A study on Clinical, Biochemical, Drug trough level and histopathological correlation of calcineurin inhibitor (CNI) toxicity in renal allograft recipient.

Gandhimohan, R (2014) A study on Clinical, Biochemical, Drug trough level and histopathological correlation of calcineurin inhibitor (CNI) toxicity in renal allograft recipient. Masters thesis, Madras Medical College, Chennai.


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INTRODUCTION : The purpose of renal replacement therapy for End Stage Renal Disease patients was to prolong and maintain quality of life. Despite the many attempts to do renal replacement in early part of 20th century, the first successful renal transplant was done in 1954 by Murray among identical twins. Introduction of calcineurin inhibitor in later part of twentieth century revolutionized the history of renal transplantation by reducing the short term morbidity and mortality. However the patients receiving calcineurin inhibitor were under the risk of calcineurin inhibitor nephrotoxicity in long run. The chronic nephrotoxic effects of calcineurin inhibitors associated with the renal parenchymal damage plays a major role in the pathogenesis of chronic renal dysfunction. Calcineurin inhibitor toxicity clinically characterized by tremor, hypertension, hypertrichosis and gum hypertrophy, biochemically by raising creatinine (graft dysfunction), hyperglycemia, hyperkalemia and hyperuricemia and histopathologicaly by isometric vacuolization, arterial nodular hyalinosis, striped fibrosis and interstitial atrophy. The effect of toxicity was reversible in short term, became irreversible in long term. Lower dose results in graft dysfunction and rejection, higher dose results in toxicity because of its narrow therapeutic index ( little difference between toxic and therapeutic doses). So it was mandatory to adjust its dosage according to measurements of the actual blood levels through therapeutic drug monitoring (TDM). The serum level of drug does not correlat with the degree of nephrotoxicity in most of the occasion because of its varied pharmacokinetics, narrow therapeutic index, individual sensitivity to toxic effects. Though there are few international studies on prevalence of calcineurin inhibitor toxicity and its clinico pathological correlation, a good study in this part of world is lacking . So, this study, attempt to find out the correlation among clinical, biochemical, drug trough level and histopathological features of calcineurin inhibitor toxicity. AIM OF THE STUDY : To study the clinical, biochemical, whole blood trough level and histopathological correlation of calcineurin inhibitors (CNI) toxicity in renal allograft recipients. CONCLUSION : 1. 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. 3. There was no significant correlation between clinical toxicity, trough level, graft dysfunction and histopathological correlation at 0-3, 3- 6, 6-9 and >9 months. 4. There was a significant correlation between tremor and elevated trough level of tacrolimus was observed at 0-3 and 3-6 months.

Item Type: Thesis (Masters)
Uncontrolled Keywords: Clinical ; Biochemical ; Drug ; trough level ; histopathological correlation ; calcineurin inhibitor ; toxicity ; renal allograft recipient.
Subjects: MEDICAL > Nephrology
Depositing User: Kambaraman B
Date Deposited: 11 Jul 2017 05:34
Last Modified: 11 Jul 2017 05:34
URI: http://repository-tnmgrmu.ac.in/id/eprint/1380

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