Acute kidney injury in cancer patients receiving anti-vascular endothelial growth factor monoclonal antibody vs. immune checkpoint inhibitors: a retrospective real-world study.

BACKGROUND: Anti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated. METHODS: Cancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression. RESULTS: A total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P < 0.001). Among 1392 propensity score matched patients, ICIs therapy (n = 696) was associated with an increased risk of sustained AKI events in the entire population (HR 2.0; 95%CI 1.3 to 2.5; P = 0.001) and especially in those with genitourinary cancer (HR 4.2; 95%CI 1.3 to 13.2; P = 0.015). Baseline serum albumin level (> 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P < 0.001). CONCLUSIONS: Among cancer patients in this real-world study, treatment with ICIs increased incidence of sustained AKI in one year. Baseline serum albumin level was an important risk factor for sustained AKI. The risk factors for sustained AKI differed between the anti-VEGF group and the ICIs group. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT06119347) on 11/06/2023.

Efficacy and safety of belimumab in patients with lupus nephritis: a real-world retrospective observational study.

OBJECTIVES: To evaluate the differences in efficacy and safety between Lupus Nephritis (LN) patients who received belimumab plus standard therapy and those who received only standard therapy in real world practice. METHODS: Patients diagnosed with LN at the First Affiliated Hospital of Wenzhou Medical University from November 2012 to July 2023 were identified, and eligible cases were divided into two groups according to whether they received additional treatment with belimumab during the course of the disease. RESULTS: A total of 1,169 LN patients were identified from our follow-up database. 112 patients receiving add-on treatment with belimumab (BLM group) and 112 control patients matched for relevant baseline characteristics were enrolled in this study. The median duration of treatment with belimumab was 13.82 [7.24, 20.29] months. Compared with the control group, the BLM group had more significant improvement in disease activity indicators such as serum albumin and complement levels, significantly lower B cell count, immunoglobulin, and earlier first attainment of renal remission, but there was no significant improvement in renal function and kidney-related events or death during the 2-year follow-up period. In the BLM group, the treatment effect of belimumab was more prominent in patients with lower levels of proteinuria. The safety profile of belimumab treatment was favorable, with a lower incidence of respiratory tract infection in the BLM group than in the control group during the follow-up period (p= 0.015). CONCLUSIONS: This real-world study revealed that add-on treatment with belimumab provided better disease remission, and the therapeutic effect was more significant in patients with lower proteinuria levels. In addition, it had a favorable safety profile and reduced the risk of respiratory tract infection.

Clinical significance of massive proteinuria in primary IgA nephropathy with and without nephrotic syndrome: a single center cohort study.

BACKGROUND: Both primary IgA nephropathy (IgAN) with and without nephrotic syndrome (NS) can present massive proteinuria (24-h urinary protein ≥3.5 g/d). The clinical significance of massive proteinuria may be different in the two entities and needs further research. METHODS: Data of 1870 patients with biopsy-proven IgAN in our hospital from January 2011 to December 2022 was retrospectively reviewed. A total of 242 IgAN patients with massive proteinuria were enrolled. Patients who presented with nephrotic syndrome at renal biopsy were included in the IgAN with NS cohort (IgAN-NS). The IgAN with nephrotic-range proteinuria cohort (IgAN-NR) consisted of 1:1 matched cases from the remaining according to age, gender, estimated glomerular filtration rate (eGFR) at baseline, and follow-up time. The clinical and pathological characteristics between the two cohorts were analyzed. RESULTS: The IgAN-NS had a significantly higher proteinuria level than the IgAN-NR (p < .001). Cluster analysis revealed that proteinuria was associated with lipids in IgAN-NS, while it was associated with inflammatory indicators in IgAN-NR. When the complete remission of proteinuria (CR) was not achieved, the Kaplan-Meier analysis showed the prognosis of IgAN-NS was significantly worse than that of IgAN-NR (p = .04). Then, our GLMM model and line chart showed that the serum albumin level of the IgAN-NR was always evidently higher than that of the IgAN-NS while the significant difference in urinary albumin/creatinine ratio between the two cohorts gradually disappeared during the short-term follow-up (1 year). Moreover, the Cox regression analysis showed that the increased serum albumin was an independent protective factor for the poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD]). CONCLUSION: The IgAN-NS had poorer clinicopathologic manifestation than IgAN-NR, including severer massive proteinuria. When the CR was not achieved, the prognosis of IgAN-NS was inferior to that of the IgAN-NR.

Clinical Significance of Persistent Hematuria Degrees in Primary IgA Nephropathy: A Propensity Score-Matched Analysis of a 10-Year Follow-Up Cohort.

INTRODUCTION: The clinical significance of persistent hematuria degrees has not been expounded in primary IgA nephropathy (IgAN) and requires further research. METHODS: From January 2003 to May 2022, a total of 684 IgAN patients with persistent hematuria were enrolled to conduct a retrospective single-center study. Patients whose hematuria degree at baseline was higher than the second tertiles of the whole were included in the high-degree hematuria cohort (Hh), and the low-degree hematuria cohort (Lh) was constructed with 1:1 matched cases from the rest according to age, gender, and estimated glomerular filtration rate (eGFR) at baseline and follow-up time. Survival was determined using the Kaplan-Meier method (K-M) and generalized linear mixed-effects model (GLMM). Risk factors for survival were determined according to the Cox proportional hazards model. RESULTS: Both the Hh and Lh consisted of 228 cases. While the demographic data and the renal function at baseline were matched, both the K-M (p = 0.02) and GLMM (p = 0.04) proved that the prognosis of the Hh was significantly worse than that of the Lh within 10 years of follow-up. The higher persistent hematuria degree was an independent risk factor (3.93; 95% confidence interval, 1.33-11.6) associated with reaching the endpoint (eGFR decreased from the baseline ≥30% continuously or reached end-stage renal disease [ESRD]). The Hh had a significantly higher proportion of crescent (p = 0.003). The prognosis of the Hh was significantly worse than that of the Lh when accompanied by the crescent and presented an indistinct difference if the crescent was absent. CONCLUSIONS: The clinicopathologic manifestation of IgAN patients with persistent high-degree hematuria was severer, and the prognosis was worse than those with persistent low-degree hematuria.

Pneumocystis pneumonia in patients with primary nephrotic syndrome.

OBJECTIVE: The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed Pneumocystis pneumonia (PCP). MATERIALS AND METHODS: We systematically reviewed medical records from 18 PNS patients with PCP admitted to our hospital from April 2007 to April 2019. A total of 180 cases were randomly selected as controls from PNS inpatients without infection. RESULTS: In PCP patients, the mean age at presentation was 48.5 years, mean duration of prednisone treatment was 3.7 months, and mean prednisone dose on admission was 31.3 mg/d. Eight patients (44.4%) had coexisting infections, most often was Cytomegalovirus (4 patients); 11 patients (61.1%) had ICU admission, and 9 patients (50%) had mechanical ventilation. PCP patients had more prednisone, more immunosuppressive therapy, lower CD4+ cell counts and hemoglobin, and higher serum creatinine than those without infections (p < 0.05). All patients survived after treatment. CONCLUSION: PCP was not unusual in PNS patients, and the most important risk factors were prednisone usage, other immunosuppressive therapy, and a lower CD4+ cell count; however, these patients had a good outcome after sufficient treatment.

Prediction of premature all-cause mortality in patients receiving peritoneal dialysis using modified artificial neural networks.

Premature all-cause mortality is high in patients receiving peritoneal dialysis (PD). The accurate and early prediction of mortality is critical and difficult. Three prediction models, the logistic regression (LR) model, artificial neural network (ANN) classic model and a new structured ANN model (ANN mixed model), were constructed and evaluated using a receiver operating characteristic (ROC) curve analysis. The permutation feature importance was used to interpret the important features in the ANN models. Eight hundred fifty-nine patients were enrolled in the study. The LR model performed slightly better than the other two ANN models on the test dataset; however, in the total dataset, the ANN models fit much better. The ANN mixed model showed the best prediction performance, with area under the ROC curves (AUROCs) of 0.8 and 0.79 for the 6-month and 12-month datasets. Our study showed that age, diastolic blood pressure (DBP), and low-density lipoprotein cholesterol (LDL-c) levels were common risk factors for premature mortality in patients receiving PD. Our ANN mixed model had incomparable advantages in fitting the overall data characteristics, and age is a steady risk factor for premature mortality in patients undergoing PD. Otherwise, DBP and LDL-c levels should receive more attention for all-cause mortality during follow-up.

Association of antiphospholipid antibodies with clinical activity and renal pathological activity in patients with lupus nephritis.

OBJECTIVES: This study aimed to investigate the association of antiphospholipid antibodies (aPL) with clinical activity and renal pathological activity in patients with lupus nephritis (LN). METHODS: Levels of anticardiolipin () antibodies, anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies and lupus anticoagulant (LAC) were measured, and other clinical and pathological data were also obtained during the same period before renal biopsy. RESULTS: A total of 83 patients with LN were included in this study, 40 patients (48.2%) in the s positive group and 43 patients in the aPL negative group. LN patients with positive aPL had significantly higher SLEDAI (p = 0.012), more hematuria (p = 0.043), lower serum C3 (p = 0.003) and C4 (p = 0.014), and a higher pathological activity index (p = 0.012), more micro-thrombosis (p = 0.046) and more C3 deposits (p = 0.038) in the glomerulus than patients with negative aPL The level of IgG- was significantly correlated with SLEDAI and serum level of C3 (r = 0.44, p < 0.001; r = -0.39, p = 0.003, respectively). The level of IgM- was significantly correlated with SLEDAI, and serum levels of C3 and C4 (r = 0.27, p = 0.014; r = -0.22, p = 0.041; r = -0.23, p = 0.035, respectively). CONCLUSIONS: Our work suggests that aPL, especially, are correlated with both clinical activity and renal pathological activity in patients with LN.

Tuberculosis spondylitis in patients on hemodialysis: Clinical features, risk factors, and outcomes in 12 patients.

The aim of this study was to investigate the clinical features, risk factors and outcomes of tuberculosis spondylitis (TBS) in patients on hemodialysis (HD). We systematically reviewed medical records from 12 HD patients with TBS admitted to our hospital from April 2008 to April 2018. A total of 120 age- and sex-matched HD patients without infections were randomly selected as controls. The incidence of TBS in our patient group was 1.5/1000 per year. The average duration from initial symptoms to diagnosis was 45.4 days (range, 11-180 days). Neurosurgery was performed in 4 (33.3%) patients. TBS was cured or improved in 11 (91.7%) patients. HD patients with TBS had significantly lower albumin and Hb levels than controls (P = .03 and P = .01). These findings indicated that lower albumin and Hb levels were possible risk factors for TBS in patients on HD, most HD patients with TBS had a good outcome after anti-TB therapy with or without surgery.

Predictors of renal outcomes in crescentic and mixed class of ANCA-associated glomerulonephritis.

BACKGROUND: The aim of this study was to investigate the predictors of renal outcomes in crescentic and mixed class of ANCA-associated glomerulonephritis. MATERIALS AND METHODS: We systematically reviewed the medical records of patients with ANCA-associated glomerulonephritis admitted to our hospital from December 2008 to December 2018, and found 30 patients with crescentic and 40 patients with mixed ANCA-associated glomerulonephritis. RESULTS: End-stage renal disease developed in 33.3 and 25% patients over a median follow-up of 45.1 and 46.7 months in the crescentic and mixed group, respectively. There was no significant difference in renal survival rates between the two histological subgroups (log-rank p = 0.558). In the Cox regression model, old age, lower estimated glomerular filtration rate (eGFR), lower normal glomeruli ratio, and a higher tubular atrophy and interstitial fibrosis ratio were significantly associated end-stage renal disease (p < 0.05 for all). Among our patients, 17.1% were at low risk, 57.1% were at medium risk, and 25.7% were at high risk according to antineutrophil cytoplasmic antibody renal risk score and end-stage renal disease developed in 8.3, 40, and 66.7%, respectively (p = 0.024). CONCLUSION: These findings indicated that the renal risk score was a better prognostic tool than Berden's classification in a cohort with crescentic and mixed histologic categories.

TCONS_00483150 as a novel diagnostic biomarker of systemic lupus erythematosus.

Aim: We aimed to identify differentially expressed Long noncoding RNAs (lncRNAs) and explore their functional roles in systemic lupus erythematosus (SLE). Materials & methods: We identified dysregulated lncRNAs and investigated their prognostic values and potential functions using MiRTarget2, catRAPID omics and Bedtools/blast/Pearson analyses. Results: Among the 143 differentially expressed lncRNAs, TCONS_00483150 could be used to distinguish patients with SLE from healthy controls and those with rheumatoid arthritis and patients with active/stable SLE from healthy controls. TCONS_00483150 was significantly correlated with anti-Rib-P antibody positivity and low C3 levels; TCONS_00483150 dysregulation might contribute to the metabolism of RNA and proteins in SLE patients. Conclusion: Overall, our findings offer a transcriptome-wide overview of aberrantly expressed lncRNAs in patients with SLE and highlight TCONS_00483150 as a potential novel diagnostic biomarker.

Clinical features, risk factors, and outcomes of septic arthritis in patients on maintenance hemodialysis.

The aim of this study was to investigate the clinical features, risk factors, and outcomes of septic arthritis in patients on maintenance hemodialysis (HD). We systematically reviewed medical records of 16 HD patients with septic arthritis admitted to our hospital from April 2008 to April 2018. A total of 16 HD in patients with bloodstream infection but without septic arthritis were randomly selected as controls. The incidence of septic arthritis in our patient group was 0.2% per year. Organisms isolated were Staphylococcus aureus in 11 (68.7%), Gram-negative bacilli in 3, streptococci in 1, and fungi in 1. Patients with septic arthritis were significantly older (72.7 ± 9.4 vs 63.5 ± 8.7 years, p = 0.035) and had more joint diseases (62.5% vs 12.5%, p = 0.003) and a longer duration of hospitalization (35.2 ± 5.7 vs 22.1 ± 3.5 days, p = 0.021) than the control group. In a logistic regression analysis, patients with older age and more joint diseases were more likely to have septic arthritis compared with controls (OR = 1.39, p = 0.024 and OR = 3.24, p = 0.003, respectively). These findings indicate that old age and joint diseases (osteoarthritis or inflammatory arthritis) were independent risk factors for septic arthritis in patients on HD when bloodstream infection occurred. Key Points • Patients with septic arthritis were significantly older and had more joint diseases than the control group. • Old age and joint diseases are independent risk factors for septic arthritis in patients on HD when bloodstream infection occurs.

Effects of parathyroid hormone and vitamin D supplementation on stroke among patients receiving peritoneal dialysis.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) patients have a high incidence of stroke and commonly have increased parathyroid hormone levels and vitamin D insufficiency. We seek to investigate the incidence of stroke and the role of parathyroid hormone and vitamin D supplementation in stroke risk among CAPD patients. METHODS: This study employed a retrospective design. We enrolled a Chinese cohort of 980 CAPD patients who were routinely followed in our department. The demographic and clinical data were recorded at the time of initial CAPD and during follow-up. The included patients were separated into non-stroke and stroke groups. The effects of parathyroid hormone and vitamin D supplementation on stroke in CAPD patients was evaluated. The primary endpoint is defined as the first occurrence of stroke, and composite endpoint events are defined as death or switch to hemodialysis during follow-up. RESULTS: A total of 757 eligible CAPD patients with a mean follow-up time of 54.7 (standard deviation, 33) months were included in the study. The median incidence of stroke among our CAPD patients was 18.9 (interquartile range, 15.7-22.1) per 1000 person-years. A significant nonlinear correlation between baseline iPTH and hazard of stroke (p-value of linear association = 0.2 and nonlinear association = 0.002) was observed in our univariate Cox regression analysis, and low baseline iPTH levels (≤150 pg/ml) were associated with an increased cumulative hazard of stroke. Multivariate Cox regression analysis indicated a significant interaction effect between age and iPTH after adjusting for other confounders. Vitamin D supplementation during follow-up was a predictive factor for stroke in our cohort. CONCLUSIONS: CAPD patients suffered a high risk of stroke, and lower iPTH levels were significantly correlated with an increased risk of stroke. Nevertheless, vitamin D supplementation may reduce the risk of stroke in these patients.

Serum uric acid is an independent predictor of renal outcomes in patients with idiopathic membranous nephropathy.

PURPOSE: Accumulating evidence suggests that a relationship exists between serum uric acid (UA) and the progression of chronic kidney disease (CKD), but information regarding idiopathic membranous nephropathy (IMN) is limited. METHODS: Patients with renal biopsy-confirmed diagnosis of IMN between 2009 and 2017 were identified. The demographic and clinical data recorded at the time of renal biopsy were considered the baseline values. The included cases were separated into three groups based on tertiles of the baseline serum UA level, and the relationship between serum UA and poor renal outcome was investigated by receiver operating characteristic (ROC) and time-event analyses. The primary endpoint was poor renal outcome, which was defined as a decrease in the estimated glomerular filtration rate to 50% of the baseline level or progression to end-stage renal disease during the follow-up. RESULTS: Of 989 cases, 572 eligible patients were included. During a median of 18 months of follow-up, 45 (7.9%) patients progressed to the primary endpoint. Both baseline serum UA and time-averaged UA levels could be used for discrimination of renal outcomes, but the difference was not significant (p value = 0.6). Our Cox regression analysis further demonstrated that baseline serum UA was an independent predictor of poor renal outcome in IMN patients, and subgroup analysis revealed a gender difference in the predictive effect of serum UA. CONCLUSIONS: Our study demonstrated that baseline serum UA was an independent predictor of poor renal outcome in patients with IMN, and a gender difference in the predictive effect was observed in our cohort.

MicroRNA-155 Mediates Obesity-Induced Renal Inflammation and Dysfunction.

Chronic inflammation is a major contributor to obesity-related renal damage. Recent studies have demonstrated that microRNA (miR)-155 is closely associated with hyperglycemia-induced nephropathy, but whether renal miR-155 participates in the inflammatory response and development of obesity-related nephropathy is unknown. In present study, we investigated the pathophysiological role of renal miR-155 in palmitic acid (PA)-treated endothelial cell and high-fat-diet (HFD)-fed mouse models by specific miR-155 sponge. Mice fed with HFD exhibited higher levels of renal miR-155, which positively correlated with urine microalbumin and blood urea nitrogen. In vitro study, mouse renal vascular endothelial cells stimulated with PA also showed higher miR-155 levels, accompanied with increased inflammatory response. Suppression of renal miR-155 effectively attenuated HFD-induced renal structural damages and dysfunction. MiR-155 sponge treatment also significantly decreased NF-κB signaling and downstream gene expression in vitro and in vivo. The obesity-increased macrophage infiltration and lipotoxicity was decreased in mouse kidney after miR-155 sponge treatment. Mechanistically, miR-155 directly targeted 3'-UTR of SHIP1/INPP5D and suppressed its expression in vitro and in vivo, whereas silence of SHIP1/INPP5D abolished the renal protective benefits of miR-155 sponge in obese mice. Taken together, present findings for the first time provided evidence for the potential role of miR-155 in obesity-related nephropathy and clarified that SHIP1/NF-κB signaling was a potential molecular mechanism.

microRNA-199a may be involved in the pathogenesis of lupus nephritis via modulating the activation of NF-κB by targeting Klotho.

Klotho is considered to have renal protective effect by prohibiting the activation of the nuclear factor (NF)-κB pathway, while the role of microRNA-199a (miR-199a)/Klotho in lupus nephritis (LN) is still unknown. A single dose of pristane (0.5 ml) was intraperitoneally injected into 8 weeks-old female mice to establish the LN model. MiR-199a mimic or miR-199a inhibitor, Klotho plasmid or Klotho siRNA, and miR-199a inhibitor plus si-Klotho were transfected into lipopolysaccharides (LPS) stimulated human embryonic kidney 293 T (HEK293 T) cells. Western Blot was adopted to measure p-P65 expression. Tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in the supernatant were determined by enzyme-linked immunosorbent assay (ELISA). The expression of Klotho was suppressed by miR-199a through direct binding to the three prime untranslated regions (3'-UTR). The high miR-199a level was accompanied by low Klotho expression in the LN kidney. MiR-199a promoted LPS-induced NF-κB activation and improved the secretion of TNF-α and IL-1ß by regulation of Klotho in HEK293 T cells. If miR-199a antagomir was administrated after 48 h of pristane administration, the expression of p-P65 and the secretion of TNF-α and IL-1ß were significantly down-regulated in LN kidney. Although the direct involvement and detailed mechanism of miR-199a in LN still need further investigation, our data show that MiR-199a could regulate the activation of NF-κB by directly targeting Klotho.

Icariin alleviates murine lupus nephritis via inhibiting NF-κB activation pathway and NLRP3 inflammasome.

AIMS: Lupus nephritis (LN) is a kidney inflammatory disease caused by systemic lupus erythematosus (SLE). Both NF-κB activation and NLRP3 inflammasome activation are implicated in LN pathogenesis, suggesting they are potential targets for LN treatment. Icariin, which is isolated from Chinese medicine Horny Goat Weed (Ying Yang Huo), has been shown to have anti-inflammation activity, and inhibit activations of both NF-κB and NLRP3 inflammasome. In present study, the effects of icariin on LN were evaluated in MRL/lpr mice. MAIN METHODS: We treated MRL/lpr mice with icariin for 8 weeks and then analyzed the renal function and kidney pathology. We monitored the levels of anti-dsDNA antibody and the deposition of immune complex after icariin treatment. We also detected the macrophage infiltration, NF-κB activation, NLRP3 inflammasome activation and inflammatory cytokine TNF-α production in MRL/lpr mice after icariin treatment. KEY FINDINGS: We found that MRL/lpr mice treated with icariin displayed significantly attenuated the renal disease. Icariin-treated mice showed significantly reduced serum anti-dsDNA antibody level and immune complex deposition. Icariin inhibited NF-κB activation and TNF-α production in MRL/lpr mice. Icariin inhibited CCL2 production and macrophage infiltration in MRL/lpr mice. Finally, icariin suppressed NLRP3 inflammasome activation and IL-1ß production in MRL/lpr mice. SIGNIFICANCE: Icariin alleviated murine lupus nephritis via inhibiting NF-κB activation and NLRP3 inflammasome activation.

Serum C3/C4 ratio is a novel predictor of renal prognosis in patients with IgA nephropathy: a retrospective study.

IgA nephropathy (IgAN) is an autoimmune disease associated with complement activation. It is unclear whether the ratio of serum C3 and C4 concentrations (C3/C4 ratio) can predict renal outcomes in IgAN patients. A total of 1503 patients diagnosed with IgAN via renal biopsy were recorded in this study. Poor renal outcomes were defined as > 50% decrease in the baseline estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD) during follow-up. In total, 712 patients meeting the exclusion/inclusion criteria were selected, and the mean follow-up period was 40.6 (12.34) months. Patients with decreased C3/C4 ratios displayed significantly more severe clinical characteristics and renal pathological features and a higher proportion of poor renal outcomes and ESRD. The optimal multivariate Cox regression models identified the C3/C4 ratio (hazard ratio (HR) 0.63, 95% CI 0.5-0.9), serum uric acid (HR 1.58, 95% CI 1.2-2.2), serum creatinine (HR 1.3, 95% CI 1.1-1.6), systolic blood pressure (HR 1.57, 95% CI 1.2-2.0) and T score (relative to T0, T1: HR 1.96, 95% CI 1.1-3.7, T2: HR 3.03, 95% CI 1.6-5.9) as strong predictors of poor renal outcomes. Subgroup analysis showed that patients with low C3/C4 ratios benefited from glucocorticoids or other immunosuppressive agents (hazard ratio 0.30 and 0.18, 95% CI 0.13-0.72 and 0.07-0.46, respectively). Serum C3/C4 ratios may be an independent novel predictor of renal outcomes in IgAN patients. Decreased C3/C4 ratios suggest poor renal outcomes and the potential to benefit from aggressive immunosuppressive therapies.

Renal outcomes in primary IgA nephropathy patients with segmental glomerular necrosis: a case-control study.

The renal prognosis and treatment of primary IgA nephropathy (IgAN) patients with segmental glomerular necrosis (SGN) remain controversial. Patients with primary IgAN confirmed by renal biopsy were enrolled. Patients with SGN on renal biopsy were selected as the necrosis group, and a propensity score matching method was used to match a control group according to age, gender, weight, height and follow-up time. A total of 825 IgAN patients were enrolled in the present study. Seventy-three (8.8%) patients with SGN were selected as the necrosis group, and 292 patients without SGN were matched as the control group. Compared to the control group, a significantly increased serum fibrinogen level (3.97 g/L vs 3.54 g/L, P=.002) and proportion of patients with macroscopic hematuria (35.6% vs 14.7%, P<.001) was observed in the necrosis group. According to the new IgA pathological classification system, crescent formation was more pronounced in the necrosis group (P=.001). The average estimated glomerular filtration rate was obviously higher in the necrosis group and decreased more slowly during follow-up. However, the time-averaged urine protein-to-creatinine ratio remained low in the necrotic group, whereas it gradually increased in the control group. SGN suggests an active renal inflammatory state, but it was not an independent risk factor for a poor renal outcome in patients treated with immunosuppressive therapy. Furthermore, patients with SGN had a more stable renal function and low urinary protein excretion during follow-up, which may be attributable to aggressive immunotherapy.

Elevated serum fibrinogen level is an independent risk factor for IgA nephropathy.

BACKGROUND: IgA nephropathy is a primary cause of renal failure, and inflammation and renal fibrosis are the main mechanisms leading to kidney damage. The serum fibrinogen level is closely related to inflammatory states, but its relationship to the prognosis of IgA nephropathy (IgAN) is unclear. MATERIALS AND METHODS: 1053 patients diagnosed with IgAN after renal biopsy were enrolled from two Nephrology Departments. Demographic and clinical data and histopathological features were collected. The patients were divided into four groups (Q1-Q4) according to the serum fibrinogen levels at the time of renal biopsy, and the relationships of serum fibrinogen levels with other risk factors and the prognosis of IgAN were investigated. RESULTS: 672 patients with proven primary IgAN were included in this study, which included a median follow-up of 36 months. Patients with higher serum fibrinogen levels had elevated serum creatinine levels, 24-hour urinary protein, and blood pressure compared with patients with the lowest levels of serum fibrinogen as well as severe renal damage at the time of renal biopsy. Univariate and multivariate Cox regression analyses confirmed that the serum fibrinogen level at the time of renal biopsy was significantly related to the prognosis of patients with IgAN. CONCLUSIONS: In patients with IgAN, an elevated serum fibrinogen level at the time of renal biopsy is associated with poor renal outcomes, which suggests the need for more aggressive early interventions. Greater benefits of aggressive treatments were observed in patients with higher serum fibrinogen levels.

A microrna screen to identify regulators of peritoneal fibrosis in a rat model of peritoneal dialysis.

BACKGROUND: Peritoneal fibrosis is a common complication in patients treated with long-term peritoneal dialysis. The aim of this study was to identify the microRNAs (miRNAs) involved in regulation of peritoneal fibrosis in a rat model of peritoneal dialysis. METHODS: Twenty-four Sprague-Dawley (SD) rats were randomly allocated into three groups: (i) Control group (Cg, n = 8); (ii) Saline group (Sg, n = 8): daily intraperitoneal injection with 0.9% normal saline; (iii) Hypertonic dialysate group (HDg, n = 8): daily intraperitoneal injection with 4.25% peritoneal dialysis solution. Rats were sacrificed after four weeks for histological evaluation of peritoneal membrane and the expression of α-SMA and COL-1. A miRNA screen was performed using microarray analysis to identify differentially expressed miRNAs, which were then validated by real-time PCR. RESULTS: Compared with the control and the saline groups, hypertonic dialysate group showed impaired peritoneal function accompanied by a spectrum of morphological changes including thicker peritoneal membrane, higher collagen deposition, infiltration of mononuclear cells and neovascularization in the peritoneum. Increased mRNA and protein levels of α-SMA and COL-1 were observed in hypertonic dialysate group, indicating the progression of peritoneal fibrosis. The miRNA screen identified 8 significantly down-regulated miRNAs (miR-31, miR-93, miR-100, miR-152, miR-497, miR-192, miR-194 and miR-200b) and one highly up-regulated miRNA (miR-122) in the hypertonic dialysate group. The results were confirmed by real-time PCR. CONCLUSIONS: Altered miRNA expression in peritoneum was found in the rat model of peritoneal fibrosis, indicating that these miRNAs may be associated with pathogenesis of peritoneal fibrosis.