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Renal tubular acidosis [keywords]
- Val2Ala mutation in the Atp6v0a4 gene causes early-onset sensorineural hearing loss in children with recessive distal renal tubular acidosis: a case report. [JOURNAL ARTICLE]
- Ren Fail 2014 Feb 24.
Abstract A young female patient born to consanguineous parents was admitted to our clinic at the age of 3 years with a 5-month history of weight loss and recurrent urinary tract infections. Based on clinical findings (delayed growth and O-bein deformity) and laboratory tests (hypokalemia, hyperchloremia, partially compensated metabolic acidosis, alkaline urine and nephrocalsinosis), a diagnosis of distal renal tubular acidosis (dRTA) was made. Then, the audiogram revealed a bilateral sensorineural hearing loss (SNHL). On follow-up, bilateral SNHL progressively worsened requiring the need for hearing aid. The ATP6V0A4 gene mutation analysis showed homozygote Val2Ala mutation. To the best of our knowledge, this is the first report describing a Turkish girl with dRTA who suffered from early-onset SNHL caused by Val2Ala mutation in the ATP6V0A4 gene.
- American Society of Nephrology Quiz and Questionnaire 2013: Electrolyte and Acid-Base. [JOURNAL ARTICLE]
- Clin J Am Soc Nephrol 2014 Feb 20.
The Nephrology Quiz and Questionnaire (NQ&Q) remains an extremely popular session for attendees of the annual meeting of the American Society of Nephrology. As in past years, the conference hall was overflowing with interested audience members. Topics covered by expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and transplantation. Complex cases representing each of these categories along with single-best-answer questions were prepared by a panel of experts. Prior to the meeting, program directors of United States nephrology training programs answered questions through an Internet-based questionnaire. A new addition to the NQ&Q was participation in the questionnaire by nephrology fellows. To review the process, members of the audience test their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. Their answers are compared in real time using audience response devices with the answers of nephrology fellows and training program directors. The correct and incorrect answers are then briefly discussed after the audience responses, and the results of the questionnaire are displayed. This article recapitulates the session and reproduces its educational value for the readers of CJASN. Enjoy the clinical cases and expert discussions.
- Regulation of the Proximal Tubule Vacuolar H+-ATPase by PKA and AMP-Activated Protein Kinase. [JOURNAL ARTICLE]
- Am J Physiol Renal Physiol 2014 Feb 19.
The vacuolar H(+)-ATPase (V-ATPase) mediates ATP-driven H+ transport across membranes.. This pump is present at the apical membrane of proton-secreting cells, such as kidney proximal tubule cells and intercalated cells. Defects in the V-ATPase and in proximal tubule function can cause renal tubular acidosis. We examined the role of PKA and AMP-activated protein kinase (AMPK) in the regulation of the V-ATPase in the proximal tubule as these two kinases co-regulate the V-ATPase in the collecting duct. As the proximal tubule V-ATPases have different subunit compositions from other nephron segments, we postulated that V-ATPase regulation in the proximal tubule could differ from other kidney tubule segments. Immunofluorescence labeling of rat ex vivo kidney slices revealed that the V-ATPase was present in the proximal tubule both at the apical pole, co-localizing with the brush border marker wheat germ agglutinin, and in the cytosol when slices were incubated in buffer alone. When slices were incubated with a cAMP analog and a phosphodiesterase inhibitor, the V-ATPase accumulated at the apical pole of S3 segment cells. These PKA activators also increased V-ATPase apical membrane expression as well as the rate of V-ATPase-dependent extracellular acidification in S3 cell monolayers relative to untreated cells. However, the AMPK activator AICAR decreased PKA-induced V-ATPase apical accumulation in proximal tubules of kidney slices and decreased V-ATPase activity in S3 cell monolayers. Our results suggest that in proximal tubule the V-ATPase subcellular localization and activity are acutely co-regulated via PKA downstream of hormonal signals and via AMPK downstream of metabolic stress.
- Central neurogenic hyperventilation and renal tubular acidosis in children with pontine gliomas. [JOURNAL ARTICLE]
- Neurology 2014 Feb 14.
Central neurogenic hyperventilation (CNH) is a rare neurologic condition that develops secondary to brainstem involvement. Approximately 35 noncomatose patients with CNH have been reported, including 7 with either a diffuse (patients 2-10 in the table) or focal (patient 1 in the table) brainstem glioma.(1-7) Although diffuse intrinsic pontine glioma (DIPG) is the most common pediatric brainstem cancer, only 1 case report described a child with DIPG who experienced CNH.(6.)
- NBCe1 as a model carrier for understanding the structure-function properties of Na(+)-coupled SLC4 transporters in health and disease. [JOURNAL ARTICLE]
- Pflugers Arch 2014 Feb 11.
SLC4 transporters are membrane proteins that in general mediate the coupled transport of bicarbonate (carbonate) and share amino acid sequence homology. These proteins differ as to whether they also transport Na(+) and/or Cl(-), in addition to their charge transport stoichiometry, membrane targeting, substrate affinities, developmental expression, regulatory motifs, and protein-protein interactions. These differences account in part for the fact that functionally, SLC4 transporters have various physiological roles in mammals including transepithelial bicarbonate transport, intracellular pH regulation, transport of Na(+) and/or Cl(-), and possibly water. Bicarbonate transport is not unique to the SLC4 family since the structurally unrelated SLC26 family has at least three proteins that mediate anion exchange. The present review focuses on the first of the sodium-dependent SLC4 transporters that was identified whose structure has been most extensively studied: the electrogenic Na(+)-base cotransporter NBCe1. Mutations in NBCe1 cause proximal renal tubular acidosis (pRTA) with neurologic and ophthalmologic extrarenal manifestations. Recent studies have characterized the important structure-function properties of the transporter and how they are perturbed as a result of mutations that cause pRTA. It has become increasingly apparent that the structure of NBCe1 differs in several key features from the SLC4 Cl(-)-HCO3 (-) exchanger AE1 whose structural properties have been well-studied. In this review, the structure-function properties and regulation of NBCe1 will be highlighted, and its role in health and disease will be reviewed in detail.
- Transient Fanconi syndrome in Quarter horses. [Journal Article, Research Support, N.I.H., Extramural]
- Can Vet J 2014 Feb; 55(2):147-51.
Two Quarter horses with weight loss had glucosuria, euglycemia, and a mild metabolic acidosis suggesting a proximal renal tubular defect. Further testing revealed transient generalized aminoaciduria, lactic aciduria, and glucosuria, indicating Fanconi syndrome. Both horses recovered with supportive therapy. This is the first report of acquired Fanconi syndrome in horses.
- Role of vacuolar ATPase and Skp1 in Sjögren's syndrome. [Journal Article]
- Med Hypotheses 2014 Mar; 82(3):319-25.
Immune mechanisms alone cannot directly account for exocrine gland dysfunction and extraglandular features such as renal tubular acidosis, neuropathy, hearing loss and fatigue in Sjögren's syndrome (SS). Absence of Vacuolar ATPase (V-ATPase) has been reported in SS related renal tubular acidosis (RTA). We hypothesise how defect in V-ATPase could account for decreased neurotransmitter release leading onto exocrine dysfunction, neuroendocrine manifestations and hearing loss which are well described manifestations in SS. S-phase-kinase-associated protein-1 (Skp1) is a constituent of RAVE which is involved in V-ATPase assembly. It is also a component of SCF ligase which is crucial in NFκB signalling. SKP1 also interacts with TRIM 21/Ro 52 which is an autoantigen in SS. By virtue of these interactions, we postulate how a defective skp1 could fit into the existing pathogenesis of SS and also account for increased risk of lymphoma in SS as well as congenital heart block in fetus of mothers with SS.
- Acute kidney injury with oxalate deposition in a patient with a high anion gap metabolic acidosis and a normal osmolal gap. [Journal Article]
- J Nephropathol 2013 Apr; 2(2):139-43.
Background:Ethylene glycol ingestion can lead to acute kidney injury from tubular deposition of oxalate crystals. The diagnosis of ethylene glycol intoxication is based on a history of ingestion, clinical examination, high anion gap metabolic acidosis, high osmolal gap, and a measured serum level of ethylene glycol. However, depending on the delay in time from ingestion to arrival to a hospital, the osmolal gap may become normal, thereby creating a confusing clinic picture for the treating clinician. Case: A 71 year-old man with a history of alcohol abuse had been unconscious for an unknown period of time. Upon hospitalization, he was found to have a high anion gap metabolic acidosis but a normal serum osmolal gap and subsequently developed acute kidney injury. The serum lactic acid and glucose levels were unremarkable, and there were no ketones in the serum. Urine analysis showed numerous red blood cells and calcium oxalate crystals. The renal biopsy showed multiple oxalate crystals in the renal tubules demonstrating birefringence under polarized light. Given the history of alcohol abuse, the clinical presentation, the unexplained high anion gap metabolic acidosis, and the biopsy findings, ethylene glycol intoxication was deemed the most likely diagnosis.
Conclusions:In cases of ethylene glycol intoxication, a high serum osmolal gap is supportive of ethylene glycol intoxication, but a normal serum osmolal gap does not exclude the diagnosis, especially when the time of ingestion is unknown. Physicians should be aware of potentially normal serum osmolal gap values in cases of ethylene glycol intoxication.
- Preoperative renal scar as a risk factor of postoperative metabolic acidosis following ileocystoplasty in patients with neurogenic bladder. [JOURNAL ARTICLE]
- Spinal Cord 2014 Jan 28.
Objectives:We investigated relation of preoperative renal scar to incidence of postoperative metabolic acidosis following ileocystoplasty in patients with neurogenic bladder.Patients:Thirty patients with neurogenic bladder, who underwent ileocystoplasty, were enrolled in the present study. Median age at ileocystoplasty was 13.9 years and median follow-up period after ileocystoplasty was 8.2 years. Metabolic acidosis was defined based on the outlined criteria: base excess (BE) is less than 0 mmol l(-1). Preoperative examination revealed that no apparent renal insufficiency was identified in blood analysis, although preoperative (99m)Tc-DMSA scintigraphy indicated abnormalities such as renal scar in 14 patients (47%). Incidence of postoperative metabolic acidosis was compared between patients with and without preoperative renal scar, which may reflect some extent of renal tubular damage.Results:Postoperative metabolic acidosis was identified in 13 patients (43%). Incidence of postoperative metabolic acidosis was significantly higher in patients with renal scar (11/14, 79%) compared with patients without renal scar (2/16, 13%; P<0.01). Particularly, all eight patients who had bilateral renal scars showed metabolic acidosis postoperatively. Compared with patients without preoperative renal scar, pH (P<0.05) and BE (P<0.01) were significantly lower postoperatively in patients with preoperative renal scar. However, there was no significant difference in PCO2. Hyperchloremia was observed in each patient with or without preoperative renal scar.Conclusion:Incidence of postoperative metabolic acidosis was significantly implicated in preoperative renal scar. If renal abnormalities are preoperatively identified in imaging tests, we need to care patients carefully regarding metabolic acidosis and subsequent comorbidities following ileocystoplasty.Spinal Cord advance online publication, 28 January 2014; doi:10.1038/sc.2013.175.
- Renal tubular dysfunction in patients with primary Sjögren syndrome. [Journal Article]
- Clin Nephrol 2014 Mar; 81(3):185-91.
Primary Sjögren's syndrome (pSS) is an important cause of renal tubular dysfunction in adults, mainly due to acquired type 1 distal renal tubular acidosis (RTA 1) and concentration defects (CD). This cross-sectional study evaluated renal tubular function of patients with pSS, by detecting proximal tubular injury (through measurements of urinary β2 microglobulin and albumin), RTA 1 (through an acidification protocol using furosemide and fludrocortisone), and CD (through water deprivation test, WDT). A total of 25 patients with pSS were evaluated and despite a preserved renal function (eGFR 92.5 ± 26.3 mL/min/1.73 m2), 24% were diagnosed as RTA 1. On the other hand, CD was diagnosed in 28% of the patients who presented worse renal function (eGFR 68.6 ± 27.7 mL/min/1.73 m2). Increased β2 microglobulin was found in 16% of the patients, and all of them had impaired renal function (eGFR 39.5 ± 11.9 mL/min/1.73 m2). These data showed a high prevalence of tubular dysfunction, mainly RTA 1 and CD, in patients with pSS, and suggest that patients with this disorder should be evaluated by the acidification protocol used in this study and WDT for proper diagnosis. Proximal tubular injury was less common, and probably associated with worsening of renal function.