Dataset Information

Histologic versus clinical remission in proliferative lupus nephritis.

ABSTRACT:

Background

Treatment 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.

Methods

Patients 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.

Results

One-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.

Conclusions

Early 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.

SUBMITTER: Malvar A

PROVIDER: S-EPMC5837387 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Histologic versus clinical remission in proliferative lupus nephritis.

Malvar Ana A Pirruccio Paola P Alberton Valeria V Lococo Bruno B Recalde Cecilia C Fazini Bernanda B Nagaraja Haikady H Indrakanti Divya D Rovin Brad H BH

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20170801 8

<h4>Background</h4>Treatment 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.<h4>Methods</h4>Patients with suspected LN were biopsied for ...[more]

PMID: 26250434

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Project description:Hydroxychloroquine (HCQ) is an antimalarial agent used to treat mucocutaneous, musculoskeletal, constitutional manifestations of systemic lupus erythematosus (SLE). This study assessed the efficacy and side effects of HCQ in children with proliferative lupus nephritis (LN). This double-blind, randomized, placebo-controlled trial study was conducted on 60 children with proliferative LN classes III and IV treated with steroids and a mycophenolate (MMF) regimen. Patients were categorized into two groups, the HCQ group (n = 30) and the placebo group (n = 30). They were evaluated initially at 6- and a 12-month follow-up by mucocutaneous, ophthalmological examination, and investigations (BUN, creatinine, 24 h proteinuria, triglycerides (TG), cholesterol, Antids-DNA, C3, C4). Disease activity was assessed using the SLE disease activity index (SLEDAI-2 k). After 12 months, TG, cholesterol, 24 h proteinuria, Antids-DNA, and SLEDAI score were significantly decreased in the HCQ group (P: 0.002, 0.012, 0.031, 0.001, respectively). After 12 months, the cumulative probabilities of developing primary end-points (LN partial and complete remission) were 40% and 60% in the HCQ group versus 53.3% and 36.7% in the placebo group (P: 0.002). After 12 months, the HCQ group experienced mucocutaneous alopecia (3.3%), hyperpigmentation (10%), and ophthalmological mild retinal changes (6.7%), but they did not differ significantly from the placebo group. Cunclusion: HCQ improved the disease and LN activity in children with proliferative LN, with documented skin hyperpigmentation and mild retinal changes following HCQ use in a few cases. This study was registered on http://www.Clinicaltrialsgov/ with trial registration number (TRN): NCT03687905, September 2018 "retrospectively registered."What is known• Hydroxychloroquine (HCQ) is documented as an adjunctive treatment in children with systemic lupus erythematosus (c-SLE) LN with efficacy in improving lupus musculoskeletal and mucocutaneous manifestations. • Due to the paucity of studies, its effects and side effects in children with LN remain unclear.What is new• This pilot randomized clinical trial assessed the efficacy and adverse effects of HCQ in children with proliferative LN. • HCQ had numerous advantages for LN, including rapid and sustained remission, antilipidemic effect, and rapid improvement of kidney functions.

Project description:IntroductionSystemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).MethodsMetabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.ResultsUrinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).ConclusionsThis pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.

Dataset Information

Histologic versus clinical remission in proliferative lupus nephritis.

Background

Methods

Results

Conclusions

Publications

Histologic versus clinical remission in proliferative lupus nephritis.

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