Estimated glomerular filtration rate and renal resistive index as possible predictive markers of mortality in systemic sclerosis

Published:February 13, 2021DOI:


      • CKD-EPI is accurate formula to estimate glomerular filtration rate in SSc patients.
      • Renal resistive index is a marker of vascular damage in SSc patients.
      • eGFR is a predictive marker of mortality for SSc and all causes.
      • RRI is a predictive marker of mortality for all causes.



      Subclinical nephropathy is underestimated in systemic sclerosis (SSc). Study aim is to evaluate the role of renal resistance indices (RRI) and estimated glomerular filtration rate (eGFR) assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as predictive markers of mortality during 10 years of follow-up in SSc patients.


      181 SSc patients (60 years, 152 females) were enrolled. At baseline, the GFR was estimated in 181 SSc patients and RRI was measured in 122 SSc patients. During a follow-up of 10 years we recorded the main complications of disease, date and causes of death.


      eGFR shows a linear negative correlation with RRI. RRI showed a correlation with systolic pulmonary artery pressure (sPAP). Overall survival is lower in SSc patients with eGFR<60 ml/min and RRI ≥0.70 than in SSc patients with eGFR≥60 ml/min (p<0.0001) and with RRI<0.70 (p<0.01) both for mortality due to SSc and all causes. In multivariate analysis, eGFR<60 ml/min [HR 6.429, 95%CI (1.006-41.08), p<0.05] and forced vital capacity (FVC) [HR 0.954, 95%CI (0.911-1), p<0.05] are predictive markers of mortality due to SSc, while eGFR [HR 3.617, 95%CI (1.370-9.554), p<0.01], RRI [HR 0.210, 95% CI (0.068-0.649), p<0.01], age [HR 1.062, 95%CI (1.023-1.103), p<0.01], FVC [HR 0.967, 95%CI (0.946-0.989), p<0.01] and disease activity index (DAI) [HR 1.663, 95%CI (1.262-2.191), p<0.0001] are predictive markers of mortality due to all causes.


      We demonstrate that eGFR is a predictive marker of mortality due to SSc and to all causes, conversely RRI is predictive marker of mortality due to all causes.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Shanmugam VK
        • Steen VD.
        Renal manifestations in scleroderma: evidence for subclinical renal disease as a marker of vasculopathy.
        Int J Rheumatol. 2010; 2010538589
        • Suebmee P
        • Foocharoen C
        • Mahakkanukrauh A
        • Suwannaroj S
        • Theerakulpisut D
        • Nanagara R.
        Correlation of Glomerular Filtration Rate Between Renal Scan and Estimation Equation for Patients With Scleroderma.
        Am J Med Sci. 2016; 352: 166-171
        • Trostle DC
        • Bedetti CD
        • Steen VD
        • Al-Sabbagh MR
        • Zee B
        • Medsger Jr., TA
        Renal vascular histology and morphometry in systemic sclerosis. A case-control autopsy study.
        Arthritis Rheum. 1988; 31: 393-400
        • Gigante A
        • Rosato E
        • Massa R
        • Rossi C
        • Barbano B
        • Cianci R
        • et al.
        Evaluation of Chronic Kidney Disease Epidemiology Collaboration equation to estimate glomerular filtration rate in scleroderma patients.
        Rheumatology (Oxford). 2012; 51: 1426-1431
        • Rosato E
        • Barbano B
        • Gigante A
        • Molinaro I
        • Quarta S
        • Pisarri S
        • et al.
        Increased intrarenal arterial stiffness may predict the occurrence of new digital ulcers in systemic sclerosis.
        Arthritis Care Res (Hoboken). 2014; 66: 1380-1385
        • van den Hoogen F
        • Khanna D
        • Fransen J
        • Johnson SR
        • Baron M
        • Tyndall A
        • et al.
        2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative.
        Ann Rheum Dis. 2013; 72: 1747-1755
        • Levey AS
        • Stevens LA
        • Schmid CH
        • Zhang YL
        • Castro 3rd, AF
        • Feldman HI
        • et al.
        CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • LeRoy EC
        • Black C
        • Fleischmajer R
        • Jablonska S
        • Krieg T
        • Medsger Jr, TA
        • et al.
        Scleroderma (systemic sclerosis): classification, subsets and pathogenesis.
        J Rheumatol. 1988; 15: 202-205
        • Furst DE
        • Clements PJ
        • Steen VD
        • Medsger Jr, TA
        • Masi AT
        • WA D'Angelo
        • et al.
        The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis.
        J Rheumatol. 1998; 25: 84-88
        • Valentini G
        • Iudici M
        • Walker UA
        • Jaeger VK
        • Baron M
        • Carreira P
        • et al.
        The European Scleroderma Trials and Research group (EUSTAR) task force for the development of revised activity criteria for systemic sclerosis: derivation and validation of a preliminarily revised EUSTAR activity index.
        Ann Rheum Dis. 2017; 76: 270-276
        • Kingdon EJ
        • Knight CJ
        • Dustan K
        • Irwin AG
        • Thomas M
        • Powis SH
        • et al.
        Calculated glomerular filtration rate is a useful screening tool to identify scleroderma patients with renal impairment.
        Rheumatology (Oxford). 2003; 42: 26-33
        • Bruni C
        • Rosato E
        • Maestripieri V
        • Gigante A
        • Tesei G
        • Bellando-Randone S
        • et al.
        The Renal Resistive Index in systemic sclerosis: Determinants, prognostic implication and proposal for specific age-adjusted cut-offs.
        Eur J Intern Med. 2019; 70: 43-49
        • Garg AX
        • Papaioannou A
        • Ferko N
        • Campbell G
        • Clarke JA
        • Ray JG.
        Estimating the prevalence of renal insufficiency in seniors requiring long-term care.
        Kidney Int. 2004; 65: 649-653
        • Rosato E
        • Gigante A
        • Barbano B
        • Cianci R
        • Molinaro I
        • Rossi C
        • et al.
        Intrarenal hemodynamic parameters correlate with glomerular filtration rate and digital microvascular damage in patients with systemic sclerosis.
        Semin Arthritis Rheum. 2012; 41: 815-821
        • Rosato E
        • Gigante A
        • Barbano B
        • Gasperini ML
        • Cianci R
        • Muscaritoli M.
        Prognostic Factors of Renal Involvement in Systemic Sclerosis.
        Kidney Blood Press Res. 2018; 43: 682-689
        • Mohamed RH
        • Zayed HS
        • Amin A.
        Renal disease in systemic sclerosis with normal serum creatinine.
        Clin Rheumatol. 2010; 29: 729-737
        • Gupta R
        • Bammigatti C
        • Dinda AK
        • Marwaha V
        • Gupta S.
        Prevalence of renal involvement in Indian patients with systemic sclerosis.
        Indian J Med Sci. 2007; 61: 91-96
        • Desai A
        • Goldschmidt RA
        • Kim GC.
        Sequential development of pulmonary renal syndrome associated with c-ANCA 3 years after development of anti-GBM glomerulonephritis.
        Nephrol Dial Transplant. 2007; 22: 926-929
        • Steen VD
        • Medsger Jr., TA
        Severe organ involvement in systemic sclerosis with diffuse scleroderma.
        Arthritis Rheum. 2000; 43 (PMID: 11083266): 2437-2444<2437::AID-ANR10>3.0.CO;2-U
        • Maurer B
        • Graf N
        • Michel BA
        • Müller-Ladner U
        • Czirják L
        Denton CP et al EUSTAR co-authors. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database.
        Ann Rheum Dis. 2015; 74: 1124-1131
        • Herrick AL
        • Peytrignet S
        • Lunt M
        • Pan X
        • Hesselstrand R
        • Mouthon L
        • et al.
        Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.
        Ann Rheum Dis. 2018; 77: 563-570
        • Wu W
        • Jordan S
        • Graf N
        • de Oliveira Pena J
        • Curram J
        • Allanore Y
        • et al.
        Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.
        Ann Rheum Dis. 2019; 78: 648-656
        • Gigante A
        • Romaniello A
        • Magrì D
        • Bonini M
        • Barbano B
        • Sardo L
        • et al.
        Correlation between intrarenal arterial stiffness and exercise tolerance in systemic sclerosis patients without renal and cardiopulmonary impairment: The role of the microvascular damage.
        Int J Cardiol. 2015; 185: 122-124
        • Rosato E
        • Leodori G
        • Gigante A
        • Di Paolo M
        • Paone G
        • Palange P.
        Reduced ventilatory efficiency during exercise predicts major vascular complications and mortality for interstitial lung disease in systemic sclerosis.
        Clin Exp Rheumatol. 2020; 38: 85-91
        • Rosato E
        • Romaniello A
        • Magrì D
        • Bonini M
        • Sardo L
        • Gigante A
        • et al.
        Exercise tolerance in systemic sclerosis patients without pulmonary impairment: correlation with clinical variables.
        Clin Exp Rheumatol. 2014; 32 (S-103-8)
        • Cianci R
        • Gigante A
        • Gasperini ML
        • Barbano B
        • Galea N
        • Rosato E.
        Late Gadolinium Enhancement in Cardiac Magnetic Resonance Imaging Is Associated with High Renal Resistive Index in Patients with Systemic Sclerosis.
        Kidney Blood Press Res. 2020; 45: 350-356
        • Livi R
        • Teghini L
        • Pignone A
        • Generini S
        • Matucci-Cerinic M
        • Cagnoni M.
        Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement.
        Ann Rheum Dis. 2002; 61: 682-686
        • Ioannidis JP
        • Vlachoyiannopoulos PG
        • Haidich AB
        • Medsger Jr, TA
        • Lucas M
        • Michet CJ
        • et al.
        Mortality in systemic sclerosis: an international meta-analysis of individual patient data.
        Am J Med. 2005; 118: 2-10
        • Perera A
        • Fertig N
        • Lucas M
        • Rodriguez-Reyna TS
        • Hu P
        • Steen VD
        • et al.
        Clinical subsets, skin thickness progression rate, and serum antibody levels in systemic sclerosis patients with anti-topoisomerase I antibody.
        Arthritis Rheum. 2007; 56: 2740-2746
        • Tyndall AJ
        • Bannert B
        • Vonk M
        • Airò P
        • Cozzi F
        • Carreira PE
        • et al.
        Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database.
        Ann Rheum Dis. 2010; 69: 1809-1815
        • Kafaja S
        • Clements PJ
        • Wilhalme H
        • Tseng CH
        • Furst DE
        • Kim GH
        • et al.
        Reliability and minimal clinically important differences of forced vital capacity: Results from the Scleroderma Lung Studies (SLS-I and SLS-II).
        Am J Respir Crit Care Med. 2018; 197: 644-652
        • Gigante A
        • Barbano B
        • Gasperini ML
        • Zingaretti V
        • Cianci R
        • Rosato E.
        Renal Parenchymal Thickness in Patients with Systemic Sclerosis Is Related to Intrarenal Hemodynamic Variables and Raynaud Renal Phenomenon.
        J Rheumatol. 2020; 47: 567-571
        • Geraci G
        • Zammuto MM
        • Cottone S
        • Mulè G.
        Renal resistive index: Beyond the hemodynamics.
        J Clin Hypertens (Greenwich). 2020; 22: 1288-1289