Combination of tacrolimus and mycophenolate mofetil in persistent proteinuria due to refractory childhood lupus nephritis

Abstract

BackgroundChildren with lupus nephritis particularly, diffuse proliferative and membranous glomerulonephritis, may necessitate potent immunosuppressive medications and occasionally combined therapy.ObjectiveTo report the beneficial effects of tacrolimus (TAC) in children with refractory lupus nephritis from a single tertiary pediatric rheumatology clinic.MethodsThis is a retrospective case series of children with refractory lupus nephritis treated with TAC after failure of aggressive immunosuppressive treatment. All patients were evaluated at the time of initiation of TAC and at last follow-up visit by assessing the following response parameters: cSLE Disease Activity Index (SLEDAI), urine protein/creatinine ratio, urine sediments, serum albumin, complement (C3 and C4), anti-double-stranded DNA (dsDNA) antibody levels, and renal function assessed by glomerular filtration rate (eGFR).ResultsThree children (two girls and one boy) with lupus nephritis and persistent nephrotic-range proteinuria failed prednisone treatment as well as sequential treatment of cyclophosphamide, mycophenolate mofetil (MMF), and rituximab. When TAC was administered along with MMF and prednisone, all patients showed improvement in response parameters, namely, SLEDAI, serum albumin, and proteinuria, and prednisone doses were significantly weaned off and discontinued in two patients. However, eGFR remained stable during the treatment period. TAC was well tolerated, and no adverse effects were observed.ConclusionTAC combined with MMF can be considered as an alternative therapeutic option for children with refractory lupus nephritis particularly those with persistent nephrotic-range proteinuria.

Analysis of time course and dose effect of tacrolimus on proteinuria in lupus nephritis patients

“…Hence, controlling proteinuria is particularly important for the treatment of lupus nephritis 8 . Many studies have found that tacrolimus has been used to treat patients with lupus nephritis and has had a good effect on controlling proteinuria 9‐11 . In addition, a published systematic review and meta‐analysis also confirmed that tacrolimus may be more effective at reducing proteinuria, having potential implications for long‐term outcome 12 .…”

Individualizing Therapy in Lupus Nephritis

“…The approach of this kind of combination therapy was tested in subsequent clinical trials 28, 29, 30, 31. Meta-analysis showed that the combination therapy is more effective for inducing remission compared with IVCY, MMF, and CNIs 22, 32, 33.…”

“…Meta-analysis showed that the combination therapy is more effective for inducing remission compared with IVCY, MMF, and CNIs 22, 32, 33. Besides initial treatment, it can also help refractory or relapsing patients achieve a renal response and reduce the use of steroids 28, 29, 30, 31. Not only tacrolimus but also cyclosporine combined with MMF can induce complete remission in LN and was well tolerated 30, 31.…”