Insulin, Sodium-Lithium Countertransport, and Microalbuminuria in Hypertensive Patients

Abstract

Both microalbuminuria (0.290 nmol/min [20 g/min]) and high sodium-lithium countertransport (SLC) in diabetic or hypertensive humans are predictive of overt nephropathy and more aggressive cardiovascular complications, perhaps induced by insulin resistance. To analyze the relationships between microalbuminuria, SLC, microalbuminuria, and insulin in essential hypertension, we studied 90 hypertensive white patients, 25 of whom had microalbuminuria and 32 of whom were healthy. When urine sampling was completed for albuminuria determination, SLC was measured; all patients then underwent standard (75 g) oral glucose load to measure basal (0 minutes) and 2-hour glucose and insulin serum levels. Glucose-insulin ratio was used as insulin sensitivity index (ISI). In both hypertensive patients with normal microalbuminuria and those with pathological microalbuminuria, plasma insulin at 120 minutes was significantly higher than in control subjects. When the patients with pathological microalbuminuria were divided into thirds on the basis of their microalbuminuria, in the lower third, we found statistically significant less fasting insulin and higher basal ISI. SLC was higher in hypertensives than normotensives and, among hypertensives, higher in the subgroup with elevated microalbuminuria. In hypertensives, we found a weak but significant correlation between SLC and microalbuminuria, independent of insulin or ISI. The prevalence of high value of SLC (0.383 mmol L 1 h 1) was significantly lower in hypertensives with normal rather than abnormal urinary albumin excretion. Our results indicate that in nondiabetic hypertensive whites, higher microalbuminuria is accompanied by signs of insulin resistance; moreover, a link exists between SLC and microalbuminuria, both predictive of aggressive complications of hypertension. (Hypertension. 1998;31[part 1]:110-113.) Key Words: insulin sodium-lithium countertransport microalbuminuria insulin resistance cardiovascular risk nephropathy M icroalbuminuria, defined as urinary albumin excretion (UAE) rate 0.290 nmol/min (20 g/min), has recently been recognized in diabetes mellitus predictive of overt ne-phropathy and more aggressive cardiovascular complications. 1-3 It has also been related to 24-hour blood pressure levels in hypertensive nondiabetic subjects 4,5 and regarded as an independent risk factor for renal and cardiovascular damage. 4,6 Increased sodium-lithium countertransport (SLC) activity is another marker of renal and cardiovascular complications in diabetes 7,8 and in essential hypertension, 9,10 where it could be linked to an insulin-resistance condition. 11-13 The aim of this study is to analyze the relationships between microalbumin-uria, SLC, and insulin in essential nondiabetic hypertensive whites. Methods We studied 90 white patients with mild to moderate essential hypertension lasting no more than 5 years and 32 healthy subjects from laboratory and ward staff with comparable body mass index, race, and gender distribution (Table 1). All gave their informed consent, and t...

Usefulness of Microalbuminuria in Cardiovascular Risk Stratification of Essential Hypertensive Patients

“…For example, it has long been recognized that echocardiography is more sensitive and specific than electrocardiograms and chest X-ray for detecting LVH [20]. Furthermore, the importance of microalbuminuria as an integrated marker of early renal and cardiovascular changes as well as an independent predictor of cardiovascular risk has been highlighted in an increasing number of studies, not only in diabetic patients [1, 2, 3]but also in hypertensive subjects and in the general population [4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19]. …”

“…The sensitivity of this method is 0.5 µg/ml, the transferrin cross-reactivity is <0.01% and the intra- and interassay coefficient of variation were ≤5.1 and ≤7.2%, respectively. Microalbuminuria was defined as an albumin excretion rate (AER) <200 and ≥20 µg/min, this latter being the 95th percentile of a control group of normal subjects [8]. The average of two AER determinations was considered for labelling all the patients as having microalbuminuria or not.…”

“…Recently, a large body of evidence has been published suggesting that the value of microalbuminuria as a predictor of organ damage [4, 5, 6, 7, 8, 9, 10, 15, 18]and of cardiovascular events and total mortality [11, 12, 13, 14, 15, 16, 17, 18, 19]may be extended to non-diabetic subjects and to patients with essential hypertension. It has been clearly demonstrated that left ventricular hypertrophy (LVH) determined by either electrocardiography (ECG) or echocardiography is a strong independent risk factor for cardiovascular morbidity and mortality in the general population and among hypertensive patients [20, 21].…”

Increased red cell sodium-lithium countertransport and lymphocyte cytosolic calcium are separate phenotypes in patients with essential hypertension

“…However, elevated SLC activity is not only present in patients with essential hypertension but also in patients with diabetic nephropathy and is a predictor of progression to microalbuminuria in nondiabetics. [27][28][29] No links of cell calcium abnormalities to target organ damage or clinical manifestations of cardiovascular disease have been reported. Since we observed an inverse relationship between Ca cyt and SLC activity, by extrapolation this may imply that high Ca cyt is not a marker for the development of end Journal of Human Hypertension organ damage.…”

Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

“…Not surprisingly, therefore, essential hypertensive patients with microalbuminuria frequently showed either mild fasting hyperglycaemia or a hyperglycaemic response to oral glucose loading. [63][64][65][66][67][68][69][70][71][72] Since a worse glucose tolerance is part of the so-called metabolic syndrome X, 73 slight elevations in UAE were also associated with its typical phenotypes, ie, hyperinsulinaemia, [63][64][65][66][67][68][69][70][71][72]74 insulin resistance, 67,68 high triglycerides and low high-density lipoprotein (HDL), 25,75,76 overweight-obesity 18,77,78 and BP sensitivity to increased sodium intake. 79 Increased concentrations of total and low-density lipoprotein (LDL)-cholesterol sometimes reported in hypertensive patients with microalbuminuria 3 have raised the intriguing possibility of a link between microalbuminuria and atherogenic lipids unrelated to the trait of the syndrome X, but the results of large-scale studies 14,18 seem to contradict that possibility.…”