Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis

Abstract

Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.

Progressive Systemic Sclerosis With Negative Antinuclear Antibodies and Absence of Raynaud’s Phenomenon: A Case Report and Literature Review

“…In the Scleroderma Family Registry and DNA repository, ANA-negative patients were more likely to develop SRC than patients with anti-topoisomerase or anti-centromere antibodies [ 6 ]. Our patient had risk factors for the development of SRC, including antecedent use of steroids (for pericardial tamponade), pericardial effusion, early disease (<4 years from diagnosis), and diffuse disease with rapidly progressive skin score [ 7 , 11 ]. SSc has a substantial burden of early mortality within five years of disease onset, although all-cause mortality was found to be similar between ANA-negative and ANA-positive patients, with ILD being the leading cause [ 6 , 12 ].…”

Recent advances in elucidating the genetic basis of systemic sclerosis

“…Another well known SSc complication is the scleroderma renal crisis (SRC), which is more frequent in ARAþ patients [51]. A GWAS of an ARAþ cohort of 99 SSc patients affected and non-affected by SRC showed suggestive associations of one SNP in the POU2F1 locus (rs2093658), one in CTNND2 (rs1859082), one in HECW2 (rs16849716) and one in GPATCH2L (rs935332) [52].…”

Evaluation of hypertension in systemic sclerosis and systemic lupus erythematosus overlap

“…39 Renal Doppler ultrasound is indicated in SSc-SLE patients with acute kidney injury and can assess for the presence of renal artery stenosis (RAS), which is important to determine prior to treatment with an angiotensinconverting enzyme (ACE) inhibitor. 28,40,41 Renal Doppler ultrasound with intrarenal hemodynamic parameters of renal resistive index (RRI) is obtained through the Doppler spectrum analysis of renal small arteries, and is established for determining renovascular damage in nonobstructive renal diseases where it correlates with biopsy findings. 42 In SSc, RRI is associated with asymptomatic renal dysfunction and may be useful in the assessment of systemic vasculopathy.…”

“…25,26 Similar to SLE, for prevention of complications from HTN, SSc patients should be educated on home BP monitoring and indications for emergency assessments. 27,28 If elevation of BP is detected, a complete blood count, complete metabolic profile, and urinalysis are initially obtained to assess for acute kidney injury and microangiopathic hemolytic anemia (Figure 1). The urinalysis in SRC can reveal hematuria and/or proteinuria, but this is mild (<1 g/day) in contrast to that associated with SLE-associated glomerular nephritis.…”