Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans.

Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m2), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.

Rizk JG ，Hsiung JT ，Arif Y ，Hashemi L ，Sumida K ，Kovesdy CP ，Kalantar-Zadeh K ，Streja E ... -  《-》

Association of Serum Triglycerides and Renal Outcomes among 1.6 Million US Veterans.

Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied. We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components. The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification. Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-lowering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials.

Soohoo M ，Hashemi L ，Hsiung JT ，Moradi H ，Budoff MJ ，Kovesdy CP ，Kalantar-Zadeh K ，Streja E ... -  《-》

Risk of Progression of Nonalbuminuric CKD to End-Stage Kidney Disease in People With Diabetes: The CRIC (Chronic Renal Insufficiency Cohort) Study.

Reduced glomerular filtration rate (GFR) in the absence of albuminuria is a common manifestation of chronic kidney disease (CKD) in diabetes. However, the frequency with which it progresses to end-stage kidney disease (ESKD) is unknown. Multicenter prospective cohort study. We included 1,908 participants with diabetes and reduced GFR enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Urinary albumin and protein excretion. Incident ESKD, CKD progression (ESKD or ≥50% reduction in estimated GFR [eGFR] from baseline), and annual rate of decline in kidney function. ESKD was ascertained by self-report and by linkage to the US Renal Data System. We used Cox proportional hazards modeling to estimate the association of albuminuria and proteinuria with incident ESKD or CKD progression and linear mixed-effects models to assess differences in eGFR slopes among those with and without albuminuria. Mean eGFR at baseline was 41.2mL/min/1.73m2. Normal or mildly increased 24-hour urinary albumin excretion (<30mg/d) at baseline was present in 28% of participants, but in only 5% of those progressing to ESKD. For those with baseline normal or mildly increased albuminuria, moderately increased albuminuria (albumin excretion, 30-299mg/d), and 2 levels of severely increased albuminuria (albumin excretion, 300-999 and ≥1,000mg/d): crude rates of ESKD were 7.4, 34.8, 78.7, and 178.7 per 1,000 person-years, respectively; CKD progression rates were 17.0, 61.4, 130.5, and 295.1 per 1,000 person-years, respectively; and annual rates of eGFR decline were -0.17, -1.35, -2.74, and -4.69mL/min/1.73m2, respectively. We were unable to compare the results with healthy controls. In people with diabetes with reduced eGFRs, the absence of albuminuria or proteinuria is common and carries a much lower risk for ESKD, CKD progression, or rapid decline in eGFR compared with those with albuminuria or proteinuria. The rate of eGFR decline in normoalbuminuric CKD was similar to that reported for the general diabetic population.

Koye DN ，Magliano DJ ，Reid CM ，Jepson C ，Feldman HI ，Herman WH ，Shaw JE ... -  《-》

Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data.

Studies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal recovery predicts kidney risk following AKI is unknown. Retrospective cohort. Patients in the Veterans Health Administration in 2011 hospitalized (> 24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerular filtration rate > 60 mL/min/1.73 m², and no diagnosis of end-stage renal disease or non-dialysis-dependent CKD: 17,049 (16.3%) with and 87,715 without AKI. Pattern of recovery to creatinine level within 0.3 mg/dL of baseline after AKI: within 2 days (fast), in 3 to 10 days (intermediate), and no recovery by 10 days (slow or unknown). CKD stage 3 or higher, defined as 2 outpatient estimated glomerular filtration rates < 60 mL/min/1.73m² at least 90 days apart or CKD diagnosis, dialysis therapy, or transplantation. Risk for CKD was modeled using modified Poisson regression and time to death-censored CKD was modeled using Cox proportional hazards regression, both stratified by AKI stage. Most patients' AKI episodes were stage 1 (91%) and 71% recovered within 2 days. At 1 year, 18.2% had developed CKD (AKI, 31.8%; non-AKI, 15.5%; P < 0.001). In stage 1, the adjusted relative risk ratios for CKD stage 3 or higher were 1.43 (95% CI, 1.39-1.48), 2.00 (95% CI, 1.88-2.12), and 2.65 (95% CI, 2.51-2.80) for fast, intermediate, and slow/unknown recovery. A similar pattern was observed in subgroup analyses incorporating albuminuria and sensitivity analysis of death-censored time to CKD. Variable timing of follow-up and mostly male veteran cohort may limit generalizability. Patients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.

Heung M ，Steffick DE ，Zivin K ，Gillespie BW ，Banerjee T ，Hsu CY ，Powe NR ，Pavkov ME ，Williams DE ，Saran R ，Shahinian VB ，Centers for Disease Control and Prevention CKD Surveillance Team ... -  《-》

Serum triglycerides and mortality risk across stages of chronic kidney disease in 2 million U.S. veterans.

In the general population, elevated triglyceride (TG) levels are an important risk factor for cardiovascular disease and mortality. However, in chronic kidney disease, the association of serum TGs with mortality is less clear. We sought to examine the association of TGs with mortality across chronic kidney disease (CKD) stages in a large cohort of U.S. veterans. We examined 2,086,904 U.S. veterans with a TG measurement obtained between a baseline period of October 2004 and September 2006, with follow-up until December 2014 (median [interquartile range {IQR}]: 9.2 [6.5, 9.9] years). Associations of TGs with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models. Patients were 64 ± 14 years old with a median (IQR) baseline TG of 129 [88, 193] mg/dL and estimated glomerular filtration rate of 76 [61, 91] mL/min/1.73 m2. More advanced CKD was associated with higher odds of TGs ≥ 240 mg/dL. Low levels of TGs < 80 mg/dL were associated with a higher risk of mortality across all stages, whereas TG levels ≥ 240 mg/dL were only associated with a higher risk of all-cause mortality in non-CKD and CKD stages 3A, 3B, and 4 (reference: TG 120 to <160 mg/dL). The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease. Similar results were observed for cardiovascular mortality, in strata by age and diabetes, and further adjustment for high-density lipoprotein and low-density lipoprotein. Associations of elevated TGs with all-cause and cardiovascular mortality were incrementally attenuated across more advanced stages of CKD.

Soohoo M ，Moradi H ，Obi Y ，Kovesdy CP ，Kalantar-Zadeh K ，Streja E ... -  《-》