In the JournalsPerspective

NAFLD predicted CKD in adults with type 1 diabetes

Measuring for nonalcoholic fatty liver disease in patients with type 1 diabetes may improve the risk prediction for chronic kidney disease, according to findings published in Diabetes Care.

A study by Giovanni Targher, MD, of the University of Verona in Italy, is the first to demonstrate that nonalcoholic fatty liver disease (NAFLD) is strongly linked to an increased incidence of CKD.

Targher and colleagues followed 261 adults with type 1 diabetes with preserved kidney function and no macroalbuminuria at baseline for an average of 5.2 years. The researchers investigated the occurrence of CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73 m², and/or macroalbuminuria. Ultrasonography was used to diagnose NAFLD.

The average eGFR at baseline was 92 ± 23 mL/min/1.73 m². Normoalbuminuria was present in 234 patients (89.7%), microalbuminuria in 27 (10.3%) and NAFLD in 131 (50.2%). During follow-up, 61 patients developed incident CKD.

NAFLD was associated with an increased risk for incident CKD (HR=2.85; 95% CI, 1.59–5.1).

The association did not appreciably diminish with adjustments for age, sex, duration of diabetes, hypertension, HbA1c and baseline eGFR (adjusted HR=2.03; 95% CI, 1.1-3.77).

No changes were seen after excluding those who had microalbuminuria at baseline (adjusted HR=1.85; 95% CI, 1.03-3.27).

The regression models for predicting CKD showed significant capability improvements when NAFLD was added to the traditional risk factors.

“This is the first study to demonstrate that NAFLD is strongly associated with an increased incidence of CKD,” the researchers wrote, “and that measurement of NAFLD improves the risk prediction of CKD, independently of traditional cardio-renal risk factors, in adults with type 1 diabetes.”

Disclosure: Targher was supported in part by grants from the University of Verona School of Medicine. Another researcher was supported in part by the Southampton National Institute for Health Research Biomedical Research Centre.

Kenneth Cusi, MD, FACP, FACE

Kenneth Cusi

  • This is an important study because it raises awareness that nonalcoholic fatty liver disease (NAFLD) is a very common problem in patients with diabetes. In our experience, this is especially true in patients with type 2 diabetes, in whom about at least two thirds have NAFLD and as many as half may have nonalcoholic steatohepatitis (NASH), the more severe form of the disease that poses a risk of future cirrhosis. However, this paper goes beyond this to say that the disease is very common in patients with type 1 diabetes, with between 40 and 50 percent at risk of developing NAFLD. Until this point, we were not aware that it was also so prevalent in type 1 diabetes.  Furthermore, this is the first longitudinal study that links NAFLD as a potential new risk factor for the development of chronic kidney disease (CKD) in diabetes.

    Limitations of the study were the small sample size, with only 261 participants, of which 61 developed CKD and only about 40 experienced increased protein in the urine.

    In addition, patients with CKD showed all the traditional risk factors for developing this complication: they were older, had more often hypertension, a longer duration of diabetes, higher HbA1c and worse kidney function to start with. In most studies, when investigators adjust for these risk factors, typically the risk of developing CKD is greatly attenuated or even completely abolished. So, to this reviewer, it was somewhat puzzling that the researchers observed only a minimal difference in this study. Lastly, liver ultrasounds used to screen for fatty liver can result in false positives and false negatives, precluding accurate NAFLD group assignment compared to the gold-standard magnetic resonance and spectroscopy (MRS) technique.  

    In summary, its most significant contribution is a call to understand the potential relationship between NAFLD and CKD in diabetes. So far, much attention has been placed on the role of NAFLD in the development of insulin resistance, dyslipidemia, type 2 diabetes, and cardiovascular disease (Cusi K. Gastroenterology, 142:711-725, 2012.), and while all aspects remain controversial, little to no attention has been paid to the possible link between NAFLD and retinopathy, neuropathy or CKD.  Clearly more carefully crafted studies are warranted to confirm (or refute) these provocative findings, but this work is a good first step in that direction.

    • Kenneth Cusi, MD, FACP, FACE
    • Professor of medicine and chief of the division of endocrinology, diabetes and metabolism
      University of Florida at Gainesville
  • Disclosures: Cusi reports no relevant financial disclosures.