Nonalbuminuric DKD May Have Lower Risk for Mortality, CVD, Renal Decline

Nonalbuminuric diabetic kidney disease (DKD) is not linked to a higher risk for mortality, cardiovascular disease (CVD) events, or renal function decline than other diabetic kidney disease phenotypes, according to the results of an observational prospective cohort study published in Diabetes Care. In fact, prognosis of nonalbuminuric DKD may be better with regard to long-term cardiovascular and renal outcomes.

Studies have shown that nonalbuminuric renal impairment has become the prevailing phenotype in patients with DKD and type 2 diabetes (T2D). Investigations into the lifetime prognosis and progression of CVD and end-stage renal disease for patients with nonalbuminuric DKD have had conflicting results.

To compare the rates of mortality, CVD events, and renal function decline in patients with T2D with varying DKD phenotypes and histories of CVD, observational data from 2953 Japanese patients (63.7% men) with T2D were analyzed. Patients with T2D, an estimated glomerular filtration rate (eGFR) of ≥30 mL/min/1.73 m², and no relevant data missing were included. The average age of patients was 58.4±8.3 years.

In this study, DKD was defined as kidney disease accompanied by diabetes, although the cause of kidney disease was not proven by biopsy. DKD was assessed by albuminuria and serum creatinine levels at baseline. At baseline, most patients did not have DKD (61.1%). Of the patients with DKD (38.9%), most were albuminuric without reduced eGFR (65.0%). Of the patients who presented with reduced eGFR (13.6%), approximately half were nonalbuminuric (50.6%). Among the 4 DKD phenotypes, patients with nonalbumineric DKD were more frequently women, were more often never-smokers (P <.001), and had lower levels of hemoglobin A1c (P <.001) and systolic blood pressure (P <.001) compared with patients with albuminuric DKD phenotypes.

During follow-up, 264 patients developed CVD and 358 patients reached the composite end point of CVD or death. The adjusted hazard ratios (aHRs) for CVD and the composite end point of CVD or death were not significantly greater in patients with nonalbuminuric DKD compared with individuals without DKD but were significantly increased in patients with albuminuric DKD with reduced eGFR (aHR, 2.32; 95% CI, 1.67-3.24; P <.001) or without reduced eGFR (aHR, 1.73; 95% CI, 1.35-2.21; P <.001). The risk for death or CVD events in patients with prior CVD was higher than in those without, regardless of DKD phenotype. The risk for death or CVD events for patients with nonalbuminuric DKD who had no history of CVD was similar to that of patients without DKD who had no history of CVD.

In fully adjusted models, incidence rates of progression to eGFR <30 mL/min/1.73 m²  in patients with DKD were lowest in patients with nonalbuminuric DKD (aHR, 5.88; 95% CI, 2.21-15.61) and highest for patients with albuminuric DKD with reduced eGFR (aHR, 77.72; 95% CI, 39.32-153.64).

Taken together, these findings indicated that the prognosis — in terms of mortality, CVD events, and declining renal function — of nonalbuminuric DKD was not siginificantly worse than that of no DKD in a group of Japanese patients with T2D, whereas albuminuric DKD phenotypes exhibited worse prognosis. Moreover, risk for death or CVD in patients with nonalbuminuric DKD and no prior CVD was not significantly higher compared with patients with no DKD and no history of CVD, whereas patients with albuminuric DKD without a history of CVD had a higher risk.

A limitation to this study was its observational nature, which prevented causality from being assessed. Further study of which therapeutic strategy is optimal for patients with nonalbuminuric DKD is warranted.

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Reference

Yokoyama H, Araki SI, Kawai K, et al. The prognosis of patients with type 2 diabetes and nonalbuminuric diabetic kidney disease is not always poor: implication of the effects of coexisting macrovascular complications [published online March 6, 2020]. Diabetes Care. doi: 10.2337/dc19-2049