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

Objective: 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). Methods: 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). Results: 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). Conclusion: HALP is a novel and potent composite parameter to predict kidney outcome in patients with IgAN.

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.

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

BACKGROUND: Renal 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. METHODS: We 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. RESULTS: During 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). CONCLUSION: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

Validation of IgA nephropathy diagnosis in the Swedish Renal Registry.

AIM: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis. METHODS: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis. RESULTS: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases. CONCLUSION: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.

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.

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.

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.

Combined Effects of the Serum IgA/C3 Ratio and Glomerular C3 Staining on the Renal Outcome in Adult Immunoglobulin A Nephropathy.

INTRODUCTION: The aim of this study was to evaluate the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgA nephropathy. METHODS: The study included 718 adult IgAN patients diagnosed based on kidney biopsy. Patients without corticosteroids or immunosuppressive drugs >1 month were regularly followed up for at least 1 year or until the study endpoint. The optimum serum IgA/C3 ratio was calculated by the AUROC-based cutoff ratio. Proteinuria, creatinine, eGFR, serum IgA, and serum C3 were evaluated at baseline. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The degree of glomerular C3 staining was semiquantitatively determined (grade 0, no or trace; grade 1, mild; grade 2, moderate; grade 3, marked) by immunofluorescence microscopy. The patients were divided into four groups by the serum IgA/C3 ratio and glomerular C3 staining. RESULTS: The baseline data suggested that when the serum IgA/C3 ratio was at the same level, patients with a high glomerular C3 staining score (≥2) always had mesangial proliferation, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis (group 1 vs. group 2; group 3 vs. group 4). When glomerular C3 staining was at the same level, proteinuria was significantly higher in patients with serum IgA/C3<2.806 (group 1 vs. group 3; group 2 vs. group 4), which was contrary to previous studies that have suggested that the serum level of IgA/C3 was associated with disease severity. Hence, this study set out to investigate the combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Renal survival analysis indicated that serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients based on the subgroup analysis. Multivariate Cox analysis demonstrated that hypertension, serum creatinine, CKD stage, T1/2 and C3 staining were independent predictive factors of renal survival. CONCLUSIONS: The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease. However, further study is required for validation in the future.

Urinary exosomal miRNA-451a can be used as a potential noninvasive biomarker for diagnosis, reflecting tubulointerstitial damage and therapeutic response in IgA nephropathy.

To investigate the potential clinical value of urinary exosomal (uE) miR-451a as a biomarker for IgAN, urinary exosomes were isolated from 40 patients with IgAN, 30 patients with primary renal diseases without IgA as disease controls (non-IgAN group) and 21 healthy controls (HCs). The expression of miR-451a within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). uE miR-451a was significantly upregulated in patients with IgAN compared to non-IgAN and HCs. The uE miR-451a level was positively correlated with the change in eGFR and negatively correlated with serum creatinine, urinary macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). A dual-luciferase reporter assay confirmed that MIF was a direct target of miR-451a. Receiver operating characteristic (ROC) curve analysis revealed that the expression of uE miR-451a showed potential diagnostic value for IgAN. Additionally, the uE miR-451a level could distinguish patients with IgAN with mild tubular atrophy/interstitial fibrosis from those with severe tubular atrophy/interstitial fibrosis. After a mean follow-up of 14.2 months, the levels of eGFR loss (ml/min/1.73 m2/year) were negatively correlated with baseline miR-451a. The levels of baseline miR-451a in the complete remission group were significantly higher than those in the non-complete remission group. uE miR-451a expression was significantly elevated in patients with IgA nephropathy and may serve as a potential biomarker for the diagnosis of IgAN and evaluation of tubulointerstitial damage, while the baseline levels of uE miR-451a may be predictors of therapeutic efficacy and disease progression.

External Validation of the International Prognosis Prediction Model of IgA Nephropathy.

BACKGROUND: The International IgA Nephropathy (IgAN) Network developed and validated two prognostic prediction models for IgAN, one incorporating a race parameter. These models could anticipate the risk of a 50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD) subsequent to an IgAN diagnosis via renal biopsy. This investigation aimed to validate the International IgA Nephropathy Prediction Tool (IIgANPT) within a contemporary Chinese cohort. METHODS: Within this study,185 patients diagnosed with IgAN via renal biopsy at the Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, between January 2012 and December 2021, were encompassed. Each patient's risk of progression was assessed utilizing the IIgANPT formula. The primary outcome, a 50% decline in eGFR or progression to ESRD, was examined. Two predictive models, one inclusive and the other exclusive of a race parameter, underwent evaluation via receiver-operating characteristic (ROC) curves, subgroup survival analyses, calibration plots, and decision curve analyses. RESULTS: The median follow-up duration within our cohort spanned 5.1 years, during which 18 patients encountered the primary outcome. The subgroup survival curves exhibited distinct separations, and the comparison of clinical and histological characteristics among the risk subgroups revealed significant differences. Both models demonstrated outstanding discrimination, evidenced by the areas under the ROC curve at five years: 0.882 and 0.878. Whether incorporating the race parameter or not, both prediction models exhibited acceptable calibration. Decision curve analysis affirmed the favorable clinical utility of both models. CONCLUSIONS: Both prognostic risk evaluation models for IgAN exhibited remarkable discrimination, sound calibration, and acceptable clinical utility.

Recurrent IgA Nephropathy or Subclinical Chronic Humoral Rejection With Predominance of Plasma Cells: A Case Report.

Both antibody-mediated rejection and recurrence of kidney disease are major causes of allograft loss. A possible strategy to address the former is donor-specific antibody (DSA) monitoring. In this patient with IgA nephropathy, DSA detection triggered biopsy 10 years after transplant despite preserved graft function and normal urinary examination. Biopsy showed mild glomerulitis, mild capillaritis, and transplant glomerulopathy with no C4d peritubular capillary staining, along with IgA-dominant mesangial immunofluorescence staining. Interstitial inflammation had a notable predominance of plasma cells, a finding that has been variably attributed to rejection and worse prognosis. Immunosuppression was optimized with the working diagnosis of recurrent IgA nephropathy and/or chronic active humoral rejection with predominance of plasma cells, with favorable response at follow-up. This case illustrates the conflicting role of DSA monitoring and allograft biopsy to optimize immunosuppression management. Despite imperfect correlation with each other and clinical outcomes, they are key to tailor therapy. In the future, characterization of the role of plasma cell infiltrates in rejection might further enable prognosis and treatment individualization.

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.

Liquid Biopsy: A New Avenue for the Diagnosis of Kidney Disease: Diabetic Kidney Disease, Renal Cancer, and IgA Nephropathy.

Kidney diseases are some of the most common healthcare problems. As the population of elderly individuals with concurrent health conditions continues to rise, there will be a heightened occurrence of these diseases. Due to the renal condition being one of the longevity predictors, early diagnosis of kidney dysfunction plays a crucial role. Currently, prevalent diagnostic tools include laboratory tests and kidney tissue biopsies. New technologies, particularly liquid biopsy and new detection biomarkers, hold promise for diagnosing kidney disorders. The aim of this review is to present modern diagnostic methods for kidney diseases. The paper focuses on the advances in diagnosing three common renal disorders: diabetic kidney disease, renal cancer, and immunoglobulin A nephropathy. We highlight the significance of liquid biopsy and epigenetic changes, such as DNA methylation, microRNA, piRNAs, and lncRNAs expression, or single-cell transcriptome sequencing in the assessment of kidney diseases. This review underscores the importance of early diagnosis for the effective management of kidney diseases and investigates liquid biopsy as a promising approach.

Identification of common and specific fibrosis-related genes in three common chronic kidney diseases.

BACKGROUND: Kidney fibrosis is the common final pathway of virtually all advanced forms of chronic kidney disease (CKD) including diabetic nephropathy (DN), IgA nephropathy (IgAN) and membranous nephropathy (MN), with complex mechanism. Comparative gene expression analysis among these types of CKD may shed light on its pathogenesis. Therefore, we conducted this study aiming at exploring the common and specific fibrosis-related genes involved in different types of CKD. METHODS: Kidney biopsy specimens from patients with different types of CKD and normal control subjects were analyzed using the NanoString nCounter® Human Fibrosis V2 Panel. Genes differentially expressed in all fibrotic DN, IgAN and MN tissues compared to the normal controls were regarded as the common fibrosis-related genes in CKD, whereas genes exclusively differentially expressed in fibrotic DN, IgAN or MN samples were considered to be the specific genes related to fibrosis in DN, IgAN and MN respectively. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of the selected genes. RESULTS: Protein tyrosine phosphatase receptor type C (PTPRC), intercellular cell adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM1), interleukin 10 receptor alpha (IL10RA) and CC chemokine receptor 2 (CCR2) were identified as the potential common genes for kidney fibrosis in different types of CKD, while peroxisome proliferator-activated receptor alpha (PPARA), lactate oxidase (LOX), secreted phosphoprotein 1 (SPP1) were identified as the specific fibrosis-associated genes for DN, IgAN and MN respectively. qRT-PCR demonstrated that the expression levels of these selected genes were consistent with the NanoString analysis. CONCLUSIONS: There were both commonalities and differences in the mechanisms of fibrosis in different types of CKD, the commonalities might be used as the common therapeutic targets for kidney fibrosis in CKD, while the differences might be used as the diagnostic markers for DN, IgAN and MN respectively. Inflammation was highly relevant to the pathogenesis of fibrosis. This study provides further insight into the pathophysiology and treatment of fibrotic kidney disease.

[IgA nephropathy]. / IgA-Nephropathie.

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. A number of further approaches are currently in clinical trials.

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

BACKGROUND: The objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN). METHODS: A 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. RESULTS: Compared 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). CONCLUSIONS: In 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.

The Impact of Obesity on Kidney Disease: Observational Cohort Study Analyzing 14,492 Kidney Biopsy Cases.

BACKGROUND: The obesity epidemic is associated with the emergence of new kidney diseases including obesity-related glomerulopathy (ORG) and metabolic syndrome-associated disorders. However, the effects of obesity on prevalence and outcome of biopsy-proven kidney disease are not well known. METHODS: We analyzed 14,492 kidney biopsies in 18 hospitals from 1979 to 2018 in Korea. Obesity was defined as a body mass index value of ≥ 30 kg/m². RESULTS: The most common disease was IgA nephropathy (IgAN) in both obese and non-obese participants (33.7% vs. 38.9%). Obesity was associated with a higher risk of focal segmental glomerulosclerosis (FSGS) and hypertensive nephropathy (HT-N) (odds ratio [OR], 1.72, 95% confidence interval [CI], 1.37-2.17; OR, 1.96, 95% CI, 1.21-3.19) and a lower risk of IgAN (OR, 0.74, 95% CI, 0.62-0.88). During the median follow up of 93.1 ± 88.7 months, obesity increased the risk of end-stage kidney disease (ESKD) in patients with IgAN (relative risk [RR], 1.49, 95% CI, 1.01-2.20) and lupus nephritis (LN) (RR, 3.43, 95% CI, 1.36-8.67). Of 947 obese individuals, ORG was detected in 298 (31.5%), and 230 participants had other kidney diseases, most commonly, IgAN (40.9%) followed by diabetic nephropathy (15.2%). Participants with ORG, when combined with other renal diseases, showed higher risks for developing ESKD compared to those with ORG alone (RR, 2.48, 95% CI, 1.09-5.64). CONCLUSION: Obesity is associated with an increased risk of FSGS and HT-N, and also increase the ESKD risk in IgAN and LN patients. ORG in obese participants may have favorable renal outcomes if it occurs alone without any other renal disease.

Serum and urine galactose deficient-IgA1 as alternative biomarkers in the management of IgA nephropathy.

INTRODUCTION: Immunoglobulin A (IgA) nephropathy (IgAN) results from abnormal accumulation of immune complexes containing galactose deficient IgA1 (Gd-IgA1) in the kidneys. About 40% of patients develop end-stage kidney disease within 20 years of renal biopsy. At present, the diagnosis and risk stratification of patients (using the international IgAN risk prediction tool) rely on renal biopsy, which is an invasive procedure. Also, treatment decisions are still dependent on proteinuria, which is not specific for IgA nephropathy. We discussed the role of serum and urine Gd- IgA1 in the diagnosis of IgAN, its association with disease progression and changes with treatment in patients with IgA nephropathy. MATERIALS AND METHODS: A systematic search of PubMed and Scopus databases was done to identify the articles that are relevant to the topic including systematic reviews and original articles. RESULTS: Several studies showed that both serum and urine Gd-IgA1 differentiate IgA nephropathy patients from healthy people and other glomerulonephropathies. Thus, it is useful as a less invasive diagnostic biomarker, although detection methods varied between studies with different sensitivities. There are various reports of its use as a prognostic parameter. Evidence is emerging for its use as a monitoring parameter for treatment. CONCLUSION: Galactose deficient IgA1 is a promising biomarker in the management of IgA nephropathy, although a more robust and standardised means of estimation is required.

Nephrotic proteinuria and hematuria with newly diagnosed IgA nephropathy after liver transplant: A case report.

BACKGROUND: IgA nephropathy is a renal lesion in patients with end-stage liver disease, called hepatic IgA nephropathy. The common manifestation of hepatic IgA nephropathy is microscopic hematuria. Sirolimus, often used to prevent organ rejection, has been reported to induce proteinuria after organ transplantation. But few cases of nephrotic proteinuria and hematuria are reported. CASE PRESENTATION: In this case, a 45-year-old male with a long history of hepatic B virus infection and liver cirrhosis, received liver transplant and was taking sirolimus as one of his immunosuppression drugs. Overt proteinuria and hematuria occurred. With no proteinuria history before, renal biopsy was performed, which indicated IgA nephropathy. CONCLUSION: We reported a liver recipient, who was taking sirolimus, developing nephrotic proteinuria and hematuria with IgA nephropathy. Further studies need to be carried out to disclose mechanism behind this phenomenon.

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

OBJECTIVE AND DESIGN: Immunoglobulin 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. SUBJECTS: A 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. METHODS: Total 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. RESULTS: IgAN 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. CONCLUSIONS: Our 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.