A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study

Abstract

To compare the long-term efficacy of corticosteroids (P) alone or in combination with cyclophosphamide (CTX), leflunomide (LEF), or Angiotensin-convertase inhibitors or angiotensin II receptor blockers (ACEI/ARB) in treatment for IgA nephropathy (IgAN), 311 patients with IgAN were identified. Therapeutic effectiveness (including progression, partial remission, complete remission) and combined renal endpoint (defined as 30% reduction in eGFR or ESRD) were compared based on different therapies. After immunosuppressive and ACEI/ARB treatment, the levels of eGFR, proteinuria and albumin were significantly improved at the last follow-up, the extent of improvement of eGFR, proteinuria, and albumin was more notable in P + CTX group and P + LEF group. 41%, 52.2%, 55.3% and 55.2% in P + CTX, P + LEF, P and ACEI/ARB group achieved complete remission, respectively. Multivariate regression analysis indicated that only proteinuria (Relative risk (RR) 0.82(0.72–0.94), P = 0.004) and tubular atrophy/interstitial fibrosis (RR 0.26(0.13–0.57), P = 0.001) were predictors for complete remission. The optimal cutoffs of eGFR was 47.085 ml/min/1.73 m2 predicting renal function recovery in P + CTX therapy. In conclusion, tubular atrophy/interstitial fibrosis and massive proteinuria were poor predictors for complete remission in IgAN, it appears as though patients may have benefited from immunosuppressive treatment but that comparison to a well-matched contemporary control group or, ideally, a randomized controlled clinical trial, would be required to show this.

Efficacy and safety of immunosuppressive therapies in the treatment of high-risk IgA nephropathy

“…Chen et al found that LEF combined with CS significantly reduced urinary protein, improved albumin and eGFR in patients with IgAN compared with supportive care. [ 56 ] The similar results has been obtained from a meta-analysis. [ 57 ] We found that the long-term efficacy of CTX+CS was better, but its safety concerns may restrict the possible benefits, which was in accordance with the study conducted by Woo et al with a minimum 10 years follow-up.…”

Cyclophosphamide use in treatment of refractory Kawasaki disease with coronary artery aneurysms

“…A recent study by Noval Rivas et al has strengthened the evidence for potential role of secretory IgA deposition in coronaries of KD patients [ 16 ]. We hypothesize that in progressive KD, these active immune cells/complexes are not fully suppressed by steroids or selective anti-cytokine therapies, and hence require direct cytotoxic alkylating mechanism of cyclophosphamide, which has been effectively used in treatment of other IgA mediated vasculidities [ 17 , 18 ]. We compared clinical management and outcomes in our series to those of 7 previously reported cases in 3 published series [ 9 – 11 ].…”

The analysis of treatment of Immunoglobulin A-nephropathy

“…По данным целого ряда исследований известно, что в некоторых случаях естественная эволюция клинических и морфологических проявлений IgAN может быть значительно изменена под влиянием лечения [16][17][18][19][20][21]. Вместе с тем подходы к лечению, определенные в известных международных и местных рекомендациях и основанные на применении блокады ренин-ангиотензиновой системы (РАС) и иммуносупрессивной терапии (ИСТ), имеют невысокую клиническую эффективность по результатам проспективных исследований, в которых частота ремиссий на ИСТ составляла 25-62% (включая полные ремиссии -7,8-55,3%) [22][23][24][25][26][27][28][29]. Как установлено нами ранее, IgAN в отечественной популяции отличается более выраженными клиническими и гистологическими проявлениями, а также неблагоприятным прогнозом, доминируя по распространенности среди других клинико-морфологических фенотипов гломерулярного повреждения [29].…”

“…Согласно полученным данным ТЭ не увеличивала вероятность развития ремиссии ни в качестве дополнения терапии БРАС, ни в комбинации с КС. Следует отметить, что частота ремиссий в сравниваемых группах достаточно высока, в том числе в сравнении с другими исследованиями [23,25,27,28]. Кроме того, цитируемые метаанализы основывались главным образом на данных ретроспективных исследований, поэтому их результаты вряд ли можно отнести к надежным.…”