacrine contact with its membrane-bound ligand EphrinA1. Following hypoxia, EphA2 was up-regulated in cortical and medullary tubular cells, while EphrinA1 was up-regulated in interstitial cells adjacent to peritubular capillaries. Moreover, erythropoietin (EPO) messenger RNA (mRNA) was strongly expressed in the border zone of infarcted kidney within the first 6 h. To gain more insight into the biological impact of EphA2 and EphrinA1 up-regulation, we activated the signalling pathways in vitro using recombinant EphrinA1/Fc or EphA2/Fc proteins. Stimulation of EphA2 forward signalling in the proximal tubular cell line HK2 increased cell attachment and laminin secretion at the baso-lateral side. Conversely, activation of reverse signalling through EphrinA1 expressed by Hep3B cells promoted EPO production at both the transcriptional and protein level. Strikingly, in co-culture experiments, juxtacrine contact between EphA2 expressing MDCK and EphrinA1 expressing Hep3B was sufficient to induce a significant up-regulation of EPO mRNA production in the latter cells, even in the absence of hypoxic conditions. The synergistic effects of EphA2 and hypoxia led to a 15-20-fold increase of EPO expression. Collectively, our results suggest an important role of EphA2/EphrinA1 signalling in kidney repair after hypoxic injury through stimulation of (i) tubular

  3. Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

    Chen, Yongwen; Zhang, Jingbo; Li, Jingyi; Zhao, Tingting; Zou, Liyun; Tang, Yan; Zhang, Xiaoping; Wu, Yuzhang

    2006-03-01

    Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells. PMID:16129490

  4. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

    Secretion of inorganic mercury (Hg2+) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg2+ was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg2+. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg2+-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp−/−) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg−1), a moderately nephrotoxic (1.5 μmol·kg−1) or a significantly nephrotoxic (2.0 μmol·kg−1) dose of HgCl2. In general, the accumulation of Hg2+ was greater in organs of bcrp−/− rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg2+ from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp−/− rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg

  5. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

    Bridges, Christy C., E-mail: bridges_cc@mercer.edu; Zalups, Rudolfs K.; Joshee, Lucy

    2015-06-01

    Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

  6. Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus.

    Weisberg, Lawrence S

    2015-08-01

    Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. PMID:25762524

  7. Acidosis láctica

    Caridad Soler Morejón

    2000-06-01

    Full Text Available Se conoce que el ácido láctico es un producto terminal del metabolismo anaeróbico de la glucosa, que, en condiciones normales, los niveles séricos alcanzan las 2 mEq/L o menos. La mayor parte del lactato se elimina de forma muy eficaz por el hígado y se utiliza en la gluconeogénesis o para obtener energía. Si se producen incrementos considerables de las cifras de lactato sérico con disminución del metabolismo de conversión de lactato a piruvato se instala un cuadro de acidosis metabólica, a menudo grave, que puede llevar al paciente a la muerte. Desde el punto de vista clínico se debe sospechar ante un paciente con acidosis metabólica no bien explicada y anión Gap elevado, el cual se encuentra por encima de 25-30 mEq/L, aún en presencia de insuficiencia renal, de cetoacidosis o de la ingestión de un tóxico. La prevención de la hipoxia hística desempeña un papel importantísimo y en este sentido todas las medidas que contribuyen a garantizar una buena perfusión hística. Se señala la importancia del control adecuado de la diabetes mellitus, la selección más adecuada de hipoglicemiantes, el aporte de tiamina en los pacientes de riesgo, entre otras medidasIt is know that lactic acid is a last product of glucose anaerobic metabolism, that, in normal conditions, serum levels reach 2 mEq/L or less. Most of lactate is released in a very efficacious way by liver and is used in gluconeogenesis or to obtain energy. If there are significant increases of serum lactate figures with a decrease of metabolism of the conversion of lactate in pyruvate, a situation of metabolic acidosis frequently serious will present, which may provoke death of patient. From the clinical point of view, it must be suspected in a patient with non well explained metabolic acidosis and a high anion gap, which is over 25-30 mEq/L, even in presence of renal failure, ketoacidosis or ingestion of a toxic agent. That prevention of tissue hypoxia play a very

  8. Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

    Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter;

    2010-01-01

    rHuEPO elevates hemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. 16 healthy males were given rHuEP...

  9. Acute renal failure due to rhabdomyolyisis

    Nieto-Ríos, John Fredy

    2016-04-01

    Full Text Available Acute renal failure is a frequent cause of morbidity and mortality in emergency, hospitalization and critical care services. In 15 % of cases it is due to rhabdomyolysis, in which there is breakdown of skeletal muscle with massive necrosis and leakage of muscle cell contents into the circulation. It has many different etiologies. The rhabdomyolysis-induced acute kidney injury results from the combination of several mechanisms, including tubular obstruction, vasoconstriction and oxidative stress. The most important therapeutic measures are: Aggressive repletion of fluids, forced diuresis and avoidance of exposure to nephrotoxic substances. In cases of severe uremia, metabolic acidosis, hiperkalemia or fluid overload it is necessary to start renal replacement therapy. As a rule, kidney function is completely recovered, but these patients have higher risk of future chronic kidney disease.

  10. Generation and Characterisation of a Pax8-CreERT2 Transgenic Line and a Slc22a6-CreERT2 Knock-In Line for Inducible and Specific Genetic Manipulation of Renal Tubular Epithelial Cells.

    Espana-Agusti, Judit; Zou, Xiangang; Wong, Kim; Fu, Beiyuan; Yang, Fengtang; Tuveson, David A; Adams, David J; Matakidou, Athena

    2016-01-01

    Genetically relevant mouse models need to recapitulate the hallmarks of human disease by permitting spatiotemporal gene targeting. This is especially important for replicating the biology of complex diseases like cancer, where genetic events occur in a sporadic fashion within developed somatic tissues. Though a number of renal tubule targeting mouse lines have been developed their utility for the study of renal disease is limited by lack of inducibility and specificity. In this study we describe the generation and characterisation of two novel mouse lines directing CreERT2 expression to renal tubular epithelia. The Pax8-CreERT2 transgenic line uses the mouse Pax8 promoter to direct expression of CreERT2 to all renal tubular compartments (proximal and distal tubules as well as collecting ducts) whilst the Slc22a6-CreERT2 knock-in line utilises the endogenous mouse Slc22a6 locus to specifically target the epithelium of proximal renal tubules. Both lines show high organ and tissue specificity with no extrarenal activity detected. To establish the utility of these lines for the study of renal cancer biology, Pax8-CreERT2 and Slc22a6-CreERT2 mice were crossed to conditional Vhl knockout mice to induce long-term renal tubule specific Vhl deletion. These models exhibited renal specific activation of the hypoxia inducible factor pathway (a VHL target). Our results establish Pax8-CreERT2 and Slc22a6-CreERT2 mice as valuable tools for the investigation and modelling of complex renal biology and disease. PMID:26866916

  11. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    Shiqi Zhang; Emmanouil Ntasis; Sarah Kabtni; Jaap van den Born; Gerjan Navis; Stephan J L Bakker; Krämer, Bernhard K.; Benito A Yard; Hauske, Sibylle J.

    2015-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubul...

  12. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

    Sabiha S. Chowdhury

    2016-08-01

    Full Text Available Along with diabetes and obesity, chronic kidney disease (CKD is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

  13. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.

    Chowdhury, Sabiha S; Lecomte, Virginie; Erlich, Jonathan H; Maloney, Christopher A; Morris, Margaret J

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  14. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. PMID:26918530

  15. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine.

    van Hoek, I; Lefebvre, H P; Peremans, K; Meyer, E; Croubels, S; Vandermeulen, E; Kooistra, H; Saunders, J H; Binst, D; Daminet, S

    2009-01-01

    Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia. PMID:19010632

  16. Citrato y litiasis renal

    Elisa E. Del Valle

    2013-08-01

    Full Text Available El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

  17. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder

    Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Ryu, Dong-Ryeol; Lee, Dong Hyeon

    2016-01-01

    Purpose To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. Material and Methods From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. Results Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. Conclusion Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID:27384686

  18. Na+ pump in renal tubular cells is regulated by endogenous Na+-K+-ATPase inhibitor from hypothalamus

    Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na+-K+-ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK1) were studied using 86Rb+ uptake and [3H]ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na+-K+-ATPase in LLC-PK1 cells. In contrast to membrane studies, no prolonged incubation with LLC-PK1 was needed to observe inhibition of Na+-K+-ATPase. HF caused a 33% inhibition of ouabain-sensitive 86Rb+ influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK186Rb+ uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na+-K+-ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes

  19. In vitro inhibition of calcium oxalate crystallization and crystal adherence to renal tubular epithelial cells by Terminalia arjuna.

    Mittal, A; Tandon, S; Singla, S K; Tandon, C

    2016-04-01

    Urolithiasis is a multifactorial disease and remains a public health problem around the world. Of all types of renal stones, calcium oxalate (CaOx) is the most common composition formed in the urinary system of the patients with urolithiasis. The present study is aimed at evaluating the antiurolithiatic properties of the Tris-Cl extract (TE) of Terminalia arjuna (T. arjuna). The antilithiatic activity of TE of T. arjuna was investigated on nucleation, aggregation, and growth of the CaOx crystals, as well as its protective potency was tested on oxalate-induced cell injury of NRK-52E renal epithelial cells. Also, in vitro antioxidant activity of TE T. arjuna bark was also determined. The TE of T. arjuna exhibited a concentration-dependent inhibition of nucleation and growth of CaOx crystals. Inhibition of aggregation of CaOx crystals remains constant. When NRK-52E cells were injured by exposure to oxalate for 48 h, the TE prevented the cells from injury and CaOx crystal adherence resulting in increased cell viability in a dose-dependent manner. The TE also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals with an IC50 at 51.72 µg/mL. The results indicated that T. arjuna is a potential candidate for phytotherapy against urolithiasis as it attains the ability to inhibit CaOx crystallization and scavenge DPPH free radicals in vitro along with a cytoprotective role. PMID:26424092

  20. Tubular Secretion in CKD.

    Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L; Meyer, Timothy W; Thummel, Ken E; Yanez, N David; Himmelfarb, Jonathan; Weiss, Noel S; Kestenbaum, Bryan R

    2016-07-01

    Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation. PMID:26614381

  1. Prevalence and European AIDS Clinical Society (EACS criteria evaluation for proximal renal tubular dysfunction diagnosis in patients under antiretroviral therapy in routine setting

    Lorenzo Pitisci

    2014-11-01

    Full Text Available Introduction: Tenofovir (TDF is an antiretroviral drug often used in combination regimen in HIV-positive patients. Adverse effects affecting kidneys consist in an increase or a new onset proteinuria, a decrease of glomerular filtration rate (GFR, and/or a proximal renal tubular dysfunction (PRTD that rarely leads to Fanconi's syndrome. EACS guidelines propose to screen PRTD in patients with chronic renal insufficiency, with a sudden decrease of eGFR, with hypophosphataemia (if non-renal causes such as vitamin D deficiency are excluded and with a new onset proteinuria. We aim to evaluate the prevalence of PRTD by comparing the group of patients under TDF to the group free of TDF, in our cohort of 300 patients. We also aim to evaluate the accuracy of EACS criteria for screening PRTD in routine settings and to assess the utility of urinary samples in PRTD diagnosis. Materials and Methods: During two consecutive years, we collected annually blood and urine samples at the same time in our outpatient clinic. We assessed kidney function, plasma levels and fractional excretion of phosphate, uric acid, potassium, plasma glucose and proteinuria. PRTD was defined by the presence of at least two out of the five following criteria: fractional excretion (FE of phosphate >20% (or >10% when serum phosphate 5.5 and serum bicarbonate 10% or potassium FE >10%. After the first year, patients with TDF regimen who were diagnosed with PRTD were shifted to TDF-free regimen and included again in the study. Results: For PRTD (first line, they are expressed in number of diagnoses/total number of patients in this group. The second line resumes the number of PRTD diagnose patients who should have been screened according to EACS criteria. Conclusions: PRTD screening according to EACS criteria is not sufficient to diagnose every case, especially minor PRTD, mainly because the prevalence is low and its diagnosis remains difficult in routine settings. We recommend performing a

  2. Lactic acidosis induced by metformin: incidence, management and prevention.

    Lalau, Jean-Daniel

    2010-09-01

    acidosis, since it provides both symptomatic and aetiological treatment (by eliminating lactate and metformin). In the third part of the review (prevention), the objective is to examine the list of contraindications to metformin (primarily related to renal and cardiovascular function). Diabetes is above all a vascular disease and metformin is a vascular drug with antidiabetic properties. Given the importance of the liver in lactate clearance, we suggest focusing on the severity of and prognosis for liver disease; renal dysfunction is only a prerequisite for metformin accumulation, which may only be dangerous per se when associated with liver failure. Lastly, in view of metformin's impressive overall effectiveness profile, it would be paradoxical to deny the majority of patients with long-established diabetes access to metformin because of the high prevalence of contraindications. The implications of these contraindications are discussed. PMID:20701406

  3. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  4. Renal failure

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  5. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  6. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D;

    1990-01-01

    of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects...... by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x...... PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal...

  7. Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells.

    Ikari, Akira; Sanada, Ayumi; Sawada, Hayato; Okude, Chiaki; Tonegawa, Chie; Sugatani, Junko

    2011-06-01

    Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is used in treatments for transplantation and cancer. Rapamycin causes hypomagnesemia, although precisely how has not been examined. Here, we investigated the effect of rapamycin on the expression of transient receptor potential melastatin 6 (TRPM6), a Mg2+ channel. Rapamycin and LY-294002, an inhibitor of phosphatidilinositol-3 kinase (PI3K) located upstream of mTOR, inhibited epidermal growth factor (EGF)-induced expression of the TRPM6 protein without affecting TRPM7 expression in rat renal NRK-52E epithelial cells. Both rapamycin and LY-294002 decreased EGF-induced Mg2+ influx. U0126, a MEK inhibitor, inhibited EGF-induced increases in c-Fos, p-ERK, and TRPM6 levels. In contrast, neither rapamycin nor LY-294002 inhibited EGF-induced increases in p-ERK and c-Fos levels. EGF increased p-Akt level, an effect inhibited by LY-294002 and 1L-6-hydroxymethyl-chiro-inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate] (Akt inhibitor). Akt inhibitor decreased TRPM6 level similar to rapamycin and LY-294002. These results suggest that a PI3K/Akt/mTOR pathway is involved in the regulation of TRPM6 expression. Rapamycin inhibited the EGF-induced increase in TRPM6 mRNA but did not inhibit human TRPM6 promoter activity. In the presence of actinomycin D, a transcriptional inhibitor, rapamycin accelerated the decrease in TRPM6 mRNA. Rapamycin decreased the expression and activity of a luciferase linked with the 3'-untranslated region of human TRPM6 mRNA. These results suggest that TRPM6 expression is up-regulated by a PI3K/Akt/mTOR pathway and rapamycin reduces TRPM6 mRNA stability, resulting in a decrease in the reabsorption of Mg2+. PMID:21073857

  8. Effects of exhaustive exercise on renal tubular apoptosis and HIF-1α expression in rats and result of total ginsenoside intervention

    Hui-ling WANG

    2014-03-01

    Full Text Available Objective To investigate the effects of high strength exhaustive exercise on apoptosis of renal tubular epithelial cells (TECs and expression of hypoxia-inducible factor-1 α (HIF-1α in rats and the effect of intervention of total ginsenoside. Methods Thirty-five male Sprague-Dawley rats were randomly divided into five groups (7 each: control group (CTL, model group (divided into two subgroups: M2 and M24; total ginsenoside group (divided into two subgroups: G2 and G24. The animal model of exhaustive exercise induced acute kidney injury (AKI was reproduced by forcing the rats running on the treadmill followed by exhaustive swimming according to the protocol. Ginsenoside [100g/(kg.d] was intragastrically gavaged 5 days before exhausting exercise in rats of G2 and G24, and the same volume of water was given to rats in model and CTL groups. Apoptosis of TECs was observed under microscope after TUNEL staining. The expressions of caspase-3 and HIF-1α in TECs were analyzed by immunohistochemical staining. The protein expression of caspase-3 and HIF-1α was determined by Western blotting. Results  In model group, 11 out of 14 rats were stranded on treadmill, and the time of exhaustive swimming was significantly shorter as compared with that of CTL group; but the endurance increased significantly in total ginsenoside groups, in which only 6/14 rats were stranded on treadmill, and the swimming time was significantly longer compared with model group (P<0.05. The TUNELpositive apoptotic cells increased in M2 and M24 groups (especially in M24 group, and they were mainly distributed in thos e TECs at the corticomedullary junction in model groups; but the number of TUNEL-positive cells decreased significantly in total ginsenoside group (G2, G24 as compared with model group (P<0.05. Immunohistochemical analysis showed that caspases-3 and HIF-1α were only weakly positive in CTL group, but significantly upregulated in M2 group, and it was stronger in M

  9. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol. PMID:26654818

  10. 肾小管上皮细胞与基底膜的粘附力学特性%The adhesive mechanical properties of renal tubular epithelial cells on matrigel

    宋关斌; 俞为群; 王东; 吴雄飞

    2000-01-01

    purpose: to investigate the adhesive properties of renal tubular epithelial cells on matrigel and compared with the following three cases: ischemia、hypoxia and ischemia & hypoxia(I/H).materials and methods: A micropipette aspiration technique was adopted to determine the adhesive mechanics of renal tubular epithelial cells on matrige. results: it showed that the adhesion of renal tubular epithelial cells on matrigel was higher than that of those three model, further more, a different factor was followed by different adhesive mechanic. conclusion: the adhesion of I/H is lower, the ischemia is higher, but all were lower compared with control. It suggested that effect of hypoxia on adhesive properties of renal tubular epithelial cells on matrigel is bigger than that of ichemia.%目的:研究模拟缺血、缺氧、缺血缺氧三种条件下肾小管上皮细胞与基底膜的粘附力学特性。材料与方法:利用微管吸吮技术测定肾小管上皮细胞与人工基底膜的粘附力。结果:模拟缺血、缺氧、缺血缺氧三种模型中肾小管上皮细胞与基底膜的粘附力均较正常情况明显降低。结论:不同模拟损伤因素对粘附力的影响不同,其中缺血缺氧组粘附力最小,单纯缺血组的影响较小。这些结果提示,在一定条件下,氧缺乏比缺血情况更能影响肾小管上皮细胞与基底膜的粘附作用。

  11. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells.

    Dana Galuska

    Full Text Available BACKGROUND: Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC in control and hyperglycemic conditions. METHODOLOGY/PRINCIPAL FINDINGS: HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86Rb(+ uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM. DNA binding activity was determined by electrical mobility shift assay (EMSA. Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase α(1-subunit protein expression, accompanied with increase in (86Rb(+ uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase α(1-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, but not 10 nM of C-peptide increased PKCε phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6, concomitant with Na,K-ATPase α(1-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase α(1-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing. CONCLUSIONS/SIGNIFICANCE: Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C-peptide. Most likely C-peptide stimulates sodium pump expression via activation of ZEB, a transcription

  12. The role of HIF-1 in up-regulating MICA expression on human renal proximal tubular epithelial cells during hypoxia/reoxygenation

    Li Fu S

    2010-11-01

    Full Text Available Abstract Background Human major histocompatibility complex class I-related chain A (MICA plays a dual role in adaptive and innate immune responses. Increasing evidence demonstrates that MICA is closely correlated with acute and chronic kidney allograft rejection. Therefore, understanding the activation mechanisms of MICA is important in kidney transplantation. We previously demonstrated that ischemia/reperfusion injury (IRI could up-regulate MICA expression on mouse kidney allografts. Since hypoxia-inducible factor-1 (HIF-1 is the master regulator of cellular adaptive responses to hypoxia during IRI, here we investigate whether HIF-1 could up-regulate MICA expression and its influence on NK cell cytotoxicity. Results We find that HIF-1alpha plays an important role in up-regulating MICA expression, inducing IFNgamma secretion and NK cell cytotoxicity during hypoxia/reoxygenation. First, we generated a HIF-1alphaDELTAODD-expressing adenovirus to stably and functionally express HIF-1alpha in human renal proximal tubular epithelial (HK-2 cells under normoxia conditions. HIF-1alpha over-expression in HK-2 cells induces MICA expression and enhances NK cell cytotoxic activity towards cells that express HIF-1alpha. Second, we used a hypoxia/reoxygenation cell model to simulate IRI in vitro and found that the suppression of HIF-1alpha by RNAi induces down-regulation of MICA expression and inhibits NK cytotoxicity. In antibody blocking experiments, an anti-MICA mAb was able to down-regulate NK cell cytotoxic activity towards HK-2 cells that over-expressed HIF-1alpha. Moreover, when NK cells were co-cultured with the HK-2 cells expressing MICA, which was up-regulated by over-expression of HIF-1alpha, there was a significant increase in the secretion of IFNgamma. In the presence of the blocking MICA mAb, IFNgamma secretion was significantly decreased. Conclusions These results demonstrate that hypoxia/reoxygenation-promoted MICA expression on HK-2 cells is

  13. Disease: H00241 [KEGG MEDICUS

    Full Text Available H00241 Combined proximal and distal renal tubular acidosis (RTA type 3) Renal tubular acidosis... (RTA) is characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostas...0 PMID:11045400 (gene) Rodriguez-Soriano J New insights into the pathogenesis of renal tubular acidosis--fro...riguez Soriano J Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13

  14. Review Study of Renal Tubular Injury Markers in the Acute Kidney Injury%急性肾损伤中肾小管损伤标志物的研究进展

    李一飞; 姚广涛

    2011-01-01

    The reports concerned with renal injury markers in recent 10 years were consulted through Science Direct database, and literature related to specific markers of renal tubular injury were compiled and analyzed. Some biomarkers have been partially verified the good sensitivity and high specificity in experimental studies and clinical observations. For example, Kidney injury molecule-1 .which would over express in the kidney injury in renal tubular epithelial cells,is sensitive to the early diagnosis of kidney cancer, ischemic and renal toxic renal injury,and detected with high stability. Liver-type fatty acid binding protein involved in local lipid metabolism of renal,with high specificity to renal proximal tubule. Its content in urine were of great value for early evaluation of various types of acute kidney injury. As a diagnostic indicator,sensitivity and specificity of Interleukin-18 were more than 90%. It could distinguish acute tubular necrosis from other types of kidney diseases, also predict the renal injury occurrence and renal function recovery. Neutrophil gelatinase-associated lipocalin was often detected as the first expressed product in the injury kidney,which changed earlier than creatinine and other markers, with obvious time advantage. All biomarkers have different characteristics and respective shortage. So joint detection were better to wider and sensitive evaluation of renal injury.%通过Science Direct数据库查阅了近10年有关肾损伤标志物的报道,对肾小管损伤特异性标志物方面的文献进行了整理和分析.一些敏感性好、特异性高的肾小管损伤标志物已在实验研究和临床观察得到了部分验证,如肾损伤分子-1,肾损伤时在肾小管上皮细胞过度表达,对肾肿瘤、缺血性和肾毒性肾损伤的早期诊断敏感性好,且检测稳定性高;肝型脂肪酸结合蛋白,参与肾局部的脂质代谢,对肾近端小管的特异性很高,其尿液含量变化在多种类型的急

  15. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypoth

  16. Metabolic evaluation in first-time renal stone formers in north India: A single center study

    Akhil Joshi

    2013-01-01

    Full Text Available The risk of stone recurrence in first-time stone formers (FTSF varies from 26% to 53%. There is no consensus regarding metabolic evaluation in these individuals. We evaluated the metabolic abnormalities in first-time renal stone forming patients in North India. Thirty-nine patients, (29 males and 10 females with mean age 39.3 ± 12.9 years who presented with nephrolithiasis for the first time were evaluated. We evaluated the calcium homeostasis [serum corrected total calcium, phosphorous, creatinine, alkaline phosphatase, albumin, parathormone (iPTH, 25-hydroxy cholecalciferol (25(OHD 3 , 1-25 di-hydroxy cholecalciferol (1,25(OH 2 D 3 ] and performed the calcium load test also. Two 24-h urine collections were taken for citrate, oxalate, calcium and uric acid. Ammonium chloride loading test for diagnosis of distal renal tubular acidosis was performed in all patients. For each of the diagnostic categories, descriptive statistics were computed for all biochemical variables. A two-tailed P-value <0.05 was regarded as significant. Metabolic abnormalities were detected in 92.3% of the patients (n = 39 studied. Of them, almost 60% had two or more metabolic abnormalities. The most common metabolic abnormality was hypo-citraturia (82%, followed by hyper-oxaluria (56% and hyper-calciuria (41%. Five percent of the patients had incomplete renal tubular acidosis, signifying the importance of the ammonium chloride loading test in patients with renal stones. None of the study patients were detected to have primary hyperparathyroidism. In three patients, the etiology could not be detected. Our findings suggest that an underlying disorder is present in majority of first-time renal stone formers. Intervention with appropriate treatment can prevent recurrences. Hence, comprehensive metabolic evaluation is recommended in all FTSF.

  17. Disease: H00429 [KEGG MEDICUS

    Full Text Available H00429 Proximal renal tubular acidosis (RTA type 2) Renal tubular acidosis (RTA) is... characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal imp...4278 PMID:11045400 (gene) Rodriguez-Soriano J New insights into the pathogenesis of renal tubular acidosis--...(gene, env_factor, marker) Rodriguez Soriano J Renal tubular acidosis: the clinical entity. J Am Soc Nephrol... 13:2160-70 (2002) PMID:11095551 (env_factor, drug) Kurtzman NA Renal tubular acidosis syndromes. South Med

  18. Disease: H00428 [KEGG MEDICUS

    Full Text Available H00428 Distal renal tubular acidosis (RTA type 1) Renal tubular acidosis (RTA) is c...haracterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal impai...a DM, Oliveira EA, Silva AC Molecular pathophysiology of renal tubular acidosis. Curr Genomics 10:51-9 (2009...) PMID:11045400 (gene) Rodriguez-Soriano J New insights into the pathogenesis of renal tubular acidosis...ne, env_factor, marker) Rodriguez Soriano J Renal tubular acidosis: the clinical

  19. Retrospective analysis of clinical and pathological data of 104 cases of renal tubular-interstitial disease%肾小管-间质疾病104例临床病理资料回顾性分析

    张宏岩; 孙瑶; 张磊

    2013-01-01

    目的 探讨肾小管-间质疾病的类型与疾病进展的关系,可为临床医生早期诊断及预防提供依据.方法 取自哈尔滨医科大学病理学教研室7 112例肾活检资料(1998年1月~2012年4月)中,诊断为肾小管-间质疾病104例,占1.46%(104/7 112).分析其临床资料,实验室检查和病理检查的相关性.结果 ①肾小管-间质性疾病的病理变化特点是:肾小球的球囊壁增厚、分层、纤维化,肾小球毛细血管壁增厚、缺血,严重的呈硬化改变;不同程度的肾小管萎缩,间质增生,炎细胞浸润和小动脉壁的增厚.②104例肾小管-间质性疾病中,有无蛋白尿之间有明显的差异(P<0.05);③有无炎细胞浸润和已浸润的多少之间有明显的差异(P<0.05);④而有关肾小球病变、肾小管萎缩、间质增生及临床实验室的其它几项指标间无明显的差异(P>0.05).结论 肾小管-间质性疾病的发生发展与有无炎细胞浸润及浸润的程度密切相关.临床表现为明显蛋白尿的患者,如果排除原发性或继发性肾小球肾炎时,早期诊断和预防可减轻肾小管萎缩、间质增生、纤维化及小动脉增厚、变性的发展.%Objective To investigate the relationship between the type and progression of the renal tubular-interstitial disease,and its value in the early diagnosis and prevention.Methods There were 104 cases of renal tubular-interstitial disease which accounts for 1.46% in all the 7 112 cases of renal biopsy in the Pathology Department of Harbin Medical University since January 1998 to April 2012.The clinical data,laboratory tests and pathological examination were analyzed.Results ①Pathological changes of tubular-interstital disease:glomerular capsule thickening,delamination,fibrosis,the glomerual capillary wall thickening,ischemia,and even sclerosis ; Varying degress of tubular atrophy,interstitial hyperplasia,inflammatory cell infiltration and thickening of small artery

  20. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis

  1. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  2. Renal failure

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  3. Nephrocalcinosis

    ... Bartter syndrome Chronic glomerulonephritis Familial hypomagnesemia Medullary sponge kidney Primary hyperoxaluria Renal transplant rejection Renal tubular acidosis Renal cortical necrosis Other possible ...

  4. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Ju, Sung Min; Kang, Jun Gue; Bae, Jun Sang; Pae, Hyun Ock; Lyu, Yeoung Su; Jeon, Byung Hun

    2015-01-01

    Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2) cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM) for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells. PMID:26089934

  5. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

    Hills, Claire E; Al-Rasheed, Nawal; Al-Rasheed, Nouf; Willars, Gary B; Brunskill, Nigel J

    2009-03-01

    The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy. PMID:19091788

  6. Mathematical Model of Ammonia Handling in the Rat Renal Medulla.

    Lorette Noiret

    Full Text Available The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and [Formula: see text], and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts.

  7. 二甲双胍引起乳酸性酸中毒的风险与糖尿病患者的肾功能%Risk of lactic acidosis caused by metformin and renal function of diabetic patients

    张林; 胡茂清

    2010-01-01

    二甲双胍是治疗2型糖尿病的一线药物,其有导致乳酸性酸中毒的风险.肾小球滤过率是评估糖尿病患者是否应用二甲双胍的标准之一.然而越来越多的证据表明二甲双胍与糖尿病患者乳酸性酸中毒的发生似乎无明显的相关性,目前尚无高质量的临床证据来指导二甲双胍在糖尿病合并肾功能不全患者中的应用,但临床上尚不能仅仅依据肾小球滤过率水平来判断是否使用二甲双胍,使用之前应评估患者使用前后的效益-风险比.在糖尿病合并肾功能不全人群中应用二甲双胍的标准尚需更多的循证医学证据.%Mefformin is in the first line of treating diabetes, though it might increase the risk of lactic acidosis. Glomerular filtration rate is one of the indexs that determines whether mefformin should be used or not. However,more and more clinical studies show that the relationship between mefformin and lactic acidosis is not clear. There are few high quality clinical evidences to guide the use of mefformin in diabetic subjects with chronic kidney disease. But in clinical practice,whether mefformin is used in these diabetic subjects or not does not just depend on glomerular filtration rate, efficiency-risk ratio should be evaluated at first. The standard of using mefformin in diabetic subjects with chronic kidney disease should be provided by more evi-dences.

  8. 肾脏黏液性管状和梭形细胞癌4例报告%Clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma

    王俊生; 林云华; 商建峰; 勇强; 姜永光

    2011-01-01

    目的 探讨肾脏黏液性管状和梭形细胞癌的临床病理特征.方法 回顾分析4例肾脏黏液性管状和梭形细胞癌患者的临床资料.女性3例,男性1例;年龄35~56岁,平均41岁;左肾2例,右肾2例;肾上极3例,肾下极1例;肿瘤直径3.5~6.5cm,平均5.5cm;无明显临床症状及体征,均为体检发现.B超检查提示,2例肾囊实性占位,为良性肿瘤;2例为厚壁型肾囊肿.CT检查提示,3例肾囊实性占位,为良性肿瘤;1例为厚壁型肾囊肿.2例行MRI检查提示,肾脏囊实性占位,为良性肿瘤.结果 4例患者均予手术治疗,术中发现肿块与肾组织的界限清楚,易分离;肿块呈囊实性,囊壁厚薄均匀,组织致密且内壁光滑.术后病理组织学检查示:2例为低度恶性上皮细胞肿瘤,1例为恶性肿瘤(透明细胞癌不排除),另1例为肾脏黏液性管状和梭形细胞癌.结论 肾脏黏液性管状和梭形细胞癌是一种具有良性肿瘤生长特性的低度恶性倾向的肿瘤.%Objective To explore the clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma. Methods Clinical data of 4 patients including 3 female and 1 male aged from 35 to 56 were analyzed retrospectively. Among the 4 cases, two tumors were in the left side and two in right. Three tumors located in the upper part of kidneys, one in the lower part. The size of tumors ranged from 3.5 to 6.5 cm. There was no obvious symptom or physical sign in all cases and the tumors were detected during healthy examination. In B type untrasonography, two patients showed cystsolid tumor and two showed thick-wall cyst of kidney. In CT scan, three patients showed cystsolid tumor and one showed thick-wall cyst of kidney. In MRI scan, two patients showed cystsolid tumor. All the imaging examinations indicated the lump was benign. Results There were clear boundaries between the tumors and normal kidney tissue and the lesions were easy to be separated

  9. Tubular Coupling

    Rosenbaum, Bernard J. (Inventor)

    2000-01-01

    A system for coupling a vascular overflow graft or cannula to a heart pump. A pump pipe outlet is provided with an external tapered surface which receives the end of a compressible connula. An annular compression ring with a tapered internal bore surface is arranged about the cannula with the tapered internal surface in a facing relationship to the external tapered surface. The angle of inclination of the tapered surfaces is converging such that the spacing between the tapered surfaces decreases from one end of the external tapered surface to the other end thereby providing a clamping action of the tapered surface on a cannula which increases as a function of the length of cannula segment between the tapered surfaces. The annular compression ring is disposed within a tubular locking nut which threadedly couples to the pump and provides a compression force for urging the annular ring onto the cannula between the tapered surfaces. The nut has a threaded connection to the pump body. The threaded coupling to the pump body provides a compression force for the annular ring. The annular ring has an annular enclosure space in which excess cannula material from the compression between the tapered surfaces to "bunch up" in the space and serve as an enlarged annular ring segment to assist holding the cannula in place. The clamped cannula provides a seamless joint connection to the pump pipe outlet where the clamping force is uniformly applied to the cannula because of self alignment of the tapered surfaces. The nut can be easily disconnected to replace the pump if necessary.

  10. Curcumin Inhibits Transforming Growth Factor-β1-Induced EMT via PPARγ Pathway, Not Smad Pathway in Renal Tubular Epithelial Cells

    Li, Rui; Wang, Yunman; Liu, Yujun; Chen, Qijing; Fu, Wencheng; Wang, Hao; Cai, Hui; Peng, Wen; Zhang, Xuemei

    2013-01-01

    Tubulointerstitial fibrosis (TIF) is the final common pathway in the end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is considered a major contributor to the TIF by increasing the number of myofibroblasts. Curcumin, a polyphenolic compound derived from rhizomes of Curcuma, has been shown to possess potent anti-fibrotic properties but the mechanism remains elusive. We found that curcumin inhibited the EMT as assessed by reduced expression of α-SMA and PAI-1, and increased E...

  11. D-Lactic Acidosis in Humans: Review of Update

    Kang, Kyung Pyo; Lee, Sik; Kang, Sung Kyew

    2006-01-01

    D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic acidosis is very rare, but D-lactic acidosis may be more common than generally believed and should be looked for in a case of metabolic acidosis in which the cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The entity should be considered as a diagnosis in a patient who presents with metabolic acidosis accompanied ...

  12. Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers

    Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect

  13. Generation of Urinary Albumin Fragments Does Not Require Proximal Tubular Uptake

    Weyer, K.; Nielsen, R; Christensen, E.I.; Birn, H

    2012-01-01

    Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin f...

  14. FARMACOFISIOLOGÍA RENAL

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  15. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris

    A. Aggarwal

    2010-08-01

    Full Text Available PURPOSE: Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as “gokhru” which is often used in ayurveda to treat various urinary diseases including urolithiasis. MATERIALS AND METHODS: The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. RESULTS: Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. CONCLUSION: The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.

  16. Rupture of Renal Transplant

    Shona Baker; Maria Popescu; Jacob A Akoh

    2015-01-01

    Background. Rupture of renal allograft is a rare and serious complication of transplantation that is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Case Presentation. LD, a 26-year-old male with established renal failure, underwent deceased donor transplantation using kidney from a 50-year-old donor with acute kidney injury (Cr 430 mmol/L). LD had a stormy posttransplant recovery and required exploration immediately for significant bleeding. On day th...

  17. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    Bhosale, Guruprasad P; Veena R Shah

    2015-01-01

    Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic acidosis (pH 6.65) that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurologi...

  18. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    Guruprasad P Bhosale

    2015-01-01

    Full Text Available Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L and severe metabolic acidosis (pH 6.65 that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid.

  19. Understanding lactic acidosis in paracetamol (acetaminophen) poisoning

    Shah, Anoop D; Wood, David M; Dargan, Paul I

    2011-01-01

    Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver sl...

  20. Moduretic-induced metabolic acidosis and hyperkalaemia.

    Wan, H. H.; Lye, M. D.

    1980-01-01

    A patient who developed significant metabolic acidosis and severe hyperkalaemia while taking Moduretic (amiloride and hydrochlorothiazide) is reported. During the period of hyperkalaemia (maximum potassium 7-6 mmol/l) the patient's whole body potassium content was normal. His acid-base balance and serum potassium returned to normal some 10 days after stopping the drug. The possible mechanism of acidosis and hyperkalaemia in this patient is discussed.

  1. Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review.

    Kamar, Fareed B; McQuillan, Rory F

    2015-01-01

    Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone. PMID:26425378

  2. The genomic analysis of lactic acidosis and acidosis response in human cancers.

    Julia Ling-Yu Chen

    2008-12-01

    Full Text Available The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.

  3. Radiological evaluation of renal transplantation

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.)

  4. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  5. CT diagnosis of renal and extrarenal complications after renal transplantation

    Methods and results of static and dynamic CT of renal transplants are presented. Validity of the method concerning morphologic and functional lesions of the organ and of extrarenal structures are outlined. Special attention is paid to functional changes and differential diagnosis of the most frequent complications after renal transplantation. Whereas CT diagnosis of renal and pararenal morphology is unquestioned, the problem of differentiating between acute tubular necrosis and acute rejection is not yet solved. Nevertheless description of renal function is possible. (orig.)

  6. High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning

    Raj Kumar Sharma

    2011-01-01

    Full Text Available Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison.

  7. Metabolic acidosis: neo-considerations for general surgeons.

    Martin, L C E; Abah, U; Bean, E; Gupta, S

    2012-11-01

    Hyperchloraemic metabolic acidosis is a documented complication of neobladder formation. However, it usually improves with time and is mild. Severe and persistent metabolic acidosis may manifest when patients undergo further surgery for other reasons. Neobladder formation following radical cystectomy or cystoprostatectomy is becoming increasingly common, and surgeons treating patients with neobladders should recognise and treat metabolic acidosis with intravenous fluids and bicarbonate. PMID:23131216

  8. Angiotensin II and Renal Tubular Ion Transport

    Patricia Valles

    2005-01-01

    Evidence for the regulation of H+-ATPase activity in vivo and in vitro by trafficking/exocytosis has been provided. An additional level of H+-ATPase regulation via protein synthesis may be important as well. Recently, we have shown that both aldosterone and angiotensin II provide such a mechanism of regulation in vivo at the level of the medullary collecting tubule. Interestingly, in this part of the nephron, the effects of aldosterone and angiotensin II are not sodium dependent, whereas in the cortical collecting duct, both aldosterone and angiotensin II, by contrast, affect H+ secretion by sodium-dependent mechanisms.

  9. Case of hereditary papillary renal cell carcinoma

    Mustafa, Sadaf; Jadidi, Nima; Faraj, Sheila F.; Rodriquez, Ronald

    2012-01-01

    Renal cell carcinoma is the most common type of renal malignancy and it originates from the renal tubular epithelium. Due to the diversity in the histopathological and molecular characteristics, it is typically subclassified into five different categories. Papillary renal cell carcinoma is one subclassification and it includes two variants: sporadic and hereditary. Although the hereditary form comprises a smaller number of cases of papillary renal cell carcinoma, an understanding of the molec...

  10. Lactic Acidosis: Current Treatments and Future Directions.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-09-01

    Mortality rates associated with severe lactic acidosis (blood pHreduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment. PMID:27291485

  11. Protocol-based metabolic evaluation in high-risk patients with renal stones in North India

    Sandeep Julka

    2012-01-01

    Full Text Available Context: Renal calculus disease has a lifetime recurrence rate of 80%. Protocol-based metabolic evaluation in high-risk subjects for recurrent renal stones reveals abnormalities in a large subset of subjects. However, such information is not available in Indian subjects. Aims: To evaluate the abnormalities by a protocol-based metabolic evaluation in patients at a high risk for recurrent renal stones. Settings and Design: Prospective, academic tertiary care center. Materials and Methods: Fifty North Indian patients (38 males and 12 females; mean age 38 ± 10.2 years with recurrent or bilateral renal stones were evaluated. All subjects underwent a protocol-based evaluation involving estimation of serum total calcium, phosphorus, creatinine, albumin, iPTH, 25(OHD 3 , 1,25(OH 2 D 3 , and a calcium load test. Estimation of daily urinary excretion of volume, oxalate, calcium, uric acid, and citrate, and urinary acidification studies were performed. Statistical Analysis Used: Descriptive statistics and t-test. Results: An underlying disorder was detected in 48 (96% patients. Almost half had two or more metabolic abnormalities. The metabolic abnormalities detected were: Hypercalciuria 26 (52% patients, renal hypercalciuria 16 (32%, absorptive hypercalciuria 6 (12%, unclassified hypercalciuria 4 (8%, hyperoxaluria 27 (54%, hyperuricosuria 9 (18%, distal renal tubular acidosis 4 (8%; 2 complete and 2 partial, primary hyperparathyroidism 3 (6%, and hypocitraturia 14 (n=18, 77%. In two patients, the etiology could not be detected. Conclusions: Protocol-based metabolic evaluation reveals metabolic abnormalities in majority of patients with nephrolithiasis. The spectrums of metabolic abnormalities are different in Indian subjects as compared to the western population.

  12. A supramolecular tubular nanoreactor.

    Li, Zhi-Qiang; Zhang, Ying-Ming; Chen, Yong; Liu, Yu

    2014-07-01

    The extremely strong noncovalent complexation between the rigid host of phthalocyanine-bridged β-cyclodextrins and the amphiphilic guest carboxylated porphyrin is employed to construct a hollow tubular structure as a supramolecular nanoreactor. A representative coupling reaction occurs in the hydrophobic interlayers of the tubular walls in pure water at room temperature, leading to an enhancement of ten times higher reaction rate without any adverse effect on catalytic activity and conversion. PMID:24890802

  13. Renal compensation to chronic hypoxic hypercapnia: downregulation of pendrin and adaptation of the proximal tubule

    de Seigneux, Sophie; Malte, Hans; Dimke, Henrik;

    2007-01-01

    The molecular basis for the renal compensation to respiratory acidosis and specifically the role of pendrin in this condition are unclear. Therefore, we studied the adaptation of the proximal tubule and the collecting duct to respiratory acidosis. Male Wistar-Hannover rats were exposed to either ...

  14. Pathophysiology and management of progressive renal disease.

    Brown, S A; Crowell, W A; Brown, C A; Barsanti, J A; Finco, D R

    1997-09-01

    Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats. PMID:9308397

  15. Hemodynamic and tubular changes induced by contrast media.

    Caiazza, Antonella; Russo, Luigi; Sabbatini, Massimo; Russo, Domenico

    2014-01-01

    The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI. PMID:24678510

  16. Glutamatergic signaling maintains the epithelial phenotype of proximal tubular cells

    Bozic, M.; de Rooij, J.; Parisi, E.; Ortega, M.R.; Fernandez, E.; Valdivielso, J.M.

    2011-01-01

    Epithelial-mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrange

  17. Hyaluronan in Tubular and Interstitial Nephrocalcinosis

    Verkoelen, Carl F.

    2007-04-01

    Hyaluronan (HA) is the major glycosaminoglycan (GAG) component of the renal medullary interstitium. HA is extremely large (up to 104 kDa) and composed of thousands repeating disaccharides of glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc). HA is synthesized by hyaluronan synthases (HASs) and degraded by hyaluronidases (Hyals). The production of HA by renomedullary interstitial cells is mediated by local osmolality. When excess water needs to be excreted, increased interstitial HA seems to antagonize water reabsorption, while the opposite occurs during water conservation. Hence, papillary interstitial HA is low and Hyal high during anti-diuresis, whereas during diuresis HA is high and Hyal low. The polyanion HA plays a role in the reabsorption of hypotonic fluid by immobilizing cations (Na+) via the carboxylate (COO-) groups of GlcUA. The binding of Ca2+ to anionic HA is probably also responsible for the fact that the papilla does not become a stone despite the extremely high interstitial phosphate and oxalate. HA is also an excellent crystal binding molecule. The expression of HA at the luminal surface of renal tubular cells leads to tubular nephrocalcinosis (tubular NC). Calcium staining methods (Von Kossa, Yasue) demonstrated that crystallization inhibitors cannot avoid the occasional precipitation of calcium phosphate in the papillary interstitium (interstitial NC). These crystals are probably immediately immobilized by the gel-like HA matrix. After ulcerating through the pelvic wall the calcified matrix becomes a Randall's plaque. The attachment of calcium oxalate crystals from the primary urine to plaque may ultimately lead to the development of clinical stones in the renal calyces (nephrolithiasis).

  18. Tubular transport and metabolism of cimetidine in chicken kidneys

    Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion

  19. Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

    Eranga S Wijewickrama

    2013-01-01

    Full Text Available Acute renal failure (ARF is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH. The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham′s test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

  20. Isolation and Characterization of a Primary Proximal Tubular Epithelial Cell Model from Human Kidney by CD10/CD13 Double Labeling

    Van der Hauwaert, Cynthia; Savary, Grégoire; Gnemmi, Viviane; Glowacki, François; Pottier, Nicolas; Bouillez, Audrey; Maboudou, Patrice; Zini, Laurent; Leroy, Xavier; Cauffiez, Christelle; Perrais, Michaël; Aubert, Sébastien

    2013-01-01

    Renal proximal tubular epithelial cells play a central role in renal physiology and are among the cell types most sensitive to ischemia and xenobiotic nephrotoxicity. In order to investigate the molecular and cellular mechanisms underlying the pathophysiology of kidney injuries, a stable and well-characterized primary culture model of proximal tubular cells is required. An existing model of proximal tubular cells is hampered by the cellular heterogeneity of kidney; a method based on cell sort...

  1. Drug-Induced Metabolic Acidosis [version 1; referees: 3 approved

    Amy Quynh Trang Pham

    2015-12-01

    Full Text Available Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics.

  2. Reliability of Tubular Joints

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    In this paper the preliminary results obtained by tests on tubular joints are presented. The joints are T-joints and the loading is static. It is the intention in continuation of these tests to perform tests on other types of joints (e.g. Y-joints) and also with dynamic loading. The purpose of th...

  3. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work. PMID:25968940

  4. An unrecognised case of metabolic acidosis following neobladder augmentation cystoplasty

    David Eldred-Evans

    2015-01-01

    Conclusion: Hyperchloremic metabolic acidosis is a well-established complication of urinary diversion. Patient with orthotopic neobladder with high residual urine and large capacity are at even higher risk of metabolic acidosis. This information should be clearly documented in the post-operative discharge documentation to ensure early recognition by non-specialists.

  5. Tubular toxicity of proteinuria.

    Baines, Richard J; Brunskill, Nigel J

    2011-03-01

    Proteinuria is a prognostic indicator of progressive kidney disease and poor cardiovascular outcomes. Abnormally filtered bioactive macromolecules interact with proximal tubular epithelial cells (PTECs), which results in the development of proteinuric nephropathy. This condition is characterized by alterations in PTEC growth, apoptosis, gene transcription and inflammatory cytokine production as a consequence of dysregulated signaling pathways that are stimulated by proteinuric tubular fluid. The megalin-cubilin complex mediates the uptake of several proteins, including albumin, into PTECs. Megalin might also possess intrinsic signaling properties and the ability to regulate cell signaling pathways and gene transcription after processing regulated intramembrane proteolysis. Megalin could, therefore, link abnormal PTEC albumin exposure with altered growth factor receptor activation, proinflammatory and profibrotic signaling, and gene transcription. Evidence now suggests that other PTEC pathways for protein reabsorption of (patho)physiological importance might be mediated by the neonatal Fc receptor and CD36. PMID:21151210

  6. Classifying Virtually Special Tubular Groups

    Woodhouse, Daniel J.

    2016-01-01

    A group is tubular if it acts on a tree with $\\mathbb{Z}^2$ vertex stabilizers and $\\mathbb{Z}$ edge stabilizers. We prove that a tubular group is virtually special if and only if it acts freely on a locally finite CAT(0) cube complex. Furthermore, we prove that if a tubular group acts freely on a finite dimensional CAT(0) cube complex, then it virtually acts freely on a three dimensional CAT(0) cube complex.

  7. Dopamins renale virkninger

    Olsen, Niels Vidiendal

    1990-01-01

    which are possible not exclusively secondary to alterations in the renal haemodynamics but may also be due to specific tubular effects. Recent investigations have revealed that dopamine does not increase RBF and GFR in patients with chronic renal failure if GFR is less than 60 ml/minute. Dopamine in low...... doses is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly......Dopamine is an endogenic catecholamine which, in addition to being the direct precursor of noradrenaline, has also an effect on peripheral dopaminergic receptors. These are localized mainly in the heart, splanchnic nerves and the kidneys. Dopamine is produced in the kidneys and the renal metabolism...

  8. Tubular closure mechanism

    This invention relates to a closure mechanism for tubular irradiation surveillance specimen assembly holder used in nuclear reactors. The closure mechanism is composed of a latching member which includes a generally circular chamber with a plurality of elongated latches depending therefrom. The latching member circumscribes part of an actuator member which is disposed within the latching member so as to be axially movable. The axial movement of the actuator actuates positioning of the latches between positions in which the latches are locked and secured within the actuator member. Means, capable of being remotely manipulated, are provided to move the actuator in order to position the latches and load the articles within the tube

  9. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  10. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy.

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  11. Renal consequences of obesity.

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  12. IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway

    Wu, Zengbin; Yu, Yang; Niu, Lei; Fei, Aihua; Pan, Shuming

    2016-01-01

    Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury. PMID:27301852

  13. Tubular biomarkers to assess progression of diabetic nephropathy.

    Tramonti, Gianfranco; Kanwar, Yashpal S

    2011-05-01

    Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy. However, Nielsen et al. report a lack of an independent correlation between these biomarkers and glomerular filtration rate. Therefore, these markers seem to offer no improvement in the management of diabetic nephropathy. PMID:21527942

  14. Effects of Total Flavonoids in Xiezhuo Chubi Decoction on the Proliferation and Uric Uptake Function of Mice Renal Tubular Epithelial Cells%泄浊除痹方总黄酮对小鼠肾小管上皮细胞增殖与尿酸吸收的影响

    吴新荣; 臧路平; 刘志刚; 孙维峰

    2012-01-01

    OBJECTIVE: To investigate the effects of total flavonoids in Xiezhuo chubi decoction on the proliferation and uric uptake function of mice renal tubular epithelial cells (RTECs) in vivo. METHODS: The RTECs were isolated from the renal tubular epithelial cells of mice by optimized primary culture method, and were cultured with total flavonoids from Xiezhuo chubi decoction of different concentrations. The activity of RTECs was assayed by MTT assay. The uric uptake medium was prepared and the uric uptake values were determined by the kit. RESULTS: The interest cells were isolated, I.e. mice renal tubular epithelial cells, and it had the function of uric uptake. The proliferation of the RTECs was inhibited by high concentrations (10, 7.5, 5.0 g·L-1) of the drug. No significant effects on the proliferation of the RTECs were observed in the low concentrations (2.5, 0,5 g·L-1); total flavonoids had no significant effect on growth activity of cells in this range of 2.5,2.0,1.5, 1.0, 0.5 g·L-1 total flavonoids inhibited uric uptake in different degree. CONCLUSION: The uric uptake function of the RETCs can be inhibited by the total flavonoids in Xiezhuo chubi decoction.%目的:研究泄浊除痹方总黄酮对小鼠肾小管上皮细胞(RTECs)增殖与尿酸吸收的影响.方法:采用优化后的小鼠RTECs原代培养方法分离该细胞,不同浓度的泄浊除痹方总黄酮孵育48 h,MTT法检测细胞活性,配制尿酸吸收培养基,进行尿酸吸收实验,采用尿酸检测试剂盒测定尿酸吸收值.结果:所分离培养的细胞为目的细胞,即小鼠RTECs,具有尿酸吸收功能;高浓度药物(10、7.5、5.0 g·L-1)对细胞增殖有不同程度的抑制作用,低浓度药物(2.5、0.5g·L-1)对细胞增殖无显著性影响;在对细胞生长活性无显著性影响的浓度梯度范围内(2.5、2.0、1.5、1.0、0.5 g·L-1),药物对尿酸吸收表现出不同程度的抑制作用.结论:泄浊除痹方总黄酮对小鼠RTECs尿酸吸收功能有一定的抑制作用.

  15. Drug-induced renal disorders.

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  16. Epithelial-to-mesenchymal transdifferentiation of renal tubular epithelial cells mediated by oxidative stress and intervention effect of probucol in diabetic nephropathy rats%氧化应激介导糖尿病大鼠肾小管上皮细胞转分化及普罗布考的干预作用

    段绍斌; 王予慧; 刘伏友; 周巧艳; 刘芳; 李莹; 凌光辉; 李瑛; 孙林

    2011-01-01

    Objective To explore the role of oxidative stress in the epithelial-tomesenchymal transition (EMT) of tubular epithelial cells and the protective effect of probucol in rat model with diabetic nephropathy (DN). Methods Thirty SD rats were randomly divided into normal control group, DN group, probucol treatment group (supplemented 1% probucol dietary). Twentyfour hours urinary protein excretion (UTP) was measured at the 3rd, the 8th and the 12th week respectively. The biochemical indicators including blood glucose (BG), lipids [triglyceride (TG), total cholesterol (TC)], low-density lipoprotein (LDL), serum creatinine (Scr), creatinine clearance rate (Ccr),kidney tissue malondialdehyde (MDA) level and glutathione peroxidase (GSH-Px) activity were assessed at the end of the 12th week in all groups. The renal pathological changes were evaluated by hematoxylin & eosin (HE) and Masson staining. The protein expression of specificity protein 1 (Sp1), α-smooth muscle actin (α-SMA) and E-cadherin was also detected and analyzed by immunohistochemistry and Western blotting. Results Compared with the normal control group,the BG, TC, LDL, Scr, 24 h UTP and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of DN group (all P<0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were higher in the DN animals than that in the other animals (all P<0.01), the expression of E-cadherin downregulated significantly in the DN animals (P<0.01). The MDA level of renal tissue was positively correlated to the expression of α-SMA and Sp1 protein in DN group (r=0.896, P<0.01; r=0.862, P<0.01, respectively), and negatively correlated to the expression of E-cadherin protein (r=-0.673, P<0.01). In the diabetic animals treated with probucol, the Scr, 24 h UTP, pathological scores, MDA content,expression of Sp1 and α-SMA in renal tissue were lower than those in the diabetic animals (all P<0.01). The Ccr and the

  17. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  18. Acid-base status determines the renal expression of Ca2+ and Mg2+ transport proteins.

    Nijenhuis, T.; Renkema, K.Y.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2006-01-01

    Chronic metabolic acidosis results in renal Ca2+ and Mg2+ wasting, whereas chronic metabolic alkalosis is known to exert the reverse effects. It was hypothesized that these adaptations are mediated at least in part by the renal Ca2+ and Mg2+ transport proteins. The aim of this study, therefore, was

  19. Renal response to acute acid loading--an organ physiological approach

    Osther, P J; Engel, K; Kildeberg, P

    2004-01-01

    OBJECTIVE: In previous studies of the renal response to acute NH4Cl acidosis no correlation was found between systemic acid-base status and the traditionally used quantity, renal net acid excretion (NAE). If NAE is to be considered a physiologically meaningful quantity then this is surprising, as......-base metabolism during acid loading than previously described methods....

  20. CD36 mediates proximal tubular binding and uptake of albumin and is upregulated in proteinuric nephropathies.

    Baines, Richard J; Chana, Ravinder S; Hall, Matthew; Febbraio, Maria; Kennedy, David; Brunskill, Nigel J

    2012-10-01

    Dysregulation of renal tubular protein handling in proteinuria contributes to the development of chronic kidney disease. We investigated the role of CD36 as a novel candidate mediator of albumin binding and endocytosis in the kidney proximal tubule using both in vitro and in vivo approaches, and in nephrotic patient renal biopsy samples. In CD36-transfected opossum kidney proximal tubular cells, both binding and uptake of albumin were substantially enhanced. A specific CD36 inhibitor abrogated this effect, but receptor-associated protein, which blocks megalin-mediated endocytosis of albumin, did not. Mouse proximal tubular cells expressed CD36 and this was absent in CD36 null animals, whereas expression of megalin was equal in these animals. Compared with wild-type mice, CD36 null mice demonstrated a significantly increased urinary protein-to-creatinine ratio and albumin-to-creatinine ratio. Proximal tubular cells expressed increased CD36 when exposed to elevated albumin concentrations in culture medium. Expression of CD36 was studied in renal biopsy tissue obtained from adult patients with heavy proteinuria due to minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. Proximal tubular CD36 expression was markedly increased in proteinuric individuals. We conclude that CD36 is a novel mediator influencing binding and uptake of albumin in the proximal tubule that is upregulated in proteinuric renal diseases. CD36 may represent a potential therapeutic target in proteinuric nephropathy. PMID:22791331

  1. Acute Isoniazid Intoxication: Convulsion, Rhabdomyolysis and Metabolic Acidosis

    OKUTUR, Sadi Kerem

    2006-01-01

    Isoniazid is one of the most commonly used antituberculous drugs. Acute intoxication is characterized by repetitious convulsions, high anion gap metabolic acidosis and coma. The basis of therapy consists of parenteral pyridoxine administration in a dose equivalent to that of isoniazid ingested. Here we present a case of acute isoniazid intoxication presenting with convulsions and metabolic acidosis with consequent rhabdomyolysis and discuss the clinical signs and pathophysiology of isoniazid ...

  2. Treatment of Lactic Acidosis with Dichloroacetate in Dogs

    Park, Robert; Arieff, Allen I.; Leach, William; Lazarowitz, Virginia C.

    1982-01-01

    Lactic acidosis is a clinical condition due to accumulation of H+ ions from lactic acid, characterized by blood lactate levels >5 mM and arterial pH 60%. Dichloroacetate (DCA) is a compound that lowers blood lactate levels under various conditions in both man and laboratory animals. It acts to increase pyruvate oxidation by activation of pyruvate dehydrogenase. We evaluated the effects of DCA in the treatment of two different models of type B experimental lactic acidosis in diabetic dogs: hep...

  3. Metformin-induced lactic acidosis: a case series

    Silvestre Joana; Carvalho Susana; Mendes Vitor; Coelho Luis; Tapadinhas Camila; Ferreira Pedro; Povoa Pedro; Ceia Fatima

    2007-01-01

    Abstract Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present ...

  4. Benign duodenocolic fistula. A case presenting with acidosis

    Benn, Marianne; Nielsen, F T; Antonsen, H K

    1997-01-01

    A case of benign duodenocolic fistula as a complication to peptic ulcer disease is presented, the case being interesting for the rarity of the diagnosis and by being complicated with acidosis. The etiology, clinical features, diagnosis, and treatment are reviewed.......A case of benign duodenocolic fistula as a complication to peptic ulcer disease is presented, the case being interesting for the rarity of the diagnosis and by being complicated with acidosis. The etiology, clinical features, diagnosis, and treatment are reviewed....

  5. Renal imaging in paediatrics

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.)

  6. The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

    Vree, T B; Guelen, P J; Jongman-Nix, B; Walenkamp, G H

    1981-07-18

    The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin. PMID:6166414

  7. Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate

    Joshua L. Rein

    2014-01-01

    Full Text Available Calcific uremic arteriolopathy (CUA is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects.

  8. Insuficiencia renal aguda.

    Carlos Hernán Mejía

    2009-10-01

    Full Text Available La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción de sodio y osmolaridad, el uroanálisis y la ecografía renal. Su tratamiento consiste en una adecuada recuperación del volumen, manejo de los diuréticos, soporte nutricional, conservación del equilibrio hidroelectrolítico y brindar terapia de diálisis si hay toxicidad urémica, hipercaliemia severa (>6.5 mEq/l, acidosis metabólica o sobrecarga severa de volumen.

  9. Akt2/PKBbeta-sensitive regulation of renal phosphate transport

    Kempe, D S; Ackermann, T F; Boini, K M; Klaus, F; Umbach, A T; Dërmaku-Sopjani, M; Judenhofer, M S; Pichler, B J; Capuano, P.; Stange, G.; Wagner, C. A.; Birnbaum, M J; Pearce, D.; Föller, M; Lang, F.

    2010-01-01

    AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockou...

  10. Internalization of Proteus mirabilis by human renal epithelial cells.

    Chippendale, G R; Warren, J W; Trifillis, A. L.; Mobley, H L

    1994-01-01

    Proteus mirabilis, a common agent of bacteriuria in humans, causes acute pyelonephritis and bacteremia. Renal epithelium provides a barrier between luminal organisms and the renal interstitium. We have hypothesized that P. mirabilis may be internalized into renal epithelium. To test this hypothesis, we added suspensions of three P. mirabilis strains (10(8) CFU) to confluent monolayers of primary cultures of human renal proximal tubular epithelial cells (HRPTEC) and, after 3 h, found the bacte...

  11. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice.

    Kawaida, K; Matsumoto, K.; Shimazu, H.; Nakamura, T.(International Center for Elementary Particle Physics and Department of Physics, The University of Tokyo, Tokyo, Japan)

    1994-01-01

    Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppre...

  12. Growth Hormone Therapy in Children with Chronic Renal Failure

    Cayir, Atilla; Kosan, Celalettin

    2014-01-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant huma...

  13. Mathematical Model of Ammonia Handling in the Rat Renal Medulla

    Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

    2015-01-01

    The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein ...

  14. General Construction of Tubular Geometry

    Mukhopadhyay, Partha

    2016-01-01

    We consider the problem of locally describing tubular geometry around a submanifold embedded in a (pseudo)Riemannian manifold in its general form. Given the geometry of ambient space in an arbitrary coordinate system and equations determining the submanifold in the same system, we compute the tubular expansion coefficients in terms of this {\\it a priori data}. This is done by using an indirect method that crucially applies the tubular expansion theorem for vielbein previously derived. With an explicit construction involving the relevant coordinate and non-coordinate frames we verify consistency of the whole method up to quadratic order in vielbein expansion. Furthermore, we perform certain (long and tedious) higher order computation which verifies the first non-trivial spin connection term in the expansion for the first time. Earlier a similar method was used to compute tubular geometry in loop space. We explain this work in the light of our general construction.

  15. Abrasion resistant tubular member

    A surface of a tubular member made of an austenite stainless steel having a molybdenum content of from 2 to 3% is subjected to a low temperature ionization nitriding treatment in a gas atmosphere of N2: from 5 to 15% by volume, H2: from 95 to 85% by volume, at a temperature of from 400 to 470degC to form a nitride layer. Since the low temperature ion nitriding treatment is thus applied, generation of ε phase which lowers corrosion resistance can be suppressed. That is, the hardened layer (nitride layer) is provided with abrasion resistance, while the inside can keep the inherent characteristic of the austenite stainless steel having high toughness. In addition, this can avoid the tendency of lowering corrosion resistance due to the formation of a ε phase caused by exposure to high temperature for a long time in order to increase the thickness of the nitrided layer. When the thickness of the tube is 1.3mm, the less than 130μm is enough for the nitride layer. Abrasion resistance can be improved by thus applying ion nitriding treatment to the austenite stainless steel containing molybdenum under controlled temperature and atmosphere. (N.H.)

  16. Hereditary Hypokalemic salt-losing tubular disorders

    The inherited hypokalemic tubular disorders are frequently summarized under the heading Bartter Syndrome since they share several clinical and biochemical findings such as renal salt wasting, hypokalemic metabolic alkalosis, normal blood pressure despite hypereninemic hyperaldosteronism and hyperplasia of the juxtaglomerular apparatus. However, careful characterization of the clinical phenotype and correlation with the clinical phenotype and the correlation with the underlying molecular basis justifies the differentiation into at least four distinct disease entities: (i) the hyperprostaglandin E syndrome or antenatal variant of Bartter syndrome (HPS/aBS), which is caused by mutations in either the Na-K-2Cl cotransporter or the potassium channel of the medullary thick ascending limb of Henle's loop; (ii) the HPS/aBS with sensorineural deafness which results from inactivating mutation in the Barttin beta-subunit of the renal chloride channels; (iii) the classic Bartter syndrome caused by mutations in the chloride channel of the distal nephron; and (iv)Gitelman's variant of Bartter syndrome which is caused by mutations of the Na-Cl cotransporter of the distal convoluted tubule. This review will summarize the clinical characteristics of these diseases and progress recently made in the identification of the underlying molecular defects that will hopefully add to the current knowledge of the pathogenesis of these diseases. (author)

  17. Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria

    Nortier, Joëlle; Deschodt Lanckman, Monique; Simon, Stéphane; Thielemans, N.-O.; De Prez, Eric; Depierreux, Michel; Tielemans, Christian; Richard-Mendes da Costa, C.; Lauwerijs, R.; Bernard, Alfred; Vanherweghem, Jean-Louis

    1997-01-01

    Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 2...

  18. Mucinous tubular and spindle cell carcinoma of the kidney associated with tuberculosis

    Saloua Krichen Makni

    2011-01-01

    Full Text Available Mucinous tubular and spindle cell carcinomas (MTSCC are low-grade renal epi-thelial neoplasms with approximately 100 documented cases reported in the literature. We report a case of MTSCC in a 79-year-old patient in association with a renal tuberculosis infection that has never been reported. Further investigations are needed to determine the frequency and true prognosis of these tumors.

  19. Lipopolysaccharide-induced acute renal failure in conscious rats

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique;

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone, a......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an...... phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  20. Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate.

    Capino, Amanda C; Dannaway, Douglas C; Miller, Jamie L

    2016-01-01

    Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity. PMID:27453705

  1. Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis

    Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W.

    2012-01-01

    Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

  2. Neurological damage arising from intrapartum hypoxia/acidosis.

    Rei, M; Ayres-de-Campos, D; Bernardes, J

    2016-01-01

    Complications occurring at any level of foetal oxygen supply will result in hypoxaemia, and this may ultimately lead to hypoxia/acidosis and neurological damage. Hypoxic-ischaemic encephalopathy (HIE) is the short-term neurological dysfunction caused by intrapartum hypoxia/acidosis, and this diagnosis requires the presence of a number of findings, including the confirmation of newborn metabolic acidosis, low Apgar scores, early imaging evidence of cerebral oedema and the appearance of clinical signs of neurological dysfunction in the first 48 h of life. Cerebral palsy (CP) consists of a heterogeneous group of nonprogressive movement and posture disorders, frequently accompanied by cognitive and sensory impairments, epilepsy, nutritional deficiencies and secondary musculoskeletal lesions. Although CP is the most common long-term neurological complication associated with intrapartum hypoxia/acidosis, >80% of cases are caused by other phenomena. Data on minor long-term neurological deficits are scarce, but they suggest that less serious intellectual and motor impairments may result from intrapartum hypoxia/acidosis. This chapter focuses on the existing evidence of neurological damage associated with poor foetal oxygenation during labour. PMID:26148854

  3. Acompanhamento laboratorial da função renal de cães sadios tratados experimentalmente com doses terapêuticas de anfotericina B Laboratorial accompaniment of kidney funtion of health dogs experimentally treated with therapeutic dosages of amphotericin B

    Flávia Santin

    2006-12-01

    Full Text Available O presente trabalho objetivou avaliar a função renal de dez cães adultos saudáveis submetidos à administração de doses terapêuticas do antifúngico anfotericina B, cuja utilização tem sido limitada pelo seu elevado potencial nefrotóxico, e avaliar o método laboratorial mais sensível e precoce de diagnóstico de lesão renal. Foram realizadas, diariamente, urinálise, excreção fracionada de sódio e potássio, dosagem sérica de creatinina e uréia e atividade urinária de gama-glutamiltransferase (GGT. Concluiu-se que a anfotericina B provoca lesões nos túbulos proximal e distal, induzindo acidose tubular renal do tipo I e Diabetes insipidus nefrogênico em cães. Avaliação da função renal, preferencialmente por dosagens de creatinina, uréia e potássio séricos, é recomendada antes de cada aplicação do fármaco. A densidade urinária foi o parâmetro mais precocemente alterado pela lesão renal. A GGT urinária não foi eficaz para o diagnóstico precoce de lesão induzida por anfotericina B.The objective of this experiment was to assess the renal function of ten healthy male adult dogs submitted to therapeutic doses of amphotericin B, whose use has been limited due to its high nephrotoxic potential, as well as to evaluate the more sensitive and early method to diagnose kidney lesions. The renal function was evaluated through daily urinalysis, fractioned excretion of sodium and potassium, serum concentration of creatinine and blood urea nitrogen (BUN and urinary activity of gamma-glutamyltransferase (GGT. It was concluded that amphotericin b provokes lesions in both proximal and distal tubules, inducing type I renal tubular acidosis and nephrogenic Diabetes insipidus in dogs. Renal function evaluation, preferably by serum creatinine, BUN and potassium dosage is recommended before each drug application. Urinalysis proved to diagnose kidney lesions in its earliest stage through a modification of the density parameters

  4. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  5. Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    Mauro Pistello

    2012-08-01

    Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  6. Litiasis renal: Modificaciones bioquímicas durante el seguimiento Renal lithiasis: Biochemical changes in the follow-up

    Francisco R. Spivacow

    2006-06-01

    Full Text Available Con el objeto de evaluar si se producen modificaciones bioquímicas durante el seguimiento de pacientes nefrolitiásicos, se estudiaron 237 pacientes (115 mujeres y 122 hombres con una edad promedio de 39 ± 8 y 42 ± 7 años respectivamente controlados durante 23.7 ± 19.3 meses. A todos se les realizó un estudio metabólico de litiasis renal inicial y como mínimo uno o más posteriormente con las mismas características que el basal. No fueron incluidos pacientes con los diagnósticos de riñón en esponja, acidosis renotubular, hiperparatiroidismo primario, malformaciones renales o infecciones urinarias. Del total de pacientes, 139 (Grupo I presentaron en el seguimiento una modificación metabólica no evidenciada en el estudio inicial, mientras que 98 (Grupo II no. El tiempo de seguimiento de los primeros, no fue significativamente diferente de aquellos que no modificaron el diagnóstico basal. Las alteraciones bioquímicas agregadas más frecuentes fueron, hipocitraturia en el 43.1%, hipercalciuria idiopática en 20.8% y alteraciones del ácido úrico en 16.5%. De 110 pacientes seguidos más de 3 años, 37 (33% recurrieron. De éstos, 25 (23% modificaron el diagnóstico metabólico basal vs. 12 (11% que mantuvieron el mismo diagnóstico (p With the aim of assessing if biochemical changes occur in the follow up of patients with renal lithiasis, 237 patients were studied (115 women and 122 men, mean age 39 ± 8 and 42 ± 7 years, respectively and controlled during 27.3 ± 19.3 months. All of them had previously undergone metabolic evaluations at baseline and one or more than one control studies afterwards. Patients with a diagnosis of sponge kidney, renal tubular acidosis, primary hyperparathyroidism, anatomical malformations of the urinary tract, or urinary infections were not included. Two populations were identified: those who presented changes in the baseline diagnosis (139 patients, Group I and those who presented no changes (98

  7. Type B Lactic Acidosis Associated With Venlafaxine Overdose.

    Iragavarapu, Chaitanya; Gupta, Tanush; Chugh, Savneek S; Aronow, Wilbert S; Frishman, William H

    2016-01-01

    Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug. PMID:25405896

  8. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

    De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

    2015-01-01

    Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII. PMID:24608516

  9. Tubular engraftment and myofibroblast differentiation of recipient-derived cells after experimental kidney transplantation

    Broekema, Martine; Harmsen, Martin C.; Koerts, Jasper A.; Van Kooten, Theo G.; Navis, Gerjan; Van Luyn, Marja J. A.; Popa, Eliane R.

    2007-01-01

    Background. In human renal allografts, recipient-derived cells engrafted in various kidney substructures, have been detected in the long term after transplantation. Here we investigated tubular engraftment and myofibroblast differentiation of recipient-derived cells at short term after experimental

  10. Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

    Ven, M.T.P. van de; Colier, W.N.J.M.; Sluijs, M.C. van der; Oeseburg, B.; Folgering, H.T.M.

    2001-01-01

    The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (5610 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl)

  11. STUDY OF RENAL FAILURE IN MALARIA

    Girish Pamappa

    2016-01-01

    Full Text Available Renal failure is a serious complication of malaria, with a mortality of 14 to 33%. In view of the significant morbidity and mortality due to acute renal failure in malaria, there is need to identify patients at an early stage and to intensify care given to reduce morbidity and mortality. AIMS  To evaluate the clinical profile of Acute Renal Failure (ARF in malaria.  To evaluate the factors associated with adverse outcome, relation of severity of renal impairment on final outcome in patients with ARF due to malaria. MATERIAL AND METHODS This study was conducted at a tertiary care hospital over a period of 12 months. STUDY DESIGN  Type of study: Prospective Analytical, Observational Study.  Sample Size: 50 patients admitted to ICU, Kidney Unit, and the Medicine Wards with Malaria and ARF. Inclusion Criteria Clinically screened patients with evidence of malarial parasites in the blood smears or by antigen detection with clinical features or biochemical evidence of acute renal failure. Exclusion Criteria  Presence of any disease or condition leading to ARF or affecting the outcome of malarial ARF.  Other causes of Fever, Jaundice and Oliguria, like Leptospirosis, Dengue. METHODOLOGY Fifty patients who fulfilled the inclusion criteria were interrogated with regards to the complaints, clinical signs. Blood tests were sent on admission. Details were recorded as per the clinical proforma. The patients were followed until their discharge/death. RESULTS Oliguria was present in only 30% of patients. 30% of patients received haemodialysis. The mortality was 12% for severe renal failure. On Univariate analysis, Acidosis and Cerebral malaria were highly significant predictors of mortality. Other significant predictors were Renal failure, Oliguria, Shock, DIC, Hyperparasitemia, Leukocytosis (TLC. On Multivariate analysis, Oliguria, Cerebral malaria, Acidosis, Shock and two or more complications were the independent predictors of mortality

  12. The Effects of Shenhua Tablet Compound on the Location of NaDC1 in Renal Tubular Epithelial Cells with Anoxia/reoxygenation%复方肾华片对缺氧/复氧肾小管上皮细胞NaDC1转运蛋白定位的影响

    魏日胞; 杨悦; 张雪光; 方谦; 张玉强

    2013-01-01

    Objective:To observe the effect of the Shenhua-containing serum on the location of Sodium-dependent dicarboxylate transporter 1 (NaDC1) in the renal tubular epithelial cells of rats.Methods:After 3 days of continuous intragastric drug administration,male Wistar rats were sacrificed and Shenhua-containing serum has been prepared and separated.Renal tubular epithelial cells (RTECs) were divided into a normal serum-GFP-empty plasmid group,a normal serum-GFP-NaDC1 plasmid group,a Shenhua-containing serum-GFP-empty plasmid group and a Shenhua-containing serum-GFP-NaDC1 plasmid group.After anoxia/reoxygenation,immunofluorescence and immunoblot were performed.Results:Immunofluorescence examinations revealed a widened distribution of NaDC1 in normal serum-GFP-empty plasmid group,normal serum-GFP-NaDC1 plasmid group and Shenhua-containing serum-GFP-empty plasmid group,in Shenhua-containing serum-GFP-NaDC1 plasmid group,NaDC1 was distributed at membrane.Immunoblot show that approximately 90% of the NaDC1 was expressed at the basolateral membrane of RTECs in Shenhua-containing serum-GFP-NaDC1 plasmid group,whereas other three groups were expressed on the apical and basolateral surfaces at the nearly equal level.Conclusion:The Shenhua-containing serum effectively promoted the recovery of the polarity of RTECs caused by anoxia/reoxygenation.%目的:观察复方肾华含药血清对缺氧/复氧模型肾小管上皮细胞钠/二羧酸协同转运蛋白1(NaDC1)的定位影响.方法:雄性wistar大鼠,灌胃给药3d后处死,分离含药血清备用.分离培养大鼠肾小管上皮细胞,随机分4组:正常血清GFP空质粒组、正常血清GFP-NaDC1质粒组、肾华含药血清GFP空质粒组和肾华含药血清GFP-NaDC1质粒组,分别进行质粒转染后,在正常培养基或肾华含药血清培养基中培养,进行缺氧/复氧处理后应用免疫荧光和生物素化免疫印迹技术观察肾小管上皮细胞NaDC1的分布变化及表达.结果:免疫荧光结

  13. Quantitative renal cinescintigraphy with iodine-123 hippuran methodological aspects, kit for labeling of hippuran

    The development of an extemporaneous kit for the labeling of ortho-iodo-hippuric acid (Hippuran) with iodine 123 allows the performance of a routine quantitative renal cinescintigraphy providing in 20 minutes, and in an absolutely non-traumatic way, a very complete renal morphofunctional study including: a cortical renal scintigraphy, sequential scintigraphies of excretory tract, renal functional curves, tubular, global, and separate clearances for each kidney. This functional quantitative investigation method should take a preferential place in the routine renal balance. The methodology of the technique is explained and compared to classical methods for estimation of tubular, global and separate clearances

  14. 尿蛋白及晚期糖基化终产物对肾小管上皮细胞溶酶体的影响%Effect of urinary proteins and advanced glycosylation end products on ly-sosomes in renal tubular epithelial cells

    邓健锟; 王淑君; 吴洪銮; 罗勉娜; 许碧华; 梁东; 潘庆军; 刘华锋; 刘伟敬

    2015-01-01

    目的:探讨慢性肾脏病( CKD)病程中所产生的病理产物尿蛋白及晚期糖基化终产物( AGE)对肾小管上皮细胞( tubular epithelial cells,TECs)溶酶体结构与功能的影响,为阻止或延缓CKD病情进展探索新思路。方法:临床上选取未经特殊治疗的微小病变肾病综合征(MCNS)患者(n=11)、糖尿病肾病(DN)患者(n=11)及活检基本正常(n=6)的肾组织标本,以溶酶体相关膜蛋白1(lysosomal-associated membrane protein 1,LAMP1)和组织蛋白酶B( cathepsin B,CB)行间接免疫荧光染色;体外以8 g/LJ尿蛋白或100 mg/L晚期糖基化终产物刺激人肾小管上皮细胞系( HK-2细胞),以LAMP1和CB行间接免疫荧光染色,检测 CB及组织蛋白酶L ( cathepsin L,CL)活性,并观察DQ-卵清蛋白降解情况。结果: MCNS及DN患者TECs存在溶酶体膜透化( lysosomal membrane per-meabilization,LMP)现象。与正常对照组相比,尿蛋白及AGE-BSA均可致HK-2细胞LMP发生率上升,CB及CL活性降低,溶酶体对DQ-卵清蛋白的降解能力降低( P<0.05)。结论: CKD病理产物尿蛋白和晚期糖基化终产物均可致TECs出现LMP现象,并使溶酶体消化功能下降,这可能是CKD肾小管间质纤维化进展的重要机制之一。%[ ABSTRACT] AIM:To investigate the effects of pathological products, urinary proteins and advanced glycosyla-tion end products ( AGE) produced in the progression of chronic kidney disease ( CKD) , on the structure and function of lysosomes in renal tubular epithelial cells ( TECs ) , and try to find a novel approach for preventing or delaying CKD. METHODS:The renal specimens of the untreated patients with minimal change nephrotic syndrome (MCNS), diabetic nephropathy (DN) or normal kidney were collected.The expression of lysosomal-associated membrane protein 1 (LAMP1) and cathepsin B ( CB) was studied in TECs by indirect

  15. Efeitos da correção da acidose metabólica com bicarbonato de sódio sobre o catabolismo protéico na insuficiência renal crônica The effects of the correction of metabolic acidosis with sodium bicarbonate on protein catabolism in chronic kidney failure

    Mafra, Denise; Burini, Roberto Carlos

    2001-01-01

    A desnutrição protéico-energética constitui problema comum aos pacientes com insuficiência renal crônica, influenciando diretamente na sua morbi-mortalidade. A acidose metabólica tem papel no catabolismo protéico, ativando a via proteolítica proteasoma-ubiquitina, dependente de adenosina trifosfato, e conjuntamente com glicocorticóides induz uma maior atividade na desidrogenase que degrada os aminoácidos de cadeia ramificada. Esta revisão teve como objetivo descrever o mecanismo pelo qual a a...

  16. Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion

    Lee, Hyun-Wook; Verlander, Jill W.; Bishop, Jesse M.; Handlogten, Mary E.; Han, Ki-Hwan; Weiner, I. David

    2012-01-01

    The Rhesus factor protein, Rh C glycoprotein (Rhcg), is an ammonia transporter whose expression in the collecting duct is necessary for normal ammonia excretion both in basal conditions and in response to metabolic acidosis. Hypokalemia is a common clinical condition associated with increased renal ammonia excretion. In contrast to basal conditions and metabolic acidosis, increased ammonia excretion during hypokalemia can lead to an acid-base disorder, metabolic alkalosis, rather than mainten...

  17. Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

    Watanabe, Shuhei; Kono, Keiji; Fujii, Hideki; Nakai, Kentaro; Goto, Shunsuke; Nishi, Shinichi

    2016-01-01

    We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction. PMID:27066493

  18. Renal manifestations of genetic mitochondrial disease

    O’Toole JF

    2014-01-01

    John F O'Toole Department of Internal Medicine, Division of Nephrology, MetroHealth Medical System, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant...

  19. Cerebrovascular response to acute metabolic acidosis in humans.

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  20. Phenylbutyrate Therapy for Pyruvate Dehydrogenase Complex Deficiency and Lactic Acidosis

    Ferriero, Rosa; Manco, Giuseppe; Lamantea, Eleonora; Nusco, Edoardo; Ferrante, Mariella I.; Sordino, Paolo; Stacpoole, Peter W.; Lee, Brendan; Zeviani, Massimo; Brunetti-Pierri, Nicola

    2014-01-01

    Lactic acidosis is a build-up of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1α subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57B6/L wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1α in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1α through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noam631 zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis. PMID:23467562

  1. Metformin-induced lactic acidosis: a case series

    Silvestre Joana

    2007-10-01

    Full Text Available Abstract Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day, perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day, glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A

  2. Hypokalemic paralysis associated with cystic disease of the kidney: case report

    Jayasinghe Saroj; Rodrigo Chaturaka; Gamakaranage Champika SSSK; Rajapakse Senaka

    2011-01-01

    Abstract Background Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia. Case presentation We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts. Conclusion The association of cystic renal disease with hypokalemia, and the possible pathophysiolo...

  3. Markers of renal function tests

    Shivaraj Gowda

    2010-01-01

    Full Text Available Background : The markers of renal function test assess the normal functioning of kidneys. These markers may be radioactive and non radioactive. They indicate the glomerular filtration rate, concentrating and diluting capacity of kidneys (tubular function. If there is an increase or decrease in the valves of these markers it indicates dysfunction of kidney. Aim: The aim of this review is to compare and analyze the present and newer markers of renal function tests which help in diagnosis of clinical disorders. Material & Methods: An extensive literature survey was done aiming to compare and compile renal function tests makers required in diagnosis of diseases. Results: Creatinine, urea, uric acid and electrolytes are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin C and β-Trace Protein. Conclusion: We conclude that further investigation is necessary to define these biomarkers in terms of usefulness in assessing renal function.

  4. Hepatocyte Growth Factor Prevents Acute Renal Failure of Accelerates Renal Regeneration in mice

    Kawaida, Kouichi; Matsumoto, Kunio; Shimazu, Hisaaki; Nakamura, Toshikazu

    1994-05-01

    Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl_2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis of renal tubular cells after renal injuries caused by HgCl_2 administration and unilateral nephrectomy and induced reconstruction of the normal renal tissue structure in vivo. Taken together with our previous finding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought renotropic factor for renal regeneration and may prove to be effective treatment for patients with renal dysfunction, especially that caused by cisplatin.

  5. Development of diabetes-induced acidosis in the rat retina.

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID:27262608

  6. α1B-Adrenoceptors mediate adrenergically-induced renal vasoconstrictions in rats with renal impairment

    Md Abdul Hye KHAN; Munavvar Abdul SATTAR; Nor Azizan ABDULLAH; Edward James JOHNS

    2008-01-01

    Aim: This study examined whether α1B-adrenoceptors are involved in mediating adrenergically-induced renal vasoconstrictor responses in rats with pathophysi-ological and normal physiological states. Methods: Male Wistar Kyoto and spon-taneously hypertensive rats were induced with acute renal failure or experimental early diabetic nephropathy by cisplatin or streptozotocin, respectively. Cisplatin-induced renal failure was confirmed by impaired renal function and pronounced tubular damage. Experimental early diabetic nephropathy was confirmed by hyperglycemia, changes in physiological parameters, and renal function. The hemodynamic study was conducted on anesthetized rats after 7 d of cisplatin (renal failure) and 4 weeks of streptozotocin (experimental early diabetic nephropathy). Results: In the rats with renal failure and experimental early dia-betic nephropathy, there were marked reductions in their baseline renal blood flow (P0.05) in the renal failure and experimental early diabetic nephropathy rats, respectively, as compared to their non-renal failure and non-diabetic nephropathy controls. In the rats with renal impairment, chloroethylclonidine caused either accentuation or attenuation (all P0.05). Conclusion: This study demonstrated the presence of functional α1B-adrenoceptors that mediated the adrenergically-induced renal vaso-constrictions in rats with renal impairment, but not in rats with normal renal function.

  7. Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

    Eugene M. Tan

    2015-01-01

    Full Text Available The approach to the patient with acute renal failure and elevated anion and osmolal gap is difficult. Differential diagnoses include toxic alcohol ingestion, diabetic or starvation ketoacidosis, or 5-oxoproline acidosis. We present a 76-year-old female with type 2 diabetes mellitus, who was found at home in a confused state. Laboratory analysis revealed serum pH 6.84, bicarbonate 5.8 mmol/L, pCO2 29 mmHg, anion gap 22.2 mmol/L, osmolal gap 17.4 mOsm/kg, elevated beta-hydroxybutyrate (4.2 mmol/L, random blood sugar 213 mg/dL, creatinine 2.1 mg/dL, and potassium 7.5 mmol/L with no electrocardiogram (EKG changes. Fomepizole and hemodialysis were initiated for presumed ethylene glycol or methanol ingestion. Drug screens returned negative for ethylene glycol, alcohols, and acetaminophen, but there were elevated urine levels of acetone (11 mg/dL. The acetaminophen level was negative, and 5-oxoproline was not analyzed. After 5 days in the intensive care unit (ICU, her mental status improved with supportive care. She was discharged to a nursing facility. Though a diagnosis was not established, our patient’s presentation was likely due to starvation ketosis combined with chronic acetaminophen ingestion. Acetone ingestion is less likely. Overall, our case illustrates the importance of systematically approaching an elevated osmolal and anion gap metabolic acidosis.

  8. Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

    Nortier, J L; Deschodt-Lanckman, M M; Simon, S; Thielemans, N O; de Prez, E G; Depierreux, M F; Tielemans, C L; Richard, C; Lauwerys, R R; Bernard, A M; Vanherweghem, J L

    1997-01-01

    Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P stage renal failure patients (4.35 micrograms/24 hr; N = 5; P two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in

  9. Trauma renal Renal trauma

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  10. Nuclear medicine in acute and chronic renal failure

    The diagnostic value of renal scintiscans in patients with acute or chronic renal failure has not been emphasized other than for the estimation of renal size. 131I OIH, 67gallium, /sup 99m/TcDTPA, glucoheptonate and DMSA all may be valuable in a variety of specific settings. Acute renal failure due to acute tubular necrosis, hepatorenal syndrome, acute interstitial nephritis, cortical necrosis, renal artery embolism, or acute pyelonephritis may be recognized. Data useful in the diagnosis and management of the patient with obstructive or reflux nephropathy may be obtained. Radionuclide studies in patients with chronic renal failure may help make apparent such causes as renal artery stenosis, chronic pyelonephritis or lymphomatous kidney infiltration. Future correlation of scanning results with renal pathology promises to further expand nuclear medicine's utility in the noninvasive diagnosis of renal disease

  11. Gremlin Activates the Smad Pathway Linked to Epithelial Mesenchymal Transdifferentiation in Cultured Tubular Epithelial Cells

    Raquel Rodrigues-Diez

    2014-01-01

    Full Text Available Gremlin is a developmental gene upregulated in human chronic kidney disease and in renal cells in response to transforming growth factor-β (TGF-β. Epithelial mesenchymal transition (EMT is one process involved in renal fibrosis. In tubular epithelial cells we have recently described that Gremlin induces EMT and acts as a downstream TGF-β mediator. Our aim was to investigate whether Gremlin participates in EMT by the regulation of the Smad pathway. Stimulation of human tubular epithelial cells (HK2 with Gremlin caused an early activation of the Smad signaling pathway (Smad 2/3 phosphorylation, nuclear translocation, and Smad-dependent gene transcription. The blockade of TGF-β, by a neutralizing antibody against active TGF-β, did not modify Gremlin-induced early Smad activation. These data show that Gremlin directly, by a TGF-β independent process, activates the Smad pathway. In tubular epithelial cells long-term incubation with Gremlin increased TGF-β production and caused a sustained Smad activation and a phenotype conversion into myofibroblasts-like cells. Smad 7 overexpression, which blocks Smad 2/3 activation, diminished EMT changes observed in Gremlin-transfected tubuloepithelial cells. TGF-β neutralization also diminished Gremlin-induced EMT changes. In conclusion, we propose that Gremlin could participate in renal fibrosis by inducing EMT in tubular epithelial cells through activation of Smad pathway and induction of TGF-β.

  12. Glomerular filtration and tubular secretion of MAG-3 in the rat kidney

    Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion

  13. The decreased expression of electron transfer flavoprotein β is associated with tubular cell apoptosis in diabetic nephropathy.

    Wang, Hua; Zhang, Haojun; Chen, Xiaohong; Zhao, Tingting; Kong, Qin; Yan, Meihua; Zhang, Bingxuan; Sun, Sifan; Lan, Hui-Yao; Li, Ning; Li, Ping

    2016-05-01

    Tubular injury is closely correlated with the development of progressive diabetic nephropathy (DN), particularly in cases of type 2 diabetes. The apoptosis of tubular cells has been recognized as a major cause of tubular atrophy, followed by tubulointerstitial fibrosis. Electron transfer flavoprotein β (ETFβ) is known as an important electron acceptor in energy metabolism, but its role in DN was not fully understood. In the present study, we examined the expression pattern of ETFβ using diabetic kidney samples and further investigated ETFβ involvement in tubular epithelial cell (TEC) apoptosis. Human renal biopsy specimens from patients with DN as well as a spontaneous rat model of diabetes using Otsuka Long-Evans Tokushima fatty (OLETF) rats, were employed in order to examine the expression of ETFβ and cell apoptosis in kidneys during the development of DN (for the rats, at 36 and 56 weeks of age respectively). Moreover, ETFβ siRNA was used to investigate the role of ETFβ in the apoptosis of renal tubular cells. Our present results showed that the expression of ETFβ in the kidneys was progressively decreased both in patients with DN and OLETF rats, which coincided with progressive renal injury and TEC apoptosis. In addition, the in vitro study demonstrated that knockdown of ETFβ caused apoptosis in tubular cells, as proven by the increased expression of pro‑apoptotic proteins and TUNEL assay. Therefore, the findings of our present study suggest that ETFβ plays an important role in renal tubular cell apoptosis during the progression of DN. PMID:27035869

  14. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    Tonguç Utku Yilmaz

    2015-01-01

    Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic/normal conditions.

  15. Acidosis ruminal en bovinos lecheros: implicaciones sobre la producción y la salud animal - Ruminal acidosis in dairy cattle: implications for animal health and production

    Granja Salcedo, Yury Tatiana

    2012-04-01

    Full Text Available ResumenLa acidosis ruminal es un importante problema en la producción de bovinos alimentados con dietas ricas en concentrados, especialmente en vacas de alta producción lechera.AbstractRuminal acidosis is a major problem in the production of cattle fed diets rich in concentrates, especially in cows of high milk production.

  16. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

    Patsouris Efstratios

    2011-04-01

    Full Text Available Abstract Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory versus normocapnic (metabolic acidosis in an ex vivo model of ventilator-induced lung injury (VILI. Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA, metabolic acidosis (MA and normocapnic-normoxic (Control - C groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain, changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024, while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276 and 40 min (P = 0.0012 compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

  17. Blood Parameters Modification at Different Ruminal Acidosis Conditions

    Roberta De Nardi

    2013-09-01

    Full Text Available This study evaluated the reliability of various blood parameters to assess the ruminal acidosis in cattle. Six whole heifers were fed three experimental rations in a 3 x 3 Latin square design. The diets had different starch levels: high (HS, medium (MS or low (CT. Ruminal pH values were continuously measured using wireless sensors. To evaluate the severity of ruminal acidosis, the amount of time per day that the pH was below 5.8, 5.5 and 5.0 was recorded. Blood samples were analyzed for complete blood count, venous blood gas and biochemical profile at 8:00 and 12:00 h. The data were analyzed according to a mixed model. Feeding on CT, MS and HS led to significant differences in DMI (7.7 vs. 6.9 vs. 5.1 kg/d; P < 0.01 which modified the amount of time per day that the pH was below 5.0 (0 vs. 12 vs. 92 min; P < 0.10. Feeding MS and HS diets led to inflammation as indicated by the significant increment of white blood cells when compared to the CT ones and to blood concentration due to the osmotic pressure at ruminal level. Furthermore a significant decrease of bicarbonate level, CO2 partial pressure and oxyhemoglobin was observed as consequence of the activation of metabolic processes aimed to prevent metabolic acidosis. No differences were observed on blood sampling time, suggesting that one daily blood sample was enough to evaluate the metabolic variations related to ruminal acidosis.

  18. Cellular acidosis inhibits assembly, disassembly, and motility of stress granules.

    Chudinova, E M; Nadezhdina, E S; Ivanov, P A

    2012-11-01

    Stress granules (SGs) are large ribonucleoprotein (RNP)-containing particles that form in cytoplasm in response to a variety of acute changes in the cellular environment. One of the general parameters of the cell environment is pH. In some diseases, as well as in muscle fatigue, tissue acidosis occurs, leading to decrease in intracellular pH. Here we studied whether decrease in pH causes the formation of SGs in cultured animal cells, whether it affects the formation of the SGs under the action of arsenite and, if such effects occur, what are the mechanisms of the influence of acidosis. Acidosis was simulated by decreasing the pH of the culture medium, which acidified the cytoplasm. We found that medium acidification to pH 6.0 in itself did not cause formation of SGs in cells. Moreover, acidification prevented the formation of SGs under treatment with sodium arsenite or sodium arsenite together with the proteasome inhibitor MG132, and it inhibited the dissociation of preformed SGs under the influence of cycloheximide. We established that pH decrease did not affect the phosphorylation of eIF2α that occurs under the action of sodium arsenite, and even caused such phosphorylation by itself. We also found that the velocity of SG motion in cytoplasm at acidic pH was very low, and the mobile fraction of SG-incorporated PABP protein revealed by FRAP was decreased. We suppose that acidic pH impairs biochemical processes favoring assembly of RNPs in stress conditions and RNP dissociation on the termination of stress. Thus, in acidosis the reaction of the cellular translation apparatus to stress is modified. PMID:23240565

  19. Metabolic Acidosis Without Clinical Signs of Dehydration in Young Calves

    Kasari, T R; Naylor, J M

    1984-01-01

    Metabolic acidosis without clinical signs of dehydration was diagnosed in four calves between nine and 21 days of age. In each calf either coma or depression with weakness and ataxia was observed. Two calves had slow deep respirations. Treatment with intravenous administration of solutions of sodium bicarbonate was accompanied by a rise in blood pH and a return to normal demeanor, ambulation and appetites, allowing these calves to return to their respective herds.

  20. Miopatias associadas a agregados tubulares

    Mary Souza Carvalho

    1993-09-01

    Full Text Available Os autores relatam a caso de paciente de 58 anos de idade do sexo masculino, com quadro de características miastênicas tanto clínica como eletromiograficamente, no qual a biópsia muscular com histoquímica e microscopia eletrônica permitiu fazer o diagnostico de miopatia associada a agregados tubulares. É chamada a atenção para o fato de que as alterações anátomo-patológicas encontradas podem estar presentes em um grupo heterogêneo de pacientes com grande variedade de sintomas, não havendo portanto motivo para considerar-se a existência de uma miopatia com agregados tubulares, já que os achados anátomo-patológicos são inespecíficos e não configuram moléstia específica.

  1. Tubular crystals of acetylcholine receptor

    1984-01-01

    Well-ordered tubular crystals of acetylcholine receptor were obtained from suspensions of Torpedo marmorata receptor-rich vesicles. They are composed of pairs of oppositely oriented molecules arranged on the surface lattice with the symmetry of the plane group p2 (average unit cell dimensions: a = 90 A, b = 162 A, gamma = 117 degrees). The receptor in this lattice has an asymmetric distribution of mass around its perimeter, yet a regular pentagonal shape; thus its five transmembrane subunits ...

  2. Modified tubularized incised plate urethroplasty

    Shivaji Mane; Jamir Arlikar; Nitin Dhende

    2013-01-01

    Aim: To share our experience of doing tubularized incised plate urethroplasty with modifications. Materials and Methods: This is a single surgeon personal series from 2004 to 2009. One hundred patients of distal hypospadias were subjected for Snodgrass urethroplasty with preputioplasty. The age range was 1 to 5 year with mean age of 2.7 years. Selection criteria were good urethral plate, without chordee and torsion needing complete degloving. Main technical modification from original Snodgras...

  3. Lactic acidosis secondary to metformin overdose: a case report

    Timbrell Simon

    2012-08-01

    Full Text Available Abstract Introduction Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. In the intensive care setting lactate and pH levels are regularly used as a useful predictor of poor prognosis. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. Case presentation We present the case of a 70-year-old Caucasian man who took a deliberate metformin overdose of unknown quantity. He had a profound lactic acidosis at presentation with a pH of 6.93 and a lactate level of more than 20mmol/L. These figures would normally correspond with a mortality of more than 80%; however, with appropriate management this patient’s condition improved. Conclusion We provide evidence that the decision to treat severe lactic acidosis in deliberate metformin overdose should not be based on arterial lactate and pH levels, as would be the case in other overdoses. We also demonstrate that appropriate treatment with hemodiafiltration and 8.4% sodium bicarbonate, even in patients with a very high lactate and low pH, can be successful.

  4. Acute phase protein response during acute ruminal acidosis in cattle

    Danscher, A. M.; Thoefner, M. B.; Heegaard, Peter M. H.;

    2011-01-01

    The aim of the study was to describe the acute phase protein and leukocyte responses in dairy heifers during acute, oligofructose-induced ruminal acidosis. The study included 2 trials involving oral oligofructose overload (17g/kg BW) to nonpregnant Danish Holstein heifers. Trial 1 included 12...... performed.Heifers receiving oligofructose developed a profound ruminal and systemic acidosis (in Trial 1 and 2 lowest ruminal pH was 4.3±0.2 and 3.8±0.02, respectively, and minimum SBE was −9.3±4.1 and −8.9±2.8, respectively). In Trial 1, SAA concentrations were higher than baseline concentrations on all...... than control heifers at 18 and 24h after overload (max. 13.7±4.3 billions/L). Feeding had no effect on plasma fibrinogen concentrations or WBC in Trial 1.Acute ruminal and systemic acidosis caused by oligofructose overload resulted in distinct acute phase protein and leukocyte responses in dairy...

  5. Radiopharmaceuticals for quantitative study of renal function

    Some topics discussed are as follows: the role of glomerular filtration and tubular reabsorption in renal function; measurement of glomerular filtration rate using inulin and derivatives labeled with 14C, 125I, 131I, and 51Cr, radioactive vitamin B12, contrast agents such as diatrizoate labeled with 125I and 131I and iothalamate labeled with 125I, and complexes of EDTA, DTPA, and citrate with 57Co, 58Co, 68Ga,/sup 99m/Tc, 111In, /sup 113m/In, /sup 114m/In, /sup 115m/In, 169Yb, and 197Hg; tubular secretion; measurement of renal plasma flow using 131I-labeled orthoiodohippurate; and measurement of renal blood flow using 197Hg-chlormerodrin, /sup 99m/Tc-pertechnetate, /sup 99m/Tc-Fe-ascorbic acid, /sup 99m/Tc-penicillamine-acetazolamide, /sup 99m/Tc-glucoheptonate, and /sup 99m/Tc-dimercaptosuccinic acid

  6. Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

    Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

    2015-01-01

    Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells i...

  7. Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

    Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI

  8. Cordyceps sinensis attenuates renal fibrosis and suppresses BAG3 induction in obstructed rat kidney

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Zong, Zhi-Hong; Du, Zhen-Xian; Li, De-Tian; Wang, Hua-Qin; Liu, Bo; Miao, Jia-Ning; Bian, Xiao-Hui

    2015-01-01

    BAG3 regulates a number of cellular processes, including cell proliferation, apoptosis, adhesion and migration, and epithelial-mesenchymal transition (EMT). However, the role of BAG3 in renal tubular EMT and renal interstitial fibrosis remains elusive. This study aimed to examine the dynamic expression of BAG3 during renal fibrosis, and to investigate the efficacy of Cordyceps sinensis (C. sinensis) on renal fibrosis. A rat model of unilateral ureteral obstruction (UUO) was established, and t...

  9. The anesthetics influence (ethilic-eter and urethane) on renal radiopharmaceuticals

    A comparative study was done using anesthetics like ether ethilic and urethane, in rats (Wistar). A significative variation was observed in the results obtained when renal radiopharmaceuticals were investigated. Using urethane, the renal uptake increase progressivelly due to the inhibition of the renal filtration and it starts to recuperate when the anesthetic effect was eliminated. Using ether ethilic the radiopharmaceuticals are quickly eliminated from the kidneys (tubular or glomerular filtration), showing that the renal function was protected. (author)

  10. Renal hemodynamics, function, and oxygenation during cardiac surgery performed on cardiopulmonary bypass: a modeling study

    Sgouralis, Ioannis; Evans, Roger G.; Gardiner, Bruce S; Smith, Julian A.; Fry, Brendan C.; Layton, Anita T.

    2015-01-01

    Abstract Acute kidney injury, a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB), is thought to be driven partly by hypoxic damage in the renal medulla. To determine the causes of medullary hypoxia during CPB, we modeled its impact on renal hemodynamics and function, and thus oxygen delivery and consumption in the renal medulla. The model incorporates autoregulation of renal blood flow and glomerular filtration rate and the utilization of oxygen for tubular ...

  11. [Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

    Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

    2013-06-01

    Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. PMID:23628119

  12. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984).

    DiBartola, S P; Rutgers, H C; Zack, P M; Tarr, M J

    1987-05-01

    The historic, physical, laboratory, and histologic findings for 74 cats with chronic renal disease were reviewed. Most cats were older, and no breed or sex predilection was detected. This most common clinical signs detected by owners were lethargy, anorexia, and weight loss. Dehydration and emaciation were common physical examination findings. Common laboratory findings were nonregenerative anemia, lymphopenia, azotemia, hypercholesterolemia, metabolic acidosis, hyperphosphatemia, and isosthenuria. The most common morphologic diagnosis was chronic tubulointerstitial nephritis of unknown cause. The other pathologic diagnoses were renal lymphosarcoma, renal amyloidosis, chronic pyelonephritis, chronic glomerulonephritis, polycystic renal disease, and pyogranulomatous nephritis secondary to feline infectious peritonitis. PMID:3583899

  13. Lipid peroxidation and renal injury in renal ischemia/reperfusion: Effect of Benincasa cerifera

    Bhalodia Y

    2009-01-01

    Full Text Available To investigate the role of the methanolic fruit extract of Benincasa cerifera on lipid peroxidation (LPO and renal pathology in ischemia/reperfusion (I/R.In experimental methodology, both renal pedicles were occluded for 60 min followed by 24 h of reperfusion. B. cerifera (500 mg/kg/day was administered orally for 5 days prior to induction of renal ischemia and was continued for 1 day after ischemia. At the end of the reperfusion period, rats were sacrificed. Sham-operated rats followed same procedure except renal arteries occlusion. LPO and histopathological analysis were done in renal tissue. Serum creatinine and urea levels were measured for the evaluation of renal function. In ischemia/reperfusion (I/R rats, malondialdehyde (MDA levels were increased significantly when compared with sham-control rats. Histological changes showed tubular cell swelling, interstitial oedema, tubular dilation and moderate-to-severe necrosis in epithelium of I/R rat as compared to sham control. The methanolic fruit extract of B. cerifera could attenuate the heightened MDA levels. I/R-induced renal injury was markedly diminished by administration of B. cerifera These results indicate that the methanolic fruit extract of B. cerifera attenuate renal damage after I/R injury of the kidney by potent antioxidant or free radical scavenging activity.

  14. Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment

    Fabris, Antonia; Bernich, Patrizia; Abaterusso, Cataldo; Marchionna, Nicola; Canciani, Chiara; Nouvenne, Antonio; Zamboni, Mauro; Lupo, Antonio; Gambaro, Giovanni

    2009-01-01

    Background and objectives: In medullary sponge kidney (MSK)—a common malformative renal condition in patients with calcium nephrolithiasis—hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither h...

  15. Species diversity regarding the presence of proximal tubular progenitor cells of the kidney

    J. Hansson

    2016-02-01

    Full Text Available The cellular source for tubular regeneration following kidney injury is a matter of dispute, with reports suggesting a stem or progenitor cells as the regeneration source while linage tracing studies in mice seemingly favor the classical theory, where regeneration is performed by randomly surviving cells. We, and others have previously described a scattered cell population localized to the tubules of human kidney, which increases in number following injury. Here we have characterized the species distribution of these proximal tubular progenitor cells (PTPCs in kidney tissue from chimpanzee, pig, rat and mouse using a set of human PTPC markers. We detected PTPCs in chimpanzee and pig kidneys, but not in mouse tissue. Also, subjecting mice to the unilateral urethral obstruction model, caused clear signs of tubular injury, but failed to induce the PTPC phenotype in renal tubules.

  16. Piperazine side-effects in a patient with pre-existing renal insufficiency

    Majid Malaki

    2014-01-01

    Piperazine as an antihelminth has many adverse effects, especially on patients with renal insufficiency. We report the use of piperazine in a girl with a moderately severe kidney disease due to Biedl Bardet syndrome. She developed coma and acute kidney injury due to acute interstitial nephritis (AIN), anemia and thrombocytopenia. The presence of fever, proteinuria, acidosis, anemia, sterile pyuria and non-oliguric renal failure strongly suggested AIN. Her problems abated mostly by discontinui...

  17. Growth speed in patients with chronic renal failure undergoing to renal transplantation between 2000 and 2009 in the Hospital Nacional de Ninos: research protocol

    The growth speed was investigated in children with chronic renal failure after renal transplantation, in the Hospital Nacional de Ninos during the study period January 2000-December 2009. Factors that have influenced are analyzed: age of onset of renal disease, etiology of renal disease, metabolic acidosis, anemia, renal osteodystrophy, episodes of infection and rejection. Besides, on the growth rate and expected family size, to intervene or prevent them in future cases. Also, the use that has given in the hospital to growth hormone, before and after renal transplantation is determined to eventually use parallel therapies to the transplantation. An echocardiographic study is recommended to perform as part of the treatment of chronic renal failure to identify the existence of left ventricular hypertrophy and heart failure, which may occur as a result of complications of the failure

  18. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of [3H]PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of [3H]6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment

  19. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    S. Kroening; E. Neubauer; B. Wullich; J. Aten; M. Goppelt-Struebe

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009; doi:10.1152/aj

  20. Recent classification of renal epithelial tumors.

    Kuroda, Naoto; Tanaka, Azusa

    2014-06-01

    The recent classification of renal tumors is based on genetic evidence as well as on histologic features. Malignant tumor includes clear cell renal carcinoma (RCC), multilocular cystic RCC, papillary RCC, chromophobe RCC, carcinoma of the collecting duct of Bellini, renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions and mucinous tubular and spindle cell carcinoma. Benign tumor is subdivided into papillary adenoma, renal oncocytoma and metanephric adenoma. Recently, new disease entities such as acquired cystic disease-associated RCC, clear cell papillary RCC and renal carcinoma with t(6;11)(p21:q12) have been discovered. In this article, we briefly review and introduce the clinical, morphological and genetic features of these tumor entities. PMID:23529139

  1. Renal biomarkers in domestic species.

    Hokamp, Jessica A; Nabity, Mary B

    2016-03-01

    Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies. PMID:26918420

  2. Alcohol misuse and renal damage.

    Cecchin, E; De Marchi, S

    1996-01-01

    Recent clinical and experimental studies have demonstrated that the habitual consumption of large amounts of ethanol has deleterious effects on the kidney. A variety of tubular defects have been described in patients with chronic alcoholism. Evidence is emerging that tubular dysfunction has an important pathophysiological role in a wide range of electrolyte and acid-base disturbances commonly observed in these patients, and possibly in alcohol-induced bone disease. These renal abnormalities are often reversible, disappearing with abstinence. However, since 1990 a few cases of a syndrome of acute tubular necrosis due to binge drinking of ethanol in the absence of other evident nephrotoxic mechanisms, or in association with the use of nonsteroidal anti-inflammatory drugs, have been reported. A link between glomerulonephritis and alcoholism has become evident. IgA nephropathy has been demonstrated at autopsy in 64% of chronic alcoholics and, more recently, the association between alcoholism and postinfectious glomerulonephritis has been described. Structural and functional abnormalities of the kidney are reported with increasing frequency in the fetal alcohol syndrome seen in children who have been prenatally exposed to ethanol. In addition, over the last few years experimental studies in vitro or in animal models have provided information about the biochemical and molecular basis of alcohol-induced injury to kidney. It is hoped that future experimental and clinical research will provide us with a more comprehensive knowledge of the mechanisms of renal damage in alcohol misuse. PMID:12893483

  3. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  4. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue

  5. Abdominal distention and renal failure in a neonate

    Bedri, Badreldin; Goodwin, Julie E.

    2013-01-01

    A term male neonate presented to his paediatrician for a routine follow-up after hospital discharge. Prenatal care had been excellent and labour and delivery had been unremarkable. He had been feeding, gaining weight and was not in distress though significant abdominal distention was noted. Lab tests revealed electrolytes derangements, metabolic acidosis and renal failure. An ultrasound revealed severe unilateral hydronephrosis and echogenic kidneys. A voiding cystourethrogram revealed the de...

  6. MR Imaging of renal transplants

    The authors report their experience in the study of renal transplant recipients by MR, in order to determine its clinical potentials. The main purpose of this work is to focus on MR patterns in relation to clinical findings of rejector or normally fuctioning kidney. Twenty-four patients were examined with a 0.5 T superconductive magnete, body coil, spin-echo pulse sequence (SE) and inversion-recovery (IR). MRI patterns could be seen in normally functioning kidneys and transplant rejections, while variable MRI findings were observed in transplants with acute tubular necrosis (ATN). In the normally functioning transplanted kidney there is a clear corticomedullary differentiation (CMD), and the extent of vascular penetration into the renal parenchyma is clearly seen. In transplant rejection, CMD is either diminished or absent, and there is no vascular penetration into the parenchyma; to differentiate acute from chronic rejections, the increase/decrease in renal size and the change in renal shape (spherical shape in acute transplant rejection) respectively must be observed. MRI proves thus to be useful in the study of renal transplants, even in case of questionable clinical findings, and in patients in whom renal biopsy is contraindicated

  7. Postoperative metabolic acidosis following the minimally invasive radiofrequency maze procedure

    Raymond Patrick Hom

    2016-01-01

    Full Text Available Purpose: Atrial fibrillation (AF is the most common arrhythmia treated in the world. While medical treatment with antiarrhythmic drugs remains the primary treatment modality, symptomatic refractory AF often requires treatment with a catheter or surgical ablation. One minimally invasive therapy is the Mini-Maze procedure, which utilizes epicardial radiofrequency ablation via a subxiphoid approach to rid the heart of arrhythmogenic atrial foci without a median sternotomy or cardiopulmonary bypass. The goal of this retrospective cohort study was to identify clinical factors associated with metabolic acidosis following the Mini-Maze procedure. Materials and Methods: After Institutional Review Board approval, we studied patients undergoing the Mini-Maze procedure, off-pump coronary artery bypass grafting or patients conventional Cox-Maze on cardiopulmonary bypass. The first base deficit value obtained in the Intensive Care Unit was used as a measure of metabolic acidosis. Using logistic regression with Akaike information criteria, we analyzed preoperative, intraoperative, and postoperative data to determine the factors associated with changes in base deficit. Results: A multivariable model using stepwise selection demonstrated that diabetes mellitus and weight were associated with a decrease in the base deficit by 2.87 mEq/L (95% CI: −5.55-−0.19 and 0.04 mEq/L (95%CI: −0.08, 0.004, respectively. Furthermore, creatinine was associated with a 1.57 mEq/L (95% CI: 0.14, 2.99 increase in the base deficit. Conclusion: The Mini-Maze procedure was not associated with postoperative metabolic acidosis. Instead, nondiabetic patients and patients with higher creatinine were associated with greater base deficits after undergoing cardiac surgery.

  8. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  9. Modified tubularized incised plate urethroplasty

    Shivaji Mane

    2013-01-01

    Full Text Available Aim: To share our experience of doing tubularized incised plate urethroplasty with modifications. Materials and Methods: This is a single surgeon personal series from 2004 to 2009. One hundred patients of distal hypospadias were subjected for Snodgrass urethroplasty with preputioplasty. The age range was 1 to 5 year with mean age of 2.7 years. Selection criteria were good urethral plate, without chordee and torsion needing complete degloving. Main technical modification from original Snodgrass procedure was spongioplasty, preputioplasty, and dorsal slit when inability to retract prepuce during surgery. Results: Average follow-up period is 23 months. Seven (7% patients developed fistula and one patient had complete preputial dehiscence. Phimosis developed in three (3% patients and required circumcision. Dorsal slit was required in seven patients. One patient developed meatal stenosis in postoperative period. All other patients are passing single urinary stream and have cosmesis that is acceptable. Conclusions: Modified tubularized incised plate urethroplasty with preputioplasty effectively gives cosmetically normal looking penis with low complications.

  10. Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats

    Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids

  11. Tubular lining material for pipelines having bends

    Moringa, A.; Sakaguchi, Y.; Hyodo, M.; Yagi, I.

    1987-03-24

    A tubular lining material for pipelines having bends or curved portions comprises a tubular textile jacket made of warps and wefts woven in a tubular form overlaid with a coating of a flexible synthetic resin. It is applicable onto the inner surface of a pipeline having bends or curved portions in such manner that the tubular lining material with a binder onto the inner surface thereof is inserted into the pipeline and allowed to advance within the pipeline, with or without the aid of a leading rope-like elongated element, while turning the tubular lining material inside out under fluid pressure. In this manner the tubular lining material is applied onto the inner surface of the pipeline with the binder being interposed between the pipeline and the tubular lining material. The lining material is characterized in that a part of all of the warps are comprised of an elastic yarn around which, over the full length thereof, a synthetic fiber yarn or yarns have been left-and/or right-handedly coiled. This tubular lining material is particularly suitable for lining a pipeline having an inner diameter of 25-200 mm and a plurality of bends, such as gas service pipelines or house pipelines, without occurrence of wrinkles in the lining material in a bend.

  12. Renal angiomyolipoma

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    Renal angiomyolipoma is a rare lesion composed of smooth muscle cells, adipose tissue and abnormal vessels. It is currently classified as a benign, non-epithelial renal tumor. It has a high incidence in patients suffering from tuberous sclerosis but is more frequently found as an isolated renal...

  13. A perspective on Serum Lactic acid, Lactic Acidosis in a Critical Care Unit

    Agela A.Elbadri

    2013-06-01

    Full Text Available Breast cancer is one of the major surgical problems encountered in Libya. Lactic acidosis is a universal complication in breast cancer patients and can be considered a possible prognostic marker. Therefore, it will be beneficial to correctly understand and review the biochemistry underlying lactic acidosis and its possible significance as a prognostic marker in critical care patients, including breast cancer.

  14. Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep

    Lettat Abderzak; Nozière Pierre; Silberberg Mathieu; Morgavi Diego P; Berger Claudette; Martin Cécile

    2012-01-01

    Abstract Background Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Results Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four w...

  15. State-of-the-art renal diagnostics in nuclear medicine

    99mTc-MAG3 is one the mostly used radiopharmaceutical for the assessment of the renal function in nuclear medicine. This review presents the pharmacokinetics of the radiopharmaceutical, which substantiates its use for the assessment of the tubular secretion and renal function. It includes a table for the absorbed dose in critical organs for different renal function agents. The treatment techniques are presented in details. For the determination of the tubular extraction rate the Tauxe method is proposes, but it is outlined that this method is not applicable to patients with ascites, edema, hypoproteinaemia or proteinuria. The clearance values are presented for persons of age 4-17 years and after 18. Captopril scintigraphy using 99mTc-MAG is described in cases with renovascular hypertension. For the renal function assay the dynamic furosemide scintigraphy is presented. Examples for the application of each method are given

  16. Individual electrostatic astigmatic tubular lenses

    Electron-optical properties of three-electrode individual astigmatic tubular lenses with similar electrode diameters are investigated. It has been assumed while calculations that gaps between the el ctrodes are infinitely small and lines separating them are presented as part of line of intersection of two cylinders with equal radius. Parameters characterizing paraxial properties of lenses and coefficients of their spherical aberration for subject position on the infinity at different ratios of electrode potential and distances between gaps are determined. The three-electrode individual lens focuses charged particle beams in one plain and it scatters them in another one in the whole chosen range of potential ratios. It is revealed that coefficients of spherical aberration in individual lenses have different signs and one of the coefficients passes through zero

  17. Protocol biopsies for renal transplantation

    Rush David

    2010-01-01

    Full Text Available Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.

  18. RENAL TUBULER ASİDOZA BAĞLI AĞIR HİPOPOTASEMİ VE SOLUNUM ARRESTİ İLE ORTAYA ÇIKAN BİR PRİMER SJÖGREN SENDROMU OLGUSU

    BAVUNOĞLU TÜFEKÇİ, Işıl; TUNÇKALE, Aydın; YİRMİBEŞÇİK, Sibel; AYATA, Ebru; Karter, Yesari; ÖZTÜRK, Esin; DOĞUSOY, Gülen

    2014-01-01

    Background.- Sjögren’s syndrome (SS) is an autoimmune exocrinopathy that involves both glandular and extraglandular systems. This disease may cause hypokalemic quadriparalysis due to distal renal tubuler acidosis (RTA).Observation.- We report here a 19-year-old girl who presented with life-threatening hypokalemic paralysis requiring admission to an intensive care unit. Biochemical investigations showed severe hypokalemia with hyperchloremic metabolic acidosis, a spot urine pH of 6.8, and a po...

  19. Renal and post-renal causes of acute renal failure in children

    Objective: To identify the causes of acute renal failure (ARF) in pediatric population along with the identification of the age and gender most affected by the failure. Subjects and Methods: The study included children under the age of 12 years who presented with signs and symptoms suggestive of ARF (oliguria/anuria, vomiting, acidotic breathing etc.) along with raised blood urea nitrogen (BUN) serum creatinine and metabolic acidosis as shown by arterial blood gases (ABGs). Patients were divided into two group on the basis of age; group A consisting of 0-2 years and group B from >2 years. Patients presenting with transient pre-renal azotaemia were excluded from the study. After providing initial emergency cover, detailed history, physical examination and investigations were carried out according to a proforma specially designed to ascertain the cause of ARF. Patients were managed for ARF as per standard recommendations and investigations completed or repeated as and when required. Results: A total of 119 patients with ARF were admitted in the ward over a period of two years constituting 1.36% of the total admissions and 16.39% of the admissions due to renal pathology. Mean age of presentation was 4.5 years 16.7% of the patients under the age of 5 years. Male predominance was noted in all ages with an overall male to female ratio of 2.3:1. Most common cause leading to ARF in younger age group was found to be hemolytic uremic syndrome [25(54.34%)] followed by septicemia [7(15.21 %)]. In older patients renal calculus disease was the most common [22(30.13%)] underlying pathology followed by pre-existing, undiagnosed chronic renal failure [16(21.91 %)]. Conclusion: ARF is fairly cotton in children especially under the age of 5 years showing a male predominance. More than 90% of the cases can be prevented by improving primary health care and by early and prompt treatment of infections. (author)

  20. Contrast media in renal insufficiency - risk and prevention

    The use of iodinated contrast media (CM) continues to be a common cause of hospital-acquired acute renal failure (ARF) and its development increases the in-hospital mortality significantly. Alterations in renal hemodynamics and direct tubular toxicity by contrast media are the primary factors believed to be responsible for contrast media-associated nephrotoxicity. We review recent insights into the pathogenesis of this complication and summarize prophylacttic strategies focussing on hydration, vasoactive pharmacological agents, alternative contrast media and 'prophylactic hemodialysis'. (orig.)

  1. Associations between Renal Hyperfiltration and Serum Alkaline Phosphatase

    Oh, Se Won; Han, Kum Hyun; Han, Sang Youb

    2015-01-01

    Renal hyperfiltration, which is associated with renal injury, occurs in diabetic or obese individuals. Serum alkaline phosphatase (ALP) level is also elevated in patients with diabetes (DM) or metabolic syndrome (MS), and increased urinary excretion of ALP has been demonstrated in patients who have hyperfiltration and tubular damage. However, little was investigated about the association between hyperfiltration and serum ALP level. A retrospective observational study of the 21,308 adults in t...

  2. Severe acute renal failure in a patient with diabetic ketoacidosis

    Al-Matrafi Jamila

    2009-01-01

    Full Text Available Acute renal failure (ARF is a rare but potentially fatal complication of diabetic ketoacidosis (DKA. Early recognition and aggressive treatment of ARF during DKA may im-prove the prognosis of these patients. We present a case report of a 12 year old female admitted to the hospital with severe DKA as the 1s t manifestation of her diabetes mellitus. She presented with severe metabolic acidosis, hypophosphatemia, and oliguric ARF. In addition, rhabdomyolysis was noted during the course of DKA which probably contributed to the ARF. Management of DKA and renal replacement therapy resulted in quick recovery of renal function. We suggest that early initiation of renal replacement therapy for patients with DKA developing ARF may improve the potentially poor outcome of patients with ARF associated with DKA.

  3. Marble brain syndrome: osteopetrosis, renal acidosis and calcification of the brain

    Jacquemin, C.; Mullaney, P.; Svedberg, E. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    1998-10-01

    Cerebral calcification in children is frequently associated with systemic metabolic disease. We present a case of ``marble brain syntrome``, which showed this abnormality. (orig.) (orig.) With 2 figs.

  4. Mucinous tubular and spindle cell carcinoma of kidney: A rare case report and review of the literature

    Geramizadeh Bita

    2009-10-01

    Full Text Available Low grade mucinous tubular and spindle cell carcinoma of kidney was newly established as a distinct renal cell carcinoma in the World Health Organization (WHO classification of 2004. Until now, less than 60 cases have been reported and the largest series represented approximately 15 patients with this type of tumor. Herein, we report a case of mucinous tubular and spindle cell carcinoma in a 63-year-old male presented with right flank pain which was diagnosed after nephrectomy. Pathologists should consider this diagnosis and its spectrum of histopathologic features in mind to ensure an accurate diagnosis.

  5. Transition of organizational category on renal cancer.

    Nagashima, Yoji; Kuroda, Naoto; Yao, Masahiro

    2013-03-01

    The incidence of kidney cancer is gradually increasing, with a rate of 2-3% per decade. The kidney develops various kinds of neoplasms, some of which are associated with familial cancer syndromes. Such cases have provided clues to identify the cancer-responsible genes. In 2004, the World Health Organization published a new classification system of renal neoplasms, incorporating recent knowledge obtained in the cytogenetic and molecular biological fields, i.e. genes responsible for each histologic subtype (von Hippel-Lindau for clear cell renal cell carcinoma, c-met for papillary renal cell carcinoma type 1, etc.). Subsequently, the Japanese classification system in 'the General Rule for Clinicopathological Study of Renal Cell Carcinoma' has been revised as the 4th edition, according to the World Health Organization system. Several novel subtypes have been introduced, i.e. mucinous tubular and spindle cell carcinoma, and Xp11.2/TFE3 translocation-associated renal cell carcinoma. Even after the publication of the classification, other novel subtypes have emerged, i.e. acquired cystic disease-associated renal cell carcinoma and tubulocystic renal cell carcinoma. Additionally, some of the subtypes seem to form families based on morphological transition, immunohistochemical features and gene expression profile. In future, the classification of renal cell carcinoma should be reorganized on the basis of molecular biological characteristics to establish personalized therapeutic strategies. PMID:23390307

  6. Tubular localization and expressional dynamics of aquaporins in the kidney of seawater-challenged Atlantic salmon

    Engelund, Morten Buch; Madsen, Steffen S

    2015-01-01

    Most vertebrate nephrons possess an inherited ability to secrete fluid in normal or pathophysiological states. We hypothesized that renal aquaporin expression and localization are functionally regulated in response to seawater and during smoltification in Atlantic salmon and thus reflect a shift in...... renal function from filtration towards secretion. We localized aquaporins (Aqp) in Atlantic salmon renal tubular segments by immunohistochemistry and monitored their expressional dynamics using RT-PCR and immunoblotting. Three aquaporins: Aqpa1aa, Aqp1ab and Aqp8b and two aquaglyceroporins Aqp3a and Aqp....... Aqp10b was expressed apically and along the lateral membrane. Aqp8b was mainly basolateral and Aqp1ab was located in sub-apical intracellular compartments. mRNAs of aqp8b and aqp10b were higher in FW smolts compared to FW parr, whereas the opposite was true for aqp1aa. Aqp mRNA levels changed in...

  7. Risk factors for mortality in children with diabetic keto acidosis from developing countries

    Varadarajan; Poovazhagi

    2014-01-01

    Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.

  8. The effect of surgery on the renal excretion of beta 2-microglobulin.

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  9. Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice

    Fern, Robert J.; Yesko, Christine M.; Thornhill, Barbara A.; Kim, Hyung-Suk; Smithies, Oliver; Chevalier, Robert L.

    1999-01-01

    A novel approach was employed to assess the contribution of the renin-angiotensin system (RAS) to obstructive nephropathy in neonatal mice having zero to four functional copies of the angiotensinogen gene (Agt). Two-day-old mice underwent unilateral ureteral obstruction (UUO) or sham operation; 28 days later, renal interstitial fibrosis and tubular atrophy were quantitated. In all Agt genotypes, UUO reduced ipsilateral renal mass and increased that of the opposite kidney. Renal interstitial c...

  10. Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia

    Heemskerk, Suzanne; van Koppen, Arianne; van den Broek, Luc; Poelen, Geert J. M.; Wouterse, Alfons C; Dijkman, Henry B. P. M.; Russel, Frans G. M.; Masereeuw, Rosalinde

    2007-01-01

    Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS−). After LPS+, proximal tubular damage and a reduction in renal...

  11. Vitamin D Receptor Attenuates Renal Fibrosis by Suppressing the Renin-Angiotensin System

    Zhang, Yan; Kong, Juan; Dilip K. Deb; Chang, Anthony; Li, Yan Chun

    2010-01-01

    Analogs of vitamin D attenuate renal injury in several models of kidney disease, but the mechanism underlying this renoprotective effect is unknown. To address the role of the vitamin D receptor (VDR) in renal fibrogenesis, we subjected VDR-null mice to unilateral ureteral obstruction for 7 days. Compared with wild-type mice, VDR-null mice developed more severe renal damage in the obstructed kidney, with marked tubular atrophy and interstitial fibrosis. Significant induction of extracellular ...

  12. Mixed organic solvents induce renal injury in rats.

    Weisong Qin

    Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  13. Genetics Home Reference: tubular aggregate myopathy

    ... M, Laporte J. Constitutive activation of the calcium sensor STIM1 causes tubular-aggregate myopathy. Am J Hum ... personal health condition should consult with a qualified healthcare professional . About Genetics Home Reference Site Map Contact ...

  14. Iatrogenic Digital Compromise with Tubular Dressings

    Corre, Kenneth A

    2009-08-01

    Full Text Available Objective: This case report describes a digit amputation resulting from an improperly applied tubular dressing. The safe application of digital tubular dressings, and the rationale behind it, is detailed to raise emergency physician (EP awareness.Methods: We present a case report of a recent iatrogenic-induced digit ischemia caused by improperly applied tube gauze. We review the literature on the subject and the likely sources of poor outcomes presented. The proper application of tubular gauze dressings is then outlined.Conclusion: EPs and emergency department personnel must be educated on the safe application of tubular gauze dressings to avoid dire outcomes associated with improper applications.[WestJEM. 2009;10:190-192.

  15. RENAL CRYOABLATION

    A. V. Govorov

    2014-08-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  16. Renal liposarcoma

    Diogo A.L. Bader

    2004-06-01

    Full Text Available INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations after a 4-year follow-up. COMMENTS: Renal liposarcoma is a rare tumor. We report one case incidentally diagnosed during a routine pre-transplantation assessment in renal donor.

  17. Adult renal cystic disease: a genetic, biological, and developmental primer.

    Katabathina, Venkata S; Kota, Gopi; Dasyam, Anil K; Shanbhogue, Alampady K P; Prasad, Srinivasa R

    2010-10-01

    Renal cystic diseases in adults are a heterogeneous group of disorders characterized by the presence of multiple cysts in the kidneys. These diseases may be categorized as hereditary, acquired, or developmental on the basis of their pathogenesis. Hereditary conditions include autosomal dominant polycystic kidney disease, medullary cystic kidney disease, von Hippel-Lindau disease, and tuberous sclerosis. Acquired conditions include cystic kidney disease, which develops in patients with end-stage renal disease. Developmental cystic diseases of the adult kidney include localized renal cystic disease, multicystic dysplastic kidney, and medullary sponge kidney. In recent years, many molecular and cellular mechanisms involved in the pathogenesis of renal cystic diseases have been identified. Hereditary renal cystic diseases are characterized by genetic mutations that lead to defects in the structure and function of the primary cilia of renal tubular epithelial cells, abnormal proliferation of tubular epithelium, and increased fluid secretion, all of which ultimately result in the development of renal cysts. A better understanding of these pathophysiologic mechanisms is now providing the basis for the development of more targeted therapeutic drugs for some of these disorders. Cross-sectional imaging provides useful information for diagnosis, surveillance, prognostication, and evaluation of treatment response in renal cystic diseases. PMID:21071372

  18. Markers of acidosis and stress in a sprint versus a conducted electrical weapon.

    Ho, Jeffrey D; Dawes, Donald M; Nystrom, Paul C; Collins, Donal P; Nelson, Rebecca S; Moore, Johanna C; Miner, James R

    2013-12-10

    Both profound acidosis and catecholamine excess have been proposed as underlying physiologic derangements in subjects at high risk for arrest related death (ARD). In this study, the objective was to determine a level of physical exertion that is "equivalent" in terms of levels of acidosis and catecholamines to a "standard" TASER X26 exposure. Data were collected on subjects who underwent a 5-s TASER X26 exposure or a sprint of variable distances during a law enforcement training exercise. Our results show that levels of acidosis and catecholamines are less among subjects exposed to the TASER X26 than among subjects who sprinted 20 yards or more. PMID:24314505

  19. Thermal CFD Analysis of Tubular Light Guides

    Ondřej Šikula; Jitka Mohelníková; Josef Plášek

    2013-01-01

    Tubular light guides are applicable for daylighting of windowless areas in buildings. Despite their many positive indoor climate aspects they can also present some problems with heat losses and condensation. A computer CFD model focused on the evaluation of temperature distribution and air flow inside tubular light guides of different dimensions was studied. The physical model of the tested light guides of lengths more than 0.60 m proves shows that Rayleigh numbers are adequate for a turbulen...

  20. Effect of FUT8 on megalin and albumin over load - induced MCP expression in renal tubular epithelial cell%FUT8对megalin功能及白蛋白负荷致肾小管上皮细胞单核细胞趋化蛋白1表达的影响

    王大鹏; 林洪丽; 郑美洁; 谢华; 沈楠; 孙艳玲

    2011-01-01

    [目的]探讨α1-6-岩藻糖基转移酶(α1-6-fucosyltransferase,FUT8)所催化的核心岩藻糖基化对低密度脂蛋白受体相关蛋白-2(LRP-2,meglain)内吞白蛋白功能和对白蛋白超负荷诱导的肾小管上皮细胞炎症的影响.[方法]用10 mg/mL的牛血清白蛋白(BSA)孵育HK-2细胞4 h建立白蛋白超负荷细胞模型,分别用FUT8siRNA或FUT8过表达载体转染,用流式细胞仪测定白蛋白的绑定和内吞以及megalin的核心岩藻糖基化水平.用免疫印迹、免疫沉淀和凝集素印迹方法测定单核细胞趋化蛋白-1(MCP-1)及megalin的蛋白表达,用单因素方差检验方法进行统计学处理.[结果]BSA的绑定和内吞有时间和浓度依赖性.BSA诱导后HK-2细胞FUT8、MCP-1明显升高.白蛋白超负荷条件下,FUT8过表达组细胞MCP-1表达水平明显高于BSA组.此外,FUT8的过表达显著提高megalin的核心岩藻糖基化水平及绑定和内吞白蛋白能力.沉默FUT8基因降低megalin的核心岩藻糖基化及绑定、内吞白蛋白能力,同时抑制MCP-1的升高,使其保持在正常表达水平.[结论]核心岩藻糖基化是megalin发挥白蛋白绑定和内吞功能的必需过程,抑制megalin蛋白合成后的核心岩藻糖基化修饰能够减轻蛋白超负荷诱导的肾小管上皮细胞炎症介质表达.%[Objective] To investigate the role of core fucosylation in megalin- mediated binding and endocytosis as well as its effect on albumin overload - induced renal tubular epithelia. [ Methods ] An albumin overload cell model of HK - 2 cell was constructed with 10 mg/mL BSA,and then FUT8siRNA or FUT8 over- expression vector was transfected into the cells. The binding and endocytosis of BSA and the core fucose on megalin were determined by flow - cytometry. The expression of MCP - 1 and megalin were detected with western blot, immunoprecipitation and lectin blot. Data were assessed by ANOVA analysis. [Results] Both of binding and endocytosis for BSA were time

  1. NLRP3炎性小体在高糖诱导大鼠肾小管上皮细胞炎性反应中的变化%The changes of NLRP3 inflammasome in the high glucose-induced inflammatory response of rat renal tubular epithelial cells

    赵宏宇; 李荣山; 于为民; 乔玉峰; 王卫; 冯娟; 郝洁芦; 邵珊

    2013-01-01

    Objective To investigate the expressions of NLRP3 inflammasome and inflammatory factor protein in the high glucose-induced rat renal tubular epithelial cells (NRK-52E) and to make clear its effect on inflammatory damage through transfection of small interfering RNA (siRNA).Methods (1)The NRK-52E cells were divided into control group and high glucose (HG) 6,12,24 and 48 h groups.Western blotting was adopted to detect the protein expressions of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1.(2) NRK-52E cells were divided into the control group,high glucose group,HG+NLRP3-siRNA group,and HG+irrespective siRNA group on the basis of the result of above-mentioned tests.After 48 h fostering,the expression of NLRP3 mRNA was detected by RT-PCR,and the expressions of NLRP3,ASC,IL-1β,IL-6,and TNF-a proteins were determined by Western blotting.Results (1) The expressions of NLRP3 and ASC were gradually increased,and the highest expression was in the 48 h group after stimulation by high glucose (P<0.05) ; the expression of caspase-1 was significantly higher than that in the control group (P<0.05).(2) Compared with the control group,the expressions of NLRP3,ASC,IL-1β,IL-6,and TNF-a proteins were significandy increased in the HG group (P < 0.05); these expressions in the HG + NLRP3-siRNA group were significantly decreased than those in the HG groups (P<0.05).Conclusion High glucose induces the activation of NLRP3 inflammasome in the NRK-52E cells,leading to the expression and release of its downstream inflammatory factors.It is assumed that the NLRP3 inflammasome may be involved in the high glucose-induced inflammatory damage in NRK-52E cells.%目的 观察高糖诱导大鼠肾小管上皮细胞(NRK-52E) NLRP3炎性小体及炎症因子蛋白的表达,并通过转染NLRP3特异性小干扰质粒(siRNA)明确NLRP3炎性小体是否参与其炎症损伤. 方法 (1)将NRK-52E细胞分为对照(NC)组及高糖(HG)6、12、24、48 h

  2. Influence of focal adhesion kinase on epithelial-mesenchymal transition of human renal proximal tubular epithelial cells induced by transforming growth factor β1%黏着斑激酶在转化生长因子β1诱导的人肾小管上皮细胞转分化中的作用

    邓冰清; 朱忠华; 张春; 杨晓; 刘建社

    2009-01-01

    Western blot.Results The expression of E-cadherin mRNA and protein was markedly decreased in HK-2 cells induced by TGF-β1,and the expression of α-SMA mRNA and protein was dramatically increased.Western blot analysis demonstrated that then protein levels of FAK and p-FAK(Tyr397)were progressively increased in a time-dependent manner in response to TGF-β1 treatment in HK-2 cells.When transfected with FAK-siRNA,the FAK mRNA and protein expression was markedly inhibited with 50% and 41%.Knockdown expression of FAK led to a severe blockage of TGF-β1-induced E-cadherin suppression and α-SMA induction.Conclusions The expression of FAK is up-regulated in HK-2 cells stimulated by TGF-β1.But the EMT induced by TGF-β1 in HK-2 cells is inhibited by FAK knockdown,which suggests that FAK plays an important role in TGF-β1-induced tubular EMT and renal fibrosis.

  3. The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis.

    Galarreta, Carolina I; Forbes, Michael S; Thornhill, Barbara A; Antignac, Corinne; Gubler, Marie-Claire; Nevo, Nathalie; Murphy, Michael P; Chevalier, Robert L

    2015-05-15

    Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, the so-called swan-neck lesion (SNL), and eventual renal failure. To determine the role of oxidative stress in cystinosis, histologic sections of kidneys from C57BL/6 Ctns(-/-) and wild-type mice were examined by immunohistochemistry and morphometry from 1 wk to 20 mo of age. Additional mice were treated from 1 to 6 mo with vehicle or mitoquinone (MitoQ), an antioxidant targeted to mitochondria. The leading edge of the SNL lost mitochondria and superoxide production, and became surrounded by a thickened tubular basement membrane. Progression of the SNL as determined by staining with lectin from Lotus tetragonolobus accelerated after 3 mo, but was delayed by treatment with MitoQ (38 ± 4% vs. 28 ± 1%, P injury molecule-1 (KIM-1) nor cell death was observed. After 9 mo, clusters of proximal tubules exhibited localized oxidative stress (4-hydroxynonenal binding), expressed KIM-1, and underwent apoptosis, leading to the formation of atubular glomeruli and accumulation of interstitial collagen. We conclude that nephron integrity is initially maintained in the Ctns(-/-) mouse by adaptive flattening of cells of the SNL through loss of mitochondria, upregulation of transgelin, and thickened basement membrane. This adaptation ultimately fails in adulthood, with proximal tubular disruption, formation of atubular glomeruli, and renal failure. Antioxidant treatment targeted to mitochondria delays initiation of the SNL, and may provide therapeutic benefit in children with cystinosis. PMID:25694483

  4. 78 FR 37584 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    2013-06-21

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, Pennsylvania; Notice of Amended... workers of U.S. Steel Tubular Products, McKeesport Tubular Operations Division, a subsidiary of...

  5. Renal failure

    2009-01-01

    2009221 Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on acute tubular necrosis rats.CHEN DAN(陈丹),et al.Div of Pediatr Nephrol,Dept Pediatr,2nd Xiangya Hosp Central South Univ,Changsha 410011,Chin J Nephrol,2009;25(3):191-197.

  6. Sequential Scintigraphy in Renal Transplantation

    Based on experience gained from more than 1600 patients with proved or suspected kidney diseases and on results on extended studies with dogs, sequential scintigraphy was performèd after renal transplantation in dogs. After intravenous injection of 500 μCi. 131I-Hippuran scintiphotos were taken during the first minute with an exposure time of 15 sec each and thereafter with an exposure of 2 min up to at least 16 min.. Several examinations were evaluated digitally. 26 examinations were performed on 11 dogs with homotransplanted kidneys. Immediately after transplantation the renal function was almost normal arid the bladder was filled in due time. At the beginning of rejection the initial uptake of radioactive Hippuran was reduced. The intrarenal transport became delayed; probably the renal extraction rate decreased. Corresponding to the development of an oedema in the transplant the uptake area increased in size. In cases of thrombosis of the main artery there was no evidence of any uptake of radioactivity in the transplant. Similar results were obtained in 41 examinations on 15 persons. Patients with postoperative anuria due to acute tubular necrosis showed still some uptake of radioactivity contrary to those with thrombosis of the renal artery, where no uptake was found. In cases of rejection the most frequent signs were a reduced initial uptake and a delayed intrarenal transport of radioactive Hippuran. Infarction could be detected by a reduced uptake in distinct areas of the transplant. (author)

  7. Renal involvement in dogs with babesiosis

    R.G. Lobetti

    2001-07-01

    Full Text Available Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium, fractional clearance of sodium (FcNa and potassium (FcK, urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n =10 and 3 groups of babesiosis cases were studied: mild uncomplicated (n =10, severe uncomplicated (n = 11, and complicated (n = 9. All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serumelectrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant

  8. Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists

    Lucia, A.; Hoyos, J; Santalla, A; Perez, M; Carvajal, A.; Chicharro, J.

    2002-01-01

    Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists.

  9. Improving the welfare of dairy goats: Feeding behaviour identifies goats at risk of subacute rumen acidosis

    Giger-Reverdin, Sylvie; Sauvant, Daniel; Duvaux-Ponter, Christine

    2013-01-01

    Main messages: Feeding behaviour is highly variable between animals. Feeding behaviour modifies rumen pH pattern and occurrence of subacute ruminal acidosis (SARA). Avoiding SARA increases animal welfare, milk production and therefore farm profit - ability.

  10. Correlation of immunosuppression scheme with renal graft complications detected by dynamic renal scintigraphy

    Dynamic renal scintigraphy allows the diagnosis of complications in patients submitted to organ transplantation, such as perfusion abnormalities, acute tubular necrosis and rejection. In this study we employed 99m Tc-DTPA scintigraphy to study patients submitted to kidney transplantation. The results obtained and the clinical findings were conjunctively analyzed in order to detect graft rejection or other complications. The type of immunosuppressive scheme used was also correlated with the observed complications. Fifty-five patients submitted to kidney transplantation from 1989 to 1999 were evaluated. All patients with nephrotoxicity received a 3-drug immunosuppressive scheme. In this study, acute rejection was the most frequent complication (40.4%) observed following transplantation. Thirteen of 15 recipients of cadaveric kidney grafts presented acute tubular necrosis. Only one false-positive case was observed when scintigraphy and clinical findings were not concordant. We suggest carrying out renal scintigraphy to follow-up post-transplantation patients. (author)

  11. On the method for calculating unilateral renal clearance using 99mTc-MAG3 renal uptake ratio

    It has been reported that the renal clearance of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), a newly developed 99mTc-labeled renal tubular agent, effectively reflects renal plasma flow and serves as a useful parameter of renal function. In this study, we investigated on the method for calculating unilateral renal clearance of 99mTc-MAG3 using renal uptake ratio (RUR) and the conversion formula between RUR and renal clearance. Renography by 99mTc-MAG3 was performed in 38 cases with various renal functions and the renal clearance was estimated by three reported methods of one-point-venous-sampling. The results by Bubeck method were most consistent with the individual clinical data. The difference in the methodology of sample measurement or the type of scintillation camera did not affect the values of RUR. The correlation between renal clearance and RUR was not significantly different among the three groups of data acquisition time for RUR, i.e., 1-2 min., 1.5-2.5 min., and 2-3 min. after tracer injection. In summary, Bubeck method and RUR between 1-3 min. after injection seems to be suitable for the establishment or the conversion formula. Using this formula unilateral renal clearance of 99mTc-MAG3 could be reliably estimated without venous sampling. (author)

  12. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Siddhesh Prabhavalkar

    2013-01-01

    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  13. Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes

    Hommel, Eva; Friberg, Lars; Mølvig, Jens;

    2010-01-01

    Increased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients...... with type 2 diabetes and normal or increased UOER....

  14. [Renal elastography].

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  15. Thermal CFD Analysis of Tubular Light Guides

    Ondřej Šikula

    2013-12-01

    Full Text Available Tubular light guides are applicable for daylighting of windowless areas in buildings. Despite their many positive indoor climate aspects they can also present some problems with heat losses and condensation. A computer CFD model focused on the evaluation of temperature distribution and air flow inside tubular light guides of different dimensions was studied. The physical model of the tested light guides of lengths more than 0.60 m proves shows that Rayleigh numbers are adequate for a turbulent air flow. The turbulent model was applied despite the small heat flux differences between the turbulent and laminar model. The CFD simulations resulted into conclusions that the growing ratio of length/diameter increases the heat transmission loss/linear transmittance as much as by 50 percent. Tubular light guides of smaller diameters have lower heat transmission losses compared to the wider ones of the same lengths with the same outdoor temperature being taken into account. The simulation results confirmed the thermal bridge effect of the tubular light guide tube inside the insulated flat roof details. The thermal transmittance of the studied light guides in the whole roof area was substituted with the point thermal bridges. This substitution gives possibility for simple thermal evaluation of the tubular light pipes in roof constructions.

  16. Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

    F. Habarou

    2015-03-01

    Full Text Available Pyruvate carboxylase (PC is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A. Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1 and type B (patient 2. Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.

  17. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  18. Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules.

    Kato, Kohtaro; Morita, Ikuo

    2011-08-01

    Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large osteoclast or TRAP+LMNC formation was observed far more in an acidosis environment than in a physiologically neutral environment. One of the major action points of acidosis was determined to be located in the last phase of preosteoclast differentiation using a co-culture system and a soluble RANKL-dependent bone marrow cell culture system. On-going osteoclast formation in an acidosis environment markedly deteriorated when the medium was replaced with physiologically neutral medium within the first 6h; however, bone marrow cells previously stimulated in an acidosis environment for 9h differentiated into TRAP+LMNC in pH 7.4 medium. Messenger RNA (mRNA) expression levels of DC-STAMP, a key molecule in cell fusion, and NFATc1 did not increase in the acidosis environment compared with those under physiologically neutral conditions. Ruthenium red, a general TRP antagonist, deteriorated acidosis-promoted TRAP+LMNC formation. 4-Alpha-PDD, a TRPV4-specific agonist, added in the last 21 h of preosteoclast differentiation, potentiated TRAP+LMNC formation in a mild acidosis environment, showing synergism between TRPV4 activation and acidosis. RN1734, a TRPV4-specific antagonist, partly inhibited acidosis-promoted TRAP+LMNC formation. We thus narrowed down the major action points of acidosis in osteoclast formation and elucidated the characteristics of this system in detail. Our results show that acidosis effectively uses TRPV4 to drive large-scale cell fusion and also utilizes systems independently of TRPV4. PMID:21575626

  19. Renal cell carcinoma: Evolving and emerging subtypes.

    Crumley, Suzanne M; Divatia, Mukul; Truong, Luan; Shen, Steven; Ayala, Alberto G; Ro, Jae Y

    2013-12-16

    Our knowledge of renal cell carcinoma (RCC) is rapidly expanding. For those who diagnose and treat RCC, it is important to understand the new developments. In recent years, many new renal tumors have been described and defined, and our understanding of the biology and clinical correlates of these tumors is changing. Evolving concepts in Xp11 translocation carcinoma, mucinous tubular and spindle cell carcinoma, multilocular cystic clear cell RCC, and carcinoma associated with neuroblastoma are addressed within this review. Tubulocystic carcinoma, thyroid-like follicular carcinoma of kidney, acquired cystic disease-associated RCC, and clear cell papillary RCC are also described. Finally, candidate entities, including RCC with t(6;11) translocation, hybrid oncocytoma/chromophobe RCC, hereditary leiomyomatosis and RCC syndrome, and renal angiomyoadenomatous tumor are reviewed. Knowledge of these new entities is important for diagnosis, treatment and subsequent prognosis. This review provides a targeted summary of new developments in RCC. PMID:24364021

  20. Hypokalemic paralysis associated with cystic disease of the kidney: case report

    Jayasinghe Saroj

    2011-04-01

    Full Text Available Abstract Background Severe hypokalemia is known to cause muscle paralysis, and renal tubular acidosis is a recognized cause. Cystic disease of the kidney is associated with severe hypokalemia. Case presentation We report a 33-year-old male patient who presented with generalized limb weakness caused by severe hypokalemia due to renal tubular acidosis, who was found to have renal medullary cysts. Conclusion The association of cystic renal disease with hypokalemia, and the possible pathophysiological basis of the development of renal cysts in patients with severe hypokalemia, are discussed.

  1. Radiation-induced changes in the kinetics of glomerular and tubular cells in the pig kidney

    Both kidneys of 13 mature female Large White pigs were irradiated with a single dose of 9.8 Gy 60Co γ rays. The pigs were killed serially between 2 to 24 weeks after irradiation. One hour prior to sacrifice bromodeoxyuridine (BrdU) (500 mg/pig) was injected intravenously. At postmortem the kidneys were removed and tissue was taken to prepare cell suspensions. The labeling index (LI) of these suspensions was determined using flow cytometry. In vivo BrdU incorporation in tubular and glomerular cells was determined immunohistochemically. The kinetics of glomerular and tubular cells was evaluated by counting the number of labeled cells/glomerules and the number of labeled tubular cells/fields of view. An average of 1200 glomeruli and 1500 fields of view/time were counted. Similar analyses were performed on renal tissue from unirradiated control animals. Flow cytometry revealed rapid and significant increases in the LI of kidney cells; 2 weeks after irradiation the LI increased from a control value of 0.18 ± 0.01 to 1.23 ± 0.22% (P < 0.001). By 4 weeks the maximal value of 2.45 ± 0.36% was seen; the LI then declined progressively but at 24 weeks after irradiation still remained significantly above control values (P < 0.001). A similar pattern of response was determined by counting the laveled glomerular and tubular cells identified immunohistochemically. However, the increase in labeled glomerular cells occurred 2 weeks after irradiation, whereas that for the tubules occurred 4 weeks after irradiation. These findings indicate that irradiation of the kidney, classically regarded as a open-quotes late-respondingclose quotes organ, is associated with rapid and significant changes in the kinetics of both tubular and glomerular cells. 28 refs., 4 figs

  2. Osteodistrofia renal

    Teles, Tobias José Freitas Trindade

    2014-01-01

    A doença renal crónica é um problema de saúde mundial, com incidência e prevalência crescentes. Apesar dos avanços científicos na compreensão da patogénese e o desenvolvimento de terapêuticas mais eficazes, a osteodistrofia renal continua a ser uma complicação importante nos doentes renais crónicos. A osteodistrofia renal abrange um espectro diverso de alterações ósseas nos doentes com doença renal crónica, classificada histologicamente por lesões de elevada ou baixa taxa de remodelação ó...

  3. Renal failure

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  4. Renal failure

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  5. Renal failure

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  6. Renal liposarcoma

    Diogo A.L. Bader; Luis A.B. Peres; Sérgio L. Bader

    2004-01-01

    INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations...

  7. Tubular solid oxide fuel cell current collector

    Bischoff, Brian L.; Sutton, Theodore G.; Armstrong, Timothy R.

    2010-07-20

    An internal current collector for use inside a tubular solid oxide fuel cell (TSOFC) electrode comprises a tubular coil spring disposed concentrically within a TSOFC electrode and in firm uniform tangential electrical contact with the electrode inner surface. The current collector maximizes the contact area between the current collector and the electrode. The current collector is made of a metal that is electrically conductive and able to survive under the operational conditions of the fuel cell, i.e., the cathode in air, and the anode in fuel such as hydrogen, CO, CO.sub.2, H.sub.2O or H.sub.2S.

  8. Early segmental changes in ischemic acute tubular necrosis of the rat kidney

    Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor; Holstein-Rathlou, N.-H.

    2004-01-01

    subsequent freeze-substitution in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted...... tubule versus the subsequent loops. The distribution of the structural lesions is in accordance with the previously reported presence of a tubulo-capillary counter-current flow in the proximal convoluted tubule and, when related to the highly variable oxygen tension in the normal renal cortex of the rat...

  9. Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

    Kim, Sejoong; Yang, Jin Young; Jung, Eun Sook; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Na, Ki Young; Han, Jin Suk

    2014-01-01

    Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham ...

  10. Renal function studies with radioisotopes: an appraisal

    The use of radioisotopes in renal disorders has grown out of the development of scintillation detectors and gamma cameras and the availability of appropriate radioactive pharmaceuticals. It is now time to approach these studies from a different point of view. What further information would the practising nephrologist or urologist, physician or surgeon like to know about patients' kidney function that is not easily obtainable by non-radioactive methods. He would like a simple and reliable measurement of individual renal function; a test to demonstrate the presence or absence of obstruction in a patient with oliguria or uraemia; some help as to whether nephrectomy or a more difficult restorative operation is better for the patient with hydronephrosis, calculus or renal artery stenosis; a measure of the degree to which an obstructive uropathy is causing an obstructive nephropathy; clarification of which kidney to operate upon first when bilateral obstructive nephropathy presents with uraemia; a quantitative index of the progress following an operation to relieve an outflow system disorder; a screening procedure for renal disorders in the hypertensive and other populations; a prognostic guide to the likely evolution of glomerulonephritis and pyelonephritis, a prediction of the onset of rejection in the renal transplant, particularly in the presence of acute tubular necrosis. This review attempts to define the extent to which renal function studies with radioisotopes meet or fail to meet these needs and to indicate areas for potential development. (author)

  11. Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome

    Cherif, Eya; Ben Hassine, Lamia; Kechaou, Ines; Khalfallah, Narjess

    2013-01-01

    Hypokalaemic rhabdomyolysis represents a medical emergency requiring rapid diagnosis and appropriate aetiological treatment. Renal tubular acidosis is a common cause of hypokalemia which can be idiopathic or secondary to systemic disorders such as Sjogren's syndrome. It can remain asymptomatic or manifest with metabolic abnormalities including hypokalemia paralysis, hypocalcaemia and hyperchloremic metabolic acidosis. Rhabdomyolysis presenting with severe hypokalemia as the first manifestatio...

  12. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  13. Renal effects of amino acids and dopamine in renal transplant recipients treated with or without cyclosporin A

    Hansen, J M; Olsen, Niels Vidiendal; Leyssac, P P

    1996-01-01

    cyclosporin A group by 31.0 +/- 4.1% and 35.9 +/- 6.6%, respectively, during infusion of dopamine, and by 18.7 +/- 6.7% and 13.9 +/- 5.3%, respectively, during infusion of amino acids. Glomerular filtration rate increased significantly in the non-cyclosporin A group and cyclosporin A group by 15.7 +/- 3...... proximal and distal tubular handling of sodium (and water) were comparable between the two groups of patients. Dopamine caused significant natriuresis in both groups. 5. In conclusion, low-dose cyclosporin A seems not to attenuate the renal haemodynamic and tubular response to infusions of amino acids and...

  14. Tubular Membrane Plant-Growth Unit

    Dreschel, Thomas W.

    1992-01-01

    Hydroponic system controls nutrient solution for growing crops in space. Pump draws nutrient solution along inside of tubular membrane in pipe from reservoir, maintaining negative pressure in pipe. Roots of plants in slot extract nutrient through membrane within pipe. Crop plants such as wheat, rice, lettuce, tomatoes, soybeans, and beans grown successfully with system.

  15. Work tool in a tubular element

    The stand, which is positioned in relation with the tubular element, has clutch disengagement means for a working rod in rotation, with at least two positioning regions on the rod. Application for laser welding a sleeve into PWR steam generator tubes

  16. Tubular spring slip joint and jar

    The present invention comprises a pressure balanced tubular spring slip-joint and jar including a generally tubular outer housing having longitudinal slot means in the wall thereof, and a hammer area of increased wall thickness at one end thereof, within which housing slidably extends a jar mandrel means having first and second longitudinally spaced enlarged diameter anvil areas, at least one fastener tapped into one of those anvil areas, the heads of said fastener protruding into said slot means. Both said housing and said mandrel means possesses axial bores therethrough, which are placed in communication via the bore of a tubular spring within the housing, whereby during extension and contraction of the slip-joint and jar means of the present invention the area within said axial bores and said spring bore is of a constant volume. The invention may be employed to provide force impulses in either longitudinal direction, said tubular spring aiding the application of those impulses when said housing and said mandrel means move relatively toward each other. By proper selection of spring length and use of a coiled spring having spaced coils, the present invention may also be employed as a bi-directional shock absorber

  17. Tubular spring slip joint and jar

    Heemstra, T. R.

    1985-04-23

    The present invention comprises a pressure balanced tubular spring slip-joint and jar including a generally tubular outer housing having longitudinal slot means in the wall thereof, and a hammer area of increased wall thickness at one end thereof, within which housing slidably extends a jar mandrel means having first and second longitudinally spaced enlarged diameter anvil areas, at least one fastener tapped into one of those anvil areas, the heads of said fastener protruding into said slot means. Both said housing and said mandrel means possesses axial bores therethrough, which are placed in communication via the bore of a tubular spring within the housing, whereby during extension and contraction of the slip-joint and jar means of the present invention the area within said axial bores and said spring bore is of a constant volume. The invention may be employed to provide force impulses in either longitudinal direction, said tubular spring aiding the application of those impulses when said housing and said mandrel means move relatively toward each other. By proper selection of spring length and use of a coiled spring having spaced coils, the present invention may also be employed as a bi-directional shock absorber.

  18. Effect of sodium bicarbonate administration on mortality in patients with lactic acidosis: a retrospective analysis.

    Hyun Jeong Kim

    Full Text Available BACKGROUND: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. METHODS: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. RESULTS: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6% died from sepsis (61.4%, hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006, catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016 was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B = 1.72, 95% CI = 1.12-2.63, p = 0.013 and sodium bicarbonate administration (Exp (B = 6.27, 95% CI = 1.10-35.78, p = 0.039. CONCLUSIONS: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate

  19. Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

    F.H.D. González

    2010-12-01

    Full Text Available Ruminal acidosis is a frequent disorder that occurs in goats as a consequence of feedingmistakes in animals not adapted to a diet of easily fermentable carbohydrates. The subacuteform of the disease is difficult to diagnose because no apparent signs are shownand the acid-base parameters may remain within the normal range. The present studyaimed at testing the hypothesis that haptoglobin (Hp and serum amyloid A (SAA,the two major acute phase proteins in ruminants, may be useful as markers of subacuteacidosis in goats.A subacute acidosis was induced in six Murciano-Granadina goats through a diet of60% mixed feed-40% alfalfa hay offered during 5 days to goats not adapted to eatmixed feed. Two goats were rumen-fistulated to investigate the effect of feeding onruminal pH. Sampling of blood and urine of all animals was done before the inductionof the acidosis, during 5 days after the onset of induction and for 18 days after theinduction (recovery period.Ruminal pH in the fistulated goats dropped to less than 5.5 during the inductionperiod, and half of the goats had diarrhea on the third day after the induction of acidosis.Acid-base parameters showed that the acid-base compensatory mechanisms wereefficient in maintaining the equilibrium. Serum Hp had a moderate increase duringthe induction period, while SAA did not change. These results suggest that Hp mightbe a potential marker for ruminal acidosis in goats.

  20. Assessment of glomerular filtration rate and effective renal plasma flow in cystic fibrosis

    A study was conducted to examine renal function in 10 healthy control subjects and eight patients with cystic fibrosis in stable condition. Sequential bolus injections of /sup 99m/Tc-DTPA and 125I-OIH were administered to assess glomerular filtration rate and effective renal plasma flow, respectively. Blood was subsequently collected for 3 hours, and urine for 24 hours. Renal clearances of both radioisotope markers were virtually identical in patients and controls. Inasmuch as neither glomerular filtration rate nor effective renal plasma flow was enhanced in patients with cystic fibrosis, increased clearance of drugs in these patients is unlikely to be the result of enhanced glomerular filtration or tubular secretion

  1. Vibration analysis of ultrasonic tubular resonators

    LIANG Zhaofeng; MO Xiping; ZHOU Guangping

    2012-01-01

    The frequency equation of the axisymmetric coupled vibration of a ultrasonic tubular resonator with both ends free is derived by an exact solution method, based on classical Fliigge thin shell theory. The dependence of the dimensionless frequency Ω on the ratio of length to radius 1/a, the ratio of radius to thickness a/h and Poisson's ratio v is investigated, and the axisymmetric coupled vibration of the ultrasonic tubular resonator with both ends shear diaphragm is compared with that with both ends free. The accuracy of two-dimensional and three-dimensional apparent elasticity method is also assessed by the comparison with the exact solution method. Finally, the mode shapes of the ultrasonic tubular resonator are calculated by the exact solution method, and its transform efficient is analyzed. The results show that as for two boundary conditions of both ends free and both ends shear diaphragm, the difference of the effect of the boundary conditions on the dimensionless frequency of the axisymmetric coupled vibration of the ultrasonic tubular resonator becomes smaller as l/a increases, and the larger a/h, the smaller the difference. Moreover, for free-free boundary conditions, the change of a/h has nearly no effect on the dimensionless frequency of the thin tubular resonator usually considered to mean a/h 〉 10. Purthermore, the dimensionless frequency Ω decreases as v in- creases for a given l/a, and the impact of v on Ω is different for different l/a, and the maximum impact will appear when l/a = π. Finally, the study also shows the three-dimensional apparent elasticity method has very high accuracy.

  2. In vivo and in vitro analysis of age-associated changes and somatic cellular senescence in renal epithelial cells.

    Birgit Berkenkamp

    Full Text Available Acute kidney injury is a major clinical problem and advanced age is associated with ineffective renal regeneration and poor functional outcome. Data from kidney injury models suggest that a loss of tubular epithelial proliferation contributes to a decrease in renal repair capacity with aging, but aging can also lead to a higher severity of inflammation and damage which may influence repair. In this study we tested intrinsic age-dependent changes in tubular epithelial proliferation in young and old mice, by injecting low-dose lead acetate as a non-injurious mitogen. In parallel, we explored in vitro techniques of studying cellular senescence in primary tubular epithelial cells (PTEC. Lead acetate induced tubular epithelial proliferation at a significantly higher rate in young as compared to old mice. Old kidneys showed significantly more senescence as demonstrated by increased p16 (INK4a, senescence associated β-galactosidase, and γH2AX(+/Ki-67(- cells. This was paralleled in old kidneys by a higher number of Cyclin D1 positive tubular cells. This finding was corroborated by a positive correlation between Cyclin D1 positivity and age in human renal biopsies. When tubular cells were isolated from mouse kidneys they rapidly lost their age-associated differences under culture conditions. However, senescence was readily induced in PTEC by γ-irradiation representing a future model for study of cellular senescence in the renal epithelium. Together, our data indicate that the tubular epithelium of aged kidney has an intrinsically reduced proliferative capacity probably due to a higher load of senescent cells. Moreover, stress induced models of cellular senescence are preferable for study of the renal epithelium in vitro. Finally, the positive correlation of Cyclin D1 with age and cellular senescence in PTEC needs further evaluation as to a functional role of renal epithelial aging.

  3. Nuclear medicine in the management of renal vein thrombosis post renal transplantation - a case study

    Renal scintigraphy allows the assessment of both perfusion and function of the transplanted kidney. Treatment of renal dysfunction depends on its cause. Nuclear medicine plays an important role in determining the cause of renal dysfunction, thereby providing appropriate intervention. Renal vein thrombosis (RVT) is a rare occurrence (1-2%) in renal transplants, and constitutes a surgical emergency. Early detection of RVT is critical in order to prevent infarction and subsequent loss of the graft. A 43-year-old woman with end stage renal disease as a result of diabetic nephropathy underwent transplantation of a living-related-donor kidney. The patient underwent a post operative Tc-MAG, scan that demonstrated good perfusion to the graft. Three days post-transplantation, the patient complained of acute pain and swelling. Creatinine increased from 0.13 to 0.16. and urine output decreased. The mTc-MAG, scan revealed dramatic deterioration, with absent perfusion to the kidney. Immediate allograft exploration was performed in theatre and RVT was revealed, followed by thrombectomy. A follow-up renal scan performed the next day demonstrated a viable kidney with improved but patchy perfusion throughout, indicating patchy cortical infarction as well as acute tubular necrosis. On day 19. the patient again complained of severe pain over the graft, and the 99mTc-MAG, scan again revealed absent perfusion, this time with residual function. Further surgical exploration confirmed re-thrombosis of the renal vein, and subsequent genetic analysis revealed that the patient had a rare mutation of her clotting Factor V gene, leading to an increased thrombogenic tendency. Following full anticoagulation, the patient was finally discharged on day 58. This case illustrates a rare case of renal allograft infarction secondary to renal vein thrombosis. The ability of nuclear medicine to provide immediate functional information helped confirm the diagnosis, and salvage the kidney

  4. Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells

    González-Guerrero, Cristian, E-mail: cristian.gonzalez@fjd.es [Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Av. Reyes Católicos 2, 28040 Madrid (Spain); Ocaña-Salceda, Carlos, E-mail: carlos.ocana@fjd.es [Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Av. Reyes Católicos 2, 28040 Madrid (Spain); Berzal, Sergio, E-mail: sberzal@fjd.es [Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Av. Reyes Católicos 2, 28040 Madrid (Spain); Carrasco, Susana, E-mail: scarrasco@fjd.es [Renal and Vascular Pathology Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Av. Reyes Católicos 2, 28040 Madrid (Spain); Fernández-Fernández, Beatriz, E-mail: bfernandez@fjd.es [Nephrology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz (IIS-FJD), Av. Reyes Católicos 2, 28040 Madrid (Spain); and others

    2013-11-01

    The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed that in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity. - Highlights: • Molecular mechanisms modulating CNI renal inflammation were investigated. • Kinases, immune receptors and ER stress mediate the inflammatory response to CNIs. • Several intracellular pathways activate NF-κB in CNIs-treated tubular cells. • A NF-κB-dependent cytokine profile characterizes CNIs-induced inflammation. • CNI nephrotoxicity was associated to inflammatory

  5. Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells

    The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed that in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity. - Highlights: • Molecular mechanisms modulating CNI renal inflammation were investigated. • Kinases, immune receptors and ER stress mediate the inflammatory response to CNIs. • Several intracellular pathways activate NF-κB in CNIs-treated tubular cells. • A NF-κB-dependent cytokine profile characterizes CNIs-induced inflammation. • CNI nephrotoxicity was associated to inflammatory

  6. 78 FR 14361 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    2013-03-05

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, PA; Notice of Initiation of...) filed on December 20, 2012 on behalf of workers of U.S. Steel Tubular Products, McKeesport...

  7. Piperazine side-effects in a patient with pre-existing renal insufficiency

    Majid Malaki

    2014-01-01

    Full Text Available Piperazine as an antihelminth has many adverse effects, especially on patients with renal insufficiency. We report the use of piperazine in a girl with a moderately severe kidney disease due to Biedl Bardet syndrome. She developed coma and acute kidney injury due to acute interstitial nephritis (AIN, anemia and thrombocytopenia. The presence of fever, proteinuria, acidosis, anemia, sterile pyuria and non-oliguric renal failure strongly suggested AIN. Her problems abated mostly by discontinuing of piperazine and supportive therapy, except anemia and thrombocytopenia.

  8. [Renal disease].

    Espinosa-Cuevas, María de Los Ángeles

    2016-09-01

    Chronic renal failure in its various stages, requires certain nutritional restrictions associated with the accumulation of minerals and waste products that cannot be easily eliminated by the kidneys. Some of these restrictions modify the intake of proteins, sodium, and phosphorus. Milk and dairy products are sources of these nutrients. This article aims to inform the reader about the benefits including milk and dairy products relying on a scientific and critical view according to the clinical conditions and the stage of renal disease in which the patient is. PMID:27603894

  9. Growth hormone in chronic renal disease

    Vishal Gupta

    2012-01-01

    Full Text Available Severe growth retardation (below the third percentile for height is seen in up to one-third children with chronic kidney disease. It is thought to be multifactorial and despite optimal medical therapy most children are unable to reach their normal height. Under-nutrition, anemia, vitamin D deficiency with secondary hyperparathyroidism, metabolic acidosis, hyperphosphatemia, renal osteodystrophy; abnormalities in the growth hormone/insulin like growth factor system and sex steroids, all have been implicated in the pathogenesis of growth failure. Therapy includes optimization of nutritional and metabolic abnormalities. Failure to achieve adequate height despite 3-6 months of optimal medical measures mandates the use of recombinant GH (rGH therapy, which has shown to result in catch-up growth, anywhere from 2 cm to 10 cm with satisfactory liner, somatic and psychological development.

  10. Renal (Kidney) Manifestations in TSC

    Full Text Available ... in TSC: renal cysts, renal angiomyolipoma and renal cell carcinoma . Renal angiomyolipomata, or angiomyolipomas, are usually the ... kidney failure, requiring dialysis or transplantation. Lastly, renal cell carcinoma, the least common renal association with TSC, ...

  11. Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis

    Wang, Qian; Paulson, O B; Lassen, N A

    1993-01-01

    by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to...... block almost completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism...

  12. Identification of neonatal near miss by systematic screening for metabolic acidosis at birth

    Bonnaerens, A.; Thaens, A.; Mesens, T.; Van Holsbeke, C; E. T. M. de Jonge; Gyselaers, Wilfried

    2011-01-01

    Aims: To evaluate the relevance of systematic screening for neonatal metabolic acidosis at birth as part of perinatal audit. Methods: For every baby, born in Ziekenhuis Oost Limburg, Genk Belgium between 1/1/2010 and 31/12/2010, cord blood was analysed to diagnose metabolic acidosis, defined as arterial or venous pH ≤ 7.05 or 7.17 respectively, in association with base excess of ≤ -10 mmol/L. Three observers identified indicators for suboptimal peripartal care with likely contribution to ...

  13. Immunohistochemical changes in kidney glomerular and tubular proteins caused by rattlesnake (Crotalus vegrandis venom Cambios inmunohistoquímicos en proteínas de túbulo y glomérulo renal causadas por el veneno de la serpiente de cascabel (Crotalus vegrandis

    María E. Girón

    2003-10-01

    Full Text Available Renal damage is an important cause of death in patients who have survived the early effects of severe crotalid envenomation. Extracellular matrix of renal tissue is altered by Crotalus toxin activities. The aim of this study was to describe how cytoskeletal proteins and basal membrane components undergo substantial alterations under the action of Crotalus vegrandis crude venom and its hemorrhagic fraction (Uracoina-1 in mice. To detect the proteins in question, the immunoperoxidase method with monoclonal and polyclonal antibodies was used. Cell types within renal lesions were characterized by phenotypic identification, by means of immunohistologic analysis of marker proteins using different primary antibodies against mesangial cells, endothelial cells, cytoskeletal proteins (intermediate filament, extracellular matrix and basal membranes. Samples for morphological study by standard procedures (biotin-streptavidin-peroxidase technique using light microscopy were processed. Positive and negative controls for each antigen tested in the staining assay were included. After crude venom and hemorrhagic fraction inoculation of mice, the disappearance of cytoskeletal vimentin and desmin and collagen proteins in the kidney was observed. In extracellular matrix and basal membranes, collagen type IV from envenomed animals tends to disappear from 24 h to 120 h after venom injection.El daño renal es una causa importante de muerte en pacientes que sobreviven a los efectos iniciales de los severos envenenamientos crotálicos. El objetivo de este estudio ha sido el describir como las proteínas del citoesqueleto y los componentes de membrana basal muestran alteraciones importantes en su manifestación, bajo la acción del veneno crudo de Crotalus vegrandis y una fracción hemorrágica (Uracoina-1 del mismo veneno ya que, la matriz extracelular del tejido renal es alterada por la actividad de estas toxinas. Para detectar las proteínas en cuestión se utiliz

  14. Biomarkers in assessing tubular lesions of the solitary kidney. The solitary kidney in special conditions.

    Gluhovschi, G H; Gadalean, Florica; Gluhovschi, Cristina; Velciov, Silvia; Petrica, Ligia; Timar, R; Anastasiu, D; Gluhovschi, A

    2013-01-01

    The paper highlights the importance of tubular lesions of the solitary kidney (SK), identified and monitored by means of urinary biomarkers, mainly N-acetyl-beta-D-glucosaminidase (NAG), albumin, alpha 1-, and beta 2-microglobulin. It is considered that the assessment of a SK should be performed with four and not three parameters as it was usually done until recently: renal function, proteinuria and blood pressure (BP), to which biomarkers should be added. The solitary kidney can result after nephrectomy for kidney transplantation. In some countries living kidney donors represent the only option for performing kidney transplantation. The SK in living donors has generally a good evolution, although sometimes renal injury manifested by proteinuria, arterial hypertension (AH), or diminution of renal function does occur. Therefore, living donors require attentive monitoring. The SK is considered to have a good evolution (even in donors), in spite of alterations of the above-mentioned clinical and biological parameters. The very infrequent cases who evolve progressively towards renal failure are not predictable, which requires monitoring of all persons with a SK. The SK represents a special situation in case of association with a disease affecting the kidney, such as urinary tract infection (UTI), diabetes mellitus, or systemic lupus erythematosus (SLE). Pregnancy occurring in a person with a SK also needs attentive follow-up. Pregnancy associated diseases, such as preeclampsia occurring in patients with a SK, impose appropriate therapeutic behaviour. The SK remains a particular entity in nephrology which needs to be carefully monitored. PMID:24620625

  15. Tubular Heart Pumping Mechanisms in Ciona Intestinalis

    Battista, Nicholas; Miller, Laura

    2015-11-01

    In vertebrate embryogenesis, the first organ to form is the heart, beginning as a primitive heart tube. However, many invertebrates have tubular hearts from infancy through adulthood. Heart tubes have been described as peristaltic and impedance pumps. Impedance pumping assumes a single actuation point of contraction, while traditional peristalsis assumes a traveling wave of actuation. In addition to differences in flow, this inherently implies differences in the conduction system. It is possible to transition from pumping mechanism to the other with a change in the diffusivity of the action potential. In this work we consider the coupling between the fluid dynamics and electrophysiology of both mechanisms, within a basal chordate, the tunicate. Using CFD with a neuro-mechanical model of tubular pumping, we discuss implications of the both mechanisms. Furthermore, we discuss the implications of the pumping mechanism on evolution and development.

  16. Glomerular tubular balance: mediation by luminal hypotonicity.

    Häberle, D A; Müller, U; Nagel, W

    1989-01-01

    Late proximal rat tubular segments were microperfused with slightly hypo- or hypertonic artificial late proximal tubular fluid (ATF) at low (11-13 nl/min) or high (30-38 nl/min) perfusion rates. Volume reabsorption, net chloride and solute reabsorption were measured as a function of length. In addition, the transepithelial resistance and voltage (Vte) were measured as a function of the applied osmotic gradient. Hypertonic solutions equilibrated to isotonicity by solute outflow rather than water influx. With hypertonic ATF the lumen positive Vte was decreased compared with free flow or with hypotonic ATF. The resistance was not significantly different between the different groups. In contrast to hypotonic ATF, hypertonic or isotonic ATF was not significantly reabsorbed. In addition, hypotonic ATF maintained its hypotonicity along the perfused segments. Its reabsorption was flow-dependent. Hypotonicity appeared to enhance solute reabsorption. PMID:2725432

  17. [Gastric emptying and metabolic acidosis. III. Study of gastric retention of a sodium citrate solution using an experimental model of metabolic acidosis in rats].

    Baracat, E C; Collares, E F

    1992-01-01

    The gastric emptying of sodium citrate solution 0.25 mEq/ml was studied in rats with metabolic acidosis induced by orogastric infusion of 0.5 M ammonium chloride solution. Two control groups were used: one infused with 0.5 M sodium chloride and the other with water. The 3 solutions content was 2 ml/100 g weight of the animal. Six hours after the infusion, there was a moderate metabolic acidosis in the group with ammonium citrate. This 6 hour interval marked the beginning of the gastric emptying study. The test meal (sodium citrate 0.25 mEq/ml) was utilized containing 6 mg% red fenol as a marker. The gastric emptying of sodium citrate was studied at 5, 10, 20 and 30 minutes after the infusion, and the results showed no differences between the 3 groups. The data suggest that the duodenal receptors to pH were more effective do determine the pattern of gastric response than the acidosis. PMID:1339143

  18. Tubular electric heater with a thermocouple assembly

    This patent relates to a thermocouple or other instrumentation which is installed within the walls of a tubular sheath surrounding a process device such as an electric heater. The sheath comprises two concentric tubes, one or both of which have a longitudinal, concave crease facing the other tube. The thermocouple is fixedly positioned within the crease and the outer tube is mechanically reduced to form an interference fit onto the inner tube

  19. Energy production with a tubular propeller turbine

    Almeida Samora, Irene; Hasmatuchi, Vlad; Münch-Alligné, C.; Franca, Mário J.; Schleiss, Anton; Helena M. Ramos

    2016-01-01

    Micro-hydropower is a way of improving the energetic efficiency of existent water systems. In the particular case of drinking water systems, several studies have showed that pressure reducing valves can be by-passed with turbines in order to recover the dissipated hydraulic energy to produce electricity. As conventional turbines are not always cost-effective for power under 20 kW, a new energy converter is studied. A five blade tubular propeller (5BTP), assessed through laboratorial tests on ...

  20. Evaluation of split renal function in models of unilateral renal injury

    Effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and filtration fraction (FF) were measured using radionuclide techniques in rat models with ureteral obstruction and transient occlusion of the renal vein or artery to determine which parameter is helpful in evaluating changes in split renal function. Three microcuries of iodine-131 orthoiodohippuric acid (I-131 hipurran) and 7 μCi of technetium-99m dietylenetriaminepentaacetic acid (Tc-99m DTPA) were injected into the femoral vein 30 min, 3 hr, 6 hr, 2 days, and one week after obstruction of the left ureter, or after releasing occlusion of the left renal vein or artery for 30 min. Blood samples were serially obtained, and immediately after that, the kidneys, ureters, and urinary bladder were excised. Split ERPF and GFR were evaluated by obtaining blood clearances of I-131 hippuran and Tc-99m DTPA, respectively. With ureteral obstruction, the split ERPF, GFR, and FF on the obstructed side were decreased significantly 6 hr, 2 days and one week after the obstruction. With transient occlusion of the renal vein or artery, the split ERPF, GFR, and FF were decreased on the occluded side. The decrease in GFR was greater than that in ERPF on the obstructed or occluded side. Tc-99m DTPA, a glomerular agent, was more useful than I-131 hipurran, a tubular agent, in evaluating acute renal dysfunction. (N.K.)