Down-regulation of PTH/PTHrP receptor in the kidney of patients with renal impairment.
OBJECTIVE
To investigate whether the down-regulation of renal parathyroid hormone/parathyroid hormone related protein (PTH/PTHrP) receptor messenger ribonucleic acid (mRNA) expression is a general phenomenon in patients with different stages of renal disease, besides chronic renal failure.


METHODS
Twenty-five patients were divided into the following groups: (1) chronic glomerulonephritis with normal renal function (GNN) (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 control without renal suffering (NC). Using relatively quantitative reverse transcription/polymerase chain reaction (RT/PCR) method, we investigated PTH/PTHrP receptor mRNA expression in renal specimens obtained through biopsy or operation. The levels of plasma C-terminal PTH, serum phosphorus and calcium were also observed at the same time.


RESULTS
Plasma C-terminal PTH levels in GNI, CRF and ARF patients were 1.90, 9.73 and 8.63 times higher than those in NC. However, the difference between GNN and NC was insignificant. CRF and ARF patients also presented 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 in the control. These two parameters for GNN and GNI patients were normal. The levels of PTH/PTHrP receptor mRNA (corrected by beta-actin mRNA) in the kidney of GNN, GNI, CRF and ARF patients was markedly decreased by up to 35.7%, 68.5%, 77.9% and 92.2%, respectively.


CONCLUSIONS
The down-regulation of renal PTH/PTHrP receptor mRNA occurs much earlier than the changes of renal function, plasma PTH, serum phosphorus and calcium in the course of human renal disease.
D000293:Adolescent; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood; D015536:Down-Regulation; D005260:Female; D005921:Glomerulonephritis / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism