OBJECTIVE To define the renal tubular functional abnormalities in patients with cystic disease of the kidneys. METHODS Patients with autosomal dominant polycystic kidney disease (ADPKD) (n = 4) and medullary sponge kidneys (MSK) (n = 3) with normal glomerular filtration rate (GFR), determined by inulin clearance, and effective renal plasma flow (ERPF), measured by p-aminohippurate clearance, underwent measurement of proximal and distal tubular functions. Proximal tubular functions were determined by the maximum reabsorption of glucose (TmGlucose) and the maximum secretion of p-aminohippurate (TmPAH). Distal tubular functions were measured by the maximum urinary concentrating and diluting mechanisms, and the urinary acidification response to acid load. RESULTS TmGlucose was low in both groups (209 +/- 25 mg/min/1.73 m2 in the ADPKD group and 110 +/- 28 mg/min/1.73 m2 in the MSK, compared with 375 +/- 40 mg/min/1.73 m2 in healthy controls; P < 0.05). Likewise, TmPAH was significantly diminished in patients with ADPKD (72 +/- 6 mg/min/1.73 m2) and MSK (63 +/- 5 mg/min/1.73 m2) when compared with healthy controls (89 +/- 4 mg/min/1.73 m2; P < 0.05). Urinary maximum concentration after fluid deprivation was impaired in both ADPKD and MSK patients, but the diluting mechanism was intact. Finally, the ability to excrete urinary ammonium and titratable acids following an oral acid load was inadequate in both the ADPKD and MSK groups. CONCLUSIONS Proximal and distal tubular functions are impaired in patients with ADPKD and MSK when GFR and ERPF are normal, indicating tubular disruption by the cysts and the alteration of the tubulo-interstitial vascular relationship.