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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

[1]  Tangchun Wu,et al.  Association of blood lipid profile with incident chronic kidney disease: A Mendelian randomization study. , 2020, Atherosclerosis.

[2]  Wenhui Jiang,et al.  Establishment and Validation of a Risk Prediction Model for Early Diabetic Kidney Disease Based on a Systematic Review and Meta-Analysis of 20 Cohorts , 2020, Diabetes Care.

[3]  Ellen F. Carney,et al.  The impact of chronic kidney disease on global health , 2020, Nature Reviews Nephrology.

[4]  J. Tuomilehto,et al.  The metabolic syndrome – What is it and how should it be managed? , 2019, European journal of preventive cardiology.

[5]  F. Fan,et al.  Metabolic Syndrome Is Associated With Rapid Estimated Glomerular Filtration Rate Decline In A Chinese Community-Based Population , 2019, Diabetes, metabolic syndrome and obesity : targets and therapy.

[6]  K. Kalantar-Zadeh,et al.  Serum triglycerides and mortality risk across stages of chronic kidney disease in 2 million U.S. veterans. , 2019, Journal of clinical lipidology.

[7]  Xiping Xu,et al.  Serum Lipids and Risk of Rapid Renal Function Decline in Treated Hypertensive Adults With Normal Renal Function , 2019, American journal of hypertension.

[8]  A. Paterson,et al.  Risk Factors for Kidney Disease in Type 1 Diabetes , 2019, Diabetes Care.

[9]  R. Liu,et al.  Plasma triglyceride levels and central obesity predict the development of kidney injury in Chinese community older adults , 2019, Renal failure.

[10]  A. Sahebkar,et al.  Fenofibrate improves renal function by amelioration of NOX‐4, IL‐18, and p53 expression in an experimental model of diabetic nephropathy , 2018, Journal of cellular biochemistry.

[11]  T. Jenssen,et al.  Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population. , 2018, Kidney international.

[12]  Predictors of chronic kidney disease in type 1 diabetes: a longitudinal study from the AMD Annals initiative , 2017, Scientific Reports.

[13]  D. Cucinotta,et al.  Plasma Triglycerides and HDL-C Levels Predict the Development of Diabetic Kidney Disease in Subjects With Type 2 Diabetes: The AMD Annals Initiative , 2016, Diabetes Care.

[14]  M. Woodward,et al.  Past Decline Versus Current eGFR and Subsequent ESRD Risk. , 2016, Journal of the American Society of Nephrology : JASN.

[15]  G. Russo,et al.  Predictors of chronic kidney disease in type 2 diabetes: A longitudinal study from the AMD Annals initiative. , 2016, Medicine.

[16]  K. Kalantar-Zadeh,et al.  Association of Serum Lipids with Outcomes in Hispanic Hemodialysis Patients of the West versus East Coasts of the United States , 2015, American Journal of Nephrology.

[17]  R. Wong,et al.  Prevalence of the metabolic syndrome in the United States, 2003-2012. , 2015, JAMA.

[18]  K. Kalantar-Zadeh,et al.  Niacin and progression of CKD. , 2015, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[19]  T. Stijnen,et al.  Effect of omega-3 fatty acids on kidney function after myocardial infarction: the Alpha Omega Trial. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[20]  Mahboob Rahman,et al.  Relation of serum lipids and lipoproteins with progression of CKD: The CRIC study. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[21]  M. Blaha,et al.  Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. , 2013, JAMA.

[22]  S. Navaneethan,et al.  Metabolic syndrome, ESRD, and death in CKD. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[23]  M. Tonelli,et al.  Association between LDL-C and risk of myocardial infarction in CKD. , 2013, Journal of the American Society of Nephrology : JASN.

[24]  D. Herrington,et al.  The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events: Multiethnic Study of Atherosclerosis , 2011, Cardiology research and practice.

[25]  M. Pisani,et al.  Validating smoking data from the Veteran's Affairs Health Factors dataset, an electronic data source. , 2011, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[26]  S. Kashyap,et al.  Metabolic syndrome and kidney disease: a systematic review and meta-analysis. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[27]  I. Wu,et al.  Metabolic syndrome loses its predictive power in late-stage chronic kidney disease progression--a paradoxical phenomenon. , 2011, Clinical nephrology.

[28]  V. Gebski,et al.  Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study , 2011, Diabetologia.

[29]  G. Beck,et al.  Hyperlipidemia and long-term outcomes in nondiabetic chronic kidney disease. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[30]  B. Astor,et al.  Risk of incident ESRD: a comprehensive look at cardiovascular risk factors and 17 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) Study. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[31]  P. Kimmel,et al.  Outcomes following diagnosis of acute renal failure in U.S. veterans: focus on acute tubular necrosis. , 2009, Kidney international.

[32]  M. Taskinen,et al.  Effects of Long-Term Fenofibrate Treatment on Markers of Renal Function in Type 2 Diabetes , 2009, Diabetes Care.

[33]  N. Vaziri,et al.  Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure. , 2009, American journal of physiology. Renal physiology.

[34]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[35]  B. Nordestgaard,et al.  Fasting and Nonfasting Lipid Levels: Influence of Normal Food Intake on Lipids, Lipoproteins, Apolipoproteins, and Cardiovascular Risk Prediction , 2008, Circulation.

[36]  Martin Adiels,et al.  Overproduction of Very Low–Density Lipoproteins Is the Hallmark of the Dyslipidemia in the Metabolic Syndrome , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[37]  R. Oberbauer,et al.  Predictors of new-onset decline in kidney function in a general middle-european population. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[38]  K. Kalantar-Zadeh,et al.  Association between serum lipids and survival in hemodialysis patients and impact of race. , 2007, Journal of the American Society of Nephrology : JASN.

[39]  K. Kalantar-Zadeh,et al.  Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome. , 2007, Journal of the American Society of Nephrology : JASN.

[40]  R. Krauss,et al.  Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement , 2005, Current opinion in cardiology.

[41]  H. Bloomfield,et al.  Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[42]  U. Ravnskov.  Inflammation, cholesterol levels, and risk of mortality among patients receiving dialysis. , 2004, JAMA.

[43]  Lijun Sun,et al.  Role of Sterol Regulatory Element-binding Protein 1 in Regulation of Renal Lipid Metabolism and Glomerulosclerosis in Diabetes Mellitus* , 2002, The Journal of Biological Chemistry.

[44]  Y. Siow,et al.  Very low-density lipoprotein stimulates the expression of monocyte chemoattractant protein-1 in mesangial cells. , 2000, Kidney international.

[45]  T. Rabelink,et al.  Early mechanisms of renal injury in hypercholesterolemic or hypertriglyceridemic rats. , 2000, Journal of the American Society of Nephrology : JASN.