Prognosis Of IgA Nephropathy Research Articles

The proteinuria selectivity index value predicts the remission of IgA nephropathy: a retrospective cohort study

IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide and leads to end-stage kidney disease. The proteinuria selectivity index (PSI) has been used to assess the prognosis in nephrotic syndrome, but its predictive value in patients with IgAN remains unclear. This single-center retrospective cohort study included patients who diagnosed with IgAN between March 2012 and March 2020. The PSI was calculated at the time of kidney biopsy. Patients were followed up from the time of kidney biopsy to kidney replacement therapy, death, transfer to another facility, or study completion. Ninety-four patients with a median age of 51 years were enrolled and divided according to the cutoff value of PSI determined by the receiver operating characteristic curve analysis into low-PSI (PSI <0.243, n = 39) and high-PSI groups (PSI ≥0.243, n = 55). The median follow-up duration was 70 months. Rates of remission of proteinuria and survival without a two-fold increase in serum creatinine were significantly better in the low-PSI group (both p < 0.01, log-rank test). Cox regression analysis showed that a low PSI was significantly associated with an increased likelihood of remission of proteinuria and hematuria (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.02–3.85 and HR 1.75; 95% CI 1.01–3.13, respectively), and a decreased risk of a two-fold increase in serum creatinine (HR 0.10; 95% CI 0.01–0.81). In conclusion, The PSI could have the potential to support the assessment of the prognosis of IgAN, in addition to established prognostic markers, by reflecting the overall glomerular permeability.

Analysis of Clinical Risk Factors of Prognosis in IgA Nephropathy Based on Machine-Learning Approaches

Analysis of Clinical Risk Factors of Prognosis in IgA Nephropathy Based on Machine-Learning Approaches

Correlation analysis of cofilin-1 with renal prognosis in primary IgA nephropathy

PurposeThe purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN).MethodsPatients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis.Results133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803).ConclusionCofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN.

Elderly versus young IgA nephropathy; an update on current data

IgA nephropathy (IgAN) is a common glomerular disease affecting individuals across the age spectrum. However, there are differences in the presentation and prognosis of IgAN between elderly and young adults. Elderly patients with IgAN tend to present with more severe kidney disturbances, worse baseline renal function, and a poorer prognosis compared to young adults. The Oxford classification contributes to the overall prognosis of IgAN in elderly patients by improving prognostic assessment, providing a better determinant of kidney survival, and combining histopathologic findings with clinical features. It offers a more comprehensive approach to understanding the disease course and predicting outcomes in elderly individuals with IgAN. Understanding these differences is a fundamental basis for pinpointing potential therapeutic targets to mitigate age-related renal pathology in IgAN patients.

High systemic inflammatory response index (SIRI) is an independent risk factor for poor outcome in IgA nephropathy patients.

The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients' outcomes. To better clarify these concerns, we conducted this investigation. This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI's optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN. A total of 981 IgAN patients were included. During a median follow-up period of 56.7months (36.8-80.4months), 122 patients progressed to the combined endpoint (12.4%). Patients were divided into a low SIRI group (SIRI ≤ 0.63, n = 312) and a high SIRI group (SIRI > 0.63, n = 669) according to the optimal cut-off value of the systemic inflammatory response index (SIRI). Further analysis showed that a higher SIRI value was significantly associated with the risk of IgAN patients reaching the composite endpoint (HR 1.62, 95% CI 1.02-2.56, p = 0.041). High SIRI is a significant and independent risk factor for renal disease progression in IgAN patients.

Analysis of the impact of obesity on the prognosis of IgA nephropathy according to renal function and sex.

Few studies have observed the direct effect of obesity on renal prognoses in immunoglobulin A nephropathy (IgAN) or separately evaluated its effects according to sex. We aimed to evaluate the direct and indirect effects of obesity on the renal outcomes of IgAN and observe these effects separately according to renal function and sex. We extracted patients with body mass index (BMI) descriptions from a multicenter retrospective cohort analysis in Japan, and excluded those with < 30 days of follow-up, diabetes mellitus, and steroid treatment. Patients were divided into normal (n = 720; 18.5 ≤ BMI < 25) and obese (n = 212; BMI ≥ 25) groups, which were then compared. The endpoints were a 1.5-fold increase in serum creatinine levels and the initiation of renal replacement therapy. The obese group was older, included more males, and was more likely have hypertension, dyslipidemia, proteinuria, tubular atrophy, and lower renal function than the normal group. Patients with an eGFR < 60mL/min/1.73m2 had well-matched characteristics between the groups; however, hypertension, low high-density lipoprotein cholesterol, and hypertriglyceridemia were more common in the obese group. Obesity contributed to tubular atrophy, even when adjusted for renal function. In addition, it contributed to proteinuria only in females. However, obesity itself was not a significant prognostic factor. Although no independent effect on renal prognosis was observed during the study period, the obese group had more risk factors for IgAN progression and obesity contributed to tubular atrophy and female proteinuria. Our results suggest that separately analyzing the prognostic effect of obesity according to sex is important.

#1486 Looking for a new role of known players: the additional value of plasmatic C3 and C4 in predicting IgA Nephropathy prognosis, an observational study

Abstract Background and Aims IgA Nephropathy (IgAN) is the most common glomerular disease worldwide [1]. Complement system activation through the alternative and lectin pathways is crucial in its pathogenesis and leads to worse outcome, eliciting the need for (new) biomarkers to assess risk of disease progression and potential response to new targeted treatments [2, 3]. Only few works have correlated serum C3 and C4 with disease activity and prognosis [4, 5]. Our work explores the potential advantages of incorporating serum C3 and C4 levels into a standardized prognostic model to assess kidney outcome in IgAN. Method This retrospective study, conducted at Sant'Orsola University Hospital in Bologna, investigated the prognostic value of serum complement C3 and C4 in patients with IgAN. The primary outcome was defined as a 40% decline in eGFR or the onset of kidney failure. The study aimed to evaluate whether the addition of serum C3 and C4 to an established predictive model, incorporating variables from the International IgA Prediction Tool (IntIgAPT), enhances the accuracy of outcome prediction. We computed the measures of goodness of fit for each model: Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), Nagelkerke R2 test (NR2) that depicts the% explained variation of the outcome based on the set of variables included, and Likelihood Ratio Test (LRT); discrimination with the c-index. Furthermore, we aimed to evaluate the characteristics of patients stratified by baseline serum C3 levels (Low &amp;lt;90 mg/dl, Medium 90-140 mg/dl, High &amp;gt;140 mg/dl). Results 101 patients were included in the cohort. 90% were Caucasian and 65.3% were male with a mean age of 42.6 years. As reported in Table 1, mean eGFR and median proteinuria levels at baseline were 70.4 ml/min/1.73 m² and 1.04 g/24 h respectively. Mean serum C3 was 114.9 mg/dL. The Low group had lower values of eGFR at baseline (47.0 vs 75.67 and 68.64 ml/min/1.73 m², p = 0.015), while the Medium group had lower values of uProt (0.75 vs 1.81 and 1.46 g/24 h, p = 0.004). During a median 54.28 months follow-up, the Low group exhibited significantly higher primary outcome incidence (16.3 events vs 2.9 and 1.7 events x 100 pts/year, p = 0.003). We computed a first model (M1) based upon IntIgAPT variables and then a second model (M2) as the same of M1 plus serum C3 and C4 at baseline (Table 2). C3 showed a negative association with outcome (OR 0.88, CI 0.78 to 0.99, p = 0.05) whereas C4 had a positive one (OR 1.21, CI 1.02 to 1.48, p = 0.05). M2 had an improved prediction accuracy than M1, as evidenced by lower AIC (49.1 vs 53.8), higher c-index (0.74 vs 0.65), and NR2 (0.76 vs 0.65). Likelihood ratio test was significant between the two (p = 0.008). Conclusion The inclusion of serum C3 and C4 in a validated prognostic model enhances prediction accuracy and improves the percentage of events explained, highlighting complement's inherent informativeness. In our population lower C3 and higher C4 levels were associated with poorer prognosis in IgAN, characterizing a more ‘Complement-Pathic’ subset of patients. This result expands the current evidence, for the first time to our knowledge, in a Caucasian-prevalent study population.

#968 Impact of the presence of acute kidney injury at the time of renal biopsy on long-term prognosis of IgA nephropathy

Abstract Background and Aims IgA nephropathy is the most common primary glomerular disease and an important cause of end-stage renal disease. Factors such as decreased renal function, persistent proteinuria, hypertension, and older age predict a poor prognosis in IgA nephropathy. Current international prediction tools for IgA nephropathy determine prognosis based on renal function using estimated glomerular filtration rate (eGFR) at the time of kidney biopsy. However, we observed differences in prognosis between patients with and without concurrent acute kidney injury (AKI) at the time of kidney biopsy. Therefore, we aimed to investigate whether renal function at the time of renal biopsy is a suitable indicator for assessing the long-term prognosis of patients with IgA nephropathy with AKI. Method We retrospectively analyzed a total of 185 patients who were diagnosed with IgA nephropathy between 2009 and 2016 at the Gyeongsang National University Hospital. Clinical data, including pathological, demographic, and laboratory findings of patients, were used. We divided the patients into two groups based on the progression rate of kidney function per year, ‘Progression’ or ‘Non-progression group’. AKI was defined according to the KDIGO Clinical Practice Guidelines. Results Among a total of 185 patients, 113 showed a sustained decline in eGFR of more than 1 ml/min/1.73 m2 per year. The mean eGFR level of the non-progression group was significantly lower than that of the progression group (p = 0.027). The percentage of patients with AKI in the non-progression group was 25%, which was higher than that in the progression group (p &amp;lt; 0.001). The two groups had no significant differences in comorbid disease, medications at kidney biopsy, and treatment. In sub-analysis, the mean eGFR at kidney biopsy was significantly lower than that in the non-AKI group (p &amp;lt; 0.001). The mean estimated risk, calculated by the international prediction tool, was significantly lower in the AKI group. On the other hand, the mean rate of actual GFR decline per year was higher in the non-AKI group (p &amp;lt; 0.001). Conclusion We confirmed a discrepancy between the predicted prognosis and the actual decline in GFR, particularly in the AKI group. We found that AKI at the time of renal biopsy was a good long-term prognostic factor. There is a need to conduct further research to confirm whether this is due to early detection of AKI and early active treatment.

#1425 Anemia in patients with IgA nephropathy: an impact on the prognosis of IgA nephropathy

Abstract Background and Aims Immunoglobulin A Nephropathy (IgAN) has several well-known predictors of renal outcomes, including persistent proteinuria, hypertension, and baseline eGFR at the time of diagnosis. However, the effect of hemoglobin (Hb) levels on the progression of IgAN is rarely reported. This study aims to evaluate the impact of Hb levels on the prognosis of IgAN and to identify risk factors for anemia in patients with IgAN. Method A retrospective analysis of the data of 855 patients diagnosed with IgAN at Kyungpook National University Hospital between January 2002 and December 2021 was performed. We obtained the data on clinical parameters and pathological findings according to the Oxford classification at the time of the kidney biopsy. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors for anemia, and a Cox proportional hazard model was used to estimate the effects of anemia on the development of end-stage kidney disease (ESKD). Results Lower serum albumin, lower eGFR, severe interstitial fibrosis, and tubular atrophy were associated with anemia in patients with IgAN. The Kaplan-Meier survival curve revealed that patients with anemia had worse renal survival than those without anemia. The multivariable Cox analysis showed that anemia was an independent risk for the progression to ESKD (HR 2.86, confidence interval 1.58–5.17, p = 0.001). In a sex-specific analysis, only the female sex showed a significant and higher risk for ESKD (hazard ratio 4.07, confidence interval 1.53–10.8, p = 0.005). Conclusion A low Hb level at the time of biopsy, even if subclinical, was an independent risk factor for the development of ESKD in patients with IgAN. Therefore, it is necessary to monitor Hb levels at the time of diagnosis and take proactive measures to reduce the risk of disease progression.

#1258 Moderate-severe intrarenal arteriosclerosis and circulating GDF-15 levels may influence the cardiac-renal prognosis of IgAN patients

Abstract Background and Aims The cardiovascular risk among patients with IgA nephropathy (IgAN) is gradually garnering increased attention. The KDIGO guidelines explicitly emphasize the importance of evaluating cardiovascular risk in the management of IgAN patients and implementing appropriate interventions when necessary. The aim of this study was to investigate the risk factors affecting cardiac-renal prognosis in patients with IgAN. Method This is a retrospective study. A total of 353 IgAN patients with regular follow-up for at least 1 year at Beijing Anzhen Hospital were recruited. Patients were divided into group A (n = 85, yes) and group B (n = 268, no) according to the occurrence of cardio-renal composite endpoint events. Clinical and pathological characteristics of the two groups were compared and analyzed. The risk factors affecting the cardiac and renal prognosis in IgAN patients were analyzed by univariate and multivariate Cox models. In addition, serum GDF-15 of IgAN patients were detected. Results Approximately 14.7% (52/353) of IgAN patients presented with cardiovascular diseases at the time of renal biopsy. 55.8% (197/353) patients presented with hypertension. Prognostic analysis showed that hypertension (HR, 1.810; 95% confidence interval, 1.073 to 3.053; P = 0.026), 24-hour urinary protein (24 hUTP) (HR, 1.081; 95% confidence interval, 1.006 to 1.162; P = 0.033), eGFR (HR, 0.980; 95% confidence interval, 0.973 to 0.987; P&amp;lt;0.001), the presence of endocapillary proliferation (E1) (HR, 1.697; 95% confidence interval, 1.079 to 2.669; P = 0.022), tubular atrophy/interstitial fibrosis (T2) (HR, 3.757; 95% confidence interval, 1.959 to 7.203; P &amp;lt; 0.001), and moderate-severe intrarenal arteriosclerosis (HR, 3.320; 95% confidence interval, 1.289 to 8.548; P = 0.013) are independent risk factors affecting the cardiac-renal prognosis of IgAN. In IgAN patients with moderate-severe intrarenal arteriosclerosis, 24-hour urinary protein (24 hUTP) (HR, 1.131; 95% confidence interval, 1.014 to 1.261; P = 0.028), eGFR (HR, 0.982; 95% confidence interval, 0.971 to 0.993; P = 0.001) and E1 (HR, 2.583; 95% confidence interval, 1.379 to 4.841; P = 0.003) are independent risk factors affecting the cardiac-renal prognosis of IgAN patients. The serum GDF-15 level is positively correlated with 24 hUTP (r = 0.405, P &amp;lt; 0.001) and negatively correlated with eGFR (r = −0.606, P &amp;lt; 0.001). Compared with those with benign cardio-renal composite outcome, the serum level of GDF-15 in IgAN with poor cardio-renal composite outcome were significantly higher (1591.69 (1001.65, 2546.36) pg/ml vs 775.85 (546.82, 1310.29) pg/ml, P &amp;lt; 0.001). Conclusion The occurrence of cardiovascular diseases in patients with IgAN is frequently observed. In addition to the conventional risk factors associated with IgAN, including hypertension, initial proteinuria, eGFR, E1 and T2 lesion, moderate-severe intrarenal arteriosclerosis also contributes to the cardiac-renal prognosis of individuals with IgAN. In IgAN patients with moderate-severe intrarenal arteriosclerosis, Oxford-E lesion is an independent risk factor affecting the cardiac-renal prognosis of IgAN patients. This study suggested that the impairment of endothelial cells could potentially serve as a link between heart and kidney disease. The circulating levels of GDF-15 might contribute to the cardiac-renal prognosis of IgAN.

The ratio of high aspartate aminotransferase to alanine aminotransferase: an independent risk factor associated with poor prognosis in IgA nephropathy.

To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. After a mean follow-up of 29months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. AAR is an independent prognostic factor in patients with IgAN.

The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy.

IgA nephropathy (IgAN), the most common type of glomerulonephritis, has great individual differences in prognosis. Many studies showed the relationship between thyroid hormones and chronic kidney disease. However, the relationship between free thyroxine (FT4), as a thyroid hormone, and IgAN is still unclear. This study aimed to evaluate the impact of FT4 on IgAN prognosis. This retrospective study involved 223 patients with biopsy-proven IgAN. The renal composite outcomes were defined as: (1) ESRD, defined as eGFR < 15 ml/(min·1.73 m2) or initiation of renal replacement therapy (hemodialysis, peritoneal dialysis, renal transplantation); (2) serum creatinine doubled from baseline; (3) eGFR decreased by more than 50% from baseline. The predictive value was determined by the area under the curve (AUC). Kaplan-Meier and Cox proportional hazards analyses assessed renal progression and prognosis. After 38 (26-54) months of follow-up, 23 patients (10.3%) experienced renal composite outcomes. Kaplan-Meier survival curve analysis showed that the renal survival rate of the IgAN patients with FT4<15.18pmol/L was lower than that with FT4≥15.18pmol/L (P < 0. 001). Multivariate Cox regression model analysis showed that FT4 was a protective factor for poor prognosis of IgAN patients, whether as a continuous variable or a categorical variable (HR 0.68, 95%CI 0.51-0.90, P =0.007; HR 0.04, 95%CI 0.01-0.20, P <0.001). ROC curve analysis showed that FT4 combined with t score had a high predictive value for poor prognosis of IgAN patients (AUC=0.881, P<0.001). FT4 was a protective factor for IgAN. In addition, FT4 combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN.

Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.MethodsA systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.DiscussionIdentifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.Systematic review registrationPROSPERO CRD42022364569

Correlation between MEST-C score in kidney biopsy of IgA nephropathy patient and prognosis

Introduction: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis, and is the most common type of glomerulopathy which leading to end-stage renal disease (ESRD). Prompt diagnosis of high-risk patients is important to initiate specific treatment early and prevent progression to ESRD. Oxford pathological classification, known as MEST-C score, attempts to predict prognosis based on pathological factors. Objectives: In this study, we evaluated the value of pathological and clinical variables in estimating the prognosis of IgAN in Iranian patients. Patients and Methods: In this retrospective cohort study, 165 specimens were reviewed by a nephropathologist, who reported the MEST-C score after the definitive diagnosis of IgAN. Patient records were reviewed to gather clinical data, including serum creatinine, 24-hour urine protein levels, diagnosis of hypertension and/or diabetes, and any treatment received. The pre-specified endpoints were determined as progression to ESRD, a reduction in estimated glomerular filtration rate (eGFR) to less than 50% of its baseline, performance of renal transplant, or death. The variables were compared in patients who had reached the pre-specified endpoints and those who had not, to estimate their prognostic value. Results: Findings showed that the urinary protein level and T-score on biopsy were significant prognostic factors. Other pathological factors such as C, S, and M scores lost their significance on multivariate analysis. Further research is needed to validate the efficacy of the MEST- C score in different racial populations. Conclusion: In our study, urinary protein level at diagnosis and T-score on biopsy were validated as prognostic factors, while M, E, S and C scores were not deemed significant. Further research is necessary to validate the MEST-C scoring system in different populations before its use in routine clinical practice.

Haemoglobin, albumin, lymphocyte, and platelet score as an independent predictor for renal prognosis in IgA nephropathy.

The haemoglobin, albumin, lymphocyte, and platelet (HALP) score, a convenient and composite laboratory biomarker, can reflect inflammation and systemic nutritional status. This study was performed to investigate the effect of the HALP score on the prognosis of patients with IgA nephropathy (IgAN). This is a retrospective single centre study that enrolled 895 biopsy-confirmed IgAN patients from June 2019 to June 2022 who were followed for more than 1 year. Kaplan-Meier curves and Cox regression analyses were performed to determine the relationship between HALP and adverse outcomes. The restricted cubic splines was used to identify the possible associations. The optimal cut-off value of HALP for renal poor outcome was identified by the area under the receiver operating characteristic curve (AUC). A total of 895 patients finally participated in the study and were divided into three groups (tertial 1-3) according to the baseline HALP score. More severe clinicopathologic features were observed in the lower HALP group, and Kaplan-Meier analysis showed patients in tertial 1 had a higher risk of kidney failure than the other groups (log-rank=11.02, P= 0.004). Multivariate Cox regression revealed that HALP score was an independent risk factor for renal prognosis in IgAN (adjusted HR: 0.967, 95% CI: 0.945-0.990, P = 0.006). The results of subgroup analysis suggested that HALP was more important in patients under the age of 50, BMI ≤ 23.9 and eGFR ≤ 90 mL/min/1.73 m2. The best cut-off HALP for renal survival was 38.83, sensitivity 72.1%, and specificity 55.9% (AUC: 0.662). Patients were further grouped according to HALP cut-off values and propensity matched. Multivariate Cox regression analysis revealed that HALP remained an independent predictor of IgAN in the matched cohort (HR 0.222, CI: 0.084-0.588, P=0.002). HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

Circulating soluble CD30 is associated with renal tertiary lymphoid structures and the progression of IgA nephropathy

BackgroundRenal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN. MethodsWe conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis. ResultsDuring a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230–9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680–65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499–100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797–278.520, P = 0.016). ConclusionElevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

Correlation of Serum Galactose-Deficient IgA1 and Oxford Class in Cases of IgA Nephropathy.

Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy. To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases on diagnosis and 3 months post treatment and its relation with histologic Oxford classification. In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using Oxford Classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used. Significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008). Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.

Prognosis of IgA Nephropathy with Stages 3b-5 CKD

Introduction: There are conflicting opinions regarding the use of immunosuppressant treatment in IgA nephropathy (IgAN) patients with an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73 m2 and persistent proteinuria with a daily excretion of ≥1.0 g. Methods: This retrospective study involved 110 IgAN patients for whom clinical data were available; of these, 90 had complete follow-up data. Patients were grouped based on whether they received immunotherapy during follow-up, their renal function, proteinuria levels, and the percentage of crescentic glomeruli observed at the time of renal biopsy. Results: The mean eGFR for the participants was 32.0 ± 10.2 mL/min/1.73 m2. The average follow-up duration was 46.1 ± 37.9 months. The mean rate of decline in eGFR was 3.6 mL/min/1.73 m2 per year. There were 43 (47.8%) composite kidney endpoints occurred in these patients. In the group that received immunotherapy, the incidence of kidney endpoint events was lower than in the untreated group (45.1% vs. 57.9%), but the difference was not statistically significant (p = 0.320). Among patients with stage CKD 3b, the incidence of endpoint events was lower than in those with stages CKD 4 and 5 (36.8% vs. 66.7%, p = 0.006). Conversely, the high proteinuria group saw a higher incidence of endpoint events compared to the low proteinuria group (51.9% vs. 23.1%), although this difference was not statistically significant (p = 0.054). Meanwhile, there was no significant difference in the incidence of endpoint events between the two crescent glomerular ratio groups (48.7% vs. 41.7%, p = 0.649). Kaplan-Meier survival analysis indicated that renal function level (p < 0.001) and proteinuria (p = 0.023) were associated with renal survival in IgAN patients. In contrast, the administration of immunosuppressive therapy (p = 0.288) and the prevalence of C lesions (p = 0.982) did not show a significant association with renal survival. Further, Cox regression analysis identified systolic blood pressure, fibrinogen, and CKD stage as risk factors for eGFR decline in IgAN patients (all p < 0.05). Conclusion: IgAN patients with stages 3b-5 CKD exhibited a poor prognosis. It appears that in this specific cohort of IgAN patients, immunosuppressive therapy may not provide significant advantages over supportive care therapeutic regimens in terms of disease management.

Advances in IgA nephropathy management, from pathological insights to personalized treatment

IgA nephropathy is a common glomerulonephritis with variable clinical outcomes. The optimal treatment for this condition remains uncertain, and corticosteroid therapy is reserved for patients unresponsive to supportive treatment. The histopathologic examination has a significant role in the diagnosis and prognosis of IgA nephropathy, but its role in the initiation of corticosteroid therapy is still under debate. Recently, targeted release formulation (TRF)-budesonide has emerged as a promising treatment due to its localized delivery to the gut and low systemic adverse effects. This brief review aims to assess recent advancements in IgA nephropathy management, focusing on applying Oxford classification in guiding corticosteroid therapy.

Glomerular deposition of fibrinogen predicts good prognosis of IgA nephropathy: a single-center cohort study

PurposeIt has been proven that fibrinogen deposition exists in IgA nephropathy (IgAN), but its clinical significance has not been identified. We aim to investigate the clinical implication of fibrinogen deposition in evaluating the activity and prognosis of IgA nephropathy.MethodsIn this cohort, 935 adult IgAN patients were divided into 3 groups according to the intensity of glomerular fibrinogen deposition. Primary outcome refers to a composite event of either a ≥ 50% reduction in eGFR or ESRD (eGFR < 15 ml/min/1.73m2, dialysis, or renal transplantation). Factors associated with fibrinogen deposition and prognosis were identified.ResultsThe results showed that the intensity of fibrinogen deposition was positively correlated with eGFR (P < 0.001), serum albumin (P = 0.041), and hemoglobin levels (P < 0.05), but negatively correlated with age (P = 0.04), serum fibrinogen levels (P < 0.001), serum C4 (P = 0.023), the proportion of patients with hypertension (P = 0.003), and the percentage of glomeruli sclerosis (P < 0.001). The prognostic analyses identified that fibrinogen deposition was an independent predictor for the progression of IgAN (P = 0.033).ConclusionOur study indicated that the deposition of renal fibrinogen can predict the prognosis of IgAN with high reliability.