Obesity has generally been thought to increase the risk of operative mortality and postoperative complications in surgical patients. No data examining obesity as a factor in cadaveric renal transplantation were available. We therefore matched obese patients undergoing cadaveric renal transplantation with nonobese control patients and retrospectively analyzed mortality, morbidity, and graft survival in each group. Patients were matched for age, sex, diabetes mellitus, PRA, graft number, cardiovascular disease, date of transplantation, and posttransplant immunosuppression. There were significant differences found in mortality (11% in obese vs. 2% in nonobese patients, P<0.01), immediate graft function (38% in obese vs. 64% in nonobese patients, P<0.01), 1-year graft survival (66% in obese vs. 84% in nonobese patients, P<0.05), and postoperative complications. Wound complications (20% vs. 2%, P<0.01), intensive-care-unit admissions (10% vs. 2%, P<0.01), reintubations (16% vs. 2%, P<0.03), and new-onset diabetes (12% vs. 0%, P<0.02) were all significantly more common in the obese group. These results suggest that an attempt at significant weight reduction is indicated in obese patients prior to renal transplantation. © 1990 by Williams & Wilkins

Hakala, TR

Holley, JL

Lopatin, WB

Shapiro, R

Starzl, TE

Tzakis, AG

English

PubMed

Name not available

Obesity as a risk factor following cadaveric renal transplantation

JEAN L. HOLLEY

RON SHAPIRO

WILLIAM B. LOPATIN

ANDREAS G. TZAKIS

THOMAS R. HAKALA

THOMAS E. STARZL

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OBESITY AS A RISK FACTOR FOLLOWING CADAVERIC RENAL TRANSPLANTATION

D-Scholarship@Pitt

........... I~ '" 1990 by Williams & Wilkina la~~ Vol 49, 387-389, No.2, February 1990 PrintNin U.S.A. -- OBESITY AS A RISK FACTOR FOLLOWING CADAVERIC RENAL TRANSPLANTATION JEAN L. HOLLEY/ RON SHAPIRO,' WILLIAM B. LoPATIN,a ANDREAS G. TZAKls.2 THOMAS R. HAKALA,a AND THOMAS E. STARZL1 The Reool-Electrolyte Division and the Department. of SfU"lery and UroIotIY at the University of Pitttburgh, PittlburBh, PenN)'lvoni4 Obesity has generally been thought to increase the . risk of operative mortality and postoperative complica-tions in surgical patients. No data examining obesity as • factor In cadaveric renal transplantation were avail-able. We therefore matched obese patients undergoing . cadaveric renal transplantation with nonobese control patients and retrospectively analyzed mortality. mor~ bldlty. and graft survival In each group. Patients were JDatched for age. sex, diabetes mellitu8, PRA, graft num-ber, cardiovascular disease, date of transplantation. and posttransplant immunosuppression. There were signif-icant differences found in mortality (11'" in obese va. 2% in nonobese patients, PsO.O 1). immediate graft func-tion (38'" in obese V8. 64% in nonobese patients. psO.Ol), I-year graft survival (66'" in obese vs. 84'" in nonobese patients, PsO.05), and postoperative com-plications. Wound complications (20% VB. 2"', PsO.Ol), intensive-care-unit admissions (10% vs. 2"', PsO.Ol). reintubations (16% V8. 2"'. PsO.03). and new-onset di-abetes (12% vs. 0"'. PsO.02) were all significantly more common in the obese group. These results suggest that an attempt at significant weight reduction is indicated in obese patients prior to renal transplantation. Obesity is generally thought to be associated with an in-creased risk in surgical patients (1). Operative mortality tends to be higher (2-4), and postoperative complications, especially wound infections (1.3-5), are more common. There are how-ever little data describing the results after cadaveric renal transplantation in obese patients. The experience at the Uni-versity of Pittsburgh was retrospectively analyzed to determine patient and graft survival as well as the incidence of various posttransplant complications. Obesity was defined as a body mass index of greater than 30, a commonly accepted definition (6, 1). A matched control group of nonobese renal transplant recipients was used for comparison. MATERIALS AND METHODS The medical records of obese patients with end-stage renal disease undergoing cadaveric renal transplantation between January 1986 and December 1988 at the University of Pittsburgh were reviewed. Living-related kidney and multiple-organ transplant recipients were excluded from the study. Obesity was defined as a body mass index (BMI = weight in Kg/height in mt) of ~PM (7). It should be noted that morbid obesity is defined as a BMI >35. Thus, only 13 of our 46 obese patients could be described as morbidly obese. The parameters examined in-cluded: (1) patient survival; (2) graft survival; (3) initial graft function I Address correspondence and reprint requests to Jean Holley, M.D., Renal-Electrolyte Division, 1191 Scai(e Hall, Pittsburgh, PA 15261. t Department of Surgery. I Department o( Urology. 387 (defined as clearance of creatinine without dialyaia by 1 week poettrana-plant); (4) duration of the operation; (5) need for reintubation postop-eratively, after initial extubation; (6) admiasion to an intensive care unit; (7) colonic diatension requiring either coIonOlCOpic or surgical decompression; (8) wound complications includinr hematoma, infec-tion, and dehiacence; (9) urinary-tract infections requiring antloiotic therapy; (10) duration of initial hospita1ization; and (11) new-onset diabetes.. n.e records of control (oonobese, BMI s27 for men, :s25 for women) patients were examined (or the same parameters as the obese patients. Each obese patient was matched with a control patient for age, sex, transplant graft number, diabetes mellitus at the time of transplanta-tion, pretranaplant panel-reactive antl'body within 30%, and pretrana-plant cardiovascular disease. defined by either a thallium streas test or coronary angiography and/or myocardial function by nuclear imaging (MUGA) or echocardiography. Control patients were also matched for date of transplantation (within 15 months) and posttranaplant irDJnu-DOSuppression. From January 1986 through January 1987, CaA and prednisone immunosuppression was used in all patients. From January 1987 through January 1988, approximately SO% of the transplant patients followed a triple-drug (azathioprine, CIA, and prednisone) immunosuppression protocol; the remaining patients were maintained on a CsA and prednisone regimen. After February 1988, all patients received the triple-drug protocol. Steroid-resistant rejection episodes were treated with a 10-14 day course of monoclonal antibody (OKT3). Patients with a high PRA (>SO%) and/or previous transplants were tleated with induction OKT3 therapy. StotistictJl methods. The statistical significance of differences be-tween proportions was determined by chi-square analysis with Yates' correction. Data were also analyzed between the matched subjects (or differences in proportions by the McNemar's test (8). Comparison among groups was performed by t test for independent samples. Sur-vival analysis was done by Mantel-Cox test. Probability less than 0.05 was considered significant. Data are given as mean values. RESULTS Table 1 demonstrates the postoperative morbidity and mor-tality observed in the 2 patient groups. Using the McNemar's test, significantly more patient deaths occurred during the initial hospital period in the obese group (5) than in the control group (1). Sepsis was the cause of all deaths in the obese patients: two of pulmonary etiology, two following cecal perfo-ration, and one due to an abdominal abscess after a long and complicated hospital course_ The patient death in the control group was secondary to sepsis caused by pyelonephritis. Figure 1 depicts patient survival over a 2-year follow-up period and shows no statistical difference between the groups but illus-trates a trend toward poorer survival in the obese patients; 1-year patient survival 89% in obese patients vs. 98% in control patients (Fig. 1). The overall patient survival at the University of Pittsburgh during this period was 93% at 1 year and 90% at 2 years after cadaveric renal transplantation. 388 TRANSPLANTATION TABLB 1. Postoperative morbidity and mortality TABLE 2. Patient group characteristics Obese Control pvalue n (") n(") Death. 5 (11) 1 (2) 0.01" Reintubation 8 (16) 1 (2) 0.03 ICU admission 10 (20) 1 (2) 0.01 Wound complications 10 (20) 1(2) 0.01 New onset diabetes 6 (12) 0 0.02 + Initial function 19 (38) 32 (64) 0.01 Duration of surgery (min) 301±123 230±69t Days of hospitalization 39±47 23±12' • McNemar's test for matched subjects. All other data expressed as results of chi -square analysis. t P:SO.OO3. • P:sO.02. UNIVERSITY OF PITISBURGH KIDNEY TRANSPLANTATION OBESE VS NON-OBESE PATIENTS PERCENT SURVIVAL ': ~___ -<> ___ <l-m. ____ • ___ .., 80. .t .t -. :::::::t:::=::: 70 K_K_~ 60 --e-.--o--.--o 50 40 30 OBESE PT SURVIVAL OBESE PT GX SURVIVAL 20 - -G-10 klk-lBbKKs~!K SURV,r'/AL NON-OBESE ~ GX SURVIVAL o~~==~~==~~~==~~ o 3 6 9 12 15 18 21 24 MONTHS FIGURE 1. Patient and graft survival for obese and nonobese groups. Initial allograft function and ultimate graft survival were both significantly worse in the obese group. Thirty-eight per· cent of the obese patients were clearing creatinine by 1 week posttransplant versus 64% of the control group (PsO.01, Table 1). One-year acturial graft survival was 66% in the obese versus 84% in the nonobese group, PsO.05 (Fig. 1). Differences between the patient groups were noted in dura-tion of surgery and hospitalization, both significantly longer in the obese patients (Table 1). The groups were matched, there-fore no differences were appreciated in mean age, sex, presence of diabetes mellitus, PRA, transplantation date, or immuno-suppressive protocol (Table 2). Significantly increased morbidity occurred in the obese group including 10 intensive-care-unit admissions, 8 reintubations, and 10 wound complications (either hematoma, infection, or dehiscence, Table 1). There was no difference between the obese and control groups in the occurrence of urinary-tract infections or colonic distension requiring colonoscopic or sur-gical intervention. Two patients in the obese group however died because of colonic distension and subsequent sepsis. Sig-nificantly more obese patients who were not diabetic before transplantation required insulin therapy for glucose control after transplantation. DISCUSSION Obesity is known to increase the risk of surgical procedures (1), but little data are available regarding the risks of obesity Obese Cn - 46) Control (n - 50) --No. transplants 50 50 Mean age (years) «.7 «.9 Sex (F/M) 21/26 23/27 Mean BMI (range) 33.5 (30-45) 23.3 (18-27) associated with renal transplantation. In 1986 Pasulka et outlined areas in which obesity increased surgical risk. included anesthetic problems of airway control and v .. rDDDD~_·_I access problems; im~red lung function in approximately third of obese patients (9); an increase in cardiac stroke leading to circulatory problems (10), thromboembolic, and wound complications; and technical considerations, inclu~ e~sureI hemostasis, anasto~otic function, and wound ap~ sltlOn (1). The overall operative mortality has not been showi to be significantly increased in obese patients undergoing var: ious surgical procedures. Trends however toward higher mor-tality rates in obese patients have been repeatedly noted (1-3: 11). Small numbers of patients in all these studies may com: promise the statistical results. We have shown a significantly decreased patient survival during the initial hospital period in the obese patients. Complications in the areas of anesthesia (1 technical COIJl. plication of venous-access placement in an obese patient) and respiratory insufficiency (reintubation, required in 16%, Table 2), as suggested by Pasulka (1), were seen in our obese patients. Additionally, complications of increased stroke work were plau-sible in 2 control patients and .. obese patients. Postoperative pulmonary edema occurred as a result of fluid administration in. the setting of end-stage renal disease, most often in patients WIth some degree of myocardial dysfunction. Ultrafiltration therapy resolved the problem in all cases. Admission to an intensive care unit was more common in the obese group (20% vs. 2%) and was prompted by the need for reintubation (8 patients,4 with associated sepsis) in most instances. Two obese patients required leu admission for cardiovascular reasons. In 1 case this was due to a perioperative myocardial infarction and in another, a supraventricular arrthymia. The most frequently reported postoperative complication in obese patients is wound infection (2-4) and wound disruption (2, 5). Postlethwait bas suggested that longer operations (due to technical difficulties), increased trauma to the abdominal wall from vigorous retraction, the low resistance of fat to infection, and an inability to obliterate dead space in the abdominal wall fat are all contributing factors (3). The in-creased wound area in obese patients has also been postulated as a major factor leading to higher rates of wound infection in these patients (12). We observed a significantly higher inci· dence of wound complications in our obese patients (20% vs. 2% in the nonobese patients, PsO.01) and also noted longer operations in the obese group. Transplant nephrectomy, urine leak, and hematoma are associated with a higher incidence of wound infection in the transplant population (13, 14). The single wound complication in the control group was associated with a urine leak. Four of the 10 wound complications seen in the obese group occurred after transplant nephrectomy, and one followed 8 wound hematoma. The remaining five, however, may reflect the combined negative effects of prolonged surgery and the low resistance of fat to infection (3). The latter factor may be amplified in the immunosuppressed state that accom-panies renal transplantation. Fi reo pr til of ob p( sil de of is! su be I.·. ileus ~ • re<ognb<d rompUcation o::~;y : ;~bortaa LB, Manu WO. oKb~ or ~ ~~ f and is often a serious cause of morbidity and tive complications aft.er cholecystectomy. Am J Surg 1971; 121: ; ;, JIlortality from cecal perforation (15, 16). Two obese patients 87. { .'{t .. ,died of sepsis relatoo to cecal perforation caused by Ogilvie's 5. Strauss RJ, Wise L. Operative risks of obesity. Surg Gynecol Obstet ~ ~~~ , " but no statistical differences in rates of colonic 6. Kral JG, Heymsfield S. Morbid obesity: definitions, epidemiology, I were notOO between the obese and control groups. and methodological problems. Gastroent Clin North Am 1987; Ste,roilti-iJldu,ced diabetes has long been recognized in the 16: 197. . . 1tK~lClUttgranspllllflt population (17). The insulin resistance and 7. Obesity in America. Dept. Health, Education and Welfare, Public ¥.;;mll81lre<J glucose tolerance seen with obesity (18,19), combined Health Service, National Institute of Health publication No. 79-steroid immunosuppression may exacerbate this metabolic 359; Nov (PHS) 1979. derangement in obese transplant recipients. The additional 8. SebeBer we. Statistics for health profeaaionaIa. Readi.nc.'MA: hyperglycemic effects of CsA (20, 21), presumably via impaired Addison-Wesley, 1984: 234. ' insulin secretion (22, 23), warrants further study in this group 9. Ray CSt Sue DY, Bray G, et at Effects of obesity on respiratory ., of patients. function. Am Rev &spir DiS 1983; 128: 501. . f ~ Initial graft function and long-term graft survival (Table 2, 10. Argarwal N, Shibutani K, SanFilippo JA. et al. Hemodynamic and I. .." .. , FiI· 1) were both significantly worse in the obese patients. The respiratory cbangee in surgery of the morbidly obese. Surgery ~ 1982; 92: 226. " . . , ,easons for these observations remain speculative and require 11. Prem KA, Mensbeba NM, McKelvey JL. Operative treatment of '! prospective study. Factors such as longer graft warm ischemia adenocarcinoma of the endometrium in obese women. Am J (7: time, due to the technical challenge the vascular anastomoses Obstet Gynecol 1965; 92: 16. . I~ offer and, secondly, possible altered esA pharmacokinetics in 12. Nystrom P-O, Jonstam A, Hojer H, et al. Incisional infection aft.er ~:r obese patients may both contribute to lower graft survival. colorectal surgery in obese patients. Acta Chir &and 1987; 153: postoperative complications in the obese patients occurred 225. significantly more often than in the control patients and no 13. Lee HM, Madge GE, Mendez-Picon G, et a1. Surgical complications doubt contributOO to poorer graft survival in the former group in renal transplant recipients. Surg Clin North Am 1978; 58: 285. 14. Kyriakides GK, Simmons RL, Najarian JS. Wound infection. in of patients. renal transplant wounds: pathogenetic and prognostic factors. Since each patient was matched for demographic character- Ann Surg 1975; 182: 770. istics, obesity was identified as an independent risk factor for 15. Powis SJA, Barna AD, Dawson-Edwards P, et al. Deocolonic prob-, successful renal transplantation. Mortality during the initial lema aft.er cadaveric renal transplantation. Br Med J 1982; 1: 99. hospital period was increased in the obese population. More 16. Stratta RJ, Starling JR, D'Alessandro AM. et al. Acute colonic wound complications and an increased need for insulin therapy ileus (pseudoobstruction) in renal transplant recipients. Surgery occurred in obese versus control patients. Serious complications 1988; 104: 616. . requiring ICU admission and reintubation were also more fre- 17. Ruiz JO, Simmon8 RL, Callender CO, et al. Steroid diabetes in quent in this group of patient8. In addition to higher rates of renal transplant recipients: pathogenetic factors and prognosis. postoperative complications and longer hospital stays, graft Surgery 1973; 73: 759. (unction in these patients was significantly worse than in the 18. Rabinowitz D, Zierler KL. Forearm metabolism in obesity and its response to intra-arterial insulin: characterization of insulin control population_ All these observations suggest that preop- resistance and evidence for adaptive hyperinsulinemia. J Clin erative weight reduction should be stressed in obese patients Invest 1962; 41: 2173. prior to kidney transplantation. Furthermore, additional study 19. Toeller M. Gries FA, Dannehl K. Natural history of glucose intol-is needed in order to elucidate the factors contributing to poorer erance in obesity: a ten year observation. Int JObes 1982; 6(suppl graft survival in obese patients. 1): 145. Acknowlt>dgments, We thank Beth Piraino, M,D., for assistance in data analysis and for reviewing the manuscript. REFERENCES 1. Pasulka PS, Bistrian BR, Benotti PN, et al. The risks of surgery in obese patil.'nts. Ann Int Med 1986; 104: 540. 2. Pitkin RM. Abdominal hysterectomy in obese women. Surg Gy-necol Obstet 1976; 142: 532. 3. Postlethwait RW. Johnson WO. Complications following surgery for duodenal ulcer in obese patients. Arch Surg 1972; 105: 438. 20. Yoshimura N, Nakai I. Ohmori Y, et al. Effect of cyclosporine on the endocrine and exocrine pancreas in kidney transplant recip-ients. Am J Kidney Dis 1988; 12: 11. 21. Roth D, Milogrom M, Esquenazi V, et al. Post transplant hyper-glycemia. Transplantation 1989; 47: 278. 22. Nielson JH, Mandrup-Paulsen T. Nerup J. Direct effects of cyclo· sporin A on human pancreatic B-cells. Diabetes 1986; 35: 1049. 23. Robertson RP. Cyclosporin-induced inhibition of insulin secretion in isolated rat islets and HIT cells. Diabetes 1986; 35: 1016. Received 12 July 1989. Accepted 17 August 1989. i I· f r i l 

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Obesity as a risk factor following cadaveric renal transplantation

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