Tubulopathy in nephrolithiasis: consequence rather than cause

To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and gamma-glutamyl transferase (gamma-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of gamma-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone.