Observation on Renal Outcomes in the Veterans Affairs Diabetes Trial

Abstract

OBJECTIVEThe Veterans Affairs Diabetes Trial (VADT) was a randomized, prospective, controlled trial of 1,791 patients with type 2 diabetes to determine whether intensive glycemic control would reduce cardiovascular events compared with standard control. The effect of intensive glycemic control and selected baseline variables on renal outcomes is reported.RESEARCH DESIGN AND METHODSBaseline mean age was 60.4 years, mean duration of diabetes was 11.5 years, HbA1c was 9.4%, and blood pressure was 132/76 mmHg. The renal exclusion was serum creatinine >1.6 mg/dL. Renal outcomes were sustained worsening of the urine albumin-to-creatinine ratio (ACR) and sustained worsening by one or more stages in the estimated glomerular filtration rate (eGFR).RESULTSIntensive glycemic control did not independently reduce ACR progression but was associated with a significant attenuation in the progression of ACR in those who had baseline photocoagulation, cataract surgery, or both. The beneficial effect of intensive glycemic control increased with increasing BMI and with decreasing diastolic blood pressure (DBP). Intensive glycemic control was associated with less worsening of eGFR with increasing baseline ACR and insulin use. Baseline systolic blood pressure, triglycerides, and photocoagulation were associated with worsening of eGFR.CONCLUSIONSIntensive glycemic control had no significant effect on the progression of renal disease in the whole cohort but was associated with some protection against increasing ACR in those with more advanced microvascular disease, lower baseline DBP, or higher baseline BMI and on worsening of eGFR in those with high baseline ACR.

Blood Pressure and Pulse Pressure Effects on Renal Outcomes in the Veterans Affairs Diabetes Trial (VADT)

“…Our results for categorical BP and PP values are in accord with our previous analysis in that baseline SBP, but not DBP, was related to a decline in eGFR (2). On-study SBP as a continuous variable showed significant risk for worsening of eGFR.…”

“…The VADT was associated with attenuation of worsening albuminuria in the intensive glycemic treatment group of patients during the trial (17). The initial results and effects of BP on the cardiovascular outcomes and renal outcomes were published recently (1,2). Baseline characteristics of subjects available for the current analyses for worsening albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) are presented in Table 1.…”

“…Nephropathy, a destructive microvascular complication of diabetes, encompasses persistent albuminuria, chronic kidney disease (CKD), arterial hypertension, and eventually end-stage renal failure (2,3). The optimal levels for systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) for renal and cardiovascular protection are less certain (1,3–10).…”

“…The primary goal was to determine whether intensive glucose control prevented major cardiovascular disease events while BP and other risk factors were controlled equally in both glycemic treatment groups (17). An analysis of risk factors and renal outcomes in the VADT has previously been published (2). This report differs from the previous study in three aspects.…”

Niacin and Progression of CKD

“…The effect of glycemic control on CKD progression was not confirmed in recent large trials. 5,6 The very low optimal blood pressure previously recommended for the prevention of progression of CKD 7 is no longer part of the guidelines in view of a lack of evidence of benefit in terms of CVD events 8 or death. 9 Furthermore, studies have shown that angiotensinconverting enzyme inhibitors and angiotensin-2 receptor blockers decrease GFR decline in patients with proteinuria, 10 but their effectiveness in patients with nonproteinuric CKD has been questioned.…”