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ardiovascular Risk Factors in Diabetic Patients Withenal Transplants

.M. Dı́az, Z. Sainz, I. Gich, L.L. Guirado, C. Facundo, E. Chuy, T. Puig, and R. Solà

ABSTRACT

There is a progressive increase in cardiovascular events post–renal transplantation anddiabetes mellitus (DM) is one of the major cardiovascular risk factors. The objective of thisstudy was to analyze the prevalence of cardiovascular risk factors and nonfatal cardiovas-cular events among renal transplant recipients, according to the status of their carbohy-drate metabolism. We studied 214 renal transplant recipients, among whom 18% diabeticand 82% were nondiabetic. The 16% prevalence of cardiovascular events were higheramong the posttransplantation DM (PTDM) group (33%) compared with the othergroups, 19% in pre–renal transplantation DM, 17% in altered baseline glycemia, and 13%in normal patients. Diabetic renal transplant recipients showed a greater prevalence ofpretransplantation ischemic cardiopathy when they were older and had a higher pretrans-plantation body mass index (BMI) a heavier smoking habit, significantly increasedmicroinflammation markers, and a greater need for antihypertensive and hypolipidemictreatment. Renal transplant recipients with altered baseline glycemia show greater BMI

after transplantation, as well as higher Hb1Ac than patients with normoglycemia.

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URING the last few years an increased worldwideprevalence of diabetes mellitus (DM) type 2 has been

ocumented1 accompanied by a higher incidence of cardio-ascular (CV) events compared with nondiabetic patients.2

here is also a progressive increase in CV events post–renalransplantation which is currently the most frequent causef mortality. Diabetes is one major CV risk factor.3 Fur-hermore, an increasing number of diabetics undergo renalransplantation and more patients develop this conditionubsequently posttransplantation DM [PTDM].4 Survival ofretransplantation diabetic (DM) patients is shorter thanhat of nondiabetic (nonDM) patients, basically due toncreased CV mortality.5 For all these reasons, the objectivef this study was to analyze the prevalence of CV riskactors and nonfatal CV events among renal transplantecipients, according to the status of their carbohydrateetabolism.

ATIENTS AND METHODS

e studied 214 patients, including 143 men (67%) and 71 women33%) of mean age of 52 years (SD, 14), who had a functioningenal graft for more than 1 year and mean posttransplantationollow-up of 5 years (range 1–20 years).

Applying the current criteria of the American Diabetes Associ-

tion, the population was divided into 18% DM (8% pretransplan- 0

041-1345/05/$–see front matteroi:10.1016/j.transproceed.2005.08.061

802

ation DM and 10% PTDM) versus 82% nonDM (8% alteredaseline glycemia and 74% normal carbohydrate metabolism).This observational prospective study data base was analyzed for

emography, posttransplantation atherosclerotic CV disease, asell as major risk factor.The results of quantitative variables were expressed as mean

alues with standard deviations and the intervals within parentheses.he results of qualitative variables are given in percentages. Chi-

quare and Student t tests were used for bivariate studies withignificance considered when P � .05.

ESULTS

he overall 16% prevalence of CV events was highermong the PTDM group (33%) compared with the otherroups: 19% for pretransplantation DM, 17% for alteredaseline glycemia, and 13% in normal patients (P � .032).As to the differential demographic factors between DM

nd nonDM, the for user group had a bulkier history of

From the Renal Transplant Unit, Nephrology Department,undació Puigvert (J.M.D., Z.S., L.L.G., C.F., E.C., R.S.), andpidemiology Department, Hospital de la Santa Creu i Sant Pau,niversitat Autónoma Barcelona, Barcelona, Spain (I.G., T.P.).Address reprint requests to J.M. Dı́az, Renal Transplant Unit,ephrology Department, Fundacı́o Puigvert, Cartagena, 340.

8025, Barcelona, Spain. E-mail: jdiaz@fundacio-puigvert.es

© 2005 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 37, 3802–3804 (2005)

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retransplantation ischemic cardiopathy (16% vs 4%; P �012); older age (57.1 vs 50.3 years; P � .006); as well asreater preoperative body weight (72.2 vs 67.4 kg; P � .02),nd body mass index (BMI) (28.3 vs 26.2 kg/m2; P � .008).o significant differences were observed regarding genderr bodyweight and BMI at the time of the study.The differences in major risk factors between the 2 (DM

nd nonDM) populations included DM patients havingmoked more and for a longer time, but no differences inlood pressure (BP) or lipids, although DM patients showedigher triglyceride values and prescriptions of more hyper-ensive agents and statins.

Although homocysteine, fibrinogen, and C-reactive proteinere higher among DM patients, the differences were not

ignificant. Neither were differences regarding renal func-ion and proteinuria (Table 1).

As to the DM subgroup, the pretransplantation DMatients were determined to be nonsmokers (0 vs 36%; P �

05), to have a higher HbA1c (8.5 vs 7.2%; P � .04), and toave a higher pretransplantation BMI (29.9 vs 27 kg/m2;� .03) than the PTDM patients.Among the nonDM subgroup, the altered baseline glycemia

atients had greater current body weight (77.8 vs 71.1 kg; P �032) and BMI (30.1 vs 27.8 kg/m2; P � .04), as well asigher Hb1Ac (5.85 vs 5.55%; P � .032). However, thereere no significant differences regarding the other studiedarameters, including pretransplantation body weight andMI.

ISCUSSION

he prevalence of nonfatal CV events 5 years after trans-lantation in our study was higher among patients withTDM. Kasiske et al6 showed that PTDM is a risk factor forenal failure and death. However, another study4 with a meanollow-up of 8 years showed that the overall mortality rate was

Table 1. CV

n � 214 D

BP (mm Hg) 131.1 (10BP (mm Hg) 74.2 (8.1P (mm Hg) 56.9 (12nti-HTA drugs 1.8 (1.2holesterol (mmol/L) 4.89 (0.8riglycerides (mmol/L) 1.89 (1.7igh-density lipoprotein cholesterol (mmol/L) 1.41 (0.4ow-density lipoprotein cholesterol (mmol/L) 2.61 (0.7tatins (%)mokers (%)ength smoking (y) 32 (14bA1c (%) 7.76 (1.9omocysteine (�mol/L) 17.1 (5.8ibrinogen (g/L) 3.92 (0.9RP (mg/L) 5.79 (7.0lbumin (g/L) 42.02 (3.2reatinine (�mol/L) 134 (46reatinine clearance (mL/min) 60.6 (29

rot. � 0.3 g/d (%) 65

igher among pre-operative DM patients (31%) comparedith the PTDM (22%) and the nonDM (16%) patients. CVeath occurred more frequently among DM patients com-ared with nonDM ones (69% vs 49%). Revanur et al7 alsohowed that recipients survival, diminished both amongreoperative DM and PTDM patients, particularly whenTDM developed in recipients younger than 55 years.Although we did not find differences among all of the

opulations regarding renal function after a 5-year follow-p, another study8 with a mean follow-up of 12 years observedhorter survival among PTDM compared with nonDM ones48% vs 70%). The survival curves clearly split at 6 years.imilar data were reported by Hariharan et al.9 However,nother study10 concluded that the survivals of both pa-ients and grafts were similar among PTDM and nonDMatients.The sole significant difference observed herein was the

ncreased tobacco factor among PTDM patients, whichould help explaining the increased CV events in this group.osio et al4 discovered that PTDM patients display in-

reased values of total cholesterol, triglycerides, and systoliclood pressure (BP) compared with preoperative DM pa-ients. Over the early years after the transplantation thereas an increased pulse pressure among preoperative DMatients compared with PTDM, however, subsequently thiseature tended to disappear. But Miles et al8 noted noignificant differences concerning BP. This disagreementay be due to the recent change in the definition of PTDM.e have found no clear data in the literature analyzing the

ncrease in microinflammation markers among the trans-lanted DM population.Patients with altered baseline glycemia shows a slightly

reater prevalence of CV events than normal patients; wenly noted postoperative increased body weight and BMI,s well as increased HB1Ac as an explanation. In fact, a

k Factors

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5–154) 131.2 (11.7, 100–166) NS90) 76.1 (7.8, 50–100) NS–92) 55.1 (11.5, 28–90) NS6) 1.4 (1.1, 0–4) .0513–6.80) 5.06 (0.80, 2.8–7.70) NS65–11.30) 1.47 (0.69, 0.33–4.10) .01453–2.42) 1.56 (0.45, 0.47–3.50) NS0–4.67) 2.82 (0.75, 1.08–5.06) NS

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6) 23 (12, 4–51) .04628–16.96) 5.58 (3.84–7.82) �.0010) 17.3 (6.8, 0.7–37) NS5–7.26) 3.77 (0.97, 1.09–6.96) NS7–33.4) 5.28 (8.93, 0.2–87) NS.9–49) 43.24 (3.64, 31.3–51.9) NS73) 146 (64, 66–465) NS.7–148.8) 58.2 (23.9, 15.4–140.5) NS

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tudy of the general population11 showed that increased CVathologies among subjects with altered baseline glycemiaompared with those who maintained normal carbohydrateetabolism.Taking into account these results, we believe that partic-

lar attention should be paid to the PTDM group. Indeed,ven above the Task Force’s recommendations,12 BP shoulde reduced to �135/80, cholesterol and triglycerides should beeduced per the National Cholesterol Education Programuidelines, smoking habit should be abandoned, glycemicontrol should be improved, and primary prevention withntiaggregating agents should be evaluated in this group.

In conclusion, diabetic renal transplant recipients show aigh prevalence of CV events following transplantation; thenes who are at greater risk are those who develop diabetesfter receiving the transplant. Diabetic renal transplantecipients show a greater prevalence of pretransplantationschemic cardiopathy when they are older, a higher BMI, aeavier smoking habit, significantly increased microinflam-ation markers, and a greater need for antihypertensive

nd hypolipidemic treatment. Renal transplant recipientsith altered baseline glycemia show greater BMI after

ransplantation as well as higher Hb1Ac than patients withormoglycemia.

EFERENCES

1. Amos AF, McCarty DJ, Zimmet P, et al: The rising burden of

iabetes and its complications. Projections of the year 2010. Diabeted 14:S7, 1997

if

2. Haffner SM, Lehto S, Ronnemaa T, et al: Mortality fromoronary heart disease in subjects with type 2 diabetes and inondiabetic subjects with and without prior myocardial infarction.

Engl J Med. 339:229, 19983. Kasiske BL: Risk factors for accelerated atherosclerosis in

enal transplant recipients. Am J Med 84:985, 19884. Cosio FG, Pesavento TE, Kim S, et al: Patient survival after

enal transplantation: impact of post-transplant diabetes. Kidneynt 62:1440, 2002

5. Arend S, Mallat M, Westendorp R, et al: Patient survival afterenal transplantation: more than 25 years follow-up. Nephrol Dialransplant 12:1672, 19976. Kasiske BL, Snyder JJ, Gilbertson D, et al: Diabetes mellitus

fter kidney transplantation in the United States. Am J Transplant:178, 20037. Revanur VK, Jardine AG, Kingsmore DB, et al: Influence of

iabetes mellitus on patient and graft survival in recipients ofidney transplantation. Clin Transplant 15:89, 20018. Miles AMV, Sumrani NB, Horowitz R, et al: Diabetes after

enal transplantation. As deleterious as non-transplant-associatediabetes? Transplantation 65:380, 19989. Hariharan S, McBride MA, Cherikk WS: Post-transplant

enal function in the first year predicts long-term kidney transplanturvival. Kidney Int. 62:311, 2002

10. Boucek P, Saudel F, Pokoma E, et al: Kidney transplantationn type 2 diabetic patients: a comparison with matched non-diabeticubjets. Nephrol Dial Transplant 17:1678, 2002

11. Bjomholt JV, Erikssen G, Aaser E, et al: Fasting bloodlucose: an underestimated risk factor for cardiovascular death.esults from a 22-year follow-up of healthy non-diabetic men.iabetes Care 22:45, 199912. Gaston RS, Basadonna G, Cosio FG, et al: Transplantation

n the diabetic patient with advanced chronic kidney disease: a taskorce report. Am J Kidney Dis 44:529, 2004