scholarly journals Prospective long-term evaluation of incomplete distal renal tubular acidosis in idiopathic calcium nephrolithiasis diagnosed (treated) by low-dose NH4CL loading – gender prevalences and impact of alkali treatment

2022 ◽  
Author(s):  
Juri Sromicki ◽  
Georg Kacl ◽  
Malin Föhl ◽  
Bernhard Hess
Keyword(s):  
Calcium Phosphate ◽  
Renal Tubular Acidosis ◽  
Alkali Treatment ◽  
Distal Renal Tubular Acidosis ◽  
Urine Ph ◽  
Calcium Stone ◽  
Stone Formers ◽  
Alkali Therapy ◽  
Renal Tubular

Abstract Purpose Prospective evaluation of the prevalence of incomplete distal renal tubular acidosis (idRTA) in idiopathic calcium stone formers (ICSF) diagnosed by half-dose ammonium chloride loading (NH4Cl, 0.05 g/kg body weight/day) and impact of alkali treatment of idRTA. Methods Evaluation of 386 consecutive idiopathic calcium stone formers (ICSF) (280 males, 106 females) for idRTA. If screening fasting urine pH was > 5.80, 1-day NH4Cl loading was performed without severe adverse effects. Normally, urine pH falls below 5.45. Results Sixty-four idiopathic calcium stone formers exhibited idRTA, one complete dRTA. Prevalence was higher in women (25.4%) than in men (13.6%). Thus, for more equilibrated comparisons, we formed pairs of 62 idiopathic calcium stone formers (ICSF) with and 62 without idRTA, matched for gender, age, BMI and serum creatinine. Idiopathic calcium stone formers with idRTA more often had hypercalciuria (p < 0.025) and urine citrate < 2 mmol/d (p < 0.05), formed calcium phosphate stones more frequently, exhibited higher numbers of stones/year (1.4 ± 1.5 vs. 0.9 ± 0.8, p = 0.034) and 2.5 times more intrarenal calcifications (4.6 ± 5.9 vs. 1.8 ± 3.6, p = 0.002). All idiopathic calcium stone formers with idRTA were recommended chronic alkali therapy. After 4–15 years of follow-up, stone events /years follow-up (stone passage or urologic intervention) were higher in patients non-adherent to alkali therapy (0.61 ± 0.92) than in patients adherent to treatment (0.11 ± 0.21, p = 0.006). Conclusion Incomplete distal renal tubular acidosis is 1.8-fold more prevalent among female idiopathic calcium stone formers, predicts more stone recurrences, predisposes to calcium phosphate stones and is associated with 2.5 times more intrarenal calcifications vs. non-idRTA patients. Chronic alkali treatment reduces clinical stone recurrences by 5.5 times. Graphical abstract

scholarly journals Results of a Gene Panel Approach in a Cohort of Patients with Incomplete Distal Renal Tubular Acidosis and Nephrolithiasis

2021 ◽  
pp. 1-6
Author(s):  
Viola D’Ambrosio ◽  
Alessia Azzarà ◽  
Eugenio Sangiorgi ◽  
Fiorella Gurrieri ◽  
Bernhard Hess ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Genetic Testing ◽  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Tubular Dysfunction ◽  
Urine Ph ◽  
Cross Sectional ◽  
Urinary Acidification ◽  
Stone Formers ◽  
Renal Tubular

<b><i>Background:</i></b> Distal renal tubular acidosis (dRTA) is characterized by an impairment of urinary acidification resulting in metabolic acidosis, hypokalemia, and inappropriately elevated urine pH. If not treated, this chronic condition eventually leads to nephrocalcinosis, nephrolithiasis, impaired renal function, and bone demineralization. dRTA is a well-defined entity that can be diagnosed by genetic testing of 5 genes known to be disease-causative. Incomplete dRTA (idRTA) is defined as impaired urinary acidification that does not lead to overt metabolic acidosis and therefore can be diagnosed if patients fail to adequately acidify urine after an ammonium chloride (NH<sub>4</sub>Cl) challenge or furosemide and fludrocortisone test. It is still uncertain whether idRTA represents a distinct entity or is part of the dRTA spectrum and whether it is caused by mutations in the same genes of overt dRTA. <b><i>Methods:</i></b> In this cross-sectional study, we investigated a group of 22 stone formers whose clinical features were suspicious of idRTA. They underwent an NH<sub>4</sub>Cl challenge and were found to have impaired urinary acidification ability. These patients were then analyzed by genetic testing with sequencing of 5 genes: <i>SLC4A1</i>, <i>ATP6V1B1</i>, <i>ATP6V0A4</i>, <i>FOXI1</i>, and <i>WDR72</i>. <b><i>Results:</i></b> Two unrelated individuals were found to have two different variants in <i>SLC4A1</i> that had never been described before. <b><i>Conclusions:</i></b> Our results suggest the involvement of other genes or nongenetic tubular dysfunction in the pathogenesis of idRTA in stone formers. However, genetic testing may represent a cost-effective tool to recognize, treat, and prevent complications in these patients.

scholarly journals Distal Renal Tubular Acidosis in Adolescence with Severe Growth Retardation and Nephrocalcinosis

2012 ◽  
Vol 52 (187) ◽  
Author(s):  
M R Sigdel ◽  
M P Kafle ◽  
K B Raut
Keyword(s):  
Metabolic Acidosis ◽  
Weight Gain ◽  
Renal Tubular Acidosis ◽  
Growth Retardation ◽  
Growth Velocity ◽  
Distal Renal Tubular Acidosis ◽  
Alkali Therapy ◽  
Renal Tubular ◽  
Severe Growth

Chronic acidosis is an important, often overlooked cause of growth retardation. Here we present the case of a girl with distal renal tubular acidosis who had visited multiple hospitals before the diagnosis was made. She presented to us in adolescence with non anion gap metabolic acidosis, hypokalemia, severe growth retardation and nephrocalcinosis. In 18 months follow up with alkali therapy, she had good weight gain and growth velocity. Keywords: growth retardation; hypokalemia; nephrocalcinosis; renal tubular acidosis.

scholarly journals THE EFFECT OF LONG TERM ALKALI THERAPY FOR RECURRENT CALCIUM STONE PATIENTS WITH DISTAL RENAL TUBULAR ACIDOSIS

1993 ◽  
Vol 84 (4) ◽  
pp. 674-679
Author(s):  
Seiji Yamaguchi ◽  
Takuo Koide ◽  
Masato Utsunomiya ◽  
Toshiaki Yoshioka ◽  
Akihiko Okuyama
Keyword(s):  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Calcium Stone ◽  
Alkali Therapy ◽  
Renal Tubular

scholarly journals Incomplete distal renal tubular acidosis from a heterozygous mutation of the V-ATPase B1 subunit

2014 ◽  
Vol 307 (9) ◽  
pp. F1063-F1071 ◽  
Author(s):  
Jianning Zhang ◽  
Daniel G. Fuster ◽  
Mary Ann Cameron ◽  
Henry Quiñones ◽  
Carolyn Griffith ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Urine Ph ◽  
293 Cells ◽  
Heterozygous Carriers ◽  
Renal Tubular ◽  
Negative Dominance

Congenital distal renal tubular acidosis (RTA) from mutations of the B1 subunit of V-ATPase is considered an autosomal recessive disease. We analyzed a distal RTA kindred with a truncation mutation of B1 (p.Phe468fsX487) previously shown to have failure of assembly into the V1domain of V-ATPase. All heterozygous carriers in this kindred have normal plasma HCO3−concentrations and thus evaded the diagnosis of RTA. However, inappropriately high urine pH, hypocitraturia, and hypercalciuria were present either individually or in combination in the heterozygotes at baseline. Two of the heterozygotes studied also had inappropriate urinary acidification with acute ammonium chloride loading and an impaired urine-blood Pco2gradient during bicarbonaturia, indicating the presence of a H+gradient and flux defects. In normal human renal papillae, wild-type B1 is located primarily on the plasma membrane, but papilla from one of the heterozygote who had kidney stones but not nephrocalcinosis showed B1 in both the plasma membrane as well as diffuse intracellular staining. Titration of increasing amounts of the mutant B1 subunit did not exhibit negative dominance over the expression, cellular distribution, or H+pump activity of wild-type B1 in mammalian human embryonic kidney-293 cells and in V-ATPase-deficient Saccharomyces cerevisiae. This is the first demonstration of renal acidification defects and nephrolithiasis in heterozygous carriers of a mutant B1 subunit that cannot be attributable to negative dominance. We propose that heterozygosity may lead to mild real acidification defects due to haploinsufficiency. B1 heterozygosity should be considered in patients with calcium nephrolithiasis and urinary abnormalities such as alkalinuria or hypocitraturia.

scholarly journals Acidose Tubular Renal Distal: Expressão Clínica Variável na Mesma Família

2019 ◽  
Vol 32 (7-8) ◽  
pp. 542
Author(s):  
Daniela Ramos ◽  
Sofia Reis ◽  
Carolina Cordinhã ◽  
Carmen Do Carmo ◽  
Clara Gomes ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Chronic Renal Disease ◽  
Genetic Disorder ◽  
Distal Renal Tubular Acidosis ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
First Case ◽  
Hyperchloremic Metabolic Acidosis ◽  
Renal Tubular

Primary distal renal tubular acidosis is a genetic disorder characterized by the inability in acidification of urine. Symptoms are usually non-specific and highly variable. We described six cases in a family with four generations affected. The first case was diagnosed in a 3-year-old child presenting with hematuria and urolithiasis. Later, his sister, sons and two nephews were studied. Although asymptomatic, they all had nephrocalcinosis and hyperchloremic metabolic acidosis with normal anionic gap, except one case with normal arterial blood gas test but with nephrocalcinosis and inability of urinary acidification. At follow-up, they all maintained nephrocalcinosis, the index case had acute renal damage and developed hypertension, but none developed chronic renal disease. The diagnosis of autosomal dominant distal renal tubular acidosis is generally made later and patients tend to present with milder disease. But the condition may manifest early and have a variable phenotypic severity spectrum. Carrying out screening through assessment of family history enables an earlier diagnosis while also allowing treatment to start sooner.

scholarly journals Idiopathic hypokalemia in lupus nephritis - A newly recognized entity

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004352021
Author(s):  
Emmanuel A. Adomako ◽  
Saira Bilal ◽  
Yu-lun Liu ◽  
Ayesha Malik ◽  
Peter N. Van Buren ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Tubular Acidosis ◽  
Serum Potassium ◽  
Serum Magnesium ◽  
Distinct Pattern ◽  
Distal Renal Tubular Acidosis ◽  
Urine Ph ◽  
Median Serum ◽  
Novel Target ◽  
Renal Tubular

Background:Various causes of hypokalemia from renal potassium wasting, including distal renal tubular acidosis, have been described in lupus nephritis (LN). We report a phenomenon of otherwise unexplained hypokalemia among a population with LN. Methods:From our population of 403 patients with LN, we identified a cohort of 20 patients with idiopathic hypokalemia (HK), defined by serum potassium < 3.5 mmol/L without any apparent explanation. This cohort is compared to 90 LN controls (CON) and 10 LN patients with distal renal tubular acidosis (RTA) from the same population. Results:The HK cases had lower median serum potassium compared to CON and RTA subjects (3.26 vs 4.00 vs 3.75 mmol/L, respectively; p < 0.001). The median serum bicarbonate was normal in HK and CON but low in RTA (26.0 vs 25.0 vs 19.4 mmol/L; p < 0.001). The median urine pH was abnormally high only in the RTA group (6.00 vs 6.25 vs 6.67; p = 0.012). The median serum magnesium was modestly lower in HK compared to the CON and RTA groups (1.73 vs 2.00 vs 1.85 mg/dL; p = 0.002). While both HK and RTA showed a higher rate of seropositivity than CON for anti-Ro/SSA (79% and 80% vs 37%, respectively; p < 0.001), only HK revealed a higher rate of seropositivity than CON for anti-RNP (84% vs 42%; p = 0.003) and only RTA showed a higher rate of seropositivity than CON for anti-La/SSB (40% vs 12%; p = 0.046). Conclusions:A syndrome of idiopathic hypokalemia was revealed in 20/403 (5%) of patients within our LN population and proved to be distinct from the renal tubular acidosis that occurs in LN. Furthermore, it was associated with a distinct pattern of autoantibodies. We speculate that idiopathic hypokalemia is the result of a novel target of autoimmunity in LN affecting renal tubular potassium transport.

Phenotype and Genotype Profile of Children with Primary Distal Renal Tubular Acidosis: A 10-Year Experience from a North Indian Teaching Institute

2021 ◽  
Author(s):  
Lesa Dawman ◽  
Karalanglin Tiewsoh ◽  
Prabal Barman ◽  
Kambagiri Pratyusha ◽  
Lalawmpuia Chaakchhuak ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Serum Potassium ◽  
Age At Onset ◽  
Genetic Defect ◽  
Distal Renal Tubular Acidosis ◽  
Response To Treatment ◽  
Indian Children ◽  
Medullary Nephrocalcinosis ◽  
Renal Tubular

AbstractPrimary distal renal tubular acidosis (dRTA) or Type 1 RTA in children is caused by a genetic defect (involved genes ATP6V0A4, ATP6V1B1, SLC4A1, FOXI1, or WDR72), which causes tubular transport defects characterized by an inability to appropriately acidify urine with resultant persistent hyperchloremic metabolic acidosis. Retrospective analysis of 28 children (14 males) under the age of 14 years with dRTA seen from 2010 to 2019 was reviewed, and detailed clinic records were analyzed. The clinical features, investigations, and response to treatment were recorded. The median age of the children at presentation was 30 months (range: 9.25–72 months), and the median age at onset of symptoms was 2 months. All the children had growth failure, polyuria, and polydipsia at presentation. Mean serum potassium, pH, bicarbonate, and anion gap at presentation was 2.3 ± 0.5 mmol/L, 7.22 ± 0.09, 13.28 ± 4.37 mmol/L, and 9.3 ± 2.18, respectively. Mean serum potassium, pH, bicarbonate at follow-up was 3.88 ± 0.6 mmol/L, 7.35 ± 0.06, and 20.13 ± 4.17 mmol/L, respectively. The median z-score for the weight for age and height for age at initial presentation was −4.77 (–7.68 to –3.74) and –4.21 (–5.42 to –2.37) and at follow-up was –3.35 (–5.29 to –1.55) and –3.84 (–5.36 to –1.63), respectively. Twenty-two (78.6%) children had medullary nephrocalcinosis. Four children had sensorineural hearing loss. Seven children had genetic testing done, and six had pathogenic or likely pathogenic variants in ATP6V1B1 and ATP6V0A4 gene. Children with dRTA have a guarded prognosis and ATP6V1B1 and ATP6V0A4 mutations are the most common implicated genetic defect in Indian children with distal RTA.

scholarly journals Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers

2017 ◽  
Vol 12 (9) ◽  
pp. 1507-1517 ◽  
Author(s):  
Nasser A. Dhayat ◽  
Michael W. Gradwell ◽  
Ganesh Pathare ◽  
Manuel Anderegg ◽  
Lisa Schneider ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Kidney Stone ◽  
Distal Renal Tubular Acidosis ◽  
Clinical Parameters ◽  
Stone Formers ◽  
Renal Tubular
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