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Renal tubular acidosis [keywords]
- Hypokalaemic periodic paralysis in rural northern India - most have secondary causes. [JOURNAL ARTICLE]
- Trop Doct 2013 Nov 25.
Hypokalaemic periodic paralysis (HPP) is a life-threatening condition. Our aim was to study the clinical profile and laboratory parameters of HPP patients and to develop an algorithm to determine the causes of HPP. 84 patients presented with HPP over a 3 year period. 58 (69.0%) were found to have renal tubular acidosis (RTA). The other causes were idiopathic HPP (8 (9.5%)), acute gastroenteritis (4 (4.8%)), suspected primary hyperaldosteronism and familial HPP (2 each (2.4%)) and suspected Gitelman/Bartter Syndrome and thyrotoxic periodic paralysis (1 each (1.2%)). The number of cases peaks in the hot season. Over a third of the patients (35.7%) had recurrent episodes. 80% had secondary HPP and therefore a biochemical evaluation is mandatory. A simple algorithm was developed. Both health professionals and patients need further education regarding this problem in order to improve diagnosis and treatment and to improve compliance.
- Determinants of brushite stone formation: a case-control study. [Journal Article]
- PLoS One 2013; 8(11):e78996.
The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear.Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed.Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA.Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect.
- Molecular diagnosis of distal renal tubular acidosis in Tunisian patients: proposed algorithm for Northern Africa populations for the ATP6V1B1, ATP6V0A4 and SCL4A1 genes. [Journal Article]
- BMC Med Genet 2013.:119.
Primary distal renal tubular acidosis (dRTA) caused by mutations in the genes that codify for the H + -ATPase pump subunits is a heterogeneous disease with a poor phenotype-genotype correlation. Up to now, large cohorts of dRTA Tunisian patients have not been analyzed, and molecular defects may differ from those described in other ethnicities. We aim to identify molecular defects present in the ATP6V1B1, ATP6V0A4 and SLC4A1 genes in a Tunisian cohort, according to the following algorithm: first, ATP6V1B1 gene analysis in dRTA patients with sensorineural hearing loss (SNHL) or unknown hearing status. Afterwards, ATP6V0A4 gene study in dRTA patients with normal hearing, and in those without any structural mutation in the ATP6V1B1 gene despite presenting SNHL. Finally, analysis of the SLC4A1 gene in those patients with a negative result for the previous studies.25 children (19 boys) with dRTA from 20 families of Tunisian origin were studied. DNAs were extracted by the standard phenol/chloroform method. Molecular analysis was performed by PCR amplification and direct sequencing.In the index cases, ATP6V1B1 gene screening resulted in a mutation detection rate of 81.25%, which increased up to 95% after ATP6V0A4 gene analysis. Three ATP6V1B1 mutations were observed: one frameshift mutation (c.1155dupC; p.Ile386fs), in exon 12; a G to C single nucleotide substitution, on the acceptor splicing site (c.175-1G > C; p.?) in intron 2, and one novel missense mutation (c.1102G > A; p.Glu368Lys), in exon 11. We also report four mutations in the ATP6V0A4 gene: one single nucleotide deletion in exon 13 (c.1221delG; p.Met408Cysfs*10); the nonsense c.16C > T; p.Arg6*, in exon 3; and the missense changes c.1739 T > C; p.Met580Thr, in exon 17 and c.2035G > T; p.Asp679Tyr, in exon 19.Molecular diagnosis of ATP6V1B1 and ATP6V0A4 genes was performed in a large Tunisian cohort with dRTA. We identified three different ATP6V1B1 and four different ATP6V0A4 mutations in 25 Tunisian children. One of them, c.1102G > A; p.Glu368Lys in the ATP6V1B1 gene, had not previously been described. Among deaf since childhood patients, 75% had the ATP6V1B1 gene c.1155dupC mutation in homozygosis. Based on the results, we propose a new diagnostic strategy to facilitate the genetic testing in North Africans with dRTA and SNHL.
- Renal rickets-practical approach. [REVIEW]
- Indian J Endocrinol Metab 2013 Oct; 17(Suppl1):S35-S44.
Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA), hypophosphatemic rickets, and vitamin D dependent rickets (VDDR). The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment.
- Two unusual cases of severe recalcitrant hypocalcemia due to aminoglycoside-induced hypomagnesemia. [Journal Article]
- Indian J Endocrinol Metab 2013 Oct; 17(Suppl 1):S206-8.
Aminoglycoside (AMG)-induced renal toxicity is well-known and may manifest with non-oliguric renal failure or renal tubular dysfunction like Fanconi-like syndrome, Barter syndrome-like syndrome or distal renal tubular acidosis (RTA). These phenomena have been described with Gentamycin and Amikacin though rarely with Kanamycin. We present two cases of pulmonary tuberculosis that were treated with Kanamycin and during the course of treatment, developed severe recalcitrant hypocalcemia along with hypomagnesemia.
- Nephrocalcinosis and distal renal tubular acidosis in Sjögren's syndrome. [JOURNAL ARTICLE]
- Nefrologia 2013 Nov 13; 33(6):860-861.
- The medaka mutation tintachina sheds light on the evolution of V-ATPase B subunits in vertebrates. [Journal Article]
- Sci Rep 2013.:3217.
Vacuolar-type H(+) ATPases (V-ATPases) are multimeric protein complexes that play a universal role in the acidification of intracellular compartments in eukaryotic cells. We have isolated the recessive medaka mutation tintachina (tch), which carries an inactivating modification of the conserved glycine residue (G75R) of the proton pump subunit atp6v1Ba/vatB1. Mutant embryos show penetrant pigmentation defects, massive brain apoptosis and lethality before hatching. Strikingly, an equivalent mutation in atp6v1B1 (G78R) has been reported in a family of patients suffering from distal renal tubular acidosis (dRTA), a hereditary disease that causes metabolic acidosis due to impaired kidney function. This poses the question as to how molecularly identical mutations result in markedly different phenotypes in two vertebrate species. Our work offers an explanation for this phenomenon. We propose that, after successive rounds of whole-genome duplication, the emergence of paralogous copies allowed the divergence of the atp6v1B cis-regulatory control in different vertebrate groups.
- Basic research: Salt wasting in distal renal tubular acidosis-new look, old problem. [Journal Article]
- Nat Rev Nephrol 2013 Dec; 9(12):712-3.
- Hypokalemic rhabdomyolysis: an unusual presentation of Sjogren's syndrome. [Journal Article]
- BMJ Case Rep 2013.
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 manifestation of Sjogren's syndrome is rare. We report a case of a 59-year-old woman who presented to our department with severe weakness of all limbs. Laboratory examination demonstrated hypokalemic rhabdomyolysis caused by distal renal tubular acidosis. Investigations revealed Sjogren's syndrome as the underlying cause of the metabolic disorders.
- SLC22A13 catalyzes unidirectional efflux of aspartate and glutamate at the basolateral membrane of type A intercalated cells in renal collecting duct. [JOURNAL ARTICLE]
- Biochem J 2013 Oct 23.
In vertebrates, SLC22A13 is an evolutionarily conserved transport protein of the plasma membrane. In human and rat, it is principally expressed in the kidney. The precise localization and physiological function are unknown. Here, immunohistochemistry revealed that expression of SLC22A13 is confined to the basolateral membrane of type A intercalated cells in rat kidney. Double-staining confirmed that SLC22A13 co-localizes with anion exchanger 1. LC-MS difference shading showed that heterologous expression of human and rat SLC22A13 in 293 cells stimulates efflux of guanidinosuccinate, aspartate, glutamate, and taurine. Time courses of uptake of 3H-aspartate and 3H-glutamate revealed that SLC22A13 counteracted endogenous uptake. By contrast, OAT2, a bidirectional glutamate transporter, increased accumulation of 3H-glutamate. Thus, SLC22A13 catalyzes unidirectional efflux. Velocity of efflux of standard amino acids was measured by LC-MS/MS. Expression of SLC22A13 strongly stimulated efflux of aspartate, taurine, and glutamate. When the intracellular concentrations of aspartate and taurine were increased by preincubation, velocities of efflux increased linearly. We propose that in type A intercalated cells, SLC22A13 compensates luminal exit of protons by mediating the basolateral expulsion of the anions aspartate and glutamate. In this context, unidirectional efflux is essential to avoid anion reentering. Loss of SLC22A13 function could cause distal tubular acidosis.