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Year : 2013  |  Volume : 23  |  Issue : 1  |  Page : 41-46

Calcineurin inhibitor induced nephrotoxicity in steroid resistant nephrotic syndrome

1 Department of Pediatrics, Division of Nephrology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Pathology, Division of Nephrology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
A Bagga
Division of Nephrology, Department of Pediatrics, 3053, Teaching Block, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-4065.107197

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Prolonged therapy with calcineurin inhibitors (CNI) is effective in patients with difficult nephrotic syndrome. However, information on prevalence and risk factors for nephrotoxicity in children with steroid-resistant nephrotic syndrome is limited. This retrospective observational study was conducted on 40 patients with steroid-resistant nephrotic syndrome treated with cyclosporine (CyA) (n = 28) or tacrolimus ( n = 12) for more than 2 years. Nephrotoxicity was defined by the presence of striped fibrosis involving ≥10% of the interstitium or nodular hyalinosis in more than one arteriole. Ten additional parameters were graded semi-quantitatively. Continuous data are presented as median and interquartile range (IQR). The median (IQR) age at onset of nephrotic syndrome and CNI therapy were 30 (21-45) and 49.5 (40-102.5) months. A second renal biopsy, following 30 (26-35) months of CNI therapy, showed histological toxicity in 10 (25%) patients. Toxicity was seen in 7 and 3 patients receiving CyA and tacrolimus, respectively, and 5 patients each with minimal change and focal segmental glomerulosclerosis. Therapy with CNI was associated with significant increases in scores for global glomerulosclerosis, tubular atrophy, interstitial fibrosis, nonnodular arteriolar hyalinosis ( P < –0.001 for all), arteriolar smooth-muscle vacuolization ( P = –0.02), juxtaglomerular hyperplasia ( P = –0.002), and tubular microcalcinosis ( P = –0.06). Risk factors for nephrotoxicity were initial resistance (OR 9; 95% CI 1.0-80.1; P = –0.049); dose of CyA (OR 9.2; 95% CI 1.1-74.6; P = –0.037); duration of heavy proteinuria (OR 1.2; 95% CI 1.0-1.4; P = –0.023); and hypertension during therapy (OR 6; 95% CI 1.3-28.3; P = –0.023). Following prolonged CNI therapy, one in four biopsies show features of toxicity. Prolonged duration of heavy proteinuria, hypertension, initial steroid resistance and high CyA dose predict the occurrence of nephrotoxicity.


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Indian Journal of Nephrology
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Online since 20th Sept '07