Comparison of the Clinical Implications among Five Different Nutritional Indices in Patients with Lupus Nephritis.
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ABSTRACT:
SUBMITTER: Ahn SS
PROVIDER: S-EPMC6682980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations. Although the approval of new therapies includes only one agent in 50 years, a number of promising new drugs are in development. Lupus nephritis is a dreaded complication of SLE as it is associated with significant morbidity and mortality. Advancing the treatment of lupus nephritis requires well-designed clinical trials and this can be challenging in SLE. The major obstacles involve identifying the correct population of patients to enroll and ensuring that a clinically appropriate and patient-centered endpoint is being measured. In this review, we will first discuss the clinical utility of endpoints chosen to represent lupus nephritis in global disease activity scales. Second, we will review completed and active trials focused on lupus nephritis and discuss the endpoints chosen. There are many important lessons to be learned from existing assessment tools and clinical trials. Reviewing these points will help ensure that future efforts will yield meaningful disease activity measures and well-designed clinical trials to advance our understanding of lupus management.
| S-EPMC4411763 | biostudies-literature
Project description:Systemic lupus erythematosus is a heterogeneous autoimmune disease marked by the presence of pathogenic autoantibodies, immune dysregulation, and chronic inflammation that may lead to increased morbidity and early mortality from end-organ damage. More than half of all systemic lupus erythematosus patients will develop lupus nephritis. Genetic-association studies have identified more than 50 polymorphisms that contribute to lupus nephritis pathogenesis, including genetic variants associated with altered programmed cell death and defective immune clearance of programmed cell death debris. These variants may support the generation of autoantibody-containing immune complexes that contribute to lupus nephritis. Genetic variants associated with lupus nephritis also affect the initial phase of innate immunity and the amplifying, adaptive phase of the immune response. Finally, genetic variants associated with the kidney-specific effector response may influence end-organ damage and the progression to end-stage renal disease and death. This review discusses genetic insights of key pathogenic processes and pathways that may lead to lupus nephritis, as well as the clinical implications of these findings as they apply to recent advances in biologic therapies.
| S-EPMC4653095 | biostudies-literature
Project description:To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings.In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ?10 versus >10; tubulointerstitial activity index (TIAI) score: ?5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ?1.There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status.Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity.
| S-EPMC4720587 | biostudies-literature
Project description:BackgroundThis study aimed to investigate fetal and maternal outcomes in women with active lupus nephritis (LN). Specifically, we compared women who had new-onset LN and those with pre-existing LN during pregnancy.MethodsPatients with active LN during pregnancy were divided into the new-onset group (LN first occurred during pregnancy) and the pre-existing group (a history of LN) on the basis of the onset time of LN. Data on clinical features, laboratory findings, and pregnancy outcome were collected and analyzed between the two groups. Multivariate logistic regression analysis was used to compare the effects of active LN on adverse pregnancy outcomes.ResultsWe studied 73 pregnancies in 69 women between 2010 and 2019. Of these, 38 pregnancies were in the pre-existing LN group and 35 were in the new-onset group. Patients with pre-existing LN had a higher risk of composite adverse fetal outcomes than those with new-onset LN [adjusted odds ratio (ORs), 44.59; 95% confidence interval (CI), 1.21-1664.82; P = 0.039]. However, the two groups had similar adverse maternal outcomes (ORs, 1.24; 95% CI, 0.36-4.29). Serum albumin and proteinuria significantly improved after pregnancy (P < 0.001). Kaplan-Meier analysis showed that the long-term renal outcome was similar between the two groups.ConclusionsPregnant patients with pre-existing LN were associated with a higher risk of composite adverse fetal outcomes than those with new-onset LN. However, these two groups of patients had similar adverse maternal outcomes. The long-term renal outcomes were not different after pregnancy between these two groups.
| S-EPMC8691084 | biostudies-literature
Project description:OBJECTIVE:Clinical trials of therapies for lupus nephritis have used many different primary outcome measures, ranging from complete response to time to end-stage renal disease. The objective of this study was to compare several possible outcome measures, using data from a large, multicenter trial of abatacept in lupus nephritis, to gain insight into which outcome measure, if any, was best able to discern differences among treatment groups. METHODS:Study patients received either abatacept or placebo, on a background of mycophenolate mofetil and glucocorticoids. Using data from this trial, the following primary outcome measures at 24 and 52 weeks were compared: complete response rate, major clinical response rate, total response rate (complete plus partial response), improvement in proteinuria, improvement in estimated glomerular filtration rate, and frequency of treatment failure. Time to complete response was also evaluated. RESULTS:Complete response rate, major clinical response rate, and time to complete response were the measures that best discriminated between the abatacept groups and placebo, and the sensitivities of these 3 measures were comparable. For these measures, sample sizes of 50 patients would have been sufficient to demonstrate a statistically significant difference between treatment and control at 52 weeks. Each of the other measures also discriminated between treatment and control, but much larger group sizes would have been required to determine statistical significance. CONCLUSION:The choice of primary outcome measure can substantially influence the ability to detect therapeutic benefit in lupus nephritis trials. This study suggests that complete response rate, major clinical response rate at 52 weeks, and time to complete response may be the most sensitive outcome measures for detecting differences among therapeutic regimens.
| S-EPMC4398144 | biostudies-literature
Project description:Lupus nephritis (LN) is an ominous complication of systemic lupus erythematosus, and the risk factors for the disease progression are not well characterized.In a retrospective study, the authors evaluated the mode of presentation and outcomes of 163 consecutive patients with biopsy-proven LN, who presented to the center between January 1999 and September 2008. Using stepwise logistic regression analysis, the authors assessed risk factors independently associated with response to treatment and to progression to end-stage renal disease (ESRD) in proliferative LN (PLN).Ninety percent of the patients belonged to minority population. Among 122 patients with class III and IV LN (PLN), 76 patients received intravenous cyclophosphamide and 38 patients received mycophenolate for induction, whereas 34 patients received intravenous cyclophosphamide and 63 patients received mycophenolate for maintenance. Thirty-six (30%) patients with PLN progressed to ESRD, and 3 patients died over a mean follow-up of 37.5 months. In multivariate analysis, chronicity index (CI) (P = 0.0007) and hypertension (P = 0.042) positively correlated with progression to ESRD and death, and CI was associated with increased probability of nonresponse to treatment (P = 0.001). In addition, mycophenolate as maintenance agent was associated with increased likelihood of sustained complete remission and partial remission (P = 0.045).In patients with LN, hypertension and a high CI are independent risk factors for progression to ESRD or death. Furthermore, a high CI is associated with poor response, and mycophenolate as a maintenance agent may improve the response to treatment.
| S-EPMC3176993 | biostudies-other
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:Over a 3 year period from June 94 to June 97, out of 28 patients of systemic lupus, 17 were diagnosed as renal lupus. Demographic data showed 12 females and 5 males, mean age being 32.2 years (range 12 to 54 years). Mean time gap between presentation and definitive diagnosis was 32.4 days (7 days to 5 years). 2 patients (11.76%) presented renal lupus, one (5.88%) with acute interstitial lung disease and the remaining had the usual systemic manifestations of lupus. Anti dsDNA antibodies were positive in all patients while ANA was negative in 3 cases. Renal involvement consisted of rapidly progressive glomerulonephritis in 2 patients (11.76%), nephrotic syndrome in 4 (23.52%) and non nephrotic range proteinuria in 11 (64.70%) patients. Mean serum creatinine at presentation was 2.4mg/dl (0.8mg/dl to 8.9 mg/dl). Three patients were dialysis dependent. Renal histology on light microscopy comprised of class II lesions in one (5.88%), class III in 4 (23.52%), class IV in 11 (64.70%-including one with crescents) and class V in one (5.88%) patient. All patients with advanced class III/IV lesions were treated with corticosteroids and cyclophosphamide pulses. Except one patient who died of pyopericardium all others improved and their serum creatinine stabilised around 2.3 mg/dl (0.8 to 4.6 mg/dl). The study highlights the importance of early diagnosis and aggressive management in this potentially treatable disease.
| S-EPMC5531826 | biostudies-other
Project description:IntroductionIn addition to glomerular lesion, renal vascular lesion is also an important prognostic marker of lupus nephritis (LN). Among patients with various vascular changes, individuals with thrombotic microangiopathy (TMA) present with severe clinical manifestations and have a high mortality. The aim of the present study was to assess the spectrum and impact of TMA on the outcomes of LN. In a prospective observational study of 2.5 years' duration, clinical and renal histopathological data regarding biopsy-proven LN were noted, and evaluation for antiphospholipid syndrome (APS) as a cause of TMA in LN was also carried out.MethodsStudy subjects were followed up actively for 6 months, and various outcomes were noted. Cases were divided into 2 groups as LN with TMA and LN without TMA, and various features were compared between the 2 groups. Outcomes recorded were complete response (CR), partial response (PR), treatment failure, and death.ResultsOf the 197 patients with LN, 50 patients (25.4%) were diagnosed with co-existing renal TMA. Five patients (10%) were found to have concomitant APS. As compared to patients without TMA, those with TMA had significantly higher rates of oliguria (P = 0.035), advanced renal injury, that is, serum creatinine > 3mg/dl (P = 0.002), fibrocellular and fibrous crescents (P = 0.01), and tubular atrophy (P = 0.001). Outcomes included CR in 15 patients (30%), PR in 10 (20%), failure in 19 (38%), and death in 6 (12%). Patients with LN with TMA had higher rates of treatment failure (P = 0.02) compared to the group without TMA.DiscussionThe presence of TMA in patients with LN is associated with adverse clinicopathological presentation and poor outcome.
| S-EPMC5733673 | biostudies-literature
Project description:Lupus nephritis (LN) is a frequent and severe manifestation of SLE. Along the decades, the epidemiology of LN and its clinical presentation have been changing. However, even though retrospective cohort studies report a decreased mortality rate and an improvement in the disease prognosis, the percentage of patients progressing into end stage renal disease (ESRD) keeps steady despite the improvements in therapeutic strategies. Current in-use medications have been available for decades now, yet over the years, regimens for optimizing their efficacy and minimizing toxicity have been developed. Therapeutic research is now moving towards the direction of precision medicine and several new drugs, targeting selectively different pathogenetic pathways, are currently under evaluation with promising results. In this review, we address the main changes and persistent unmet needs in LN management throughout the past decades, with a focus on prognosis and upcoming treatments.
| S-EPMC7751166 | biostudies-literature