Search

Abstract Purpose The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). Methods Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known. [ABSTRACT FROM AUTHOR]

Background: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. Methods: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46–69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. Results: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02–20.6), p = 047, 0.95 (0.94–0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4–5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. Conclusions: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the correlation between podocyte related biomarker cofilin-1 and renal function, and explore the value of cofilin-1 in predicting the risk of renal adverse prognosis in IgA nephropathy (IgAN). Methods: Patients with primary IgAN diagnosed by initial renal biopsy performed in our hospital from January 2019 to February 2022 were included. This study was a prospective cohort study. All IgAN patients were detected the expression of cofilin-1 and other related biomarkers (RhoA, NGAL) in urine by enzyme-linked immunosorbent assay (ELISA) and follow-up at least 6 months. We also collected baseline clinicopathologial data of IgAN. The decreased renal function group was defined as baseline eGFR < 60 ml/min/1.73m2. Logistic and Cox regression model were used to analyze the correlation among cofilin-1 and renal prognosis. Results: 133 IgAN patients were included, with a male-to-female ratio of 1.25:1 and an age of 37.67 ± 13.78 years, as well as an average of eGFR was 71.63 (40.42,109.33) ml/min/1.73m2. 56 patients (42.1%) had decreased renal function at baseline, with the average of eGFR was 34.07 (16.72, 49.21) ml/min/1.73 m2. 12 of which developed to renal adverse prognosis. The average of follow-up time was 22.035 ± 8.992 months. The multivariate regression analysis showed that increased urinary cofilin-1 was an independent risk factor associated with baseline renal function decline and renal adverse prognosis in IgAN patients (P < 0.05). ROC curves showed great efficacy of urinary cofilin-1 levels in diagnosing baseline renal function decline and predicting renal adverse prognosis (the area under the ROC curve was 0.708 and 0.803). Conclusion: Cofilin-1 as a novel biomarker of podocyte lesion is closely related to renal function decline in IgAN. Cofilin-1 has certain clinical value in predicting the risk of renal adverse prognosis. Podocyte fusion affects the renal prognosis of IgAN. [ABSTRACT FROM AUTHOR]

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described. The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown. Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA depositionwas significantly lower than that in patients with classic anti-GBMdisease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5mmol/L, IQR:270.0~702.0 vs. 515.8~1231.2mmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2mmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2mmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in themesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition. Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease. [ABSTRACT FROM AUTHOR]

Background Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. Methods This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. Results The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mOsm/kg H2O, which decreased to 97.6 ± 23.8 mOsm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the 1-month values of U-Osm showed higher variability (160.2 ± 83.8 mOsm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. Conclusions U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice. [ABSTRACT FROM AUTHOR]

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

Background Primary membranous nephropathy (pMN) is one of the most common types of glomerulonephritis, with a third of patients progressing to renal insufficiency. Various prognostic factors have been reported, of which urinary protein and renal function are the most critical parameters. Fractional excretion of total protein (FETP) indicates protein leakage that accounts for creatinine kinetics and serum protein levels. In this study, we investigated the association between FETP and renal prognosis in pMN. Methods We retrospectively identified 150 patients with pMN. FETP was calculated as follows: (serum creatinine × urine protein)/(serum protein × urine creatinine) %. We divided the patients into three groups according to FETP values and compared the clinicopathological findings. The primary outcome was an estimated glomerular filtration rate (eGFR) decrease of ≥30% from the baseline level. Results FETP was associated with urinary protein and renal function, Ehrenreich and Churg stage, and global glomerulosclerosis. The primary outcome was observed in 38 patients (25.3%), and the frequency of the primary outcome was higher in the high FETP group (P  = .001). FETP is higher than protein–creatinine ratio (PCR) in the area under the curve. In the multivariate analysis adjusted for age, eGFR, PCR and treatment, FETP was significantly associated with primary outcome (adjusted hazard ratio, 8.19; P  = .019). Conclusions FETP is a valuable indicator that can reflect the pathophysiology and is more useful than PCR as a predictor of renal prognosis in patients with Japanese pMN. [ABSTRACT FROM AUTHOR]

Background: Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD. Methods: In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3 years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD. Results: Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3 years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function. Conclusion: Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3 years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD. [ABSTRACT FROM AUTHOR]

Combined administration of tazobactam-piperacillin (T/P) is a risk factor for the development of vancomycin (VCM)-induced nephrotoxicity (VIN). We herein investigated the incidence, clinical characteristics, and prognosis of VIN in elderly patients treated with VCM and T/P. Patients admitted to the Tokyo Metropolitan Institute for Geriatrics and Gerontology who were administered VCM and T/P were included in this study. Patient backgrounds, serum VCM concentrations, and VCM and T/P dosage were also investigated. The patients were divided into VIN and non-VIN groups and compared. In the VIN group, time to onset of VIN and time to recovery of renal function were investigated. Of 53 patients, 10 (18.9%) developed VIN. Median time to VIN onset was 9.0 (1-24) days. Eight (80%) of the ten patients in the VIN group recovered their renal function. Serum VCM concentrations in the VIN group varied from 5.0 to 20.1 µg/mL; some patients developed VIN even when their serum VCM concentrations were low. This study suggests that the incidence of VCM and T/P-induced nephrotoxicity in elderly patients is not higher than that previously reported in a study that included younger patients. Additionally, when VCM is administered in combination with T/P, VIN may occur even at low serum VCM concentrations, and reduced renal function estimated based on serum creatinine concentration may not be associated with the development of VIN, Furthermore, the combination of VCM and T/P may not specifically worsen the renal prognosis in elderly patients with VIN. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the clinicopathological profiles and prognosis of membranous nephropathy in different subtypes classified by serum PLA2R antibody (SAb) and glomerular PLA2R antigen staining (GAg). Methods: A total of 372 biopsy-proven membranous nephropathy (MN) cases, unrelated to lupus, with urine protein > 2 g/24 h and eGFR > 25 mL/min/1.73 m2 were included and categorized into four groups according to the presence or absence of PLA2R antibody and glomerular PLA2R antigen staining. Clinical profiles were compared among four subtypes. Treatment response and renal outcomes were compared among four groups with primary MN. Cox and logistic regression models were used to examine the association between time-to-renal progression and early remission within 6 months in the four subgroups with primary MN. Results: MN patients who were SAb−/GAg+ presented with a more severe disease onset, whereas those who were SAb−/GAg− had a mild clinical manifestation with a higher prevalence of MN-associated secondary causes. During a median follow-up of 79.2 months (IQR: 48.70–97.40), SAb+/GAg− was identified as an independent risk factor for renal progression [HR: 9.17, 95% CI: 2.26–37.16, p < 0.01] and early remission [OR: 0.06, 95% CI: 0.01–0.56, p = 0.01] in primary MN. Additionally, SAb−/GAg− with primary MN showed an independent association with spontaneous remission after adjusting for age, sex, baseline proteinuria, and eGFR (Before adjustment: OR: 8.33, 95% CI: 1.89–36.76, p = 0.0; after adjustment: OR: 12.25, 95% CI: 2.48–60.53, p < 0.01). Conclusion: Our findings indicated that SAb+/GAg−MN patients exhibited a more severe disease onset and had a poorer prognosis, necessitating an aggressive treatment approach. On the other hand, in the SAb−/GAg− group, the elimination of secondary causes should be considered, and a watchful waiting approach may be appropriate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum neutrophil extracellular traps （NETs), tumor necrosis factor-like weak inducer of apoptosis （TWEAK), peripheral blood cluster of differentiation （CD)4+T/CD8+T ratio and disease activity and rena prognosis in patients with lupus nephritis （LN). Methods:137 LN patients （LN group） who were admitted to the Department of Nephrology, Affiliated Hospital of North Sichuan Medical College from August 2021 to August 2022 were selected, patients were divided into mild activity group （52 cases), moderate activity group （45 cases） and severe activity group （40 cases） according to the systemic lupus erythematosus disease activity index （SLEDAI）-2000 score. After 1 years of follow-up, patients were divided into poor prognosis group（43 cases） and good prognosis group （94 cases） according to the occurrence of kidney-related endpoint events, another 76 healthy volunteers （control group） were selected during the same period. The levels of serum NETs and TWEAK were detected by enzyme-linked immunosorbent assay, and the proportion of CD4+T/CD8+T in peripheral blood was detected by flow cytometry. The correlation between serum NETs, TWEAK, peripheral blood CD4+T/CD8+T and SLEDAI-2000 score in LN patients were analyzed by Spearman correlation analysis, the factors of poor prognosis in LN patients were analyzed by multivariate Logistic regression analysis, the predictive value of serum NETs, TWEAK and peripheral blood CD4+T/CD8+T for poor prognosis in LN patients were analyzed by receiver operating characteristic curve. Results: Compared with control group, the levels of serum NETs and TWEAK in LN group were increased, and the peripheral blood CD4+T/CD8+T was decreased （P＜0. 05). The serum NETs and TWEAK in mild activity group, moderate activity group and severe activity group increased in turn, and the peripheral blood CD4+T/CD8+T decreased in turn （P＜0. 05). SLEDAI-2000 score in LN patients was positively correlated with serum NETs and TWEAK, and negatively correlated with peripheral blood CD4+T/CD8+T （P＜0. 05）Chronic kidney disease stage 4, elevated SLEDAI-2000 score, elevated NETs and elevated TWEAK were independent risk factors for poor prognosis in LN patients, increased estimated glomerular filtration rate and elevated CD4+T/CD8+T were independent protective factors （P＜0. 05). The area under the curve of serum NETs, TWEAK and peripheral blood CD4+T/CD8+T combined to predict poor prognosis in LN patients was 0. 943, which was greater than 0. 790, 0. 788 and 0. 799 predicted by serum NETs, TWEAK and peripheral blood CD4+T/CD8+T alone （P＜0. 05). Conclusions: The levels of serum NETs and TWEAK in LN patients are increase, and the peripheral blood CD4+T/CD8+T is decrease, which are closely relate to disease activity and poor renal prognosis, serum NETs and TWEAK combine with peripheral blood CD4+T/CD8+ T has a high value in predicting renal prognosis in LN patients. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between serum phosphorus and immunoglobulin A (IgA) nephropathy progression remains uncertain, especially normal-range serum phosphorus. Therefore, we herein examined the relationship between the normal-range serum phosphorus and the progression of IgA nephropathy. Methods: One hundred sixty-two patients with primary IgA nephropathy were divided into three groups according to tertiles of baseline serum phosphorus (first tertile: 0.73–1.04 mmol/L; second tertile: 1.04–1.21 mmol/L; third tertile: 1.21–1.60 mmol/L). Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration. The composite outcome was defined as a decrease of at least 50% in eGFR from baseline or end-stage kidney disease (ESKD). The association of serum phosphorus with IgA nephropathy progression was estimated using Cox proportional hazards models, adjusting for potential confounders. Results: During a median 16 month follow-up period, 15 patients reached a composite outcome. In the crude Cox proportional hazard model, baseline serum phosphorus as a continuous variable was associated with increased risk for adverse renal outcomes [hazard ratio (HR) = 63.510, 95% confidence interval (CI) = 3.953–1020.284, P = 0.003], and the high tertile of serum phosphorus group had an increased risk of the composite outcome by using the low tertile group as the reference (HR = 11.895, 95% CI = 1.522–92.993, P = 0.018). After adjustment for traditional risk factors, the high tertile of serum phosphorus group was significantly related to IgA nephropathy progression compared with the low tertile group (HR = 9.424, 95% CI = 1.019–87.165, P = 0.048). Conclusions: Relatively higher serum phosphorus levels within the normal range were significantly associated with the progression of IgA nephropathy. [ABSTRACT FROM AUTHOR]

Introduction: Perirenal fat is a pad that fills the retroperitoneal space outside the kidney, which affects kidney function in various ways. However, the association between perirenal fat and IgA nephropathy (IgAN) has not yet been elucidated. This study aimed to investigate the role of perirenal fat in predicting IgAN progression. Methods: A total of 473 patients with biopsy-proven IgAN and follow-up information were recruited, and perirenal fat thickness (PFT) was measured using color Doppler ultrasonography at renal biopsy. Patients were divided into two groups according to the median PFT: the low-PFT group (PFT ≤1.34 cm, n = 239) and the high PFT group (PFT >1.35 cm, n = 234). A total of 473 healthy participants were included in the control group. Basic clinical characteristics were assessed at the time of renal biopsy, and the relationship between PFT and combined endpoints was analyzed. The renal composite endpoints were defined as a two-fold increase in blood creatinine level, end-stage renal disease (dialysis over 3 months). Kaplan-Meier survival analysis was used to explore the role of PFT in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association between PFT and renal prognosis in patients with IgAN. Results: Compared to healthy subjects, patients with IgAN showed significantly higher PFT. After a median follow-up of 50 months, 75 of 473 patients (15.9%) with IgAN reached renal composite endpoints. Among those, 13 of 239 patients (5.4%) were in the low PFT group, and 62 of 234 patients (26.5%) were in the high PFT group (p < 0.001). The results of three Cox regression models (including demographics, pathological and clinical indicators, and PFT) demonstrated that a higher PFT was significantly associated with a higher risk of reaching renal composite endpoints in patients with IgAN. Conclusion: This study indicated a positive relationship between PFT at renal biopsy and renal progression in patients with IgAN, suggesting that perirenal fat might act as a marker of poor prognosis in patients with IgAN.

Background: The standard method for assessing chronic renal damage is renal biopsy, which has limitations due to its invasiveness. Ultrasound elastography is a non-invasive technique that quantifies tissue elasticity and can be used to determine Young's modulus (YM). Although this breakthrough technology has been successfully employed to evaluate liver stiffness and the extent of fibrosis, its application in kidney-related conditions still needs improvement. Methods: Our study aimed to verify the correlation between renal elastography and the chronic histological score determined via renal biopsy, evaluate the correlation between elastography and response to treatment in the short-term follow-up (6 months), and compare elastography data between renal disease patients (AKD-P) and healthy controls (HP). Results: The analyzed population consisted of 82 patients (41 HP and 41 AKD-P). The AKD-P were divided into responders (R) or non-responders (NR) based on the criteria established by the guidelines. No association was found between renal stiffness and chronic histological score. Elastography data revealed median YM values of 6.15 kPa for AKD-P and 12.2 kPa for HP, with a statistically significant difference. The median YM values of the R and NR groups were 7.4 KPa and 5.6 KPa, respectively (p = 0.037). Conclusions: Patient responsiveness was associated with YM, with lower values observed in the NR group. We also found that the healthy controls exhibited significantly higher YM values than the renal disease population. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define "diabetic kidney disease" or "diabetic nephropathy" precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD. Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR<90 mL/min/1.73 m², n = 119) excluding other causes of chronic kidney disease. We further developed diagnostic models to improve the ability to predict the risk of developing DKD by screening potential risk factors using univariate and multivariate logistic regression analysis. Calibration plots and curve analysis were used to validate the model and clinical usefulness. Next, we screened patients with relatively normal estimated glomerular filtration rate (eGFR) (≥90 mL/min/1.73 m²) to investigate whether tubular injury markers could accurately predict the risk of DKD in patients with normal renal function. We defined the rate of GFR decline as a prognostic indicator of renal function in patients and collected the information of the re-hospitalized DKD patients to determine whether the relevant indicators had an impact on the renal prognosis. Results: The patients with DKD had higher levels of tubular injury markers than patients with DM. URBP, α1-MG, eGFR were statistically different in both univariate and multivariate logistic regression analyses and displayed great predictive power after modeling with an area under curve of 0.987. The calibration curve showed medium agreement. Decision curve showed it would add more net benefits for clinical decision. After adjusting eGFR and serum creatinine (Scr), URBP was demonstrated to be associated with early renal function impairment. Conclusion: Tubular injury markers play an important role in early diabetic renal function impairment. [ABSTRACT FROM AUTHOR]

Background: The synthesis of growth differentiation factor-15 (GDF-15) is induced by inflammation, hypoxia, and oxidative stress and is receiving great interest as a predictive biomarker for cardiovascular disease. However, its detailed impact on patients with renal disease remains uncertain. Methods: Patients who underwent renal biopsy for evaluation of renal disease between 2012 and 2017 in our institute were prospectively included. Serum GDF-15 levels were measured and its association with baseline characteristics and its impact on the 3-year composites of renal prognosis (composites of > 1.5 folds of serum creatinine and renal replacement therapy) were investigated. Results: A total of 110 patients (64 [42, 73] years old, 61 men) were included. The median serum GDF-15 level at baseline was 1885 (998, 3496) pg/mL. A higher serum GDF-15 level was associated with comorbidities including diabetes mellitus, anemia, renal impairment, and pathologic features including crescent formation, hyaline degeneration, and interstitial fibrosis (p < 0.05 for all). Serum GDF-15 level was a significant predictor of 3-year composite renal outcomes with an odds ratio per 100 pg/mL of 1.072 (95% confidence interval 1.001–1.103, p = 0.036) after adjustment for potential confounders. Conclusions: Serum GDF-15 levels were associated with several renal pathological features and renal prognosis in patients with renal diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent the progression of renal disease to end-stage renal disease (ESRD). The aim of this study was to evaluate predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN. Methods A retrospective analysis of ninety-four patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic curve (ROC) was used to evaluate their renal prognostic value. Results The median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened in the RRS group in order of low, medium, and high RRS (P

Aims/Introduction: Diabetic kidney disease (DKD) is defined as diabetes with impaired renal function, elevated urinary albumin excretion, or both. DKD is one of the most common microvascular complications of diabetes and plays an important role in the cause of end-stage renal disease (ESRD). About 5% of people with type 2 diabetes (T2DM) already have kidney damage at the time they are diagnosed, but other triggers of renal insufficiency, such as obesity, hyperlipidemia, glomerular atherosclerosis are often present, making it difficult to define “diabetic kidney disease” or “diabetic nephropathy” precisely in epidemiology or clinical practice. Therefore, the aim of this study is to identify diabetic patients with CKD at an early stage, and evaluate the value of tubular injury markers including α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), N-acetyl-beta-D-glucosaminidase (NAG) and Urinary retinol binding protein (URBP) in the development of diabetes to DKD.Materials and methods: We recruited a total of 182 hospitalized patients with T2DM in the First Affiliated Hospital of Zhengzhou University from February 2018 to April 2023. We collected basic clinical characteristics and laboratory biochemical parameters of the patients. Based on their levels of urinary albumin creatinine ratio (UACR) and glomerular filtration rate (GFR), patients were divided into DM group (UACR≤30 mg/g and eGFR≥90 mL/min/1.73 m2, n = 63) and DKD group (UACR>30 mg/g or eGFR

Abstract Objective The study’s purpose is to explore the link of serum albumin on renal progression in patients with chronic kidney disease (CKD). Methods This study was a secondary analysis of a prospective cohort study in which a total of 954 participants were non-selectively and consecutively collected from the research of CKD-ROUTE in Japan between November 2010 and December 2011. We evaluated the association between baseline ALB and renal prognosis (initiation of dialysis or 50% decline in eGFR from baseline) and renal function decline (annual eGFR decline) using the Cox proportional-hazards and linear regression models, respectively. We performed a number of sensitivity analyses to ensure the validity of the results. In addition, we performed subgroup analyses. Results The included patients had a mean age of (66.86 ± 13.41) years, and 522 (69.23%) were male. The mean baseline ALB and eGFR were (3.89 ± 0.59) g/dL and (33.43 ± 17.97) ml/min/1.73 m2. The annual decline in eGFR was 2.65 mL/min/1.73 m2/year. 218 (28.9%) individuals experienced renal prognosis during a median follow-up period of 36.0 months. The baseline ALB was inversely linked with renal prognosis (HR = 0.61, 95%CI: 0.45, 0.81) and renal function decline (β = -1.41, 95%CI: -2.11, -0.72) after controlling for covariates. The renal prognosis and ALB had a non-linear connection, with ALB’s inflection point occurring at 4.3 g/dL. Effect sizes (HR) were 0.42 (0.32, 0.56) and 6.11 (0.98, 38.22) on the left and right sides of the inflection point, respectively. There was also a non-linear relationship between ALB and renal function decline, and the inflection point of ALB was 4.1 g/dL. The effect sizes(β) on the left and right sides of the inflection point were -2.79(-3.62, -1.96) and 0.02 (-1.97, 1.84), respectively. Conclusion This study shows a negative and non-linear association between ALB and renal function decline as well as renal prognosis in Japanese CKD patients. When ALB is lower than 4.1 g/dL, ALB decline was closely related to poor renal prognosis and renal function decline. From a therapeutic point of view, reducing the decline in ALB makes sense for delaying CKD progression.

Background: The revised KDIGO guidelines recommend maintaining systolic blood pressure (sBP) < 120 mmHg in patients with chronic kidney disease (CKD), based on cardiovascular and survival benefits. However, the renal benefit of this strategy remains less clear. Methods: We used data of routine health checkups in Japan. Persons whose estimated glomerular filtration rate (eGFR) was < 60 mL/min/1.73 m2 in 2015 without end-stage disease were followed until 2020. We estimated the 5-year benefit of hypothetical targeted sBP control using parametric g-formula modeling, accounting for both time-fixed and time-varying confounding variables. Four sensitivity analyses, including analysis using a marginal structural model (MSM) and positive control outcome analysis, were also done. Results: We enrolled 28,972 persons with CKD (median age: 54 years, male: 69%, baseline eGFR [median]: 56 mL/min/1.73m2). As compared with the natural course without a targeted intervention, there was no renoprotective effect of targeted sBP control, with a 5-year difference in eGFR of 0.65 mL/min/1.73 m2 (95% confidence interval − 0.42 to 1.65 mL/min/1.73 m2). MSM analysis found a similar result. In contrast, the positive control analysis using the cardiovascular outcome showed that targeted sBP control would reduce the cardiovascular disease incidence by 6.0% over 5 years. Conclusions: A targeted sBP control strategy maintaining < 120 mmHg may not yield a renoprotective effect for patients with stage 3–4 CKD, although it was expected to offer a cardiovascular benefit. Future research may be warranted in higher-risk populations, such as elderly people or those with more advanced kidney disease. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent the progression of renal disease to end-stage renal disease (ESRD). The aim of this study was to evaluate predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN. Methods: A retrospective analysis of ninety-four patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic curve (ROC) was used to evaluate their renal prognostic value. Results: The median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened in the RRS group in order of low, medium, and high RRS (P < 0.05). Within the RVLs group, the renal prognosis of the groups with severe and moderate RVLs was worse than that of the group without RVLs (P = 0.012, P < 0.001), and the group with mild RVLs was close to that of the group without RVLs. ROC analysis showed that the AUC of RRS, BVAS, RVLs score, RVLs score combined with RRS (RVLs score & RRS, RR), RVLs score, and RRS combined with BVAS (RVLs score & RRS & BVAS, RRB) were 0.865, 0.624, 0.763, 0.910, and 0.942, respectively. The predictive power of RRB and RR was comparable and significantly better than the RRS, BVAS, and RVLs score. Based on simplicity and validity, RR was selected as the best predictor, and the relationship between RRS, RVLs score, and RR was calculated using a linear fit, resulting in the linear equation RR = -0.4766 + 0.1231 × RVLs score + 0.395 × RRS (P < 0.001). Conclusions: In AAGN, the predictive power of RR for renal prognosis was superior to that of RRS, BVAS, and RVLs score. RR may serve as a new predictor of renal prognosis in AAGN. [ABSTRACT FROM AUTHOR]

Background Anti-neutrophil cytoplasmic antibody (ANCA) kinetic in ANCA-associated vasculitis with glomerulonephritis (AAV-GN) has been suggested to be associated with AAV relapse. Few studies have focused on its association with renal prognosis. Thus we aimed to investigate the relationship between ANCA specificity and the evolutive profile and renal outcomes. Methods This multicentric retrospective study included patients diagnosed with ANCA-GN since 1 January 2000. Patients without ANCA at diagnosis and with fewer than three ANCA determinations during follow-up were excluded. We analysed estimated glomerular filtration rate (eGFR) variation, renal-free survival and relapse-free survival according to three ANCA profiles (negative, recurrent and persistent) and to ANCA specificity [myeloperoxidase (MPO) or proteinase 3 (PR3)]. Results Over a follow-up of 56 months [interquartile range (IQR) 34–101], a median of 19 (IQR 13–25) ANCA determinations were performed for the 134 included patients. Patients with a recurrent/persistent ANCA profile had a lower relapse-free survival (P  = .019) and tended to have a lower renal survival (P  = .053) compared with those with a negative ANCA profile. Patients with a recurrent/persistent MPO-ANCA profile had the shortest renal survival (P  = .015) and those with a recurrent/persistent PR3-ANCA profile had the worst relapse-free survival (P  = .013) compared with other profiles. The negative ANCA profile was associated with a greater eGFR recovery. In multivariate regression analysis, it was an independent predictor of a 2-fold increase in eGFR at 2 years [odds ratio 6.79 (95% confidence interval 1.78–31.4), P  = .008]). Conclusion ANCA kinetic after an ANCA-GN diagnosis is associated with outcomes. MPO-ANCA recurrence/persistence identifies patients with a lower potential of renal recovery and a higher risk of kidney failure, while PR3-ANCA recurrence/persistence identifies patients with a greater relapse risk. Thus ANCA kinetics may help identify patients with a smouldering disease. [ABSTRACT FROM AUTHOR]

Background: Clinical factors affecting renal prognosis in patients with immunoglobulin A nephropathy (IgAN) and low urinary protein excretion (U-Prot) remain unclear. This study evaluated such factors in patients with clinical grade I (CG-I) IgAN with U-Prot < 0.5 g/day. Methods: This secondary analysis of a previous retrospective study included 394 patients with CG-I IgAN. The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine levels from baseline. Factors related to renal prognosis were examined using univariate and multivariate Cox regression analyses. CG-I was divided into C-Grade Ia (CG-Ia) (n = 330) with baseline eGFR ≥ 60 ml/min/1.73 m2, and C-Grade Ib (CG-Ib) (n = 64) with baseline eGFR < 60 ml/min/1.73 m2. Outcome incidence was compared between conservative and aggressive therapy (corticosteroids and/or tonsillectomy) groups. Results: Overall outcome incidence was significantly higher in CG-Ib than in CG-Ia; the cumulative incidence was significantly higher in CG-Ib (hazard ratio, 9.67; 95% confidence interval, 2.90–32.23). Older age, higher IgA levels, eGFR < 60 mL/min/1.73 m2, lower eGFR at baseline were independent prognostic factors for CG-I. Older age, lower eGFR, higher IgA levels at baseline, and U-Prot remission at 1-year post-diagnosis were independent prognostic factors for CG-Ib. Aggressive therapy tended to suppress the cumulative outcome incidence compared with conservative therapy in CG-Ib (p = 0.087). Conclusion: An eGFR < 60 mL/min/1.73 m2 is a significant predictor of renal prognosis in patients with IgAN and U-Prot < 0.5 g/day. [ABSTRACT FROM AUTHOR]

ObjectiveThe aim of this study is to explore the prevalence and clinicopathological associations between anti-C1qA08 antibodies and anti-monomeric CRP (mCRP) a.a.35-47 antibodies and to explore the interaction between C1q and mCRP.MethodsNinety patients with biopsy-proven lupus nephritis were included from a Chinese cohort. Plasma samples collected on the day of renal biopsy were tested for anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies. The associations between these two autoantibodies and clinicopathologic features and long-term prognosis were analyzed. The interaction between C1q and mCRP was further investigated by ELISA, and the key linear epitopes of the combination of cholesterol binding sequence (CBS; a.a.35-47) and C1qA08 were tested by competitive inhibition assays. The surface plasmon resonance (SPR) was used to further verify the results.ResultsThe prevalence of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were 50/90 (61.1%) and 45/90 (50.0%), respectively. Levels of anti-C1qA08 antibodies and anti-mCRP a.a.35-47 antibodies were negatively correlated with serum C3 concentrations ((0.5(0.22-1.19) g/L vs. 0.39(0.15-1.38) g/L, P=0.002) and (0.48(0.44-0.88) g/L vs. 0.41(0.15-1.38) g/L, P=0.028), respectively. Levels of anti-C1qA08 antibodies were correlated with the score of fibrous crescents and tubular atrophy (r=-0.256, P=0.014 and r=-0.25, P=0.016, respectively). The patients with double positive antibodies showed worse renal prognosis than that of the double negative group (HR 0.899 (95% CI: 0.739-1.059), P=0.0336). The binding of mCRP to C1q was confirmed by ELISA. The key linear epitopes of the combination were a.a.35-47 and C1qA08, which were confirmed by competitive inhibition experiments and SPR.ConclusionThe combination of anti-C1qA08 and anti-mCRP a.a.35-47 autoantibodies could predict a poor renal outcome. The key linear epitopes of the combination of C1q and mCRP were C1qA08 and a.a.35-47. A08 was an important epitope for the classical pathway complement activation and a.a.35-47 could inhibit this process.

Background and aim: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. We aimed to evaluate whether obesity is a risk factor for IgAN patients. Methods: A total of 1054 biopsy-proven IgAN patients were analyzed in this retrospective study. Patients were divided into four groups according to their body weight index (BMI) at the period of renal biopsy: underweight group (BMI< 18.5, N=75), normal weight group (18.5=BMI<24, N=587), overweight group (24=BMI<28, N=291) and obesity group (28=BMI, N=101). The endpoint of our study was end stage renal disease (ESRD: eGFR <15 mL/min/1.73 m2 or having renal replacement treatment). Kaplan-Meier analyses and Cox proportional hazard models were performed to evaluate renal survival. Propensity-score matching (PSM) was performed to get the matched cohort to evaluate the role of obesity in IgAN patients. Besides, the effect modification of obesity and hypertension in IgAN patients was clarified by the synergy index. Results: IgAN patients complicated with obesity had more severe renal dysfunction at the time of renal biopsy than those with optimal body weight. In addition, patients with obesity tended to have higher risk of metabolic disorders, such as hyperuricemia (64.4% vs 37%, p<0.001), hypertriglyceridemia (71.3% vs 32.5%, p<0.001) and hypercholesterolemia (46.5% vs 35.6%, p=0.036). It was observed that obesity patients had higher rate of unhealthy behaviors, such as smoking (27.7% vs 16.4%, p=0.006) and alcohol drinking (29.7% vs 19.9%, p=0.027). Although obesity was not confirmed as an independent risk factor for IgAN patients, we found that IgAN patients with obesity presented with higher incidence of hypertension, as well as lower event-free renal survival rate (logrank p < 0.001), especially in patients with 24-h urine protein = 1g (log-rank p =0.002). In addition, the synergy index showed that there was positive interaction between obesity and hypertension in IgAN. Conclusion: Obesity is an important risk factor for IgAN patients when combined with hypertension. Hypertension appears to be common in obese IgAN patients. [ABSTRACT FROM AUTHOR]

Objective: The study's purpose is to explore the link of serum albumin on renal progression in patients with chronic kidney disease (CKD). Methods: This study was a secondary analysis of a prospective cohort study in which a total of 954 participants were non-selectively and consecutively collected from the research of CKD-ROUTE in Japan between November 2010 and December 2011. We evaluated the association between baseline ALB and renal prognosis (initiation of dialysis or 50% decline in eGFR from baseline) and renal function decline (annual eGFR decline) using the Cox proportional-hazards and linear regression models, respectively. We performed a number of sensitivity analyses to ensure the validity of the results. In addition, we performed subgroup analyses. Results: The included patients had a mean age of (66.86 ± 13.41) years, and 522 (69.23%) were male. The mean baseline ALB and eGFR were (3.89 ± 0.59) g/dL and (33.43 ± 17.97) ml/min/1.73 m2. The annual decline in eGFR was 2.65 mL/min/1.73 m2/year. 218 (28.9%) individuals experienced renal prognosis during a median follow-up period of 36.0 months. The baseline ALB was inversely linked with renal prognosis (HR = 0.61, 95%CI: 0.45, 0.81) and renal function decline (β = -1.41, 95%CI: -2.11, -0.72) after controlling for covariates. The renal prognosis and ALB had a non-linear connection, with ALB's inflection point occurring at 4.3 g/dL. Effect sizes (HR) were 0.42 (0.32, 0.56) and 6.11 (0.98, 38.22) on the left and right sides of the inflection point, respectively. There was also a non-linear relationship between ALB and renal function decline, and the inflection point of ALB was 4.1 g/dL. The effect sizes(β) on the left and right sides of the inflection point were -2.79(-3.62, -1.96) and 0.02 (-1.97, 1.84), respectively. Conclusion: This study shows a negative and non-linear association between ALB and renal function decline as well as renal prognosis in Japanese CKD patients. When ALB is lower than 4.1 g/dL, ALB decline was closely related to poor renal prognosis and renal function decline. From a therapeutic point of view, reducing the decline in ALB makes sense for delaying CKD progression. [ABSTRACT FROM AUTHOR]

Purpose: IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide. However, the effect of the degree of tubulointerstitial lesions (TIL) on the renal prognosis of these patients is uncertain. Methods: All biopsy-proven primary IgAN patients from a single center (≥ 14 years old) were retrospectively examined from January 2006 to December 2011. According to the Oxford classification for tubulointerstitial lesions in IgAN, eligible patients were assigned to T0 or T1/2 groups. The clinicopathological features of these groups were compared and multivariate models were used to identify the effect of tubulointerstitial lesions on renal prognosis. The composite endpoint was end-stage renal disease or doubling of serum creatinine. Results: We initially identified 1570 patients with IgAN and examined 988 patients who completed follow-up examinations (mean: 49 months). There were 506 patients in the T0 group (51.2%) and 482 in the T1/2 group (48.8%). The 1-year, 3-year, and 5-year incidences of the composite endpoint were 0.2%, 1.5%, 7.7% in the T0 group, and 1.9%, 9.9%, 18.1% in the T1/2 group. An adjusted multivariate model indicated the hazard ratio for reaching the composite endpoint was 9.3 for patients with T1/2 rather than T0 (reference group). A multivariate logistic analysis of the T1/2 group indicated the independent risk factors for reaching the composite endpoint were decreased eGFR, hypertension, hyperlipidemia, proteinuria, global glomerulosclerosis, and segmental glomerulosclerosis. Conclusion: More severe tubulointerstitial lesions (> 25%, T1/2) were an independent predictor of poor renal prognosis in patients with IgAN. [ABSTRACT FROM AUTHOR]

Background: Cryoglobulinemic glomerulonephritis (Cryo-GN), caused by circulating cryoglobulins, has varied etiology and clinical-pathologic manifestations. This study aimed to investigate the clinicopathological spectrum and outcome of patients with various Cryo-GN in China. Methods: A retrospective review of 74 Chinese patients with biopsy-proven cryoglobulin-related renal lesions in Peking University First Hospital from 2010 to 2020 was performed. Results: The mean age at diagnosis was 52.9 ± 15.0 years, and the female-to-male ratio was about 2/5. For the etiology screening, serum/urine monoclonal immunoglobulin could be detected on immunofixation electrophoresis in 34% of patients, including 6 patients who had hematological malignancies. Fifty-seven percent of patients had HBV infection, far more than HCV infection (5%). Ten percent of patients had other infections, and 27% of patients were classified as essential or idiopathic. Eleven out of the 15 patients with type II cryoglobulinemia had a consistent monotype of serum monoclonal immunoglobulins and monoclonal cryoprecipitate. The clinical manifestations were similar between various types of cryoglobulinemia. Hematuria, proteinuria, hypertension, anemia, and chronic renal insufficiency were the most common features. Fifty-three percent of patients presented with nephrotic syndrome, and 32% experienced acute kidney injury. Hypocomplementemia, serum-positive rheumatoid factor activity, and skin lesions were reported in 45%, 29%, and 28% of patients, respectively. After a median of 24 months follow-up, 18 patients reached end-stage kidney disease. The clone-targeted treatment could retard the renal deterioration compared with immunosuppressive therapy. Conclusions: This was the largest single-center, clinicopathological retrospective study of Cryo-GN in China. Our data strongly support the association between monoclonal gammopathy and type II Cryo-GN. The renal responsive rate of immunosuppressant therapy is still suboptimal. The clone-targeted treatment shows promising effects in patients with type I or II Cryo-GN.

The scoring of crescents (Cs) was recently added to the Oxford classification for IgA nephropathy (IgAN). Because of the short-term use of the C score in clinical practice, its validity and applicability need to be verified. We, retrospectively, analyzed the clinicopathological data of 144 primary IgAN patients diagnosed at our hospital from March 2017 to March 2019 and with complete ≥6-month follow-up data. We found that the C score was positively correlated with the Lee’s classification in the assessment of renal pathological changes and significantly correlated with increased proteinuria and decreased estimated glomerular filtration rate. Univariate Cox regression analysis showed an association of C formation with IgAN prognosis, and multivariate Cox regression indicated Cs as an independent prognosis factor. The optimal proportion of Cs for prognosis prediction by the receiver operating characteristic curve was 11%. Kaplan–Meier survival curve revealed a significantly decreased renal survival rate in patients with C proportions ≥11%. Further multivariate Cox regression analysis confirmed that the C proportion ≥11% is an independent risk factor for poor prognosis of IgAN patients. Our findings demonstrate that Cs are independently related to the prognosis of patients with IgAN, and the proportion of Cs ≥11% is an independent risk factor for poor outcomes.

Purpose Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes. Material and methods We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the Somatex® intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months. Results Eight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis. Conclusion Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex® intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity. [ABSTRACT FROM AUTHOR]

The histopathological findings of the glomeruli from whole slide images (WSIs) of a renal biopsy play an important role in diagnosing and grading kidney disease. This study aimed to develop an automated computational pipeline to detect glomeruli and to segment the histopathological regions inside of the glomerulus in a WSI. In order to assess the significance of this pipeline, we conducted a multivariate regression analysis to determine whether the quantified regions were associated with the prognosis of kidney function in 46 cases of immunoglobulin A nephropathy (IgAN). The developed pipelines showed a mean intersection over union (IoU) of 0.670 and 0.693 for five classes (i.e., background, Bowman's space, glomerular tuft, crescentic, and sclerotic regions) against the WSI of its facility, and 0.678 and 0.609 against the WSI of the external facility. The multivariate analysis revealed that the predicted sclerotic regions, even those that were predicted by the external model, had a significant negative impact on the slope of the estimated glomerular filtration rate after biopsy. This is the first study to demonstrate that the quantified sclerotic regions that are predicted by an automated computational pipeline for the segmentation of the histopathological glomerular components on WSIs impact the prognosis of kidney function in patients with IgAN. [ABSTRACT FROM AUTHOR]

Abstract IgA nephropathy (IgAN) patients often suffer from arterial and/or arteriolar sclerosis (AAS); however, it is unclear whether these features are associated with a poor prognosis. This retrospective cohort study aimed to analyse the prognosis of IgAN patients with AAS and assess whether treatment with renin–angiotensin system inhibitors (RASI) improved their survival. The study included 678 IgAN patients, who were grouped into AAS0 (n = 340; AAS absent) and AAS1 (n = 338; AAS present) groups. Each patient's clinical, laboratory, and histological backgrounds and 20‐year renal prognosis were analysed. In the AAS1 group, the impact of RASI initiated during the follow‐up period on the renal prognosis was also evaluated after adjustments for background characteristics. IgAN patients with AAS had significantly higher age, blood pressure, body mass index, total cholesterol, uric acid levels, and proteinuria than patients without AAS; they also had more severe histological findings, decreased renal function, and lower survival rates than those without AAS (64.0 versus 84.7%, p

Background: The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. Methods: We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. Results: The median age at renal biopsy was 39 years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8 months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5 year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. Conclusion: Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death. [ABSTRACT FROM AUTHOR]

Background Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. Methods We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed. Results Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P < 0.0001). In multivariate Cox analysis, lymphopaenia was an independent risk factor for ESKD [hazard ratio 4.47 (95% confidence interval 2.06–9.72), P < 0.001]. Conclusions Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis. [ABSTRACT FROM AUTHOR]

Background: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. Methods: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. Results: The initial eGFR change was − 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. Conclusions: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan. [ABSTRACT FROM AUTHOR]

Objective To investigate the demographic and clinicopathological features and renal outcomes of Chinese patients with C3 glomerulonephritis in the setting of monoclonal gammopathy. Methods Patients with renal biopsy-proven C3 glomerulonephritis and detectable serum and/or urine monoclonal immunoglobulin from 2006 to 2018 in Peking University First Hospital were included, their clinical data, renal pathology type, treatment, and prognosis were collected and analyzed. Results Nineteen patients were enrolled, accounting for 24% of C3GN patients in the study period. The mean age of onset was 55 years old and the gender ratio was 4/15 (female/male). The mean eGFR at biopsy was 49.55 ± 29.81 ml/min/1.73m2. The prominent clinical manifestations included nephrotic syndrome (58%), anemia (68%), microscopic hematuria and leukocyturia (58%), and hypocomplementemia (13, 68%). The IgG was the most common isotype of monoclonal Ig on immunofixation electrophoresis. Kidney biopsies revealed a relatively prominent MPGN pattern. Only two patients had direct evidence of monocle immunoglobulins acting as C3GN pathogenic factors. Two patients had concurrent TMA-like renal injuries. The median renal survival was 12 and 15 months, respectively in patients receiving conservative therapy and immunosuppressant therapy, without statistical significance. The efficacy of clone-targeted therapy needed further investigation. Plasma exchange therapy only improved one patient’s renal outcome. Conclusions This is the first case series report of C3GN combined with monoclonal Ig in northern China. The renal prognosis of these patients is poor, and immunosuppressant therapies show no advantage over supportive therapy in renal prognosis, while the benefit of clone-targeted chemotherapy is still requiring investigation.

The scoring of crescents (Cs) was recently added to the Oxford classification for IgA nephropathy (IgAN). Because of the short-term use of the C score in clinical practice, its validity and applicability need to be verified. We, retrospectively, analyzed the clinicopathological data of 144 primary IgAN patients diagnosed at our hospital from March 2017 to March 2019 and with complete ≥6-month follow-up data. We found that the C score was positively correlated with the Lee’s classification in the assessment of renal pathological changes and significantly correlated with increased proteinuria and decreased estimated glomerular filtration rate. Univariate Cox regression analysis showed an association of C formation with IgAN prognosis, and multivariate Cox regression indicated Cs as an independent prognosis factor. The optimal proportion of Cs for prognosis prediction by the receiver operating characteristic curve was 11%. Kaplan–Meier survival curve revealed a significantly decreased renal survival rate in patients with C proportions ≥11%. Further multivariate Cox regression analysis confirmed that the C proportion ≥11% is an independent risk factor for poor prognosis of IgAN patients. Our findings demonstrate that Cs are independently related to the prognosis of patients with IgAN, and the proportion of Cs ≥11% is an independent risk factor for poor outcomes. [ABSTRACT FROM AUTHOR]

Background: Despite the high mortality of cardiovascular disease (CVD) in diabetic patients with renal injury, few studies have compared cardiovascular characteristics and outcomes between patients with diabetic nephropathy (DN) and non-diabetic renal disease (NDRD). Methods: A total of 326 type 2 diabetes mellitus patients with renal biopsy were assigned to DN and NDRD groups. Echocardiography and Doppler ultrasound were performed to evaluate left ventricular hypertrophy (LVH) and peripheral atherosclerosis disease (PAD). Renal and cardiovascular survival rates were compared between the DN and NDRD groups by Kaplan-Meier analysis. Risk factors for renal and cardiovascular events in DN patients were identified by a Cox proportional hazards model. Results: In total, 179 patients entered the DN group (54.9%) and 147 made up the NDRD group (45.1%). The presence of diabetic retinopathy, family history of diabetes, and dependence on insulin therapy were associated with the presence of DN. DN patients had more CVD with more severe LVH and PAD. Poorer renal (log-rank χ2 = 26.534, p < 0.001) and cardiovascular (log-rank χ2 = 16.257, p < 0.001) prognoses were seen in the DN group. DR (HR 1.539, 95% CI 1.332–1.842), eGFR (HR 0.943, 95% CI 0.919–0.961), and 24-h proteinuria (HR 1.211, 95% CI 1.132–1.387) were identified as risk factors for renal endpoints. Age (HR 1.672, 95% CI 1.487–1.821), HbA1C (HR 1.398, 95% CI 1.197–1.876), and 24-h proteinuria (HR 1.453, 95% CI 1.289–1.672) were associated with cardiovascular endpoints. Conclusion: Patients with DN had more severe CVD along with poorer renal and cardiovascular prognoses than those with NDRD.

Background Patients with chronic kidney disease (CKD) were excluded in most trials that investigated the effects of urate-lowering agents, such as febuxostat and allopurinol, in hyperuricemic patients. This exclusion leads to uncertainty regarding the efficacy of febuxostat in patients with CKD. Due to the high prevalence of hyperuricemia in patients with CKD, we aimed to assess the effect of febuxostat on improving patient outcomes concerning cardiovascular events and survival compared with those treated with allopurinol among patients with CKD. Methods We conducted a retrospective cohort study using Japanese nationwide administrative data from Jan 1, 2013, to Sep 30, 2020. Patients aged over 60 years diagnosed with CKD were included in this study if they were prescribed either febuxostat or allopurinol. The primary outcome was the occurrence of cardiovascular events including myocardial infarction, stroke, unstable angina requiring urgent revascularization, and all-cause deaths. We estimated hazard ratios (HR) and 95% CI using a Cox proportional hazard regression model adjusted for comorbidities, medications, and laboratory data. We also assessed defined starting kidney replacement therapy as a secondary endpoint treating death as a competing risk using the Fine & Gray regression model. Results A total of 21,015 patients included those with febuxostat (n=17,796) and those with allopurinol (n=3,219). The association between the type of drug and the occurrence of cardiovascular events did not show a significant difference (0.107 vs. 0.116 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.381). Similar results were seen for all-cause deaths (0.060 vs. 0.068 events per patient-year; adjusted HR 0.877, 95% CI: 0.760 to 1.012, P=0.073). Regarding the secondary endpoint, the association between the type of drug and the timing of starting kidney replacement therapy did not show a significant difference (0.118 vs. 0.097 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.425). Conclusion The use of febuxostat was neither associated with a decreased risk of cardiovascular events or deaths nor with the timing of starting kidney replacement therapy compared to the use of allopurinol in patients with CKD., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Ayumi Shintani is compensated by Kyowa Kirin, and the payment is made to the institution. Financial relationships: Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to her. Ayumi Shintani declare(s) personal fees from Eisai. Payment was made to her. Ayumi Shintani declare(s) personal fees from Maruho. Payment was made to her. Ayumi Shintani declare(s) personal fees from Novo Nordisk Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Pfizer. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Torii Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Janssen Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kisei Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mallinckrodt Pharmaceuticals. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mitsubishi Tanabe Pharma Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Shinyaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from Ono Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Merck Biopharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nipro Corporation. Payment was made to her. Yuta Nonomiya declare(s) a grant from Osaka Metropolitan University. An annual fellowship of 3.9 million yen is paid to the author. Yasutaka Ihara declare(s) employment from Daiichi Sankyo. Yasutaka Ihara is an employee of Daiichi Sankyo. Kazuhiko Tsuruya declare(s) a grant from Teijin. Kazuhiko Tsuruya declare(s) a grant from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Teijin. Kazuhiko Tsuruya declare(s) personal fees from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Sanwa Chemical. Kazuhiko Tsuruya declare(s) personal fees from Fuji. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to the institution and to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Shionogi Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Abbvie. Payment was made to her. Ayumi Shintani declare(s) personal fees from Asahi Kasei Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from AstraZeneca plc. Payment was made to her. Ayumi Shintani declare(s) personal fees from Astellas Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bayer Yakuhin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bristol Myers Squibb. Payment was made to her. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Sanofi K.K. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Kayaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from JCR Pharmaceuticals Co. Payment was made to her. Ayumi Shintani declare(s) personal fees from MSD. Payment was made to her. Hisako Yoshida declare(s) personal fees from Organization for Clinical Medicine Promotion. Other relationships: Febuxostat is sold by the following companies, which I declared in the COI: Teijin, DAIICHI SANKYO ESPHA CO., LTD., and NIPRO CORPORATION. Allopurinol is sold by the following companies, which I declared in the COI: NIPRO ES PHARMA and Shionogi Pharma Co. ., (Copyright © 2024, Otani et al.)

Introduction: Anti-GBM diseases with IgA deposition in the mesangial region are rarely described.The factors influencing renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition are unknown., Methods: We searched the pathological reports of the First Affiliated Hospital of Zhengzhou University from 2015 to 2023 and found that a total of 72 patients with the anti-GBM disease and 25 patients combined with mesangial IgA deposition. We studied the clinical and pathological features, renal prognosis, and the factors affecting renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition., Results: Their median age was 44 years, and their age distribution was unimodal. The proportion of oliguria or anuria in patients with anti-GBM disease combined with mesangial IgA deposition was significantly lower than that in patients with classic anti-GBM disease (13.04 vs. 42.31%, p=0.030). Their 24-hour urinary protein excretion was significantly higher [median:3.25 vs. 1.12g/24h, Interquartile range(IQR):1.032~3.945 vs. 0.63~1.79g/24h, p=0.020], serum creatinine (SCr) level at the initial diagnosis was lower(median:456.0 vs. 825.5μmol/L, IQR:270.0~702.0 vs. 515.8~1231.2μmol/L, p=0.002), peak SCr level was lower (median: 601.0 vs. 907.2μmol/L, IQR: 376.5~937.0 vs. 607.0~1361.2μmol/L, p=0.007), and their serum complement 3(C3) level was higher(median: 1.275 vs. 1.015g/L, IQR:1.097~1.462 vs. 0.850~1.220g/L, p=0.027). They had better renal outcomes during follow-up (p<0.001). After adjustment for hypertension, oliguria or anuria, and crescents%, IgA deposition in the mesangial region was still an independent protective factor (p=0.003) for ESRD in anti-GBM patients. Hypertension (p=0.026) and SCr levels at initial diagnosis (p=0.004) were risk factors for renal prognosis in patients with anti-GBM disease combined with mesangial IgA deposition., Discussion: Patients with anti-GBM disease combined with mesangial IgA deposition have less severe renal impairment and better renal prognosis than patients with classic anti-GBM disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ning, Zhao, Liu, Qi and Zhao.)

To investigate the demographic and clinicopathological features and renal outcomes of Chinese patients with C3 glomerulonephritis in the setting of monoclonal gammopathy. Patients with renal biopsy-proven C3 glomerulonephritis and detectable serum and/or urine monoclonal immunoglobulin from 2006 to 2018 in Peking University First Hospital were included, their clinical data, renal pathology type, treatment, and prognosis were collected and analyzed. Nineteen patients were enrolled, accounting for 24% of C3GN patients in the study period. The mean age of onset was 55 years old and the gender ratio was 4/15 (female/male). The mean eGFR at biopsy was 49.55 ± 29.81 ml/min/1.73m2. The prominent clinical manifestations included nephrotic syndrome (58%), anemia (68%), microscopic hematuria and leukocyturia (58%), and hypocomplementemia (13, 68%). The IgG was the most common isotype of monoclonal Ig on immunofixation electrophoresis. Kidney biopsies revealed a relatively prominent MPGN pattern. Only two patients had direct evidence of monocle immunoglobulins acting as C3GN pathogenic factors. Two patients had concurrent TMA-like renal injuries. The median renal survival was 12 and 15 months, respectively in patients receiving conservative therapy and immunosuppressant therapy, without statistical significance. The efficacy of clone-targeted therapy needed further investigation. Plasma exchange therapy only improved one patient's renal outcome. This is the first case series report of C3GN combined with monoclonal Ig in northern China. The renal prognosis of these patients is poor, and immunosuppressant therapies show no advantage over supportive therapy in renal prognosis, while the benefit of clone-targeted chemotherapy is still requiring investigation. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) patients often suffer from arterial and/or arteriolar sclerosis (AAS); however, it is unclear whether these features are associated with a poor prognosis. This retrospective cohort study aimed to analyse the prognosis of IgAN patients with AAS and assess whether treatment with renin–angiotensin system inhibitors (RASI) improved their survival. The study included 678 IgAN patients, who were grouped into AAS0 (n = 340; AAS absent) and AAS1 (n = 338; AAS present) groups. Each patient's clinical, laboratory, and histological backgrounds and 20‐year renal prognosis were analysed. In the AAS1 group, the impact of RASI initiated during the follow‐up period on the renal prognosis was also evaluated after adjustments for background characteristics. IgAN patients with AAS had significantly higher age, blood pressure, body mass index, total cholesterol, uric acid levels, and proteinuria than patients without AAS; they also had more severe histological findings, decreased renal function, and lower survival rates than those without AAS (64.0 versus 84.7%, p < 0.001). Multivariate Cox regression analysis incorporating clinical and histological findings and treatments revealed AAS as an independent factor for disease progression (hazard ratio: 2.23, p = 0.010). Participants in the AAS1 group treated with RASI during follow‐up had a significantly higher renal survival rate than those who were not (75.5 versus 44.3%, p = 0.013). In conclusion, AAS was found to be associated with serious clinical, laboratory, and histological findings and poor prognosis. RASI initiated during the follow‐up period was found to improve renal prognosis. [ABSTRACT FROM AUTHOR]

BackgroundComplex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN.MethodsThis retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of 1 g/day (p < 0.001).ConclusionAn elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.

Background: Novel criteria for the remission of Immunoglobulin A nephropathy (IgAN) based on an opinion survey of Japanese nephrologists and literature review were proposed in 2013. This single-center, longitudinal retrospective cohort study was conducted to validate this criteria. Methods: Present study included the IgAN patients diagnosed between 2001 and 2005 in the Juntendo University Hospital. Remission of hematuria was defined as three consecutive dipstick test results of (−) to (±) or a red blood cell count < 5 in urinary sediment per high-power field during at least 6 months. Remission of proteinuria was defined as three consecutive dipstick results of (−) to (±) during at least 6 months. We categorized four groups according to the remission status which was assessed 2 years after the renal biopsy. The primary outcome was a 50% increase in the serum creatinine over the baseline. We evaluated the slope of eGFR decline (mL/min/1.73 m2/year) and a decrease in the eGFR of 30% from baseline eGFR as the secondary outcome, respectively. Results: A total of 74 patients (male: 47.3%, median age: 30 years) were included and were followed for a median of 86.5 months. During the period, forty-one patients achieved neither remission of proteinuria nor hematuria (NR). Twelve patients met the primary study outcome. A survival analysis revealed that the NR had the worst prognosis and the steepest slope of eGFR decline. Conclusion: Although further validation in a large cohort is necessary, these novel remission criteria for IgAN patients appear to predict the renal prognosis. [ABSTRACT FROM AUTHOR]

Background: Complex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN. Methods: This retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m2 or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan–Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis. Results: The NLR had the highest AUROC, which was 0.633 (p < 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p < 0.001) and 24-hour urine protein (r = 0.18, p < 0.001) and negatively correlated with eGFR (r = 0.14, p < 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan–Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p < 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of >1 g/day (p < 0.001). Conclusion: An elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions. [ABSTRACT FROM AUTHOR]