A Study on Clinical, Biochemical, Drug Trough Level and Histopathological Correlation of Calcineurin Inhibitor (CNI) Toxicity in Renal Allograft Recipients


Authors : R. Gandhimohan, M. Seenivasan, N. Gopalakrishnan.

Volume/Issue : Volume 4 - 2019, Issue 2 - February

Calcineurin inhibitor revolutionized the renal allograft transplant outcome. However it causes nephrotoxicity in long run. The serum trough level of the drug does not correlate with degree of nephrotoxicity because of its varied pharmocokinetics, narrow therapeutic index, and individual sensitivity to toxic levels. Toxicity clinically characterised by tremor, hypertension, hyperuricemia, histopathologically by isometric vacuolization, arterial nodular hyalinosis, striped fibrosis and interstitial atrophy. This study conducted at Rajiv Gandhi Government General hospital, Chennai from June 2012 to June2013. Sixty one patients were included in this study. Clinical toxic features, drug trough level, biochemical parameters were recorded in 0-3, 3-6, 6-9, more than 9 months were recorded. Allograft biopsy and histopathology examinations were done when required with patient consent. Prevalence of clinical calcineurin inhibitor toxicity was 60.7 %( 37), 39.3% (24), 25.4% (15) and 23.3%(10) at 0-3, 3-6, 6-9, and >9 months respectively. Among clinical features tremor and hypertension were present in majority of the recipients [tremor: 39.3% (24), 34.4% (21) , 25.4% (15) and 20.9% (9); hypertension: 39.3% (24), 31.1% (19), 13.6% (6) and 7% (3) at 0-3, 3-6, 6-9 and >9 months respectively]. NODAT was present in 4.9% (93) in 0-3 & 3-6 months, 6.8% (4) in 6-9 months and 2.3% (1) in more than 9 months. Graft dysfunction was in 37.7% (23), 23% (14) , 37.3% (22), and 7% (3) at 0-3, 3-6, 6-9 month and thereafter. Elevated trough level was seen in 29.5% (18), 27.9% (17), 32.2% (19) and 18.6% (8) at 0-3, 3-6, 6-9 month and thereafter. In our study a significant correlation between tremor, clinical toxicity and elevated trough (Co) level at 3-6 and 6-9 month (P<0.001) was observed. There was no significant correlation between clinical toxicity, trough level, graft dysfunction and histopathological correlation at 0-3, 36, 6-9 and >9 months. There was a significant correlation between tremor and elevated trough level of calcineurin inhibitor was observed at 3-6 and 6-9 months.

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