Avinandan Banerjee, Smita Subhash Divyaveer
*, Praveen Malvade, Tanima Das Bhattacharya, Chetan Mahajan, Vaibhav Tiwari, Arpita Raychaudhury, Dipankar Sircar, Sanjay Dasgupta, Arunansu Bandyopadhyay, Debabrata Sen, Rajendra Pandey
1 Department of Nephrology, Institute of Post Graduate Medical Education & Research, Seth Sukhlal Karnani Memorial Hospital, Kolkata, India
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.
Implication for health policy/practice/research/medical education:
Treatment of steroid resistant nephrotic syndrome (SRNS) is challenging. Tacrolimus (TAC) has been found effective in previous trials however its potential side effects of acute and chronic nephrotoxicity continues to be a concern. In this study we targeted a lower dose range of TAC. Only one patient developed reversible acute kidney injury which improved by lowering the dose. Protocol biopsies at one year showed a small percentage of patients having increased/new onset chronicity. As a comparator group was not available it remains difficult to ascertain if this was due to TAC or the disease per se. However, it is likely that lower dose range of TAC would result in lesser long-term toxicity while being equally efficacious as the higher/wide dose range.
Please cite this paper as: Banerjee A, Divyaveer SS, Malvade P, Bhattacharya TD, Mahajan C, Tiwari V, et al. A prospective trial of safety and efficacy of low-dose tacrolimus therapy in steroid resistant nephrotic syndrome. J Nephropharmacol. 2018;7(1):18-23. DOI: 10.15171/npj.2018.05.