Graded Exercise Testing and Training After Renal Transplantation: A Preliminary Study

TODD D. MILLER, M.D., RAY W. SQUIRES, Ph.D., GERALD T. GAU, M.D., Division of Cardiovascular Diseases and Internal Medicine; DUANE M. ILSTRUP, M.S., Department of Health Sciences Research; PETER P. FROHNERT, M.D., Division of Nephrology and Internal Medicine; SYLVESTER STERIOFF, M.D., Section of Transplantation Surgery

Aerobic exercise training has been used as part of the treatment for a variety of chronic disorders, most notably cardiovascular disease. In order to determine the feasibility and utility of regular exercise after renal transplantation, the responses of 10 patients to graded exercise testing were compared before training (Tl), immediately after a program of supervised exercise training (T2), and a mean of 2.2 years after completion of the supervised program (T3). Supervised exercise sessions began a mean of 17 days postoperatively and continued for a mean of 5.5 weeks. Patients were encouraged to continue regular unsupervised exercise thereafter. All patients easily tolerated the supervised exercise sessions, which consisted of treadmill walking and cycle ergometry. Exercise capacity improved 90% between Tl and T2 and an additional 12% between T2 and T3. On the average, patients achieved a normal exercise capacity by 8 weeks after transplantation. Of the 10 patients, 7 had continued regular exercise training at T3. The observed increase in aerobic exercise capacity was probably related to im­proved renal function, an increased hemoglobin concentration, and the surgical healing process as well as the exercise training. We conclude that supervised exercise training for selected patients after renal transplantation is feasible and worthwhile.

Aerobic exercise training has been advocated as part of the treatment plan for a variety of chronic diseases. In the prevention of or rehabilitation associated with cardiovascular diseases, habitual exercise has received the most widespread appli­cation and acceptance where it has been shown to improve functional status, reduce symptoms, potentially improve mortality, and reduce risk factors.1 Regular exercise has been suggested to benefit patients with other medical conditions such as noncoronary heart disease, intermittent claudication, hypertension, diabetes mellitus, hyperlipidemia, obesity, chronic pulmonary dis­ease, depression, cancer, osteoporosis, arthritis, and chronic renal failure.2-6 Patients with end-

Address reprint requests to Dr. R. W. Squires, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905.

stage renal disease are usually severely decondi-tioned. Although the effects of exercise training on patients receiving hemodialysis have been evaluated,6,7 the effects of long-term aerobic ex­ercise on renal transplant patients have not been investigated. We report our preliminary expe­rience with both early and late graded exercise testing and training in 10 patients who had undergone renal transplantation.

PATIENTS AND METHODS The study subjects were 10 patients (6 men and 4 women; mean [±SD] age 32.4 + 9.2 years, range 15 to 45 years) with end-stage renal disease who underwent renal transplantation at our institu­tion between January 1982 and April 1984. They constituted a select population in that they had an uncomplicated hospital course postopera-

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774 EXERCISE AFTER RENAL TRANSPLANTATION Mayo Clin Proc, September 1987, Vol 62

tively, were free of acute infection or rejection, were ambulatory and possessed no contraindica­tions to graded exercise testing, were referred for exercise training by their personal nephrologist, and agreed to participate in the program.

The causes of renal failure were diabetes mel-litus in three patients, chronic glomerulonephri-tis in two patients, and hypertension, Alport's syndrome, IgA nephropathy, focal glomerulo-nephritis, and congenital renal dysplasia in one patient each. Seven patients had undergone rou­tine hemodialysis immediately before transplan­tation for a mean of 3.4 ± 2 . 1 months. The allografts were from living related donors in seven patients and from cadavers in three.

At the time of entrance of the 10 patients into the exercise program, they were receiving the following medications: azathioprine (9), cortico-steroids (9), /3-blockers (4), diuretics (3), other antihypertensives (4), warfarin (3), insulin (3), dipyridamole (2), cyclosporine (1), levothyroxine (1), and aspirin (1).

The study design included graded exercise test­ing before training (Tl), immediately after a pe­riod of supervised exercise training (T2), and approximately 2 years after completion of the supervised exercise program (T3). The duration of time between T2 and T3 was determined for each patient individually by the transplant team follow-up procedures. Symptom-limited treadmill exercise tests with use of either the Naughton or the Bruce protocol were performed to assess aero­bic exercise capacity.8 Patients were not allowed to support their weight on the treadmill hand­rails. Continuous multilead electrocardiographic monitoring in conjunction with periodic blood pressure measurement and perceived exertion ratings (Borg scale9) were used. Test endpoints were subject fatigue or physician judgment. Ex­ercise capacity in the units of multiples of resting metabolism (METs; 3.5 ml 0 2 · kg"1 · min"1 per MET) was estimated by using standard tables.8

Blood chemistry and hematologic values were assessed preoperatively and at Tl , T2, and T3.

The exercise program began as soon after transplantation as possible from a medical and logistical standpoint—that is, after the removal of indwelling catheters and intravenous lines. Most subjects were near the time of hospital dismissal at program entrance and continued in the program as outpatients. The modes of phys­ical activity used were walking on motor-driven

treadmills and cycle ergometry. Standard warm-up and cool-down procedures were used.1 Exercise sessions were medically supervised. Exercise in­tensity was prescribed initially at 40% to 60% of maximal exercise capacity by using exercise heart rate and perceived exertion ratings. The duration of exercise began conservatively at 10 minutes per sesssion and was increased gradu­ally to 25 to 40 minutes per session. Patients were encouraged to attend three supervised sessions per week and to walk ad libitum on their own. No attempt was made to quantify ad libitum walking. The duration of the supervised exercise program was determined for each patient indi­vidually by the transplant team postsurgical follow-up procedures. Patients remained near the medical center and able to participate in the supervised program for variable periods, depend­ing on their clinical situation. At the conclusion of the program, patients were given individual­ized home exercise prescriptions on the basis of our usual guidelines1 and encouraged to continue regular exercise training (unsupervised).

Data were analyzed by using repeated-measures analysis of variance with the Student-Newman-Keuls test for multiple comparisons. Data are reported as means ± SD.

RESULTS The supervised exercise program began a mean of 17.0 ± 6.5 days (range, 8 to 28 days) after transplantation. The mean duration of the exer­cise program was 38.7 ± 8.7 days (range, 28 to 56 days) and included 15.5 ± 4.7 (range, 10 to 25) supervised exercise sessions. The exercise train­ing sessions were well tolerated by all patients. The mean exercise intensity during supervised exercise training sessions increased from 2.2 + 0.4 METs to 5.3 ± 1.8 METs (P<0.01). The mean duration of exercise increased from 10.0 ± 2.4 minutes for the first session to 30 ± 2.4 minutes for the final session (P<0.01).

At the time of follow-up (T3; 2.2 ± 0.9 years after completion of the supervised exercise pro­gram), 7 of the 10 patients reported participation in regular exercise training (including one high school student who was active in physical edu­cation classes). Of the 10 patients, 6 had full-time employment, 2 were fully active housewives, and 1 was a full-time student; 1 patient was unem­ployed but was looking for work.

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Table 1 lists values for selected hematologic variables measured preoperatively and at Tl , T2, and T3. Hemoglobin concentration and he-matocrit increased significantly from program entrance to program completion. A further sig­nificant increase was noted for the interval be­tween program completion and follow-up. Serum creatinine decreased dramatically from pretrans-plantation levels to program entrance and re­mained unchanged thereafter.

Treadmill exercise testing data are presented in Table 2. The time intervals between the trans­plant operation and the exercise tests at Tl, T2, and T3 were 14.2 ± 4.9, 57.3 ± 19.6, and 781.5 + 333.3 days, respectively. Figure 1 shows the change in peak METs from Tl to T3 for the 10 patients. Estimated peak METs increased 90% from Tl to T2. Between T2 and T3, peak METs increased another 12%, although this second im­provement in exercise capacity did not reach statistical significance. Peak heart rate was sig­nificantly higher (+17.7 beats/min) at T2 than at Tl. At T2 and T3, peak heart rates were not significantly different. Systolic blood pressure was not significantly different at Tl , T2, or T3. Perceived exertion ratings at peak exercise were similar for all three test periods, an indication of a similar degree of overall fatigue. Tests in­terpreted as fulfilling electrocardiographic crite­ria for ischemia (in two patients) were distributed as follows: one at Tl and T3; two at T2. For patients who had exercise test results suggestive of ischemia, cardiologic follow-up studies were

Table 1.—Selected Blood Constituents Measured (Means + SD) in 10 Patients Immediately Before

Transplantation (Pre), at Entry Into the Exercise Program (Tl), at Program Completion (T2),

and at Follow-Up (T3) Variable Pre Tl T2 T3

3.5 ± 1.7 12.3 ±1.3* 14.2 + 1.5+ Hemoglobin (g/dl) 8.6 ± l.i

Hematocrit (%) 25.1 + 5.6 25.1 ± 4.9 36.9 + 4.0* 42.3 ± 4.5+

Creatinine (mg/dl) 8.7 ± 1.6+. 1.2 ± 0.4 1.3 + 0.4 1.4 ± 0.7

Potassium (meq/L) 4.6 ± 0.5 4.3 ± 0.7 4.1 ± 0.5 4.2 ± 0.6

Value is significantly different (P<0.05) from: *Pre,Tl ,andT3. tPre, T l , andT2 . tT l ,T2 ,andT3 .

Table 2.—Treadmill Test Results (Means ± SD) at Peak Exercise in 10 Patients at Entry Into the Exercise

Program (Tl), at Program Completion (T2), and at Follow-Up (T3)

Variable Tl T2 T3 5.1 + 1.9t 9.7 ± 2.4 10.9 ± 2.7 METs*

(beats/min) 132.5 + 22.4f 150.2 ± 18.8 147.4 ± 17.9 Systolic blood pressure (mm Hg) 152.5 + 23.0 171.7 ± 36.1 160.2 ± 19.6

Perceived exertion rating} 15.4 + 1.6 16.9 + 2.4 16.9 ± 1.1

*Multiples of resting metabolic rate (3.5 ml 0 2 · kg-1 · min-1

per MET). tValue is significantly different (P<0.01) from T2 and T3. JBorg scale.9

done, including a repeat treadmill test in one patient (who had a normal result) and a rest and exercise radionuclide angiogram in the other pa­tient (who had a normal result).

DISCUSSION The major finding in the current study was that selected renal transplant patients can participate safely in an early postoperative aerobic exercise conditioning program and can achieve a normal exercise capacity by 8 weeks after transplanta­tion. Our patients were able to achieve a mean estimated aerobic capacity of almost 10 METs (35 ml O2 · kg-1 · min~1) within 2 months after transplantation, which corresponds to 100% of the predicted mean exercise capacity of healthy persons of similar age.8

Although we did not conduct exercise tests in our patients preoperatively, patients with end-stage renal disease generally have profoundly reduced capacities for physical activity. Only an estimated 30% of patients receiving maintenance dialysis are able to perform more activity than general self-care.10 Hemodialysis patients have aerobic capacities that have been measured at two-thirds the normal value for healthy persons of similar age and sex.11 The reasons for the observed poor physical work capacity in these patients are not entirely understood, but related factors may be chronically reduced hemoglobin concentrations, abnormal skeletal muscle metab­olism that results in early lactate formation and fatigue, uremic negative inotropic substances,

776 EXERCISE AFTER RENAL TRANSPLANTATION Mayo Clin Proc, September 1987, Vol 62

16

14

12

10

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6

4

2

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Fig. 1. Peak exercise capacity in units of multiples of resting metabolism (METS) on treadmill testing in 10 renal trans­plant patients at entry into aerobic exercise program (Tl), at program completion (T2), and at follow-up a mean of 2.2 years after completion of supervised exercise program (T3). Numbers identify individual patients at the three test periods. Dashed line denotes the mean.

and a reduced peak exercise heart rate possibly due to decreased cardiac sensitivity to sympa­thetic stimulation.12

Painter and Zimmerman13 reported a 42% im­provement in measured aerobic capacity in 13 renal transplant patients who underwent exer­cise testing preoperatively and a mean of 4 months after transplantation. Their patients did not participate in exercise training postopera-tively. In contrast, our current study showed a 90% increase in estimated aerobic capacity for the interval between 2 and 8 weeks postoperatively in patients who performed moderate regular aero­bic exercise.

At 1 to 3 years after transplantation, our pa­tients were able to achieve estimated peak exer­cise intensities of almost 11 METs (38.5 ml O2 · kg"1 ■ min1) , which corresponds to 110% of the mean capacity for healthy persons of similar age. We were encouraged that 7 of our 10 patients had continued regular exercise training during this

time interval. Painter and colleagues11 measured aerobic capacity in 20 patients who had under­gone renal transplantation 1 to 14 years (mean, 3.25 years) before testing. The 13 female and 7 male patients (mean age, 35 years) attained ex­ercise capacities that corresponded to 93% of age-predicted values. These patients had not received home exercise guidelines.

Exercise training in patients who undergo re­nal transplantation seems to result in improved exercise capacity. In the current study, however, a nonexercising control group was not available for comparison; thus, conclusions must be cau­tiously drawn. The observed increase in exercise capacity in the current study was probably re­lated to improved renal function and postsurgical healing (spontaneous increase in physical work capacity) as well as to the exercise training pro­gram. The measured increase in hemoglobin con­centration between Tl and T2 (mean increase of 3.8 g/dl) resulted in an increase in oxygen-carrying capacity of 45% and undoubtedly was partially responsible for the observed increase in aerobic capacity.

Nine of the 10 patients in the present study were receiving prednisone (20 mg/day). Gluco-corticoids are known to cause proximal muscle atrophy and decreased contraction force, which could result in a reduced exercise capacity. Horber and associates14 reported, however, that physical activity can reverse this corticosteroid-related myopathy in patients taking low to mod­erate doses of prednisone (13 mg/day). We found no evidence in our patient population of a below-average exercise capacity related to muscle weakness.

Patients with end-stage renal disease have an increased risk of developing coronary artery dis­ease. Modification of risk factors seems prudent in this patient population, with particular empha­sis on cessation of smoking, adequate treatment of hypertension and diabetes mellitus, and con­trol of blood lipids. In a report by Bagdade and co-workers,15 renal-failure patients with abnor­mal blood lipid profiles did not necessarily have improved lipid profiles after successful renal transplantation. Thus, the potential beneficial effects of long-term exercise training, such as increased high-density lipoprotein cholesterol, de­creased serum triglycerides, and reduced stores of body fat, may be important in this patient population.

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CONCLUSION Our 10 renal transplant patients easily tolerated an aerobic exercise testing and training program. The favorable results regarding exercise ability and employment status are indicative of the ex­cellent rehabilitation potential after renal trans­plantation. We conclude that supervised exercise training beginning soon after renal transplanta­tion is feasible and worthwhile. We believe that supervised exercise programs and detailed home exercise guidelines should be provided to selected patients after renal transplantation.

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7. Goldberg AP, Geltman EM, Gavin JR III, Carney RM, Hagberg JM, Delmez JA, Naumovich A, Oldfield MH, Harter HR: Exercise training reduces coronary risk and effectively rehabilitates hemodialysis patients. Nephron 42:311-316, 1986

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9. Borg GAV: Perceived exertion: a note on "history" and methods. Med Sei Sports Exerc 5:90-93,1973

10. Gutman RA, Stead WW, Robinson RR: Physical activity and employment status of patients on maintenance di­alysis. N Engl J Med 304:309-313,1981

11. Painter P, Messer-Rehak D, Hanson P, Zimmerman SW, Glass NR: Exercise capacity in hemodialysis, CAPD, and renal transplant patients. Nephron 42:47-51, 1986

12. Kettner A, Goldberg A, Hagberg J, Delmez J, Harter H: Cardiovascular and metabolic responses to submaximal exercise in hemodialysis patients. Kidney Int 26:66-71, 1984

13. Painter P, Zimmerman SW: Exercise in end-stage renal disease. Am J Kidney Dis 7:386-394,1986

14. Horber FF, Scheidegger JR, Grünig BE, Frey FJ: Evi­dence that prednisone-induced myopathy is reversed by physical training. J Clin Endocrinol Metab 61:83-88, 1985

15. Bagdade J, Casaretto A, Albers J: Effects of chronic uremia, hemodialysis, and renal transplantation on plasma lipids and lipoproteins in man. J Lab Clin Med 87:37-48,1976