The European distal renal tubular acidosis registry: a 5-year analysis

BACKGROUND: Distal renal tubular acidosis (dRTA) is characterized by metabolic acidosis, growth failure nephrocalcinosis, nephrolithiasis and chronic kidney disease (CKD). Previous retrospective data suggested improved outcome with adequate metabolic control, but confirmation from prospective data is lacking. Since 2019, the European dRTA registry has collected prospective data on patients with dRTA. Herein we present results of the first data analysis. METHODS: The registry is hosted as a subregistry of the European Rare Kidney Disease Network (www.ERKnet.org). In addition to the standard items of growth and plasma creatinine, additional data on plasma and urine biochemistries, genetics, treatment and clinical manifestations were collected from February 2019 through May 2024. Logistic regression analysis was used to identify predictors of CKD and impairedgrowth. RESULTS: Of the 214 patients enrolled in the registry, only 22% were >18 years at the last visit. A genetic cause was documented in 69% of patients.On average, low blood bicarbonate levels (<22 mmol/L) and hypercalciuria were observed in 42% and 25% of patients, respectively, independently from age. Multivariable analysis showed that height standard deviation score (SDS) was positively associated with serum bicarbonate levels (p=0.008) and with early diagnosis (p=0.005). Further modelling based on odds ratios indicated that height SDS increased progressively with serum bicarbonate levels until they reached 22-24 mmol/L. Patients aged >30 years had significantly lower eGFR (p<0.001) and the overall prevalence of CKD ≥stage 2 was 36%. Patients with SLC4A1 variants were at higher risk of CKD>1 (p=0.013). CONCLUSION: Our results in this primarily paediatric cohort highlight the importance of metabolic control and support increasing the blood bicarbonate level for therapy to 24 mmol/L to improve growth. Compared to the overall population, patients with dRTA are at higher risk of CKD from childhood, particularly if they have underlying SLC4A1 variants.