Abstract:

Objective: There is no consensus therapy for patients with Alport syndrome. Clinical studies in small samples of patients with Alport syndrome showed that calcineurin inhibitor Cyclosporine A(CsA) might be effective in reducing proteinuria and arrest the progression of chronic renal failure. No data is available for the other calcineurin inhibitor Tacrolimus(FK506) in patients with Alport syndrome. Methodology: In this paper, we conducted a prospective short-term study of the efficacy of FK506 in 5 patients who proved non-repsonsive to ACEI and traditional Chinese herbal medicine. Their age ranged from 8～42 years (averaged 18.5 years), sex was 4 male and 1 female, and inheritance mode 4 X-linkage and 1 autosomal ressesive. All the 5 patients underwent percutanious  biopsy and satisfied the Flinter’s diagnostic criteria for Alport syndrome, and had pathologic evidence of collagen IV chains abnormalities both in kidney and/or skin biopsy specimen. FK506 was administered at a dosage of 0.15mg/kg/d for the first 8 weeks and then tapered to 0.10mg/kg/d for the weeks followed. The target trough serum concentration of FK506 was 5～8ng/dl. Efficacy and side-effects of FK506 were observed at an interval of 2～4weeks during the follow-up. Results: The target trough level of FK506 was achieved in the proposed therapeutic window range in 4 of the 5 patients, with one of CYP3A5-*1/*1 genotype failed to achieved the target ranges. In the end of the second week and the fourth week of follow-up, all the five patients experienced a marked reduction of 24-hour urinary protein excretion, and an elevation of serum albumin level during the weeks followed.  No patient experienced a further improvement of proteinuria after 8 weeks. Two of the 5 patients withdrew the medication because of side-effects as renal toxicity and/or abnormal glucose metabolism. One patient dropped out of the study because of inefficacy associated with failure to achieve targeted trough serum level of FK506. Prolonged therapy (36 weeks and 40 weeks) in another 2 patients showed that serum albumin maintained at 33～35g/L and proteinuria fluctuating between 0.5～2.5 g/L. Side-effect of renal toxicity (30% elevation of serum creatinine above baseline level), gastro-intestinal disorders, and abnormality of glucose metabolism were observed during the first 8 weeks. Conclusion:  The short-term efficacy of FK506 is observed in the patients with progressive Alport syndrome, with improvement of proteinuria and hypoalbuminemia. Long-term efficacy of FK506 for patients with progressive Alport syndrome remained uncertain until further studies’ evaluation.

Key words: Alport syndrome, , tacrolimus, curative effect