Lower Risk Of End-stage Renal Disease Research Articles

#1672 High level of HDL-C is associated with a higher risk of ESRD and all-cause mortality in patients with DM and CKD

Abstract Background and Aims Previous studies have regarded high-density lipoprotein cholesterol (HDL-C) as ‘good cholesterol’; however, recent research has unveiled a higher incidence of adverse events among individuals with extremely elevated HDL-C levels. Method Two cohorts of subjects were analyzed in this study. In the first cohort, a total of 375 participants with DKD who underwent renal-biopsy between January 2008 and September 2020, from West China Hospital T2DM-DKD cohort, were enrolled for the longitudinal observational study. Additionally, 3,262 participants with DM and chronic kidney disease (CKD) from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included. Kaplan-Meier curves and Cox proportional hazard models were used to analyze the association between HDL-C concentration and the incidence of end-stage renal disease (ESRD) as well as all-cause mortality. Results Patients were divided into three groups based on HDL-C levels. After a median follow-up of 36 months, 44% of the patients developed ESRD in T2DM-DKD cohort. Patients in Group 3 (HDL-C ≥1.55 mmol/L) exhibited a higher risk of ESRD compared to Group 1 (HDL-C <1.03 mmol/L). After adjusting for confounders, Group 3 patients still had a significantly higher risk of ESRD (adjusted HR: 1.68, 95% CI: 1.03, 2.71). Analysis of HDL subfractions revealed that a higher HDL3/HDL2 ratio was associated with a lower risk of ESRD. Furthermore, in the NHANES cohort, higher HDL-C levels were linked to a higher risk of all-cause mortality during a median follow-up of 75 months as the result of the weighted Kaplan-Meier curves (p = 0.02). Notably, in patients with CKD stages 1-2, Group 3 participants had a significantly higher hazard ratio (HR: 1.61, 95% CI: 1.19, 2.19) after adjusting for confounders. Conclusion This study challenges the notion of HDL-C as ‘good cholesterol’ in patients with DKD, as higher HDL-C levels were associated with increased risks of ESRD and all-cause mortality. Additionally, the study highlights the potential protective effect of a higher HDL3/HDL2 ratio against ESRD. These findings contribute to reevaluating the role of HDL-C and its subfractions in DKD patients.

Long-term Evolution of Estimated Glomerular Filtration Rate in Patients With Antiviral Treatment for Hepatitis C Virus Infection

Data regarding the long-term evolution of estimated glomerular filtration rate (eGFR) in patientsreceiving antiviral treatment for hepatitis C virus are limited. A total of 1987 patients with eGFR ≥15 mL/min/1.73m2 who received interferon or direct-acting antiviral treatment were prospectively enrolled in this cohort study. The eGFR was assessed biannually by the Chronic Kidney Disease Epidemiology Collaboration equation from the time point of sustained virologic response (SVR12). Multivariate generalized estimated equation was used to assess the association between the factors of interest and evolution of eGFR following antiviral treatment. Multivariate Cox regression analysis was used to assess the relative risk of end-stage renal disease (ESRD), defined as an eGFR <15 mL/min/1.73m2. Patients who achieved SVR12 (adjusted slope coefficient difference: 2.36 mL/min/1.73 m2/year; 95% confidence interval [CI], 1.50 to 3.32; P < .001) were associated with eGFR improvement, compared with those who did not achieve SVR12. Among patients who achieved SVR12, the eGFR evolution was comparable (adjusted slope coefficient difference: 0.31 mL/min/1.73m2/year; 95% CI,-0.34 to 0.96; P= .35) in those treated with interferon or direct-acting antiviral. The incidence rates of ESRD in patients who achieved and did not achieve SVR12 were 0.06 per 100 person-years and 0.37 per 100 person-years. Patients who achieved SVR12 were associated with a lower risk of ESRD (adjusted hazard ratio, 0.24; 95% CI, 0.05-0.68; P= .021). The long-term eGFR evolution and risk of ESRD are significantly improved in patients who achieve SVR12 with anti- hepatitis C virus treatment.

Investigation of FADS Gene Cluster Single Nucleotide Polymorphisms in End-Stage Renal Disease Compared With Normal Controls.

End-stage renal disease (ESRD) is a public health problem with a high burden. The condition is associated with abnormalities in lipid metabolism. The fatty acid desaturase (FADS) gene cluster includes three genes that are significantly correlated with a number of pathologic conditions related to abnormal lipid levels. In the current study, we genotyped rs174556, rs99780, and rs7115739 single nucleotide polymorphisms within the FADS cluster in a population of ESRD patients and healthy controls. The rs174556 of the FADS1 gene and rs99780 of the FADS2 gene were not associated with the risk of ESRD in any inheritance model. However, the rs7115739 of FADS3 was associated with the risk of ESRD in all models except for the recessive model. The T allele of this SNP was significantly less prevalent among cases compared with controls [odds ratio (OR) (95% CI) = 0.44 (0.25–0.77), P value = 0.004]. GT and TT genotypes has been shown to decrease the risk of ESRD in a codominant model [OR (95% CI) = 0.49 (0.26–0.92) and OR (95% CI) = 0.18 (0.02–1.6), respectively; P value = 0.019]. In the dominant model, GT + TT status was associated with lower risk of ESRD [OR (95% CI) = 0.45 (0.24–0.82), P value = 0.0078]. Assessment of association between this SNP and risk of ESRD in an overdominant model revealed that GT genotype decreases the risk of this condition [OR (95% CI) = 0.5 (0.27–0.94), P value = 0.029]. Taken together, the rs7115739 of FADS3 is suggested as a putative modulator of the risk of ESRD in the Iranian population.

Association between Dental Scaling and Reduced Risk of End-Stage Renal Disease: A Nationwide Matched Cohort Study.

Periodontitis is prevalent in patients with chronic kidney disease (CKD) and is also associated with kidney function decline. It is unclear whether dental scaling treatment prevents the progression of CKD. In a nationwide cohort study, Taiwan’s National Health Insurance Research Database was used to select people with CKD. Propensity score-matching procedures were performed to compare the long-term risk of end-stage renal disease (ESRD) between CKD patients with and without the receipt of dental scaling. A total of 33,637 matched pairs with CKD were included, with 503,373 person-years of follow-up for analyses. Dental scaling was significantly associated with a lower risk of ESRD (adjusted hazard ratio (aHR): 0.83, 95% confidence interval (CI): 0.77–0.90). In addition, there was a dose-dependent relationship between the frequency of dental scaling and a reduced risk of ESRD. Dental scaling was also linked to reduced risks of major adverse cardiovascular events (aHR: 0.91, 95% CI: 0.87–0.95), sepsis (aHR: 0.81, 95% CI: 0.77–0.85), and all-cause mortality (aHR: 0.81, 95% CI: 0.76–0.87). Dental scaling was significantly associated with lower risks of progression to ESRD in patients with CKD. Regular dental scaling may serve as a prophylactic measure for kidney function decline.

Associations Between Using Chinese Herbal Medicine and Long-Term Outcome Among Pre-dialysis Diabetic Nephropathy Patients: A Retrospective Population-Based Cohort Study.

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear. Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan’s National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis. Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value <0.001), and the risk of mortality was 0.42 (95% CI: 0.36–0.49; p-value <0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55–0.63; p-value <0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.), Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf., Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs. Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials.

Antibody subtypes and titers predict clinical outcomes in ANCA-associated vasculitis.

The objective of this study is to evaluate the association between antineutrophil cytoplasmic autoantibody (ANCA) subtype and ANCA titers on clinical outcomes and disease activity among a cohort of patients from Central Appalachia diagnosed with ANCA-associated vasculitis (AAV) over a 3-decade period. This is a retrospective chart review of all patients diagnosed with AAV. ANCA subtypes (myeloperoxidase (MPO) and proteinase 3 (PR3)) and titers at the time of diagnosis and at the time of relapse or last follow-up were evaluated along with patient outcomes. Outcomes of interest included relapse, development of end-stage renal disease (ESRD) and mortality. Sensitivity analysis and multivariable analysis were performed. Of the 202 patients, 111 patients were MPO-ANCA positive and 91 patients were PR3-ANCA positive. Relapse was more frequent among patients with PR3-ANCA compared to MPO-ANCA (35% vs 12%, p < 0.001). In both ANCA subgroups, the strongest predictor of relapse was an increase in titers prior to relapse, HR 8.1 (95% CI 1.6-40), p 0.009. Patients who achieved serological remission had a lower risk of ESRD [sub-HR 0.31 (95% CI 0.11-0.89)] and mortality [HR (95% CI) 0.24 (0.07-0.7)]. PR3-ANCA was associated with higher risk of ESRD [sub-HR 3.1 (95% CI 1.1-8.5)]. There was no difference in mortality between patients with MPO-ANCA and PR3-ANCA. Our study supports the use of both ANCA subtypes and titer levels for predicting clinical outcomes in patients receiving treatment for AAV. Monitoring of ANCA antibody titers may be useful since both serological remission and increase in titers provide prognostic information.

Renal outcomes and all-cause death associated with sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL 3 Korea).

AimsTo investigate the effectiveness of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors on the risk of progression to end‐stage renal disease (ESRD) and all‐cause mortality in a broad range of patients with type 2 diabetes (T2D) using a Korean nationwide cohort.Materials and MethodsUsing data from the Korean National Health Insurance Service database from January 2014 to December 2017, a total of 701 674 patients were identified with T2D. We divided these patients into new users of SGLT2 inhibitors and new users of other glucose‐lowering drugs (oGLDs). Using propensity scores, patients in the two groups were matched 1:1. We assessed the risk of ESRD and all‐cause death.ResultsThere were 45 016 patients in each group, and baseline characteristics were well balanced between the groups. The patients' mean age was 58.1 ± 10.6 years and mean estimated glomerular filtration rate (eGFR) was 89.2 ± 27.4 mL/min/1.73m2, and 8% of patients had proteinuria. We identified 167 incident ESRD cases and 1070 all‐cause deaths during follow‐up. Use of SGLT2 inhibitors versus oGLDs was associated with a lower risk of ESRD (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.34 to 0.65) and all‐cause death (HR 0.82, 95% CI 0.73 to 0.93). In a subgroup analysis by eGFR, initiation of SGLT2 inhibitor treatment, compared with oGLD treatment, was associated with lower risk of progression to ESRD among patients with eGFR 60 to 90 mL/min/1.73m2 and those with eGFR < 60 mL/min/1.73m2, and a lower risk of all‐cause death was associated with SGLT2 inhibitors versus oGLDs in patients with eGFR ≥90 and 60 to 90 mL/min/1.73m2.ConclusionIn this large nationwide study of Korean patients with T2D, initiation of SGLT2 inhibitors versus oGLDs was associated with lower risk of ESRD and all‐cause death.

Sex-specific association between type 1 diabetes and the risk of end-stage renal disease: a systematic review and meta-analysis.

This meta-analysis was conducted given the inconsistent findings of studies regarding the sex discrepancy in the relationship between type 1 diabetes (T1D) and the risk of end-stage renal disease (ESRD). Articles published on PubMed between January 1, 1966 and March 31, 2019 were systematically retrieved without language restrictions. The included articles all presented sex-specific data of the incidence rate ratio, standardized incidence or mortality ratio, hazard ratio, relative risk, or odds ratio, or provided data to estimate the association between T1D and ESRD or kidney disease-related mortality. The gender-specific effect estimates and pooled ratio (female-to-male) for ESRD and for deaths from T1D-related renal disease were acquired via a random-effects meta-analysis with inverse variance weighting, regardless of heterogeneity evaluated based on the I2 statistic. Nineteen studies, including 122,842 individuals, were finally selected for this meta-analysis. Sex differences in effect estimates were found in ESRD (pooled ratio = 0.81 (95% confidence interval 0.69-0.94)) with considerable heterogeneity (I2 = 66.9%), but not in mortality with T1D-associated renal disease. Women with T1D have a lower risk of ESRD compared with that in men, but this finding may be biased by potential confounding factors and must be verified by other well-planned prospective studies.

Risk of End-Stage Renal Disease in Psoriatic Patients: Real-World Data from a Nationwide Population-Based Cohort Study

Psoriasis is a chronic inflammatory skin disorder mediated by the T-cell–related immune response. Psoriatic patients may have a variety of comorbidities, but their risk of end-stage renal disease (ESRD), particularly according to the subtype of psoriasis, is unclear. We investigated the risk of ESRD in patients with psoriasis according to the subtype of psoriasis and history of systemic therapy for psoriasis. A total of 2,121,228 adults (1,590,921 in the control group and 530,307 in the psoriasis group) were enrolled in this nationwide population-based cohort study until 2015. During follow-up, 1,434 of the subjects in the psoriasis group developed ESRD. After adjusting for confounding factors, psoriasis was associated with the risk of ESRD (hazard ratio (HR) 1.58, 95% confidence interval [95% CI] 1.47–1.68). The psoriatic arthritis group (HR 7.60, 95% CI 1.90–30.41) had a higher risk of ESRD than the control group. Interestingly, no such association was detected in the systemically treated group (HR 1.07, 95% CI 0.80–1.41). Moreover, the acitretin-treated group had a lower risk of ESRD (HR 0.658, 95% CI, 0.494–0.875) than the non-systemically treated group. In conclusion, the risk of developing ESRD in patients with psoriasis differed according to the type of treatment and the presence of arthritis.

Poor accordance to a DASH dietary pattern is associated with higher risk of ESRD among adults with moderate chronic kidney disease and hypertension

The Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure, an important risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, it is unclear whether adherence to a DASH diet confers protection against future ESRD, especially among those with pre-existing CKD and hypertension. We examined whether a DASH diet is associated with lower risk of ESRD among 1,110 adults aged≥ 20 years with hypertension and CKD (estimated glomerular filtration rate, eGFR 30-59 ml/min/1.73 m2) enrolled in the National Health and Nutrition Examination Survey (1988-1994). Baseline DASH diet accordance score was assessed using a 24-hour dietary recall questionnaire. ESRD was ascertained by linkage to the U.S. Renal Data System registry. We used the Fine-Gray competing risks method to estimate the relative hazard (RH) for ESRD after adjusting for sociodemographics, clinical and nutritional factors, eGFR, and albuminuria. Over a median follow-up of 7.8 years, 18.4% of subjects developed ESRD. Compared to the highest quintile of DASH diet accordance, there was a greater risk of ESRD among subjects in quintiles 1 (RH=1.7; 95% CI 1.1-2.7) and 2 (RH 2.2; 95% CI 1.1-4.1). Significant interactions were observed with diabetes status and race/ethnicity, with the strongest association between DASH diet adherence and ESRD risk observed in individuals with diabetes and in non-Hispanic blacks. Low accordance to a DASH diet is associated with greater risk of ESRD in adults with moderate CKD and hypertension, particularly in non-Hispanic blacks and persons with diabetes.

Improvement of Outcomes in Patients with Lupus Nephritis: Management Evolution in Chinese Patients from 1994 to 2010

To assess how the longterm outcomes have changed over the past decades in Chinese patients with lupus nephritis (LN). The trends in patient manifestation at presentation, treatment pattern, and therapeutic effects were evaluated. A cohort of biopsy-proven patients with LN (n = 1945) from January 1994 to December 2010 was analyzed. Treatment regimens, treatment response, renal relapse, and renal outcome were compared at different time periods (1994-1998, 1999-2004, and 2005-2010). Patients in the later periods had shorter duration of disease, lower serum creatinine value and chronicity at biopsy, and more frequent followup. They were more likely to receive standard-of-care therapies, which included cyclophosphamide, mycophenolate mofetil, and combination therapy. Patients in the later periods had higher probabilities of achieving remission (p < 0.001) and lower probabilities of experiencing renal flare (p = 0.007). The 5-year renal survival rates were 92.6%, 90.6%, and 94.3% in 1994-1998, 1999-2004, and 2005-2010, respectively. The 5-year risk of endstage renal disease (ESRD) did not differ between 1994-1998 and 1999-2004, but was significantly lower in 2005-2010 (HR 0.40, 95% CI 0.19-0.85 vs 1999-2004). In multivariable Cox analysis, standard therapy was independently associated with lower risk of ESRD (adjusted HR 0.72, 95% CI 0.52-0.98, p = 0.04). Variables of renal damage at biopsy (renal function, activity index, and chronicity index) were independently associated with poor outcome. The outcomes of Chinese patients with LN have improved from 1994 to 2010. With the increased use of standard therapies, the remission rates have increased and renal relapse has decreased.

Improvement in Mortality and End-Stage Renal Disease in Patients With Type 2 Diabetes After Acute Kidney Injury Who Are Prescribed Dipeptidyl Peptidase-4 Inhibitors

ObjectiveTo focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and MethodsData from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. ResultsOf a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P<.001) after adjustments for CKD, advanced CKD, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker use. In contrast, the risk of major adverse cardiovascular events and hospitalized heart failure did not differ significantly between groups. ConclusionDipeptidyl peptidase-4 inhibitor users had a lower risk of ESRD and mortality than did nonusers among patients with diabetes after weaning from dialysis-requiring AKI. Therefore, a prospective study of AKI to CKD transitions after episodes of AKI is needed to optimally target DPP4i interventions.

Urine Complement Proteins and the Risk of Kidney Disease Progression and Mortality in Type 2 Diabetes.

OBJECTIVEWe examined the association of urine complement proteins with progression to end-stage renal disease (ESRD) or death in people with type 2 diabetes and proteinuric diabetic kidney disease (DKD).RESEARCH DESIGN AND METHODSUsing targeted mass spectrometry, we quantified urinary abundance of 12 complement proteins in a predominantly Mexican American cohort with type 2 diabetes and proteinuric DKD (n = 141). The association of urine complement proteins with progression to ESRD or death was evaluated using time-to-event analyses.RESULTSAt baseline, median estimated glomerular filtration rate (eGFR) was 54 mL/min/1.73 m2 and urine protein-to-creatinine ratio 2.6 g/g. Sixty-seven participants developed ESRD or died, of whom 39 progressed to ESRD over a median of 3.1 years and 40 died over a median 3.6 years. Higher urine CD59, an inhibitor of terminal complement complex formation, was associated with a lower risk of ESRD (hazard ratio [HR] [95% CI per doubling] 0.50 [0.29–0.87]) and death (HR [95% CI] 0.56 [0.34–0.93]), after adjustment for demographic and clinical covariates, including baseline eGFR and proteinuria. Higher urine complement components 4 and 8 were associated with lower risk of death (HR [95% CI] 0.57 [0.41–0.79] and 0.66 [0.44–0.97], respectively); higher urine factor H–related protein 2, a positive regulator of the alternative complement pathway, was associated with greater risk of death (HR [95% CI] 1.61 [1.05–2.48]) in fully adjusted models.CONCLUSIONSIn a largely Mexican American cohort with type 2 diabetes and proteinuric DKD, urine abundance of several complement and complement regulatory proteins was strongly associated with progression to ESRD and death.

Achieving Sustained Virological Response in Liver Transplant Recipients With Hepatitis C Decreases Risk of Decline in Renal Function.

The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end-stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT. The mean estimated glomerular filtration rate (eGFR) at baseline (3 months after LT) was similar in the sustained virological response (SVR; n=145) and non-SVR group (n=59; 69±21 versus 65±33 mL/minute/1.73m2 ; P=0.27). In the unadjusted Cox proportional regression analysis, the presence of SVR was associated with an 88% lower risk of CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05-0.31) and 86% lower risk of ESRD (odds ratio, 0.14; 95% CI, 0.05-0.35). Similar results were found after adjusting for propensity score and time-dependent Cox regression analyses. The estimated slopes of eGFR based on a 2-stage mixed model of eGFR were calculated. Patients with SVR had a less steep slope in eGFR (-0.60 mL/minute/1.73 m2 /year; 95% CI, -1.50 to 0.30; P = 0.190) than recipients without SVR (-2.53 mL/minute/1.73 m2 /year; 95% CI, -3.99 to -1.07; P = 0.001), and the differences in the slopes were statistically significant (P = 0.026). In conclusion, in LT recipients with chronic HCV infection, achieving SVR significantly lowers the risk of decline in renal function and progression to ESRD independent of the AVT therapy used.

The effect of continuity of care on the incidence of end-stage renal disease in patients with newly detected type 2 diabetic nephropathy: a retrospective cohort study

BackgroundDiabetic nephropathy requires periodic monitoring, dietary modification, and early intervention to prevent the disease severity within limited resource settings. To emphasize the importance of continuous care for chronic diseases, various studies have focused on the association between continuity of care (COC) and common adverse outcomes. However, studies aimed at understanding the effect of COC on the incidence of chronic diseases, such as end-stage renal disease (ESRD), are few. The aim of this study was to determine whether there is an association between COC and the incidence of ESRD among patients with diabetic nephropathy. Moreover, we identified individual- and hospital-level factors associated with the incidence of ESRD among diabetic nephropathy patients.MethodsWe conducted a retrospective cohort study using the administrative National Health Insurance claims data from 2005 to 2012 in the Republic of Korea. The dependent variable, a binary variable, was the incidence of ESRD due to diabetic renal complication. In addition, using the COC index as a binary variable with a cutoff point of 0.75, we divided patients into a ‘Good COC group’ (COC index≥0.75) and a ‘Bad COC group’ (COC index< 0.75). The survival analysis was performed using the Cox proportional hazards models.ResultsAmong 3565 diabetic renal complication patients, ESRD occurred among 83 diabetes mellitus patients (2.3%). Nephropathy patients with lower COC level (< 0.75) had 1.99 times higher risk of ESRD incidence (95% confidence interval [CI]:1.27–3.12). In addition, the lowest income level patients had higher hazard ratio (HR) of ESRD than the highest income level patients (HR: 1.69 95% CI: 0.95–2.98), while patients with disabilities had 2.70 higher HR of ESRD than patients without disabilities (95% CI: 0.64–43).ConclusionsAmong patients with diabetic renal complication, higher continuity of care was associated with lower risk of ESRD. It is therefore recommended that continuous follow-up be encouraged to prevent ESRD among diabetic renal complication patients. Moreover, disparities in health outcomes between socially vulnerable groups including patients with disabilities and those in the lowest income level should be addressed.

Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes

Background: Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD. Methods: SAA concentration was measured in serum samples obtained at the start of follow-up. Multivariate proportional hazards models were employed to examine the magnitude of the risk of ESRD or death across tertiles of SAA concentration after adjustment for traditional risk factors. The C statistic was used to assess the additional predictive value of SAA relative to traditional risk factors. Results: Of 256 participants (mean ± SD glomerular filtration rate [iothalamate] = 148 ± 45 mL/min, and median [interquartile range] urine albumin/creatinine = 39 [14-221] mg/g), 76 developed ESRD and 125 died during a median follow-up period of 15.2 and 15.7 years, respectively. After multivariable proportional hazards regression, participants in the 2 highest SAA tertiles together exhibited a 53% lower risk of ESRD (hazard ratio [HR] 0.47, 95% CI 0.29-0.78), and a 30% lower risk of death (HR 0.70, 95% CI 0.48-1.02), compared with participants in the lowest SAA tertile, although the lower risk of death was not statistically significant. Addition of SAA to the ESRD model increased the C statistic from 0.814 to 0.815 (p = 0.005). Conclusions: Higher circulating SAA concentration is associated with a reduced risk of ESRD in American Indians with type 2 diabetes.

Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality

Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

Dietary polyunsaturated fatty acids and incidence of end-stage renal disease in the Southern Community Cohort Study.

BackgroundWhether polyunsaturated fatty acids (PUFA) are associated with end-stage renal disease (ESRD) in populations with a high burden of risk factors for kidney disease is unknown. We sought to determine whether PUFA intake is associated with ESRD.MethodsWe conducted a nested case–control study of ESRD within the Southern Community Cohort Study (SCCS), a prospective cohort of low-income blacks and whites in the southeastern US (2002–2009). Through 2012, 1,074 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3,230 controls by age, sex and race. Dietary intake of total, n-3 or n-6 PUFA was assessed from a validated food frequency questionnaire administered at baseline. Odds ratios (ORs) and 95 % confidence intervals (CIs) were computed from logistic regression models that included matching variables, body mass index, smoking, diabetes, hypertension, education, income, total energy intake and percent energy from protein and saturated fat.ResultsThe mean (SD) age of participants was 55 (9) years. Most participants were women (55 %), black (87 %), with hypertension (67 %) and on average obtained 8 % of their energy from PUFA. Higher PUFA intake was marginally associated with a lower risk of ESRD in adjusted analyses. The adjusted odds ratios (95 % confidence intervals) for ESRD for the 5th vs. 1st quintile of PUFA were 0.79 (0.60–1.05; P trend = 0.06) for total PUFA, 0.81 (0.61–1.06; P trend = 0.04) for n-6 PUFA and 0.93 (0.71–1.21; P trend = 0.45) for n-3 PUFA.ConclusionsWe observed a marginally significant inverse trend between dietary PUFA intake and ESRD incidence, mainly driven by n-6 fatty acid intake. Our findings require replication but suggest that a diet rich in n-6 PUFA may prevent ESRD development in a population with a high burden of kidney disease risk factors.

The effect of renin–angiotensin system blockade on the incidence of end-stage renal disease in IgA nephropathy

The impact of renin-angiotensin system blockade (RASB) on the incidence of end-stage renal disease (ESRD) remains unclear in IgA nephropathy (IgAN). This study assessed associations between RASB treatment and the incidence of ESRD in IgAN using propensity score approaches. We retrospectively analyzed 1273 patients with IgAN biopsied between 1979 and 2010. Propensity scores were calculated using logistic regression. Associations between RASB and ESRD were examined using a Cox regression model adjusted by inverse probability of treatment weighted, regression, stratification and matching. During follow-up (median 5.1years), 130 patients developed ESRD. With Cox regression adjusted by inverse probability of treatment weighted, RASB use was significantly associated with a lower risk of ESRD (hazard ratio 0.58; 95% confidence interval 0.42-0.80). Significant associations were observed for other propensity score-based approaches. In stratified analysis, a beneficial association between RASB and ESRD was observed in patients ≥35years, with hypertension, reduced estimated glomerular filtration rate (<60mL/min/1.73m2), mesangial proliferation and segmental glomerulosclerosis (P for interaction <0.05), and tended to be greater in patients with proteinuria (≥1.0g/24h), extracapillary proliferation and receiving methylprednisolone pulse therapy (P for interaction <0.10). Treatment with RASB was associated with a lower incidence of ESRD in the real-world practice of IgAN.

Obesity, metabolic health, and the risk of end-stage renal disease

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reason for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by presence or absence of metabolic syndrome and adjusted for demographic, lifestyle and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95%CI 0.52,0.95), but not those with (hazard ratio, 1.06) metabolic syndrome. In models stratified by weight and metabolic health, compared to normal weight (BMI 18.5–24.9 kg/m2) participants without metabolic syndrome the overweight individuals (BMI 25–29.9) and obese individuals (BMI of 30 or more) with metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with metabolic syndrome.