Renal AND Renal tubular acidosis [keywords]
- Advanced ureteroscopy for stone disease: characteristics of renal papillae in kidney stone formers. [JOURNAL ARTICLE]
- Minerva Urol Nefrol 2016 Jul 21.
The mechanism of kidney stone formation is not well understood. To better understand the pathophysiology for specific kidney stone compositions and systemic diseases associated with kidney stones, endoscopic papillary mapping studies with concurrent biopsies have been conducted. This review will summarize the findings of these studies and proposed mechanisms for thirteen disease processes associated with kidney stones.A review of the literature was performed identifying thirteen studies that endoscopically mapped and biopsied renal papillae of different stone formers. These studies characterized renal papillae based on amount of Randall's plaque, Bellini duct pathology, papillary contour changes, presence of attached stones, pitting, and frequently papillary and cortical biopsies. The groups studied and reviewed here are kidney stone formers who have a history of idiopathic calcium oxalate stone formation, cystinuria, brushite stones, gastric bypass, ileostomy, small bowel resection, primary hyperparathyroidism, distal renal tubular acidosis (dRTA), primary hyperoxaluria, idiopathic calcium phosphate stone formation, medullary sponge kidney (MSK), uric acid stones, and struvite stones. A proposed standardized scoring system for papillary pathology was also reviewed.The series showed various degrees and types of changes to the renal papillae and corresponding histopathologic changes for each type of stone former reviewed. Those with predominantly alone Randall's plaque pathology had less tissue damage versus those with extensive Bellini duct lesions who had more interstitial fibrosis and cortical pathology. Randall's plaques are associated with stone formers who have low urinary volume, high urinary calcium, and acidic urine and thus are frequently seen in those with brushite stones, primary hyperparathyroidism, small bowel resection, and idiopathic calcium phosphate stone formers. Bellini duct plugging and pathology is theorized to occur via free solution crystallization, ductal obstruction, inflammation, cellular injury, fibrosis, and acidification defects.Ureteroscopic manifestations of stone disease can vary from normal appearing papillae to significantly diseased appearing papillae. Some diseases have very characteristic papillary changes.Further studies are necessary to fully elucidate the mechanisms of stone formation in patients with nephrolithiasis.
- Successful treatment of proximal renal tubular acidosis and Fanconi syndrome with vitamin D replacement. [Case Reports]
- Saudi J Kidney Dis Transpl 2016 Jul-Aug; 27(4):812-5.
Proximal renal tubular acidosis (RTA), also known as Type II RTA, is characterized by a defect in the ability to reabsorb bicarbonate (HCO 3 ) in the proximal tubule. It is usually associated with generalized dysfunction of the proximal tubule as part of Fanconi syndrome. Very few case reports in the literature support Vitamin D deficiency as a cause of proximal RTA. We present a case of a young female who presented with proximal RTA and Fanconi syndrome and excellently responded to Vitamin D replacement. Thus, work-up for the etiology of proximal RTA should include Vitamin D levels since replacement of this vitamin in those who are deficient can lead to cure of such patients.
- Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment. [JOURNAL ARTICLE]
- Urolithiasis 2016 Jul 13.
Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH4Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH4Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.
- Recurrent Attacks of Hypokalemic Quadriparesis: An Unusual Presentation of Primary Sjögren Syndrome. [Journal Article]
- Intern Med 2016; 55(13):1797-800.
We herein report the case of a 64-year old woman with recurrent attacks of hypokalemic quadriparesis which resulted from distal renal tubular acidosis (dRTA) secondary to Sjögren syndrome. The patient presented with sudden onset quadriparesis. A physical examination showed symmetric weakness of all four limbs. Severe hypokalemia (1.8 mEq/L), accompanied by normal anion gap metabolic acidosis, a positive urine anion gap and an inappropriately high urine pH pointed toward the diagnosis of dRTA. Further investigations disclosed primary Sjögren syndrome, which had not previously been recognized. On the basis of the current report and a review of the literature we suggest investigating the possibility of Sjögren syndrome in all patients with clinically unexplained dRTA.
- Recent advances in understanding renal ammonia metabolism and transport. [JOURNAL ARTICLE]
- Curr Opin Nephrol Hypertens 2016 Jun 29.
The purpose of this review is to provide a succinct description of the recent findings that advance our understanding of the fundamental renal process of ammonia metabolism and transport in conditions relevant to the clinician.Recent studies advance our understanding of renal ammonia metabolism. Mechanisms through which chronic kidney disease and altered dietary protein intake alter ammonia excretion have been identified. Lithium, although it can acutely cause distal renal tubular acidosis, was shown with long-term use to increase urinary ammonia excretion, and this appeared to be mediated, at least in part, by increased Rhcg expression. Gene deletion studies showed that the ammonia recycling enzyme, glutamine synthetase, has a critical role in normal-stimulated and acidosis-stimulated ammonia metabolism and that the proximal tubule basolateral bicarbonate transporter, NBCe1, is necessary for normal ammonia metabolism. Finally, our understanding of the molecular ammonia species, NH3 versus NH4, transported by Rh glycoproteins continues to be advanced.Fundamental studies have been recently published that advance our understanding of the regulation of ammonia metabolism in clinically important circumstances, and our understanding of the mechanisms and regulation of proximal tubule ammonia generation, and the mechanisms through which Rh glycoproteins contribute to ammonia secretion.
- A novel mutant Na(+) /HCO3(-) cotransporter NBCe1 in a case of compound-heterozygous inheritance of proximal renal tubular acidosis. [JOURNAL ARTICLE]
- J Physiol 2016 Jun 24.
Proximal Renal Tubular Acidosis (pRTA) is a rare, recessively-inherited disease characterized by abnormally acidic blood, blindness, and below average height and weight. pRTA is typically associated with homozygous mutation of SLC4A4. SLC4A4 encodes the electrogenic sodium bicarbonate cotransport protein NBCe1, a membrane protein that acts to maintain intracellular and plasma pH. We present the first description of a case of compound-heterozygous inheritance of pRTA. The individual has inherited two mutations in NBCe1: p. Arg510His (R510H) and p.Gln913Arg (Q913R), one from each parent. In addition to the usual features of pRTA, the patient exhibits unusual signs such as muscle spasms and fever. We have recreated these mutant transporters for expression in model systems. We find that both of the mutant proteins exhibit substantial intracellular retention when expressed in mammalian renal cell lines. When expressed in Xenopus oocytes, we find that the R510H- and Q913R-mutant NBCe1 molecules exhibit apparently normal Na(+) /HCO3 (-) cotransport activity, but that Q913R is associated with an unusual HCO3 (-) -independent anion leak. We conclude that reduced accumulation of NBCe1 protein in the basolateral membrane of proximal-tubule epithelia is the most likely cause of pRTA in this case. We further note that the Q913R-associated anion-leak could itself be pathogenic if expressed to the plasma membrane of mammalian cells, compromising the benefit of strategies to enhance mutant NBCe1 accumulation in the plasma membrane. This article is protected by copyright. All rights reserved.
- The urine albumin-to-creatinine ratio is a reliable indicator for evaluating complications of chronic kidney disease and progression in IgA nephropathy in China. [Journal Article]
- Clinics (Sao Paulo) 2016 May; 71(5):243-50.
This study investigated the correlation between the albumin-to-creatinine ratio in the urine and 24-hour urine proteinuria and whether the ratio can predict chronic kidney disease progression even more reliably than 24-hour proteinuria can, particularly in primary IgA nephropathy.A total of 182 patients with primary IgA nephropathy were evaluated. Their mean urine albumin-to-creatinine ratio and 24-hour proteinuria were determined during hospitalization. Blood samples were also analyzed. Follow-up data were recorded for 44 patients. A cross-sectional study was then conducted to test the correlation between these parameters and their associations with chronic kidney disease complications. Subsequently, a canonical correlation analysis was employed to assess the correlation between baseline proteinuria and parameters of the Oxford classification. Finally, a prospective observational study was performed to evaluate the association between proteinuria and clinical outcomes. Our study is registered in the Chinese Clinical Trial Registry, and the registration number is ChiCTR-OCH-14005137.A strong correlation (r=0.81, p<0.001) was found between the ratio and 24-hour proteinuria except in chronic kidney disease stage 5. First-morning urine albumin-to-creatinine ratios of ≥125.15, 154.44 and 760.31 mg/g reliably predicted equivalent 24-hour proteinuria 'thresholds' of ≥0.15, 0.3 and 1.0 g/24 h, respectively. In continuous analyses, the albumin-to-creatinine ratio was significantly associated with anemia, acidosis, hypoalbuminemia, hyperphosphatemia, hyperkalemia, hypercholesterolemia and higher serum cystatin C. However, higher 24-hour proteinuria was only associated with hypoalbuminemia and hypercholesterolemia. Higher tubular atrophy and interstitial fibrosis scores were also associated with a greater albumin-to-creatinine ratio, as observed in the canonical correlation analysis. Finally, the albumin-to-creatinine ratio and 24-hour proteinuria were associated with renal outcomes in univariate analyses.This study supports the recommendation of using the albumin-to-creatinine ratio, rather than 24-hour proteinuria, to monitor proteinuria and prognosis in primary IgA nephropathy.
- A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis. [Journal Article]
- Clin Kidney J 2016 Jun; 9(3):424-8.
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.
- Cystinosis in Eastern Turkey. [JOURNAL ARTICLE]
- J Pediatr Endocrinol Metab 2016 Jun 7.
This study was conducted to investigate CTNS (cystinosin, lysosomal cystine transporter) gene mutations and the clinical spectrum of nephropathic cystinosis among patients diagnosed with the disease in a single center in Turkey.Patients' clinical and laboratory data were extracted from an electronic health registry. Molecular CTNS gene analysis was performed using either next-generation sequencing or Sanger sequencing.Eleven patients (age range: 1.5-12 years) from nine families were identified. The presenting complaint was growth retardation in seven patients; polydipsia and polyuria in three patients; and vomiting in two patients. At presentation, electrolyte loss was noted in all patients, of which eight patients presented with metabolic acidosis, and three patients presented with metabolic alkalosis. All patients also presented with proteinuria and glucosuria, and four patients developed varying degrees of renal insufficiency, for which peritoneal dialysis was initiated in one patient. Cystine crystals were detected via ocular examination in one patient at presentation. No cystine crystals were detected among patients who underwent bone marrow aspiration. In the CTNS gene, a p.T7FX7 (c.18-21del4bp) mutation was detected in three patients, whereas a p.E227E (c.681 G>A) (homozygous) mutation was detected in eight patients.We detected two distinct mutations, p.T7FX7 (c.18-21del4bp) and p.E227E (c.681 G>A) (homozygous), in the CTNS gene in 11 patients with cystinosis from the East Anatolian region of Turkey. Patients with a homozygous c.681 G>A (p.E227E) mutation are more likely to develop chronic renal failure and should be monitored closely, whereas patients with a p.T7FX7 (c.18-21del4bp) mutation have a milder phenotype. Additionally, metabolic alkalosis does not exclude cystinosis, although cystinosis is a cause of proximal renal tubular acidosis.
- Mutations in ATP6V1B1 and ATP6V0A4 genes cause recessive distal renal tubular acidosis in Mexican families. [Journal Article]
- Mol Genet Genomic Med 2016 May; 4(3):303-11.
Autosomal recessive distal renal tubular acidosis (dRTA) is a rare disease characterized by a hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia, nephrocalcinosis, and conserved glomerular filtration rate. In some cases, neurosensorial deafness is associated. dRTA is developed during the first months of life and the main manifestations are failure to thrive, vomiting, dehydration, and anorexia.Nine unrelated families were studied: seven children, a teenager, and an adult with dRTA. Hearing was preserved in four children. Coding regions of the genes responsible for recessive dRTA were analysed by Sanger sequencing.Molecular defects were found in the genes ATP6V1B1 and ATP6V0A4. We identified three homozygous variants in ATP6V1B: a frameshift mutation (p.Ile386Hisfs*56), a nucleotide substitution in exon 10 (p.Pro346Arg), and a new splicing mutation in intron 5. Three patients were homozygous for one novel (p.Arg743Trp) and one known (p.Asp411Tyr) missense mutations in the ATP6V0A4 gene. Three patients were compound heterozygous: one proband displayed two novel mutations, the frameshift mutation p.Val52Metfs*25, and a large deletion of exons 18-21; two probands showed the missense mutation p.Asp411Tyr and as a second mutation, p.Arg194Ter and c.1691+2dup, respectively.ATP6V0A4 and ATP6V1B1 genes were involved in recessive dRTA of Mexican families. All ATP6V1B1 mutations detected were homozygous and all patients developed sensorineural hearing loss (SNHL) early in infancy. ATP6V0A4 mutations were found in one infant and three children without SNHL, and in one teenager and one adult with SNHL confirming the phenotypic variability in this trait. The mutation p.Asp411Tyr detected in four Mexican families was due to a founder effect. Screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA in this population.