Renal functional reserve and microalbuminuria in offspring of hypertensive parents.

Abstract

Renal functional reserve, microalbuminuria, and plasma atrial natriuretic factor were measured in 21 offspring (9.5 +/- 0.5 years of age, mean +/- SEM) of hypertensive parents and in eight children (10 +/- 0.5 years of age) with no family history of hypertension who were used as a control group. Renal functional reserve was evaluated by measurement of the changes in creatinine clearance after an oral protein load of 45 g/m2. Atrial natriuretic factor levels were determined before and 60 minutes after the protein load, and microalbuminuria in fractional urine before and 120 minutes after the same stimulus as well as in a 24-hour urine collection. All children in the control group significantly increased their creatinine clearance after the protein load (preload, 122 +/- 12; 60 minutes, 144 +/- 9; 120 minutes, 154 +/- 11; 180 minutes, 144 +/- 9 ml/min/1.73 m2; all values were significant vs. preload, p less than 0.005). In contrast, only 13 of 21 offspring of hypertensive parents increased their creatinine clearance to values within 2 SD of the increase shown by the control group (preload, 144 +/- 11; 60 minutes, 153 +/- 7; 120 minutes, 202 +/- 13 ml/min/1.73 m2; p less than 0.001 vs. preload; 180 minutes, 214 +/- 19 ml/min/1.73 m2, p less than 0.001 vs. preload). The remaining eight offspring of hypertensive parents showed no detectable changes (nonresponders) (preload, 189 +/- 18; 60 minutes, 146 +/- 11; 120 minutes, 170 +/- 14; 180 minutes, 168 +/- 13 ml/min/1.73 m2; all values p = NS). No changes in atrial natriuretic factor after the protein load were observed in any group. Offspring of hypertensive parents presented higher microalbuminuria levels in 24-hour urine specimens (3.1 micrograms/min, tolerance factor [TF]2.2) than controls (2.1 micrograms/min, TF 1.5) (p less than 0.05). Although microalbuminuria increased significantly after the water load in the control group (p less than 0.05) and in the offspring of hypertensive parents (p less than 0.01), it returned to baseline at 120 minutes in the former but not in the latter (p less than 0.05 vs. baseline). The lack of renal functional reserve in nonresponders was significantly related (p less than 0.05) to the presence of higher levels of microalbuminuria. We conclude that the absence of renal functional reserve and increased microalbuminuria in some normotensive children who are offspring of essential hypertensive parents can indicate that subtle alterations in renal function may precede the onset of clinical hypertension.

Glomerular Hyperfiltration, High Renin, and Low- Extracellular Volume in High Blood Pressure

“…Our observations are consistent with 2 previous studies of normotensive subjects with a family history of hypertension. 7,12 These findings contrast with other studies reporting normal GFR in subjects predisposed to hypertension. 8,11,[47][48][49] The reasons for the discrepancies are not immediately obvious, but the studies differ substantially in the populations examined, the definition of predisposition, the age of subjects, and the methods of measuring GFR.…”

“…[7][8][9][10][11][12] Few data exist in relation to extracellular fluids, but 1 study has suggested that exchangeable sodium is reduced in young hypertensive subjects. 13 Animal models of genetic hypertension show renal phenotypic abnormalities during the development of hypertension, but their exact nature depends on the specific strain.…”

Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression

“…22 Lastly, it has been observed that normotensive children of hypertensive parents have increased urinary albumin excretion, which may further support the premise that microalbuminuria is an early finding in individuals with a predisposition to hypertension. 23 Although the aforementioned studies underscore an important role for the kidneys, the etiology of essential hypertension is almost certainly multifactorial. Accordingly, microalbuminuria may reflect additional processes that may contribute to both renal dysfunction and the pathogenesis of hypertension.…”

Microalbuminuria in salt-sensitive patients. A marker for renal and cardiovascular risk factors.

“…Like in early diabetic renal disease, 48 microalbuminuria may be present in normotensive subjects with a genetic risk for hypertension. 49 - 50 According to this hypothesis, the increase in serum levels of atherogenic lipoproteins would be a consequence rather than the cause of microalbuminuria. In support of this notion is the evidence that urinary losses of large amounts of proteins may lead to increased serum levels of total and LDL cholesterol as well as Lp(a).…”