Longitudinal Analysis of Blood Pressure, Lipid, and Glycemic Control in Diabetic Patients With Nephropathy Attending a Hospital Outpatient Clinic and Their Relationship to Renal Function, Mortality, and Cardiovascular Morbidity Free

Clinical trials have shown that optimal blood pressure (BP) control slows the deterioration of renal function in diabetic nephropathy (1), with specific renoprotection from ACE inhibition therapy (2). The benefit of glycemic control is less well established (3). Studies have demonstrated the efficacy of lipid control in the primary and secondary prevention of coronary heart disease in diabetic and nondiabetic people (4,5). Therefore, it is important that patients with diabetic nephropathy use a multiple risk-factor approach (6). Few data are available on BP, lipid, and glycemic control in the nontrial setting. We recently audited the use of therapies proven beneficial in a high-risk group of diabetic patients with overt nephropathy and completed a retrospective analysis of putative renal-failure progression factors from 1992 to 1999.

Data were extracted from our Diabetic Nephropathy Database (Microsoft Access 1997). Mean systolic BP (SBP), diastolic BP (DBP), HbA_1c, total serum cholesterol (TC), BMI, and serum creatinine (CR) at baseline and follow-up, as well as demographic data including age, sex, age at diagnosis, duration of diabetes, diabetes type, length of follow-up, presence of retinopathy, smoking status, and date of death were documented for each patient. The number of patients from 1992 to 1999 with new ischemic heart disease (IHD), cerebrovascular disease (CVD), and peripheral vascular disease events with no previous history were also determined. Documented drug classes included statins, fibrates, β-blockers, calcium channel blockers, α-blockers, ACE-inhibitors (ACEI), angiotensin-II receptor antagonists, loop diuretics, thiazide diuretics, and aspirin. All patients with a CR >120 μmol/l, a positive dipstick proteinuria on at least three occasions (of which two were consecutive), and at least 2 years of follow-up data were selected from the database. Renal function for each patient was estimated using the inverse of serum CR (1/CR), and change in renal function was estimated as the rate of change of 1/CR (Δ1/CR). Two patient groups were created for comparison— deterioration in renal function versus stable or improved renal function. The British Hypertension Society recommendation of a BP ≤140/80 mmHg (7) defined optimal BP control, and the Joint British Society recommendation of a TC ≤5 mmol/l (8) defined optimal lipid control. An HbA_1c ≤7.5% defined optimal glycemic control (9,10).

A total of 260 patients had diabetic nephropathy with a mean ± SD BP of 146/72 ± 23/14 mmHg. Δ1/CR deteriorated in 61% of patients. In this group, SBP was higher (153 ± 24 vs. 136 ± 17 mmHg, P < 0.0001), more patients had a SBP >140 mmHg (70 vs. 40%, P < 0.001), and there were more deaths (33 vs. 15%, P = 0.001) compared with the patients in whom Δ1/CR remained stable or improved. In addition, 47 and 29% of patients achieved optimal glycemic and lipid control, respectively. Relatively few patients were taking aspirin (44%), lipid-lowering (20%), or ACEI (39%) therapy. Using simple regression, SBP was the strongest predictor of Δ1/CR (r = 0.23, P < 0.001), death (hazard ratio [HR] 95% CI 2.2 [1.6–4.1]), and IHD (HR 1.9 [1.4–3.4]). Using multiple regression, SBP was a strong predictor of death (HR 2.7 [1.5–4.9]) and IHD (HR 2.4 [1.7–5.5]), but not a strong predictor of Δ1/CR (P = NS). Using simple regression, DBP was a predictor of death (HR 1.7 [1.2–7.8]) and IHD (HR 1.5 [1.1–5.7]), but this significance was lost using multiple regression. TC was a predictor of IHD events using simple regression (HR 3.1 [2.2–6.8]) and multiple regression (HR 2.1 [1.5–5.7]). Lack of ACEI therapy was a predictor of death when using simple regression (odds ratio [OR] 95%CI 1.7 [1.2–3.9]), but not when using multiple regression. Using multiple regression, patients not on aspirin therapy had worse renal function (β = −232 × 10⁻⁶, P = 0.002) and an increased risk of death (OR 2.8 [1.9–4.3]) and CVD (OR 2.2 [1.7–6.5]) compared with patients receiving aspirin treatment.

The mean ± SD BP of 146/72 ± 23/14 mmHg achieved in our patients is very close to the reported values in the tight BP arm of the UKPDS trial (144/82 ± 14/7 mmHg) (11), thus demonstrating that reasonable BP control can be achieved in routine clinical practice. Low use of therapies proven beneficial, unsatisfactory glycemic and lipid control, and the importance of SBP in determining renal function decline in our patients reinforced the need for multiple risk-factor intervention in patients with diabetic nephropathy.