IgA Nephropathy Patients Research Articles

Distinct characteristics and prognosis of IgA nephropathy patients with nephrotic syndrome: a propensity score-matched cohort study.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally. While nephrotic syndrome (NS) is uncommon in IgAN, its significance remains unclear. We conducted a retrospective analysis of 170 IgAN patients, classifying them into NS (n = 85) and non-NS (n = 5) groups. Our study aims to compare their clinical characteristics, treatment responses, and prognoses. Patients were selected based on renal biopsy from 2003 to 2020. Propensity score matching ensured comparability. Clinical, pathological, and immunological data were analyzed. Composite endpoints were defined as end-stage kidney disease (ESKD) or a 30% decline in estimated glomerular filtration rate (eGFR). NS patients showed higher eGFR (74.3 ± 36.8 vs. 61.5 ± 33.6 mL/min.1.73 m2, p = 0.02), severe hematuria (35.0 (4.7,147.5) vs. 4.0 (1.8,45,0) cells/μl, p < 0.001), severe foot process effacement (p = 0.01), and lower C3 levels (1.0 ± 0.3 vs. 1.1 ± 0.2 g/L, p = 0.03). In contrast, the non-NS group had higher BMI (24.3 ± 4.0 vs. 26.8 ± 3.7 kg/m2, p < 0.001) and elevated serum uric acid levels (376 (316,417) vs. 400 (362, 501) mmol/L, p = 0.001), suggesting metabolic factors might contribute to their condition. Both groups exhibited similar MESTC scores. NS patients had higher complete remission rates (26.2% vs. 14.1%, p = 0.04). Cox regression revealed NS independently associated with a higher risk of composite endpoints (HR = 1.97, 95% CI 1.05-3.72, p = 0.04). Linear mixed models did not show significant eGFR trajectory differences. This study has established that IgAN patients with NS exhibit distinct characteristics, including active disease and increased complement activation. NS is independently associated with a poorer prognosis, emphasizing the need for targeted interventions in this subgroup.

Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study

Background The clinical significance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) has been less explored and remains a topic of debate. Therefore, our study aimed to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of IgAN patients. Methods A unicentric retrospective study was conducted on 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. They were followed until end-stage kidney disease (ESKD), death, or until the end of the study in January 2021, with a median follow-up of 7 years. An independent pathologist evaluated the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions following a comprehensive protocol. Results In our cohort, 70% had mesangial IgM-positive deposits, while 30% were IgM-negative. Both groups were similar in age, sex, prevalence of arterial hypertension, Charlson comorbidity scores, kidney function (eGFR and proteinuria), pathology findings (Oxford MEST-C score, IgG and C3 immune deposition), and TEM analysis. Treatment with RASI and immunosuppression, and death rates were also comparable. However, 37% of IgM-positive patients progressed to ESKD, significantly higher than the 11% in the IgM-negative group. Univariate and multivariate Cox proportional hazards regression analyses identified lower eGFR, higher Oxford MEST-C score, and mesangial IgM deposits as independent factors associated with shorter kidney survival. Conclusions Our study highlights mesangial IgM deposition as a potential risk factor for ESKD in patients with advanced IgAN, laying a foundation for further research in this area.

Oral bacteria induce IgA autoantibodies against a mesangial protein in IgA nephropathy model mice.

IgA nephropathy (IgAN) is caused by deposition of IgA in the glomerular mesangium. The mechanism of selective deposition and production of IgA is unclear; however, we recently identified the involvement of IgA autoantibodies. Here, we show that CBX3 is another self-antigen for IgA in gddY mice, a spontaneous IgAN model, and in IgAN patients. A recombinant antibody derived from gddY mice bound to CBX3 expressed on the mesangial cell surface in vitro and to glomeruli in vivo. An elemental diet and antibiotic treatment decreased the levels of autoantibodies and IgAN symptoms in gddY mice. Serum IgA and the recombinant antibody from gddY mice also bound to oral bacteria of the mice and binding was competed with CBX3. One species of oral bacteria was markedly decreased in elemental diet-fed gddY mice and induced anti-CBX3 antibody in normal mice upon immunization. These data suggest that particular oral bacteria generate immune responses to produce IgA that cross-reacts with mesangial cells to initiate IgAN.

Are Platelet-Related Parameters Prognostic Predictors of Renal and Cardiovascular Outcomes in IgA Nephropathy?

Background: IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as the platelet (PLT) count, platelet-to-albumin ratio (PAR), and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. We were interested in whether platelet-related parameters are risk factors for ESKD and CV events in IgAN patients. Methods: In a monocentric retrospective study, 124 IgAN patients were divided into two groups based on the cut-off value of the PAR. All-cause mortality, major CV events, and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results: The patients' mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that the PLR, PAR, and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS), the PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, the PLR correlated with albuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusions. Elevated PARs and PLRs may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they were related to CV events in IgAN. The determination of PARs and PLRs can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in IgAN.

Kidney Failure Events, Cardiovascular Disease Events, and All-Cause Mortality in Patients with IgA Nephropathy in a Real-World Database.

IgA nephropathy (IgAN) associated glomerular injury leads to proteinuria, hematuria, and progressive loss of glomerular filtration rate, with progression to kidney failure (KF). This retrospective study evaluated the prognostic effects of proteinuria and progression to KF on cardiovascular disease (CVD)/mortality events and KF/mortality events in the United States. We conducted a non-interventional, retrospective cohort study in adult IgAN patients using Optum's de-identified Market Clarity Data (01/01/2007 to 03/31/2021). Adult (≥18 years old) patients with at least two signs, disease, symptoms natural language processing term entries for IgAN, within 180 days and ≥30 days apart within the identification period were included. Outcomes were assessed by time-dependent proteinuria (≥1 g/day vs. <1 g/day) and KF status (pre vs. post). Descriptive statistics were used for categorical and continuous variables. Multivariable Cox proportional hazard models with time-dependent predictors were used to estimate differences across groups. Pre-KF patients with proteinuria ≥1 g/day were more likely to have a CVD/mortality event during follow-up (adjusted hazard ratio [HR; 95% CI]: 1.80 [1.12-2.89]; p<0.001) or a KF/mortality event (adjusted HR [95% CI]: 2.10 [1.73-2.56]; p<0.001). Post-KF patients were more likely to have a CVD/mortality event during follow-up (adjusted HR [95% CI]: 3.28 [2.82-3.81]; p<0.001). Elevated proteinuria and progression to KF was associated with higher risk of CVD/mortality events. Elevated pre-KF proteinuria was also associated with progression to KF/mortality events. Based on our real-world retrospective database analysis, we hypothesize that novel IgAN therapies that reduce proteinuria and slow the rate of progression to KF have the potential to reduce CVD risk, improve kidney outcomes and prolong/increase overall survival.

Hydroxychloroquine Induces Remission for IgA Nephropathy With Mild to Moderate Proteinuria: A Single-Centered Retrospective Analysis.

Hydroxychloroquine (HCQ) influences both toll-like receptor (TLR) signaling and leukocyte activation, which are speculated to play a role in the pathogenesis of IgA nephropathy (IgAN). This is a single-centered retrospective study involving 426 IgAN patients diagnosed from May 2016 to August 2020. All patients were matched according to a propensity score matching (PSM) to produce three groups: renin-angiotensin-aldosterone system inhibitors (RAASi) group (RAASi only), corticosteroids group (corticosteroids only or combined with RAASi), and HCQ group (HCQ only or combined with RAASi), consisting of 63 patients for each group. After PSM, the median urine protein/creatinine ratio (UPCR) of overall patients was 0.91 g/g, while their median serum creatinine was 87.00 μmol/L. After the median follow-up period of 11.03 months, the total remission rates of the RAASi group, corticosteroids group, and HCQ groups were 49.21% (n = 31), 74.60% (n = 47), and 52.38% (n = 33), respectively (p = 0.017). Thirteen (6.88%) patients experienced a decline in estimated glomerular filtration rate (eGFR) of more than 25% from baseline, including six (9.52%) patients in the RAASi group, three (4.76%) patients in the corticosteroids group, and four (6.35%) patients in HCQ group (p = 0.677). One (1.59%) patient in the HCQ group had blurred vision and continued to use HCQ after ruling out retinal lesions by ophthalmic examination. HCQ is effective in inducing remission and well-tolerated in IgAN patients with mild to moderate proteinuria.

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study in Caucasians

Objective and designImmunoglobulin A nephropathy (IgAN) is a kidney disease characterized by the accumulation of IgA deposits in the glomeruli of the kidney, leading to inflammation and damage to the kidney. The inflammatory markers involved in IgAN remain to be defined. Gene expression analysis platforms, such as the NanoString nCounter system, are promising screening and diagnostic tools, especially in oncology. Still, their role as a diagnostic and prognostic tool in IgAN remains scarce. In this study, we aimed to validate the use of NanoString technology to identify potential inflammatory biomarkers involved in the progression of IgAN.SubjectsA total of 30 patients with biopsy-proven IgAN and 7 cases of antineutrophil cytoplasmic antibody (ANCA)-associated pauci-immune glomerulonephritis were included for gene expression measurement. For the immunofluorescence validation experiments, a total of 6 IgAN patients and 3 controls were included.MethodsTotal RNA was extracted from formalin-fixed paraffin-embedded kidney biopsy specimens, and a customized 48-plex human gene CodeSet was used to study 29 genes implicated in different biological pathways. Comparisons in gene expression were made between IgAN and ANCA-associated pauci-immune glomerulonephritis patients to delineate an expression profile specific to IgAN. Gene expression was compared between patients with low and moderate risk of progression. Genes for which RNA expression was associated with disease progression were analyzed for protein expression by immunofluorescence and compared with controls.ResultsIgAN patients had a distinct gene expression profile with decreased expression in genes IL-6, INFG, and C1QB compared to ANCA patients. C3 and TNFRSF1B were identified as potential biomarkers for IgAN progression in patients early in their disease course. Protein expression for those 2 candidate genes was upregulated in IgAN patients compared to controls. Expression of genes implicated in fibrosis (PTEN, CASPASE 3, TGM2, TGFB1, IL2, and TNFRSF1B) was more pronounced in IgAN patients with severe fibrosis compared to those with none.ConclusionsOur findings validate our NanoString mRNA profiling by examining protein expression levels of two candidate genes, C3 and TNFRSF1B, in IgAN patients and controls. We also identified several upregulated mRNA transcripts implicated in the development of fibrosis that may be considered fibrotic markers within IgAN patients.

Characteristics of renal pathology and coagulation function in IgA nephropathy and IgA vasculitis associated nephritis

BackgroundThe objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN).MethodsA total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed.ResultsCompared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P < 0.001) was lower in IgAN group. The pathological results revealed that patients with IgAN have a greater degree of chronic kidney injury compared to patients with IgAVN. In addition, the levels of plasma D-Dimers (1415.92 ± 1774.69 vs. 496.78 ± 711.91 ng/mL, P < 0.001) and fibrinogen degradation products (FDP) (3.92 ± 4.73 vs. 1.63 ± 2.46 µg/mL, P = 0.001) were significantly higher in IgAVN patients than in IgAN patients. The deposition of fibrinogen in the renal tissues was more severe and the cumulative partial remission rate was higher in patients with IgAVN as compared to those with IgAN (P = 0.001).ConclusionsIn comparison, IgAN patients had poorer renal function, whereas IgAVN patients had more severe coagulation abnormalities. These findings provide a basis for the differentiation of the two diseases at an early stage.

Microangiopathy associated with poor outcome of immunoglobulin A nephropathy: a cohort study and meta-analysis

ABSTRACT Background Microangiopathy (MA) lesions are not rare in immunoglobulin A nephropathy (IgAN) and have been suggested to have a potential role in increasing risk in renal function decline. However, this suggestion has not been universally accepted. We aimed to investigate its role in our cohort and in multiple studies through a systematic meta-analysis. Methods This cohort study included 450 IgAN patients, confirmed by renal biopsy, at Tongji Hospital, China, from January 2012 to December 2016. Clinical data were collected and analysed. We systematically searched PubMed and Web of Science for studies investigating the association between MA lesions and IgAN. Results In our cohort, IgAN patients with MA were significantly older and had higher blood pressure, more proteinuria, worse kidney function and increased uric acid levels compared with patients without MA. When comparing pathological features with the non-MA group, the MA group exhibited more global glomerulosclerosis and interstitial fibrosis/tubular atrophy. MA lesions were independently associated with a composite kidney outcome in IgAN patients {adjusted hazard ratio 2.115 [95% confidence interval (CI) 1.035–4.320], P = .040}. Furthermore, this relationship was validated in a meta-analysis involving 2098 individuals from five independent cohorts. The combined data showed a 187% adjusted risk of poor renal outcome in IgAN patients with MA compared with patients without MA [adjusted risk ratio 2.87 (95% CI 2.05–4.02; I2 = 53%). Conclusion MA lesions could serve as a valuable predictor for disease progression in patients with IgAN, extending beyond the widely recognized Oxford MEST-C score.

The efficacy and safety of hydroxychloroquine versus leflunomide in patients with IgA nephropathy: a single-center experience

PurposeTo date, our understanding of IgA nephropathy (IgAN) pathophysiology has remained incomplete; therefore, treatment remains largely empiric, and the efficacy and safety of immunosuppressants remain controversial. We aimed to assess the efficacy and safety of hydroxychloroquine and leflunomide therapy in a retrospective cohort of patients with IgAN.MethodsWe screened the IgAN registration database in our department, and a total of 159 kidney patients with biopsy-confirmed IgAN were enrolled, with 57 patients receiving hydroxychloroquine plus a renin-angiotensin system inhibitor (hydroxychloroquine group), 52 patients receiving leflunomide plus a renin-angiotensin system inhibitor (leflunomide group), and 50 patients receiving only a renin-angiotensin system inhibitor (renin-angiotensin system inhibitor-only group). Changes in proteinuria, hematuria, and the estimated glomerular filtration rate (eGFR), as well as adverse events, were analyzed during the follow-up period.ResultsAt the end of 6-month follow-up, proteinuria significantly decreased by 70.36 (57.54, 79.33)%, 57.29 (46.79, 67.29)% and 41.20 (25.76, 48.94)% in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, respectively, compared to baseline (all P values < 0.001). Hematuria significantly decreased by 71.07 (56.48, 82.47)% in the leflunomide group (P < 0.001). The eGFR improved by 3.72 ± 2.97%, 3.16 ± 2.00% and 1.91 ± 2.41%, respectively, in the hydroxychloroquine, leflunomide and renin-angiotensin system inhibitor-only groups, but without statistical significance. No serious adverse events occurred during the follow-up period.ConclusionBoth hydroxychloroquine combined with a renin-angiotensin system inhibitor and leflunomide combined with a renin-angiotensin system inhibitor were more effective than a renin-angiotensin system inhibitor alone in improving proteinuria in IgAN patients. Hydroxychloroquine was more effective in reducing proteinuria, and leflunomide showed superiority in reducing hematuria. Our results need to be verified in large-scale randomized controlled trials.Graphical abstract

Association between urinary C4d levels and disease progression in IgA nephropathy.

C4d mesangial deposition, a hallmark of lectin pathway activation in immunoglobulin A nephropathy (IgAN), has been shown to be associated with risk of kidney failure. To date, the relationship between urinary C4d and renal outcome remain unelucidated. A total of 508 patients with biopsy-proven IgAN were enrolled in this study, whose baseline urine samples at the time of biopsy were collected and the levels of urinary C4d were quantified by enzyme-linked immunosorbent assay. The time-averaged C4d (TA-C4d) and the change in proteinuria were measured in sequential urine samples obtained from IgAN patients. The kidney progression event was defined as a 50% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease or death. After a median follow-up of 36 months, 70 (13.8%) of the participants reached the kidney progression event. Higher levels of urinary C4d/Ucr were found to be associated with decreased eGFR, massive proteinuria, lower serum albumin levels, hypertension, and severe Oxford E and T scores. Upon adjusting for traditional risk factors (including demographics, eGFR, proteinuria, hypertension, Oxford pathologic score and immunosuppressive therapy), elevated levels of urinary C4d/Ucr were independently associated with an increased risk of chronic kidney disease progression [adjusted hazard ratio (HR) per standard deviation increment of log-transformed C4d/Ucr: 1.46; 95% CI 1.04-2.06; P=.030]. In reference to the low C4d group, the risk of poor renal outcome increased for the high C4d group (adjusted HR 1.93; 95% CI 1.05-3.54; P=.033). Additionally, a low baseline C4d level was independently associated with a favorable proteinuria response to immunosuppressive therapy at 3 months (adjusted relative risk 2.20; 95% CI 1.04-4.63, P=.038). The urinary C4d, serving as a non-invasive biomarker, is associated with the progression of IgAN and holds the potential to predict proteinuria response in this disease.

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.

Distribution of Subgingival Bacteria in Chronic Periodontitis Patients Correlated with IgA Nephropathy.

Several studies indicated that chronic periodontitis (CP) and its subgingival bacteria correlated with IgA nephropathy (IgAN). Previous research has shown that prevalence of IgAN in chronic periodontitis patients is significantly higher than that in non CP patients in Xinjiang especially in ethnic Uyghur. The aim of this study is to investigate the distribution of plaque bacterial microbes in CP and IgAN patients and to find correlation between CP and IgAN. All of the subgingival plaque samples including 7 healthy controls (N group), 8 CP patients, 14 IgAN patients, and 14 CP with IgAN patients were obtained from ethnic Uyghur people. To investigate the distribution of plaque microbe in Uyghur CP and IgAN patients, the 16s rRNA sequencing and comparative analysis of subgingival bacteria were performed. There were no statistically differences in the community richness estimator (Chao) and the diversity estimator (Shannon index) among four groups. The abundance of Burkholderiales (order), Ottowia (genus) in the plaque microbes were significantly higher in CP with IgAN patients than CP patients. The abundance of Eubacterium (genus) was significantly higher in CP with IgAN patients than IgAN patients. The abundance of Veillonella (genus) was significantly higher while Streptococcus (genus), Tannerella (genus) were significantly lower in CP patients than healthy volunteers. The composition and abundance of subgingival plaque microbes in Uyghur CP and IgAN patients were significantly different at several levels. Which suggested that abundance of subgingival bacteria is correlated to CP and IgAN.

Treatment of Patients with IgA Nephropathy: Evaluation of the Safety and Efficacy of Mycophenolate Mofetil.

Immunoglobulin A nephropathy (IgAN), characterized by aberrant IgA immune complex deposition, is the most prevalent primary glomerular disease and the main cause of end-stage renal disease, causing a significant physical and psychological burden on people worldwide. Conventional therapeutic approaches, such as renin-angiotensin-aldosterone system inhibitors and corticosteroids, may not achieve sufficient effectiveness and may produce major side events in the past. The previous data in Asian populations indicated that mycophenolate mofetil (MMF) might significantly advance the development of a new therapy strategy for IgAN. The effectiveness and safety of MMF in patients with IgAN will be investigated in this study. A literature search was conducted on June 30th, 2023, by searching the following databases: PubMed and the Cochrane Library according to predefined criteria. To investigate the renoprotective benefits and safety of MMF, statistical analyses were performed using Cochrane's Review Manager Version 5.3. The meta-analysis included nine randomized controlled studies that fulfilled the inclusion criterion. In the Asian population, the results revealed a substantial difference in remission rates between the MMF group and the control group (OR: 2.53, 95% CI: 1.02, 6.30, P = 0.05). MMF can increase the rate of decrease in proteinuria in IgAN patients when compared with controls in Asians (OR: 7.34, 95% CI: 2.69, 20.08, P = 0.0001), and MMF can reduce the urinary protein in patients with IgAN in Asians (WMD: -0.61, 95% CI: -1.15, -0.08, P = 0.02). Interestingly, these studies on Asians were conducted in China. However, the differences in remission rate, rate of decrease in proteinuria, and urinary protein reduction between the MMF group and control group were not found in overall populations and in the Caucasian population. The differences in complete remission rate, partial remission rate, serum creatinine (SCr) doubling rate, rate of 50% increase in SCr, and rate of need for renal replacement treatment between the MMF group and control group were not found in Asians, Caucasians, and overall populations. The difference in the rate of side effects between the MMF group and the control group was not found. MMF protects renal function and is a safe medication for treating Chinese IgAN patients. MMF might significantly advance the development of a new therapy strategy for IgAN in the Chinese population.

Development and validation of a diagnostic nomogram to evaluate tubular atrophy/interstitial fibrosis of IgA nephropathy.

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.

Effectiveness and Safety of Spironolactone in the Treatment of IgA Nephropathy: A Retrospective Self-Controlled Study.

It is crucial to utilize combination therapy for immunoglobulin A nephropathy (IgAN) patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in the management of IgAN patients. Adult IgAN patients treated with spironolactone were evaluated. Patients were separated into two categories according to whether 24-h proteinuria was reduced by more than 20% after 2 months of spironolactone treatment compared to baseline levels. Eighty-eight patients were analyzed and 24-h proteinuria decreased from 0.93 g to 0.70 g (p &lt; 0.001) after 2 months of treatment with spironolactone, accompanied by a slight decrease in eGFR from 75.7 to 73.9 mL/min/1.73 m2 (p = 0.033). Intriguingly, 47 patients in the effective mineralocorticoid receptor antagonist (MRA) group showed less endocapillary hypercellularity (p = 0.040). In the ineffective group, 18 patients discontinued MRA treatment because 24-h proteinuria increased from 0.83 g to 1.04 g, while the other 23 patients continued with spironolactone and proteinuria decreased to 0.57 g in the sixth month (p = 0.001). Furthermore, 12 patients with persistent high proteinuria during prednisone therapy were added with spironolactone. 24-proteinuria was dropped from 0.95 g to 0.73 g at the second month and to 0.50 g at the sixth month. In our study, we confirmed spironolactone's efficacy in reducing urine protein excretion in IgA nephropathy patients within 2 months of treatment. However, response varied among patients, with those showing endocapillary proliferation (E1) in renal biopsies having poor spironolactone responsiveness. Administering MRAs to patients with eGFR over 30 mL/min did not result in hyperkalemia, indicating the treatment's safety.

Association of time-averaged serum uric acid level with clinicopathological information and long-term outcomes in patients with IgA nephropathy.

Whether serum uric acid (SUA) at baseline could been identiûed as a risk factor for progression in IgA nephropathy (IgAN) patients remains unclear, therefore, long- term SUA control levels must be monitored. We aimed to investigate the relevant factors affecting time-averaged SUA (TA-SUA) and to assess the prognostic value of TA-SUA in IgAN. This retrospective study included 152 patients with IgAN. The relationships between TA-SUA and clinicopathological features and renal outcomes (defined as the doubling of the baseline serum creatinine level or end-stage renal disease) were analyzed in groups divided by quartiles of TA-SUA levels, the presence of hyperuricemia, and sex. Patients with high TA-SUA levels had higher levels of baseline SUA, blood urea nitrogen (BUN), triglycerides, serum C3 and serum C4 and were more likely to be male and have hypertension, proteinuria, poor renal function, and pathological injuries including high grades of tubular atrophy/interstitial fibrosis (T1-T2). These patients had a poorer prognosis compared with patients with low TA-SUA levels. The TA-SUA level was positively correlated with baseline age and BUN, triglycerides, serum C3, and serum C4 levels, and negatively correlated with baseline eGFR. Survival curve analysis indicated that persistent hyperuricemia was associated with significantly poorer renal outcomes than normo-uricemia in both men and women. The TA-SUA level also was an independent predictor of renal outcome in patients with IgAN, with optimal cutoû values of 451.38 µmol/L (area under the curve (AUC) = 0.934) for men and 492.83 µmol/L (AUC = 0.768) for women. The TA-SUA level is associated with triglyceride level, complement component levels, renal function, and pathological severity of IgAN, and it may be a prognostic indicator in male and female patients with IgAN.

IgA nephropathy

IgA nephropathy (IgAN) is the most frequent primary form of glomerulonephritis. The origin of IgAN is only partially understood and appears to involve the occurrence of IgA1, which is normally secreted by mucous membranes, in the circulation followed by its glomerular deposition and inflammatory changes. Clinically, IgAN mostly follows an inapparent course and the disease is often only first diagnosed by kidney biopsy when kidney function disorders are already manifested. Key prognostic indicators include the extent of proteinuria and the already manifested evidence of irreversible kidney damage. Treatment includes supportive measures. The effectiveness of high-dose systemic corticosteroid treatment in European patients is uncertain and controversial due to the adverse side effects. Nefecon (encapsulated budesonide) is the first specific drug licensed for treatment of high risk IgAN patients. Anumber of further approaches are currently in clinical trials.

MMF as Immunosuppressive Therapy in IgA Nephropathy

Introduction: IgA Nephropathy (IgAN) is the most common cause of primary glomerulonephritis in developed countries. Treatment with ACEI/ARB has strong evidence in managing IgAN. If there is evidence of progression, immunosuppression is recommended. KDIGO guidelines do not advise Mycophenolate Mofetil’s (MMF) use in non-Chinese population currently. Methods: In this study, we reviewed immunosuppression with MMF retrospectively in IgAN patients managed at the Sussex Kidney Unit (SKU) – Brighton – United Kingdom. This was assessed using the primary measures of renal survival without requiring renal replacement therapy (RRT) and proteinuria reduction to &gt;50% of the diagnosis baseline. Twenty-five patients diagnosed with IgAN between 2011 and 2020 and had been treated with MMF were retrospectively reviewed. Data was collected until January 2023, including laboratory results, histopathology, clinic letters, and medication. For those on RRT, data was collected up until the start of RRT. Results: Twenty- Five patients were reviewed; 24 were white Caucasians, and 1 was ethnically Asian. MMF was used in all 25 patients. Three patients were treated with MMF alone and 17 in combination with steroids. Five patients had prednisolone and cyclophosphamide for three months, followed by MMF maintenance. The average treatment duration was 2 years, and the average dose was 1g BD. Five patients progressed to end-stage renal disease (ESRD), and 3 had renal transplants. Twenty patients maintained renal survival; the mean eGFR at diagnosis was 45.6+/-34.1 and, at the time of review, was 56.1+/-26.6. Of the 17 patients who presented with AKI, 5 recovered to normal renal function, 5 had end-stage renal disease (ESRD), 4 had improvements, and 3 showed a decrease in eGFR. Overall, 70.6% of AKI patients recovered to normal or CKD levels. Eighty % of the patients had renal survival without RRT during the review. Twenty patients achieved more than 50% reduction of proteinuria, with five patients having proteinuria less than 0.3 g/24 hours and nine patients less than 0.5 g/24 hours. Comparison between the proteinuria at diagnosis and at the assessment time was significant (P&lt;0.001). Conclusions: Mycophenolate mofetil effectively maintained renal survival and improved proteinuria in IgA nephropathy patients indicated for immunosuppression. The treatment was well tolerated by all patients.

Alterations in oxidative stress biomarkers and helper T-cell subgroups in patients with periodontitis and IgA nephropathy.

Investigating the changes in the oxidative stress levels and helper T lymphocyte (Th) subsets in patients with periodontitis and IgA nephropathy (IgAN) to determine their relationship. IgAN has a high prevalence, poor prognosis, and no effective cure. Accumulating evidence has implicated a close relationship between periodontitis and chronic kidney diseases, in which both IgAN and chronic periodontitis show chronic inflammation and abnormal metabolism. However, few studies have been conducted on the relationship between the two diseases from this perspective. We divided 86 IgAN patients into patients with healthy periodontium (IgAN-H, n = 34) and patients with periodontitis IgAN (IgAN-P, n = 52); moreover, we divided 72 systemically healthy participants into patients with periodontitis (H-P, n = 35) and participants with healthy periodontium (H-H, n = 37). The proportions of Th subsets in peripheral blood were estimated using flow cytometry. Cytokine levels in plasma were assessed using cytokine assay kits. Enzyme-linked immunosorbent assay was used to evaluate the plasma levels of oxidative stress. Our results from analyzing the Th cell subsets indicated that Th2 cell counts in the IgAN-P group were significantly lower than those in the IgAN-H group, while Th17 cell counts were increased (p < 0.05). Moreover, the Th1/Th2 ratio and interleukin-6 levels in the IgAN-P group were significantly higher than those in the H-H group (p < 0.01). Compared with that in the H-H group, in the remaining three groups, plasma total oxidation state (TOS) levels were increased (p < 0.01), while plasma total antioxidant state (TAS) levels were decreased (p < 0.05). Furthermore, estimated glomerular filtration rate was negatively correlated with the probing depth and gingival bleeding index. IgAN was a risk factor for periodontitis, while TAS was a protective factor for periodontitis. The oxidative stress index (OSI) might be valuable for distinguishing periodontitis patients from healthy controls (area under the receiver operator characteristic curve = 0.951). IgAN is an independent risk factor of periodontitis, and the Th17 cell-mediated inflammatory response might be associated with the occurrence of periodontitis in patients with IgAN. Patients with coexisting IgAN and periodontitis exhibit increased oxidative stress, in which TOS and OSI are potential biomarkers for diagnosing periodontitis.