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Habitual excessive dietary salt intake and blood pressure levels in renal transplant recipients
Habitual Excessive Dietary Salt Intake and Blood Pressure Levels in Renal Transplant Recipients
JOHN
H. KALBFLEISCH,
LEE A.
HEBERT,
Ph.D.
M.D.
Columbus, Ohio JACOB
LEMANN,
WALTER JOSEPH Milwaukee,
JR.,
F. PIERING, A. BERES,
M.D. M.D.
M.D.
Wisconsin
From the Department of Medicine and the VA Research Service, Medical College of Wisconsin, Milwaukee, Wisconsin and the Department of Medicine, Chii State University, Cotumbus, Ohio. Supported in part by Grants NIH RR-00058, AM15089. and Ht.-25404. Requests for reprints should be addressed to Dr. Lee A. Hebert, Ohio State University, 466 West 10th Ave., Columbus, Ohio 43210. Manuscript accepted on January 26, 1982.
We observed that renal transplant recipients with good graft function (mean serum creatinine level 1.5 mg/dl f 0.5 SD, N = 68) had dietary salt intakes (estknated from serial measurements of 24-hour sodlum excretion rate) which averaged 43 percent hlgbsr than that of a comparable group of heatthy sub@cts. There was no correlation between Mood pressure levels and satt intake and, desptto the htgh dietary satt intake, hypertension was present in onty 29 pattents and was usuatty mtid; mean systolic and diastotic Mood pressures were 132f lOmmHgand8gf7mmH&r~~~whlkthepatients were receiving antihypertensive medication (median number of standard doses of antihypertensive medication was 1.0 doses/ patient per day). These observations suggest that high dietary satt intake does not exert a powerful blood pressure elevating effect, since any effect of high dietary salt intake to raise Mood pressure should have been magnified In the renal transplant rectpients because of their reduced renal mass and their chronic glucocorticoid therapy. During the serial follow-up of our patients with successful kidney grafts we observed that their urinary sodium excretion, a measure of salt intake, was consistently much higher than that observed in healthy subjects eating normal diets. Since it has been suggested that excessive dietary salt intake may predispose a patient to the development of hypertension [I-3], we have examined the relationship between dietary salt intake and blood pressure levels in our patients. Renal transplant recipients are apt subjjcts for such a study since their reduced renal mass [4] and long-term glucocorticoid therapy [5] promote sodium retention and should magnify the effect of a higher dietary salt intake to raise blood pressure. Another asset of the present study is that abundant data on blood pressure levels and dietary salt intake were available on each patient. In all previous studies of the relationship between salt intake and blood pressure level, salt intake was estimated from either the dietary history or relatively few measurements of urinary sodium excretion obtained over a relatively brief period. Such approaches to estimate salt intake are not optimal because dietary history is often unreliable as a measure of salt intake, and urinary sodium excretion tends to vary widely from day to day rendering a small number of measurements unreliable as an estimate of the prevailing dietary salt intake [6-81. Thus, the present study represents a more detailed analysis of the relationship between dietary salt intake and blood pressure levels than has previously been reported.
August 1982
The Annrlcan
Journal ef Medicine
Volume 73
205
SALT INTAKE AND HYPERTENSION-KALEFLEISCH ET AL.
TABLE I
Clinical Data on the Health Control Subjects and Transplant Patients of this Study Recipients NotTaking Healthy Adults
Number of subjects Age (years) Weight (kg) Systolic pressure (mm Hg) Diastolic pressure (mm Hg) Urinary creatinine excretion (mgiday) Serum creatinine concentration (mg/lOO ml) Creatinine clearance (ml/min) Urinary sodium excretion (mmol/day) UtiV/Weight uN,v/uCrv
Antihypertensive Medication
All Recipients
39 32f 69f 118 f 78 f 1598
RecipientsTaking Antihypertensive Medication 29 38f 74f 132 f 89 f 1650
80 20 to 40 736 15 NA NA 1800 f 480
68 35f 72f 124 f 83 f 1620
1.1 f 0.2
1.5 f 0.3t
1.5 f 0.3$
1.5 f 0.3x
1 IO f 24 167f62
80 f 2Ot 224 f 55t
78 f 2Ot 217 f 57t
82 f 2Oi 234 f 51x
2.26 f 0.69 0.099 f 0.032
3.25 f O-83$ 0.142 f 0.034t
3.25 f 0.82f 0.138 f 0.027$
3.24 f 0.855 0.148 f 0.041t
12 15 12 8 f 405’
l
13 15 9 7 f 415”’
11 13 10’ 7’ f 396
UN,V = 24 hr urinary sodium excretion rate; Uc,V = 24 hr urinary creatinine excretion rate; NA = not available. p
l
l
METHODS The data analyzed in this study were obtained from the clinical records of the renal transplant recipients of the Medical College of Wisconsin at the Milwaukee Regional Medical Center. The patients selected for study had stable renal function with a serum creatinine level of 2.5 mg/dl or less and were free from diseases that cause renal sodium retention or wasting. The patients were not aware that data were being collected to examine the relationship between dietary salt intake and blood pressure levels. Serial measurements of body weight, blood pressure, serum creatinine concentration, and 24-hour urinary excretion of creatinine and sodium were obtained on two to 16 occasions (mean 7 f 3) in 68 patients. Individual 24-hour urine values were excluded from analysis if, at the time of collection of the urine specimen, there was evidence of a sudden weight change of more than 1 kg. There were 25 women and 43 men whose ages ranged from 14 to 58 years (mean age 34 f 13 years). The measurements were made every three to six months beginning three months after grafting. The period of observations ranged from three to 60 months. Ninetyane percent of the patients were followed for more than 24 months. The number and type of diuretics and other antihypertensive agents administered, if any, were recorded. A standard dose of an antihypertensive medication was defined as follows: hydrochlorothiazide, 50 mg; furosemide, 40 mg; methyldopa, 250 mg; propanoloi, 40 mg; metoprolol, 50 mg; and hydralazine, 25 mg. All patients were eating an unrestricted diet and none were receiving sodium bicarbonate therapy. Ail patients received azathioprine and prednisone or methylprednisolone according to a dose schedule previously described [9]. Almost all of the patients
206
August 1992
were receiving maintenance doses of azathioprine and steroids at the time of this study. Measurements of body weight, serum creatinine concentration, and 24-hour urinary excretion of creatinine and sodium were also made in 80 healthy, nonobese adults (59 men and 21 women) who were eating self-selected diets. These individuals ranged in age from 20 to 40 years, were free of cardiovascular renal diseases and were taking no drugs. The data are statistically summarized by presentation of means and standard deviations for patient groups. For continuous variates the independent sample t test was used to assess differences between the means of differing groups of patients or healthy control subjects. Simple linear regression and correlation analysis was used to assess and determine the straight-line relationship between two variables. Ninety-five percent confidence zones about regression lines were obtained from the confidence interval formulas for future observations. Multiple regression analysis was used to assess the joint influence of several independent (but correlated) variates on systolic and diastolic blood pressures. levels of significance are indicated herein. RESULTS
Sodium Excretion. As shown in Table I, there were no significant differences in body weight between the patients and the control subjects, but the patients excreted slightly less creatinine in their urine. The mean serum creatinine concentration was higher in the patients and, as a consequence, mean creatinine ciearante was lower. Daily urinary sodium excretion, whether expressed on an absolute basis or per unit
The American Journal of Medicine Volume 73
SALT
HEALTHY
INTAKE
AND
HYF’ERTENSIDN-KALBFLEISCH
SUBJECTS
400
0
URINE 300
Na 200 mmol/day
ET AL.
22
/??TJZ
100 0
I
I
50
60
1
1
I
70
80
90
BODY WEIGHT .
I
I
100
110
Kg
_
.
. . . .
..
. ..
Figure 1. Daily urinary sodium (Na) excretion as a function of OoUy weignt N) neanny aams eating their usual self-selected diets. The mean regression relationship: Uinaty Ne, mmoUday = 15 + 2.5 kg body weight; r = 0.59, is shown by the heavy line whereas the lighter lines show the 95 percent confidence zone for the relationship.
:* .e. 8 KIDNEY
400
URINE
TRANSPLANT
PATIENTS
.
.
300
.
l
.
.
.
.
l
Na
”
0
200
.
0.
y.
:
mmoliday
.
’
;_.
.
0.
l
.
.
.
:
0.
.
0.
100
l
l
.
.
0
60
60
70
BODY
80
WEIGHT
90
100
li0
Kg
Figure 2. Daily urinary sodium (Na)excretion as a functkm of body weight in kkfney transplant @en&s eatm thsir usual self-se&teddMs. The datapoints are vim on the 95mnt confidencezone for the sang reWonship in h&thy a&&s. For all the kMney transplant patients the mean regression relationship is urinary Na, mmoilday = 97 -t 1.8 kg body weight; r = 0.47.
August
1982
The
Amwlcan
JourMl
d Modkkw
vohlma
73
207
SALT INTAKE AND HYPERTENSION-KALBFLEISCH
TABLE II
Simple Linear Correlation Coefficients
All Patients Systolic blood pressure with Age Weight Ccr UNav
Diastolic blood pressure with Age Weight Ccr UNav
Ccr = creatinine rate. p
ET AL.
Patients Not Taking Antihypertensive Medication
Patients Taking Antihypertensive Medication
0.34’ 0.35” -0.10 0.04
0.23 0.40+ -0.22 0.10
0.22 0.18 -0.15 -0.32
0.29+ 0.40’ -0.05 0.15
0.31 0.46’ 0.01 0.14
0.06 0.27 -0.30 -0.04
clearance;
U&V
= 24 hr urinary sodium excretion
l
creatinine or per unit body weight, was significantly greater among the transplant patients than among the healthy subjects. Figure 1 shows that urinary sodium excretion among the healthy adults was significantly related to body weight, an expected result, since in the absence of sweating or abnormal gastrointestinal fluid losses, urinary sodium excretion closely matches dietary salt intake, and subjects with higher lean body mass can be expected to eat greater quantities of food and, thus more salt. A similar relationship between sodium excretion and urinary creatinine excretion was also observed: urinary sodium, mmol/day = 37 i- 0.072 X urinary creatinine, mg/day, r = 0.55. Figure 2 shows the data points for daily urinary sodium excretion as a function of body weight for each of the transplant patients, superimposed upon the same relationship in normal subjects (Figure 1). As can be seen, the data points for all but five of the patients were on or above the mean regression relationship for normal subjects, and the data points for 13 of the patients were above the 95 percent confidence zone. The differences in urinary sodium excretion between the patients and the normal subjects was even more striking when the urinary sodium excretion rate was expressed per gram of urinary creatinine. This analysis showed that 67 of 68 patients had urinary sodium excretion rates above the mean regression line for normal subjects and 20 of the patients had urinary sodium excretion rates above the 95 percent confidence zone established for healthy individuals. For each patient the mean Blood Pressure Levels. systolic and mean diastolic blood pressures during the
208
August 1982
The American Journal of Medicine
Volume 73
period of observation were calculated. Table I shows the average of the individual means for blood pressure measurements in the 68 patients; the 39-patient subgroup not taking antihypertensive medication and the 29-patient subgroup taking antihypertensive medications. Both systolic and diastolic blood pressures were significantly higher in the subgroup taking the medication than they were in the subgroup not taking the medication (p
The role of dietary salt intake in the pathogenesis of hypertension is controversial [lo]. However, the prevailing view is that in many individuals, a high-salt intake will lead eventually to elevated blood pressure and, in established hypertension, a high-salt intake will further elevate blood pressure [ l-3, lo- 151. The evidence that a high dietary salt intake leads to hypertension in man is based largely on epidemiologic studies which have compared dietary salt intake and blood pressure levels in different societies. In general, it has been found that societies with a high dietary salt intake have a greater incidence of hypertension than do societies with a low dietary salt intake [2, lo]. These studies, however, have been criticized on the grounds that, in addition to differences in dietary salt intake, these societies have cultural and genetic differences which could account for the differences in blood pressure levels. Furthermore, most intrasocietal evaluations
SALT INTAKE AND HYPERTENSION-KALBFLEISCH
of the relationship between salt intake and blood pressure have failed to demonstrate a significant correlation between the two [6, lo]. The latter studies, however, have been criticized on the grounds that salt intake is already excessive in the societies studied and is at a level that can support hypertension. Thus, variations within that excessive level of salt intake may have little further effect on blood pressure [lo]. A further criticism of these studies is that the assessment of blood pressure levels and salt intake were based on relatively few measurements per patient and these measurements can be expected to vary widely from day to day in each patient [ 6-81. Thus, such data may yield inaccurate estimates of the prevailing level of salt intake and the blood pressure level. This study shows that, despite habitual excessive dietary salt intake and an apparent predisposition to dietary salt-related hypertension, the incidence of hypertension in the transplant population was only slightly higher than that expected in the general Milwaukee population * Furthermore, when hypertension was present in the transplant patient, it was usually mild and well controlled with a single daily dose of a diuretic. It is unlikely that the modest incidence and the mildness of hypertension in the patients with high dietary salt intake are the result of renal salt wasting by the allograft or by the patient’s native kidneys. Most of the patients had negligible or no urine output from their native kidneys at tha tima of renal transplantation, and significant renal salt wasting by renal allografts with adequate and stable renal function has not previously
been reported nor have we observed such a phenom-
ET AL
enon. Diuretic therapy itself also appears not to be the cause of the chronic increase in urinary sodium excretion in the group taking the medication since diuretics do not increase the appetite for salt [ 171. Thus, it seems likely that the high 24-hour urinary sodium excretion rates observed in our patients are the result of a primary increase in dietary salt intake. Interestingly, when patients were questioned at the conclusion of the study regarding their level of salt intake, most perceived their salt intake to be less than normal. This misperception could be the result of a change in the taste threshold for salt or it could be an attempt on the part of the patients to conceal their dietary “rebound hedonism” which so commonly occurs in renal transplant recipients who have received a successful graft after months or years of dietary restrictions. In favor of the former hypothesis is the recent demonstration by Mahajan et al. [ 181 of decreased perception of saltiness by renal transplant recipients. Regardless of these considerations, the present data indicate that among renal transplant recipients with adequate and stable levels of renal function, remarkably high dietary salt intakes are well tolerated. Nevertheless, high dietary salt intake should not be encouraged in renal transplant patients since there is no evidence that a high salt intake is of benefit to the patient. We conclude that a high dietary salt intake does not exert a powerful blood pressure elevating effect in renal transplant recipients who have adequate renal function. Furthermore, these data imply that a high dietary salt intake has even less of a blood pressure elevating effect among individuals with normal renal function. ACKNOWLEDGMENT
l
In the age rangeof 35 to 44 years, approximately30 percent of
white menand 40 percentof the black men in the generalMilwaukeepopulationhave systolic blood pressuresgreeterthan 140
the
mm H9 and/or diastolic blood pressuresgreater than 90 mm Hg 1161.
The authors gratefully acknowledge the assistance of Dr. Nancy Adams and Elizabeth and Paul Hebert in the collection of data, and the secretarial assistance of Carmela Price and Sandy Taylor.
REFERENCES 1.
2. 3.
4. 5. 6.
Dahl LK: Salt and hypertension.Am J Clin Nub 1972; 25: 231-244. Freis ED: Salt, volume and the penetrationof hypertension. Circulation1976; 53(4): 569-595. FinnR, McCoonocbieK, Box MO, et al.: Bloodpressureand salt intake: an intra-populationstudy. Lencet 1961; I: 1097. Haddy FJ: Mechanism. preventionand therapy of sodiumdependenthypertension.Am J h&d 1960; 69: 746-756. Siegel RR, Luke RG, HellebuschAA: Reductionof toxicityof corbieroid therapyafter renaltransplentetion. Am J Med 1972: 53: 159-169. Liu K, Cooper R, McKeeverJ, et al.: Assessmentof the association between habitual salt intake and high blood
Au@
7. 6.
9.
10. 11.
1982
pressure:methodologicalproblems.Am J Epidemioll979; llO(2): 219-226. PickeringG: Salt intake and essentialhypertension.CardicvascularReviewsand Reports 1960; l(1): 13-17. CumminsRO. SheperAG, WalkerM: Methodologicel problems with estimation of salt intake. Lencet 1961; I: 13731374. BreitenfieldRV, Hebert LA, LernennJ Jr, et al.: Stability of renal transplant function with alternate-day corticosteroid therapy. JAMA 1960; 224(2): 151-156. Swales JD: Dietary salt and hypertension. Lancet 1980; I: 1177-1179. KempoerW: Treatment of hypertensive vascular disease with rice diet. Am J Med 1948; 4: 545-577.
The Amerkan
Journal of Medkke
Volume 73
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SALT INTAKE AND HYPERTENSION-KALBFLEISCH
12.
13.
14.
210
ET AL.
VP, Dahl LK, Cotzias GC, et al.: Dietary treatment of hypertension. Clinical and metabolic studies of patients on the rice-fruit diet. The Hospital of the Rockefeller Institute for Medical Research, New York: 1950. Corcoran AC, Taylor RD, Page IH: Controlled observations on the effect of low sodium diet therapy in essential hypertension. Circulation 1951; 3(l): 1-16. Parijs J, Joossens JV, Van der Linden L, et al.: Moderate sodium restriction and diuretics in the treatment of hypertension. Am Heart J 1973; 85(l): 22-34. Dole
August 1982
The American Journal of Medlclne
15. 16. 17. 18.
Volume 73
Morgan T, Gillies A, Morgan G, et al.: Hypertension treated by salt restriction, Lancet 1978; 1: 227-230. ltskovitz l-Q Kochar MS, Anderson AJ, et al.: Patterns of blood pressure in Milwaukee. JAMA 1977; 238(8): 864-868. Bing RF, Thurston H, Swales JD: Salt intake and diuretic treatment of hypertension. Lancet, 1979; 2: 12 1- 122. Mahajan S, Bornstein K, Abraham J, et al.: Hypogeusia in renal transplant patients (abstract) 14th Annual Meeting, American Society of Nephrology, November 22-24, 1981, Washington, DC.: 171A.
JOHN
H. KALBFLEISCH,
LEE A.
HEBERT,
Ph.D.
M.D.
Columbus, Ohio JACOB
LEMANN,
WALTER JOSEPH Milwaukee,
JR.,
F. PIERING, A. BERES,
M.D. M.D.
M.D.
Wisconsin
From the Department of Medicine and the VA Research Service, Medical College of Wisconsin, Milwaukee, Wisconsin and the Department of Medicine, Chii State University, Cotumbus, Ohio. Supported in part by Grants NIH RR-00058, AM15089. and Ht.-25404. Requests for reprints should be addressed to Dr. Lee A. Hebert, Ohio State University, 466 West 10th Ave., Columbus, Ohio 43210. Manuscript accepted on January 26, 1982.
We observed that renal transplant recipients with good graft function (mean serum creatinine level 1.5 mg/dl f 0.5 SD, N = 68) had dietary salt intakes (estknated from serial measurements of 24-hour sodlum excretion rate) which averaged 43 percent hlgbsr than that of a comparable group of heatthy sub@cts. There was no correlation between Mood pressure levels and satt intake and, desptto the htgh dietary satt intake, hypertension was present in onty 29 pattents and was usuatty mtid; mean systolic and diastotic Mood pressures were 132f lOmmHgand8gf7mmH&r~~~whlkthepatients were receiving antihypertensive medication (median number of standard doses of antihypertensive medication was 1.0 doses/ patient per day). These observations suggest that high dietary satt intake does not exert a powerful blood pressure elevating effect, since any effect of high dietary salt intake to raise Mood pressure should have been magnified In the renal transplant rectpients because of their reduced renal mass and their chronic glucocorticoid therapy. During the serial follow-up of our patients with successful kidney grafts we observed that their urinary sodium excretion, a measure of salt intake, was consistently much higher than that observed in healthy subjects eating normal diets. Since it has been suggested that excessive dietary salt intake may predispose a patient to the development of hypertension [I-3], we have examined the relationship between dietary salt intake and blood pressure levels in our patients. Renal transplant recipients are apt subjjcts for such a study since their reduced renal mass [4] and long-term glucocorticoid therapy [5] promote sodium retention and should magnify the effect of a higher dietary salt intake to raise blood pressure. Another asset of the present study is that abundant data on blood pressure levels and dietary salt intake were available on each patient. In all previous studies of the relationship between salt intake and blood pressure level, salt intake was estimated from either the dietary history or relatively few measurements of urinary sodium excretion obtained over a relatively brief period. Such approaches to estimate salt intake are not optimal because dietary history is often unreliable as a measure of salt intake, and urinary sodium excretion tends to vary widely from day to day rendering a small number of measurements unreliable as an estimate of the prevailing dietary salt intake [6-81. Thus, the present study represents a more detailed analysis of the relationship between dietary salt intake and blood pressure levels than has previously been reported.
August 1982
The Annrlcan
Journal ef Medicine
Volume 73
205
SALT INTAKE AND HYPERTENSION-KALEFLEISCH ET AL.
TABLE I
Clinical Data on the Health Control Subjects and Transplant Patients of this Study Recipients NotTaking Healthy Adults
Number of subjects Age (years) Weight (kg) Systolic pressure (mm Hg) Diastolic pressure (mm Hg) Urinary creatinine excretion (mgiday) Serum creatinine concentration (mg/lOO ml) Creatinine clearance (ml/min) Urinary sodium excretion (mmol/day) UtiV/Weight uN,v/uCrv
Antihypertensive Medication
All Recipients
39 32f 69f 118 f 78 f 1598
RecipientsTaking Antihypertensive Medication 29 38f 74f 132 f 89 f 1650
80 20 to 40 736 15 NA NA 1800 f 480
68 35f 72f 124 f 83 f 1620
1.1 f 0.2
1.5 f 0.3t
1.5 f 0.3$
1.5 f 0.3x
1 IO f 24 167f62
80 f 2Ot 224 f 55t
78 f 2Ot 217 f 57t
82 f 2Oi 234 f 51x
2.26 f 0.69 0.099 f 0.032
3.25 f O-83$ 0.142 f 0.034t
3.25 f 0.82f 0.138 f 0.027$
3.24 f 0.855 0.148 f 0.041t
12 15 12 8 f 405’
l
13 15 9 7 f 415”’
11 13 10’ 7’ f 396
UN,V = 24 hr urinary sodium excretion rate; Uc,V = 24 hr urinary creatinine excretion rate; NA = not available. p
l
l
METHODS The data analyzed in this study were obtained from the clinical records of the renal transplant recipients of the Medical College of Wisconsin at the Milwaukee Regional Medical Center. The patients selected for study had stable renal function with a serum creatinine level of 2.5 mg/dl or less and were free from diseases that cause renal sodium retention or wasting. The patients were not aware that data were being collected to examine the relationship between dietary salt intake and blood pressure levels. Serial measurements of body weight, blood pressure, serum creatinine concentration, and 24-hour urinary excretion of creatinine and sodium were obtained on two to 16 occasions (mean 7 f 3) in 68 patients. Individual 24-hour urine values were excluded from analysis if, at the time of collection of the urine specimen, there was evidence of a sudden weight change of more than 1 kg. There were 25 women and 43 men whose ages ranged from 14 to 58 years (mean age 34 f 13 years). The measurements were made every three to six months beginning three months after grafting. The period of observations ranged from three to 60 months. Ninetyane percent of the patients were followed for more than 24 months. The number and type of diuretics and other antihypertensive agents administered, if any, were recorded. A standard dose of an antihypertensive medication was defined as follows: hydrochlorothiazide, 50 mg; furosemide, 40 mg; methyldopa, 250 mg; propanoloi, 40 mg; metoprolol, 50 mg; and hydralazine, 25 mg. All patients were eating an unrestricted diet and none were receiving sodium bicarbonate therapy. Ail patients received azathioprine and prednisone or methylprednisolone according to a dose schedule previously described [9]. Almost all of the patients
206
August 1992
were receiving maintenance doses of azathioprine and steroids at the time of this study. Measurements of body weight, serum creatinine concentration, and 24-hour urinary excretion of creatinine and sodium were also made in 80 healthy, nonobese adults (59 men and 21 women) who were eating self-selected diets. These individuals ranged in age from 20 to 40 years, were free of cardiovascular renal diseases and were taking no drugs. The data are statistically summarized by presentation of means and standard deviations for patient groups. For continuous variates the independent sample t test was used to assess differences between the means of differing groups of patients or healthy control subjects. Simple linear regression and correlation analysis was used to assess and determine the straight-line relationship between two variables. Ninety-five percent confidence zones about regression lines were obtained from the confidence interval formulas for future observations. Multiple regression analysis was used to assess the joint influence of several independent (but correlated) variates on systolic and diastolic blood pressures. levels of significance are indicated herein. RESULTS
Sodium Excretion. As shown in Table I, there were no significant differences in body weight between the patients and the control subjects, but the patients excreted slightly less creatinine in their urine. The mean serum creatinine concentration was higher in the patients and, as a consequence, mean creatinine ciearante was lower. Daily urinary sodium excretion, whether expressed on an absolute basis or per unit
The American Journal of Medicine Volume 73
SALT
HEALTHY
INTAKE
AND
HYF’ERTENSIDN-KALBFLEISCH
SUBJECTS
400
0
URINE 300
Na 200 mmol/day
ET AL.
22
/??TJZ
100 0
I
I
50
60
1
1
I
70
80
90
BODY WEIGHT .
I
I
100
110
Kg
_
.
. . . .
..
. ..
Figure 1. Daily urinary sodium (Na) excretion as a function of OoUy weignt N) neanny aams eating their usual self-selected diets. The mean regression relationship: Uinaty Ne, mmoUday = 15 + 2.5 kg body weight; r = 0.59, is shown by the heavy line whereas the lighter lines show the 95 percent confidence zone for the relationship.
:* .e. 8 KIDNEY
400
URINE
TRANSPLANT
PATIENTS
.
.
300
.
l
.
.
.
.
l
Na
”
0
200
.
0.
y.
:
mmoliday
.
’
;_.
.
0.
l
.
.
.
:
0.
.
0.
100
l
l
.
.
0
60
60
70
BODY
80
WEIGHT
90
100
li0
Kg
Figure 2. Daily urinary sodium (Na)excretion as a functkm of body weight in kkfney transplant @en&s eatm thsir usual self-se&teddMs. The datapoints are vim on the 95mnt confidencezone for the sang reWonship in h&thy a&&s. For all the kMney transplant patients the mean regression relationship is urinary Na, mmoilday = 97 -t 1.8 kg body weight; r = 0.47.
August
1982
The
Amwlcan
JourMl
d Modkkw
vohlma
73
207
SALT INTAKE AND HYPERTENSION-KALBFLEISCH
TABLE II
Simple Linear Correlation Coefficients
All Patients Systolic blood pressure with Age Weight Ccr UNav
Diastolic blood pressure with Age Weight Ccr UNav
Ccr = creatinine rate. p
ET AL.
Patients Not Taking Antihypertensive Medication
Patients Taking Antihypertensive Medication
0.34’ 0.35” -0.10 0.04
0.23 0.40+ -0.22 0.10
0.22 0.18 -0.15 -0.32
0.29+ 0.40’ -0.05 0.15
0.31 0.46’ 0.01 0.14
0.06 0.27 -0.30 -0.04
clearance;
U&V
= 24 hr urinary sodium excretion
l
creatinine or per unit body weight, was significantly greater among the transplant patients than among the healthy subjects. Figure 1 shows that urinary sodium excretion among the healthy adults was significantly related to body weight, an expected result, since in the absence of sweating or abnormal gastrointestinal fluid losses, urinary sodium excretion closely matches dietary salt intake, and subjects with higher lean body mass can be expected to eat greater quantities of food and, thus more salt. A similar relationship between sodium excretion and urinary creatinine excretion was also observed: urinary sodium, mmol/day = 37 i- 0.072 X urinary creatinine, mg/day, r = 0.55. Figure 2 shows the data points for daily urinary sodium excretion as a function of body weight for each of the transplant patients, superimposed upon the same relationship in normal subjects (Figure 1). As can be seen, the data points for all but five of the patients were on or above the mean regression relationship for normal subjects, and the data points for 13 of the patients were above the 95 percent confidence zone. The differences in urinary sodium excretion between the patients and the normal subjects was even more striking when the urinary sodium excretion rate was expressed per gram of urinary creatinine. This analysis showed that 67 of 68 patients had urinary sodium excretion rates above the mean regression line for normal subjects and 20 of the patients had urinary sodium excretion rates above the 95 percent confidence zone established for healthy individuals. For each patient the mean Blood Pressure Levels. systolic and mean diastolic blood pressures during the
208
August 1982
The American Journal of Medicine
Volume 73
period of observation were calculated. Table I shows the average of the individual means for blood pressure measurements in the 68 patients; the 39-patient subgroup not taking antihypertensive medication and the 29-patient subgroup taking antihypertensive medications. Both systolic and diastolic blood pressures were significantly higher in the subgroup taking the medication than they were in the subgroup not taking the medication (p
The role of dietary salt intake in the pathogenesis of hypertension is controversial [lo]. However, the prevailing view is that in many individuals, a high-salt intake will lead eventually to elevated blood pressure and, in established hypertension, a high-salt intake will further elevate blood pressure [ l-3, lo- 151. The evidence that a high dietary salt intake leads to hypertension in man is based largely on epidemiologic studies which have compared dietary salt intake and blood pressure levels in different societies. In general, it has been found that societies with a high dietary salt intake have a greater incidence of hypertension than do societies with a low dietary salt intake [2, lo]. These studies, however, have been criticized on the grounds that, in addition to differences in dietary salt intake, these societies have cultural and genetic differences which could account for the differences in blood pressure levels. Furthermore, most intrasocietal evaluations
SALT INTAKE AND HYPERTENSION-KALBFLEISCH
of the relationship between salt intake and blood pressure have failed to demonstrate a significant correlation between the two [6, lo]. The latter studies, however, have been criticized on the grounds that salt intake is already excessive in the societies studied and is at a level that can support hypertension. Thus, variations within that excessive level of salt intake may have little further effect on blood pressure [lo]. A further criticism of these studies is that the assessment of blood pressure levels and salt intake were based on relatively few measurements per patient and these measurements can be expected to vary widely from day to day in each patient [ 6-81. Thus, such data may yield inaccurate estimates of the prevailing level of salt intake and the blood pressure level. This study shows that, despite habitual excessive dietary salt intake and an apparent predisposition to dietary salt-related hypertension, the incidence of hypertension in the transplant population was only slightly higher than that expected in the general Milwaukee population * Furthermore, when hypertension was present in the transplant patient, it was usually mild and well controlled with a single daily dose of a diuretic. It is unlikely that the modest incidence and the mildness of hypertension in the patients with high dietary salt intake are the result of renal salt wasting by the allograft or by the patient’s native kidneys. Most of the patients had negligible or no urine output from their native kidneys at tha tima of renal transplantation, and significant renal salt wasting by renal allografts with adequate and stable renal function has not previously
been reported nor have we observed such a phenom-
ET AL
enon. Diuretic therapy itself also appears not to be the cause of the chronic increase in urinary sodium excretion in the group taking the medication since diuretics do not increase the appetite for salt [ 171. Thus, it seems likely that the high 24-hour urinary sodium excretion rates observed in our patients are the result of a primary increase in dietary salt intake. Interestingly, when patients were questioned at the conclusion of the study regarding their level of salt intake, most perceived their salt intake to be less than normal. This misperception could be the result of a change in the taste threshold for salt or it could be an attempt on the part of the patients to conceal their dietary “rebound hedonism” which so commonly occurs in renal transplant recipients who have received a successful graft after months or years of dietary restrictions. In favor of the former hypothesis is the recent demonstration by Mahajan et al. [ 181 of decreased perception of saltiness by renal transplant recipients. Regardless of these considerations, the present data indicate that among renal transplant recipients with adequate and stable levels of renal function, remarkably high dietary salt intakes are well tolerated. Nevertheless, high dietary salt intake should not be encouraged in renal transplant patients since there is no evidence that a high salt intake is of benefit to the patient. We conclude that a high dietary salt intake does not exert a powerful blood pressure elevating effect in renal transplant recipients who have adequate renal function. Furthermore, these data imply that a high dietary salt intake has even less of a blood pressure elevating effect among individuals with normal renal function. ACKNOWLEDGMENT
l
In the age rangeof 35 to 44 years, approximately30 percent of
white menand 40 percentof the black men in the generalMilwaukeepopulationhave systolic blood pressuresgreeterthan 140
the
mm H9 and/or diastolic blood pressuresgreater than 90 mm Hg 1161.
The authors gratefully acknowledge the assistance of Dr. Nancy Adams and Elizabeth and Paul Hebert in the collection of data, and the secretarial assistance of Carmela Price and Sandy Taylor.
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