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 calcium phosphate (CaP) precipitation is thought to accelerate progression to end-stage renal failure in chronic kidney diseases. In phosphorus (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 lithium (Li) clearance (ePTpc-Li) or as a fixed 0.7 fraction of glomerular filtration rate (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 ± 0.47 mg/dL for ePTpc-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, P < .001 for all); ePTpc was inversely correlated with Ccr and directly with PTH, fractional P excretion and excretion (UpV) corrected for GFR (P < .001 for all), but not with Pp. ePTpc-Li and ePTpc-70 were significantly correlated (r = 0.62, P < .001), but ePTpc-70 was lower than the 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.