Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy.

BACKGROUND: Immunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients. METHODS: This was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People's Hospital and Hechi People's Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used. RESULTS: After propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p < 0.01). Separately, the effect was significant in moderate- and high-risk but not in low-risk patients. Key influencing factors including age, blood pressure, albumin and total cholesterol levels, with slight differences among patients at different risk. CONCLUSIONS: This study demonstrates the efficacy of immunosuppressive therapy in non-low-risk PMN patients. The key factors affecting renal prognosis in patients with different risk levels are emphasized to help provide individualized treatment.

Inverse relationship between LDL-C/HDL-C ratio and atrial fibrillation in chronic kidney disease patients.

Atrial fibrillation (AF) is more prevalent in individuals with chronic kidney disease (CKD) compared to the general population. While a potential inverse correlation between lipid levels and AF has been proposed, it remains unclear if this relationship applies to CKD patients. This study examined the connection between the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) and the likelihood of AF in CKD patients. Data was gathered from 21,091 consecutive CKD patients between 2006 and December 31, 2015. We examined the link between the LDL-C/HDL-C ratio and AF in CKD patients through binary logistic regression, as well as various sensitivity and subgroup analyses. The dataset that backs up these analyses is available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230189 . Of the 21,091 CKD patients, 211 (1.00%) were diagnosed with AF. The cohort, predominantly male (79.93%), had a mean age of 60.89 ± 10.05 years. The mean LDL-C/HDL-C ratio was 1.39 ± 0.35. After adjusting for covariates, a significant inverse association was observed between the LDL-C/HDL-C ratio and the incidence of AF in CKD patients (OR = 0.422, 95% CI 0.273-0.652, P = 0.00010). The robustness of these findings was confirmed through sensitivity analysis. Subgroup analysis revealed a strong correlation between the LDL-C/HDL-C ratio and incident AF in patients without hypertension (HR = 0.26, 95% CI 0.15-0.45). Conversely, this association was absent in hypertensive patients (HR = 1.09, 95% CI 0.54-2.17). Our research shows an independent inverse correlation between the LDL-C/HDL-C ratio and the risk of AF in CKD patients. It is advised to refrain from excessively aggressive reduction of LDL levels in CKD patients, as this could elevate the risk of developing AF.

Defining the threshold: triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio's non-linear impact on tubular atrophy in primary membranous nephropathy.

Background: Hyperlipidemia is common in primary membranous nephropathy (PMN) patients, and tubular atrophy (TA) is an unfavorable prognostic factor. However, the correlation between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and TA is controversial. Therefore, our study aimed to investigate the association between the TG/HDL-C ratio and TA in PMN patients. Methods: We conducted a cross-sectional study and collected data from 363 PMN patients at Shenzhen Second People's Hospital from January 2008 to April 2023. The primary objective was to evaluate the independent correlation between the TG/HDL-C ratio and TA using binary logistic regression model. We used a generalized additive model along with smooth curve fitting and multiple sensitivity analyses to explore the relationship between these variables. Additionally, subgroup analyses were conducted to delve deeper into the results. Results: Of the 363 PMN patients, 75 had TA (20.66%). The study population had a mean age of 46.598 ± 14.462 years, with 217 (59.78%) being male. After adjusting for sex, age, BMI, hypertension, history of diabetes, smoking, alcohol consumption, UPRO, eGFR, HB, FPG, and ALB, we found that the TG/HDL-C ratio was an independent risk factor for TA in PMN patients (OR=1.29, 95% CI: 1.04, 1.61, P=0.0213). A non-linear correlation was observed between the TG/HDL-C ratio and TA, with an inflection point at 4.25. The odds ratios (OR) on the left and right sides of this inflection point were 1.56 (95% CI: 1.17, 2.07) and 0.25 (95% CI: 0.04, 1.54), respectively. Sensitivity analysis confirmed these results. Subgroup analysis showed a consistent association between the TG/HDL-C ratio and TA, implying that factors such as gender, BMI, age, UPRO, ALB, hypertension and severe nephrotic syndrome had negligible effects on the link between the TG/HDL-C ratio and TA. Conclusion: Our study demonstrates a non-linear positive correlation between the TG/HDL-C ratio and the risk of TA in PMN patients, independent of other factors. Specifically, the association is more pronounced when the ratio falls below 4.25. Based on our findings, it would be advisable to decrease the TG/HDL-C ratio below the inflection point in PMN patients as part of treatment strategies.

Correlation Analysis between Intrarenal Small Artery Intimal Thickening and Clinicopathological Features and Prognosis in Primary Membranous Nephropathy Patients.

BACKGROUND: Primary membranous nephropathy (PMN) is the most common pathological type of nephrotic syndrome in adults. Intrarenal small artery intimal thickening can be observed in most renal biopsies. The purpose of this study was to investigate the association between intrarenal small artery intimal thickening and clinicopathological features and prognosis in PMN patients. METHODS: Data were continuously collected from patients who were diagnosed with PMN in Shenzhen Second People's Hospital (The First Affiliated Hospital of Shenzhen University) from 2008 to 2021 for a retrospective cohort study. Regression analysis and survival analysis were used to analyze the relationship between intrarenal small artery intimal thickening and renal prognosis in PMN patients. RESULTS: 300 PMN patients were enrolled in this study, including 165 patients (55%) with intrarenal small artery intimal thickening. Patients with intimal thickening were older, with higher BMI, systolic blood pressure and diastolic blood pressure, serum uric acid, a higher proportion of hypertension, acute kidney injury, nephrotic syndrome, more urine protein, and lower eGFR. Multivariate Cox regression analysis showed that after adjusting for age, gender, hypertension, BMI, urine protein, eGFR, and the use of ACEI/ARB and hormone immunosuppressants, intimal thickening was a risk factor for renal prognosis in PMN patients (HR = 3.68, 95% CI 1.36-9.96, p < 0.05). Kaplan-Meier survival curve analysis showed that the incidence of reaching the renal composite outcome was higher in the intimal thickening group (p < 0.05). CONCLUSION: The prognosis of PMN patients with intrarenal small artery intimal thickening is worse, so early intervention is very important for these patients.

Triglyceride: A mediator of the association between waist-to-height ratio and non-alcoholic fatty liver disease: A second analysis of a population-based study.

Objective: Increasing evidence suggests that an increased waist-to-height ratio (WHtR) may increase the risk of non-alcoholic fatty liver disease (NAFLD). Whether this association is due to WHtR itself or mediated by WHtR-associated increases in triglyceride (TG) is uncertain. On that account, our research aims to disentangle these relationships. Methods: In this cross-sectional study, 14251 participants who participated in the medical examination program were consecutively and non-selectively collected in Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables were WHtR and NAFLD, respectively. Triglyceride was the mediating factor. The correlation between WHtR, TG, and NAFLD risk factors was examined using spearman correlation analysis. The association between WHtR or TG and NAFLD was examined using multiple logistic regression. In order to determine whether TG mediated the association between WHtR and NAFLD, a mediation analysis was performed. Results: The mean age of the included individuals was 43.53 ± 8.89 years old, and 7411 (52.00%) were male. The mean WHtR and TG were 0.46 ± 0.05, 0.89 ± 0.63, respectively. The prevalence rate of NAFLD was 2507 (17.59%). Individuals with NAFLD had significantly higher levels of WHtR and TG than those without NAFLD (P<0.05). After adjusting covariates, the multivariate linear regression analysis showed that WHtR was positively associated with TG. That was, for every 0.1 increase in WHtR, TG increased by 0.226mmol/L (ß=0.226, 95%CI: 0.206, 0.247). Multiple logistic regression analysis indicated that WHtR (OR=8.743, 95%CI: 7.528, 10.153) and TG (OR=1.897, 95%CI: 1.732, 2.078) were positively associated with NAFLD. The mediation analysis showed that WHtR had a direct, significant effect on NAFLD (ß=0.139, 95%CI: 0.126, 0.148), and TG partially mediated the indirect effect of WHtR on NAFLD (ß=0.016, 95% CI: 0.013-0.019). TG contributed to 10.41% of WHtR-related NAFLD development. Conclusion: Findings suggest a mediation link between WHtR and TG and the risk of NAFLD. The significance of TG as a mediator deserves recognition and consideration.

Elevated gamma-glutamyl transferase to high-density lipoprotein cholesterol ratio has a non-linear association with incident diabetes mellitus: A second analysis of a cohort study.

OBJECTIVE: Evidence regarding the association between the GGT/HDL-c ratio and incident diabetes is still limited. On that account, our research aims to survey the link of the GGT/HDL-c ratio with the risk of diabetes. METHODS: In this retrospective cohort study, data of 15,171 participants who participated in the medical examination program were collected in Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables were the baseline GGT/HDL-c ratio and diabetes during the follow-up, respectively. The Cox proportional-hazards regression model was used to explore the association between the GGT/HDL-c ratio and diabetes risk. A Cox proportional hazards regression with the cubic spline smoothing was used to recognize non-linear relationships between the GGT/HDL-c ratio and incident diabetes. RESULTS: After adjusting covariates, the results showed that the GGT/HDL-c ratio was positively associated with incident diabetes (HR = 1.013, 95% CI: 1.002, 1.024). There was also a non-linear relationship between the GGT/HDL-c ratio and the risk of diabetes, and the inflection point of the GGT/HDL-c ratio was 6.477. The HR on the left and right sides of the inflection point was 2.568 (1.157, 5.699) and 1.012 (1.001, 1.023), respectively. The sensitivity analysis demonstrated the robustness of the results. Besides, the performance of the FPG + GGT/HDL-c ratio was better than FPG + GGT, FPG + HDL-c, and FPG in predicting diabetes. CONCLUSION: This study demonstrates a positive and non-linear relationship between the GGT/HDL-c ratio and incident diabetes in the Japanese population. The GGT/HDL-c ratio is strongly related to diabetes risk when it is <6.477.

A mixed-method evaluation of the relationship between Oxford classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy.

Introduction: This study aimed to investigate the relationship between Oxford Classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy (IgAN). Methods: The study was a single-center retrospective cohort study involving 358 patients with primary IgAN who were treated at the Shenzhen Second People's Hospital, China, between January 2011 and May 2021. Multivariate linear regression and generalized additive mixed models (GAMMs), adjusted for traditional risk confounders, were used to evaluate the correlation between scores for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C) (known as the Oxford Classification MEST-C score system), with proteinuria/creatinine ratio (PCR) at the time of renal biopsy and longitudinal changes in PCR, respectively. Results: The median PCR was 1061 mg/g, and it increased on average by 68.82 mg/g per year in these patients. Among patients with renal insufficiency, compared with patients without relative lesions, those with E present (E1) (1153.44; 95% confidence interval [CI], 188.99-2117.89 mg/g) and C > 0 (C1/2) (1063.58; 95% CI, 185.25-1941.90 mg/g) were associated with increased PCR levels at the time of renal biopsy. What's more, S present (S1) (194.96; 95% CI, 54.50-335.43 mg/g per year) was associated with the fastest PCR increase; C > 0 (C1/2) (147.59; 95% CI, 8.32-286.86 mg/g per year) and T >25% (T1/2) (77.04; 95% CI, 7.18-146.89 mg/g per year), were also correlated with a faster PCR increase. In patients with normal kidney function, associations between S1 (55.46; 95% CI, 8.93-101.99 mg/g per year) and E1 (94.02; 95% CI, 21.47-166.58 mg/g per year) and PCR change could be observed. Additionally, in patients with overweight/obesity, S1 (156.09; 95% CI, 52.41-259.77 mg/g per year), E1 (143.34; 95% CI, 35.30-251.38 mg/g per year), T1/2 (116.04; 95% CI, 22.58-209.51 mg/g per year), as well as C1/2 (134.03; 95% CI, 41.73-226.32 mg/g per year) were associated with noticeably quicker PCR increase. Conclusions: Overall, E1 and C1/2 were independently associated with raised proteinuria levels at the time of renal biopsy, and S1, E1, T1/2, C1/2 were independently associated with a longitudinal increase in proteinuria in the patients with IgAN, especially in those with renal insufficiency or overweight/obesity, suggesting that currently available treatments might not be satisfactory, and weight control might be beneficial. Individual therapy development might benefit from the use of the Oxford Classification system.

Glomerulosclerosis predicts poor renal outcome in patients with idiopathic membranous nephropathy.

OBJECTIVE: This study aimed to investigate the association between the proportion of glomerulosclerosis (focal segmental glomerulosclerosis and/or global glomerulosclerosis) and renal prognosis in patients with idiopathic membranous nephropathy (IMN). METHODS: A retrospective analysis performed from January 2008 to December 2017 in the First Affiliated Hospital of Shenzhen University by renal biopsy confirmed 200 patients with IMN, and their clinical pathology and prognosis were compared. Patients were divided into three groups on the basis of glomerular sclerosis proportion tertiles: low (Tertile1 group, proportion of glomerulosclerosis, 0-0%), middle (Tertile2 group, proportion of glomerulosclerosis, 0-5.5%) and high (Tertile3 group, proportion of glomerulosclerosis, 5.8-72.7%) tertiles. The follow-up endpoints were decreased estimated glomerular filtration rate (eGFR) by 20%, end-stage renal disease, and all-cause mortality. RESULTS: (1) Both, the Tertile1 and Tertile2, groups had significantly lower albumin level and higher 24-h urine protein level than that in the Tertile3 group. Regarding treatment, as the proportion of glomerulosclerosis increases, a more aggressive treatment with glucocorticoids and immunosuppressants should be provided. (2) Correlation analysis showed that the proportion of glomerulosclerosis was positively associated with age (P < 0.05). However, it was negatively associated with eGFR (P < 0.05). (3) Renal tubular atrophy and renal interstitial inflammatory cell infiltration were considered independent correlative factors for glomerulosclerosis. Kaplan-Meier analysis revealed that renal survival rate was significantly lower in patients with a proportion of glomerulosclerosis ≥ 6.45% than in patients with a proportion of glomerulosclerosis < 6.45%. Cox regression analysis revealed that as the proportion of glomerulosclerosis increases, the risk of renal outcomes increases gradually. CONCLUSIONS: Patients in the Tertile3 (higher proportion of glomerulosclerosis) group had more severe renal pathological damage compared to patients in the Tertile1 and Tertile2 groups. Glomerulosclerosis is a risk factor for renal function progression and poor renal prognosis in patients with IMN. As the proportion of glomerulosclerosis increases, the risk of renal endpoint events increases gradually.