Nephrocalcinosis: unveiling renal tubulopathies in the genomic era

Abstract Introduction: The diagnosis of nephrocalcinosis (NC) is challenging due to difficulties in radiologic detection, clinical heterogeneity, and its broad etiological spectrum that includes both genetic and non-genetic causes. This study aimed to uncover, in a pioneering manner, the distinct NC etiologies in a Brazilian cohort according to age of onset. Methods: This retrospective cross-sectional study was based on 96 medical records of outpatients (66 adults and 30 children) with NC, who had followed a comprehensive investigation. Results: Distal renal tubular acidosis was the leading cause of NC in both children (43.3%) and adults (22.7%), followed by other tubulopathies mostly in children (36.7%), and primary hyperparathyroidism in adults (19.7%). Pediatric patients exhibited more electrolyte disorders (47%), failure to thrive (50%), and sensorineural hearing loss (23%) than adults. Conversely, adults presented more associated nephrolithiasis (73%), low back pain (42%), and lower estimated glomerular filtration rate than children (85 versus 106 mL/min/1.73m2). According to phenotype, genetic suspicion had been raised in 96.7% of children and 57.6% of adults. Nevertheless, the availability of genetic tests was low in the whole cohort. Conclusion: This study represents a novel contribution to the national scientific landscape, revealing a limited access to genetic tests for patients with nephrocalcinosis, likely due to cost and availability constraints in the public healthcare system, and showed that a clinically oriented laboratory protocol may provide more precise indications. Notably, a phenotype suggestive of monogenic disease among 57.6% of adults with NC justifies the need for more frequent genetic investigations in this group.