A prospective trial of safety and efficacy of low-dose tacrolimus therapy in steroid resistant nephrotic syndrome

Abstract

Introduction: A Significant proportion of steroid-resistant nephrotic syndrome (SRNS) patients who do not achieve remission will progress to end-stage renal disease (ESRD). Objectives: Calcineurin inhibitors (CNIs) are recommended as a first line therapy in SRNS but the data on tacrolimus (TAC) and its potential nephrotoxicity in SRNS patients is limited. Patients and Methods: This is a prospective single arm study conducted at IPGMER Kolkata from August 2013 to December 2015. All SRNS patients underwent kidney biopsy before the initiation of therapy. Patients with identified secondary causes of FSGS, eGFR ≤ 45 mL/min/1.73 m2, or more than 5% of interstitial fibrosis and tubular atrophy (IFTA) on biopsy were excluded. TAC was given 0.075 mg/kg (adjusted to maintain TAC trough level i.e. T0 of 5-7 ng/mL) with low-dose steroids. Those who completed 12 months of TAC underwent second biopsy. Primary outcome was a percent of partial or complete remission (CR) or refractory. Secondary outcome was time to achieve remission, relapses, and proportion of patients who had adverse effects. Results: Thirty-two patients were enrolled. Overall remission was seen in 28 patients (87.5%). CR was seen in 17 (53.13%) and partial remission (PR) was seen in 11 (34.38%). Four patients (12.5%) were refractory to therapy. Average time to achieve PR was 72.53 ± 62.57days while average time to achieve CR was 63.84 ± 27.32 days. Mean TAC dose required was 1.75 ±0.86 mg. Thirteen patients (40.63%) had relapses. One patient needed admission for diarrhea. All other adverse effects were managed on outdoor basis. None required discontinuation of TAC therapy. Compared with the baseline biopsy two patients had increase in IFTA and another one developed IFTA on one year protocol biopsy. Conclusion: Low dose TAC maintaining trough levels (T0) of 5 to 7 ng/mL with low dose steroid is an effective option for patients with SRNS. It is well tolerated and efficacious in achieving remission.

Keywords

• Steroid resistant nephrotic syndrome
• Minimal change disease
• Focal segmental glomerulosclerosis
• Tacrolimus
• Kidney biopsy
• Trough level
• Interstitial fibrosis
• Tubular atrophy