Renal Involvement in Systemic Sclerosis: An Update

Abstract

Background: Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. Summary: Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and lifethreatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients' outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.

Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review

“…Renal diseases in SSc patients may manifest in different clinicopathological settings, and scleroderma renal crisis is the most severe life-threatening complication [ 57 , 58 ]. In a 154 patient retrospective analysis, Trombetta et al found a high ratio of kidney involvement at lower vitamin D levels [ 22 ], and Groseanu et al reported scleroderma renal crisis more frequently in patients with vitamin D deficiency in their cohort with SSc [ 30 ].…”

Biomarkers of Disease Activity in Systemic Sclerosis

“…In case of renal involvement, even though SRC has become quite a rare complication in SSc patients, most of the research is focused on this life-threatening complication [7,40]. The latest research supports a potential role for altered Wnt signaling in SRC pathogenesis and indicates that anti-RNA polymerase III autoantibodies seem to be one of the most promising biomarker of renal involment in SSc [31,32] as well as chemerin, which high level is associated with renal function impairment [13].…”

Distinct Metalloproteinase Expression and Functions in Systemic Sclerosis and Fibrosis: What We Know and the Potential for Intervention

“…While many point toward detrimental MMP functions during inflammation, one study has shown inhibited MMP synthesis can lead to excessive collagen deposition in fibrotic intestinal muscles (Bailey et al, 2012). Kidney involvement is also prevalent in SSc patients, leading to scleroderma renal crisis (SRC), promoted by interstitial fibrosis amongst other risk factors (Steen, 2014;Chrabaszcz et al, 2020). Direct MMP involvement in SSc-associated renal fibrosis has not been identified, but numerous studies imply a detrimental role of MMPs in early stages of kidney diseases with ECM-degradative features in later stages during scarring and fibrosis (Ke et al, 2017;Zakiyanov et al, 2019).…”