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Low HDL and High Triglycerides Increase Risk of Kidney Disease

These factors are tied to increased nephropathy risk in type 2 diabetes patients.

Despite the achievement of blood glucose, blood pressure, and LDL-cholesterol (LDL-C) targets, the risk for diabetic kidney disease (DKD) remains high among patients with type 2 diabetes. This observational retrospective study investigated whether diabetic dyslipidemia—that is, high triglyceride (TG) and/or low HDL-cholesterol (HDL-C) levels—contributes to this high residual risk for DKD.

Among a total of 47,177 patients attending Italian diabetes centers, 15,362 patients with a baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, normoalbuminuria, and LDL-C ≤130 mg/dL completing a 4-year follow-up were analyzed. The primary outcome was the incidence of DKD, defined as either low eGFR (<60 mL/min/1.73 m2) or an eGFR reduction >30% and/or albuminuria.

Having low HDL cholesterol levels and high triglyceride levels can indicate a higher risk of developing diabetic kidney disease (DKD) in people with type 2 diabetes, according to an Italian study.  HDL cholesterol is sometimes referred to as the ‘good cholesterol’ because having higher level of HDL cholesterol is linked with better health.

In the early stages of kidney disease, there are no symptoms; but if allowed to progress, signs such as breathlessness, water retention (such as swollen ankles) and malnutrition will appear in the later stages of the condition.

With the right interventions, kidney disease can be halted, which is why it is important that people with diabetes have their kidney function tested each year.

In the study, none of the participants had any sign of kidney disease at the start of the study, and were monitored over four years. Through the study, the patients were monitored for the onset of kidney disease and cholesterol levels.

The findings showed that participants with triglyceride levels of 1.7 mmol/l or more had a 35% increased risk of developing an initial sign of kidney disease (low eGFR or albuminuria). Participants with low HDL levels (below 1 mmol/l in men and below 1.3 mmol/l in women) had a 44% increased risk of having a sign of kidney disease. The findings show that high triglyceride levels and low HDL levels can each indicate an increased risk of developing kidney disease within a few years.

Overall, 12.8% developed low eGFR, 7.6% an eGFR reduction >30%, 23.2% albuminuria, and 4% albuminuria and either eGFR <60 mL/min/1.73 m2 or an eGFR reduction >30%. TG ≥150 mg/dL increased the risk of low eGFR by 26%, of an eGFR reduction >30% by 29%, of albuminuria by 19%, and of developing one abnormality by 35%. HDL-C <40 mg/dL in men and <50 mg/dL in women were associated with a 27% higher risk of low eGFR and a 28% risk of an eGFR reduction >30%, with a 24% higher risk of developing albuminuria and a 44% risk of developing one abnormality. These associations remained significant when TG and HDL-C concentrations were examined as continuous variables, and were only attenuated by multivariate adjustment for numerous confounders.

A key question that the findings raise is what leads to low HDL and high triglyceride levels in the first place and how to improve this situation. High triglyceride levels and low HDL are usually signs of an unhealthy lifestyle, and the positive news is that this can certainly be changed.

The association between dyslipidemia and microvascular disease is also supported by recent epidemiological studies. In the ADVANCE Study, the only longitudinal study with a number of participants and follow-up duration comparable with those in this study, the risk of developing renal events associated with lower HDL-C levels was 19%, which is similar to the findings in this study.

The researchers note that their study’s results are in keeping with these cross-sectional findings, demonstrating the independent role of dyslipidemia across a wide set of covariates and confounders, starting with a population with similar baseline characteristics.  Furthermore, the researchers point out that both a study by Sacks et al. and this study enrolled patients who had controlled LDL-C levels, allowing better dissection of the role of a high TG/low HDL-C phenotype on DKD.

From the results of the study it was concluded that in a large population of outpatients with diabetes, low HDL-C and high TG levels were independent risk factors for the development of DKD over 4 years. Chronic diabetic kidney disease (DKD) is the major cause of end-stage renal disease worldwide.

Practice Pearls:

  • Hyperglycemia and hypertension are the main risk factors for DKD development and progression.
  • In spite of the achievement of recommended targets for blood glucose and blood pressure, the residual risk for diabetic nephropathy remains high among patients with type 2 diabetes.
  • Despite improvements in blood glucose and blood pressure control as a result of these guidelines, many patients still develop DKD, and the residual risk for this complication remains high.

The study is published online, ahead of print, by the Diabetes Care journal. : Diabetes Care 2016 Sep; dc161246. http://dx.doi.org/10.2337/dc16-1246