Etiology and outcomes of primary renal tubular acidosis.

Background: This study investigates the etiology, outcomes, and genotype-phenotype correlations in patients with renal tubular acidosis (RTA) at a tertiary care center in New Delhi.

Methods: This cross-sectional study included children and young adults with RTA who underwent clinical, biochemical, radiological and/or genetic evaluations between July 2020 and December 2024. We report clinical phenotype, anthropometry, metabolic control and progression to chronic kidney disease (CKD) in relation to genotype of distal RTA.

Results: Of 135 patients enrolled, 69 had distal RTA. The yield of genetic testing was 72% in distal RTA and 88.7% in Fanconi syndrome. Variants in SLC4A1 (42.4%) and ATP6V1B1 (28.8%) were the most common etiologies of distal RTA. Compared to other etiologies, patients with SLC4A1 variants were older at symptom onset (P = 0.008). Hematological abnormalities were more frequent in patients with biallelic compared to heterozygous SLC4A1 variants (50% vs. 12.5%; P = 0.18). Nephrocalcinosis and metabolic control were similarly prevalent across genetic categories of distal RTA. Sensorineural hearing loss was more common with ATP6V1B1 than with ATP6V0A4 variants (61.5% vs. 22.2%, P = 0.099) and did not vary by metabolic control. At median follow-up of 5-years, 74.1% of patients with distal RTA had short stature, 74.6% had poor metabolic control and 2.9% had progressed to CKD G3-5.

Conclusions: This study outlines the genetic etiology and phenotype of distal RTA in south Asia. Over short-term follow-up, poor metabolic control and severe stunting were common, while CKD was uncommon.