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

BACKGROUND: IgA 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. METHODS: A 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. DISCUSSION: Identifying 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 REGISTRATION: PROSPERO CRD42022364569.

[Anti-Proteinuric Effect of GLP1-RA as Add-On to SGLT2-i and ACE-i in a Diabetic Patient with IgA Nephropathy].

Immunoglobulin A (IgA) nephropathy is a common glomerulonephritis, but its treatment remains matter of debate. Recommendation for corticosteroids has been supported, but renin-angiotensin inhibitors, RAAS, and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are increasingly used because of a better benefit/safety balance in comparison with systemic steroids and immunosuppressive treatments. In this case report, a patient with type 2 diabetes (T2DM) and biopsy-proven nephrotic IgA-related nephropathy documented a rapid meaningful reduction of proteinuria and the effect was persistent for 2 years, after receiving the treatment with a GLP1-RA on top of the previous treatment with ACE-inhibitors and SGLT2-i. Considering the beneficial effects of GLP1-RA in diabetes related chronic kidney disease, the present case report supports the notion that these drugs could also represent a beneficial treatment option in IgA nephropathy.

Medullary sponge kidney with IgA nephropathy: a case report and literature review.

BACKGROUND: Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy. CASE PRESENTATION: A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient's clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy. CONCLUSIONS: Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

IgA nephropathy in a child with X-linked agammaglobulinemia: a case report.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the Bruton tyrosine kinase (BTK) gene. Individuals diagnosed with XLA are at an increased risk of developing autoimmune diseases. However, renal involvement are rare in cases of XLA. CASE PRESENTATION: In this report, we discussed a specific case involving a 6-year-old boy with XLA who experienced recurrent upper respiratory tract infections since the age of one. He presented with symptoms of hematuria and proteinuria, and renal pathology confirmed the presence of immunoglobulin (Ig) A nephropathy. Treatment comprised glucocorticoids, mycophenolate mofetil, and intermittent intravenous immunoglobulin replacement therapy. Consequently, there was a remission of proteinuria and a partial improvement in hematuria. CONCLUSIONS: In this study, we describe the first case of IgA nephropathy associated with XLA. This is an interesting phenotype found in XLA, and it provides valuable insights into the process of autoimmunity and the regulation of immune function in individuals with XLA. Based on our findings, we recommend the evaluation of immunoglobulin levels in patients diagnosed with IgA nephropathy.

Simultaneous Occurrence of Collagen Type III Glomerulopathy and Immunoglobulin A Nephropathy: A Rare Case Report.

BACKGROUND Collagen type III glomerulopathy (CG) is a rare disease with poorly understood pathogenesis, usually identified by abnormal collagen type III accumulation in glomeruli and manifesting as progressive deterioration of kidney function with nephrotic-range proteinuria. Immunoglobulin A nephropathy (IgAN) is the most prevalent glomerulopathy worldwide and is a leading cause of end-stage renal disease as a result of progressive fibrotic changes. Fibrosis is primarily caused by collagen type III deposition, which may explain the simultaneous occurrence of IgAN and CG. CASE REPORT A young man presented with clinical and laboratory evidence of chronic kidney injury, including long-term nephrotic-range proteinuria and microscopic hematuria. Partial improvement in proteinuria was achieved with steroid therapy and conservative management. As the non-invasive workup was inconclusive, and a complete recovery of kidney function was not achieved, a kidney biopsy was done. Histopathological microscopic examination revealed advanced IgA nephropathy, Oxford classification M0E1S1T2C0, with features highly suggestive of type III collagen glomerulopathy. CONCLUSIONS We described a case of collagen type III glomerulopathy, also known as collagenofibrotic glomerulopathy, and its association with concurrent immunoglobulin A nephropathy in a healthy man presenting with chronic proteinuria and microscopic hematuria. As the number of reported cases in the Middle East is rising, we present this report to improve understanding and greater recognition of such cases.

A case of crescentic glomerulonephritis with exacerbation of pre-existing IgA nephropathy after COVID-19.

BACKGROUND: Relapses or new-onset IgA nephropathy (IgAN) have been documented in patients after vaccination against SARS-CoV-2; however, only one adult patient has been reported in whom pre-existing IgAN worsened during coronavirus disease 2019 (COVID-19). CASE: We present the first pediatric case with biopsy-proven IgAN and genetically confirmed Alport syndrome, who developed end-stage kidney disease after an exacerbation of IgAN associated with COVID-19. The patient`s basal serum creatinine was 0.7-0.9 mg/dL before infection. He had not been vaccinated against COVID-19. He was admitted to the hospital with edema, hypertension, an elevated serum creatinine of 4.7 mg/ dL, and massive proteinuria. Three months before admission, he had been admitted to another hospital with COVID -19 and an elevated serum creatinine (1.9 mg/dL), but no biopsy had been performed at that time. The kidney biopsy revealed IgAN with 50% fibrocellular crescents with sclerosed glomeruli, tubular atrophy, and interstitial fibrosis. His serum creatinine did not decrease even after five administrations of pulse steroids, and hemodialysis was initiated. CONCLUSION: In conclusion, COVID -19 may pose a high risk for exacerbation of pre-existing glomerular disease. It is therefore necessary to closely monitor the kidney function of patients with underlying glomerulonephritis during and after COVID-19 and consider an early biopsy if serum creatinine does not return to baseline levels. In addition, this case report highlights the clinical importance of the co-occurence of IgAN and Alport syndrome.

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.

Coexistence of anti-glomerular basement membrane disease and IgA nephropathy: an illustrative case and comprehensive literature review.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune condition characterized by the presence of positive anti-GBM autoantibodies, linear deposition of immunoglobulin G (IgG) along the GBM and severe kidney injury. In a limited number of cases, the association of anti-GBM disease with other glomerulonephritis has been reported. Herein, we present the case of a 66-year-old female patient with progressive worsen kidney function and decreased urine output. A renal biopsy revealed crescent glomerulonephritis with lineal IgG deposition along the GBM and mesangial IgA deposition, which supported the diagnosis of concurrent anti-GBM disease and IgA nephropathy (IgAN). In an extensive literature review, we identified a total of thirty-nine patients were reported anti-GBM disease combined with IgAN. The clinical characteristics of these patients demonstrate that the anti-GBM disease combined with IgAN tends to be milder with a more indolent course and a better prognosis than the classic anti-GBM disease, and its potential pathogenesis deserves to be further explored.

A multi-center randomized controlled trial to investigate potential effects of exercise therapy on renal function stratified by renal disorders and renal pathology: beneficial or harmful effect in immunoglobulin a nephropathy.

BACKGROUND: The effects of exercise therapy (ET) on renal function in chronic kidney disease (CKD) remain unclear. METHODS: In a randomized controlled trial (UMIN-CTR number: UMIN000038415), we investigated whether ET affects renal function in CKD; eligible patients had undergone renal biopsy in the past 3 months. We stratified patients by disease (immunoglobulin A [IgA] nephropathy, n = 16; diabetic nephropathy, n = 4; benign nephrosclerosis, n = 13; and other CKD types, n = 13) and randomized them to 12 weeks' observation and 24 weeks' ET comprising home-based aerobic exercise 3×/week and resistance training 2×/week (intervention group) or usual care (non-intervention group). Primary endpoint was creatinine-based estimated glomerular filtration rate (eGFR) or serum cystatin C-based eGFR (eGFRcys). Secondary endpoints included urinary protein and exercise tolerance. RESULTS: Seventy patients were enrolled, 50 fulfilled the inclusion criteria, but 4 discontinued before randomization. No items significantly differed between week 0 to 24 in either group (intervention group, n = 23; non-intervention group, n = 23) or between groups at week 24 (intention-to-treat population) in the total study population. The eGFRcys slope showed no significant intergroup difference in the observation period, but eGFRcys improved significantly in IgA nephropathy patients (n = 16) in the intervention group (stratified comparison; week 0, 48.3 ± 18.2; week 24, 51.6 ± 17.6; p = 0.043). In these patients, urinary protein was significantly worse at week 24 in the non-intervention group (p = 0.046) and worsened significantly less in the intervention group (p = 0.039). CONCLUSION: ET did not improve renal function overall in CKD patients but might help maintain renal function in patients with IgA nephropathy.

Clinical and pathological findings of IgA nephropathy following SARS-CoV-2 infection.

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis.

AIM: The purpose of this study was to determine efficacy and safety of hydroxychloroquine (HCQ) for patients with IgA nephropathy (IgAN). METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure and VIP database up to February 2023 were searched for associated studies comparing HCQ with any other nonHCQ for treating IgAN. The effects of proteinuria, a 50% decrease in proteinuria, estimated glomerular filtration rate (eGFR) and adverse events in patients with IgAN were examined in a meta-analysis. Data were extracted and pooled using RevMan 5.3. RESULTS: Three randomized controlled trials (RCTs), two retrospective and two prospective studies (675 patients) that matched our inclusion criteria were identified. Compared with a control group, HCQ significantly reduced proteinuria (mean difference (MD): -0.26, 95% confidence interval (CI): -0.44 to -0.08, p < 0.01). Patients receiving HCQ plus renin-angiotensin system inhibitors (RASSi) had a better efficacy in proteinuria alleviation and a 50% decrease in proteinuria compared with control groups (MD: -0.38, 95% CI: -0.50 to -0.25, p < 0.001 and relative risk (RR) = 3.31, 95% CI: 1.73 to 6.36, p < 0.001). No appreciable variations were observed in eGFR between HCQ groups and control groups in treating patients with IgAN (MD: -2.00, 95% CI: -4.36 to 0.36, p = 0.10). Moreover, no serious adverse events were observed during HCQ treatment. CONCLUSIONS: Our results indicate HCQ is an efficient, secure treatment for IgAN.

Clinical application value of Ultrafast Pulse Wave Velocity in early cardiovascular injury of Immunoglobulin A nephropathy.

AIM: To investigate the application and the related influencing factors of ultrafast pulse wave velocity (ufPWV) in the evaluation of carotid artery elasticity in patients with Immunoglobulin A nephropathy (IgAN). MATERIAL AND METHODS: A total of 156 IgAN patients and 50 healthy individuals were selected as the control group. The ufPWV technique was employed to measure carotid arterial elasticity parameters, including carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (BS-PWV) and pulse wave velocity at the end of systole (ES-PWV). RESULTS: Across the three groups (control group, IgAN patients with normal renal function, and IgAN patients with renal dysfunction) there was an increasing trend observed in cIMT, BS-PWV, and ES-PWV. Additionally, ES-PWV exhibited higher sensitivity than BS-PWV. Correlation analysis revealed that BS-PWV and ES-PWV were positively correlated with age, body mass index (BMI), systolic blood pressure (SBP), high-sensitivity C-reactive protein (hs-CRP), creatinine (Cr), blood urea nitrogen (BUN), and uric acid (UA) and negatively correlated with estimated glomerular filtration rate (eGFR). CONCLUSION: The ufPWV technique allows for the rapid and direct measurement of arterial elasticity parameters in the neck and represents a novel approach for the early diagnosis and quantitative assessment of arterial stiffness risk in IgAN patients.

Corticosteroid in IgA nephropathy with moderate proteinuria: A retrospective cohort study.

BACKGROUND: Corticosteroids remain contentious as a therapeutic option for IgA nephropathy. We conducted a retrospective cohort study to explore whether corticosteroid therapy is efficient and safe for IgAN patients with moderate proteinuria. METHODS: A total of 336 patients with renal biopsy-confirmed IgAN, estimated glomerular filtration (eGFR) over 15 mL/min/1.73 m2 and urine protein levels of 0.75-3.5 g/d were enrolled. According to the treatment protocol, we classified the enrolled patients into two groups: one receiving corticosteroids and the other receiving supportive care. Complete remission, partial remission, and no remission were applied to describe the efficacy assessments. The endpoint was defined as a 40% reduction in eGFR, the onset of ESRD, or renal disease-related death. RESULTS: Clinical and pathological progression risk factors were higher in corticosteroid-treated individuals. Logistic regression analysis revealed that the corticosteroid group was considerably related to a higher remission rate after adjustment for confounding factors. The occurrence of serious adverse events between the two groups was not found to be statistically significantly different. Then, we matched 95 couples of patients with similar baseline levels in both groups by propensity score matching. The results showed that corticosteroid-treated patients showed higher overall and complete remission rates than untreated patients. However, due to the relatively short follow-up period, no significant differences in the incidence of endpoint and survival analyses have been observed thus far. CONCLUSION: Corticosteroid therapy may benefit IgAN patients with moderate proteinuria via proteinuria reduction and renal function preservation.

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future.

The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.