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Effects of Hemodialysis and Renal Transplantation on Pulmonary Function
Effects of Hemodialysis and Renal Transplantation on Pulmonary Function* Zoltan Zarday, M.D.; James J. Benjamin, M.D., F.G.G.P.; Spencer K. Koerner, M.D.; Frank J. Veith, M.D., F.G.G.P.; Marvin L. Gliedman, M.D., and Robert Soberman, M.D.
A group of patients with normal chest x-ray films accepted for a renal transplantation program underwent serial pulmonary function studies. Vital capacity and maximum ventilation decreased slightly. Parameters of abnormal pulmonlK'Y function did not change after hemodialysis. Maximum voluntary ventilation increased significantly after successful renal transplantation. which could represent an overall improvement of these patients. The impairment of the cWfusing capacity for carbon monoxide was related to the anemia accompanying renal disease, and not to the azotemia itself. We conclude that in evaluating a chronic uremic patient's pulmonary status, the chest x-ray examination is most important.
Since 1901 mention has been made of lung disease occurring in the course of uremia. 1 The radiologic picture is rather characteristic and consists of fluffy perihilar infiltrates with clear areas peripherally.2 Pathologically the entity is variable." The lungs are heavy and rubbery and 20 percent show a fibrinous pleuritis. Fibrinous deposits have also been seen in the alveoli along with macrophage accumulation and variable amounts of protein-rich edema fluid. Pulmonary function impairment in uremia is likely because of the changes in the lungs or because of the frequent presence of congestive heart failure. Previous physiologic data on these patients are scant. In one Scandinavian study the authors noted hypoxia in eight and hypercapnia in two of 12 uremic subjects whose pulmonary failure was presumed to be due to obstruction of bronchi, parenchymal lung changes, or defective ventilation and perfusion or both." No pulmonary function tests were performed in those patients. Henkin and co-workers" reported clearing of respiratory symptoms and improvement of the chest x-ray picture after peritoneal dialysis in uremic patients. As the uremia again developed after dialysis, the pulmonary symptoms returned and progressively increased until the next dialysis was undertaken. °From the Departments of Medicine and Surgery, Monte6ore Hospital and Medical Center, and the Albert Einstein CoIlege of Medicine, Bronx, New York. Reprint requests: Dr. Zarday, 250 East 73rd Street, New York, New York 10021
532
Since venous pressure and circulation time remained normal in this group of patients, we felt that causes other than congestive heart failure were responsible for the pulmonary abnormalities. Tidal volume, forced expiratory volume, total lung capacity, helium equilibration time, cardiac output and blood volume remained normal. There was marked improvement in vital capacity and maximum voluntary ventilation with dialysis. The purpose of the present investigation was to determine whether any pathophysiologic pulmonary abnormalities exist in patients with end-stage renal disease which are related to the uremic condition. Are any tests needed to discover these changes if the chest x-ray film is normal? Are these abnormalities, if present, reversible with hemodialysis or successful renal transplantation? MATERIAL AND METHODS
We studied both men and women patients, age 15 to 45 with end stage renal disease who were admitted to OUT renal transplant program. The following groups of patients were excluded from the study: (1) those with known pre-existing pulmonary disease ( bronchial asthma, pulmonary emphysema); (2) those with congestive heart failure; (3) those who were unable to cooperate. A general physical examination and a chest x-ray picture was taken before each study, and if the latter was abnormal, the patient was eliminated from the study. All patients had undergone hemodialysis for several weeks before the first tests were done. Pulmonary function studies were carried out on the days before and after
CHEST, VOL. 63, NO.4, APRIL, 1973
HEMODIALYSIS AND RENAL TRANSPLANTATION EFFECTS ON PULMONARY FUNCTION hemodialysis. The time interval between the end of hemodialysis and the postdialysis study was 8 to 16 hours. Blood transfusions were not given. The same studies were done two to three weeks after renal transplantation at a time when the function of the transplanted kidney was good as defined by a blood urea nitrogen level less than 40 mg percent or creatinine clearances over 30 ml per minute. Vital capacity (VC), maximal voluntary ventilation (MVV), forced vital capacity ( FVC), forced expiratory volume in one (FEV d, and three seconds (FEV 3 ), and functional residual capacity (FRC), were performed with a Godart Pulmotest. Arterial blood was analyzed for pH, P02 and PC02 with an Instrumentation Laboratory blood gas analyzer, model 113. Single breath diffusion capacity for carbon monoxide (DL co) was performed with a Collins box-balloon repirometer and a Godart carbon monoxide analyzer. Determination of blood urea nitrogen (BUN), and hematocrit was done in clinical laboratories by routine methods. Hemodialysis was carried out on Travenol twin-coil artificial kidneys for an average of 6 hours twice a week with How rates of 150 to 200 ml/min. Renal transplantation was carried out according to standard procedures. None of the patients included in the study required dialysis after transplantation. They all received azathioprine and corticosteroids in varying doses as immunosuppressive agents. RESULTS
Figure 1 shows the data on vital capacity in seven patients. Values are expressed as percent of predicted normal values. The mean value for the group (before dialysis) was 79±7 (SE). The same group after dialysis had a mean value of 79±6 (SE), and after transplantation this value rose to 85±7 (SE). These changes were not statistically significant. The data for the maximum voluntary ventilation are presented in Figure 2. The mean predialysis value for the group of seven patients was 9O±1l Pt. No.
VC 110 % of predicted
.,MVV 180 % of predicted
Pt. No.
160 140
_
••lIIm"
120 100 80
..~td;..
~.,~.~:lIII;;~
60
...--
~: ••••••••••••
t
OfL-_..a.... t
t
..I.-
POSTDIALYSIS
PREDIALYSIS
..I.-_
POSTTRANSPLANT
FIGURE 2. Maximum voluntary ventilation (MVV) before and after hemodialysis and after renal transplantation.
percent (SE). After dialysis the value of predicted normals was unchanged 9O± 10 (SE), but after transplantation the mean value rose to 107± 10 (SE ). When differences between the predialysis and post-transplant period (6MVV) were calculated by pair analysis, significant differences were found (17±6, p<0.05). This difference was even more pronounced when the postdialysis and post-transplant periods were compared ( 16±4,
. ---....
./ OLeo % of pred icted
90
80
100
533
Pt. No.
• -~. _.._",,,,,,,,,,,,,,,e ~ ""'"",,,.......0"'""""'""''''''''''''' 1
90
70
80
60
70 60
•••••
50
t PREDIALYSIS FIGURE
POSTTRANSPLANT
1. Vital capacity (VC) before and after hemodialysis
and after renal transplantation.
CHEST, VOL. 63, NO.4, APRIL, 1973
PRE-
POST-
POST-
DIALYSIS
DIALYSIS
TRANSPLANT
3. Diffusing capacity for carbon monoxide (DL('() before and after hemodialysis and after renal transplantation. FIGURE
534
ZARDAY ET AL
p
In the group under study the parameters measured varied over a wide range of predicted values in the uremic state and were not related to renal function. The values did not change significantly after dialysis although the uremic status of the patients usually improves by about 50 percent to 60 percent as expressed by the conventional biochemi100 90 80 70 60 50 40 30
'0
Leo
% of predicted
••
• • •
•
•
•
•
•
• •
•• •• • •• • •
00 20 40 BUN mg%-
60
80
100
120
140
160
FIGURE 4. Correlation between blood urea nitrogren (BUN) and diffusing capacity for carbon monoxide (DLco).
120
OLeo % of predicted
110
•
100
• •
90 80
•
70 60 50 40
• •
• • •
• • y= t.r«
+ /8.0
r=0.58
30
°0~----:5~----:l10~~:--~-~-~~~-~-~~ 15 20 25
30
35
40
45
50
HCT%FIGURE 5. Correlation between hematocrit (HCT) and diffusing capacity for carbon monoxide (DI.co).
cal parameters (blood urea nitrogen, serum creatinine, potassium and phosphorus). All values showed a slight improvement in the post-transplant period. The improvement in MVV was statistically significant. This increase, however, may reflect a general improvement in the patients' physical condition and muscle strength, rather than any specific pulmonary improvement. No correlation between the DLco and blood urea nitrogen could be found, which is further evidence that azotemia by itself does not change pulmonary function. However, a strongly positive correlation was established, when hematocrit was plotted against DLco. This is consistent with the findings of others.v" According to the "correction equation" given for anemia," chronic uremic patients having 5 to 6 gm of hemoglobin would be entitled to a 70 percent decrease of DLco. Accordingly, the group of patients studied here did not have inappropriately low values. The fact that arterial P02 did not deteriorate after exercise also speaks against any impairment of diffusion. We, therefore, conclude that this group of patients, ie uremic patients with normal chest x-ray films do not have any irreversible pulmonary disease. Their diminished pulmonary function is attributable to their marked anemia rather than to any pathologic or biochemical abnormalities of uremia. Since anemia cannot be reversed by acute or chronic hemodialysis, but is reversible by successful transplantation, this procedure will correct the existing pulmonary insufficiency to the extent the anemia is corrected. In evaluating these patients, we suggest that the ordinary chest x-ray film CHEST, VOL. 63, NO.4, APRIL, 1973
HEMODIALYSIS AND RENAL TRANSPLANTATION EFFECTS ON PULMONARY FUNCTION
is sufficient to make the diagnosis of uremic lung. A normal chest x-ray examination makes the presence of pulmonary changes unlikely. REFERENCES
1 Lange W: Ueber eine eigentumliche Erkrankung der kleinen Bronchien und Bronchiolen (Bronchitis und Bronchitidis obliterans). Deutsch Arch KIin Med 70:342-364, 1901 2 Doniach I: Uremic edema of the lungs. Am J Roentgenol 58:620-628, 1947 3 Hopps HC, Eissler RW: Uremic pneumonitis. Am J Path 21:261-273, 1955
535
4 Erlanson P, Lindholm T, Lindquist B, et al: Artificial respiration in severe renal failure with pulmonary insufficiency. Acta Med Scand 166:81-96, 1960 5 Henkin RI, Maxwell MH, Murray JF: Uremic pneumonitis. A clinical physiological study. Ann Intern Med 57: 10011008, 6 Rankin J, McNeill RS, Forster HE: The effect of anemia on the alveolar-capillary exchange of carbon monoxide in man. J CUn Invest 40: 1328-1330, 1961 7 Dinakara P, Blumenthal WS, Johnston RF, et al: The effect of anemia on pulmonary diffusing capacity with derivation of a "correction equation." Am Rev Resp Dis 102:965-969, 1970
Early Heliocentric Astronomy The most amazing achievement of this period (third century BC) is the heliocentric theory. Aristarchus of Samos, a contemporary of Euclid and Apollonius, appears to be the first to have given a full and detailed account of this view, though it is possible that it was held in the Academy towards the end of the fourth century. At any rate, we have the reliable testimony of Archimedes that Aristarchus did hold this theory. We also found references to it in Plutarch. The gist of the theory was that the earth and the planets move around the sun which, together with the stars, remains fixed, the
CHEST, VOL. 63, NO.4, APRIL, 1973
earth revolving on its own axis while it runs through its orbit. That the earth turns on its axis once a day was known already to Heraclides, a fourth century Academic. The theory of Aristarchus was thus by no means an utter novelty. Copernicus, it may be noted, in effect merely revived or rediscovered the theory of the astronomer from Samos. A marginal entry of the name of Aristarchus in one of Copernicus' manuscripts puts this beyond doubt. Russell B: Wisdom of the West, Garden City, New York, 1959
A group of patients with normal chest x-ray films accepted for a renal transplantation program underwent serial pulmonary function studies. Vital capacity and maximum ventilation decreased slightly. Parameters of abnormal pulmonlK'Y function did not change after hemodialysis. Maximum voluntary ventilation increased significantly after successful renal transplantation. which could represent an overall improvement of these patients. The impairment of the cWfusing capacity for carbon monoxide was related to the anemia accompanying renal disease, and not to the azotemia itself. We conclude that in evaluating a chronic uremic patient's pulmonary status, the chest x-ray examination is most important.
Since 1901 mention has been made of lung disease occurring in the course of uremia. 1 The radiologic picture is rather characteristic and consists of fluffy perihilar infiltrates with clear areas peripherally.2 Pathologically the entity is variable." The lungs are heavy and rubbery and 20 percent show a fibrinous pleuritis. Fibrinous deposits have also been seen in the alveoli along with macrophage accumulation and variable amounts of protein-rich edema fluid. Pulmonary function impairment in uremia is likely because of the changes in the lungs or because of the frequent presence of congestive heart failure. Previous physiologic data on these patients are scant. In one Scandinavian study the authors noted hypoxia in eight and hypercapnia in two of 12 uremic subjects whose pulmonary failure was presumed to be due to obstruction of bronchi, parenchymal lung changes, or defective ventilation and perfusion or both." No pulmonary function tests were performed in those patients. Henkin and co-workers" reported clearing of respiratory symptoms and improvement of the chest x-ray picture after peritoneal dialysis in uremic patients. As the uremia again developed after dialysis, the pulmonary symptoms returned and progressively increased until the next dialysis was undertaken. °From the Departments of Medicine and Surgery, Monte6ore Hospital and Medical Center, and the Albert Einstein CoIlege of Medicine, Bronx, New York. Reprint requests: Dr. Zarday, 250 East 73rd Street, New York, New York 10021
532
Since venous pressure and circulation time remained normal in this group of patients, we felt that causes other than congestive heart failure were responsible for the pulmonary abnormalities. Tidal volume, forced expiratory volume, total lung capacity, helium equilibration time, cardiac output and blood volume remained normal. There was marked improvement in vital capacity and maximum voluntary ventilation with dialysis. The purpose of the present investigation was to determine whether any pathophysiologic pulmonary abnormalities exist in patients with end-stage renal disease which are related to the uremic condition. Are any tests needed to discover these changes if the chest x-ray film is normal? Are these abnormalities, if present, reversible with hemodialysis or successful renal transplantation? MATERIAL AND METHODS
We studied both men and women patients, age 15 to 45 with end stage renal disease who were admitted to OUT renal transplant program. The following groups of patients were excluded from the study: (1) those with known pre-existing pulmonary disease ( bronchial asthma, pulmonary emphysema); (2) those with congestive heart failure; (3) those who were unable to cooperate. A general physical examination and a chest x-ray picture was taken before each study, and if the latter was abnormal, the patient was eliminated from the study. All patients had undergone hemodialysis for several weeks before the first tests were done. Pulmonary function studies were carried out on the days before and after
CHEST, VOL. 63, NO.4, APRIL, 1973
HEMODIALYSIS AND RENAL TRANSPLANTATION EFFECTS ON PULMONARY FUNCTION hemodialysis. The time interval between the end of hemodialysis and the postdialysis study was 8 to 16 hours. Blood transfusions were not given. The same studies were done two to three weeks after renal transplantation at a time when the function of the transplanted kidney was good as defined by a blood urea nitrogen level less than 40 mg percent or creatinine clearances over 30 ml per minute. Vital capacity (VC), maximal voluntary ventilation (MVV), forced vital capacity ( FVC), forced expiratory volume in one (FEV d, and three seconds (FEV 3 ), and functional residual capacity (FRC), were performed with a Godart Pulmotest. Arterial blood was analyzed for pH, P02 and PC02 with an Instrumentation Laboratory blood gas analyzer, model 113. Single breath diffusion capacity for carbon monoxide (DL co) was performed with a Collins box-balloon repirometer and a Godart carbon monoxide analyzer. Determination of blood urea nitrogen (BUN), and hematocrit was done in clinical laboratories by routine methods. Hemodialysis was carried out on Travenol twin-coil artificial kidneys for an average of 6 hours twice a week with How rates of 150 to 200 ml/min. Renal transplantation was carried out according to standard procedures. None of the patients included in the study required dialysis after transplantation. They all received azathioprine and corticosteroids in varying doses as immunosuppressive agents. RESULTS
Figure 1 shows the data on vital capacity in seven patients. Values are expressed as percent of predicted normal values. The mean value for the group (before dialysis) was 79±7 (SE). The same group after dialysis had a mean value of 79±6 (SE), and after transplantation this value rose to 85±7 (SE). These changes were not statistically significant. The data for the maximum voluntary ventilation are presented in Figure 2. The mean predialysis value for the group of seven patients was 9O±1l Pt. No.
VC 110 % of predicted
.,MVV 180 % of predicted
Pt. No.
160 140
_
••lIIm"
120 100 80
..~td;..
~.,~.~:lIII;;~
60
...--
~: ••••••••••••
t
OfL-_..a.... t
t
..I.-
POSTDIALYSIS
PREDIALYSIS
..I.-_
POSTTRANSPLANT
FIGURE 2. Maximum voluntary ventilation (MVV) before and after hemodialysis and after renal transplantation.
percent (SE). After dialysis the value of predicted normals was unchanged 9O± 10 (SE), but after transplantation the mean value rose to 107± 10 (SE ). When differences between the predialysis and post-transplant period (6MVV) were calculated by pair analysis, significant differences were found (17±6, p<0.05). This difference was even more pronounced when the postdialysis and post-transplant periods were compared ( 16±4,
. ---....
./ OLeo % of pred icted
90
80
100
533
Pt. No.
• -~. _.._",,,,,,,,,,,,,,,e ~ ""'"",,,.......0"'""""'""''''''''''''' 1
90
70
80
60
70 60
•••••
50
t PREDIALYSIS FIGURE
POSTTRANSPLANT
1. Vital capacity (VC) before and after hemodialysis
and after renal transplantation.
CHEST, VOL. 63, NO.4, APRIL, 1973
PRE-
POST-
POST-
DIALYSIS
DIALYSIS
TRANSPLANT
3. Diffusing capacity for carbon monoxide (DL('() before and after hemodialysis and after renal transplantation. FIGURE
534
ZARDAY ET AL
p
In the group under study the parameters measured varied over a wide range of predicted values in the uremic state and were not related to renal function. The values did not change significantly after dialysis although the uremic status of the patients usually improves by about 50 percent to 60 percent as expressed by the conventional biochemi100 90 80 70 60 50 40 30
'0
Leo
% of predicted
••
• • •
•
•
•
•
•
• •
•• •• • •• • •
00 20 40 BUN mg%-
60
80
100
120
140
160
FIGURE 4. Correlation between blood urea nitrogren (BUN) and diffusing capacity for carbon monoxide (DLco).
120
OLeo % of predicted
110
•
100
• •
90 80
•
70 60 50 40
• •
• • •
• • y= t.r«
+ /8.0
r=0.58
30
°0~----:5~----:l10~~:--~-~-~~~-~-~~ 15 20 25
30
35
40
45
50
HCT%FIGURE 5. Correlation between hematocrit (HCT) and diffusing capacity for carbon monoxide (DI.co).
cal parameters (blood urea nitrogen, serum creatinine, potassium and phosphorus). All values showed a slight improvement in the post-transplant period. The improvement in MVV was statistically significant. This increase, however, may reflect a general improvement in the patients' physical condition and muscle strength, rather than any specific pulmonary improvement. No correlation between the DLco and blood urea nitrogen could be found, which is further evidence that azotemia by itself does not change pulmonary function. However, a strongly positive correlation was established, when hematocrit was plotted against DLco. This is consistent with the findings of others.v" According to the "correction equation" given for anemia," chronic uremic patients having 5 to 6 gm of hemoglobin would be entitled to a 70 percent decrease of DLco. Accordingly, the group of patients studied here did not have inappropriately low values. The fact that arterial P02 did not deteriorate after exercise also speaks against any impairment of diffusion. We, therefore, conclude that this group of patients, ie uremic patients with normal chest x-ray films do not have any irreversible pulmonary disease. Their diminished pulmonary function is attributable to their marked anemia rather than to any pathologic or biochemical abnormalities of uremia. Since anemia cannot be reversed by acute or chronic hemodialysis, but is reversible by successful transplantation, this procedure will correct the existing pulmonary insufficiency to the extent the anemia is corrected. In evaluating these patients, we suggest that the ordinary chest x-ray film CHEST, VOL. 63, NO.4, APRIL, 1973
HEMODIALYSIS AND RENAL TRANSPLANTATION EFFECTS ON PULMONARY FUNCTION
is sufficient to make the diagnosis of uremic lung. A normal chest x-ray examination makes the presence of pulmonary changes unlikely. REFERENCES
1 Lange W: Ueber eine eigentumliche Erkrankung der kleinen Bronchien und Bronchiolen (Bronchitis und Bronchitidis obliterans). Deutsch Arch KIin Med 70:342-364, 1901 2 Doniach I: Uremic edema of the lungs. Am J Roentgenol 58:620-628, 1947 3 Hopps HC, Eissler RW: Uremic pneumonitis. Am J Path 21:261-273, 1955
535
4 Erlanson P, Lindholm T, Lindquist B, et al: Artificial respiration in severe renal failure with pulmonary insufficiency. Acta Med Scand 166:81-96, 1960 5 Henkin RI, Maxwell MH, Murray JF: Uremic pneumonitis. A clinical physiological study. Ann Intern Med 57: 10011008, 6 Rankin J, McNeill RS, Forster HE: The effect of anemia on the alveolar-capillary exchange of carbon monoxide in man. J CUn Invest 40: 1328-1330, 1961 7 Dinakara P, Blumenthal WS, Johnston RF, et al: The effect of anemia on pulmonary diffusing capacity with derivation of a "correction equation." Am Rev Resp Dis 102:965-969, 1970
Early Heliocentric Astronomy The most amazing achievement of this period (third century BC) is the heliocentric theory. Aristarchus of Samos, a contemporary of Euclid and Apollonius, appears to be the first to have given a full and detailed account of this view, though it is possible that it was held in the Academy towards the end of the fourth century. At any rate, we have the reliable testimony of Archimedes that Aristarchus did hold this theory. We also found references to it in Plutarch. The gist of the theory was that the earth and the planets move around the sun which, together with the stars, remains fixed, the
CHEST, VOL. 63, NO.4, APRIL, 1973
earth revolving on its own axis while it runs through its orbit. That the earth turns on its axis once a day was known already to Heraclides, a fourth century Academic. The theory of Aristarchus was thus by no means an utter novelty. Copernicus, it may be noted, in effect merely revived or rediscovered the theory of the astronomer from Samos. A marginal entry of the name of Aristarchus in one of Copernicus' manuscripts puts this beyond doubt. Russell B: Wisdom of the West, Garden City, New York, 1959