Outcome of low dose cyclophosphamide for induction phase treatment of lupus nephritis, a single center study

Abstract

BackgroundThe current standard for induction phase treatment of lupus nephritis is steroid combined with mycophenolate mofetil or pulse intravenous cyclophosphamide (IVC). The lowest dose of IVC recommended for induction therapy is that used in the Euro-Lupus Trial. It is not known whether same cumulative dose of IVC would be effective when given over six months.MethodsWe carried out a prospective, observational study on 41 patients of biopsy-proven lupus nephritis (class III, IV, V or mixed). For induction, patients received six pulses of monthly IVC (500 mg each), along with steroid. Patients were followed up monthly until one month beyond completion of the sixth pulse. The outcomes assessed were complete remission (proteinuria < 200 mg/day or urine albumin nil with serum albumin >35 gm/L, stable estimated glomerular filtration rate (eGFR) if normal at baseline or increase in eGFR by 25 % if abnormal at baseline and normal urinary sediment), response (complete or partial remissions), complications of therapy and death.ResultsTwenty two patients (53.7 %) had class IV nephritis. Eighteen patients (43.9 %) achieved complete remission, 16 (39.0 %) achieved partial remission, yielding an overall response rate of 82.9 %. Nephrotic range proteinuria (UTP ≥ 3 g/day) and severe hypoalbuminemia (serum albumin < 20 g/L) at baseline influenced remission (p <0.05). Infection, seen in 12 patients (29.3 %), was the most common complication. Four deaths (9.6 %) were observed, all due to infection.ConclusionsFor induction phase treatment, Nepalese patients with lupus nephritis responded favorably to steroid and low dose IVC of 3 grams given as six monthly pulses.

Effect of GSTP1 polymorphism on efficacy and safety of cyclophosphamide aggressive therapy in lupus nephropathy patients

“…The remission criteria were set at 24-h urinary protein < 200 mg/day. Of the 34 patients, 18 (43.9%) achieved complete remission at 3 and 6 months after treatment [18]. Even though the remission criteria differed slightly from those in the present study, the remission rate was comparable.…”

“…Sigdel et al [18] conducted a similar study in SLE nephropathy patients in Nepal. In their study, the dose of intravenous CYC was 500 mg monthly for 6 months, and intravenous MP (0.5-1 g) was used for only 3 days.…”

“…Conversely, another study [22] reported that GSTP1 variant 105 I/V was related to a reduced risk of neutropenia and leukopenia in breast cancer patients receiving cancer chemotherapy. With regards to the treatment of SLE with CYC immunosuppressive therapy, reports regarding the risk of toxicities in GSTP1 polymorphic patients are limited, although infection and leukopenia due to myelotoxicities have always been major limiting factor in lupus therapy [18]. When used as cancer chemotherapy, the initial course of CYC for patients with no hematologic deficiency usually consists of 40-50 mg/kg given intravenously in divided doses over a period of 2-5 days.…”

Systematic evaluation of different doses of cyclophosphamide induction therapy for lupus nephritis

“…The results were consistent with a recent retrospective study of a single central low-dose CTX inductive therapy for patients with type III/IV/V LN. [ 35 ] In addition, research studies have investigated low-dose CTX, tacrolimus, and mycophenolate mofetil induction therapy for patients with type III and type IV LN. There were no obvious statistical differences among 3 groups in safety and efficacy.…”

Analysis of the Clinical Effects of the Combination of Mycophenolate Mofetil with Either Tacrolimus or Cyclophosphamide

“…The incidence rate of LN in China has gradually increased ( 3 ). Presently, the primary aim of the treatment of LN is to prevent the degeneration of renal function and to achieve its normalization ( 4 ), including an inductive (controlling immune-mediated inflammation through cytotoxicity and hormone therapy) and maintenance treatment (keeping LN at a low activity level through immunosuppression) ( 5 ). Moreover, mycophenolate mofetil is a common prescription drug used for the maintenance treatment ( 6 ).…”