A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Obrișcă, Bogdan; Vornicu, Alexandra; Procop, Alexandru; Herlea, Vlad; Terinte-Balcan, George; Gherghiceanu, Mihaela; Ismail, Gener

doi:10.3390/biomedicines10061409

Cited by 5 publications

(6 citation statements)

References 87 publications

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“…8,11 In fact, discrepancies between the severity of tubulointerstitial and vascular lesions and that of the glomerular compartment have been observed in kidney biopsies. 21 Consistent with this observation, a negative impact of tubulointerstitial involvement on kidney survival has been reported in LN, regardless of the extent of glomerular damage. [8][9][10][11][12][13]22,23 Both TII and IFTA independently predict progression to ESKD, especially if these lesions are more severe and extensive (≥50%).…”

Section: Discussionsupporting

confidence: 71%

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Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Rodelo

Aguirre

Ortegón

et al. 2023

Lupus

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Objective To assess the effect of tubulointerstitial inflammation (TII) and interstitial fibrosis and tubular atrophy (IFTA) on kidney survival in lupus nephritis (LN). Methods Two hundred eighty five patients with biopsy-proven LN were retrospectively studied. Kidney survival was defined as the time from initial biopsy to end-stage kidney disease (ESKD), dialysis, or transplant. Kidney survival analysis was performed by the Kaplan–Meier method and the statistical difference between survival curves compared by the log-rank test. Cumulative incidence functions with competing risk of death for kidney survival were also graphed. Multivariable Cox proportional hazards regression and competing-risk analyses were performed to identify independent predictors of ESKD. Results Fifty-seven patients (20%) progressed to ESKD during a median time of 4.2 (2.0–55.2) months after biopsy. TII was present in 206 (72.3%) biopsies, while IFTA in 99 (34.7%) biopsies. Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA in both the Kaplan–Meier ( p = 0.018) and the competing-risk analyses ( p = 0.017). Patients with class IV ± V LN had worse kidney survival than those with non-class IV LN by the Kaplan–Meier method ( p = 0.050), but not in the competing-risk analysis ( p = 0.154). Worse kidney survival was also found among those with fibrous crescents than those without, in both the Kaplan–Meier ( p = 0.010) and the competing-risk ( p = 0.011) analyses. By multivariable Cox regression analysis, older age (HR 1.04, 95% CI 1.01–1.07) and class IV ± V LN (HR 5.06, 95% CI 1.82–14.09) were associated with higher risk of ESKD after adjusting for sex, ethnicity, TII, and IFTA. By competing-risk analyses, class IV ± V LN (SHR 3.32, 95% CI 1.25–8.83) and no response to immunosuppressive therapy (SHR 4.55, 95% CI 1.54–13.41) were associated with a higher risk of ESKD, while eGFR >90 mL/min/1.73 m2 (SHR 0.98 for each ml/min/1.73 m 2 , 95% 0.97–0.99) with a lower risk. Conclusions Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA. Worse kidney survival was also found among those with class IV LN and fibrous crescents versus those without IV LN and fibrous crescents, respectively.

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Section: Discussionsupporting

confidence: 71%

“…Forty-one percent of the patients were hypertensive. The median (IQR) SLEDAI score at the time of the biopsy was 18 (14)(15)(16)(17)(18)(19)(20)(21)(22). The frequencies of the clinical and immunological 2012 SLICC criteria are shown in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Rodelo

Aguirre

Ortegón

et al. 2023

Lupus

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“…A class IV regression was observed in only 1 patient (3.8%) toward class III, which does not imply any degree of greater clinical importance given that the proposed treatment for both classes (III and IV) would be the same [28,29].…”

Section: Nossent Et Al Demonstrated That Only a Chronicity Index Of >3mentioning

confidence: 77%

Comparison of Histopathological Findings with Clinical Response among Patients Undergoing Consecutive Renal Biopsy for Lupus Nephritis in 2008-2021

Villadiego-Rojas¹,

Aroca-Martínez²,

Cadena-Bonfanti³

et al. 2023

Act Scie Nutr

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Introduction: Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease involving several systems and has a high occurrence in areas such as the kidney, central nervous system, and vascular and serous structures. Furthermore, SLE poses a significant and increased risk of infections as well as an increase in morbidity and mortality. This increase is due to the presence of risk factors such as the use of corticosteroids, immunosuppressive drugs, and cytotoxic agents; changes in renal function; leukopenia, hypoalbuminemia; and alterations in both renal function and immunological profile (complement, anti-DNA).Renal biopsy (RB) is a safe method for obtaining renal tissue for the diagnosis and prognosis of SLE. Although complications, such as hemorrhage, are rare, if they do occur, they usually do so during the first 8-24 hours of the procedure. This diagnostic method is the best tool to diagnose lupus nephritis. Hence, we conducted a study to determine the histological changes in patients with lupus nephritis who were evaluated with consecutive biopsies from 2008 to 2021. Materials and Methods:An observational, analytical, and retrospective study was conducted using information collected from the RB database. Data on SLE and/or lupus nephritis recorded in this database by Clínica de la Costa uninterruptedly from 2008 to 2021.Patients with a diagnosis of SLE were selected based on at least four diagnostic criteria of the American College of Rheumatology.Those who had undergone renal puncture biopsy according to the consensus criteria of the group of systemic autoimmune diseases of the Spanish Society of Nephrology were selected.Results: A significant increase was observed in chronicity rates. Conclusion:Consecutive renal biopsy in LN allows early identification of the progress of the histopathological lesion. In this study, 30.7% of class III patients in their first renal biopsy presented histologicalprogress toward class IV in their consecutive biopsy.

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“…In order to overcome the limitations of the Oxford Classification, we attempted to evaluate the impact of LM pattern of glomerular injury and to define the role of mesangial C3 deposition in IgAN. This approach may be viewed as similar to LN, where IS treatment is guided by the ISN/RPS class and prognostication takes into account individual lesions encompassed in the NIH activity and chronicity index [ 17 , 26 ]. In this regard, the mesangioproliferative pattern of IgAN, which resembles class II LN, had the best renal outcome among the proliferative patterns with a 5-year renal survival over 90% and a mean eGFR decline of -0.29 ml/min/y.…”

Section: Discussionmentioning

confidence: 99%

“…This approach may be regarded as reminiscent of that for patients with lupus nephritis (LN). Accordingly, patients with LN show a weak correlation between clinical features and histological findings and the tissue-based information is essential to guide the immunosuppressive therapy [ 17 ]. While the current treatment stratification in IgAN relies solely on clinical variables (persistent proteinuria and eGFR level), the possibility of incorporation the tissue-based information into treatment-selection algorithms, while appealing, needs to be tested in prospective, randomized clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition

Obrișcă,

Mocanu,

Jurubiță

et al. 2024

BMC Nephrol

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Background There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN. Methods We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year. Results This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m2 and 1.5 g/day (IQR:0.8–3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and − 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21–9.2). Conclusions We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN.

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A Histology-Guided Approach to the Management of Patients with Lupus Nephritis: Are We There Yet?

Cited by 5 publications

References 87 publications

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Comparison of Histopathological Findings with Clinical Response among Patients Undergoing Consecutive Renal Biopsy for Lupus Nephritis in 2008-2021

Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition

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