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.

scholarly journals Preservation of intercalated cell H(+)-ATPase in two patients with lupus nephritis and hyperkalemic distal renal tubular acidosis.

1997 ◽  
Vol 8 (7) ◽  
pp. 1109-1117
Author(s):  
B Bastani ◽  
D Underhill ◽  
N Chu ◽  
R D Nelson ◽  
L Haragsim ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Tubular Acidosis ◽  
Frozen Section ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Renal Tubular Acidosis ◽  
Intercalated Cells ◽  
Urine Ph ◽  
Control Serum ◽  
Renal Tubular

In patients with Sjögren's syndrome and a secretory-defect distal renal tubular acidosis (dRTA), absence of vacuolar H(+)-ATPase from collecting duct intercalated cells has been reported. The H(+)-ATPase was examined in two patients with lupus nephritis and hyperkalemic (presumed voltage defect) dRTA. Both patients had a positive urine anion gap, alkaline urine despite acidemia, no rise in urine PCO2 with alkaluria, a urine pH > 5.5, and urine potassium excretion rate not significantly increased after 80 mg of intravenous furosemide. In both patients, immunocytochemistry of renal biopsy frozen sections with an anti-H(+)-ATPase monoclonal antibody showed bright staining of the proximal tubule brush border and collecting duct intercalated cells. In one patient, routine immunofluorescence analysis of a frozen section of her kidney biopsy with antihuman IgG showed staining of the collecting duct, indicative of autoantibodies to this segment. Moreover, rat kidney sections incubated with her serum showed labeling of the intercalated cells. On immunoblots of human kidney microsomal membranes performed with serum from both patients, an immunoreactive polypeptide was observed at M(r) approximately 56 kD that was not seen with control serum. Neither patient's sera reacted with affinity-purified bovine H(+)-ATPase or with lysates from 293 cell fibroblasts in which either of both isoforms of the human H(+)-ATPase B subunit (56 kD) were expressed. These findings demonstrate that the spectrum of dRTA includes the preservation of H(+)-ATPase in intercalated cells, in patients with presumed voltage defect dRTA. Moreover, some patients may have autoantibodies to the intercalated cells that are not directed to subunits of the H(+)-ATPase.

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.

Renal Tubular Acidosis in a Patient with Recurrent Metabolic Alkalosis

PEDIATRICS ◽  
1983 ◽  
Vol 72 (2) ◽  
pp. 207-210
Author(s):  
Leonard C. Hymes ◽  
Barry L. Warshaw
Keyword(s):  
Renal Tubular Acidosis ◽  
Serum Potassium ◽  
Metabolic Alkalosis ◽  
Failure To Thrive ◽  
Unusual Presentation ◽  
Potassium Depletion ◽  
Type I ◽  
Serum Bicarbonate ◽  
Urine Ph ◽  
Renal Tubular

A 7-month-old infant with failure to thrive and recurrent episodes of vomiting and metabolic alkalosis was evaluated. Urine pH, serum bicarbonate, and urine Pco2-blood Pco2 studies were consistent with the diagnosis of distal renal tubular acidosis (RTA-type I). Analysis of serum potassium and chloride levels during periods of alkalosis and acidosis revealed that potassium depletion and hypochloremic volume contraction served to maintain the alkalotic state despite the presence of an underlying chronic acidosis. This case represents an unusual presentation for renal tubular acidosis and suggests that, under certain conditions, renal tubular acidosis may predispose to the maintenance of a metabolic alkalosis.

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.

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.

Vanadate causes hypokalemic distal renal tubular acidosis

1992 ◽  
Vol 262 (3) ◽  
pp. F449-F453 ◽  
Author(s):  
E. Dafnis ◽  
M. Spohn ◽  
B. Lonis ◽  
N. A. Kurtzman ◽  
S. Sabatini
Keyword(s):  
Renal Tubular Acidosis ◽  
Potassium Concentration ◽  
Plasma Potassium ◽  
Distal Renal Tubular Acidosis ◽  
Urine Ph ◽  
A Value ◽  
Blood Ph ◽  
Collecting Tubule ◽  
Renal Tubular ◽  
Collecting Tubules

Considerable evidence supports the presence of an H(+)-K(+)-ATPase along the mammalian nephron. Inhibition of this enzyme might be expected to reduce acid excretion while increasing potassium excretion, thus causing hypokalemic distal renal tubular acidosis (RTA). In this study we administered vanadate at a dose of 5 mg/kg ip for 10 days to rats. These animals developed hypokalemic distal RTA with a blood pH of 7.22 +/- 0.01, a plasma bicarbonate of 15.2 +/- 0.6 meq/l, and a plasma potassium of 3.28 +/- 0.06 meq/l. The vanadate-treated animals had a urine pH of 6.70 +/- 0.09, a value significantly higher than NH4Cl-treated animals with the same degree of acidemia (urine pH = 5.25 +/- 0.04). When cortical collecting tubules (CCT) from these animals were microdissected and H(+)-K(+)-ATPase was measured, it was decreased by approximately 75% (P less than 0.001); but H(+)-ATPase was no different from control. In medullary collecting tubule, H(+)-K(+)-ATPase was also decreased but less than in CCT. Muscle potassium concentration in the vanadate-treated animals was significantly lower than in controls. These results demonstrate that vanadate causes hypokalemic distal RTA in association with inhibition of collecting tubule H(+)-K(+)-ATPase activity.

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

Inherited Proximal and Distal Renal Tubular Acidosis

2017 ◽  
Author(s):  
Patricia Valles ◽  
Jesus Moran-Farias ◽  
Daniel Batlle
Keyword(s):  
Metabolic Acidosis ◽  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Anion Gap ◽  
Intercalated Cells ◽  
Acid Excretion ◽  
Acid Base ◽  
Urine Ph ◽  
Renal Tubular ◽  
Net Acid Excretion

Acid-base homeostasis by the kidney is maintained through proximal tubular reclamation of filtered bicarbonate and the excretion of the daily acid load by collecting duct type A intercalated cells. The impairment of either process results in renal tubular acidosis (RTA), a group of disorders characterized by a reduced net acid excretion and a persistent hyperchloremic, non–anion gap metabolic acidosis. The primary or hereditary forms of proximal (pRTA) and distal renal tubular acidosis (dRTA) have received increased attention because of advances in the understanding of the molecular mechanism, whereby mutations in the main proteins involved in acid-base transport result in either reduced bicarbonate reabsorption or reduced H+ secretion and impaired acid excretion. dRTA is characterized by reduced net acid excretion and an inability to lower urine pH despite severe acidemia (but minimal HCO3– wastage). pRTA (type 2), by contrast, is characterized by marked HCO3– wastage but preserved ability to lower urine pH when plasma HCO3– (and therefore filtered HCO3–) is below a certain threshold. In children with dRTA, growth retardation caused by chronic metabolic acidosis is the key manifestation but is fully reversible with appropriate alkali therapy if initiated early in life. A striking manifestation of many patients with dRTA is the development of severe hypokalemia that may cause muscle paralysis. In this review, we discuss these types of hereditary RTA and the mechanisms involved in the genesis of these inherited tubular disorders. This review contains 5 figures, 1 table, and 103 references. Key words: Proximal renal tubular acidosis (pRTA), Distal renal tubular acidosis (dRTA), Hyperchloremic, non–anion gap metabolic acidosis, Hypokalemia, Fractional HCO3– excretion, Urinary gap, Fanconi Syndrome.ATP6V1B1 and ATP6V0A4 gene mutations . Intercalated cells ,

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