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.

A case of parathyroid carcinoma with acute renal failure and microscopic nephrocalcinosis / 대한내과학회지

Parathyroid carcinoma is a very rare disease in patients with primary hyperparathyroidism. Renal impairment and bone disease in the case of parathyroid carcinoma is common due to hypercalcemia. Renal diseases, including nephrocalcinosis, nephrolithiasis, and renal failure are frequent compared with those of benign parathyroid tumors. Nephrocalcinosis is a disorder of increased calcium content and deposition within renal parenchyma. Most cases reporting parathyroid carcinoma have shown medullary calcinosis on radiologic images, but there has been no definitive report of microscopic nephrocalcinosis which does not have a positive radiologic finding. In the case reported herein, a 50-year-old woman had experienced general weakness and a decline in vision. She had hypercalcemia and acute renal failure and the renal biopsy revealed nephrocalcinosis. The PTH level was elevated (940.47 pg/mL) and the parathyroid tumor was localized based on several radiologic findings. Capsular invasion was noted at the time right parathyroidectomy, indicative of parathyroid carcinoma, thus we carried out ipsilateral thyroidectomy. Hypercalcemia was improved after surgery, but renal function was not improved completely due to microscopic nephrocalcinosis.