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Mortality Rates Due to Chronic Kidney Disease in Diabetes

Apr 7, 2018
 

Mortality rates increased in adults with diabetes, low estimated glomerular filtration rate in absence of albuminuria.

Diabetes affects many U.S adults and its prevalence keeps increasing over the years. Poor management of diabetes can cause many complications, including increased risk of cardiovascular disease, chronic kidney failure, and even mortality. Studies have shown that the increased mortality risk is mainly noted in patients with chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) <60ml/min/1.73 m2 or increased urine albumin excretion. Therefore, interventions such as improved blood pressure control and use of renin-angiotensin-aldosterone system (RAAS) blockers help prevent CKD and may help reduce diabetes-associated mortality.

This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) and examined mortality trends from 1988 to 2006 due to CKD phenotypes in the U.S adults with diabetes. It was hypothesized that the proportion of deaths of patients with diabetes occurring in eGFR < 60ml/min/1.73 m2 without increased urine albumin excretion has increased over time. The study population included adults greater than 20 years of age, those who had diabetes defined by physician diagnosis, fasting glucose >126 mg/dL, hemoglobin A1c > 6.5%, or use of glucose-lowering medications.  A total of 1,834, 1,067, 1,160, and 1,781 sampled adults with diabetes were included in the analyses of results for years 1988–1994, 1999–2002, 2003–2006, and 2007–2010, respectively.

Diabetes prevalence increased from 8% during the year 1988-1994 to 11.8% in the years 2007-2010 in the US. There was also an increased use of RAAS inhibitor and statins and decrease in overall LDL-cholesterol and blood pressure levels and increased presence of comorbid conditions like heart failure and cancer over time. Overall incidence of number of adults with diabetes and eGFR <60ml/min/1.73 m2 regardless of urine albumin levels increased by 134% from 1988 to 2010. In addition, it was found that the mortality risk for adults with diabetes and eGFR <60ml/min/1.73 m2 with albumin to creatinine ratio (ACR) <30mg/g increased from 35 deaths per 1,000 person-years during 1988-1994 to 51 deaths per 1,000 person-years during the years 2003-2006. It was found that in patients with diabetes and eGFR < 60ml/min/1.73 m2 and ACR ≥  30mg/g mortality risk decreased over time. Overall, the percentage of deaths occurring in eGFR < 60ml/min/1.73 m2 increased from 32.2% during the years 1988-1994 to 44.7% during years 2003-2006.

Low eGFR defined as eGFR < 60ml/min/1.73 m2 affects one in six U.S adults with diabetes and more than half of adults with diabetes and low eGFR do not have increased urine albumin excretion. More than one in five deaths in American population with diabetes occurs in patients with eGFR < 60ml/min/1.73 m2 and ACR <30 mg/g and this mortality rate have been increasing over time from 1988 to 2010. The  decrease in mortality risk in patients with diabetes and eGFR < 60ml/min/1.73 m2 and ACR ≥  30mg/g may probably be due to improved blood glucose control, blood pressure control, and increased use of medications such as RAAS inhibitors. The use of RAAS inhibitors and levels of blood pressure were significantly lower in later years.

Over time, the mortality rates have been decreasing in most adults with diabetes and increased urine albumin excretion. In contrast, mortality rates have been increasing for people with diabetes with low eGFR in the absence of increased urine albumin excretion. The glucose-lowering medications, including sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists have shown both renal and cardiovascular benefits in patients with diabetes without increased urine albumin excretion. Use of these medications have been proven to reduce mortality in this patient population.

This study based diabetic kidney disease on eGFR and ACR values. The limitation of this study, therefore, is that low eGFR in the absence of increased urine albumin excretion may be due to non-diabetes disease processes such as tubulointerstitial disease. Furthermore, the definition of diabetes can be different across different physicians and maybe lead to a difference in prevalence estimates.

Practice Pearls:

  • In adults with diabetes and eGFR <60 ml/min/1.73 m^2 and an ACR < 30mg/g, mortality rates increased over time.
  • In adults with diabetes with low eGFR and ACR >30 mg/g, mortality rates decreased over time.
  • Optional interventions are needed to decrease mortality rate in those with diabetes with a low eGFR and ACR <30 mg/g. Use of glucose-lowering medications such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 agonists have shown benefit in this patient population.

Reference:

Kramer H, Boucher R, Leehey D et al. Increasing Mortality in Adults With Diabetes and Low Estimated Glomerular Filtration Rate in the Absence of Albuminuria. Diabetes Care. 2018.

Vidhi Patel, Pharm. D. Candidate 2018, LECOM School of Pharmacy