Antiproteinuric effect of ARB in lupus nephritis patients with persistent proteinuria despite immunosuppressive therapy

Abstract

Recent immunosuppressive treatments for lupus nephritis have improved renal survival rate, however, there still exists lupus nephritis refractory to these treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease blood pressure but also to have an independent renoprotecting effect by interrupting renin-angiotensin system. The aim of this study was to evaluate whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in this trial were twelve patients with lupus nephritis who were diagnosed by renal biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive treatments. ARB, losartan or candesartan, was administered for six months. Various clinical parameters were compared before and after ARB administration. Proteinuria decreased after ARB treatment in 83% of the patients and the median amount of proteinuria significantly decreased from 2530 mg/gCr to 459 mg/gCr (P = 0.03). In addition, serum albumin and cholesterol levels were significantly improved. Systolic blood pressure significantly decreased, but none had symptoms of hypotension. The antiproteinuric effect of ARB did not correlate with the reduction of blood pressure. Interestingly, higher total complement activity levels before ARB treatment were associated with a greater reduction of proteinuria. The addition of ARB would be a safe and effective treatment for lupus nephritis with persistent proteinuria despite corticosteroids and/or immunosuppressive treatments.

Keywords

angiotensin II blocker ARB lupus nephritis proteinuria

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References

Austin HA , Balow JE. Natural history and treatment of lupus nephritis . Semin Nephrol 1999; 19: 2-11 .

Austin HA , Balow JE. Treatment of lupus nephritis . Semin Nephrol 2000; 20: 265-276 .

Ruggenti P , Schieppati A , Remuzzi G. Progression, remission, regression of chronic renal diseases . Lancet 2001; 357: 1601-1608 .

Russo D , Pisani A , Balleta MM et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy . Am J Kidney Dis 1999; 33: 851-856 .

Brenner BM , Cooper ME , de Zeeuw D et al. , for the RENAAL Study Investigators . Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy . N Engl J Med 2001; 345: 861-869 .

Lewis EJ , Hunsicker LG , Clarke WR et al. , for the Collaborative Study Group . Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes . N Engl J Med 2001; 345: 851-860 .

Hochberg MC. Updating the American College of Rheumatology revised criteria for classification of systemic lupus erythematosus . Arthritis Rheum 1997; 40: 1725-1725 .

Bombardier C , Gladman DD , Urowitz MB , Caron D , Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE . Arthritis Rheum 1992; 35: 630-640 .

Fiehn C , Hajjar Y , Mueller K , Waldherr R , Ho AD , Andrassy K. Improved clinical outcome of lupus nephritis during the past decade: importance of early diagnosis and treatment . Ann Rheum Dis 2003; 62: 435-439 .

10.

Remuzzi G , Bertani T. Pathophysiology of progressive nephropathies . N Engl J Med 1998; 339: 1448-1456 .

11.

Peterson JC , Adler S , Burkart JM et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study . Ann Intern Med 1995; 123: 754-762 .

12.

Wapstra FH , Navis G , de Jong PE , de Zeeuw D. Prognostic value of the short-term antiproteinuric response to ACE inhibition for prediction of GFR decline in patients with nondiabetic renal disease . Exp Nephrol 1996; 4(Suppl 1): 47-52 .

13.

Miyauchi N , Nakamura Y. Antiproteinuric effect of an angiotensin II receptor antagonist in membranous nephropathy . Nephron 2001; 88: 183-184 .

14.

Odabas AR , Cetinkaya R , Selcuk Y , Bilen H. Effect of losartan treatment on the proteinuria in normotensive patients having proteinuria due to secondary amyloidosis . Usp J Med Sci 2001; 106: 183-188 .

15.

Cao Z , Cooper ME. Role of angiotensin II in tubulointerstitial injury . Semin Nephrol 2001; 21: 554-562 .