End-proximal tubule phosphate concentration increases as GFR falls in humans: measurement by means of a lithium clearance-based methodology.

BACKGROUND: Microscopic nephrocalcinosis secondary to intratubular CaP precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In P-loaded uninephrectomized rats intratubular CaP crystal formation and progressive tubular damage occurred when end-proximal tubule P concentration (ePTpc) increased above a threshold level.

METHODS: We have calculated ePTpc in humans by urine P and creatinine concentration, with the end-proximal tubule fluid volume calculated either as Li clearance (ePTpc-Li) or as a fixed 0.7 fraction of GFR, as published (ePTpc-70). Healthy people undergoing living transplant kidney donation before (DON-pre, n = 70) and after (DON-post, n = 64) nephrectomy, and 25 patients with stage 2-5 CKD, were investigated while on regular free diet.

RESULTS: ePTpc showed a stepwise increase with decreasing functional renal mass (DON-pre 2.51 ± 0.99 and 1.56 ± 0.47mg/dl for -Li and -70 calculation,  respectively;  DON-post 3.43 ± 1.14 and 2.18 ± 0.44;  CKD 5.68 ± 3.30 and 3.00 ± 1.30,  <0.001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and P excretion corrected for GFR (p < 0.001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r = 0.62, p < 0.001), but ePTpc-70 was lower than corresponding ePTpc-Li. Levels of ePTpc increased above a suggested dangerous threshold when daily UpV/GFR was higher than about 10 mg/mlCcr.

CONCLUSIONS: ePTpc progressively increases in humans as functional renal mass falls independently from plasma P levels. Main determinants of ePTpc rise are GFR fall, degree of phosphaturia per unit GFR, and P intake corrected for GFR. It may become a novel, potentially useful, indicator to guide management of CKD patients.