Introduction:
IgA Nephropathy patients with nephrotic range proteinuria are traditionally being treated with systemic steroids on top of RAS inhibition. The use of enteric released budesonide has now emerged as safe and effective alternative but many case are refractory to both. There are many reports of refractory IgAN which responds to Tacrolimus, but the unmet need is dose and duration of therapy not fixed in any trial, and identification of the candidates who are most likely to respond. Through this case series we highlighted 4 cases of refractory IgAN, with similar clinical and biopsy features, and tried to identify the IgAN patients who may respond to CNI monotherapy.
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Methods:
52 cases of biopsy proven IgA Nephropathy patients were followed and evaluated for their baseline demographic, clinical and laboratory parameters like age, sex, proteinuria, hematuria (gross and microscopic), hypertension, BMI, serum creatinine (eGFR) as well as light microscopy biopsy findings (MEST-C scoring, IFTA ) and treatment intervention outcome. We are presenting a case series of four patients who did not respond well to standard immunosuppression protocol but responded well to CNI monotherapy. All four patients were normotensive, non-obese, nondiabetic with normal renal function (eGFR>60 ml/min) and no hematuria (either micro or macroscopic). Biopsy of 2 patients had only sclerosis and 2 had some mesangial proliferation on top of sclerosis, no IFTA, but all four had IgA deposition(3+) in biopsy After 3 months of unsatisfactory response on conservative management (RAS inhibition and lifestyle changes), all were started on systemic steroid (prednisolone) in the dose of 1 mg/kg followed by tapering, the total duration being 6 months. 3 patients were non-responders and 1 had immediate relapse on withdrawal. So all were started on enteric released budesonide 9mg BD. 3 patients were non responsive and one developed toxicity. So all were then initiated on tacrolimus( 0.075 mg/kg in 2 divided doses with target whole blood tacrolimus level being 5 to 7). They were followed up every month for efficacy and safety.
Results:
BASELINE CHARACTERISTICS:
PRIOR THERAPIES:
TACROLIMUS THERAPY:
All 4 patients on tacrolimus achieved complete remission at 4,6,6 and 7 months respectively (cut off being kept at 800 mg/day proteinuria). The eGFR remained preserved with no adverse effect reported. . All these patients are under close follow up and are maintaining remission on tacrolimus.
Conclusions:
This case series had shown CNI monotherapy might be an important choice in the subset of IgAN who present with nephrotic range proteinuria, no hematuria and no hypertension. Considering biopsy features of FSGS and high proteinuria in all 4 patients, podocytopathy can be the mechanism. Tacrolimus can act by immunological or non immunological mechanism or by cytoskeletal stabilisation of podocytes. This hypothesis may be tested in a larger cohort with IgAN with similar clinical features and biopsy findings, to find optimal dose and duration of treatment . We know IgAN with MCD like picture in LM , may respond well to steroids. This may be FSGS subset with IgA in IF , who will improve with CNI.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.