Sequential Immunosuppressive Therapy in Progressive IgA Nephropathy

AbstractBackgroundThere is some controversy regarding the efficacy and safety of immunosuppressive agents for the treatment of kidney diseases. The recent STOP-IgAN and TESTING studies have focused attention on the application of immunosuppressive agents in IgA nephropathy (IgAN). This study investigated the benefits and risks of immunosuppressive agents in IgAN.MethodsMEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), and adverse events in patients with IgAN, and trial sequential analyses were also performed for outcomes.ResultsTwenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. Steroids (weighted mean difference [WMD] −0.70, 95% confidence interval [CI] −1.2 to −0.20), non-steroidal immunosuppressive agents (NSI) (WMD −0. 43, 95% CI −0.55 to −0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) (WMD −1.46, 95% CI −2.13 to −0.79) therapy significantly reduced proteinuria levels in patients with IgAN. Steroid treatment significantly reduced the risk for end-stage renal disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79). The immunosuppressive therapy group showed significant increases in gastrointestinal, hematological, dermatological, and genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia was more common in the control group.ConclusionImmunosuppressive therapy can significantly reduce proteinuria and ESRD risk in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care is required in the application of immunosuppressive agents in IgAN.

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MO278IMMUNOSUPPRESSIVE THERAPY VERSUS SUPPORTIVE CARE IN IGA NEPHROPATHY PATIENTS WITH STAGE 3 AND 4 CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab104.0036 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Gabriel Stefan ◽

Simona Stancu ◽

Adrian Dorin Zugravu ◽

Nicoleta Petre ◽

Gabriel Mircescu

Keyword(s):

Chronic Kidney Disease ◽

Retrospective Study ◽

Kidney Disease ◽

Supportive Care ◽

Survival Time ◽

Immunosuppressive Therapy ◽

Iga Nephropathy ◽

Composite Endpoint ◽

Renal Survival ◽

Cox Regression Analysis

Abstract Background and Aims The use of immunosuppressive therapy for IgA nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial. Method We performed a monocentric retrospective study on 83 consecutive IgAN patients (age 41 [33-56] years, 72% male, eGFR 36.1 [25.4-47.5] mL/min) with stage 3 or 4 CKD and proteinuria ≥ 0.75g/day who received uncontrolled supportive care (Supp) (n=36), corticosteroids (CS) (n=14) or CS combined with monthly pulses of cyclophosphamide (CS+CFM) (n=33) between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018). Results Patients were followed for a median of 29 (95%CI 25.2, 32.7) months, and 12 (15%) patients experienced the composite endpoint. There were no differences between the three studied groups regarding age (Supp 46 [33.5-61.0] vs CS 40 [33-47] vs CS+CFM 41 [34-48] years), eGFR (Supp 37.7 [27.5-49.2] vs CS 40.3 [32.5-54.6] vs CS+CFM 31.5 [22.7-44.3] mL/min), proteinuria (Supp 1.9 [1.4-3.5] vs CS 1.3 [1.0-1.7] vs CS+CFM 1.7 [1.1-2.9] g/g creatinine), MESTC score (Supp 2.5 [1.5-4.0] vs CS 2 [0-2] vs CS+CFM 3 [2-3]), hypertension (Supp 94% vs CS 86% vs CS+CFM 94%) and therapy with renal angiotensin system inhibitors (Supp 83% vs CS 64% vs CS+CFM 67%). Mean renal survival time for the entire cohort was 81.0 (95%CI 73.1, 89.0) months; we found similar renal survival time between the three groups (Supp 79.0 (95%CI 66.5, 91.6) vs CS 69.3 (95%CI 47.7, 91.0) vs CS+CFM 73.7 (95%CI 66.0, 81.4) months, p=0.4). In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better renal survival when compared to supportive therapy (Table 1). Conclusion Within the limitation of a retrospective study, we found no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared to supportive care.

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Should Immunosuppressive Therapy Be Used in Slowly Progressive IgA Nephropathy?

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2016.03.001 ◽

2016 ◽

Vol 68 (2) ◽

pp. 184-186 ◽

Cited By ~ 2

Author(s):

John Feehally ◽

Jonathan Barratt

Keyword(s):

Immunosuppressive Therapy ◽

Iga Nephropathy

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Clinicopathological Characteristics, Role of Immunosuppressive Therapy and Progression in IgA Nephropathy with Hyperuricemia

Kidney & Blood Pressure Research ◽

10.1159/000491809 ◽

2018 ◽

Vol 43 (4) ◽

pp. 1131-1140 ◽

Cited By ~ 1

Author(s):

Yiping Ruan ◽

Fuyuan Hong ◽

Jiabin Wu ◽

Miao Lin ◽

Chen Wang ◽

...

Keyword(s):

Immunosuppressive Therapy ◽

Iga Nephropathy ◽

Clinicopathological Characteristics

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Plasma Exchange as an Adjunctive Therapy for Crescentic IgA Nephropathy

American Journal of Nephrology ◽

10.1159/000448767 ◽

2016 ◽

Vol 44 (2) ◽

pp. 141-149 ◽

Cited By ~ 8

Author(s):

Xinfang Xie ◽

Jicheng Lv ◽

Sufang Shi ◽

Li Zhu ◽

Lijun Liu ◽

...

Keyword(s):

Plasma Exchange ◽

Immunosuppressive Therapy ◽

Iga Nephropathy ◽

Severe Pneumonia ◽

Rank Test ◽

Urine Protein Excretion ◽

Protein Excretion ◽

Log Rank Test ◽

Active Complement

Background: Crescentic IgA nephropathy (CreIgAN) has a poor prognosis despite aggressive immunosuppressive therapy. The efficacy of plasma exchange (PE) in CreIgAN is not well defined. Methods: Twelve patients with severe CreIgAN who received PE as addition to routine immunosuppressive therapy, followed for more than 6 months, were involved. Twelve matched historical controls who received immunosuppressive therapy alone were selected by propensity score matching. Renal survival, plasma IgA-IgG complex and active complement products were assessed. Results: Nine men and 3 women received a median of 7 PE courses (range 5-10). Their baseline urine protein excretion rate was 5.8 (4.5-8.7) g/day, and their serum creatinine level was 705.3 ± 296.4 μmol/l. During a mean follow-up of 15.6 months (6-51 months), 6 of the 12 PE group patients were free of dialysis, while all the control patients were dialysis dependent (6 of 12 vs. 0 of 12, p = 0.014). In the PE group, dialysis had to be restarted for 1 patient owing to the development of severe pneumonia and pulmonary failure. PE was associated with a higher kidney survival rate (log rank test, p = 0.026) during follow-up. It also significantly decreased plasma IgA-IgG complex levels (pre-PE: 85.3 ± 25.9% vs. post-PE: 38.4 ± 12.4%, p < 0.001) and plasma and urinary active complement product levels, including C3a, C5a and soluble C5b-9. The latter levels remained low until the last follow-up. Conclusion: This study indicated that PE could increase renal recovery rates in severe CreIgAN.

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