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Hypertension. 1995;25:1315-1321

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(Hypertension. 1995;25:1315-1321.)
© 1995 American Heart Association, Inc.

Articles

Albuminuria in Association With Insulin and Sodium-Lithium Countertransport in Young African Americans With Borderline Hypertension

Bonita Falkner; Harvey Kushner; Sandra Levison; Mitzy Canessa

From the Medical College of Pennsylvania and Hahnemann University, Philadelphia, and the Brigham and Women's Hospital, Boston, Mass.


*    Abstract
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 *Abstract
down arrowIntroduction
 down arrowMethods
 down arrowResults
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 down arrowReferences
 
Abstract The purpose of this study was to determine whether early nephropathy, evidenced by urinary albumin excretion, can be detected in young African American subjects with only borderline hypertension, and whether there is a relationship of albuminuria with insulin resistance and with sodium-lithium countertransport activity. Clinically well young African American men and women including normotensive (blood pressure <135/85 mm Hg, n=41) and borderline hypertensive (blood pressure >=135/85 mm Hg, n=26) individuals were studied. Each subject underwent an oral glucose tolerance test and euglycemic hyperinsulinemic clamp study. Albuminuria was measured on timed urine collections. Sodium-lithium countertransport activity was assayed in fresh red blood cells at 280 mmol/L Na+ for full saturation of external Na+ sites. The sum of insulin levels during glucose tolerance was significantly greater in the borderline hypertensive compared with the normotensive subjects (P=.014), and insulin-stimulated glucose utilization during the clamp was significantly lower in borderline hypertensive compared with normotensive subjects (P=.016). Albuminuria was greater in borderline hypertensive compared with normotensive subjects (P=.002). Albuminuria was significantly correlated with fasting plasma insulin concentration (r=.44, P<.002) and the sum of insulins during the glucose tolerance test (r=.45, P<.002). Sodium-lithium countertransport correlated with albuminuria (r=.31, P<.05) as well as significantly with insulin-stimulated glucose utilization during the clamp (r=.44, P<.001). These data indicate that young African Americans with only borderline hypertension have greater albuminuria than normotensive subjects and suggest that albuminuria is linked with insulin resistance and alterations of sodium-lithium countertransport that may increase the risk for nephropathy.


Key Words: hypertension, borderline • albuminuria • blacks • insulin • blood pressure • sodium


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
The prevalence of hypertension is greater in African Americans than in Caucasians,1 2 as is the morbidity associated with hypertension, including hypertensive kidney failure.3 4 5 The excess incidence of end-stage renal disease in African Americans may be due to undetected or inadequately treated hypertension. However, deterioration in renal function has been detected in some African American patients with essential hypertension despite good blood pressure (BP) control.5 These observations raise the possibility that factors other than pressure trauma to the renal vasculature may be mediating the progression of renal injury. Urinary albumin excretion (UAE) can be detected in Caucasian populations with essential hypertension,6 7 and UAE higher than 30 mg/24 h is associated with greater cardiovascular risk.8 9 Elevated UAE in patients with insulin-dependent diabetes mellitus (IDDM) is predictive of the development of clinical nephropathy.10 More recent reports suggest that an increase in UAE in patients with essential hypertension can also be predictive of renal injury or developing nephropathy.11

Increased sodium-lithium countertransport (SLC) activity in red blood cells (RBCs) has been demonstrated in IDDM patients who have clinical renal disease.12 13 Nosadini et al11 also reported that nondiabetic patients with essential hypertension who have elevated SLC activity also have renal and cardiac hypertrophy and increased UAE. Several investigations have established an independent correlation of insulin resistance and hyperinsulinemia with essential hypertension,14 15 and this relationship is also present in African Americans.16 17 In addition, elevated SLC activity has been detected in patients with essential hypertension who were also insulin resistant.18 19

These reports suggest a linkage of insulin resistance with elevated SLC activity in hypertension. Although the evidence that insulin resistance and high SLC activity convey an increased risk for cardiovascular morbidity, including nephropathy, is as yet speculative, most of the data have been gathered from patients with well-established hypertension, and few data are available on an African American population. The purpose of this study was to determine whether early nephropathy, evidenced by UAE, can be detected in young African American subjects with only borderline hypertension and whether there is a relationship of UAE with insulin resistance and SLC.


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Population
This study was conducted in a young clinically well population of African Americans. We used an oral glucose tolerance test (OGTT) to measure plasma glucose and insulin concentrations after a standard glucose challenge. We used a euglycemic hyperinsulinemic clamp procedure to quantify insulin-stimulated glucose utilization. Timed urine collections were analyzed for albumin excretion, and SLC was measured in fresh RBCs. The protocol for this study was approved by the Institutional Review Board of the Medical College of Pennsylvania. Written informed consent was obtained from all participants at the time of enrollment. Subjects were all young adult African Americans ranging in age from 28 to 33 years. Each participant was drawn from a population that has been under study in ongoing investigations of BP regulation since adolescence. Individuals with either IDDM or non–insulin-dependent diabetes mellitus (NIDDM) were excluded. No subject was taking antihypertensive medication at the time of study.

Procedures
Enrollment assessment consisted of physical examination, anthropometric measurements (height, weight, computed body mass index), and BP determination. Casual systolic (first phase) and diastolic (fifth phase) BP measurements were obtained by auscultation with the use of a mercury column sphygmomanometer with subjects in the seated position after a 10-minute rest period. The average of two determinations was used as the BP at the time of the metabolic evaluation. A history of the subject's diet was taken and he or she was asked to continue her or his usual dietary patterns through the completion of the protocol. For this population, the dietary average consisted of 14% protein, 31% fat, and 55% carbohydrate. No subject's diet deviated significantly from this average. After the enrollment assessment, each subject returned to the clinical research unit for an OGTT that was scheduled in the morning following a 12-hour fast. A fasting blood sample was obtained, and then a 75-g glucose solution (Glucola, Ames Laboratories) was taken orally. Blood samples were obtained at 30, 60, and 120 minutes after ingestion of the glucose load. Each blood sample was immediately centrifuged. Plasma was removed and stored at -80°C until the samples were assayed for glucose and insulin concentrations.

The euglycemic hyperinsulinemic clamp was used for measurement of insulin-stimulated glucose utilization.20 21 During steady-state hyperinsulinemia, the glucose infusion rate required to maintain euglycemia quantifies insulin-stimulated glucose metabolism (in milligrams per kilogram per minute). In both nonobese and obese young black men, we have demonstrated that with steady-state hyperinsulinemia at a level of 70 to 80 µU/mL greater than fasting, endogenous glucose production is completely suppressed during the final 60 minutes of the procedure.22 Because the target level of steady-state hyperinsulinemia in the present study was at least 70 to 80 µU/mL greater than fasting, endogenous glucose production is completely suppressed, and the glucose infusion rate required to maintain euglycemia is an adequate index of total insulin-stimulated glucose utilization.21

Each subject was scheduled to return to the clinical research unit for the euglycemic clamp procedure at 8 AM after a 12-hour overnight fast. The euglycemic clamp procedure was conducted according to methods previously described.17 In brief, the subject rested for at least 20 minutes after placement of venous catheters for infusion and sample withdrawal. Before the onset of euglycemic hyperinsulinemia, three samples were withdrawn for determination of fasting plasma glucose and fasting plasma insulin concentrations. Euglycemic hyperinsulinemia was established with a primed constant infusion of insulin, using the method of Rizza et al21 to compute the insulin priming dose and infusion rate. The target clamped insulin concentration was 70 to 80 µU/mL of insulin above fasting concentration, which was achieved with an infusion rate of 40 mU/m2 per minute.21 Glucose was administered as 20% dextrose in water (Abbott Laboratories). The precise glucose concentration in the 20% dextrose stock solution was measured, and this value was used in the calculation of glucose infusion rate with the negative feedback equation of DeFronzo et al.20 A personal computer was programmed to utilize this iterative negative feedback equation, which was amended for 10-minute plasma glucose sampling. Euglycemic hyperinsulinemia was maintained for 120 minutes. During the final 60 minutes of steady-state hyperinsulinemia, insulin-stimulated glucose utilization was determined from the glucose infusion rate. The coefficient of variation for clamped plasma glucose concentration was less than 5% during the final 60 minutes of the procedure. A poststudy urine sample was obtained and analyzed for glucose.

Two timed overnight urine collections were obtained from each subject. The first urine collection was completed on the morning of the OGTT and the second on the morning of the clamp procedure. In addition, a timed urine collection was obtained during the OGTT, and a fourth timed urine collection was obtained during the clamp. Each of the urine collections was assayed for albumin and creatinine concentrations. UAE was determined in micrograms per minute and in milligrams albumin per gram creatinine.

Insulin (Eli Lilly) was mixed with normal saline to a concentration of 1000 mU/mL. All solutions were delivered by syringe pumps (model 22, Harvard Apparatus). Plasma glucose concentration was analyzed with the glucose oxidase technique (Glucostat, model 27, Yellow Springs Instrument Co). Plasma insulin concentration and UAE were determined with a solid-phase radioimmunoassay (Coat-A-Count, Diagnostic Products Corp). Urinary creatinine concentration was determined by the creatinine kinase method (Creatinine Analyzer 2, Beckman Instruments).

The SLC assay was performed on RBCs that were obtained after an overnight fast. Blood for the SLC assay was drawn into heparinized tubes and centrifuged at 2000g for 4 minutes at 4°C. The plasma and buffy coat were removed by aspiration, and the RBCs were suspended at 20% in cold preserving solution22 and shipped overnight to Boston in Styrofoam buckets containing crushed ice. The next morning the RBCs were prepared for the SLC assay according to methods previously described.23

The SLC assay measures the transport of Li+ coupled to the Na+ gradient as external Na+-stimulated Li+ efflux. Saturation of internal sites is obtained by loading RBCs with 8 mmol/L of cell Li+ with the nystatin procedure. For determination of Vmax it is necessary to increase the Na+ concentration in the efflux media to more than twice the apparent affinity constant (Km). Previous experiments performed in hypertensive subjects indicated that Li+ efflux was a linear function of external Na+ between 0 and 150 mmol/L and did not reach saturation even at 150 mmol/L Na+.24 25 For this reason, a different method was developed to increase external Na+ to 280 mmol/L and to avoid cell shrinkage by setting isosmotic conditions.23 24 25 This new 600 mOsm/L procedure is fully described below.

(1) Li+ loading of RBCs. Packed RBCs (4 mL) were suspended at 4°C for 20 minutes in 20 mL nystatin Li+ loading solution containing (mmol/L) LiCl 20, KCl 265, and sucrose 50 as well as 40 mg/L nystatin; the final osmolarity was 600±10 mOsm/L. Subsequently, the cell suspension was centrifuged, the supernatant discarded, and the loading solution (without nystatin) renewed and incubated for an additional 10 minutes at 4°C. Nystatin was removed by addition of 5 mL warm (37°C) nystatin washing solution (NWS) and incubation of the cell suspension for 10 minutes at 37°C. NWS contained (mmol/L) KCl 265, sucrose 50, glucose 10, and potassium phosphate buffer 1.0 (pH 7.4 at 37°C, 600±10 mOsm/L) as well as 0.1% albumin. Nystatin removal was ensured by four more washes with NWS. The mean cation content of Li+-loaded RBCs was Li+, 15±2; K+, 238±10; and Na+, 1.4±0.2 mmol/L of cells (mean±SEM, n=50).

(2) Lithium efflux. For measurement of Vmax, Li+ efflux was determined by incubation of Li+-loaded RBCs in 280 mmol/L choline chloride and Na+ medium (280 mmol Na+ per liter). The Na+ medium contained (mmol/L) MOPS-Tris 10 (pH 7.4 at 37°C), MgCl2 1.0, and ouabain 0.1. The choline medium contained (mmol/L) choline chloride 300, MgCl2 1.0, MOPS-Tris 10 (pH 7.4 at 37°C), and ouabain 0.1.

Efflux was started by addition of 0.7 mL of 50% hematocrit cell suspension to 7 mL medium preincubated at 37°C (final hematocrit, 3% to 4%). Duplicate samples were taken after incubation times of 10, 25, and 40 minutes, and the medium was separated by centrifugation at 4°C for 10 minutes at 6000g. The Li+ concentration of the efflux medium samples was determined by atomic absorption spectrophotometry using standards with the same composition as the flux medium. At every time point, the Li+ content of the medium (Lim) in millimoles per liter of cells (or micromoles per milliliter of cells) was calculated as follows:


where Lic is the Li+ concentration of the efflux medium in micromoles per liter, Hto is the hematocrit of the cell suspension, and CS is cell suspension.

Li+ efflux into both media was calculated from the slope±SEM of the linear regression analysis of Li+ content of the media (millimoles per liter of cells) versus time of the six time samples. Na+-stimulated Li+ efflux was calculated as the difference between Li+ efflux into the Na+ and choline media.

Data Analysis
Two-way ANOVA was used to test for significant differences in means (normotensive versus hypertensive subjects, men versus women). Tests for interactions were conducted between BP and gender groups. Instead of using a repeated-measures ANOVA and post hoc t tests for the OGTT data, we compared plasma insulin levels at each time point separately and used the total sum of insulin to compare the entire curves across all time points. Differences in means and interactions were considered statistically significant at a value of P<.05. Bivariate correlations among numerically continuous variables were examined using Pearson correlation coefficients. Stepwise multiple linear regressions were used to examine multiple correlations among variables and to build a regression model of the measures of UAE on other variables.


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowReferences
 
Our study sample was drawn from a population that has been studied longitudinally since childhood.16 25 26 Enrollment assessment, OGTT, and the euglycemic hyperinsulinemic clamp procedure were completed on 67 subjects. The study group consisted of normotensive (n=41, 61%) and borderline hypertensive (n=26, 39%) young adult African Americans without clinical abnormalities in carbohydrate metabolism. We have previously categorically defined our population as normotensive (BP <135 mm Hg systolic and <85 mm Hg diastolic) or borderline hypertensive (BP >=135 mm Hg systolic or >=85 mm Hg diastolic) based on repeated BP measurements since late adolescence.16 27 Table 1 provides descriptive data on this clinical sample. The participants in this study were within a narrow age range, with a mean of 29.7 years. According to definition, those with borderline hypertension had significantly higher systolic and diastolic BP values than normotensive subjects. Body mass index was greater in the borderline hypertensive subjects, but in this sample the difference in body mass index between the BP groups did not reach statistical significance. Plasma creatinine concentrations and calculated clearance values were in the normal range for both BP and gender groups.


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  		Table 1. African American Study Population

Fig 1 depicts the plasma insulin response to the glucose challenge during the OGTT for normotensive and borderline hypertensive subjects. The curves show a higher plasma insulin concentration for the hypertensive compared with the normotensive subjects. The computed sum of insulin values was significantly greater for the hypertensive subjects (405±54 µU/mL [2906±387 pmol/L]) than normotensive subjects (296±33 µU/mL [2123±237 pmol/L], P=.014). Two-way ANOVA showed that there was also a significant gender difference, with women having a greater sum of insulin concentration during the OGTT than men (386±42 versus 299±42 µU/mL [2769±301 versus 2145±301 pmol/L], respectively, P=.025). Fig 2 provides data on insulin-stimulated glucose utilization determined during the clamp procedure. Borderline hypertensive subjects had significantly lower glucose uptake than normotensive subjects (5.0±0.6 versus 6.3±0.4 mg/kg per minute, respectively, P=.016), indicating insulin resistance in the hypertensive compared with the normotensive subjects. There was a gender difference, with women exhibiting a significantly lower insulin-stimulated glucose utilization compared with men (5.2±0.4 versus 6.3±0.6 mg/kg per minute, respectively, P=.023).



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  		Figure 1. Line graph shows mean values for plasma insulin concentration plotted at 0, 30, 60, and 120 minutes during oral glucose tolerance test for normotensive (lower line) and borderline hypertensive (upper line) subjects. By two-way ANOVA the area under the curve (sum of insulins) is greater for borderline hypertensive than normotensive subjects (P=.014), and the insulin response is greater for women than men (P=.025). To convert insulin values to picomoles per liter, multiply by 7.175.



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  		Figure 2. Bar graph shows insulin-stimulated glucose utilization (M) determined during the clamp procedure for men (open bars) and women (hatched bars) in each blood pressure group. M is significantly lower for borderline hypertensive compared with normotensive subjects (P=.016). M is also significantly lower in women compared with men (P=.023). To convert glucose from milligrams to millimoles, multiply by 0.00555.

The reliability of the measured UAE in this population was determined using the two overnight timed collections. The correlation of UAE on these two samples was r=.59, P<.001. Fig 3 depicts the mean values for UAE on the first overnight collection for the population stratified by BP group and gender. Borderline hypertensive subjects had a significantly greater UAE (P=.002) than normotensive subjects, and women had a significantly greater UAE than men (P=.03). Analysis of the second overnight urine collection produced the same results. Results from the analysis of UAE measured during the OGTT were identical to those of the overnight samples: during the OGTT, UAE was significantly greater in the borderline hypertensive compared with the normotensive subjects (P<.002) and women compared with men (P<.03). Measurement of UAE on urine collections obtained during the insulin clamp study detected similar trends between BP and gender groups, but the differences did not reach statistical significance. Table 2 provides the results of the bivariate correlation analysis of UAE with plasma insulin concentration for the total study population. Significant correlations were present for fasting insulin and the sum of insulin values during the OGTT.



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  		Figure 3. Bar graph shows mean urinary albumin excretion (UAE) rate for men (open bars) and women (hatched bars) in each blood pressure group. By two-way ANOVA, UAE is significantly greater for borderline hypertensive compared with normotensive subjects (P=.002). UAE is also greater in women compared with men (P=.03), with the greatest UAE observed in borderline hypertensive women.


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  		Table 2. Bivariate Correlation Analysis for Urinary Albumin Excretion

The bivariate analysis of UAE with Vmax for SLC also demonstrated a statistically significant correlation (P<.05, Table 2). However, when a two-way ANOVA was applied to the SLC data for examination of SLC activity by BP group (normotensive versus borderline hypertensive) and gender (men versus women), SLC was not significantly different between normotensive subjects (0.26±0.02 mmol/L cells per hour) and borderline hypertensive subjects (0.32±0.04 mmol/L cells per hour, P=.09) or between men (0.28±0.03 mmol/L cells per hour) and women (0.29±0.02 mmol/L cells per hour). Thus, although there was a significant but small correlation of UAE with SLC, we could not demonstrate the expected higher SLC in the hypertensive subjects. However, there was a statistically significant negative correlation of SLC with insulin-stimulated glucose utilization determined by the hyperinsulinemic clamp procedure (Fig 4; r=-.44, P<.001). Each subject was then classified as insulin sensitive or insulin resistant,19 and the two-way ANOVA was repeated comparing insulin-sensitive to insulin-resistant groups within each BP group. In this analysis, as shown in Fig 5, SLC was significantly greater in the insulin-resistant group (0.33±0.03 mmol/L cells per hour) compared with the insulin-sensitive group (0.23±0.04 mmol/L cells per hour, P=.03). Therefore, elevated SLC activity appeared to be most strongly associated with insulin resistance.



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  		Figure 4. Scatterplot shows sodium-lithium countertransport activity measured in red blood cells plotted with measure of insulin-stimulated glucose utilization (M) for each normotensive ({triangleup}) and borderline hypertensive ({blacktriangleup}) subject. The correlation analysis is significant (r=-.44, P<.002, n=67).



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  		Figure 5. Bar graph shows mean values for sodium-lithium countertransport activity (Vmax) for subject subgroups defined as insulin sensitive (open bars) or insulin resistant (hatched bars) according to the value for glucose utilization determined by the clamp procedure.22 By two-way ANOVA, sodium-lithium countertransport is significantly greater in insulin-resistant compared with insulin-sensitive subjects (P=.03).

We used stepwise multiple regression analysis to examine the contribution of insulin, insulin resistance, SLC, body mass index, and BP to UAE. There was a statistically significant regression of UAE on plasma insulin concentration (P<.001) and BP group (P<.05). Table 3 lists multiple regression statistics. This model demonstrates that the principal correlate of UAE is plasma insulin concentration, with BP group a secondary correlate. When SLC was used as the dependent variable, the principal correlate by stepwise multiple regression was insulin-stimulated glucose utilization.


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  		Table 3. Stepwise Multiple Regression Model


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
The results of this study indicate that compared with normotensive subjects, young African Americans with only borderline to mild hypertension exhibit greater UAE. The UAE correlates with plasma insulin concentration—both fasting insulin concentration and insulin response to glucose challenge. The UAE also correlates with insulin resistance as determined by insulin clamp. The maximal rate of SLC, which is usually elevated in Caucasian hypertensive populations, was not significantly greater in these young African Americans with borderline hypertension. However, the SLC activity did correlate significantly with measures of insulin resistance.

UAE at levels not detectable by usual clinical methods, or microalbuminuria, has been detected in IDDM12 and NIDDM.28 29 The predictive value for the development of clinical proteinuria is high in both IDDM (75%)30 and NIDDM (80%).31 Microalbuminuria in NIDDM is associated with increased mortality28 29 and is considered to be a risk factor for cardiovascular disease.32

Elevated rates of UAE have also been reported in patients with established hypertension.6 7 33 Bigazzi et al7 reported that 40% of patients with mild to moderate hypertension had UAE exceeding 30 mg/24 h, although they did not find a direct correlation between UAE and BP. Gerber et al6 reported UAE greater than 15 mg/24 h in 31% of hypertensive compared with 8.6% of normotensive subjects, as well as a direct association of BP with urinary albumin level.6 In these two reports, the mean age of the hypertensive subjects was slightly over 50 years, and the levels of diastolic BP were 98 to 102 mm Hg. Our study was conducted on African Americans who were approximately 20 years younger (mean age, 30 years), with a lower mean BP in the borderline hypertensive subjects (90 mm Hg) than the hypertensive subjects in the above two studies. Although the UAE in our population was lower than that reported in older patients, with more long-standing and severe hypertension, the presence of greater UAE in those with only borderline hypertension suggests that UAE is not only a direct consequence of elevated BP.

The association of hyperinsulinemia, insulin resistance, or both with hypertension in some patients has been established.14 15 In this population of young African Americans, we have previously reported lower insulin-stimulated glucose utilization and higher plasma insulin concentration in borderline hypertensive compared with normotensive subjects.17 19 27 As demonstrated again in the present study, the African Americans with only borderline hypertension express evidence of insulin resistance with hyperinsulinemia. Our data on the insulin response to glucose challenge and UAE are similar to those reported by Bianchi et al.34 These investigators also reported a greater total insulin response during an OGTT in hypertensive compared with normotensive subjects, and their data demonstrated a direct correlation between the insulin area under the curve and UAE. As seen in Figs 1 and 4, our population of African Americans expressed similar results although this group is again younger, with milder BP elevation, than the Caucasian group studied by Bianchi et al.

Sodium transport across cell membranes appears to be altered in hypertensive individuals. SLC and Na+-H+ exchange are elevated in hypertensive Caucasians compared with normotensive subjects.35 Several investigations indicate that this transporter may be a genetic marker for essential hypertension.36 37 Doria et al18 demonstrated that hypertensive patients selected for elevated SLC activity were also insulin resistant, whereas those hypertensive subjects with SLC activity similar to that of the normotensive subjects were insulin sensitive. In their Caucasian population they found a strong negative correlation between SLC and insulin sensitivity as measured by the insulin clamp.

Compared with Caucasians, SLC is lower in populations of African origin.38 39 In a biracial study, Johnson et al40 examined SLC in African Americans with NIDDM. As in other reports, they found that SLC was lower in both normotensive and hypertensive African Americans compared with Caucasians. However, African Americans with both NIDDM and hypertension had significantly higher SLC than all nondiabetic African Americans, including those with hypertension. We have found comparable results in this study on a younger nondiabetic population of African Americans. Within this group, there is a significant negative correlation of SLC with insulin-stimulated glucose utilization, and SLC is significantly higher in those subjects with insulin resistance. In these young African Americans, the association of elevated SLC activity with hypertension depends on the presence of insulin resistance. This observation is consistent with other reports that describe a stronger association between SLC activity and metabolic variables than the association of SLC activity with BP.19 41 42

Elevated SLC activity has been shown to be a risk-predicting marker in hypertensive patients.11 43 Nosadini et al11 described a subset of hypertensive patients having elevated SLC activity. Compared with hypertensive subjects with normal levels of SLC activity, this subgroup had left ventricular hypertrophy, elevated glomerular filtration rates, larger kidney volume, and higher UAE rates. Our data demonstrate that intermediate phenotypes that predict risk for cardiovascular disease—namely, elevated SLC activity, insulin, and/or insulin resistance—can be detected in a young African American population. The linkage of UAE with insulin and elevated SLC activity in young African Americans with only borderline hypertension suggests that the albuminuria is a response to metabolic factors rather than a response only to BP elevation.


*    Acknowledgments
 
This work was supported by grants DK-46107 and HL-51547 from the National Institutes of Health, Bethesda, Md.


*    Footnotes
 
Reprint requests to Bonita Falkner, MD, Department of Pediatrics, Medical College of Pennsylvania, 3300 Henry Ave, Philadelphia, PA 19129.

Received November 1, 1994; first decision November 29, 1994; accepted February 1, 1995.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

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