Abstract / Summary
Abstract Background Calcium phosphate (CaP) nephrolithiasis is typically associated with idiopathic hypercalciuria, alkaline urine, and medullary nephrocalcinosis, and often reflects the interaction of acquired factors with complex genetic susceptibility rather than a single monogenic defect. In this context, we describe a CaP-predominant stone former with a heterozygous likely pathogenic SLC7A9 variant to emphasize integrating genetic findings with stone composition and serial urinary metabolic phenotyping. Case presentation A 44-year-old Caucasian multiparous woman presented with a six‑year history of recurrent bilateral nephrolithiasis, medullary nephrocalcinosis, and prior ureteroscopic lithotripsy. Stone analysis showed 90% CaP and 10% calcium oxalate. Serial 24-hour urines evolved from low urine volume and hypocitraturia with elevated CaP supersaturation to persistent hypercalciuria (up to 299 mg/day) with alkaline urine (pH ~ 6.4-6.8), while oxalate and citrate normalized. A nephrolithiasis/nephrocalcinosis gene panel revealed a heterozygous likely pathogenic SLC7A9 variant; no cystine was detected in stones, qualitative cystine screen, or amino acid analysis. Management focused on high fluid intake, sodium restriction, normal dietary calcium, moderated animal protein, and low‑dose hydrochlorothiazide; cystine-directed (thiol) therapy and potassium citrate were deferred given the absence of clinical cystinuria. The clinical, biochemical, and imaging profile supported CaP stone formation driven by idiopathic hypercalciuria and urinary alkalinization rather than cystine supersaturation. This discordant presentation of calcium-based stones in the setting of cystinuria carrier status constrained therapeutic options, as cystine-directed therapies were not indicated and alkali therapy required caution due to the risk of further increasing CaP supersaturation. Conclusions This case reinforces the educational value of focusing on the clinical phenotype: identification of a heterozygous likely pathogenic SLC7A9 variant should not, in isolation, establish a diagnosis of cystinuria when stone composition and urinary biochemistry support CaP nephrolithiasis. Management should remain guided by established principles based on stone composition, urine chemistry, and imaging.