- Email: [email protected]
Post–Renal Transplantation Weight Gain: Its Causes and Its Consequences
Post–Renal Transplantation Weight Gain: Its Causes and Its Consequences J.M. Díaz, Z. Sainz, A. Oliver, L.I. Guirado, C. Facundo, R. García-Maset, and R. Solà ABSTRACT Objective. A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. Methods. Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase ⬍10% (group 2); and BMI increase ⬎10% (group 3). Results. The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m2. The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.
T
HE CAUSES of weight gain among both the general and the renal transplant populations are multifactorial including genetic heredity, age, ethnic group, calorie intake, and exercise. The tendency to increased body mass index (BMI) after renal transplantation has been associated with effects of immunosuppressants on corporal fat and water composition,1 in addition to other contributory causes. The objective of this study was to analyze the causes and consequences of this weight gain. MATERIAL AND METHODS Two hundred twelve renal transplant recipients, including 142 males (67%) and 70 females (33%) of mean age 52 years (SD, 14), carried functional renal grafts for more than 1 year and showed a mean follow-up of 5 years (range, 1–20). The patients were divided into 3 groups according to this evolution: BMI loss (group 1); BMI increase ⬍10% (group 2); and BMI increase ⬎10% (group 3). This observational prospective study analyzed various demographic, anthropometric, and clinical variables. The quantitative variables were expressed as mean values, with standard deviations and ranks between parentheses. The result of qualitative variables were expressed as percentages. Chi-square Student t, and analysis of variance (ANOVA) tests were applied according to the type of variable. Value of P ⬍ .05 was considered
significant. The weight ranks were defined as per the BMI-based World Health Organization (WHO) classification.2
RESULTS
The mean BMI gain was 6.2% (SD, 10.8; ⫺19.4/54.7), which translated into a weight gain of 3.9 kg (68.3–72.2 kg; P ⬍ .001), and a BMI gain of 1.4 kg/m2 (24.8 –26.2 kg/m2; P ⬍ .001) at the time of transplantation, 10.3% of patients were obese, a percentage that increased to 17.9% 5 years later. The population under study was almost equally divided into 3 groups (33.5% group 1; 33.5% group 2; and 33% group 3). The results displayed in Table 1 show that group 3 patients were younger. There were no significant differences in gender (although females were more prone to From the Renal Transplant Unit, Nephrology Department (J.M.D., Z.S., L.I.G., C.F., R.G.-M., R.S.) and Laboratory Service, Fundació Puigvert (A.O.), Universitat Autónoma Barcelona, Barcelona, Spain. Address reprint requests to J.M. Díaz, Renal Transplant Unit, Nephrology Department, Fundació Puigvert, Universitat Autónoma Barcelona, Cartagena, 340. 08025. Barcelona, Spain. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.200
Transplantation Proceedings, 37, 3839 –3841 (2005)
3839
3840
DÍAZ, SAINZ, OLIVER ET AL Table 1. Baseline Parameters According to Post–Renal Transplantation BMI Increase n ⫽ 212
Group 1
Group 2
Group 3
P
Females (%) Age (y) Pre–renal transplantation diabetes (%) Acute rejection (%) Pre–renal transplantation BMI (kg/m2) SBP (mm Hg) DBP (mm Hg) Anti-HTA drugs (%) Cholesterol (mmol/L) Triglycerides (mmol/L) HDL-cholesterol (mmol/L) LDL-cholesterol (mmol/L) Statins (%) Post–renal transplantation DM (%) HbA1c (%) Metabolic syndrome (%) Homocysteine (mol/L) Fibrinogen (g/L) CRP (mg/L) Albumin (g/L) Creatinine (mol/L) Creatinine clearance (mL/min) Proteinuria ⬎0.3 g/d (%) CV events (%)
29.6 53.2 (14.4) 8.5 36.6 25.7 (4.2) 131.3 (12.7) 75.5 (8.4) 77.5 4.83 (0.85) 1.39 (0.7) 1.59 (0.52) 2.59 (0.77) 45.1 11.3 5.5 (0.52) 10.5 18.2 (7.12) 3.93 (1.07) 7.32 (13.2) 42.2 (4.4) 161 (79) 49 (21) 18.3 16.9
33.4 54.5 (14) 9.9 38 24.4 (3.5) 131.1 (11.2) 75.7 (8.2) 78.9 5.18 (0.8) 1.64 (0.86) 1.56 (0.42) 2.86 (0.75) 49.3 11.3 5.65 (0.57) 19.6 17.4 (6.64) 3.52 (0.73) 3.55 (3.7) 44.3 (2.8) 137 (52) 57 (24) 9.9 14.1
37.1 47.2 (11.8) 4.3 42.9 24.2 (3.9) 131 (10.7) 76.1 (7.2) 85.7 5.1 (0.74) 1.59 (1.26) 1.46 (0.42) 2.9 (0.69) 44.3 7.1 5.6 (0.56) 25.8 16.1 (6.19) 3.97 (0.99) 5.28 (5.9) 42.7 (3.2) 136 (47) 66 (26) 18.6 15.6
.63 .003 .59 .73 .06 .98 .91 .04 .023 .29 .25 .035 .81 .59 .33 .10 .18 .016 .047 .03 .027 .001 .27 .90
Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; HTA, hypertension; HDL, high-density lipoprotein; LDL, low-density lipoprotein; DM, diabetes mellitus; CRP, c-reactive protein; CV, cardiovascular.
gaining weight), in preoperative diabetes, in incidence of acute rejection episodes or in baseline BMI. The blood pressure was similar in all 3 groups at the time of performing the study, but more group 3 patients needed antihypertensive treatment. Progressive increases in total and low-density lipoprotein (LDL)-cholesterol were also observed as patients gained BMI. There were differences according to whether patients were treated with statins. No differences were found regarding the behavior of carbohydrate metabolism; however, with weight gain more patients feel into the metabolic syndrome criteria. Homocysteine values were the same in all 3 groups, but groups 1 and 3 showed a less favorable micro-inflammatory profile, namely, increased fibrinogen and c-reactive protein as well as decreased albumin. The mean creatinine clearance level was also found to be better in group 3 than group 1. No differences were seen in proteinuria. We failed to observe a difference between the 3 groups regarding the number of nonfatal post-operative cardiovascular events. DISCUSSION
Weight gain in our study was less than in other studies. Merion et al3 observed a 9-kg increase in nonobese patients and a 14-kg increase in obese patients, similar to the findings of Gill et al4 who observed a total increase of 8.5 kg. Similar results were seen regarding the BMI increase. In our series, there was an increase of 6.2% at 5 years, whereas in other studies the increase was 10.9% during the first year and 15.3% at 5 years.5
The 10.3% incidence of obese patients at baseline increased to 17.9% at 5 years postoperative. These figures are remarkably lower than those of other series,6 which reported the prevalence of baseline obesity to be 20%–25%. Age has been the only factor that we showed to correlate with an increased BMI after grafting, consistent with the results of 2 other studies.5,7 These analyses concluded that women had a greater postoperative BMI, whereas we only suggested a trend toward this finding. Also in other studies5,7 as well as in ours, no higher prevalence of acute rejection episodes were observed within the weight gain group. Clunk et al verified that the incidence of acute rejection episodes was inversely related to weight gain because the patients who did not experience acute rejection gained 2.5% more weight during the first year than those who had had at least 1 acute rejection episode. Merion et al3 reported that the steroid dose administered per kilogram of body weight was lower among obese patients, possibly explaining the increased risk of rejection. We have not been able to study the effect of ethnicity because all of our patients were white. However, similar to other authors, we did not confirm that patients who were obese preoperatively gained more BMI than nonobese ones.7 Increased BMI in our study the translated to a greater need for antihypertensive treatment, to increased cholesterol and LDL-cholesterol values, and to a tendency among nondiabetic patients to display the metabolic syndrome. As
WEIGHT GAIN
a matter of fact, Kasiske et al8 observed an increased incidence of posttransplantation diabetes among patients who were obese at the time of transplantation. These results suggest that patients who experienced a greater increase in BMI also showed increased microinflammation markers, as is known to occur among the general population.9 Regarding the progress of graft function, the literature shows controversies during long-term follow-up, as to whether obesity is a negative factor for graft survival, although most studies using 5-year data suggest that it is not.10,11 However, a progressive reduction in graft survival starts after 5 years. In our study, the group of patients who gained more weight enjoyed better renal function after 5 years, with no increase in the number of patients with significant proteinuria, although we did not control for antiproteinuric treatment with either ACEI or angiotensin receptor blockers. It is possible that our institutional policy, for graft distribution namely, young donor to young recipient, explains these results. A reduced 5-years survival of obese compared with nonobese patients has been observed in some studies.5,12 This reduction may be due to the cardiovascular disorders that existed prior to the procedures, including an increased prevalence of ischemic cardiopathy. However, a study performed in Spain13 failed to observe a survival difference at 5 years. Although patients who did not increase their BMI by ⬎10% had more cardiovascular risk factors, they did not have a greater incidencely nonfatal cardiovascular events. Perhaps the circumstances of their younger age and their better renal function acted as protective factors. In conclusion, the mean BMI increase at 5 years following renal transplantation was 6.2%. Young patients experi-
3841
enced the greatest BMI increase posttransplantation. They would benefit the most from dietary control. Patients who increased their BMI by ⬎10% had a worse overall cardiovascular profile than the others, but at 5 years follow-up they did not show more nonfatal cardiovascular events. REFERENCES 1. Isiklar I, Akin O, Demirag A: Effects of renal transplantation on body composition. Transplant Proc 30:831, 1998 2. James PT, Leach R, Kalamara E, et al: The worldwide obesity epidemic. Obes Res 9:S228, 2001 3. Merion RM, Twork AM, Rosenberg L, et al: Obesity and renal transplantation. Surg Gynecol Obstet 172:367, 1991 4. Gill IS, Hodge EE, Novick AC, et al: Impact of obesity on renal transplantation. Transplant Proc 25:1047, 1993 5. Johnson CP, Gallagher-Lepak S, Zhu YR, et al: Factors influencing weight gain after renal transplantation. Transplantation 56:822, 1993 6. Friedman AN, Miskulin DC, Rosenberg IH, et al: Demographics and trends in oveweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis 41:480, 2003 7. Clunk JM, Chin-Yu Lin, Curtis JJ: Variables affecting weight gain in renal transplant recipients. Am J Kidney Dis 38:349, 2001 8. Kasiske BI, Snyder JJ, Gilbertson D, et al: Diabetes after kidney transplantation in the United States. Am J Transplant 30:777, 1998 9. Visser M, Bouter LM, Mc Quillan GM, et al: Elevated C-reactive protein levels in overweight and obese adults. JAMA 282:2131, 1999 10. Yamamoto S, Hanley E, Hahn AB, et al: The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys. Clin Transplant 16:252, 2002 11. Johnson DW, Isbel NM, Brown AM, et al: The effect of obesity on renal transplant outcomes. Transplantation 74:675, 2002 12. Modlin CS, Flechner SM, Goormastic M, et al: Should obese patients lose weight before receiving a kidney transplant? Transplantation 64:599, 1997 13. Orofino L, Pascual J, Quereda C, et al: Influence of overweight on survival of kidney transplant. Nephrol Dial Transplant 12:855, 1997
T
HE CAUSES of weight gain among both the general and the renal transplant populations are multifactorial including genetic heredity, age, ethnic group, calorie intake, and exercise. The tendency to increased body mass index (BMI) after renal transplantation has been associated with effects of immunosuppressants on corporal fat and water composition,1 in addition to other contributory causes. The objective of this study was to analyze the causes and consequences of this weight gain. MATERIAL AND METHODS Two hundred twelve renal transplant recipients, including 142 males (67%) and 70 females (33%) of mean age 52 years (SD, 14), carried functional renal grafts for more than 1 year and showed a mean follow-up of 5 years (range, 1–20). The patients were divided into 3 groups according to this evolution: BMI loss (group 1); BMI increase ⬍10% (group 2); and BMI increase ⬎10% (group 3). This observational prospective study analyzed various demographic, anthropometric, and clinical variables. The quantitative variables were expressed as mean values, with standard deviations and ranks between parentheses. The result of qualitative variables were expressed as percentages. Chi-square Student t, and analysis of variance (ANOVA) tests were applied according to the type of variable. Value of P ⬍ .05 was considered
significant. The weight ranks were defined as per the BMI-based World Health Organization (WHO) classification.2
RESULTS
The mean BMI gain was 6.2% (SD, 10.8; ⫺19.4/54.7), which translated into a weight gain of 3.9 kg (68.3–72.2 kg; P ⬍ .001), and a BMI gain of 1.4 kg/m2 (24.8 –26.2 kg/m2; P ⬍ .001) at the time of transplantation, 10.3% of patients were obese, a percentage that increased to 17.9% 5 years later. The population under study was almost equally divided into 3 groups (33.5% group 1; 33.5% group 2; and 33% group 3). The results displayed in Table 1 show that group 3 patients were younger. There were no significant differences in gender (although females were more prone to From the Renal Transplant Unit, Nephrology Department (J.M.D., Z.S., L.I.G., C.F., R.G.-M., R.S.) and Laboratory Service, Fundació Puigvert (A.O.), Universitat Autónoma Barcelona, Barcelona, Spain. Address reprint requests to J.M. Díaz, Renal Transplant Unit, Nephrology Department, Fundació Puigvert, Universitat Autónoma Barcelona, Cartagena, 340. 08025. Barcelona, Spain. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.200
Transplantation Proceedings, 37, 3839 –3841 (2005)
3839
3840
DÍAZ, SAINZ, OLIVER ET AL Table 1. Baseline Parameters According to Post–Renal Transplantation BMI Increase n ⫽ 212
Group 1
Group 2
Group 3
P
Females (%) Age (y) Pre–renal transplantation diabetes (%) Acute rejection (%) Pre–renal transplantation BMI (kg/m2) SBP (mm Hg) DBP (mm Hg) Anti-HTA drugs (%) Cholesterol (mmol/L) Triglycerides (mmol/L) HDL-cholesterol (mmol/L) LDL-cholesterol (mmol/L) Statins (%) Post–renal transplantation DM (%) HbA1c (%) Metabolic syndrome (%) Homocysteine (mol/L) Fibrinogen (g/L) CRP (mg/L) Albumin (g/L) Creatinine (mol/L) Creatinine clearance (mL/min) Proteinuria ⬎0.3 g/d (%) CV events (%)
29.6 53.2 (14.4) 8.5 36.6 25.7 (4.2) 131.3 (12.7) 75.5 (8.4) 77.5 4.83 (0.85) 1.39 (0.7) 1.59 (0.52) 2.59 (0.77) 45.1 11.3 5.5 (0.52) 10.5 18.2 (7.12) 3.93 (1.07) 7.32 (13.2) 42.2 (4.4) 161 (79) 49 (21) 18.3 16.9
33.4 54.5 (14) 9.9 38 24.4 (3.5) 131.1 (11.2) 75.7 (8.2) 78.9 5.18 (0.8) 1.64 (0.86) 1.56 (0.42) 2.86 (0.75) 49.3 11.3 5.65 (0.57) 19.6 17.4 (6.64) 3.52 (0.73) 3.55 (3.7) 44.3 (2.8) 137 (52) 57 (24) 9.9 14.1
37.1 47.2 (11.8) 4.3 42.9 24.2 (3.9) 131 (10.7) 76.1 (7.2) 85.7 5.1 (0.74) 1.59 (1.26) 1.46 (0.42) 2.9 (0.69) 44.3 7.1 5.6 (0.56) 25.8 16.1 (6.19) 3.97 (0.99) 5.28 (5.9) 42.7 (3.2) 136 (47) 66 (26) 18.6 15.6
.63 .003 .59 .73 .06 .98 .91 .04 .023 .29 .25 .035 .81 .59 .33 .10 .18 .016 .047 .03 .027 .001 .27 .90
Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; HTA, hypertension; HDL, high-density lipoprotein; LDL, low-density lipoprotein; DM, diabetes mellitus; CRP, c-reactive protein; CV, cardiovascular.
gaining weight), in preoperative diabetes, in incidence of acute rejection episodes or in baseline BMI. The blood pressure was similar in all 3 groups at the time of performing the study, but more group 3 patients needed antihypertensive treatment. Progressive increases in total and low-density lipoprotein (LDL)-cholesterol were also observed as patients gained BMI. There were differences according to whether patients were treated with statins. No differences were found regarding the behavior of carbohydrate metabolism; however, with weight gain more patients feel into the metabolic syndrome criteria. Homocysteine values were the same in all 3 groups, but groups 1 and 3 showed a less favorable micro-inflammatory profile, namely, increased fibrinogen and c-reactive protein as well as decreased albumin. The mean creatinine clearance level was also found to be better in group 3 than group 1. No differences were seen in proteinuria. We failed to observe a difference between the 3 groups regarding the number of nonfatal post-operative cardiovascular events. DISCUSSION
Weight gain in our study was less than in other studies. Merion et al3 observed a 9-kg increase in nonobese patients and a 14-kg increase in obese patients, similar to the findings of Gill et al4 who observed a total increase of 8.5 kg. Similar results were seen regarding the BMI increase. In our series, there was an increase of 6.2% at 5 years, whereas in other studies the increase was 10.9% during the first year and 15.3% at 5 years.5
The 10.3% incidence of obese patients at baseline increased to 17.9% at 5 years postoperative. These figures are remarkably lower than those of other series,6 which reported the prevalence of baseline obesity to be 20%–25%. Age has been the only factor that we showed to correlate with an increased BMI after grafting, consistent with the results of 2 other studies.5,7 These analyses concluded that women had a greater postoperative BMI, whereas we only suggested a trend toward this finding. Also in other studies5,7 as well as in ours, no higher prevalence of acute rejection episodes were observed within the weight gain group. Clunk et al verified that the incidence of acute rejection episodes was inversely related to weight gain because the patients who did not experience acute rejection gained 2.5% more weight during the first year than those who had had at least 1 acute rejection episode. Merion et al3 reported that the steroid dose administered per kilogram of body weight was lower among obese patients, possibly explaining the increased risk of rejection. We have not been able to study the effect of ethnicity because all of our patients were white. However, similar to other authors, we did not confirm that patients who were obese preoperatively gained more BMI than nonobese ones.7 Increased BMI in our study the translated to a greater need for antihypertensive treatment, to increased cholesterol and LDL-cholesterol values, and to a tendency among nondiabetic patients to display the metabolic syndrome. As
WEIGHT GAIN
a matter of fact, Kasiske et al8 observed an increased incidence of posttransplantation diabetes among patients who were obese at the time of transplantation. These results suggest that patients who experienced a greater increase in BMI also showed increased microinflammation markers, as is known to occur among the general population.9 Regarding the progress of graft function, the literature shows controversies during long-term follow-up, as to whether obesity is a negative factor for graft survival, although most studies using 5-year data suggest that it is not.10,11 However, a progressive reduction in graft survival starts after 5 years. In our study, the group of patients who gained more weight enjoyed better renal function after 5 years, with no increase in the number of patients with significant proteinuria, although we did not control for antiproteinuric treatment with either ACEI or angiotensin receptor blockers. It is possible that our institutional policy, for graft distribution namely, young donor to young recipient, explains these results. A reduced 5-years survival of obese compared with nonobese patients has been observed in some studies.5,12 This reduction may be due to the cardiovascular disorders that existed prior to the procedures, including an increased prevalence of ischemic cardiopathy. However, a study performed in Spain13 failed to observe a survival difference at 5 years. Although patients who did not increase their BMI by ⬎10% had more cardiovascular risk factors, they did not have a greater incidencely nonfatal cardiovascular events. Perhaps the circumstances of their younger age and their better renal function acted as protective factors. In conclusion, the mean BMI increase at 5 years following renal transplantation was 6.2%. Young patients experi-
3841
enced the greatest BMI increase posttransplantation. They would benefit the most from dietary control. Patients who increased their BMI by ⬎10% had a worse overall cardiovascular profile than the others, but at 5 years follow-up they did not show more nonfatal cardiovascular events. REFERENCES 1. Isiklar I, Akin O, Demirag A: Effects of renal transplantation on body composition. Transplant Proc 30:831, 1998 2. James PT, Leach R, Kalamara E, et al: The worldwide obesity epidemic. Obes Res 9:S228, 2001 3. Merion RM, Twork AM, Rosenberg L, et al: Obesity and renal transplantation. Surg Gynecol Obstet 172:367, 1991 4. Gill IS, Hodge EE, Novick AC, et al: Impact of obesity on renal transplantation. Transplant Proc 25:1047, 1993 5. Johnson CP, Gallagher-Lepak S, Zhu YR, et al: Factors influencing weight gain after renal transplantation. Transplantation 56:822, 1993 6. Friedman AN, Miskulin DC, Rosenberg IH, et al: Demographics and trends in oveweight and obesity in patients at time of kidney transplantation. Am J Kidney Dis 41:480, 2003 7. Clunk JM, Chin-Yu Lin, Curtis JJ: Variables affecting weight gain in renal transplant recipients. Am J Kidney Dis 38:349, 2001 8. Kasiske BI, Snyder JJ, Gilbertson D, et al: Diabetes after kidney transplantation in the United States. Am J Transplant 30:777, 1998 9. Visser M, Bouter LM, Mc Quillan GM, et al: Elevated C-reactive protein levels in overweight and obese adults. JAMA 282:2131, 1999 10. Yamamoto S, Hanley E, Hahn AB, et al: The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys. Clin Transplant 16:252, 2002 11. Johnson DW, Isbel NM, Brown AM, et al: The effect of obesity on renal transplant outcomes. Transplantation 74:675, 2002 12. Modlin CS, Flechner SM, Goormastic M, et al: Should obese patients lose weight before receiving a kidney transplant? Transplantation 64:599, 1997 13. Orofino L, Pascual J, Quereda C, et al: Influence of overweight on survival of kidney transplant. Nephrol Dial Transplant 12:855, 1997