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Urinary albumin to creatinine ratio predicts left ventricular hypertrophy in essential hypertension
AJH–April 2001–VOL. 14, NO. 4, PART 2
measurement together with blood and urine sampling. Ethical approval was obtained by the local ethics committee. Results are given as mean⫾SEM, blood pressures are in mmHg, sodium excretions are in mol min-1 and urine volumes are in mls. off immersion, on tolbutamide, off tolbutamide, on tolbutamide, off tolbutamide off immersion on immersion on immersion sodium 126.9⫾14.7 excretion urine volume 195.7⫾11.4 systolic BP 128.7⫾4.0 diastolic BP 76.7⫾8.7
204.5⫾31.8
250.1⫾12.4
350.5⫾32.8
241.7⫾9.7 130.9⫾9.1 78.3⫾3.6
306.5⫾25.9 132.1⫾9.0 78.8⫾3.9
375.1⫾22.6 135.7⫾8.1 81.5⫾2.8
As shown in the above table, water immersion produced a significant diuresis (p⫽0.002) and natriuresis (p⬍0.0001). Tolbutamide also produced a diuresis on the dry control days (p⫽0.008), however this diuretic effect was less marked when it was administered on a immersion day, where the diuresis failed to reach statistical significance, when compared to a dry control day on tolbutamide (p⫽0.065). There was a significant natriuresis with tolbutamide (p⫽0.044) and this natriuretic effect was enhanced on immersion (p⫽0.012). The largest differences in the mean systolic and diastolic blood pressures were between the readings taken on the control dry days, without the tolbutamide and the readings taken on the immersion days with tolbutamide, however these differences were not significant (systolic p⫽0.466, diastolic p⫽0.208). This study suggests that short-term administration of tolbutamide results in a diuresis which is not significantly enhanced by volume expansion. It also results in a natriuresis, which is enhanced by volume expansion. This does not provide an explanation for the hypertension caused by first generation sulphonylureas. Further study is needed with tolbutamide administration over a longer term. We speculate that the natriuretic effect may be due to the actions of tolbutamide on the ascending loop on Henle. Key Words: tolbutamide, hypertension, immersion
P-183 REGRESSION OF GLOMERULAR INJURY IN SALTSENSITIVE HYPERTENSION Mddalena Veronesi, Brain Johnston, Ahmed G. Adam, Leopoldo Raij. 1 Hypertension & Nephrology, VAMC & University of MN, Minneapolis, MN, United States Studies in humans have shown that pancreatic transplantation not only arrests but can reverse diabetic nephropathy (NEJM ’98). Experimentally studies have suggested that in chronic renal failure due to either renal ablation (5/6 Nx) or toxic nephropathy due to puromycin, interruption of the renin angiotensin system (RAS) may not only arrest progression but may in fact reverse glomerular injury (KI ’91, ’94). Dahl salt sensitive (DS) rats fed high dietary salt develop hypertension and severe renal injury. We designed a 12 week study to evaluate whether the treatment with an angiotensin receptor-1 (AT1-R) blocker {Candesartan (Cande) given by gavage 10 mg/kg/day} may reverse glomerular injury. DS rats were fed 4% NaCl for 6 weeks and then divided into 3 groups: 1- (HS) was sacrificed, 2- (HS/LS) switched to Low salt (0.5% NaCl), 3- (HS/ LS⫹Cande) switched to 0.5% NaCl and treated with Cande. A 4th group was kept on 0.5% NaCl for the duration of the study. Systolic blood pressure (SBP), 24-hr urinary protein excretion (U-Pr) and kidney weight (KW) were measured. Glomerular injury (GIS) was scored semi-quantitatively to assess the severity and the distribution of lesions as previously described (KI ’84). Results:
Groups HS (n⫽6) HS/LS (n⫽6) HS/LS⫹Cande (n⫽6) LS (n⫽6)
91A
POSTERS: Kidney and Hypertension
Time of sacrifice (Weeks)
SBP (mmHg)
KW (g)
U-Pr (mg/24hrs)
GIS
6 12
223⫾13 202⫾3
1.7⫾0.06 1.7⫾0.07
130⫾25 104⫾14 #
87⫾14 50⫾8#␦
12 12
143⫾6* 154⫾2*
1.5⫾0.05* 1.4⫾0.03*
35⫾10* 53⫾2*
20⫾3* 10⫾7*
(p ⬍ 0.05, * in comparison to HS, to LS, # to HS/LS⫹Cande, ␦ to HS)
Thus, reduction of dietary salt (HS/LS) did not significantly reduce SBP or U-Pr, although it modestly reduced GIS. On the other hand, AT1-R blockade (HS/LS⫹Cande) normalized SBP, U-Pr, and not only arrested, but reversed glomerular injury. Clinically, longitudinal studies with serial renal biopsies should reveal a) whether AT1-R blockade can reverse glomerular injury and b) whether doses beyond those necessary for blood pressure control are required for this effect. Key Words: Glomerular injury, renin angiotensin system, AT1- receptor blocker
P-184 URINARY ALBUMIN TO CREATININE RATIO PREDICTS LEFT VENTRICULAR HYPERTROPHY IN ESSENTIAL HYPERTENSION G. P. Vyssoulis, E. A. Karpanou, J. K. Rizos, A. E. Giannakopoulou, M. A. Toutouza, D. A. Belegrinos, P. K. Toutouzas. 1Cardiology Department of Athens University, Athens, Greece It has been reported recently that spot albumin-creatinine ratio predicts left ventricular hypertrophy in young hypertensive African-American men. To test this, we studied 2300 untreated, non diabetic Caucasian patients with essential hypertension, 1271 men and 1029 women, 51.4⫾12.4 years old. Urinary albumin and creatinine were measured over 24 hours and their ratio (ACR) was calculated, while left ventricular hypertrophy (LVH) was determined by echocardiogram. Patients with LVH had higher ACR (38.3 vs 19.7 mg/g p⬍0.0001), with higher values in patients with eccentric LVH (39.1 mg/g), differentiating among LV geometry patterns (F⫽82 p⬍0.0001). Patients with ACR ⬎30mg/g had higher LV mass index values (145 vs 133 g/m2 p⬍0.0001) and higher LVH incidence (71.8 vs 37.3% p⬍0.0001). Thus, the sensitivity of increased ACR in predicting LVH was rather low (46.5%) but the specificity was high (83.2%) with odds ratio 4.3:1. The relationship of ACR to LV mass index was strong (r⫽0.365) and remained significant after correction for age (r⫽0.311), diastolic blood pressure (r⫽0.309) or serum creatinine (r⫽0.254). It is concluded that elevated ACR is a high specific marker of LVH in hypertensive patients. Key Words: Urinary albumin, Creatinine, Left ventricular hypertrophy
P-185 MICROALBUMINURIA CONTROLLING FACTORS IN NON-DIABETICS PATIENTS WITH ESSENTIAL HYPERTENSION G. P. Vyssoulis, E. A. Karpanou, A. E. Giannakopoulou, M. A. Toutouza, J. D. Barbetseas, D. A. Belegrinos, P. K. Toutouzas. 1 Cardiology Department of Athens University, Athens, Greece Microalbuminuria is an independent cardiovascular risk factor in hypertensive patients. Diabetics most often display micro-and macroalbuminuria, while the controlling factors in non-diabetic hypertensives are explored in this paper. We studied 2700 consecutive untreated patients with uncomplicated arterial hypertension. Diabetics were excluded, and in dubious cases glucose tolerence tests were done. Urinary albumin excretion was measured in 24hour urinary collection. The mean microalbumin value was 29.5⫾28.9 mg/L, while 44.1% patients had values over 20 mg/L. Patients were grouped according to selected characteristics, as below. Factor
n
YES
NO
p
r value
p
Males Smoking Obesity 1 Waist/Hips ⬎55 years old Dyslipidaemia High PRA LVH
1486 1017 1465 1415 993 948 1170 1416
31,0⫾32,9 32,6⫾31,9 31,0⫾30,5 35,4⫾32,6 33,1⫾31,3 33,7⫾27,1 36,8⫾32,0 35,5⫾32,8
27,7⫾25,4 27,7⫾40,0 27,8⫾28,8 23,0⫾24,7 27,4⫾28,6 27,2⫾30,9 24,0⫾26,6 22,9⫾24,3
0,006 0,001 0,009 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001
0,054 0,080 0,086 0,177 0,127 0,106 0,130 0,275
0,005 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001
It is concluded that high renin male patients burdened with smoking,
measurement together with blood and urine sampling. Ethical approval was obtained by the local ethics committee. Results are given as mean⫾SEM, blood pressures are in mmHg, sodium excretions are in mol min-1 and urine volumes are in mls. off immersion, on tolbutamide, off tolbutamide, on tolbutamide, off tolbutamide off immersion on immersion on immersion sodium 126.9⫾14.7 excretion urine volume 195.7⫾11.4 systolic BP 128.7⫾4.0 diastolic BP 76.7⫾8.7
204.5⫾31.8
250.1⫾12.4
350.5⫾32.8
241.7⫾9.7 130.9⫾9.1 78.3⫾3.6
306.5⫾25.9 132.1⫾9.0 78.8⫾3.9
375.1⫾22.6 135.7⫾8.1 81.5⫾2.8
As shown in the above table, water immersion produced a significant diuresis (p⫽0.002) and natriuresis (p⬍0.0001). Tolbutamide also produced a diuresis on the dry control days (p⫽0.008), however this diuretic effect was less marked when it was administered on a immersion day, where the diuresis failed to reach statistical significance, when compared to a dry control day on tolbutamide (p⫽0.065). There was a significant natriuresis with tolbutamide (p⫽0.044) and this natriuretic effect was enhanced on immersion (p⫽0.012). The largest differences in the mean systolic and diastolic blood pressures were between the readings taken on the control dry days, without the tolbutamide and the readings taken on the immersion days with tolbutamide, however these differences were not significant (systolic p⫽0.466, diastolic p⫽0.208). This study suggests that short-term administration of tolbutamide results in a diuresis which is not significantly enhanced by volume expansion. It also results in a natriuresis, which is enhanced by volume expansion. This does not provide an explanation for the hypertension caused by first generation sulphonylureas. Further study is needed with tolbutamide administration over a longer term. We speculate that the natriuretic effect may be due to the actions of tolbutamide on the ascending loop on Henle. Key Words: tolbutamide, hypertension, immersion
P-183 REGRESSION OF GLOMERULAR INJURY IN SALTSENSITIVE HYPERTENSION Mddalena Veronesi, Brain Johnston, Ahmed G. Adam, Leopoldo Raij. 1 Hypertension & Nephrology, VAMC & University of MN, Minneapolis, MN, United States Studies in humans have shown that pancreatic transplantation not only arrests but can reverse diabetic nephropathy (NEJM ’98). Experimentally studies have suggested that in chronic renal failure due to either renal ablation (5/6 Nx) or toxic nephropathy due to puromycin, interruption of the renin angiotensin system (RAS) may not only arrest progression but may in fact reverse glomerular injury (KI ’91, ’94). Dahl salt sensitive (DS) rats fed high dietary salt develop hypertension and severe renal injury. We designed a 12 week study to evaluate whether the treatment with an angiotensin receptor-1 (AT1-R) blocker {Candesartan (Cande) given by gavage 10 mg/kg/day} may reverse glomerular injury. DS rats were fed 4% NaCl for 6 weeks and then divided into 3 groups: 1- (HS) was sacrificed, 2- (HS/LS) switched to Low salt (0.5% NaCl), 3- (HS/ LS⫹Cande) switched to 0.5% NaCl and treated with Cande. A 4th group was kept on 0.5% NaCl for the duration of the study. Systolic blood pressure (SBP), 24-hr urinary protein excretion (U-Pr) and kidney weight (KW) were measured. Glomerular injury (GIS) was scored semi-quantitatively to assess the severity and the distribution of lesions as previously described (KI ’84). Results:
Groups HS (n⫽6) HS/LS (n⫽6) HS/LS⫹Cande (n⫽6) LS (n⫽6)
91A
POSTERS: Kidney and Hypertension
Time of sacrifice (Weeks)
SBP (mmHg)
KW (g)
U-Pr (mg/24hrs)
GIS
6 12
223⫾13 202⫾3
1.7⫾0.06 1.7⫾0.07
130⫾25 104⫾14 #
87⫾14 50⫾8#␦
12 12
143⫾6* 154⫾2*
1.5⫾0.05* 1.4⫾0.03*
35⫾10* 53⫾2*
20⫾3* 10⫾7*
(p ⬍ 0.05, * in comparison to HS, to LS, # to HS/LS⫹Cande, ␦ to HS)
Thus, reduction of dietary salt (HS/LS) did not significantly reduce SBP or U-Pr, although it modestly reduced GIS. On the other hand, AT1-R blockade (HS/LS⫹Cande) normalized SBP, U-Pr, and not only arrested, but reversed glomerular injury. Clinically, longitudinal studies with serial renal biopsies should reveal a) whether AT1-R blockade can reverse glomerular injury and b) whether doses beyond those necessary for blood pressure control are required for this effect. Key Words: Glomerular injury, renin angiotensin system, AT1- receptor blocker
P-184 URINARY ALBUMIN TO CREATININE RATIO PREDICTS LEFT VENTRICULAR HYPERTROPHY IN ESSENTIAL HYPERTENSION G. P. Vyssoulis, E. A. Karpanou, J. K. Rizos, A. E. Giannakopoulou, M. A. Toutouza, D. A. Belegrinos, P. K. Toutouzas. 1Cardiology Department of Athens University, Athens, Greece It has been reported recently that spot albumin-creatinine ratio predicts left ventricular hypertrophy in young hypertensive African-American men. To test this, we studied 2300 untreated, non diabetic Caucasian patients with essential hypertension, 1271 men and 1029 women, 51.4⫾12.4 years old. Urinary albumin and creatinine were measured over 24 hours and their ratio (ACR) was calculated, while left ventricular hypertrophy (LVH) was determined by echocardiogram. Patients with LVH had higher ACR (38.3 vs 19.7 mg/g p⬍0.0001), with higher values in patients with eccentric LVH (39.1 mg/g), differentiating among LV geometry patterns (F⫽82 p⬍0.0001). Patients with ACR ⬎30mg/g had higher LV mass index values (145 vs 133 g/m2 p⬍0.0001) and higher LVH incidence (71.8 vs 37.3% p⬍0.0001). Thus, the sensitivity of increased ACR in predicting LVH was rather low (46.5%) but the specificity was high (83.2%) with odds ratio 4.3:1. The relationship of ACR to LV mass index was strong (r⫽0.365) and remained significant after correction for age (r⫽0.311), diastolic blood pressure (r⫽0.309) or serum creatinine (r⫽0.254). It is concluded that elevated ACR is a high specific marker of LVH in hypertensive patients. Key Words: Urinary albumin, Creatinine, Left ventricular hypertrophy
P-185 MICROALBUMINURIA CONTROLLING FACTORS IN NON-DIABETICS PATIENTS WITH ESSENTIAL HYPERTENSION G. P. Vyssoulis, E. A. Karpanou, A. E. Giannakopoulou, M. A. Toutouza, J. D. Barbetseas, D. A. Belegrinos, P. K. Toutouzas. 1 Cardiology Department of Athens University, Athens, Greece Microalbuminuria is an independent cardiovascular risk factor in hypertensive patients. Diabetics most often display micro-and macroalbuminuria, while the controlling factors in non-diabetic hypertensives are explored in this paper. We studied 2700 consecutive untreated patients with uncomplicated arterial hypertension. Diabetics were excluded, and in dubious cases glucose tolerence tests were done. Urinary albumin excretion was measured in 24hour urinary collection. The mean microalbumin value was 29.5⫾28.9 mg/L, while 44.1% patients had values over 20 mg/L. Patients were grouped according to selected characteristics, as below. Factor
n
YES
NO
p
r value
p
Males Smoking Obesity 1 Waist/Hips ⬎55 years old Dyslipidaemia High PRA LVH
1486 1017 1465 1415 993 948 1170 1416
31,0⫾32,9 32,6⫾31,9 31,0⫾30,5 35,4⫾32,6 33,1⫾31,3 33,7⫾27,1 36,8⫾32,0 35,5⫾32,8
27,7⫾25,4 27,7⫾40,0 27,8⫾28,8 23,0⫾24,7 27,4⫾28,6 27,2⫾30,9 24,0⫾26,6 22,9⫾24,3
0,006 0,001 0,009 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001
0,054 0,080 0,086 0,177 0,127 0,106 0,130 0,275
0,005 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001 ⬍0,0001
It is concluded that high renin male patients burdened with smoking,