Baseline serum creatinine levels predict renal hemodynamic response to short-term endurance exercise training in African American hypertensives

AJH–May 2003–VOL. 16, NO. 5, PART 2

P-155 EFFECT OF ANGIOII BLOCKADE WITH VALSARTAN AND BENAZEPRIL ON RENAL DAMAGE IN OBESE ZUCKER RATS Oscar Go´ mez, Paula Vieitez, Esther Ruiz, Olga Gonza´ lez-Albarra´ n, Gema Garcı´a Romero de Tejada, Jose M Sancho, Rafael Garcı´a-Robles. Endocrinology Dpt, Hospital Ramo´ n y Cajal, Madrid, Madrid, Spain; Medicina Dpt, Alcala´ de Henares University, Alcala´ de Henares, Madrid, Spain. Hypertension is a main factor risk factor for the progression of diabetic nephropathy. AngioII inhibition is well described that ameliorates this progression. In the present work, we investigated the effects of ARAII, Valsartan and the ACEI, Benazepril in monotheraphy and in combination at different doses on the evolution of BP and renal expression of several growth factors in obese Zucker rats. Fifty five animals were divided in seven groups according to the treatment: CONTROL (vehicle, n⫽10); VAL-I, 2.28 mg/Kg/day, n⫽10); VAL-II, 22.8 mg/Kg/day, n⫽5); BEN-I (0.28 mg/Kg/day, n⫽10); BEN-II (2.28 mg/Kg/day, n⫽5); VAL-BEN-I, 2.28 0.28 mg/Kg/day, n⫽10); VAL-BEN-II (22.8 2.28 mg/Kg/day, n⫽5). Animals were followed during 8 months and systemic and renal parameters were measured periodically. At the end, animals were sacrified and in every kidney removed to evaluate the expression of TGF-␤1, TNF-␣, VEGF and PDGF-␤ by western blot. All the treated groups showed a significant decrease of systolic and diastolic blood pressure vs. control group (p⬍0.01), however no differences were observed among the treated ones. On the other hand, the expression of all the growth factors showed a gradation in decreased expression of the growth factors that attain maximum blockade in the VAL-BEN-II group (p⬍0.01). These data indicate that angiotensin II blockade produces a nephroprotective effect, in addition to the reducing blood pressure. Key Words: Growth factors, Valsartan, benazepril

P-156 PREVALENCE OF RENAL INSUFFICIENCY IN HYPERTENSIVE PATIENTS Munavvar Izhar, Nahla Hassabou, Renee Ellis, Arshad Asghar, Rajesh Nambiar, Pawan Chopra, Emad Basta, Gilberto Neri. Department of Preventive Medicine, Rush-Presbyterian-St.-Luke’sMedical Center, Chicago, IL; Department of Internal Medicine, St.Anthony Memorial Health Center, Michigan City, MI; Department of Internal Medicine, Cook County Hospital, Chicago, IL. The finding of an altered renal function is assaociated with an increase in cardiovascular risk. Physicians need to pay more attention to assessment of renal damage in hypertensive patients. The objective of this retrospective analyses is to estimate the prevalence of mild chronic renal insufficiency (MCRI) in hypertensive patients seen at our tertiary referral clinic. We analyzed clinical and biochemical data from 400 essential hypertensive patients followed at our clinic. Mild Chronic Renal insufficiency was defined as a serum creatinine ⱖ1.5 mg/dl in men and ⱖ1.4 mg/dl in women, or a creatinine clearance estimated by the Cockroft-Gault formula. A prevalence of mild chronic renal insufficiency was found in 8% of the patients according to serum creatinine levels. However, this prevalence increased to 18.5% when the diagnostic criteria for chronic renal insufficiency was the estimation using the Cockcroft-Gault formula.

POSTERS: Kidney and Hypertension

95A

Demographic and Clinical Data N Age (years) Males Females Weight (Kg) Diabetes SBP (mm Hg) DBP (mm Hg) Serum Creatinine

400 220 (55%) 180 (45%) 400 60 (15%) 400 400 400

MEAN

SD

51.9

10.46

70.28

11.94

152.74 93.78 1.18

22.97 12.06 0.28

The presence of renal insufficiency is more prevalent than previously thought. This is especially true if the estimated creatinine clearance (Cockroft-Gault formula) is considered routinely in the evaluation of all hypertensive patients. Still better would be a creatinine clearance estimation by 24 hour urine collection.Altered renal function is associated with a significant increase in cardiovascular risk. Hence, there is an increased need to pay attention to manifestations of renal damage in the assessment of hypertensive patients. Key Words: Renal insufficiency, hypertension

P-157 BASELINE SERUM CREATININE LEVELS PREDICT RENAL HEMODYNAMIC RESPONSE TO SHORTTERM ENDURANCE EXERCISE TRAINING IN AFRICAN AMERICAN HYPERTENSIVES Jennifer M Jones, David Vizcaino, Thomas C Dowling, Matthew R Weir, Jennifer J Johnson, Jung-Jun Park, Brian D Hand, Thomas Obisesan, Michael D. Brown. Department of Kinesiology, University of Maryland, College Park, College Park, MD; Department of Pharmacy Practice and Science, University of Maryland Medical Center, Baltimore, MD; Department of Medicine, University of Maryland Medical Center, Baltimore, MD; Department of Medicine, Howard University, Washington, DC. Hypertension and end-stage renal disease (ESRD) are thought to be pathologically linked, in which renal dysfunction may contribute to, or be the result of hypertension. Aerobic exercise training (AEX) has been shown to improve effective renal plasma flow (ERPF) in hypertensive Japanese subjects. The purpose of the present study was to determine if the initial level of kidney function, as indicated by baseline serum creatinine concentration, would contribute to renal hemodynamic response to short-term endurance exercise training in African American (AA) hypertensives. Eleven (7 women, 4 men) sedentary, moderately obese, nondiabetic, hypertensive (SBP 148⫾3 mmHg, DBP 89⫾3 mmHg) AA (mean age 59.6⫾1.2 years) completed 7 consecutive days of AEX for 50 min/day at 65% of heart rate reserve. Fasting blood chemistries and serum creatinine levels were measured at baseline, glomerular filtration rate (GFR) and ERPF were measured during continuous infusion of iothalamate and PAH, respectively, before and after AEX. Average baseline serum creatinine concentration was 1.04⫾0.06 (range 0.8-1. 4 mg/dl). Short-term AEX did not change average GFR (125.2 ⫾ 6.9 vs. 130.3 ⫾ 9.0 ml/min/1.73 m2, P⫽0.37; range -23 to ⫹27%) or ERPF (452.2 ⫾ 26.5 vs. 449.1 ⫾ 38.8 ml/min/1.73 m2, P⫽0.87; range -35 to ⫹12%). There was a significant inverse relationship between baseline serum creatinine concentration and the % change in GFR (r⫽ -0.63, P⫽0.04), and a trend toward an inverse relationship between baseline serum creatinine and % change in ERPF (r⫽ -0.55, P⫽0.08), with short-term AEX. Subjects with baseline serum creatinine ⱕ 1.1 mg/dl increased GFR with short-term AEX and those with serum creatinine ⱖ1.1 mg/dl decreased GFR. In addition, the baseline GFR was also predictive of the % change in GFR (r ⫽-0.42, P⫽0.05). The results indicate that GFR and ERPF responses to short-term AEX are affected by baseline serum creatinine level. Depending on a hypertensive individual’s initial level

96A

POSTERS: Kidney and Hypertension

of renal function, exercise training may or may not benefit renal function, as indicated by changes in GFR. Key Words: Exercise, hypertension, renal function

AJH–May 2003–VOL. 16, NO. 5, PART 2

P-159 NAⴙ/Hⴙ EXCHANGE ACTIVITY AND DIURETIC RESPONSE TO NOVEL NHE3 INHIBITORS IN THE SPONTANEOUSLY HYPERTENSIVE RAT (SHR) Michael S LaPointe, Daniel Batlle. Division of Nephrology, Northwestern University; VA Chicago HCS/Lakeside, Chicago, IL.

P-158 BLOOD OXYGEN LEVEL-DEPENDANT MAGNETIC RESONANCE IMAGING IN RENAL ARTERY STENOSIS Laurent Juillard, Lilach O Lerman, David G Kruger, John A Haas, Brian C Rucker, Stephen J Riederer, Juan C Romero. Physiology, Mayo Clinic, Rochester, MN; Hypertension, Mayo Clinic, Rochester, MN; MRI Research Lab, Mayo Clinic, Rochester, MN. Background: Ischemic nephropathy is a common cause of end-stage renal disease. Exploration of the mechanisms of deterioration of renal function is limited due to lack of non invasive techniques available to study the single kidney. The Blood Oxygen Level-Dependent (BOLD) MRI method can measure desoxyhemoglobin and therefore estimates indirectly renal oxygen content, but has never been evaluated in renal artery stenosis (RAS). This study was therefore designed to test if BOLD can detect renal hypoxia induced by RAS. Methods: RAS was induced in 8 pigs using an occluder placed around the right renal artery. Renal blood flow (RBF) was measured continuously with an ultrasound probe. BOLD signal was measured bilaterally in the cortex and medulla (as the slope of the logarithm of MR signal) at baseline and at the lower limit of RBF autoregulation. The measurements were then repeated during six sequential graded decreases in RBF (80 to 0%) of baseline and during recovery. Results: At baseline, BOLD signals were not significantly different between the right and the left kidneys. In the occluded kidney, BOLD signal of the cortex (19.3⫾1.9/s) and the medulla (17.3⫾2.0/s) increased during occlusion gradually and significantly (p⬍0.0001) to a maximum (at total occlusion) of 33.8⫾2.0/s (⫹79%) and 29.8⫾2.3/s (⫹78%) respectively, and returned to baseline values during recovery. Conclusion: This study shows that the BOLD technique can non invasively detect change in intra-renal oxygenation during an acute reduction of RBF. This study provides a strong rational for developing the BOLD method for the detection and evaluation of renal hypoxia induced by RAS, which may be potentially be applicable in humans.

We recently reported that NHE3 protein abundance and activity are increased in proximal tubules in both the pre-hypertensive and hypertensive SHR as compared to WKY rats. The present study examined Na⫹/H⫹ exchange in brush border membrane vesicles (BBMV) and the effect of in vivo infusion of two novel specific NHE-3 inhibitors, S3226 and S1611 on blood pressure and renal function in SHR and age matched WKY rats 10-17 weeks of age. In the presence of the NHE-1 inhibitor, cariporide, Na⫹/H⫹ exchange activity (NHE3) was increased in BBMV from the SHR (1238⫾89, n⫽11 vs 935⫾47, n⫽10 units/5 sec, p⬍0.01). In vivo studies revealed that there were no differences in renal function between SHR and WKY rats after correction for body weight (table). Infusion of S3226 or S1611, resulted in significant increases in urine flow and Na and Li excretions in both rat strains, although neither the absolute excretion rates, nor the percent changes from baseline were different between SHR and WKY rats (Table). Neither S3226 nor S1611 acutely lowered blood pressure in either rat strain. GFR ml/min/kg SHR control WKY control

6.0 ⫾ 0.5 5.3 ⫾ 0.4

SHR S3226 WKY S3226 SHR S1611 WKY S1611

15 ⫾ 19 26 ⫾ 13* ⫺4.9 ⫾ 5.3 ⫺0.5 ⫾ 11

Urine Flow ul/min/kg

UNaV umol/min/kg

48 ⫾ 6 6.9 ⫾ 1.1 60 ⫾ 9 5.2 ⫾ 1.1 percent change from controls 116 ⫾ 44* 267 ⫾ 84* 75 ⫾ 24* 93 ⫾ 59* 61 ⫾ 37* 114 ⫾ 64* 35 ⫾ 13* 95 ⫾ 19*

FE Na %

FE Li %

BP mm Hg

0.85 ⫾ 0.15 0.72 ⫾ 0.17 (%) 252 ⫾ 64* 168 ⫾ 61* 132 ⫾ 74* 110 ⫾ 32*

25 ⫾ 3 26 ⫾ 5

178 ⫾ 1 115 ⫾ 1

87 ⫾ 21* 95 ⫾ 36* 35 ⫾ 11* 51 ⫾ 10*

⫺3 ⫾ 6 ⫺4 ⫾ 4 ⫺3 ⫾ 3 ⫺3 ⫾ 7

* Significant change from respective controls

We conclude that NHE3 activity is increased in the adult SHR as compared to WKY rats. This likely contributes to similar rates of Na excretion which reflects Na retention in the face of severe hypertension. Further, specific NHE3 inhibition results in natriuresis and diuresis but does not affect blood pressure when infused acutely. The potential therapeutic effect of chronic NHE3 inhibition, however, needs to be examined. Key Words: Sodium hydrogen exchange, SHR, NHE3

P-160 CARDIAC TROPONIN T (CTNT) LEVELS IN CHRONIC RENAL FAILURE (CRF) PATIENTS (ptes) Marian Goicoechea, Maria Jose Gutierrez, Soledad Garcia De Vinuesa, Francisco Gomez-Campdera, Paula Blanco, Jose Luno. Nephrology, Hospital Gregorio Maran˜ on, Madrid, Spain.

Key Words: Ischemic nephropathy, experimental renal artery stenosis, MRI BOLD

A significant and continuing controversy over cTnT levels is their specificity as serum marker of cardiac injury in patients with CRF. An increase in serum cTnT levels may be associated with subclinical myocardial injury and/or abnormalities of troponins catabolism induced by renal failure and/or hemodialysis itself. The aim of this study was to evaluate the factors which are associated with serum cTnT levels in a large population of patients (pts) with chronic renal failure. 176 consecutive outpatients (109 M, 67 F) were included. The exclusion criteria were any cardiovascular event during the three months preceding the start of the study. Prevalent cardiovascular disease, arterial pressure, antihypertensive drugs and lifestyle habits were recorded. We choose ECG criteria for left ventricular hypertrophy diagnosis. Routine clinical chemical variables and ischemic myocardial markers (mioglobin, CK-MB mass and cTnT) were measured. The pts were divided in two groups: group A (with normal renal function, creatinine levels ⱕ1.3 mg/dl) (n⫽ 58) and group B (with renal insufficiency, creatinine levels ⬎ 1.3 mg/dl) (n⫽118).