Long-Term Efficacy and Safety of Quadruple Therapy in Childhood Diffuse Proliferative Lupus Nephritis

Abstract

In this study, we evaluated the frequency, clinical presentation, treatment protocols, prognostic factors, and outcome in children with diffuse proliferative lupus nephritis (DPLN). Between June 1990 and December 2004, 46 patients were diagnosed to have systemic lupus erythematosus (SLE), and 26 of them (56.5%) were found to have DPLN. Renal manifestations were present in 25 patients, and the majority of them presented with severe renal findings, such as nephrotic syndrome and renal failure. All patients were given a quadruple therapy protocol including 6-12 monthly courses of methyl prednisolone pulse therapy combined with oral prednisolone, oral cyclophosphamide, azathioprine, and dipyridamole. Nineteen of these patients were regularly followed up with a mean follow-up period of 5.9 years. Complete remission was achieved in 15 of 19 patients, and chronic renal failure developed in four patients. Renal survival rate was calculated to be 78.9% at the end of 5, 10, and 14 years. Although nephrotic range proteinuria, hypoalbuminemia, renal failure, and activity index above 12/24 at presentation seemed to be associated with poor prognosis, no significant difference could be found. Hypertension and chronicity index greater than 6/12 were found to be bad prognostic predictors. We concluded that satisfactory results were achieved with our quadruple therapy protocol; thus, more aggressive and expensive therapies can be avoided and preserved for more serious and persistent diseases.

Childhood- and adult-onset lupus: an update of similarities and differences

“…To date, the only study comparing MMF to CYC for induction of remission in childhood lupus nephritis showed superiority of the former for class III nephritis [75][76][77][78][79][80][81][82][83][84][85][86]. However, despite showing efficacy in membranous nephropathy, MMF failed to attenuate disease progression in pediatric patients with class IV nephritis [87].…”

“…In an attempt to overcome the obstacle of CYC-induced side effects, a quadruple therapy protocol may be employed, although, again, there are no randomized data to support its generalized use [85]. To date, the only study comparing MMF to CYC for induction of remission in childhood lupus nephritis showed superiority of the former for class III nephritis [75][76][77][78][79][80][81][82][83][84][85][86].…”

Cyclophosphamide and Lupus Nephritis: When, How, For How Long?

“…During follow-up (median 4.5 years), no significant differences were found for any outcome measures including normal serum creatinine at last follow-up (86% in all patients), renal flares (45%), median time to renal flare (36 months in AZA, 20 months in IV-CY, 12 months in the steroids group, P=0.15), and overall renal survival (97% in AZA, 89% in IV-CY, 75% in the steroids group, P=0.38). The authors concluded that AZA and IV-CY were equally efficacious in the treatment of acute renal failure in pediatric lupus nephritis [38,39].…”

“…Demircin et al [38] treated 19 children with diffuse proliferative (class IV) lupus nephritis (65% had proteinuria >40 mg m −2 h −1 and hypoalbuminemia, 62% had impaired renal function) with a multi-drug therapy consisting of six to 12 monthly pulses of IV-MP (30 mg kg −1 day −1 , maximum 1 g) given consecutively for 3 days, followed by oral administration of prednisone, oral administration of CY (2 mg/kg) for 2-3 months, followed by AZA (0.2 mg/kg) and dipyridamole (5 mg kg −1 day −1 ). Maintenance therapy included low-dose oral administration of prednisone, dipyridamole, and AZA for at least 5 years.…”

An Update on Treatment and Outcome of Lupus Nephritis in Children

“…Cyclophosphamide Cyclophosphamide (CYC) has been the most frequently used drug for decades in the induction therapy of LN, which was initially used in oral form (1-3 mg/kg/day) [4,16]. After intravenous (IV) CYC was introduced and was shown to be superior to daily oral CYC, induction protocols in most…”