Renal disease in systemic sclerosis (scleroderma), including scleroderma renal crisis
- John Varga, MD
John Varga, MD
- John and Nancy Hughes Professor of Medicine
- Northwestern University Feinberg School of Medicine
- Andrew Z Fenves, MD
Andrew Z Fenves, MD
- Associate Professor
- Harvard Medical School
- Division of Nephrology and Department of Medicine
- Massachusetts General Hospital
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Gary C Curhan, MD, ScD
Gary C Curhan, MD, ScD
- Section Editor — Chronic Kidney Disease
- Professor of Medicine
- Harvard Medical School
The pathologic hallmarks of systemic sclerosis (SSc, scleroderma) are uncontrolled accumulation of collagen and widespread vascular lesions characterized by thickening of the vascular wall and narrowing of the vascular lumen. (See "Pathogenesis of systemic sclerosis (scleroderma)".)
Scleroderma may affect only the skin and subjacent tissues, or it may be associated with systemic involvement. The term systemic sclerosis is used when the characteristic skin lesions are associated with internal organ involvement. (See "Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults".)
Renal involvement is common in patients with SSc, with the most serious manifestation being scleroderma renal crisis (SRC), which occurs in a minority of patients. (See 'Prevalence and manifestations of renal disease' below.)
SRC is characterized by three major features (see 'Clinical features' below):
●Abrupt onset of moderate to severe hypertension that is typically associated with an increase in plasma renin activity
- Traub YM, Shapiro AP, Rodnan GP, et al. Hypertension and renal failure (scleroderma renal crisis) in progressive systemic sclerosis. Review of a 25-year experience with 68 cases. Medicine (Baltimore) 1983; 62:335.
- Shapiro AP, Medsger TA Jr.. Renal involvement in systemic sclerosis. In: Diseases of Kidney, 4th ed, Schrier R, Gottschalk C (Eds), Little, Brown, Boston 1988. p.2272.
- TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol 1961; 84:359.
- Steen VD, Syzd A, Johnson JP, et al. Kidney disease other than renal crisis in patients with diffuse scleroderma. J Rheumatol 2005; 32:649.
- Steen VD, Medsger TA Jr, Osial TA Jr, et al. Factors predicting development of renal involvement in progressive systemic sclerosis. Am J Med 1984; 76:779.
- Eason RJ, Tan PL, Gow PJ. Progressive systemic sclerosis in Auckland: a ten year review with emphasis on prognostic features. Aust N Z J Med 1981; 11:657.
- O'Callaghan CA. Renal manifestations of systemic autoimmune disease: diagnosis and therapy. Best Pract Res Clin Rheumatol 2004; 18:411.
- Penn H, Howie AJ, Kingdon EJ, et al. Scleroderma renal crisis: patient characteristics and long-term outcomes. QJM 2007; 100:485.
- Teixeira L, Mouthon L, Mahr A, et al. Mortality and risk factors of scleroderma renal crisis: a French retrospective study of 50 patients. Ann Rheum Dis 2008; 67:110.
- Denton CP, Lapadula G, Mouthon L, Müller-Ladner U. Renal complications and scleroderma renal crisis. Rheumatology (Oxford) 2009; 48 Suppl 3:iii32.
- Guillevin L, Bérezné A, Seror R, et al. Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatology (Oxford) 2012; 51:460.
- Steen VD, Medsger TA Jr. Long-term outcomes of scleroderma renal crisis. Ann Intern Med 2000; 133:600.
- Helfrich DJ, Banner B, Steen VD, Medsger TA Jr. Normotensive renal failure in systemic sclerosis. Arthritis Rheum 1989; 32:1128.
- DeMarco PJ, Weisman MH, Seibold JR, et al. Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial. Arthritis Rheum 2002; 46:2983.
- Domsic RT, Rodriguez-Reyna T, Lucas M, et al. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma. Ann Rheum Dis 2011; 70:104.
- Doré A, Lucas M, Ivanco D, et al. Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis. Arthritis Care Res (Hoboken) 2013; 65:1385.
- Kohno K, Katayama T, Majima K, et al. A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment. Clin Nephrol 2000; 53:479.
- Steen VD, Medsger TA Jr. Case-control study of corticosteroids and other drugs that either precipitate or protect from the development of scleroderma renal crisis. Arthritis Rheum 1998; 41:1613.
- Montanelli G, Beretta L, Santaniello A, Scorza R. Effect of dihydropyridine calcium channel blockers and glucocorticoids on the prevention and development of scleroderma renal crisis in an Italian case series. Clin Exp Rheumatol 2013; 31:135.
- Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum 2005; 35:35.
- Nguyen B, Assassi S, Arnett FC, Mayes MD. Association of RNA polymerase III antibodies with scleroderma renal crisis. J Rheumatol 2010; 37:1068; author reply 1069.
- Denton CP, Sweny P, Abdulla A, Black CM. Acute renal failure occurring in scleroderma treated with cyclosporin A: a report of three cases. Br J Rheumatol 1994; 33:90.
- Pham PT, Pham PC, Danovitch GM, et al. Predictors and risk factors for recurrent scleroderma renal crisis in the kidney allograft: case report and review of the literature. Am J Transplant 2005; 5:2565.
- Donohoe JF. Scleroderma and the kidney. Kidney Int 1992; 41:462.
- Batal I, Domsic RT, Shafer A, et al. Renal biopsy findings predicting outcome in scleroderma renal crisis. Hum Pathol 2009; 40:332.
- Hudson M, Baron M, Tatibouet S, et al. Exposure to ACE inhibitors prior to the onset of scleroderma renal crisis-results from the International Scleroderma Renal Crisis Survey. Semin Arthritis Rheum 2014; 43:666.
- Gouge SF, Wilder K, Welch P, et al. Scleroderma renal crisis prior to scleroderma. Am J Kidney Dis 1989; 14:236.
- Zwettler U, Andrassy K, Waldherr R, Ritz E. Scleroderma renal crisis as a presenting feature in the absence of skin involvement. Am J Kidney Dis 1993; 22:53.
- Poormoghim H, Lucas M, Fertig N, Medsger TA Jr. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum 2000; 43:444.
- Arnaud L, Huart A, Plaisier E, et al. ANCA-related crescentic glomerulonephritis in systemic sclerosis: revisiting the "normotensive scleroderma renal crisis". Clin Nephrol 2007; 68:165.
- Kamen DL, Wigley FM, Brown AN. Antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis in scleroderma--a different kind of renal crisis. J Rheumatol 2006; 33:1886.
- Karpinski J, Jothy S, Radoux V, et al. D-penicillamine-induced crescentic glomerulonephritis and antimyeloperoxidase antibodies in a patient with scleroderma. Case report and review of the literature. Am J Nephrol 1997; 17:528.
- Gliddon AE, Doré CJ, Black CM, et al. Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril. Arthritis Rheum 2007; 56:3837.
- Steen VD, Costantino JP, Shapiro AP, Medsger TA Jr. Outcome of renal crisis in systemic sclerosis: relation to availability of angiotensin converting enzyme (ACE) inhibitors. Ann Intern Med 1990; 113:352.
- Beckett VL, Donadio JV Jr, Brennan LA Jr, et al. Use of captopril as early therapy for renal scleroderma: a prospective study. Mayo Clin Proc 1985; 60:763.
- Rajendran PR, Molitor JA. Resolution of hypertensive encephalopathy and scleroderma renal crisis with an angiotensin receptor blocker. J Clin Rheumatol 2005; 11:205.
- Cheung WY, Gibson IW, Rush D, et al. Late recurrence of scleroderma renal crisis in a renal transplant recipient despite angiotensin II blockade. Am J Kidney Dis 2005; 45:930.
- Cozzi F, Marson P, Cardarelli S, et al. Prognosis of scleroderma renal crisis: a long-term observational study. Nephrol Dial Transplant 2012; 27:4398.
- Penn H, Quillinan N, Khan K, et al. Targeting the endothelin axis in scleroderma renal crisis: rationale and feasibility. QJM 2013; 106:839.
- Abbott KC, Trespalacios FC, Welch PG, Agodoa LY. Scleroderma at end stage renal disease in the United States: patient characteristics and survival. J Nephrol 2002; 15:236.
- Paul M, Bear RA, Sugar L. Renal transplantation in scleroderma. J Rheumatol 1984; 11:406.
- Merino GE, Sutherland DE, Kjellstrand CM, et al. Renal transplantation for progressive systemic sclerosis with renal failure: case report and review of previous experience. Am J Surg 1977; 133:745.
- Bleyer AJ, Donaldson LA, McIntosh M, Adams PL. Relationship between underlying renal disease and renal transplantation outcome. Am J Kidney Dis 2001; 37:1152.
- Gibney EM, Parikh CR, Jani A, et al. Kidney transplantation for systemic sclerosis improves survival and may modulate disease activity. Am J Transplant 2004; 4:2027.
- Chang YJ, Spiera H. Renal transplantation in scleroderma. Medicine (Baltimore) 1999; 78:382.
- Steen VD, Medsger TA Jr. Improvement in skin thickening in systemic sclerosis associated with improved survival. Arthritis Rheum 2001; 44:2828.
- Medsger TA Jr, Masi AT, Rodnan GP, et al. Survival with systemic sclerosis (scleroderma). A life-table analysis of clinical and demographic factors in 309 patients. Ann Intern Med 1971; 75:369.
- Medsger TA Jr, Masi AT. Survival with scleroderma. II. A life-table analysis of clinical and demographic factors in 358 male U.S. veteran patients. J Chronic Dis 1973; 26:647.
- Steen VD, Medsger TA Jr. Severe organ involvement in systemic sclerosis with diffuse scleroderma. Arthritis Rheum 2000; 43:2437.
- PREVALENCE AND MANIFESTATIONS OF RENAL DISEASE
- SCLERODERMA RENAL CRISIS
- Clinical features
- Risk factors
- - Diffuse skin involvement
- - Glucocorticoid use
- - Autoantibodies
- - Cyclosporine
- - Other risk factors
- Diagnosis and differential diagnosis
- - ACE inhibitors and other antihypertensive agents
- - Avoidance of glucocorticoids
- - Angiotensin-converting enzyme inhibitors
- Monitoring serum creatinine
- Unproven efficacy of angiotensin II receptor blockers
- - Non-angiotensin-converting enzyme inhibitor therapy
- - Initial approach
- - Long-term therapy
- Addition of other antihypertensive drugs
- End-stage renal disease
- - Efficacy of angiotensin-converting enzyme inhibitors
- - Dialysis
- - Renal transplantation
- Minimum wait time for transplantation
- Recurrent scleroderma renal crisis
- Patient survival
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS