Higher recipient body mass index is associated with post-transplant delayed kidney graft function
2011; Elsevier BV; Volume: 80; Issue: 2 Linguagem: Inglês
10.1038/ki.2011.114
ISSN1523-1755
AutoresMiklos Z. Molnar, Csaba P. Kövesdy, István Mucsi, Suphamai Bunnapradist, Elani Streja, Mahesh Krishnan, Kamyar Kalantar‐Zadeh,
Tópico(s)Renal and Vascular Pathologies
ResumoTo examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m2. After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22–24.99 kg/m2, overweight patients (BMI 25–29.99 kg/m2), mild obesity patients (BMI 30–34.99 kg/m2), and moderate-to-severe obesity patients (BMI 35 kg/m2 and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF. To examine whether a higher body mass index (BMI) in kidney recipients is associated with delayed graft function (DGF), we analyzed data from 11,836 hemodialysis patients in the Scientific Registry of Transplant Recipients who underwent kidney transplantation. The patient cohort included women, blacks, and diabetics; the average age was 49 years; and the mean BMI was 26.8 kg/m2. After adjusting for relevant covariates, multivariate logistic regression analyses found that one standard deviation increase in pretransplant BMI was associated with a higher risk of DGF (odds ratio (OR) 1.35). Compared with patients with a pretransplant BMI of 22–24.99 kg/m2, overweight patients (BMI 25–29.99 kg/m2), mild obesity patients (BMI 30–34.99 kg/m2), and moderate-to-severe obesity patients (BMI 35 kg/m2 and over) had a significantly higher risk of DGF, with ORs of 1.30, 1.42, and 2.18, respectively. Similar associations were found in all subgroups of patients. Hence, pretransplant overweight or obesity is associated with an incrementally higher risk of DGF. Delayed graft function (DGF) is a well-known complication affecting kidney allograft outcomes in the immediate post-transplantation period and is defined as the need for at least one session of dialysis treatment in the first week after receiving a kidney transplant;1.Yarlagadda S.G. Coca S.G. Garg A.X. et al.Marked variation in the definition and diagnosis of delayed graft function: a systematic review.Nephrol Dial Transplant. 2008; 23: 2995-3003Crossref PubMed Scopus (282) Google Scholar DGF is attributed to ischemia reperfusion and immunological injury of the graft.2.Perico N. Cattaneo D. Sayegh M.H. et al.Delayed graft function in kidney transplantation.Lancet. 2004; 364: 1814-1827Abstract Full Text Full Text PDF PubMed Scopus (759) Google Scholar The prevalence of DGF varies from 4 to 10% in living donor2.Perico N. Cattaneo D. Sayegh M.H. et al.Delayed graft function in kidney transplantation.Lancet. 2004; 364: 1814-1827Abstract Full Text Full Text PDF PubMed Scopus (759) Google Scholar and 5–50% in deceased donor kidney transplants.3.Ojo A.O. Wolfe R.A. Held P.J. et al.Delayed graft function: risk factors and implications for renal allograft survival.Transplantation. 1997; 63: 968-974Crossref PubMed Scopus (839) Google Scholar, 4.Koning O.H. van Bockel J.H. van der Woude F.J. et al.Risk factors for delayed graft function in University of Wisconsin solution preserved kidneys from multiorgan donors. European Multicenter Study Group on Organ Preservation.Transplant Proc. 1995; 27: 752-753PubMed Google Scholar, 5.Sellers M.T. Gallichio M.H. Hudson S.L. et al.Improved outcomes in cadaveric renal allografts with pulsatile preservation.Clin Transplant. 2000; 14: 543-549Crossref PubMed Scopus (61) Google Scholar, 6.Gjertson D.W. Impact of delayed graft function and acute rejection on graft survival.Transplant Proc. 2002; 34: 2432Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar, 7.Hassanain M. Tchervenkov J. Cantarovich M. et al.Delayed graft function has an equally bad impact on deceased donor renal graft survival in both standard criteria donors and expanded criteria donors.Transplant Proc. 2009; 41: 133-134Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar The occurrence of DGF may significantly complicate the immediate post-transplant management by increasing morbidity and mortality,8.Yarlagadda S.G. Coca S.G. Formica Jr, R.N. et al.Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis.Nephrol Dial Transplant. 2009; 24: 1039-1047Crossref PubMed Scopus (538) Google Scholar, 9.Tapiawala S.N. Tinckam K.J. Cardella C.J. et al.Delayed graft function and the risk for death with a functioning graft.J Am Soc Nephrol. 2010; 21: 153-161Crossref PubMed Scopus (143) Google Scholar prolonging patient hospitalization,10.Almond P.S. Matas A.J. Canafax D.M. Fixed-rate reimbursement fails to cover costs for patients with delayed graft function.Pharmacotherapy. 1991; 11: 126S-129SPubMed Google Scholar and inflating health care costs.10.Almond P.S. Matas A.J. Canafax D.M. Fixed-rate reimbursement fails to cover costs for patients with delayed graft function.Pharmacotherapy. 1991; 11: 126S-129SPubMed Google Scholar, 11.Almond P.S. Troppmann C. Escobar F. et al.Economic impact of delayed graft function.Transplant Proc. 1991; 23: 1304PubMed Google Scholar, 12.Rosenthal J.T. Danovitch G.M. Wilkinson A. et al.The high cost of delayed graft function in cadaveric renal transplantation.Transplantation. 1991; 51: 1115-1118Crossref PubMed Scopus (138) Google Scholar Overweight (body mass index (BMI) 25- 30 kg/m2) at the time of kidney transplantation are common among North American dialysis patients.13.Friedman A.N. Miskulin D.C. Rosenberg I.H. et al.Demographics and trends in overweight and obesity in patients at time of kidney transplantation.Am J Kidney Dis. 2003; 41: 480-487Abstract Full Text PDF PubMed Scopus (203) Google Scholar Pretransplant obesity may have differential effects on short-versus long-term post-transplant outcomes. Some studies report poorer long-term post-kidney transplant outcomes in obese dialysis patients14.Holley J.L. Shapiro R. Lopatin W.B. et al.Obesity as a risk factor following cadaveric renal transplantation.Transplantation. 1990; 49: 387-389Crossref PubMed Scopus (138) Google Scholar, 15.Pirsch J.D. Armbrust M.J. Knechtle S.J. et al.Obesity as a risk factor following renal transplantation.Transplantation. 1995; 59: 631-633Crossref PubMed Scopus (131) Google Scholar, 16.Pischon T. Sharma A.M. Obesity as a risk factor in renal transplant patients.Nephrol Dial Transplant. 2001; 16: 14-17Crossref PubMed Scopus (75) Google Scholar, 17.Ghahramani N. Reeves W.B. Hollenbeak C. Association between increased body mass index, calcineurin inhibitor use, and renal graft survival.Exp Clin Transplant. 2008; 6: 199-202PubMed Google Scholar mainly due to cardiovascular complications,18.Lentine K.L. Rocca-Rey L.A. Bacchi G. et al.Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review.Transplantation. 2008; 86: 303-312Crossref PubMed Scopus (64) Google Scholar whereas other studies have found no association between pretransplant BMI and long-term post-transplant outcomes,19.Howard R.J. Thai V.B. Patton P.R. et al.Obesity does not portend a bad outcome for kidney transplant recipients.Transplantation. 2002; 73: 53-55Crossref PubMed Scopus (110) Google Scholar, 20.Schold J.D. Srinivas T.R. Guerra G. et al.A ‘weight-listing’ paradox for candidates of renal transplantation?.Am J Transplant. 2007; 7: 550-559Crossref PubMed Scopus (81) Google Scholar, 21.Marcen R. Fernandez A. Pascual J. et al.High body mass index and posttransplant weight gain are not risk factors for kidney graft and patient outcome.Transplant Proc. 2007; 39: 2205-2207Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 22.Johnson D.W. Isbel N.M. Brown A.M. et al.The effect of obesity on renal transplant outcomes.Transplantation. 2002; 74: 675-681Crossref PubMed Scopus (207) Google Scholar including our recent study in10,090 kidney transplant recipients.23.Streja E. Molnar M.Z. Kovesdy C.P. et al.Associations of pre-transplant weight and muscle mass with mortality in renal transplant recipients.Clin J Am Soc Nephrol. 2011; (e-pub ahead of print 17 March 2011)PubMed Google Scholar In contrast, pretransplant obesity is usually associated with such untoward short-term complications, such as surgical wound infections or dehiscence.24.Lynch R.J. Ranney D.N. Shijie C. et al.Obesity, surgical site infection, and outcome following renal transplantation.Ann Surg. 2009; 250: 1014-1020Crossref PubMed Scopus (181) Google Scholar More recent studies report that obese renal transplant recipients have higher risk of developing diabetes mellitus or diverse postoperative complications.19.Howard R.J. Thai V.B. Patton P.R. et al.Obesity does not portend a bad outcome for kidney transplant recipients.Transplantation. 2002; 73: 53-55Crossref PubMed Scopus (110) Google Scholar, 22.Johnson D.W. Isbel N.M. Brown A.M. et al.The effect of obesity on renal transplant outcomes.Transplantation. 2002; 74: 675-681Crossref PubMed Scopus (207) Google Scholar, 24.Lynch R.J. Ranney D.N. Shijie C. et al.Obesity, surgical site infection, and outcome following renal transplantation.Ann Surg. 2009; 250: 1014-1020Crossref PubMed Scopus (181) Google Scholar, 25.Bennett W.M. McEvoy K.M. Henell K.R. et al.Morbid obesity does not preclude successful renal transplantation.Clin Transplant. 2004; 18: 89-93Crossref PubMed Scopus (48) Google Scholar, 26.Massarweh N.N. Clayton J.L. Mangum C.A. et al.High body mass index and short- and long-term renal allograft survival in adults.Transplantation. 2005; 80: 1430-1434Crossref PubMed Scopus (68) Google Scholar However, it is not known whether overweight or obesity has a negative impact on other short-term complications, in particular DGF. To the best of our knowledge, only a small case–control study (n=80) by Espejo et al.27.Espejo B. Torres A. Valentin M. et al.Obesity favors surgical and infectious complications after renal transplantation.Transplant Proc. 2003; 35: 1762-1763Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar showed that obese patients have higher risk of DGF after kidney transplantation, whereas Yamamoto et al.28.Yamamoto S. Hanley E. Hahn A.B. et al.The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys.Clin Transplant. 2002; 16: 252-256Crossref PubMed Scopus (81) Google Scholar (n=28) found no meaningful association between obesity and DGF. Obesity is associated with higher sympathetic activity,29.Gosmanov A.R. Smiley D.D. Robalino G. et al.Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects.Am J Physiol Endocrinol Metab. 2010; 299: E953-E958Crossref PubMed Scopus (36) Google Scholar, 30.Lambert E. Sari C.I. Dawood T. et al.Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults.Hypertension. 2010; 56: 351-358Crossref PubMed Scopus (157) Google Scholar which along with imminent administration of calcineurin inhibitors may lead to renal vasoconstriction and decreased kidney perfusion, resulting in DGF. Moreover, obesity is associated with longer operative time and longer ischemic time,31.Olarte I.G. Hawasli A. Kidney transplant complications and obesity.Am J Surg. 2009; 197: 424-426Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar which is associated with elevated risk of DGF.32.Sharma A.K. Tolani S.L. Rathi G.L. et al.Evaluation of factors causing delayed graft function in live related donor renal transplantation.Saudi J Kidney Dis Transpl. 2010; 21: 242-245PubMed Google Scholar, 33.Jensen H. Ladefoged J. Influence of warm and cold ischemia time on initial function and one-year survival of renal allografts.Clin Nephrol. 1976; 5: 256-259PubMed Google Scholar Given these biologically plausible hypotheses and the foregoing inconsistent data, we sought to examine whether recipients’ high BMI has a bearing on early post-transplant graft function in a large and contemporary, incident cohort of kidney transplant recipients throughout the United States. We hypothesized that higher pretransplant BMI during the months immediately before kidney transplantation is associated with higher prevalence of DGF in post-transplant patient. The original 5-year (July 2001–June 2006) national database of all DaVita dialysis patients included 164,789 adult subjects. This database was linked via unique identifiers to the national Scientific Registry of Transplant Recipients (SRTR) registry that included all transplant waitlisted people and kidney transplant recipients until June 2007 (Figure 1). Out of 37,766 DaVita dialysis patients who were identified in the SRTR database, 17,629 had undergone one or more kidney transplantations during their life time, including 14,508 patients who had undergone their first kidney transplantation between July 2001 and July 2007. After excluding those without electronically recorded data (n=1), peritoneal dialysis patients (n=2092), subjects who lacked data from baseline quarter, or those with outlier values for age (>99 or <16 years; n=579), there were 11,836 hemodialysis patients who met all inclusion and exclusion criteria and who subsequently underwent their first kidney transplantation during the observation period. Table 1 compares the demographic, clinical, transplant-related, and pretransplant laboratory characteristics of the patients with (n=2628) and without (n=9208) DGF. Patients with DGF were 2 years older and more likely to be diabetic or African American or to have Medicare as their primary insurance. Patients with DGF had lower serum albumin and hemoglobin levels and were more likely to receive kidneys from deceased donors with longer cold ischemic time. Additionally, patients with DGF had a higher pretransplant BMI by 1.2 kg/m2 than those without DGF (Table 1).Table 1Demographic, clinical, and laboratory characteristics for 11,836 long-term hemodialysis patients who received kidney transplantsVariableAllWith DGFWithout DGFP-valueN (%)11,836 (100)2628 (22.2)9208 (77.8)NAAge (years)49±1450±1348±14<0.001Gender (% women)383439<0.001Diabetes mellitus (%)262926<0.001Race/ethnicity (%) Whites463948<0.001 African Americans273525<0.001 Hispanics1414140.85 Asians4340.01Dialysis vintage time (%) <6 months12614<0.001 6–24 months281931<0.001 2–5 years364135 5 years243421<0.001Primary insurance (%) Medicare525950<0.001 Medicaid3330.47 Private insurance1614170.003 Other201422<0.001Marital status (%) Married4746480.26 Divorced6660.65 Single2728270.17 Widowed3330.98BMI (kg/m2)26.8±6.028.0±6.726.4±5.7<0.001Kt/V (dialysis dose)1.61±0.351.60±0.331.62±0.360.055nPCR (g/kg/day)1.05±0.251.06±0.251.05±0.260.01Serum albumin (g/dl)4.02±0.374.00±0.374.03±0.38<0.001 Creatinine (mg/dl)10.6±3.211.1±3.110.5±3.2<0.001 Bicarbonate (mg/dl)21.9±3.422.2±3.321.8±3.4<0.001 TIBC (mg/dl)212±40208±39213±41<0.001 Ferritin (ng/ml)aMedian (IQR).469 (249–731)534 (299–786)448 (236–717)<0.001 Phosphorus (mg/dl)5.95±1.545.97±1.575.94±1.530.41 Calcium (mg/dl)9.43±0.749.42±0.779.44±0.730.23Blood hemoglobin (g/dl)12.3±1.212.2±1.312.3±1.20.001 WBC (× 103/l)6.8±2.06.9±2.16.8±2.10.24 Lymphocyte (% total of WBC)23±823±823±80.22Pretransplant transfusion (%)313630<0.001Number of HLA mismatches4 (3–5)4 (2–5)4 (3–5)<0.001PRA (%)aMedian (IQR).0 (0–3)0 (0–4)0 (0–3)0.21Cold ischemia time (hours)aMedian (IQR).14 (4–22)19 (12–25)12 (2–20)<0.001EDC kidney (%)192317<0.001Donor type (% of living)321038<0.001Donor age (years)39±1542±1538±15<0.001Abbreviations: BMI, body mass index; DGF, delayed graft function; EDC, extended donor criteria; HLA, human leukocyte antigen; IQR, interquartile range; NA, not available; nPNA, normalized protein nitrogen appearance; PRA, panel reactive antibody (last value before transplant); TIBC, total iron-binding capacity; WBC, white blood cell.Data are from the last or second-to-last calendar quarter before transplantation. Values are in percentage or mean±s.d. or median (IQR), as appropriate.a Median (IQR). Open table in a new tab Abbreviations: BMI, body mass index; DGF, delayed graft function; EDC, extended donor criteria; HLA, human leukocyte antigen; IQR, interquartile range; NA, not available; nPNA, normalized protein nitrogen appearance; PRA, panel reactive antibody (last value before transplant); TIBC, total iron-binding capacity; WBC, white blood cell. Data are from the last or second-to-last calendar quarter before transplantation. Values are in percentage or mean±s.d. or median (IQR), as appropriate. Table 2 shows the results of multivariate logistic regression analyses. Pretransplant BMI was an important predictor of DGF in univariate analysis. One s.d. (s.d.=6.0 kg/m2) increase of pretransplant BMI was associated with 30% higher risk of DGF (odds ratio (OR)=1.30; 95% confidence interval (CI): 1.24–1.36). The association between pretransplant BMI and the risk of DGF in the entire cohort are shown in Figure 2 and Supplementary Figure S1 in the Appendix online. After adjusting for case mix and malnutrition–inflammation complex syndrome variables, pretransplant BMI remained an independent and significant predictor of DGF (Table 2). This association remained significant after adjusting for transplant-related variables: 1 s.d. increase of pretransplant BMI was associated with a 35% higher risk of DGF (OR=1.35; 95% CI: 1.27–1.45). Compared with patients with pretransplant with BMI in high normal range (22–24.99 kg/m2), the patient groups with overweight (25–29.99 kg/m2), mild obesity (30–34.99 kg/m2), and moderate-to-severe obesity (≥35 kg/m2) had 30, 42, and 118%, respectively, higher risk of DGF in the fully adjusted model (P<0.05; Figure 2). Patients with pretransplant BMI higher than 35 kg/m2 had 87% higher risks of DGF than individuals with pretransplant BMI lower than 35 kg/m2 (OR=1.87; 95% CI: 1.52–2.30). Qualitative similar results were found when different cutoff points for BMI were used (Table 2). The association of BMI with DGF was monotonously incremental when BMI was modeled as a continuous variable and using fractional polynomials and cubic splines (Supplementary Figure S1 online). These associations persist in sensitivity analyses including after inclusion of peritoneal dialysis patients (Supplementary Figure S2 online).Table 2Multivariate logistic regression models showing pretransplant weight and BMI and their ORs and 95% CI for delayed graft functionPretransplant weightUnadjustedCase mix adjustedCase mix and MICS adjustedCase mix, MICS, and transplant data adjustedOR (95% CI)P-valueOR (95% CI)P-valueOR (95% CI)P-valueOR (95% CI)P-valueWeight (kg; +1 s.d.)1.29 (1.24–1.35)<0.0011.32 (1.25–1.39)<0.0011.33 (1.25–1.41)<0.0011.34 (1.26–1.44)<0.001BMI (kg/m2; +1 s.d.)1.30 (1.24–1.36)<0.0011.29 (1.23–1.36)<0.0011.33 (1.26–1.41)<0.0011.35 (1.27–1.44) 25 (kg/m2) vs BMI≤25 (kg/m2) (ref.)1.48 (1.44–1.75)<0.0011.53 (1.38–1.69)<0.0011.53 (1.37–1.72)<0.0011.57 (1.39–1.79) 30 (kg/m2) vs BMI≤30 (kg/m2) (ref.)1.54 (1.39–1.71)<0.0011.51 (1.35–1.68)<0.0011.50 (1.33–1.69)<0.0011.48 (1.30–1.70) 35 (kg/m2) vs BMI≤35 (kg/m2) (ref.)1.78 (1.53–2.08)<0.0011.82 (1.55–2.13)<0.0011.84 (1.53–2.21)<0.0011.87 (1.52–2.30) 40 (kg/m2) vs BMI≤40 (kg/m2) (ref.)2.25 (1.72–2.96)<0.0012.34 (1.77–3.10)<0.0012.51 (1.80–3.50)<0.0012.78 (1.88–4.12) 1, indicating a higher risk. Most interaction tests did not exhibit small P-values, indicating lack of major effect modification by the examined characteristics, except for diabetes and extended donor criteria. The association between pretransplant BMI and DGF was stronger in non-diabetic patients and in recipients of an extended donor criteria kidney (Supplementary Table S1 online). Of note, in deceased donor subgroup, each s.d. increase of BMI was associated with 36% risk of DGF (OR (95% CI): 1.36 (1.26–1.46)). In living donor subgroup, each s.d. increase of BMI was associated with 33% (OR (95% CI): 1.33 (1.14–1.56)) risk of DGF. The interaction term was not significant (P=0.88; Supplementary Table S1 online). Download .doc (.06 MB) Help with doc files Supplementary Table 1 In 11,836 kidney transplant recipients with comprehensive pre- and post-transplant data, higher pretransplant BMI during the last calendar quarter of hemodialysis treatment was associated with higher risk of DGF during the first post-transplant week. Compared with patients with pretransplant BMI between 22 and 24.99 kg/m2, the overweight and obese patients with higher pretransplant BMI (25–29.99 kg/m2, 30–34.99 kg/m2, and ≥35 kg/m2) had incrementally higher risk, that is, 30, 42, and 118% higher risk of DGF, whereas lower BMI <22 kg/m2 tended to show ~25% lower DGF risk. The associations between pretransplant BMI and DGF were rather consistent across diverse demographic, clinical, and laboratory subgroups. These finding may have important implications for pretransplant management of waitlisted patients. DGF is a common short-term post-transplant complication and occurs in 5–50% of all kidney transplant recipients. It is especially more frequent with deceased donor kidneys.3.Ojo A.O. Wolfe R.A. Held P.J. et al.Delayed graft function: risk factors and implications for renal allograft survival.Transplantation. 1997; 63: 968-974Crossref PubMed Scopus (839) Google Scholar, 4.Koning O.H. van Bockel J.H. van der Woude F.J. et al.Risk factors for delayed graft function in University of Wisconsin solution preserved kidneys from multiorgan donors. European Multicenter Study Group on Organ Preservation.Transplant Proc. 1995; 27: 752-753PubMed Google Scholar, 5.Sellers M.T. Gallichio M.H. Hudson S.L. et al.Improved outcomes in cadaveric renal allografts with pulsatile preservation.Clin Transplant. 2000; 14: 543-549Crossref PubMed Scopus (61) Google Scholar, 6.Gjertson D.W. Impact of delayed graft function and acute rejection on graft survival.Transplant Proc. 2002; 34: 2432Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar The well-known deleterious effects of DGF in the immediate post-transplant period are multiple and include complications of the immediate post-transplant patient care in the hospital. However, there may be even long-term impact of DGF. Most,34.Gentil M.A. Alcaide M.P. Algarra G.R. et al.Impact of delayed graft function on cadaveric kidney transplant outcome.Transplant Proc. 2003; 35: 689-691Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 35.Arias M. Impact of the delayed graft function in hypersensitized kidney transplant patients.Transplant Proc. 2003; 35: 1655-1657Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar but not all,36.Boom H. Mallat M.J. de Fijter J.W. et al.Delayed graft function influences renal function, but not survival.Kidney Int. 2000; 58: 859-866Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar, 37.Marcen R. Orofino L. Pascual J. et al.Delayed graft function does not reduce the survival of renal transplant allografts.Transplantation. 1998; 66: 461-466Crossref PubMed Scopus (87) Google Scholar studies report an association between DGF and reduced long-term graft survival rate. A systematic review reported that DGF is associated with a 41% increased risk of graft loss,8.Yarlagadda S.G. Coca S.G. Formica Jr, R.N. et al.Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis.Nephrol Dial Transplant. 2009; 24: 1039-1047Crossref PubMed Scopus (538) Google Scholar 38% increased risk of acute rejection in the first year, and a higher serum creatinine concentration at 3.5 years of follow-up.8.Yarlagadda S.G. Coca S.G. Formica Jr, R.N. et al.Association between delayed graft function and allograft and patient survival: a systematic review and meta-analysis.Nephrol Dial Transplant. 2009; 24: 1039-1047Crossref PubMed Scopus (538) Google Scholar Overweight and obesity are highly prevalent at the time of kidney transplantation.13.Friedman A.N. Miskulin D.C. Rosenberg I.H. et al.Demographics and trends in overweight and obesity in patients at time of kidney transplantation.Am J Kidney Dis. 2003; 41: 480-487Abstract Full Text PDF PubMed Scopus (203) Google Scholar Previous reports have described conflicting associations between BMI and various outcomes in kidney transplant recipients. Early studies showed higher risk of postoperative complications31.Olarte I.G. Hawasli A. Kidney transplant complications and obesity.Am J Surg. 2009; 197: 424-426Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar and early surgical wound infections24.Lynch R.J. Ranney D.N. Shijie C. et al.Obesity, surgical site infection, and outcome following renal transplantation.Ann Surg. 2009; 250: 1014-1020Crossref PubMed Scopus (181) Google Scholar in obese patients. Lentine et al.18.Lentine K.L. Rocca-Rey L.A. Bacchi G. et al.Obesity and cardiac risk after kidney transplantation: experience at one center and comprehensive literature review.Transplantation. 2008; 86: 303-312Crossref PubMed Scopus (64) Google Scholar reported higher incidence of cardiovascular event, including heart failure and atrial fibrillation, and early postoperative complications in obese versus non-obese patients. Several other studies, however, did not find any association between pretransplant BMI and mortality.19.Howard R.J. Thai V.B. Patton P.R. et al.Obesity does not portend a bad outcome for kidney transplant recipients.Transplantation. 2002; 73: 53-55Crossref PubMed Scopus (110) Google Scholar, 21.Marcen R. Fernandez A. Pascual J. et al.High body mass index and posttransplant weight gain are not risk factors for kidney graft and patient outcome.Transplant Proc. 2007; 39: 2205-2207Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar, 22.Johnson D.W. Isbel N.M. Brown A.M. et al.The effect of obesity on renal transplant outcomes.Transplantation. 2002; 74: 675-681Crossref PubMed Scopus (207) Google Scholar Chang et al.38.Chang S.H. Coates P.T. McDonald S.P. Effects of body mass index at transplant on outcomes of kidney transplantation.Transplantation. 2007; 84: 981-987Crossref PubMed Scopus (163) Google Scholar reported that obesity per se was not associated with poorer kidney transplant outcomes, although it was associated with factors that led to poorer graft and patient survival. Indeed, patients with a BMI ≥30 kg/m2 receiving single pediatric kidneys had better death-censored graft survival rates when compared with non-obese patients.39.Balamuthusamy S. Paramesh A. Zhang R. et al.The effects of body mass index on graft survival in adult recipients transplanted with single pediatric kidneys.Am J Nephrol. 2009; 29: 94-101Crossref PubMed Scopus (5) Google Scholar Zaydfudim et al.40.Zaydfudim V. Feurer I.D. Moore D.R. et al.Pre-transplant overweight and obesity do not affect physical quality of life after kidney transplantation.J Am Coll Surg. 2010; 210: 336-344Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar reported that pretransplant overweight and obese status did not affect physical quality of life after kidney transplantation. In our study, the association between the pretransplant BMI and the risk of DGF was rather linear, incremental, consistent across virtually subgroups, and robust, even after adjusting for several important confounders. Only few studies examined the association between BMI and DGF, and found conflicting or equivocal results. A small case–control study (n=80) showed the obese patients have higher risk of DGF after kidney transplantation,27.Espejo B. Torres A. Valentin M. et al.Obesity favors surgical and infectious complications after renal transplantation.Transplant Proc. 2003; 35: 1762-1763Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar whereas Yamamoto et al.28.Yamamoto S. Hanley E. Hahn A.B. et al.The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys.Clin Transplant. 2002; 16: 252-256Crossref PubMed Scopus (81) Google Scholar(n=28) found no association between obesity and DGF. These studies were likely underpowered and used inconsistent definitions of DGF. Several potential mechanisms may contribute to the observed associations. A biologically plausible explanation is that obesity is associated with longer operative time of longer and warm ischemic time,31.Olarte I.G. Hawasli A. Kidney transplant complications and obesity.Am J Surg. 2009; 197: 424-426Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar which are per se risk factors of DGF.32.Sharma A.K. Tolani S.L. Rathi G.L. et al.Evaluation of factors causing delayed graft function in live related donor renal transplantation.Saudi J Kidney Dis Transpl. 2010; 21: 242-245PubMed Google Scholar, 33.Jensen H. Ladefoged J. Influence of warm and cold ischemia time on initial function and one-year survival of renal allografts.Clin Nephrol. 1976; 5: 256-259PubMed Google Scholar Obesity is associated with high sympathetic activity,29.Gosmanov A.R. Smiley D.D. Robalino G. et al.Effects of oral and intravenous fat load on blood pressure, endothelial function, sympathetic activity, and oxidative stress in obese healthy subjects.Am J Physiol Endocrinol Metab. 2010; 299: E953-E958Crossref PubMed Scopus (36) Google Scholar, 30.Lambert E. Sari C.I. Dawood T. et al.Sympathetic nervous system activity is associated with obesity-induced subclinical organ damage in young adults.Hypertension. 2010; 56: 351-358Crossref PubMed Scopus (157) Google Scholar which results in renal vasoconstriction. Moreover, the prompt administration of calcineurin inhibitors after transplantation, probably in higher doses given to overweight or obesity, may aggravate vasoconstriction and further compromise graft perfusion, increasing the risk of DGF. Another potential explanation is the linkage between obesity and increased prothrombotic activity and endothelial dysfunction.41.Darvall K.A. Sam R.C. Silverman S.H. et al.Obesity and thrombosis.Eur J Vasc Endovasc Surg. 2007; 33: 223-233Abstract Full Text Full Text PDF PubMed Scopus (232) Google Scholar Body fat mass, in particular central obesity, is associated with higher levels of thrombin generation.42.Beijers H.J. Ferreira I. Spronk H.M. et al.Body composition as determinant of thrombin generation in plasma: the Hoorn study.Arterioscler Thromb Vasc Biol. 2010; 30: 2639-2647Crossref PubMed Scopus (44) Google Scholar, 43.Ay L. Kopp H.P. Brix J.M. et al.Thrombin generation in morbid obesity: significant reduction after weight loss.J Thromb Haemost. 2010; 8: 759-765Crossref PubMed Scopus (81) Google Scholar Obesity is also a risk factor for venous thromboembolic disease.44.Stein P.D. Beemath A. Olson R.E. Obesity as a risk factor in venous thromboembolism.Am J Med. 2005; 118: 978-980Abstract Full Text Full Text PDF PubMed Scopus (428) Google Scholar Increased prothrombotic activity and endothelial dysfunction may contribute to the risk of graft microthrombosis,45.Casserly L.F. Dember L.M. Thrombosis in end-stage renal disease.Semin Dial. 2003; 16: 245-256Crossref PubMed Scopus (135) Google Scholar which per se may have an important role in DGF.46.McCall S.J. Tuttle-Newhall J.E. Howell D.N. et al.Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies.Transplantation. 2003; 75: 1847-1852Crossref PubMed Scopus (35) Google Scholar There are potential limitations to our study. Like all observational studies, our study too cannot prove causality. Patients who were excluded from analyses were likely different from the included ones, but their proportion was relatively small. In the SRTR data set, more detailed data about immunosuppression therapy such as calcineurin inhibitor dose or blood level or the induction therapy, which may also have an effect on the risk of DGF, do not exist. Additional limitation is the uncertainty about the use of BMI as a measure of obesity. BMI per se may not be an appropriate measure to characterize nutritional status, body composition, obesity, or muscle mass in dialysis patients.47.Postorino M. Marino C. Tripepi G. et al.Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease.J Am Coll Cardiol. 2009; 53: 1265-1272Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar, 48.Noori N. Kopple J.D. Kovesdy C.P. et al.Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 2258-2268Crossref PubMed Scopus (231) Google Scholar, 49.Noori N. Kovesdy C.P. Dukkipati R. et al.Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis.Am J Clin Nutr. 2010; 92: 1060-1070Crossref PubMed Scopus (86) Google Scholar, 50.Locatelli F. Fouque D. Heimburger O. et al.Nutritional status in dialysis patients: a European consensus.Nephrol Dial Transplant. 2002; 17: 563-572Crossref PubMed Scopus (207) Google Scholar, 51.Miller J.E. Kovesdy C.P. Norris K.C. et al.Association of cumulatively low or high serum calcium levels with mortality in long-term hemodialysis patients.Am J Nephrol. 2010; 32: 403-413Crossref PubMed Scopus (68) Google Scholar, 52.Kovesdy C.P. Czira M.E. Rudas A. et al.Body mass index, waist circumference and mortality in kidney transplant recipients.Am J Transplant. 2010; 10: 2644-2651Crossref PubMed Scopus (145) Google Scholar To better characterize nutritional status, additional parameters such as waist circumference would be needed.48.Noori N. Kopple J.D. Kovesdy C.P. et al.Mid-arm muscle circumference and quality of life and survival in maintenance hemodialysis patients.Clin J Am Soc Nephrol. 2010; 5: 2258-2268Crossref PubMed Scopus (231) Google Scholar, 50.Locatelli F. Fouque D. Heimburger O. et al.Nutritional status in dialysis patients: a European consensus.Nephrol Dial Transplant. 2002; 17: 563-572Crossref PubMed Scopus (207) Google Scholar, 51.Miller J.E. Kovesdy C.P. Norris K.C. et al.Association of cumulatively low or high serum calcium levels with mortality in long-term hemodialysis patients.Am J Nephrol. 2010; 32: 403-413Crossref PubMed Scopus (68) Google Scholar, 52.Kovesdy C.P. Czira M.E. Rudas A. et al.Body mass index, waist circumference and mortality in kidney transplant recipients.Am J Transplant. 2010; 10: 2644-2651Crossref PubMed Scopus (145) Google Scholar To the best of our knowledge, our study is the first examining the association between pretransplant BMI and immediate post-transplant DGF in such a large and nationally representative patient population. Other strengths of our study include the high number of patients, the multilevel adjustments including for laboratory data, and the contemporary nature of the cohort (2001–2007). In our large and contemporary national cohort of 11,836 kidney transplant recipients, pretransplant BMI is associated with risk of DGF, even after extensive multivariate adjustment. The association between pretransplant BMI and DGF was consistent in all examined subgroups. Despite data indicating an obesity paradox with greater survival of overweight and obese hemodialysis patients,47.Postorino M. Marino C. Tripepi G. et al.Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease.J Am Coll Cardiol. 2009; 53: 1265-1272Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar, 49.Noori N. Kovesdy C.P. Dukkipati R. et al.Survival predictability of lean and fat mass in men and women undergoing maintenance hemodialysis.Am J Clin Nutr. 2010; 92: 1060-1070Crossref PubMed Scopus (86) Google Scholar, 53.Kopple J.D. Zhu X. Lew N.L. et al.Body weight-for-height relationships predict mortality in maintenance hemodialysis patients.Kidney Int. 1999; 56: 1136-1148Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar, 54.Kalantar-Zadeh K. Streja E. Kovesdy C.P. et al.The obesity paradox and mortality associated with surrogates of body size and muscle mass in patients receiving hemodialysis.Mayo Clin Proc. 2010; 85: 991-1001Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar careful trials of closely supervised weight reduction may be needed to examine whether immediate post-transplant outcomes including risk of DGF can be improved.
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