Ricard Cervera1,2, Luis F Quintana3,4,5, Manuel Ferreira Gomes1, Claudia Mardones1, Marc Xipell6,2,7, Miquel Blasco6,2,7, Manel Solé7,8, Gerard Espinosa1,2, Adriana García-Herrera7,8. 1. Department of Autoimmune Diseases, Hospital Clínic, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain. 2. Department of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain. 3. Department of Nephrology and Renal Transplantation, Hospital Clínic, Barcelona, Spain. lfquinta@clinic.cat. 4. Department of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain. lfquinta@clinic.cat. 5. Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud de España (CSUR), Barcelona, Spain. lfquinta@clinic.cat. 6. Department of Nephrology and Renal Transplantation, Hospital Clínic, Barcelona, Spain. 7. Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud de España (CSUR), Barcelona, Spain. 8. Department of Pathology, Hospital Clínic, Department of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
Abstract
BACKGROUND AND OBJECTIVE: Lupus nephritis (LN) is a major complication in patients with systemic lupus erythematosus (SLE). Tubulointerstitial injury is an inflammatory process that, if not attenuated, can promote renal damage. Despite this, the current 2003 ISN/RPS "glomerulocentric" classification does not include a score for tubulointerstitial injury. We sought to establish predictors for tubulointerstitial injury and to determine their influence on renal outcomes. METHODS: This is a retrospective study of a cohort of 166 patients with biopsy-proven LN diagnosed in a Spanish referral center, with a median follow-up of 86 months. Chronic tubulointerstitial lesions were defined as interstitial fibrosis and tubular atrophy (IF/TA), whereas tubulointerstitial inflammation (TII) was defined as an acute interstitial lesion. Activity (0-24) and chronicity (0-12) indices were assigned. OUTCOME: Composite outcome, defined as advanced CKD or development of kidney failure. RESULTS: The prevalence of tubulointerstitial lesions was 69.3%. Eighty-one of the biopsies had features of tubulointerstitial inflammation and only 6 of these 81 (7%) patients had moderate/severe tubulointerstitial inflammation. The incidence of interstitial fibrosis and tubular atrophy was 56.6%. Renal survival was shorter in patients with moderate/severe as compared with absent/mild interstitial fibrosis and tubular atrophy (median: 15-19 years, p = 0.009). In the Cox regression model, the grade of interstitial fibrosis and tubular atrophy was independently associated with shorter renal survival (hazard ratio: 3.9, 95% CI 1.4-10.5; p = 0.008) after adjusting for degree of IF/TA and hypertension or diabetes. CONCLUSIONS: The extent of tubulointerstitial inflammation emerged as an independent predictor of renal survival after adjusting for the grade of interstitial fibrosis and tubular atrophy and co-morbid conditions including hypertension or diabetes. Regarding disease duration at the time of renal biopsy, no significant association was found between the interstitial fibrosis and tubular atrophy groups. The results reported herein need to be validated in future studies to include also groups of patients who usually have a worse prognosis. Consensus on histological classification is needed to aid in defining prognosis.
BACKGROUND AND OBJECTIVE: Lupus nephritis (LN) is a major complication in patients with systemic lupus erythematosus (SLE). Tubulointerstitial injury is an inflammatory process that, if not attenuated, can promote renal damage. Despite this, the current 2003 ISN/RPS "glomerulocentric" classification does not include a score for tubulointerstitial injury. We sought to establish predictors for tubulointerstitial injury and to determine their influence on renal outcomes. METHODS: This is a retrospective study of a cohort of 166 patients with biopsy-proven LN diagnosed in a Spanish referral center, with a median follow-up of 86 months. Chronic tubulointerstitial lesions were defined as interstitial fibrosis and tubular atrophy (IF/TA), whereas tubulointerstitial inflammation (TII) was defined as an acute interstitial lesion. Activity (0-24) and chronicity (0-12) indices were assigned. OUTCOME: Composite outcome, defined as advanced CKD or development of kidney failure. RESULTS: The prevalence of tubulointerstitial lesions was 69.3%. Eighty-one of the biopsies had features of tubulointerstitial inflammation and only 6 of these 81 (7%) patients had moderate/severe tubulointerstitial inflammation. The incidence of interstitial fibrosis and tubular atrophy was 56.6%. Renal survival was shorter in patients with moderate/severe as compared with absent/mild interstitial fibrosis and tubular atrophy (median: 15-19 years, p = 0.009). In the Cox regression model, the grade of interstitial fibrosis and tubular atrophy was independently associated with shorter renal survival (hazard ratio: 3.9, 95% CI 1.4-10.5; p = 0.008) after adjusting for degree of IF/TA and hypertension or diabetes. CONCLUSIONS: The extent of tubulointerstitial inflammation emerged as an independent predictor of renal survival after adjusting for the grade of interstitial fibrosis and tubular atrophy and co-morbid conditions including hypertension or diabetes. Regarding disease duration at the time of renal biopsy, no significant association was found between the interstitial fibrosis and tubular atrophy groups. The results reported herein need to be validated in future studies to include also groups of patients who usually have a worse prognosis. Consensus on histological classification is needed to aid in defining prognosis.
Authors: J R Brentjens; M Sepulveda; T Baliah; C Bentzel; B F Erlanger; C Elwood; M Montes; K C Hsu; G A Andres Journal: Kidney Int Date: 1975-05 Impact factor: 10.612
Authors: Suzanne Wilhelmus; Ingeborg M Bajema; George K Bertsias; Dimitrios T Boumpas; Caroline Gordon; Liz Lightstone; Vladimir Tesar; David R Jayne Journal: Nephrol Dial Transplant Date: 2015-04-28 Impact factor: 5.992
Authors: Michelle Petri; Ana-Maria Orbai; Graciela S Alarcón; Caroline Gordon; Joan T Merrill; Paul R Fortin; Ian N Bruce; David Isenberg; Daniel J Wallace; Ola Nived; Gunnar Sturfelt; Rosalind Ramsey-Goldman; Sang-Cheol Bae; John G Hanly; Jorge Sánchez-Guerrero; Ann Clarke; Cynthia Aranow; Susan Manzi; Murray Urowitz; Dafna Gladman; Kenneth Kalunian; Melissa Costner; Victoria P Werth; Asad Zoma; Sasha Bernatsky; Guillermo Ruiz-Irastorza; Munther A Khamashta; Soren Jacobsen; Jill P Buyon; Peter Maddison; Mary Anne Dooley; Ronald F van Vollenhoven; Ellen Ginzler; Thomas Stoll; Christine Peschken; Joseph L Jorizzo; Jeffrey P Callen; S Sam Lim; Barri J Fessler; Murat Inanc; Diane L Kamen; Anisur Rahman; Kristjan Steinsson; Andrew G Franks; Lisa Sigler; Suhail Hameed; Hong Fang; Ngoc Pham; Robin Brey; Michael H Weisman; Gerald McGwin; Laurence S Magder Journal: Arthritis Rheum Date: 2012-08
Authors: Jan J Weening; Vivette D D'Agati; Melvin M Schwartz; Surya V Seshan; Charles E Alpers; Gerald B Appel; James E Balow; Jan A Bruijn; Terence Cook; Franco Ferrario; Agnes B Fogo; Ellen M Ginzler; Lee Hebert; Gary Hill; Prue Hill; J Charles Jennette; Norella C Kong; Philippe Lesavre; Michael Lockshin; Lai-Meng Looi; Hirofumi Makino; Luiz A Moura; Michio Nagata Journal: J Am Soc Nephrol Date: 2004-02 Impact factor: 10.121
Authors: George K Bertsias; Maria Tektonidou; Zahir Amoura; Martin Aringer; Ingeborg Bajema; Jo H M Berden; John Boletis; Ricard Cervera; Thomas Dörner; Andrea Doria; Franco Ferrario; Jürgen Floege; Frederic A Houssiau; John P A Ioannidis; David A Isenberg; Cees G M Kallenberg; Liz Lightstone; Stephen D Marks; Alberto Martini; Gabriela Moroni; Irmgard Neumann; Manuel Praga; Matthias Schneider; Argyre Starra; Vladimir Tesar; Carlos Vasconcelos; Ronald F van Vollenhoven; Helena Zakharova; Marion Haubitz; Caroline Gordon; David Jayne; Dimitrios T Boumpas Journal: Ann Rheum Dis Date: 2012-07-31 Impact factor: 19.103