Nephrocalcinosis: unveiling renal tubulopathies in the genomic era

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.

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.

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.

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.