Glomerular normofiltration in hypertension may mask a state of former hyperfiltration

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Objective: In the majority of hypertensive subjects normofiltration represents a state of preserved renal function. However, previous research has shown that some normofilterers may represent a group of former hyperfilterers with increased risk of microalbuminuria. We did a prospective study to investigate whether in hypertensive normofilterers with former glomerular hyperfiltration, clinical characteristics differ from those of true normofilterers. Design and methods: Creatinine clearance (CrCl) and albumin excretion rate (AER) were measured at entry and after 8.5 years of follow-up, in 534 young-to-middle-age stage 1 hypertensive subjects from the HARVEST (mean age 34.6±8.3 years, 69% men). Glomerular hyperfiltration was defined as a CrCl≥150 ml/min/1.73m2. Baseline ambulatory BP, 24h urinary epinephrine, echocardiographic data, and routine blood tests were also obtained. Results: At follow-up end, 442 participants were normofilterers. Of these, 395 had normal CrCl also at baseline (true normofilterers, Group 1) whereas 47 subjects had a baseline CrCl ≥150 ml/min/1.73m2 (former hyperfilterers, Group 2). Participants of Group 2 had higher age-and-sex-adjusted systolic blood pressure (p=.007) than those of Group 1. In addition, 24h urinary epinephrine (p<.001), heart rate (p=.05), ambulatory night-time BP fall (p=.004), and left ventricular end-systolic stress (p=.01) were higher in Group 2. During the follow-up, subjects of Group 2 had a greater baseline-adjusted increase in glucose than those of Group 1 (p=.03) and a tendency to the impairment in the other metabolic data. At follow-up end, microalbuminuria was 5.3% in subjects of Group 1 and was 36.2% in those of Group 2 (p<0.0001). This difference held true in a multivariable logistic regression in which several confounders, ambulatory blood pressure, baseline AER, and other risk factors were taken into account (p<0.0001). Conclusions: These data show that hypertensive normofilterers with former hyperfiltration are a distinct subgroup characterized by higher sympatho-adrenergic activity and poorer metabolic profile. These patients are at increased risk of renal damage and should be treated earlier for hypertension