Kidney biopsy in lupus nephritis after achieving clinical renal remission: paving the way for renal outcome assessment
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC9613421 | biostudies-literature | 2022 Jun
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:IntroductionLimited evidence exists that clinical trial treatment response criteria predict long-term outcomes in Asian patients with lupus nephritis (LN).MethodsThis retrospective analysis of prospectively collected data from the Hong Kong Queen Mary Hospital Cohort categorized adults with biopsy-proven LN (Class III, IV, V, or mixed [III ± V, IV ± V]) after standard treatment for 2 years postbiopsy and immunosuppression induction according to modified primary efficacy renal response (mPERR: estimated glomerular filtration rate [eGFR] ≥ 60 ml/min per 1.73 m2 or ≤ 20% below biopsy value AND urine protein-to-creatinine ratio [uPCR] ≤ 0.7) and modified complete renal response (mCRR; eGFR ≥ 90 ml/min per 1.73 m2 or ≤ 10% below biopsy value AND uPCR ≤ 0.5). Associations between 2-year mPERR/mCRR status and long-term kidney survival and mild chronic kidney disease (CKD) or worse (stage ≥ 3) were assessed.ResultsOf the 176 Chinese patients, 64.2% achieved mPERR and 43.8% achieved mCRR at 2 years postbiopsy. After mean follow-up of 15.3 years, significantly higher proportions of mPERR and mCRR responders versus nonresponders achieved long-term kidney survival (mPERR: 85.8% vs. 71.4%; P = 0.029; mCRR: 92.2% vs. 71.7%; P < 0.001). mPERR and mCRR achievement was associated with adjusted risk reductions for kidney nonsurvival of 60% (P = 0.034) and 86% (P < 0.001), respectively. Adjusted risk for mild CKD or worse (stage ≥ 3) was 82% (P = 0.013) and 87% (P = 0.012) lower for mPERR and mCRR responders, respectively, versus nonresponders.ConclusionIn Chinese patients with LN, mPERR and mCRR at 2 years postbiopsy predict superior long-term kidney outcomes and lower CKD progression risk.
| S-EPMC11652096 | biostudies-literature
Project description:Lupus nephritis (LN) is a severe manifestation of SLE, characterised by subendothelial and/or subepithelial immune complex depositions in the afflicted kidney, resulting in extensive injury and nephron loss during the acute phase and eventually chronic irreversible damage and renal function impairment if not treated effectively. The therapeutic management of LN has improved during the last decades, but the imperative need for consensual outcome measures remains. In order to design trials with success potentiality, it is important to define clinically important short-term and long-term targets of therapeutic and non-therapeutic intervention. While it is known that early response to treatment is coupled with favourable renal outcomes, early predictors of renal function impairment are lacking. The information gleaned from kidney biopsies may provide important insights in this direction. Alas, baseline clinical and histopathological information has not been shown to be informative. By contrast, accumulating evidence of pronounced discrepancies between clinical and histopathological outcomes after the initial phase of immunosuppression has prompted investigations of the potential usefulness of per-protocol repeat kidney biopsies as an integral part of treatment evaluation, including patients showing adequate clinical response. This approach appears to have merit. Hopefully, clinical, molecular or genetic markers that reliably reflect kidney histopathology and portend the long-term prognosis will be identified. Novel non-invasive imaging methods and employment of the evolving artificial intelligence in pattern recognition may also be helpful towards these goals. The molecular and cellular characterisation of SLE and LN will hopefully result in novel therapeutic modalities, maybe new taxonomy perspectives, and ultimately personalised management.
| S-EPMC7046967 | biostudies-literature
Project description:ObjectivesTo observe the induction efficacy of mycophenolate mofetil and cyclophosphamide under different complete remission (CR) criteria in children with proliferative lupus nephritis, and to further explore the factors influencing the judgment of remission.MethodsFrom 2003 to 2019, children who diagnosed proliferative lupus nephritis underwent induction therapy of MMF or CYC in three hospitals were consecutively collected. Based on this population, we compared CR rates between two groups under six CR criteria selected from related recommendations and clinical trials. Then degrees and impact factors of disagreement among CR rates evaluated by selected criteria would be analyzed by Kappa test and multivariable logistic-regression models.ResultsA total of 161 children were included in this study, 27 patients received induction therapy of mycophenolate mofetil (MMF) and 134 patients recieved cyclophosphamide (CYC). Under different CR criteria, CR rates in MMF group fluctuated between 18.5%-74.1% and that in CYC group ranged from 16.4%-73.9%. Moreover, comparison between the two drugs in induction treatment under different criteria showed an opposite trend in efficacy. The results of six criteria were inconsistent, with pair-to-pair Kappa values ranging from 0.118 to 0.858. The most important factors leading to disagreement in judgment were urinary protein and urinary red blood cells.ConclusionsThe definition of complete response, especially the factors of the urinary protein and urinary red blood cells, significantly impacts the clinical judgment of children with lupus nephritis.
| S-EPMC8205752 | biostudies-literature
Project description:ObjectiveThis observational study was a retrospective analysis of prospectively collected Hopkins Lupus Cohort data to compare longterm renal survival in patients with lupus nephritis (LN) who achieved complete (CR), partial (PR), or no remission following standard-of-care LN induction therapy.MethodsEligible patients with biopsy-proven LN (revised American College of Rheumatology or Systemic Lupus Collaborating Clinics criteria) were identified and categorized into ordinal (CR, PR, or no remission) or binary (response or no response) renal remission categories at 24 months post-diagnosis [modified Aspreva Lupus Management Study (mALMS) and modified Belimumab International Lupus Nephritis Study (mBLISS-LN) criteria]. The primary endpoint was longterm renal survival [without endstage renal disease (ESRD) or death].ResultsIn total, 176 patients met the inclusion criteria. At Month 24 postbiopsy, more patients met mALMS remission criteria (CR = 59.1%, PR = 30.1%) than mBLISS-LN criteria (CR = 40.9%, PR = 16.5%). During subsequent followup, 18 patients developed ESRD or died. Kaplan-Meier plots suggested patients with no remission at Month 24 were more likely than those with PR or CR to develop the outcome using either mALMS (p = 0.0038) and mBLISS-LN (p = 0.0097) criteria for remission. Based on Cox regression models adjusted for key confounders, those in CR according to the mBLISS-LN (HR 0.254, 95% CI 0.082-0.787; p = 0.0176) and mALMS criteria (HR 0.228, 95% CI 0.063-0.828; p = 0.0246) were significantly less likely to experience ESRD/mortality than those not in remission.ConclusionRenal remission status at 24 months following LN diagnosis is a significant predictor of longterm renal survival, and a clinically relevant endpoint.
| S-EPMC5932209 | biostudies-literature
Project description:ObjectivePatients with lupus nephritis (LN) have a 26-fold higher mortality rate compared with their peers. Kidney biopsy, the gold standard diagnostic method for LN, may have an average wait time of more than 50 days. Other gaps in quality process measures during LN visits have also been reported. A subspecialty multidisciplinary clinic (MDC) can provide better care and quality in LN; therefore, we aimed to examine how an LN MDC impacted time to biopsy, time to treatment, and other quality measures.MethodsWe included all validated patients with LN who underwent diagnostic kidney biopsies between the 2011 to 2017 pre-MDC period and the 2018 to 2020 post-MDC period. We compared time to biopsy and treatment and quality measures between the two periods and examined factors associated with timely LN diagnosis, defined as a biopsy within 21 days.ResultsDuring the pre- and post-MDC periods, 53 and 21 patients with LN underwent a diagnostic biopsy, respectively. We found a decrease in the median time to biopsy from 26 days to 16 days after starting the LN clinic (P = 0.014). Beyond clinical factors, the presence of social factors, such as being of a non-White race and having food insecurity, were associated with 54% lower odds of timely diagnosis (adjusted Hazards Ratio [aHR] = 0.46; 95% confidence interval: 0.22-0.93; P = 0.031). We found higher odds of quality measure performance during the post- versus pre-MDC period.ConclusionWait times to diagnose LN decreased by 40% and higher quality measure performance was noted after establishing an LN MDC. Systemic and social barriers predicted delays in diagnosis that may be addressed by MDCs.
| S-EPMC9274336 | biostudies-literature
Project description:Prediction of prognosis in patients who have lupus nephritis is inadequate, limiting individualization of potentially toxic therapy. Advances in tissue molecular techniques offer new approaches to study mechanisms underlying kidney injury, and add to prognostic information gleaned from biopsy specimens. Analysis of mRNA expression in formalin-fixed, paraffin-embedded renal biopsy specimens is limited by both quantity and quality of RNA, requiring RNA pre-amplification, which can introduce bias. Accordingly, we developed a new technique for RNA extraction from human kidney formalin fixed paraffin embedded biopsy specimens, and used Taqman low-density arrays Applied Biosystems, Carlsbad, CA to simultaneously measure 48 mRNAs in duplicate, in a single biopsy. We extracted mRNA from more than 150 blocks to determine the quantity and vintage of biopsy tissue suitable for analysis using this protocol. We then used Taqman low-density arrays to identify suitable housekeeping genes in lupus nephritis. Finally, we measured expression of 48 mRNA transcripts in archived lupus biopsy specimens (n = 54). We identified that the mRNA levels of three transcripts (MMP7, EGF, COL1A1) relate to pathological indices of kidney injury and kidney function at the time of biopsy; these were associated with parallel changes in expression of these proteins. This new method for measurement of kidney biopsy mRNA expression has enabled us to identify tissue biomarkers of kidney damage and function, and potentially can increase the information yielded from diagnostic kidney biopsy specimens to improve tailoring of therapy.
| S-EPMC3128621 | biostudies-literature
Project description:BackgroundIn Henoch-Schönlein nephritis (HSN), a risk factor for unfavorable outcome is prolonged proteinuria, but the value of renal biopsies in prognosis assessment is debatable.MethodsWe evaluated serial renal biopsies from 26 HSN patients. Follow-up biopsy occurred at median 2.1 years after diagnostic biopsy. Patients formed two groups at the follow-up biopsy: patients without proteinuria (group I; n = 11) and with proteinuria (group II; n = 15). Biopsies underwent evaluation according to three classifications: International Study of Kidney Disease in Children (ISKDC), Oxford (MEST-C), and semiquantitative classification (SQC) including an activity and chronicity score. Analysis also included expression of pro-fibrotic (alpha-smooth muscle actin and vimentin) and inflammatory (P-selectin glycoprotein ligand-1) molecules in the diagnostic biopsy specimens. Definition of unfavorable outcome was active renal disease or reduced renal function at last follow-up.ResultsBetween the biopsies, SQC chronicity score increased in 22 (85%) patients, whereas activity score and ISKDC grade decreased in 21 (81%) and 17 (65%), respectively. Of the MEST-C parameters, endocapillary proliferation (from 83 to 13%; p < 0.001) and crescents (from 63 to 25%; p = 0.022) showed significant reduction, and segmental glomerulosclerosis (from 38 to 79%; p = 0.006) significant increment. These changes occurred similarly in groups I and II. Expression of the pro-fibrotic and inflammatory molecules showed no clinically significant differences between groups I and II. None in group I and five (33%) patients in group II had unfavorable outcome (p = 0.053).ConclusionsOur results suggest that follow-up biopsies provide limited additional information to clinical symptoms in HSN outcome prediction.
| S-EPMC7056733 | biostudies-literature
Project description:At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient's long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.
| S-EPMC6769814 | biostudies-literature
Project description:BackgroundTreatment response in lupus nephritis (LN) is defined clinically, without consideration of renal histology. Few studies have systematically examined histologic responses to induction therapy. In LN patients who underwent protocol kidney biopsies after induction immunosuppression, we describe the renal histology of the second biopsy and correlate histologic activity and damage with short- and long-term kidney outcomes.MethodsPatients with suspected LN were biopsied for diagnosis (Biopsy 1), and those with proliferative LN were rebiopsied after induction (Biopsy 2). Histologic activity and damage at each biopsy were calculated as the National Institutes of Health activity and chronicity indices. Complete and partial renal responses after induction and after long-term follow-up were determined clinically.ResultsOne-third of patients who achieved a complete clinical response after induction had persistently high histologic activity, and 62% of patients who had complete histologic remission on rebiopsy were still clinically active. Chronic renal damage increased after induction even in complete clinical responders. Chronicity at Biopsy 2 associated with long-term kidney function and development of chronic kidney disease.ConclusionsEarly clinical and histologic outcomes are discordant in proliferative LN, and neither correlates with long-term renal outcome. The kidney accrues chronic damage rapidly and despite clinical response in LN. Preservation of kidney function may require therapeutic targeting of both chronic damage and inflammation during LN induction treatment.
| S-EPMC5837387 | biostudies-literature
Project description:Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients.
| S-EPMC9699516 | biostudies-literature