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Renal disease in sarcoidosis patients in a German multicentric retrospective cohort study

Published:January 17, 2023DOI:https://doi.org/10.1016/j.rmed.2023.107121

      Highlights

      • The prevalence of renal sarcoidosis was 27.5% in a multicentric German cohort.
      • Patients with renal sarcoidosis received glucocorticoids, azathioprine, and mycophenolate mofetil more frequently.
      • Higher soluble interleukin-2 receptor (sIL-2R) levels were associated with a risk of an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2.
      • Almost all patients with biopsy-confirmed renal sarcoidosis had an eGFR <60 ml/min/1.73 m2, proteinuria >300 mg/g creatinine, or a pathologic urine sediment combined with an elevated soluble interleukin-2 receptor.
      • A dedicated renal workup should be performed in all patients with a recent diagnosis of sarcoidosis.

      Abstract

      Introduction

      Sarcoidosis is a systemic granulomatous disease potentially affecting every organ system. Renal involvement is reportedly rare, and the evidence consists of case reports and cohort studies. Systematic investigations are scarce and show a varying prevalence ranging from <1% to 30–50%.

      Methods

      We retrospectively analyzed data from patients with a recent diagnosis of sarcoidosis from five tertiary care centers focusing on renal sarcoidosis.

      Results

      We analyzed data from 327 patients with sarcoidosis between 2001 and 2021. Of 327 patients, 109 (33.3%) had probable or definite renal sarcoidosis. 90 (27.5%) had histopathologic confirmation. 57 (64%) had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The most prominent associated finding was an elevated soluble interleukin-2 receptor. Patients with renal sarcoidosis more frequently received glucocorticoids than other non-renal sarcoidosis patients (92% vs. 78%, p < 0.01). Also, azathioprine (38% vs. 16%, p < 0.001) and mycophenolate mofetil (5% vs. 1%, p < 0.05) were more frequently used in renal sarcoidosis compared to non-renal sarcoidosis, whereas methotrexate was used less frequently (7% vs. 17%, p < 0.05).

      Conclusions

      Our data of the largest cohort with biopsy-confirmed renal sarcoidosis demonstrate a higher prevalence (27.5% of all patients) than previously published with a relevant disease burden. The urinary findings in most cases were only mildly abnormal, and some patients did not have renal biopsy despite abnormal urinary results. A renal workup should be performed in all patients with a new diagnosis of sarcoidosis.

      Keywords

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      References

        • Grunewald J.
        • Grutters J.C.
        • Arkema E.V.
        • Saketkoo L.A.
        • Moller D.R.
        • Müller-Quernheim J.
        Sarcoidosis.
        Nat. Rev. Dis. Prim. 2019; 5: 45https://doi.org/10.1038/s41572-019-0096-x
        • Milman N.
        • Selroos O.
        Pulmonary sarcoidosis in the Nordic countries 1950-1982. Epidemiology and clinical picture.
        Sarcoidosis. 1990; 7: 50-57
        • Arkema E.V.
        • Grunewald J.
        • Kullberg S.
        • Eklund A.
        • Askling J.
        Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden.
        Eur. Respir. J. 2016; 48: 1690-1699https://doi.org/10.1183/13993003.00477-2016
        • Dumas O.
        • Abramovitz L.
        • Wiley A.S.
        • Cozier Y.C.
        • Camargo Jr., C.A.
        Epidemiology of sarcoidosis in a prospective cohort study of U.S. Women.
        Ann. Am. Thorac. Soc. 2016; 13: 67-71https://doi.org/10.1513/AnnalsATS.201508-568BC
        • Ungprasert P.
        • Carmona E.M.
        • Utz J.P.
        • Ryu J.H.
        • Crowson C.S.
        • Matteson E.L.
        Epidemiology of sarcoidosis 1946–2013: a population based study.
        Mayo Clin. Proc. 2016; 91: 183-188https://doi.org/10.1016/j.mayocp.2015.10.024
        • Pietinalho A.
        • Hiraga Y.
        • Hosoda Y.
        • Lofroos A.B.
        • Yamaguchi M.
        • Selroos O.
        The frequency of sarcoidosis in Finland and Hokkaido, Japan. A comparative epidemiological study.
        Sarcoidosis. 1995; 12: 61-67
        • Baughman R.P.
        • Teirstein A.S.
        • Judson M.A.
        • Rossman M.D.
        • Yeager H.
        • Bresnitz E.A.
        • DePalo L.
        • Hunninghake G.
        • Iannuzzi M.C.
        • Johns C.J.
        • McLennan G.
        • Moller D.R.
        • Newman L.S.
        • Rabin D.L.
        • Rose C.
        • Rybicki B.
        • Weinberger S.E.
        • Terrin M.L.
        • Knatterud G.L.
        • Cherniak R.
        Case Control Etiologic Study of Sarcoidosis (ACCESS) research group, Clinical characteristics of patients in a case control study of sarcoidosis.
        Am. J. Respir. Crit. Care Med. 2001; 164: 1885-1889https://doi.org/10.1164/ajrccm.164.10.2104046
        • Iannuzzi M.C.
        • Fontana J.R.
        Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics.
        JAMA. 2011; 305: 391-399https://doi.org/10.1001/jama.2011.10
        • Baughman R.P.
        • Teirstein a S.
        • a Judson M.
        • Rossman M.D.
        • Yeager Jr., H.
        • a Bresnitz E.
        • DePalo L.
        • Hunninghake G.
        • Iannuzzi M.C.
        • Johns C.J.
        • McLennan G.
        • Moller D.R.
        • Newman L.S.
        • Rabin D.L.
        • Rose C.
        • Rybicki B.
        • Weinberger S.E.
        • Terrin M.L.
        • Knatterud G.L.
        • Cherniak R.
        Clinical characteristics of patients in a case control study of sarcoidosis.
        Am. J. Respir. Crit. Care Med. 2001; 164: 1885-1889https://doi.org/10.1164/rccm2104046
        • Markevitz N.
        • Epstein Shochet G.
        • Levi Y.
        • Israeli-Shani L.
        • Shitrit D.
        Sarcoidosis in Israel: clinical outcome status, organ involvement, and long-term follow-up.
        Lung. 2017; 195: 419-424https://doi.org/10.1007/s00408-017-0015-4
        • Mañá J.
        • Rubio-Rivas M.
        • Villalba N.
        • Marcoval J.
        • Iriarte A.
        • Molina-Molina M.
        • Llatjos R.
        • García O.
        • Martínez-Yélamos S.
        • Vicens-Zygmunt V.
        • Gámez C.
        • Pujol R.
        • Corbella X.
        Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis.
        Medicine. 2017; 96e7595https://doi.org/10.1097/MD.0000000000007595
        • Rajakariar R.
        • Sharples E.J.
        • Raftery M.J.
        • Sheaff M.
        • Yaqoob M.M.
        Sarcoid tubulo-interstitial nephritis: long-term outcome and response to corticosteroid therapy.
        Kidney Int. 2006; https://doi.org/10.1038/sj.ki.5001512
        • Mahevas M.
        • Lescure F.X.
        • Boffa J.-J.
        • Delastour V.
        • Belenfant X.
        • Chapelon C.
        • Cordonnier C.
        • Makdassi R.
        • Piette J.-C.
        • Naccache J.-M.
        • Cadranel J.
        • Duhaut P.
        • Choukroun G.
        • Ducroix J.P.
        • Valeyre D.
        Renal sarcoidosis: clinical, laboratory, and histologic presentation and outcome in 47 patients.
        Medicine. 2009; 88: 98-106https://doi.org/10.1097/MD.0b013e31819de50f
        • Löffler C.
        • Löffler U.
        • Tuleweit A.
        • Waldherr R.
        • Uppenkamp M.
        • Bergner R.
        Renal sarcoidosis: epidemiological and follow-up data in a cohort of 27 patients.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2015; 31: 306-315
        • Bergner R.
        • Hoffmann M.
        • Waldherr R.
        • Uppenkamp M.
        Frequency of Kidney Disease in Chronic Sarcoidosis, Sarcoidosis Vasculitis and Diffuse Lung Diseases. vol. 20. 2003: 126-132
        • Bergner R.
        • de Groot K.
        • Müller G.A.
        • Korsten P.
        Frequency of organ manifestations in chronic sarcoidosis.
        Ann. Rheum. Dis. 2017; 76 (LP – 721): 721
        • Yassari F.
        • Kiani A.
        • Taghavi K.
        • Abdi E.
        • Emami H.
        • Seifi S.
        • Abedini A.
        Renal disorders in pulmonary sarcoidosis patients.
        Iranian J. Kidney Dis. 2019; 13: 21-26
        • Robson M.G.
        • Banerjee D.
        • Hopster D.
        • Cairns H.S.
        Seven cases of granulomatous interstitial nephritis in the absence of extrarenal sarcoid.
        Nephrol. Dial. Transplant. 2003; 18: 280-284https://doi.org/10.1093/ndt/18.2.280
        • McCoy R.C.
        • Tisher C.C.
        Glomerulonephritis associated with sarcoidosis.
        Am. J. Pathol. 1972; 68: 339-358
        • Taylor R.G.
        • Fisher C.
        • Hoffbrand B.I.
        Sarcoidosis and membranous glomerulonephritis : a significant association. 1982; 284: 1297-1298
        • Vanhille P.
        • Beaudoin D.
        • Mougenot B.
        • Striker L.
        • Lemaitre V.
        • Fleury D.
        • Gobert P.
        [Rapidly progressing glomerulonephritis with mesangial IgA deposits in sarcoidosis].
        Nephrologie. 1986; 7: 207-209
        • Molle D.
        • Baumelou A.
        • Beaufils H.
        • Vannier R.
        • Legrain M.
        Membranoproliferative glomerulonephritis associated with pulmonary sarcoidosis.
        Am. J. Nephrol. 1986; 6: 386-387https://doi.org/10.1159/000167198
        • Khan I.H.
        • Simpson J.G.
        • Catto G.R.
        • MacLeod A.M.
        Membranous nephropathy and granulomatous interstitial nephritis in sarcoidosis.
        Nephron. 1994; 66: 459-461https://doi.org/10.1159/000187864
        • Wachtell K.
        • Molzen A.H.
        • Hansen F.M.
        [Nephrocalcinosis and urolithiasis as primary symptoms in Boeck's sarcoidosis].
        Ugeskr Laeger. 1996; 158: 1685-1686
        • Toda T.
        • Kimoto S.
        • Nishio Y.
        • Ehara T.
        • Sasaki S.
        Sarcoidosis with membranous nephropathy and granulomatous interstitial nephritis.
        Intern. Med. 1999; 38: 882-886
        • Ponce C.
        • Gujral J.S.
        Renal failure and hypercalcemia as initial manifestations of extrapulmonary sarcoidosis.
        South. Med. J. 2004; 97: 590-592
        • Monge M.
        • Miquel O.
        • Dugardin F.
        • Modeliar S.S.
        • Glerant J.-C.
        • Hacene S.
        • Cordonnier C.
        • Makdassi R.
        • Choukroun G.
        Sarcoidosis and the kidney: not only the granulomatous interstitial nephritis.
        Clin. Nephrol. 2009; 71: 192-195
        • Crouser E.D.
        • Maier L.A.
        • Wilson K.C.
        • Bonham C.A.
        • Morgenthau A.S.
        • Patterson K.C.
        • Abston E.
        • Bernstein R.C.
        • Blankstein R.
        • Chen E.S.
        • Culver D.A.
        • Drake W.
        • Drent M.
        • Gerke A.K.
        • Ghobrial M.
        • Govender P.
        • Hamzeh N.
        • James W.E.
        • Judson M.A.
        • Kellermeyer L.
        • Knight S.
        • Koth L.L.
        • Poletti V.
        • Raman S.V.
        • Tukey M.H.
        • Westney G.E.
        • Baughman R.P.
        Diagnosis and detection of sarcoidosis. An official American thoracic society clinical practice guideline.
        Am. J. Respir. Crit. Care Med. 2020; 201 (e26–e51)https://doi.org/10.1164/rccm.202002-0251ST
        • Levey A.S.
        • Stevens L.A.
        Estimating GFR using the CKD Epidemiology collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions.
        Am. J. Kidney Dis. 2010; 55: 622-627https://doi.org/10.1053/j.ajkd.2010.02.337
        • Judson M.A.
        • Costabel U.
        • Drent M.
        • Wells A.
        • Maier L.
        • Koth L.
        • Shigemitsu H.
        • Culver D.A.
        • Gelfand J.
        • Valeyre D.
        • Sweiss N.
        • Crouser E.
        • Morgenthau A.S.
        • Lower E.E.
        • Azuma A.
        • Ishihara M.
        • Morimoto S.-I.
        • Tetsuo Yamaguchi T.
        • Shijubo N.
        • Grutters J.C.
        • Rosenbach M.
        • Li H.-P.
        • Rottoli P.
        • Inoue Y.
        • Prasse A.
        • Baughman R.P.
        • Organ T.W.S.
        Assessment instrument investigators, the WASOG sarcoidosis organ assessment instrument: an update of a previous clinical tool.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2014; 31: 19-27
        • Therneau T.M.
        • Atkinson E.J.
        • Foundation M.
        An Introduction to Recursive Partitioning Using the RPART Routines.
        2022
        • Stevenson M.
        • Nunes T.
        • Heuer C.
        • Marshall J.
        • Sanchez J.
        • Thornton R.
        • Reiczigel J.
        • Robison-Cox J.
        • Sebastiani P.
        • Solymos P.
        • Yoshida K.
        • Jones G.
        • Pirikahu S.
        • Firestone S.
        • Kyle R.
        • Popp J.
        • Jay M.
        epiR: Tools for the Analysis of Epidemiological Data. R Package Version 0.9-96.
        2018 (accessed)
        • Wetzels J.F.M.
        • Kiemeney L.a.L.M.
        • Swinkels D.W.
        • Willems H.L.
        • den Heijer M.
        Age- and gender-specific reference values of estimated GFR in caucasians: the nijmegen biomedical study.
        Kidney Int. 2007; 72: 632-637https://doi.org/10.1038/sj.ki.5002374
        • Martusewicz-Boros M.M.
        • Boros P.W.
        • Wiatr E.
        • Fijołek J.
        • Roszkowski-Śliz K.
        Systemic treatment for sarcoidosis was needed for 16% of 1810 Caucasian patients.
        Clin. Respiratory J. 2017; : 1-5https://doi.org/10.1111/crj.12664
        • Ungprasert P.
        • Crowson C.S.
        • Matteson E.L.
        Epidemiology and clinical characteristics of sarcoidosis: an update from a population-based cohort study from Olmsted County, Minnesota.
        Rheumatism. 2017; 69: 16-22https://doi.org/10.4081/reumatismo.2017.965
        • Judson M.A.
        The clinical features of sarcoidosis: a comprehensive review.
        Clin. Rev. Allergy Immunol. 2015; 49: 63-78https://doi.org/10.1007/s12016-014-8450-y
        • Jankowski J.
        • Floege J.
        • Fliser D.
        • Böhm M.
        • Marx N.
        Cardiovascular disease in chronic kidney disease.
        Circulation. 2021; 143: 1157-1172https://doi.org/10.1161/CIRCULATIONAHA.120.050686
        • Rastelli F.
        • Baragetti I.
        • Buzzi L.
        • Ferrario F.
        • Benozzi L.
        • Di Nardo F.
        • Devoti E.
        • Cancarini G.
        • Mezzina N.
        • Napodano P.
        • Gallieni M.
        • Santoro D.
        • Buemi M.
        • Pecchini P.
        • Malberti F.
        • Colombo V.
        • Colussi G.
        • Sabadini E.
        • Remuzzi G.
        • Argentiero L.
        • Gesualdo L.
        • Gatti G.
        • Trevisani F.
        • Slaviero G.
        • Spotti D.
        • Baraldi O.
        • La Manna G.
        • Pignone E.
        • Saltarelli M.
        • Heidempergher M.
        • Tedesco M.
        • Genderini A.
        • Ferro M.
        • Rollino C.
        • Roccatello D.
        • Guzzo G.
        • Clari R.
        • Barbara Piccoli G.
        • Comotti C.
        • Brunori G.
        • Cameli P.
        • Bargagli E.
        • Rottoli P.
        • Dugo M.
        • Cristina Maresca M.
        • Bertoli M.
        • Giozzet M.
        • Brugnano R.
        • Giovanni Nunzi E.
        • D'Amico M.
        • Minoretti C.
        • Acquistapace I.
        • Colturi C.
        • Minola E.
        • Camozzi M.
        • Tosoni A.
        • Nebuloni M.
        • Ferrario F.
        • Dell'Antonio G.
        • Cusinato S.
        • Feriozzi S.
        • Pozzi C.
        Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2021; 38e2021017https://doi.org/10.36141/svdld.v38i3.11488
        • Mehta R.
        • Shah G.
        • Adler W.
        • Kittur D.
        Soluble interleukin 2 receptor (sIL-2R) levels in renal transplant recipients.
        Clin. Transplant. 2004; 18: 67-71https://doi.org/10.1111/j.1399-0012.2004.00221.x
      1. X. Chen, Y. Li, X. Ding, J. Zou, B. Shen, Z. Liu, W. Lv, X. Cao, F. Xiang, The significance of serum levels of soluble interleukin-2 receptor in patients undergoing maintenance hemodialysis, Ren. Fail.. 42 (n.d.) 419–427. https://doi.org/10.1080/0886022X.2020.1761388.

        • Larsson J.
        • Graff P.
        • Bryngelsson I.L.
        • Vihlborg P.
        Sarcoidosis and Increased Risk of Comorbidities and Mortality in sweden, Sarcoidosis Vasculitis and Diffuse Lung Diseases. vol. 37. 2020: 104-135https://doi.org/10.36141/svdld.v37i2.9142
        • Jeon M.H.
        • Kang T.
        • Yoo S.H.
        • Swan H.S.
        • Kim H.J.
        • Ahn H.S.
        The Incidence, Comorbidity and Mortality of Sarcoidosis in Korea, 2008-2015: A Nationwide Population-Based Study, Sarcoidosis Vasculitis and Diffuse Lung Diseases. vol. 37. 2020: 24-36https://doi.org/10.36141/svdld.v37i1.7660
        • Gerke A.K.
        Morbidity and mortality in sarcoidosis.
        Curr. Opin. Pulm. Med. 2014; 20: 472-478https://doi.org/10.1097/MCP.0000000000000080
        • Mahmoud A.R.
        • Dahy A.
        • Dibas M.
        • Abbas A.S.
        • Ghozy S.
        • El-Qushayri A.E.
        Association between sarcoidosis and cardiovascular comorbidity: a systematic review and meta-analysis.
        Heart Lung. 2020; 49: 512-517https://doi.org/10.1016/j.hrtlng.2020.03.013
        • Van Domburg R.T.
        • Hoeks S.E.
        • Welten G.M.J.M.
        • Chonchol M.
        • Elhendy A.
        • Poldermans D.
        Renal insufficiency and mortality in patients with known or suspected coronary artery disease.
        J. Am. Soc. Nephrol. 2008; 19: 158-163https://doi.org/10.1681/ASN.2006101112
        • Mahmoodi B.K.
        • Matsushita K.
        • Woodward M.
        • Blankestijn P.J.
        • Cirillo M.
        • Ohkubo T.
        • Rossing P.
        • Sarnak M.J.
        • Stengel B.
        • Yamagishi K.
        • Yamashita K.
        • Zhang L.
        • Coresh J.
        • De Jong P.E.
        • Astor B.C.
        Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis.
        Lancet. 2012; 380: 1649-1661https://doi.org/10.1016/S0140-6736(12)61272-0
        • Hilderson I.
        • Van Laecke S.
        • Wauters A.
        • Donck J.
        Treatment of renal sarcoidosis: is there a guideline? Overview of the different treatment options.
        Nephrol. Dial. Transplant. 2014; 29: 1841-1847https://doi.org/10.1093/ndt/gft442
        • Löffler C.
        • Löffler U.
        • Tuleweit A.
        • Waldherr R.
        • Uppenkamp M.
        • Bergner R.
        Renal Sarcoidosis: epidemiological and follow-up data in a cohort of 27 patients.
        Sarcoidosis Vasc. Diffuse Lung Dis. 2014; : 31
        • Bergner R.
        • Löffler C.
        Renal sarcoidosis: approach to diagnosis and management.
        Curr. Opin. Pulm. Med. 2018; 24: 513-520https://doi.org/10.1097/MCP.0000000000000504