Effect of valsartan on urinary protein excretion and renal function in patients with chronic renal allograft nephropathy.
Chronic allograft nephropathy (CAN) remains a significant cause of late renal allograft loss. Although many factors may be involved in pathogenesis, the hemodynamic and fibrogenic consequences of long-term therapy with cyclosporine (CsA) have been implicated as important potentially reversible causes. CsA's effect on CAN is mediated in part through increased renal expression of TGF-beta, which can be modified by administration of angiotensin receptor blockers (ARBs). A pilot study was undertaken to evaluate the safety and efficacy of the ARB valsartan on renal function and proteinuira in patients with CAN. Ten patients on CsA-based therapy with evidence of CAN received valsartan in an initial dose of 80 mg/d, force titrated to 160 mg/d after 4 weeks, for a total of 52 weeks. Renal function was evaluated by serum creatinine, 24-hour creatinine clearance (CrCl), and isotope, GFR and urinary protein by 24-hour protein excretion. The 10 patients were aged 20 to 71 years and had been transplanted for 88.2 +/- 64.8 months at the time of study. After 52 weeks of valsartan therapy mean blood pressure (BP) fell from 152/88 mm Hg to 138/77 mm Hg (P =.06); serum creatinine rose from 206 +/- 55 micromol/L to 238 +/- 81 micromol/L (P =.22.); GFR fell from 39.8 +/- 17.6 to 31.9 +/- 19 mL/min (P =.23); and urine protein fell from 2.16 +/- 2.7 to 1.12 +/-.095 g/24 hours (P =.13). Side effects of valsartan therapy were few and included transient hyperkalemia in 2/10 patients. The small rise in serum creatinine and fall in GFR observed were not statistically significant. Urine protein fell by more than 50%, though the small patient numbers in this pilot study prevent this from achieving statistical significance. It is concluded that valasartan reduces BP and proteinuria in CAN patients without inducing a serious worsening in renal function. Valsartan may have a role to play in the management of patients with CAN.
Muirhead
N
N
London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.
House
A
A
Hollomby
D J
DJ
Jevnikar
A M
AM
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000188:drug therapy / Q000503:physiopathology / Q000652:urine; D011188:Potassium / Q000378:metabolism; D011507:Proteinuria / Q000139:chemically induced*; D013777:Tetrazoles / Q000627:therapeutic use*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D003404:Creatinine; D014633:Valine; D011188:Potassium