Distal Renal Tubular Acidosis Research Articles

Sjogren’s Syndrome Presenting as Hypokalemic Paralysis Secondary to Distal Renal Tubular Acidosis: A Case Report

Sjogren’s Syndrome Presenting as Hypokalemic Paralysis Secondary to Distal Renal Tubular Acidosis: A Case Report

Quadriplegia In Accidently Diagnosed Distal Renal Tubular Acidosis with Pneumonia (Case Report)

Distal renal tubular acidosis (RTA1) is a rare disease. It confirms the lab’s data and rules out other differential diagnoses. Late evaluation can interfere with healthy development. We explain a 38-year-old patient with a late and accidental RTA1 diagnosis. Correct treatment with alkali consumption and potassium citrate improves her general condition and eliminates further weakness attacks. Early diagnosis is crucial for patient development and morbidity avoidance with accurate treatments.

Compound Heterozygous Loss of Allele Coding for KCNJ16 in an Adult Presenting as Recurrent Hypokalemic Periodic Paralysis with Metabolic Acidosis and Hypokalemia

A 20-year-old male presented with fever and rapidly progressive muscle weakness. He had hypokalemia and metabolic acidosis, suggesting renal tubular acidosis (RTA). Further investigation revealed distal RTA with preserved acidification. A channelopathy was suspected. Whole exome sequencing identified a novel biallelic mutation in the KCNJ16 gene, which encodes the Kir5.1 protein. This is the first reported case of an Indian adult with biallelic KCNJ16 mutations presenting as pure renal phenotype without sensory neural hearing loss or cardiac manifestation.

Nephrocalcinosis, distal renal tubular acidosis and skeletal abnormality in two siblings with ROGDI-related Kohlschütter-Tönz syndrome.

Kohlschütter-Tönz (KTS) is a rare autosomal recessive, genetically heterogeneous disorder characterized by a triad of early-onset seizures, global developmental delay or regression, and amelogenesis imperfecta of both temporary and permanent teeth. To date, 66 cases have been reported in the literature, of which 44 with genetic confirmation. Here we report the observation of sibling pairs in a family from a small village in India who presented with nephrocalcinosis, distal renal tubular acidosis, and skeletal abnormality. Nephrocalcinosis has only been reported once before in an individual affected with KTS. Trio exome sequencing revealed a novel, homozygous, likely pathogenic variant, c.646-2_649del, in exon 9 of the ROGDI gene (NM_024589.3) in the first child. Sanger sequencing confirmed homozygosity in both children. Both parents are heterozygous carriers of the same variant. Further research needs to be done to identify the exact mechanism by which ROGDI-encoded protein deficiency leads to nephrocalcinosis and distal renal tubular acidosis.

Understanding renal tubular acidosis.

Renal tubular acidosis is a group of disorders characterised by metabolic acidosis, hyperchloraemia, normal anion gap, and potassium imbalance. Genetic mutations, drugs or acquired disorders disrupt the function of various transport proteins and enzymes in the renal tubules, causing diminished bicarbonate reabsorption or inability to excrete hydrogen ions, leading to proximal (type 2) and distal (type 1) renal tubular acidosis, respectively. These conditions are typically associated with hypokalaemia, which, if severe, can cause muscle paralysis and dangerous cardiac arrhythmias. A rare mixed variant (type 3), including features of both type 1 and type 2 renal tubular acidosis, has also been described. On the other hand, aldosterone deficiency or resistance leads to the hyperkalaemic form of renal tubular acidosis (type 4). If untreated, renal tubular acidosis can lead to long-term severe complications such as growth retardation, osteoporosis, rickets, osteomalacia, and renal calculi. Moreover, renal tubular acidosis might be the initial presentation of a more severe underlying pathology, such as autoimmune disease or plasma cell dyscrasias. A better understanding of the condition can help physicians diagnose and treat it early and prevent adverse outcomes.

7289 An interesting case of Diabetes Mellitus Type 1 induced Renal Tubal Acidosis Type 1

Abstract Disclosure: R. Ripa: None. A. Itani: None. S.K. Patel: None. Introduction: Renal Tubular Acidosis (RTA) are a group of disorders that involve dysfunctional transporters and channels in the renal system. These disorders can be acquired (idiopathic, medication side effects, and medical disorders) or inherited. The most common type worldwide is type 4 RTA, the main cause is diabetic nephropathy leading to hypoaldosteronism. The association of type 1 RTA with diabetes has rarely been reported in studies. Here, we report the presentation, diagnosis and management of a rare case of type 1 RTA in a patient with a history of diabetes mellitus type 1. Case: A male in his 50s with a 30-year history of uncontrolled type 1 diabetes mellitus on insulin pump and coronary artery disease presented to his cardiologist with worsening chest pain, fatigue, polyuria, weight loss of 15 lbs, and recent insulin pump change. Blood tests revealed serum bicarbonate of 10 mmol/L and he was sent to the hospital. On examination, he was hypotensive and bradycardic with dry mouth and decreased skin turgor. His blood tests were consistent with type 1 RTA, he was treated with intravenous fluids containing bicarbonate plus potassium and transitioned to oral potassium citrate on discharge. He underwent renal biopsy as work up was unrevealing for a cause of type 1 RTA. Biopsy revealed normal glomeruli with negative immunofluorescence and Congo red stain. The biopsy, however, did show mild patchy chronic interstitial fibrosis with lymphocytes and mild tubular atrophy. At one year follow up, he remained on oral potassium citrate with resulting serum bicarbonate of 26 mmol/L and a normal renal function. Discussion: Diabetes mellitus can lead to a variety of renal pathologies, specifically metabolic acidosis that can be either seen as diabetic ketoacidosis or hyporeninemic hypoaldosteronism (Type 4 RTA). In our patient, despite being a diabetic, he did not present with either elevated anion gap, ketonuria or hyperkalemic hyperchloremic acidosis typical of type 4 RTA. He was noted to have hypokalemic hyperchloremic acidosis, with a positive urine anion gap, and an alkaline urine, all characteristic of type 1 RTA. Acquired distal RTA occurs more commonly due to certain medications or autoimmune diseases as in Sjögren’s syndrome. The relationship between distal RTA and Sjögren’s syndrome has already been established, unlike the relationship with type 1 diabetes. There have been few case reports of distal RTA in association with type 1 diabetes mellitus, implying a possible autoimmune pathology. Prior case reports also not only had patients who were insulin dependent, but diabetes was present for more than a decade at least suggesting chronicity of disease is needed. Traditional management consists of alkaline therapy and treatment of the underlying disease, or removal of offending medication. In this case, we hope to highlight distal RTA in a diabetic who doesn’t meet criteria for DKA or type 4 RTA. Presentation: 6/1/2024

Distal Renal Tubular Acidosis as Initial Presentation of Sjogren Syndrome in Pregnancy

Distal Renal Tubular Acidosis as Initial Presentation of Sjogren Syndrome in Pregnancy

Worsening of Distal Renal Tubular Acidosis (dRTA) as a Sign of Recurrent Autoimmune Hepatitis after Liver Transplant

Worsening of Distal Renal Tubular Acidosis (dRTA) as a Sign of Recurrent Autoimmune Hepatitis after Liver Transplant

Sex Differences in Primary Distal Renal Tubular Acidosis

Sex Differences in Primary Distal Renal Tubular Acidosis

Decoding the Renal Puzzle: Idiopathic Distal Renal Tubular Acidosis in a 23-Year-Old Woman with Nephrocalcinosis and Metabolic Acidosis

Decoding the Renal Puzzle: Idiopathic Distal Renal Tubular Acidosis in a 23-Year-Old Woman with Nephrocalcinosis and Metabolic Acidosis

Chronic Hypokalemia Secondary to Distal Renal Tubular Acidosis Induced by Sodium Valproate

Chronic Hypokalemia Secondary to Distal Renal Tubular Acidosis Induced by Sodium Valproate

Prevalence of kidney failure in adults diagnosed with hereditary tubulopathies.

Inherited tubulopathies are rare kidney diseases with few data available in the literature regarding their long-term renal prognosis. This study aimed to evaluate the prevalence of kidney failure in adults with confirmed genetic tubulopathy and to describe the corresponding clinical and genetic findings. In this observational cohort study, we focused on genetic tubulopathies assumed to impact kidney function. In all adult patients genetically diagnosed in our laboratory between 2001 and 2019, we estimated Glomerular Filtration Rate (eGFR) at diagnosis using the Modification of diet in renal disease (MDRD) formula. Kidney failure was defined as an eGFR < 60ml/min/1.73m2. A total of 2145 patients underwent genetic testing, confirming a genetic tubulopathy in 1031 cases (48%). We identified 116 patients out of 885 with available data with kidney failure, mostly diagnosed with Dent disease and distal renal tubular acidosis (respectively, 31% and 20%), followed by familial hypomagnesemia with hypercalciuria and nephrocalcinosis and renal hypophosphatemia/infantile hypercalcemia. Renal prognosis appeared particularly impacted in familial hypomagnesemia with hypercalciuria and nephrocalcinosis and Dent disease, while preserved in Gitelman syndrome. In this cohort, 13% of adults with genetic tubulopathy had kidney failure at diagnosis, with this rate varying greatly according to tubulopathies and suggesting a significant impact on renal prognosis. Even in adults, genetic analyses yield a good diagnostic rate in selected patients, and should be performed as soon as possible, in order to improve the renal management of patients and their relatives.

A Case Report on Proximal Renal Tubular Acidosis with Ocular Findings

A Case Report on Proximal Renal Tubular Acidosis with Ocular Findings

Left Ventricular Systolic Dysfunction in NBCe1-B/C-Knockout Mice.

Congenital proximal renal tubular acidosis (pRTA) is a rare systemic disease caused by mutations in the SLC4A4 gene that encodes the electrogenic sodium bicarbonate cotransporter, NBCe1. The major NBCe1 protein variants are designated NBCe1-A, NBCe1-B, and NBCe1-C. NBCe1-A expression is kidney-specific, NBCe1-B is broadly expressed and is the only NBCe1 variant expressed in the heart, and NBCe1-C is a splice variant of NBCe1-B that is expressed in the brain. No cardiac manifestations have been reported from patients with pRTA, but studies in adult rats with virally induced reduction in cardiac NBCe1-B expression indicate that NBCe1-B loss leads to cardiac hypertrophy and prolonged QT intervals in rodents. NBCe1-null mice die shortly after weaning, so the consequence of congenital, global NBCe1 loss on the heart is unknown. To circumvent this issue, we characterized the cardiac function of NBCe1-B/C-null (KOb/c) mice that survive up to 2 months of age and which, due to the uninterrupted expression of NBCe1-A, do not exhibit the confounding acidemia of the globally null mice. In contrast to the viral knockdown model, cardiac hypertrophy was not present in KOb/c mice as assessed by heart-weight-to-body-weight ratios and cardiomyocyte cross-sectional area. However, echocardiographic analysis revealed reduced left ventricular ejection fraction, and intraventricular pressure-volume measurements demonstrated reduced load-independent contractility. We also observed increased QT length variation in KOb/c mice. Finally, using the calcium indicator Fura-2 AM, we observed a significant reduction in the amplitude of Ca2+ transients in paced KOb/c cardiomyocytes. These data indicate that congenital, global absence of NBCe1-B/C leads to impaired cardiac contractility and increased QT length variation in juvenile mice. It remains to be determined whether the cardiac phenotype in KOb/c mice is influenced by the absence of NBCe1-B/C from neuronal and endocrine tissues.

Abstract P427: Novel SNVs of NBCe1, D405E and I803M mutants, reduced cell-surface expression and transport activity.

Introduction: The electrogenic Na + /HCO 3 - cotransporter NBCe1 is mainly expressed in proximal renal tubule, and regulate pH homeostasis and plasma volume. NBCe1 homozygous mutation causes many symptoms, including severe hypotension, proximal renal tubular acidosis (RTA), and extrarenal phenotype (migraine, mental retardation, mineral bone disorder and ocular abnormalities). Hypothesis: Undetermined single nucleotide variants (SNVs) in NBCe1 will be crucial role of sodium and bicarbonate transport. Methods: We identified the missense mutations (D405E and I803M) in NBCe1 variant A (kidney type) from the NCBI database. We conducted a comparative analysis of cellular localization and cell protein expression using confocal microscopy and western blotting. Furthermore, we performed functional analysis in D405E and I803M SNVs using two-electrode voltage clamp method. Results: Immunofluorescence analysis with confocal microscopy revealed that the D405E and I803M variants were present predominantly in the cell-surface in HEK293 cells. Western blotting in HEK293 cells confirmed that the D405E and I803M variants were significantly reduced protein expression level (25% in D405E and 57% in I803M) compared with WT, respectively. Moreover, electrophysiological analysis revealed that D405E and I803M variants were significantly reduced transport activity. These consisting data suggest that cell-expression level and transport activity are comparable. Conclusion: These data illustrate the diverse physiological consequences of distinct SNVs and underscore the importance of functional characterization in membrane transport proteins.

Evaluation of Metabolic and Biochemical Abnormalities in Pediatric Population With Nephrocalcinosis in Southwestern Iran

This retrospective study aimed to evaluate the metabolic and biochemical abnormalities in children with nephrocalcinosis to identify its important risk factors and better understand the disease pathophysiology. Data were collected from the medical records of 163 children diagnosed with nephrocalcinosis. Their clinical and laboratory characteristics at admission were recorded, and a 24-hour urinalysis was performed to measure parameters such as calcium, oxalate, citrate, uric acid, magnesium, and cystine. Family history of kidney stones and parental consanguinity were present in 58.8% and 58.2% of patients, respectively. The most common underlying conditions were hyperparathyroidism (24%), distal renal tubular acidosis (16.6%), and medullary sponge kidney (12.9%). The main abnormalities included hypocitraturia (65.2%), hypercalciuria (51.9%), hypomagnesuria (44.6%), hyperoxaluria (39.1%), hyperuricosuria (31.5%), vitamin D deficiency (30.06%), and metabolic acidosis (27%). Patients with kidney stones and failure to thrive had higher rates of hypercalciuria. Metabolic acidosis was more common in those with parental consanguinity and vitamin D deficiency. Renal failure at final follow-up was more evident in older patients, those with parental consanguinity, hypokalemia, acidosis, and hyperparathyroidism. End-stage renal disease was more frequent in patients with consanguineous parentage, hyperparathyroidism, hypokalemia, and acidosis. Parental consanguinity, family history of kidney stones, and urinary metabolic disorders are important risk factors for pediatric nephrocalcinosis. This highlights the need for genetic counseling, screening, and monitoring of biochemical abnormalities. Early diagnosis and timely treatment are crucial to maintain glomerular function and prevent kidney failure.

Hypokalemic paralysis and proximal renal tubular acidosis secondary to tenofovir-induced Fanconi syndrome: A contributing cause of death

Nucleotide reverse transcriptase inhibitors (NRTIs, primarily cidofovir and adefovir, less likely tenofovir) pose a well-known risk of nephrotoxicity. Acute renal failure, nephrogenic diabetes insipidus (NDI), and Fanconi syndrome (FS) are the primarily reported renal adverse effects associated with NRTIs. In this report, we describe a case of a 52-year-old female who presented to the outpatient department of a tertiary-care facility with polyuria, polydipsia, convulsions, myalgias, and hypokalemic paralysis (quadriparesis) after 10 months exposure to tenofovir disoproxil fumarate (TDF), which she was taking for HIV and Hepatitis-B virus coinfection. The patient developed hypokalemic paralysis and proximal renal tubular acidosis (pRTA) with normal anion gap hyperchloremic metabolic acidosis. On evaluation, renal tubulopathy was evident, which was resolved post-TDF discontinuation and therapeutic corrections. A diagnosis of TDF-induced FS, pRTA, and NDI were considered, as there were no clear alternative explanations. This report also highlights the characteristics of TDF-induced FS from the published case reports in the Indian context.

Phytate Effects on Incomplete Distal Renal Tubular Acidosis.

Background: Adults who have incomplete distal renal tubular acidosis (dRTA) may present with recurrent urolithiasis due to metabolic acidosis, leading to bone resorption, which in turn causes hypercalciuria and urine alkalinization (pH > 6.0). Oral potassium citrate is the most commonly used treatment for dRTA, but some patients cannot tolerate this treatment. The objective of this single-arm study was to evaluate the effect of phytate, an inhibitor of bone resorption, on calciuria of patients with incomplete dRTA. Methods: The calciuria levels of 16 patients who had incomplete dRTA with urolithiasis and could not tolerate potassium citrate treatment were recorded before (baseline) and after 6 months of treatment with oral calcium magnesium phytate (380 mg every 12 h). There were no dietary modifications or other treatments. Results: The baseline calciuria was 317 ± 81 mg/24 h and the level after 6 months was 221 ± 38 mg/24 h (p < 0.005). Conclusions: Our results suggest that calcium magnesium phytate should be considered as an alternative or adjunctive treatment for hypercalciuria in patients with incomplete dRTA.

Hypokalemia Secondary to Distal Renal Tubular Acidosis as a Manifestation of Primary Sjögren Syndrome

Hypokalemia Secondary to Distal Renal Tubular Acidosis as a Manifestation of Primary Sjögren Syndrome

Clinical characteristics and genetic profile of children with WDR72-associated distal renal tubular acidosis: a nationwide experience.

Limited data, primarily from small case series, exist regarding the clinical profile, genetic variants, and outcomes of WDR72-associated distal renal tubular acidosis (WDR72-dRTA). Our study enrolled children diagnosed with WDR72-dRTA below 18years of age from 9 Indian centers and analyzed their clinical characteristics, genetic profiles, and outcomes. Potential genotype-phenotype correlations were explored. We report 22 patients (59% female) with WDR72-dRTA who were diagnosed at a median age of 5.3 (3, 8) years with polyuria (n = 17; 77.3%), poor growth (16; 72.7%), and rickets (9; 40.9%). Amelogenesis imperfecta was present in 21 (95.5%) cases. At presentation, all patients had normal anion gap metabolic acidosis; hypokalemia and nephrocalcinosis were seen in 17 (77.3%) patients each. Seven (31.8%) patients had concomitant proximal tubular dysfunction. Genetic analysis identified biallelic nonsense variants in 18 (81.8%) patients, including novel variants in 6 cases. A previously reported variant, c.88C > T, and a novel variant, c.655C > T, were the most frequent variants, accounting for 10 (45.5%) cases. Over a median follow-up of 1.3 (1, 8) years, the height velocity improved by 0.74 (0.2, 1.2) standard deviation scores, while 3 children (13.6%) progressed to chronic kidney disease (CKD) stage 2, with eGFR ranging from 67 to 76mL/min/1.73 m2, respectively, after 11.3-16years of follow-up. No specific genotype-phenotype correlation could be established. WDR72-dRTA should be considered in children with typical features of amelogenesis imperfecta and dRTA. Biallelic nonsense variants are common in Asians. While most patients respond well to treatment with improved growth and preserved eGFR, on long-term follow-up, a decline in eGFR may occur.