The predictive value and response to immunosuppressive therapy of IgA nephropathy patients with crescents in a large retrospective Chinese cohort
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PROVIDER: S-EPMC10689141 | biostudies-literature | 2023 Jun
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Project description:IntroductionCrescents, especially those found at a percentage greater than 50%, are often associated with rapid progression of kidney disease in IgA nephropathy (IgAN). The mechanism of crescents forming in IgAN is still unclear. In this study, we aimed to evaluate whether excess complement activation participates in the formation of crescents in IgAN.MethodsOne hundred IgAN patients with various proportions of crescents-24 with 1%-24%, 27 with 25%-49%, 21 with 50%-74% 12 with more than 75%, and 16 without crescents-were included. Urinary concentrations of mannose-binding lectin (MBL), Bb, C4d, C3a, C5a, and soluble C5b-9 (sC5b-9) were measured at the time of biopsy. Receiver operating characteristic (ROC) curves were performed to evaluate predictive ability of renal survival for urine complement activation. In addition, historical C4d, C5b-9, and C3d were stained by immunohistochemistry.ResultsIgAN patients with more than 50% crescent formation showed higher complement activation levels than the other patients (urinary C3a/creatinine (C3a/Cr): 6.7295 ng/mg, interquartile range (IQR) 1.4652-62.1086 ng/mg vs. 0.1055 ng/mg, IQR 0-1.4089 ng/mg; urinary C5a/Cr: 15.6202 ng/mg, 4.3127-66.7347 ng/mg vs. 0.3280 ng/mg, IQR 0.0859-2.4439 ng/mg; urinary sC5b-9/Cr: 98.6357 ng/mg, 8.8058-1,087.4578 ng/mg vs. 1.4262 ng/mg, 0.0916-11.0858 ng/mg, all p-values <0.001). The levels of urinary MBL and C4d representing lectin complement pathway showed a linear association with the proportion of crescents (r = 0.457 and 0.562, respectively, both p-values <0.001). Combined urine complement products could increase the predictive ability compared with crescents alone from 0.904 to 0.944 (p = 0.062) with borderline significance. Moreover, the glomerular C4d deposition rate elevated with the increase of proportions of crescents.ConclusionExcess complement activation may be involved in the formation of crescents, especially diffuse crescent formation, in patients with IgAN. Urinary C4d correlated with the proportion of crescents and was a potential biomarker for disease monitoring in crescentic IgAN.
| S-EPMC8477028 | biostudies-literature
Project description:Crescents involving more than 50% of glomeruli in IgA nephropathy (IgAN) signify a rapid deterioration of renal function. However, little is known about the prognosis of IgAN patients presenting crescents in less than 50% of glomeruli. We aimed to investigate the clinicopathological characteristics and outcomes of IgAN patients with different proportions of crescents.From January 2000 to December 2011, biopsy-proven primary IgAN patients with histological crescents formation were enrolled in this retrospective cohort study. The patients were divided into 4 groups on the basis of crescent proportion as follows: <5%, 5% to 9%, 10% to 24%, and ≥25%. The primary endpoint was defined as the doubling of baseline serum creatinine (SCr) and/or end-stage renal disease (ESRD), and the secondary endpoint was death.A total of 538 crescent-featured IgAN patients were followed up and included in the analysis. The median crescent proportion was 8.0%. An increasing crescent proportion was associated with a reduced estimated glomerular filtration rate (eGFR), decreased level of hemoglobin, and increased amount of urine protein excretion. After a median follow-up period of 51 months (range 12-154 months), the endpoint events-free survival rate of the above 4 groups were 69.9%, 47.7%, 43.8%, and 40.6%, respectively (Log rank=13.7, P= 0.003), when we incorporated death with renal outcome as a composite endpoint. Multivariate Cox regression analyses adjusting for eGFR, hypertension, proteinuria, and the Oxford-MEST classification demonstrated the predictive significance of an increasing crescent proportion with renal survival and mortality (each increase by 5% [log-transformed]: HR=1.51, 95% CI 1.08-2.11, P = 0.02). Further comparisons of patients with small proportions of crescents (<5%) and those absent of such pathological lesion showed that the 2 groups of patients had comparable prognosis.An increasing crescent proportion was identified as an independent predictor for unfavorable clinical outcomes in IgAN. Therefore, a small proportion of crescents, over 5% particularly, should be paid more attention in clinical practice.
| S-EPMC5369886 | biostudies-literature
Project description: Not available
| S-EPMC7066485 | biostudies-literature
Project description:BackgroundA working group on the Oxford classification of IgA nephropathy (IgAN) recently reported that crescents detected in kidney tissue predicted a worse renal outcome. However, this finding must be validated in independent cohorts before it can be widely applied to clinical practice.MethodsBiopsy-proven IgAN patients were continuously recruited from two large renal centers in China from 1989 to 2014. All patients were followed for more than 1 year unless end stage renal disease (ESRD) occurred within 12 months. Crescents were defined as focal cellular or fibrocellular crescent formations. IgAN patients without detectable crescents were recruited to the C0 group. Patients with crescents in less than or more than 1/4 of all glomeruli were recruited to the C1 or C2 group, respectively. Primary outcome was defined as the time to ESRD, and the secondary outcome was defined as the time to an estimated glomerular filtration rate (eGFR) decline equal to or greater than 50% or to ESRD.ResultsIn total, 1152 IgAN patients were recruited in this study. Among all patients, 53.7% were in the C0 group, 38.8% were in the C1 group, and 7.5% were in the C2 group. Compared to patients in the C0 group, patients in the C1 or C2 group were younger, had more urinary protein excretion and lower eGFR, and presented with more severe mesangial hypercellularity, endocapillary proliferation or tubular atrophy/interstitial fibrosis. After 45 months of follow-up, ESRD had occurred in 80 (12.9%), 46 (10.3%) and 18 (20.9%) of patients in the C0, C1 and C2 groups, respectively. By multivariable Cox regression analysis, inclusion in the C1 (HR = 1.07, 95% CI 0.71-1.63), C2 (HR = 0.84, 95% CI 0.41-1.73), or C1 or C2 group (HR = 1.02, 95% CI 0.68-1.52) was not associated with a higher rate of ESRD than inclusion in the C0 group after adjusting for age, gender, eGFR, mean arterial pressure (MAP), MEST scores, and immunosuppressive treatment. However, in patients with nephrotic-range proteinuria, patients in either the C1 or C2 group had a higher rate of the primary outcome, ESRD (HR = 2.54, 95% CI 1.14-5.66) after adjusting for age, gender, eGFR, MAP, MEST scores, and immunosuppressive treatment. Similar results were found when we evaluated the association between crescents and the secondary outcome.ConclusionsIgAN patients with crescents had more severe clinical and pathological manifestations than those without crescents. However, we failed to replicate the association between crescents and renal function progression in Chinese IgAN patients followed for more than 1 year.
| S-EPMC5934890 | biostudies-literature
Project description: Not available
| S-EPMC7136355 | biostudies-literature
Project description:BackgroundIgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and remains a leading cause of chronic kidney disease and end-stage renal disease. The disease prevalence, clinical and pathological phenotypes, the underlying pathogenic molecular mechanisms, and the response to treatments are highly heterogeneous in different ethnic populations, which raise the concern that IgAN may differ across different parts of the world.SummaryFrom a Chinese perspective, we stated the disease burden of IgAN, summarized genome-wide association studies and research into pathological molecules, and compared them with findings based on other populations. The emerging biomarkers, indigenous clinical trials, and major challenges for Chinese researchers and nephrologists in studying IgAN are also discussed.Key messagesIn this review, we described a higher risk of major susceptible loci in mucosal immunity, IgA production, and complement activation pathways in Chinese patients with IgAN. With our understanding of the pathogenesis of IgAN, novel biomarkers are emerging. Although there are challenges for conducting high-quality clinical trials in China, it is still feasible to conduct innovative and well-designed studies of IgAN. In the future, international collaborations on research infrastructure would be helpful to advance clinical and basic research in China.
| S-EPMC9677733 | biostudies-literature
Project description:The role of immunosuppression in IgA nephropathy (IgAN) is controversial. In the Supportive Versus Immunosuppressive Therapy for the Treatment of Progressive IgA Nephropathy (STOP-IgAN) Trial, 162 patients with IgAN and proteinuria >0.75 g/d after 6 months of optimized supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR≥60 ml/min per 1.73 m2: 6-month corticosteroid monotherapy; GFR=30-59 ml/min per 1.73 m2: cyclophosphamide for 3 months followed by azathioprine plus oral prednisolone). Coprimary end points were full clinical remission and GFR loss ≥15 ml/min per 1.73 m2 during the 3-year trial phase. In this secondary intention to treat analysis, we separately analyzed data from each immunosuppression subgroup and the corresponding patients on supportive care. Full clinical remission occurred in 11 (20%) patients receiving corticosteroid monotherapy and three (6%) patients on supportive care (odds ratio, 5.31; 95% confidence interval, 1.07 to 26.36; P=0.02), but the rate did not differ between patients receiving immunosuppressive combination and controls on supportive care (11% versus 4%, respectively; P=0.30). The end point of GFR loss ≥15 ml/min per 1.73 m2 did not differ between groups. Only corticosteroid monotherapy transiently reduced proteinuria at 12 months. Severe infections, impaired glucose tolerance, and/or weight gain in the first year were more frequent with either immunosuppressive regimen than with supportive care. In conclusion, only corticosteroid monotherapy induced disease remission in a minority of patients who had IgAN with relatively well preserved GFR and persistent proteinuria. Neither immunosuppressive regimen prevented GFR loss, and both associated with substantial adverse events.
| S-EPMC5748925 | biostudies-literature
Project description:End-stage liver disease (ESLD) is the most common cause of secondary immunoglobulin A nephropathy (IgAN). Multiple mechanisms have been proposed to explain the association between liver disease and IgAN. Although some mechanisms are expected to reverse in patients after liver transplant, the long-term renal prognosis is unclear for these patients.This observational retrospective cohort study examined the renal outcomes of 14 patients who had IgAN with end-stage liver disease and subsequently underwent either liver transplant alone or combined liver and kidney transplant at a single tertiary care center.Of the 7 patients who underwent liver transplant alone, hematuria persisted in 2, 4 had progressive loss of kidney function with worsening proteinuria in 3 but only 1 reached end-stage renal disease 5 years posttransplant. Among 7 combined liver and kidney transplant recipients, 1 had histologic and 1 had histologic and clinical recurrence of IgAN without kidney allograft loss.IgAN in patients with advanced liver disease does not necessarily resolve after liver transplant but has overall favorable renal outcomes.
| S-EPMC5540631 | biostudies-other
Project description:BackgroundThe Oxford classification of IgA nephropathy (IgAN) was revised in 2016 which lacked sufficient evidence for prognostic value of subclassification of focal segmental glomerular sclerosis (S lesion), and the proper proportion of S lesion for subclassification remains undetermined.AimThis study aimed to explore the predictive value of the new subclassification of S score on renal outcomes of IgAN patients.Methods348 patients with IgAN-associated S lesion were enrolled. According to the optimal cut-off of 25% established by receiver operating characteristic (ROC) curves, we divided S1 patients into two groups: S1a group (S lesion < 25%) and S1b group (S lesion ≥ 25%). IgAN patients with mild lesion (M0E0S0T0C0) were set as the control group. The clinical features at renal biopsy, pathological findings, and follow-up parameters (follow-up time ranged from 1 to 5 years) were collected. We used univariate and multivariate analyses to assess whether the subclassification of S score could refine risk prediction and clinical utility.ResultsWe demonstrated that S lesion ≥ 25% was associated with a more rapid GFR loss and a lower rate of complete remission of proteinuria even adjusted for multiple clinic pathological variables, compared to S1a group (All p values <.05). And the ratio of glomeruli with T lesion and crescents were higher in patients with S lesion ≥ 25%. Data showed that IgAN patients with S lesion ≥ 25% were at an increased risk of poor renal outcomes even with immunosuppression.ConclusionThis study might recommend new subclassification of S scores (S0 (no S lesion), S1 (S lesion <25% of glomeruli), and S2 (S lesion ≥ 25% of glomeruli)) for the Oxford classification. This model may also help to evaluate pros and cons of immunosuppressive therapy in IgAN patients with different level of S lesion.KEY MESSAGESS lesion ≥ 25% is an independent risk factor for poor renal outcome in IgAN patients.This new subclassification of S scores may help to evaluate pros and cons of immunotherapy in IgAN patients with different level of S lesion.
| S-EPMC8032344 | biostudies-literature
Project description:BackgroundPozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents.MethodsIn this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels).ResultsThere was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups.ConclusionsBoth the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness.Trial registrationClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.
| S-EPMC8780312 | biostudies-literature