RARE DISEASE
Distal renal tubular acidosis
Distal renal tubular acidosis
Distal renal tubular acidosis
Synonyms: Classic RTA, Familial distal primary acidosis, Renal tubular acidosis type 1, dRTA
Synonyms: Classic RTA, Familial distal primary acidosis, Renal tubular acidosis type 1, dRTA
Synonyms: Classic RTA, Familial distal primary acidosis, Renal tubular acidosis type 1, dRTA
Drug discovery
2
drugs
With orphan designations
Overview
Distal Renal Tubular Acidosis (dRTA) is a disorder of impaired urinary acidification in the distal nephron, causing hyperchloremic metabolic acidosis. It arises from genetic mutations (e.g., ATP6V1B1, SLC4A1) or secondary causes (autoimmune diseases, medications). Key features include hypokalemia, nephrolithiasis, nephrocalcinosis, and bone demineralization. Diagnosis involves urinary pH >5.3 despite systemic acidosis and confirmed via acid-loading tests [1][2][6][9].
Population
Rare; hereditary forms (autosomal dominant/recessive) are more prevalent in consanguineous populations (e.g., North Africa, Southeast Asia). Acquired dRTA is associated with autoimmune diseases (e.g., Sjögren’s syndrome, SLE) or medications (e.g., amphotericin B) [2][4][14].
Onset varies: autosomal recessive forms present in infancy/childhood; autosomal dominant and acquired forms often manifest in adolescence/adulthood [2][6][11].
Burden
Complications: Nephrolithiasis (56%), CKD progression, osteomalacia/rickets, growth failure in children, and sensorineural hearing loss (genetic forms) [2][9][11].
Long-term impact: Chronic treatment adherence is critical; untreated cases risk renal failure [3][6][12].
Economic/psychosocial: Frequent monitoring, lifelong therapy, and reduced quality of life due to recurrent hospitalization and comorbidities [4][6].
Therapies
Alkali therapy: Sodium bicarbonate (1–8 mEq/kg/day) or potassium citrate to correct acidosis, hypokalemia, and reduce stone risk [1][3][12].
Targeted management: Potassium supplementation for hypokalemia; address underlying causes (e.g., immunosuppression for autoimmune-associated dRTA) [3][9][13].
Monitoring: Regular serum electrolytes, urinary calcium/citrate, and renal function to prevent CKD progression [2][6][12].
Categories: rare genetic diseases, rare renal diseases, rare transplant-related disorders
Research Papers
400 drug discovery papers about Distal renal tubular acidosis, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
400 drug discovery papers about Distal renal tubular acidosis, with 1 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Whole exome sequencing identifies three novel variants and establishes the molecular diagnosis of ATP6V0A4-related distal renal tubular acidosis in a lebanese infant.
Distal renal tubular acidosis (dRTA) is a rare inherited disorder characterized by impaired urinary acidification, leading to metabolic acidosis, hypokalemia, nephrocalcinosis, and growth impairment. Pathogenic variants in ATP6V0A4 are among the most common genetic causes of autosomal recessive dRTA. We report a Lebanese infant presenting with failure to thrive, recurrent vomiting, severe hyperchloremic metabolic acidosis, hypokalemia, and bilateral nephrocalcinosis, in whom whole-exome sequencing (WES) was performed to establish the molecular diagnosis and perform a comprehensive genomic evaluation. WES identified three novel variants, including a novel homozygous likely pathogenic ATP6V0A4 variant, consistent with the patient's phenotype. Two additional novel variants in TTN and CEP290 were also detected. Family segregation analysis confirmed the inheritance pattern of all three variants and refined the interpretation of the additional genomic findings. The patient showed sustained clinical and biochemical improvement to alkali therapy, with normalization of biochemical abnormalities and improvement in growth during follow-up. This report expands the molecular spectrum of ATP6V0A4-related dRTA and illustrates the clinical utility of comprehensive WES combined with segregation analysis for accurate molecular diagnosis, variant interpretation, genetic counseling, and the evaluation of additional genomic findings in rare inherited disorders.
2026-08-03 | Renal cysts in WDR72-associated distal renal tubular acidosis: expanding the phenotypic spectrum.
Pathogenic variants in the WDR72 gene are known to cause hypoplastic amelogenesis imperfecta (AI) and have recently been linked to distal renal tubular acidosis (dRTA). This case report highlights an unusual presentation of WDR72-associated dRTA with renal cysts. A 12-year-old boy presented with difficulty walking, lower limb deformities, and significant growth retardation. On examination, hypoplastic AI, rickets, and short stature were present. Biochemical investigations showed hypokalemia, hypophosphatemia, elevated alkaline phosphatase, and hypercalciuria. Imaging revealed medullary nephrocalcinosis and renal cysts. Clinical exome sequencing identified a homozygous pathogenic nonsense variant in WDR72 (NM_182758.4): c.2934G > A (p.Trp978Ter), consistent with autosomal recessive inheritance. He was diagnosed with dRTA and managed with potassium citrate and phosphate supplementation. Over two years, the patient showed improved growth velocity and reduced hypercalciuria, though nephrocalcinosis and renal cysts persisted. This case of WDR72-associated dRTA complicated by renal cyst formation is an underrecognized phenotype of this rare disorder. It further highlights that delayed diagnosis and prolonged, uncorrected tubulopathy may result in structural renal injury that is not fully reversible with treatment. Systematic renal evaluation, including biochemical assessment and renal ultrasonography, is strongly warranted in all children presenting with AI, particularly in the presence of concurrent growth failure, electrolyte disturbances, or rachitic changes, to facilitate early diagnosis and mitigate the risk of long-term renal sequelae.
2026-08-03 | Nephrogenic Diabetes Insipidus Presenting with Hypokalemic Paralysis in an Adolescent with Primary Sjögren's Syndrome: A Case Report.
Diabetes insipidus (DI) is a rare disorder characterized by polyuria, polydipsia, and dilute urine. Nephrogenic diabetes insipidus (NDI) secondary to distal renal tubular acidosis (dRTA) in primary Sjögren's syndrome (pSS) is exceedingly rare in children. A 16-year-old girl presented with hypokalemic paralysis (potassium 1.89 mmol/L), polyuria (>5 L/day),and growth retardation (height 141 cm, <3rd percentile). Laboratory studies revealed dRTA with secondary NDI. Autoimmune workup confirmed pSS. A systematic literature review identified only five similar pediatric cases. Initial management with hydrochlorothiazide exacerbated hypokalemia and precipitated hypochloremic metabolic alkalosis. Switching to amiloride combined with glucocorticoids and potassium supplementation normalized electrolytes, reduced urine output to 1.5 L/day, and resulted in catch-up growth at the 6-month follow-up. This case highlights the pathophysiologic cascade of pSS-related dRTA causing secondary NDI and underscores the importance of early recognition and tailored diuretic selection in adolescents.
2026-06-29 | Tislelizumab-induced distal renal tubular acidosis presenting with life-threatening hypokalemia: a case report.
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) affecting multiple organs. Distal renal tubular acidosis (dRTA) as a renal irAE is exceedingly rare, often delaying diagnosis due to nonspecific symptoms. A 63-year-old man with stage IIIA lung squamous cell carcinoma developed recurrent nausea and vomiting after three cycles of nab-paclitaxel/carboplatin combined with tislelizumab. Laboratory evaluation revealed profound metabolic acidosis (CO2-CP nadir 11.6 mmol/L) and life-threatening hypokalemia (serum potassium nadir 1.1 mmol/L), requiring ICU admission and mechanical ventilation. Despite aggressive intravenous potassium supplementation (up to 20 mEq/h), hypokalemia paradoxically worsened. Urine pH was 7.0 during systemic acidosis, indicating impaired renal acidification. After excluding other causes, a diagnosis of tislelizumab-induced dRTA was established. Tislelizumab was discontinued, and treatment with oral potassium citrate and prednisone (60 mg/day, tapered over 5.5 months) led to complete resolution of metabolic abnormalities. Over one year of follow-up, the patient has maintained normal renal function without recurrence and achieved a major partial response of his lung cancer. This first reported case of tislelizumab-induced dRTA highlights the need for vigilance when encountering unexplained, potassium-refractory electrolyte disturbances during ICI therapy, emphasizing early diagnosis, drug discontinuation, and pathophysiology-guided therapy.
2026-06-11 | Table 1_Tislelizumab-induced distal renal tubular acidosis presenting with life-threatening hypokalemia: a case report.docx
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) affecting multiple organs. Distal renal tubular acidosis (dRTA) as a renal irAE is exceedingly rare, often delaying diagnosis due to nonspecific symptoms. A 63-year-old man with stage IIIA lung squamous cell carcinoma developed recurrent nausea and vomiting after three cycles of nab-paclitaxel/carboplatin combined with tislelizumab. Laboratory evaluation revealed profound metabolic acidosis (CO2-CP nadir 11.6 mmol/L) and life-threatening hypokalemia (serum potassium nadir 1.1 mmol/L), requiring ICU admission and mechanical ventilation. Despite aggressive intravenous potassium supplementation (up to 20 mEq/h), hypokalemia paradoxically worsened. Urine pH was 7.0 during systemic acidosis, indicating impaired renal acidification. After excluding other causes, a diagnosis of tislelizumab-induced dRTA was established. Tislelizumab was discontinued, and treatment with oral potassium citrate and prednisone (60 mg/day, tapered over 5.5 months) led to complete resolution of metabolic abnormalities. Over one year of follow-up, the patient has maintained normal renal function without recurrence and achieved a major partial response of his lung cancer. This first reported case of tislelizumab-induced dRTA highlights the need for vigilance when encountering unexplained, potassium-refractory electrolyte disturbances during ICI therapy, emphasizing early diagnosis, drug discontinuation, and pathophysiology-guided therapy.
2026-08-13 | Whole exome sequencing identifies three novel variants and establishes the molecular diagnosis of ATP6V0A4-related distal renal tubular acidosis in a lebanese infant.
Distal renal tubular acidosis (dRTA) is a rare inherited disorder characterized by impaired urinary acidification, leading to metabolic acidosis, hypokalemia, nephrocalcinosis, and growth impairment. Pathogenic variants in ATP6V0A4 are among the most common genetic causes of autosomal recessive dRTA. We report a Lebanese infant presenting with failure to thrive, recurrent vomiting, severe hyperchloremic metabolic acidosis, hypokalemia, and bilateral nephrocalcinosis, in whom whole-exome sequencing (WES) was performed to establish the molecular diagnosis and perform a comprehensive genomic evaluation. WES identified three novel variants, including a novel homozygous likely pathogenic ATP6V0A4 variant, consistent with the patient's phenotype. Two additional novel variants in TTN and CEP290 were also detected. Family segregation analysis confirmed the inheritance pattern of all three variants and refined the interpretation of the additional genomic findings. The patient showed sustained clinical and biochemical improvement to alkali therapy, with normalization of biochemical abnormalities and improvement in growth during follow-up. This report expands the molecular spectrum of ATP6V0A4-related dRTA and illustrates the clinical utility of comprehensive WES combined with segregation analysis for accurate molecular diagnosis, variant interpretation, genetic counseling, and the evaluation of additional genomic findings in rare inherited disorders.
2026-08-03 | Renal cysts in WDR72-associated distal renal tubular acidosis: expanding the phenotypic spectrum.
Pathogenic variants in the WDR72 gene are known to cause hypoplastic amelogenesis imperfecta (AI) and have recently been linked to distal renal tubular acidosis (dRTA). This case report highlights an unusual presentation of WDR72-associated dRTA with renal cysts. A 12-year-old boy presented with difficulty walking, lower limb deformities, and significant growth retardation. On examination, hypoplastic AI, rickets, and short stature were present. Biochemical investigations showed hypokalemia, hypophosphatemia, elevated alkaline phosphatase, and hypercalciuria. Imaging revealed medullary nephrocalcinosis and renal cysts. Clinical exome sequencing identified a homozygous pathogenic nonsense variant in WDR72 (NM_182758.4): c.2934G > A (p.Trp978Ter), consistent with autosomal recessive inheritance. He was diagnosed with dRTA and managed with potassium citrate and phosphate supplementation. Over two years, the patient showed improved growth velocity and reduced hypercalciuria, though nephrocalcinosis and renal cysts persisted. This case of WDR72-associated dRTA complicated by renal cyst formation is an underrecognized phenotype of this rare disorder. It further highlights that delayed diagnosis and prolonged, uncorrected tubulopathy may result in structural renal injury that is not fully reversible with treatment. Systematic renal evaluation, including biochemical assessment and renal ultrasonography, is strongly warranted in all children presenting with AI, particularly in the presence of concurrent growth failure, electrolyte disturbances, or rachitic changes, to facilitate early diagnosis and mitigate the risk of long-term renal sequelae.
2026-08-03 | Nephrogenic Diabetes Insipidus Presenting with Hypokalemic Paralysis in an Adolescent with Primary Sjögren's Syndrome: A Case Report.
Diabetes insipidus (DI) is a rare disorder characterized by polyuria, polydipsia, and dilute urine. Nephrogenic diabetes insipidus (NDI) secondary to distal renal tubular acidosis (dRTA) in primary Sjögren's syndrome (pSS) is exceedingly rare in children. A 16-year-old girl presented with hypokalemic paralysis (potassium 1.89 mmol/L), polyuria (>5 L/day),and growth retardation (height 141 cm, <3rd percentile). Laboratory studies revealed dRTA with secondary NDI. Autoimmune workup confirmed pSS. A systematic literature review identified only five similar pediatric cases. Initial management with hydrochlorothiazide exacerbated hypokalemia and precipitated hypochloremic metabolic alkalosis. Switching to amiloride combined with glucocorticoids and potassium supplementation normalized electrolytes, reduced urine output to 1.5 L/day, and resulted in catch-up growth at the 6-month follow-up. This case highlights the pathophysiologic cascade of pSS-related dRTA causing secondary NDI and underscores the importance of early recognition and tailored diuretic selection in adolescents.
2026-06-29 | Tislelizumab-induced distal renal tubular acidosis presenting with life-threatening hypokalemia: a case report.
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) affecting multiple organs. Distal renal tubular acidosis (dRTA) as a renal irAE is exceedingly rare, often delaying diagnosis due to nonspecific symptoms. A 63-year-old man with stage IIIA lung squamous cell carcinoma developed recurrent nausea and vomiting after three cycles of nab-paclitaxel/carboplatin combined with tislelizumab. Laboratory evaluation revealed profound metabolic acidosis (CO2-CP nadir 11.6 mmol/L) and life-threatening hypokalemia (serum potassium nadir 1.1 mmol/L), requiring ICU admission and mechanical ventilation. Despite aggressive intravenous potassium supplementation (up to 20 mEq/h), hypokalemia paradoxically worsened. Urine pH was 7.0 during systemic acidosis, indicating impaired renal acidification. After excluding other causes, a diagnosis of tislelizumab-induced dRTA was established. Tislelizumab was discontinued, and treatment with oral potassium citrate and prednisone (60 mg/day, tapered over 5.5 months) led to complete resolution of metabolic abnormalities. Over one year of follow-up, the patient has maintained normal renal function without recurrence and achieved a major partial response of his lung cancer. This first reported case of tislelizumab-induced dRTA highlights the need for vigilance when encountering unexplained, potassium-refractory electrolyte disturbances during ICI therapy, emphasizing early diagnosis, drug discontinuation, and pathophysiology-guided therapy.
2026-06-11 | Table 1_Tislelizumab-induced distal renal tubular acidosis presenting with life-threatening hypokalemia: a case report.docx
Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) affecting multiple organs. Distal renal tubular acidosis (dRTA) as a renal irAE is exceedingly rare, often delaying diagnosis due to nonspecific symptoms. A 63-year-old man with stage IIIA lung squamous cell carcinoma developed recurrent nausea and vomiting after three cycles of nab-paclitaxel/carboplatin combined with tislelizumab. Laboratory evaluation revealed profound metabolic acidosis (CO2-CP nadir 11.6 mmol/L) and life-threatening hypokalemia (serum potassium nadir 1.1 mmol/L), requiring ICU admission and mechanical ventilation. Despite aggressive intravenous potassium supplementation (up to 20 mEq/h), hypokalemia paradoxically worsened. Urine pH was 7.0 during systemic acidosis, indicating impaired renal acidification. After excluding other causes, a diagnosis of tislelizumab-induced dRTA was established. Tislelizumab was discontinued, and treatment with oral potassium citrate and prednisone (60 mg/day, tapered over 5.5 months) led to complete resolution of metabolic abnormalities. Over one year of follow-up, the patient has maintained normal renal function without recurrence and achieved a major partial response of his lung cancer. This first reported case of tislelizumab-induced dRTA highlights the need for vigilance when encountering unexplained, potassium-refractory electrolyte disturbances during ICI therapy, emphasizing early diagnosis, drug discontinuation, and pathophysiology-guided therapy.
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Drug Discovery Landscape
2 orphan drug designations for Distal renal tubular acidosis.
2 orphan drug designations for Distal renal tubular acidosis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
fixed-dose combination of potassium citrate and potassium bicarbonate | small molecules | FDA | 2022-12-09 | — | Advicenne |
Potassium citrate monohydrate, Potassium hydrogen carbonate [Sibnayal] | small molecules | EMA | 2017-06-20 | — | [INACTIVE] Advicenne |
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