DOWN-REGULATION OF PTH PTHRP RECEPTOR IN THE KIDNEY OF PATIENTS WITH RENAL IMPAIRMENT/

Objective To investigate whether the downregulation of renal parathyro id hormone,;parathyroid hormone related protein (PTH/PTHrP) receptor m essenger ribonucleic acid (mRNA) expression is a general phenomenon in patients with different stages of renal disease, besides chronic rena l failure. Methods Twenty-five patients were divided into the followin g groups: (1) chronic glomerulonephritis with normal renal function (G NN) (2) chronic glomerulonephritis with moderate renal insufficiency ( GNI) (3) severe chronic renal failure undergoing maintenance dialysis (CRF) (4) acute renal failure during oliguric phase (ARF) (5) normal c ontrol without renal suffering (NC). Using relatively quantitative rev erse transcription/polymerase chain reaction (RT/PCR) method, we inves tigated PTH/PTHrP receptor mRNA expression in renal specimens obtained through biopsy or operation. The levels of plasma C-terminal PTH, ser um phosphorus and calcium were also observed at the same time. Results Plasma C-terminal PM levels in GNI, CRF and ARF patients were 1.90, 9 .73 and 8.63 times higher than those in NC. However, the difference be tween GNN and NC was insignificant. CRF and ARF patients also presente d obviously elevated serum phosphorus (1.61, 1.86 vs 1.14 mmol/L) and reduced serum calcium (1.82, 1.71 vs 2.26 mmol/L) compared with that i n the control, These two parameters for GNN and GNI patients were norm al. The levels of PTH/PTHrP receptor mRNA (corrected by beta-actin mRN A) in the kidney of GNN, GNI, CRF and ARF patients was markedly decrea sed by up to 35.7%, 68.5%, 77.9% and 92.2%, respectively.Conclusions T he down-regulation of renal PTH/PTHrP receptor mRNA occurs much earlie r than the changes of renal function, plasma PTH, serum phosphorus and calcium in the course of human renal disease.