Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions

Abstract

Introduction Lupus nephritis (LN) affects nearly 60% of patients with systemic lupus erythematosus and up to 30% of them will progress to end-stage renal disease (ESRD), despite receiving aggressive immunosuppressive therapy. The prognostic value of ISN/RPS classification is controversial. Therefore, we aimed to identify clinical and pathological predictors of outcome in LN patients independent of this classification. Material and methods Thirty-seven patients with LN who underwent percutaneous kidney biopsy between 1997 and 2016 were included in this study. Twenty clinical and twenty histological variables were tested for their association with a composite end-point of doubling of serum creatinine, ESRD and death. Univariate and multivariate Cox proportional hazard regression analysis were performed to identify independent predictors of outcome. Results During a median follow-up period of 48 months (IQR: 17.5-120 months), 21.6% of patients reached the composite end-point. The overall survival rate of our cohort was 89% at one year, 86% at five years, 74% at 10 years and 64% at 20 years. Patients with Class IV LN showed the worst prognosis with 44% survival at 10 years, while those who additionally showed crescents and global sclerosis on kidney biopsy had an even lower survival of 21% and 0% at 10 years, respectively. After multivariate adjustment, we identified estimated glomerular filtration rate at baseline (HR, 0.91 per ml/min /1.73 m; 95% CI, 0.84 to 0.99), 24-hour proteinuria at baseline (HR, 2.04 per g/d; 95% CI, 1.19 to 3.5), crescents (HR, 1.068 per %; 95% CI, 1.003 to 1.091), global sclerosis (HR, 1.036 per %; 95% CI, 0.984 to 1.091), presence of adhesions (HR, 9.2; 95% CI, 1.38 to 61.2) and tubulitis (HR, 13.1; 95% CI; 1.3 to 131) as independent predictors of outcome in our cohort of LN. Conclusions Our study identified glomerular (crescents, global sclerosis, adhesions) and tubulointerstitial (tubulitis) lesions, in addition to clinical variables (renal function, 24-hour proteinuria), as important predictors of renal outcome, independent of the ISN/RPS classification. We suggest that the ISN/RPS classification could be improved by a quantitative assessment of glomeruli with active and chronic lesions and by a greater emphasis given to tubulointerstitial lesions.

Time to recovery from Proteinuria and its related factors in patients with lupus nephritis

“…In comparison to other studies, the patients responded to treatment in less time and proteinuria recovery happened earlier in this study (3,6,12). Similar to our research, recovery from proteinuria was de ned as proteinuria < 0.5 g/24 h in the study of Touma Z in 2014 (7).…”

“…The reason for this discrepancy is that the recovery time was differently accomplished between the two studies in other hand; Touma et al registered proteinuria recovery only if happened twice respectively whereas in our study one-time proteinuria < 0.5 g in 24 hours was little enough to categorize patients as recovered from proteinuria. Also in this research the only criteria for protein loss in urine was a 24-hour urine analysis measuring proteinuria but Touma et al have used dip stick or spot ratio of urine creatinine if they did not have access to 24-hour urine samples (6). Hernandez et al (22) showed more similar results with study in which 69% of patients after 6 months and 86% after 12 months of treatment beginning were recovered from proteinuria.…”

“…It affects the kidneys in about 50% of SLE patients (3). Among Iranian population, LN occurred at a young age and mostly in females (6).…”

“…Although potent anti-in ammatory and immunosuppressive therapies end in CKD or ESRD in many patients (3) LN is considered as a poor prognosis indicator and an important risk factor for morbidity and mortality in SLE (3). Approximately, 30% of patients will progress to end-stage renal disease (ESRD) despite immunosuppressive therapy (6).…”

2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis

“…17 18 Tubulointerstitial lesions, such as interstitial fibrosis and tubular atrophy, are associated with poor outcome. [19][20][21] A revision of the 2003 ISN/RPS classification has recently been proposed and awaits endorsement. 22…”