Diagnosis, Management and Prevention of Scleroderma Renal Disease

Abstract and Introduction

Abstract

Purpose of Review: Renal complications are important in scleroderma (systemic sclerosis) and include scleroderma renal crisis. This is a medical emergency that requires careful management. Recent cohort studies have highlighted key aspects of management and outcome and these are reviewed.
Recent Findings: Two recent articles have reported the course of scleroderma renal crisis, and examined risk factors, clinical outcomes and prognostic markers in large contemporary scleroderma cohorts. Diffuse skin disease, early rapidly progressing skin disease, anti-RNA polymerase antibodies and genetic factors are all nonmodifiable risk factors. Use of corticosteroids is associated with scleroderma renal crisis. Over half of cases of scleroderma renal crisis require dialysis; just under half of these will be able to discontinue dialysis over the following 2 years. Despite clear improvement in 12-month survival, which is a testament to the efficacy of angiotensin-converting enzyme inhibitors in renal crisis, long-term mortality remains significant, especially with ongoing dialysis.
Summary: Renal involvement remains a major complication of scleroderma. Long-term outcome after renal crisis remains poor despite the use of angiotensin-converting enzyme inhibitors. There is no evidence at present to support the use of angiotensin-converting enzyme inhibitors prophylactically. The mechanisms and significance of chronic renal impairment in scleroderma need to be better defined.

Introduction

The first descriptions of acute renal failure associated with systemic sclerosis led to an appreciation of the important link between this prototypic fibrotic disease and vascular injury. Historically, scleroderma renal crisis (SRC) was almost invariably fatal, with most patients dying within 3 months of presentation. This dire outcome was transformed with the routine use of angiotensin-converting enzyme inhibitor (ACEI) drugs, which were introduced in the late 1970s. Although there has never been a prospective controlled trial, robust retrospective data point to a reversal in prognosis such that the majority of patients survive the acute renal crisis when treated with ACEI. As such, this became the first, and perhaps the most dramatic, example of effective therapy in systemic sclerosis (SSc). The importance of this advance in terms of understanding the disease pathogenesis and illustrating that a highly selective drug can apparently influence the underlying disorder of SSc cannot be overstated. Despite this major advance, it has become apparent that the overall outcome in SRC remains unsatisfactory in terms of disease outcome, morbidity and the frequent need for renal replacement therapy.

Although SRC is the most prominent renal manifestation of SSc, there are other important complications including chronic renal impairment, which may impact on treatment and outcome, and a number of inflammatory renal disorders. Clinically most important is glomerulonephritis, as its treatment differs from that of SRC.

In this article, current aspects of diagnosis and management of SRC are discussed in the context of two major recent series describing large cohorts of patients. Potential strategies for prevention and future advances in therapy are discussed. Other renal complications of SSc are reviewed. General discussion of the management of chronic renal disease in SSc is considered.