Treatment for lupus nephritis

 

Abstract

Background

Lupus nephritis is the renal manifestation of systemic lupus erythematosus (SLE) - a disease mainly affecting young women with substantial morbidity and mortality. It is classified by the World Health Organization (WHO) criteria I - VI based on histology. WHO Class IV is a diffuse proliferative glomerulonephritis which has the worst prognosis without treatment, with a reported 17% five year survival in the era 1953-1969. This survival was 82% in the early 1990's and continues to improve. An important factor behind this has been the use of cytotoxics such as cyclophosphamide in addition to steroids.

Objectives

To assess the benefits and harms of different treatments in biopsy-proven proliferative lupus nephritis (LN).

Search methods

We searched the Cochrane Renal Group's specialised register (January 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 1, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles.

Selection criteria

Randomised controlled trials (RCTs) and quasi-RCTs comparing treatments for PLN in both adult and paediatric patients with Class III, IV , Vc, Vd lupus nephritis were included. All treatments were considered.

Data collection and analysis

Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as risk ratio (RR) and measurements on continuous scales are reported as mean differences (MD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity.

Main results

Of 920 articles identified, 25 were RCTs suitable for inclusion, which enrolled 915 patients. The majority compared cyclophosphamide or azathioprine plus steroids versus steroids alone. Cyclophosphamide plus steroids reduced the risk of doubling of serum creatinine (RR 0.59, 95% CI 0.40 to 0.88) compared to steroids alone but had no impact on mortality (RR 0.98, 95% CI 0.53 to 1.82). The risk of ovarian failure was significantly increased (RR 2.18, 95% CI 1.10 to 4.34). Azathioprine plus steroids reduced the risk of all cause mortality compared to steroids alone (RR 0.60, 95% CI 0.36 to 0.99), but did not alter renal outcomes. Neither therapy was associated with increased risk of major infection.

No benefit was found with addition of plasma exchange to cyclophosphamide or azathioprine plus steroids for mortality ( RR 0.71, 95% CI 0.50 to 1.02), doubling of serum creatinine (RR 0.17, 95% CI 0.02 to 1.26) or end-stage renal failure (RR 1.24, 95% CI 0.60 to 2.57). There was also no increased risk of major infection (RR 0.69 , 95% CI 0.35 to 1.37) .

Authors' conclusions

Until future RCTs of newer agents are completed, the current use of cyclophosphamide combined with steroids remains the best option to preserve renal function in proliferative LN. The smallest effective dose and shortest duration of treatment should be used to minimise gonadal toxicity, without compromising efficacy.

 

Plain language summary

A combination of cyclophosphamide or azathioprine with steroids can improve kidney function in people with severe lupus nephritis

Lupus nephritis is an inflammation of the kidneys caused by lupus. Lupus (systemic lupus erythematosus - SLE) is a disease of the immune system that usually affects women. The person produces antibodies against various components of their cells, particularly DNA. Some develop kidney disease or failure. The review found that adding cyclophosphamide or azathioprine to steroids has better results than steroids alone. This combination of drugs improves the functioning of the kidneys but has not been shown to reduce kidney failure. More research is needed to refine the use of these treatments and find new drugs. Cyclophosphamide may lead to infertility.

 

摘要

背景

紅斑性狼瘡腎炎的治療

狼瘡性腎炎是全身紅斑性狼瘡的腎臟表現，主要影響年輕女性且具有相當的死亡率和併發症。世界衛生組織 (WHO) 以組織學的表現來分級，可分為I～VI級。第IV級是廣泛增生性腎炎，若不治療會有最差的預後。因為根據1953到1969年的統計資料發現，第IV級狼瘡性腎炎若不治療，五年存活率為17% 。1990年代初期，狼瘡性腎炎的存活率上升到82% 並且持續在改善。其中一項重要的因素是因為除了類固醇之外，還使用了細胞毒殺劑例如cyclophosphamide。

目標

評估不同的治療對於已做過切片證實為增生性狼瘡性腎炎 (LN) 的好處及壞處。

搜尋策略

我們搜尋了Cochrane Renal Group's specialised register (2003年1月), CENTRAL 考科藍圖書館2003年第一期), MEDLINE (1966 – 2003年1月31日), EMBASE (1980 – 2003年1月31日) 以及人工搜尋回收文章的參考資料列表。

選擇標準

以隨機及半隨機對照實驗的方式，比較成人及孩童病患的增生性狼瘡性腎炎 (PLN) ，組織學上第III、IV、Vc、Vd級的狼瘡性腎炎也包括在內。所有的治療都被考慮。

資料收集與分析

兩位研究者分別獨立的蒐集資料並評估資料品質，若有差異則以相互討論來解決。使用二分效應模型和連續數值評量，來評估相對風險和加權平均差在95% 的信賴區間裡。針對研究品質、藥物種類以及給藥途徑也進行了次級分析，希望可以找出差異性的原因。

主要結論

搜尋到的920篇文章，只有25篇是隨機對照實驗可進行分析，這其中包括了915位病患。比較類固醇合併cyclophosphamide或azathioprine的治療方式，以及單獨使用類固醇兩組間的差異。結果發現cyclophosphamide加上類固醇，比起單獨使用類固醇治療，可以減少血清肌酸酐倍增的危險性 (RR 0.59, 95% CI 0.40～0.88) ，但對於死亡率沒有影響 (RR 0.98, 95% CI 0.53～1.82) 。另外，卵巢性腺功能衰竭的危險性會顯著的增加 (RR 2.18, 95% CI 1.10～4.34) 。至於Azathioprine加上類固醇，比起單獨使用類固醇治療，可減少所有因素所造成的死亡率 (RR 0.60, 95% CI 0.36～0.99) ，但不能改善腎功能的預後。不管哪一種治療方式，都會增加嚴重感染的機會。另外，類固醇合併cyclophosphamide或azathioprine的這種治療方式，若再加上血漿置換，對於死亡率 (RR 0.71, 95% CI 0.50～1.02) 、血清肌酸酐倍增 (RR 0.17, 95% CI 0.02～1.26) 、進展到末期腎臟衰竭的機會 (RR 1.24, 95% CI 0.60～2.57) ，或嚴重感染的機會 (RR 0.69, 95% CI 0.35～1.37) 則沒有改善。

作者結論

除非未來的新藥有完整的隨機對照實驗，目前在增生性狼瘡性腎炎合併使用cyclophosphamide及類固醇仍然是保留腎功能最好的選擇。不管效果如何，為了儘可能地減少對性腺的毒性，應該在最低有效劑量和最短使用時間的考量下使用藥物。

翻譯人

本摘要由馬偕醫院賴傳才翻譯。

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

類固醇合併cyclophosphamide或azathioprine可以改善重度紅斑性狼瘡腎炎患者的腎功能。紅斑性狼瘡腎炎是一種因為紅斑性狼瘡而導至的腎臟炎性反應。全身紅斑性狼瘡是一種主要發生在女性患者的自體免疫疾病，而這些患者會產生自體抗體對抗自體的各種細胞，因此有些患者會出現腎疾病甚至腎衰竭。經由本篇綜論發現，類固醇合併cyclophosphamide或azathioprine的治療方式，比起單獨使用steroid會有較好的預後，因為合併治療可以改善腎功能，但還是無法減少發生腎衰竭的機會。因此，我們需要更多的研究來證實我們目前所使用的藥物，以及一些新發展的治療。Cyclophosphamide可能會導致不孕。