- Email: [email protected]
Chronic Renal Disease in Renal Transplant Patients: Management of Cardiovascular Risk Factors
Chronic Renal Disease in Renal Transplant Patients: Management of Cardiovascular Risk Factors G. Fernández-Fresnedo, C. Gómez-Alamillo, J.C. Ruiz, A.L.M. de Francisco, and M. Arias ABSTRACT Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Despite improvements in short-term patient and graft outcomes, there has been no major improvement in long-term outcomes. The aim of this study was to determine the prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, chronic kidney disease, and obesity, and the impact of their control among 526 stable renal transplant recipients according to the guidelines in the general population. Mean blood pressure was 133 ⫾ 16/81 ⫾ 9 mm Hg. The proportion of patients on antihypertensive therapy was 75%, and on ACE inhibitors or angiotensin II receptor blockers, 26%. The mean cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were 195 ⫾ 41, 115 ⫾ 32, 51 ⫾ 17, and 137 ⫾ 75 mg/dL, respectively. The proportion of patients on statin treatment was 49.7%, and those with body mass indices between 25 and 30, 30 and 35, and ⬎35 kg/m2 were 35%, 15%, and 4%. We observed a high prevalence of chronic kidney disease, hypertension, dyslipidemia, and obesity among renal transplant patients. Suboptimal control was frequent and control of some of these complications was far below targets established for nontransplant patients despite progressive intensification of therapy with functional graft decline. The findings of this study may have an impact on the management of renal transplant recipients. IDNEY TRANSPLANTATION is the treatment of choice for patients with end-stage renal disease. Despite improvements in short-term patient and graft outcomes, there has been no major improvement in long-term success. Cardiovascular disease, infections, and malignancies contribute to reduced patient survival and, therefore, reduce functional allograft life.1 Cardiovascular disease is now the major cause of death in renal transplant recipients, especially after the first year posttransplantation.2 Interventions that seek to improve long-term outcomes in kidney transplant recipients must address disease progression, comorbid conditions, and patient mortality.3 The aim of this study was to determine the prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, chronic kidney disease (CKD), and obesity, and to analyze the level of control of these factors in a stable renal transplant population according to the guidelines for the general population (Kidney Disease Outcomes Quality Initiative [K/DOQI]).
K
MATERIAL AND METHODS This descriptive, cross-sectional study of 526 stable renal transplant recipients who were at least 6 months posttransplantation included a medical record review of demographic data, body mass index,
blood pressure, and medication use (immunosuppressive, antihypertensive, and antiaggregant drugs, erythropoietin use). Laboratory data (only the 3 most recent values were recorded) included: creatinine, estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, hemoglobin, total cholesterol, low-density lipoprotein (LDL), highdensity lipoprotein (HDL), triglycerides, glycemia, glycosylated hemoglobin, and 24-hour urine protein excretion. The data were summarized using proportions or mean values as appropriate.
RESULTS
The mean time after transplantation was 9.56 ⫾ 6.18 years. Thirty-four percent of patients were males, the overall mean age was 53.12 ⫾ 12 years, and 90% of patients had a primary transplant. Sixty percent of patients were on cyclosporine treatment, 38% on tacrolimus treatment, and 3% without calcineurin inhibitors. Table 1 shows the demographic characteristics. From the Nephrology Service, University Hospital Marqués de Valdecilla, Santander, Spain. Address reprint requests to Gema Fernández-Fresnedo, Servicio de Nefrologı´a, Hospital Marqués de Valdecilla, Avda de Valdecilla, 39008, Santander, Spain. E-mail: [email protected]
© 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.02.075
Transplantation Proceedings, 41, 1637–1638 (2009)
1637
1638
FERNÁNDEZ-FRESNEDO, GÓMEZ-ALAMILLO, RUIZ ET AL Table 1. Demographic Characteristics
Recipient age (y) Donor age (y) Time on dialysis (y) Gender (% male) HLA mismatches (A/B/DR) Cold ischemia time (h) Native kidney disease (%) Congenital Glomerulonephritis Vascular Diabetes Unknown Others No. of transplants (%) 1st 2nd and following Serum creatinine at study (mg/dL)
53.12 ⫾ 12 41.36 ⫾ 15.81 4.13 ⫾ 3.57 34 0.98 ⫾ 0.64/1.02 ⫾ 0.71/0.95 ⫾ 0.67 20.61 ⫾ 5.18 13.2 36.2 11.2 4.1 14.2 21.1 90 10 1.7 ⫾ 0.9
Graft Function
CKD was present in 90% of patients and eGFR by the abbreviated MDRD equation yielded a mean value of 54 ⫾ 26 mL/min/1.73 m2; 75% of patients were CKD stages 2 and 3 (31% and 44%). The 24-hour mean protein excretion was 480 ⫾ 1500 mg/d. Upon multivariate analysis, graft function was related to donor age (relative risk [RR] 1.23; 95% confidence interval [CI] 1.1–1.43; P ⬍ .01) and proteinuria (RR 1.02; 95% CI 1.01–1.2; P ⬍ .01). Sixty percent of patients had ⬍150 mg/d; 30%, between 150 mg and 1 g/d; and 10%, ⬎1 g/d of proteinuria. ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) treatment was more frequent among proteinuric patients (P ⬍ .05). Hypertension
The mean blood pressure was 133 ⫾ 16/81 ⫾ 9 mm Hg. The proportion of patients on antihypertensive therapy was 75%, and on ACEI or ARB, 26%. The percentages of patients with blood pressures lower than 140 or 90 mm Hg and lower than 130 or 80 mm Hg were 68%/78% and 50%/38%, respectively. Hypertension and uncontrolled hypertension were prevalent, increasing significantly with CKD stage (P ⬍ .05). Lipid Parameters
The mean cholesterol, LDL, HDL, and triglycerides were 195 ⫾ 41, 115 ⫾ 32, 51 ⫾ 17, and 137 ⫾ 75 mg/dL, respectively. The proportion of patients on statin treatment was 49.7%. The percentages of patients with cholesterol ⬍200 mg/dL, LDL ⬍100 mg/dL, and triglycerides ⬍200 mg/dL were 59%, 29%, and 86%, respectively. Among the patients on statin treatment, the proportions with cholesterol ⬍200 mg/dL and LDL ⬍100 mg/dL were 55% and 49%, respectively. There was no relationship between suboptimal control and CKD stage.
Diabetes Mellitus
Among diabetic patients, the mean glycosylated hemoglobin was 6.8% with 35% showing levels ⬎7%. There was no relationship between suboptimal control and CKD stage. Obesity
The proportions of patients with body mass indices between 25 and 30, 30 and 35, and ⬎35 kg/m2 were 35%, 15%, and 4%, respectively. Anemia
The mean hemoglobin decreased as the CKD stage increased. Anemia (Hb ⬍ 11 g/dL) was present in 5.4%, increasing significantly from stage 1 to 5: namely, 3%, 12%, 19%, 30%, and 50%, respectively (P ⬍ .001). Likewise, the use of erythropoietin increased significantly as the CKD stage increased (P ⬍ .001). Upon multivariate analysis, serum hemoglobin correlated with donor age (RR 1.1; 95% CI 1.01–1.3; P ⬍ .01), gender (RR 1.03; 95% CI 1.01–1.4; P ⬍ .01), and eGFR (RR 1.5; 95% CI 1.3–2; P ⬍ .01). Finally, only 15% of patients were on anti-aggregant treatment. DISCUSSION
The findings of this study may have an impact on the management of renal transplant recipients. We observed a high prevalence of CKD, hypertension, dyslipidemia, uncontrolled diabetes, and obesity among renal transplant patients. Suboptimal control was frequent with multifactorial reasons for failure to achieve management target, in these patients. Epidemiological and interventional studies in the general population have identified several risk factors for cardiovascular disease, including age, hypertension, diabetes, and dyslipidemia.4 These risk factors are also valid in renal transplant patients.5 The risk-modification strategies useful in the general population are likely also to be effective in transplant patients. Besides, the rates of adverse effects are manageable and the therapeutic index of most interventions is favorable. We often do not pay attention to the potential of these factors in renal transplant recipients, mainly because we are too focused on the renal allograft compared with other accompanying comorbid diseases.6 REFERENCES 1. Chapman JR, O’Connell PJ, Nankivell BJ: Chronic renal allograft dysfunction. J Am Soc Nephrol 16:3015, 2005 2. Kasiske BL, Guijarro C, Massy ZA, et al: Cardiovascular disease after renal transplantation. J Am Soc Nephrol 7:158, 1996 3. Karthikeyan V, Karpinski J, Nair RC, et al: The burden of chronic kidney disease in renal transplant recipients. Am J Transplant 4:262, 2003 4. Levey AS, Beto JA, Coronado BE, et al: Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 32:853, 1998 5. Fernández-Fresnedo G, Rodrigo E, Valero R, et al: Traditional cardiovascular risk factors as clinical markers after kidney transplantation. Transplant Rev 20:88, 2006 6. Ojo AO, Hanson JA, Wolfe RA, et al: Long-term survival in renal transplant recipients with graft function. Kidney Int 57:307, 2000
K
MATERIAL AND METHODS This descriptive, cross-sectional study of 526 stable renal transplant recipients who were at least 6 months posttransplantation included a medical record review of demographic data, body mass index,
blood pressure, and medication use (immunosuppressive, antihypertensive, and antiaggregant drugs, erythropoietin use). Laboratory data (only the 3 most recent values were recorded) included: creatinine, estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, hemoglobin, total cholesterol, low-density lipoprotein (LDL), highdensity lipoprotein (HDL), triglycerides, glycemia, glycosylated hemoglobin, and 24-hour urine protein excretion. The data were summarized using proportions or mean values as appropriate.
RESULTS
The mean time after transplantation was 9.56 ⫾ 6.18 years. Thirty-four percent of patients were males, the overall mean age was 53.12 ⫾ 12 years, and 90% of patients had a primary transplant. Sixty percent of patients were on cyclosporine treatment, 38% on tacrolimus treatment, and 3% without calcineurin inhibitors. Table 1 shows the demographic characteristics. From the Nephrology Service, University Hospital Marqués de Valdecilla, Santander, Spain. Address reprint requests to Gema Fernández-Fresnedo, Servicio de Nefrologı´a, Hospital Marqués de Valdecilla, Avda de Valdecilla, 39008, Santander, Spain. E-mail: [email protected]
© 2009 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/09/$–see front matter doi:10.1016/j.transproceed.2009.02.075
Transplantation Proceedings, 41, 1637–1638 (2009)
1637
1638
FERNÁNDEZ-FRESNEDO, GÓMEZ-ALAMILLO, RUIZ ET AL Table 1. Demographic Characteristics
Recipient age (y) Donor age (y) Time on dialysis (y) Gender (% male) HLA mismatches (A/B/DR) Cold ischemia time (h) Native kidney disease (%) Congenital Glomerulonephritis Vascular Diabetes Unknown Others No. of transplants (%) 1st 2nd and following Serum creatinine at study (mg/dL)
53.12 ⫾ 12 41.36 ⫾ 15.81 4.13 ⫾ 3.57 34 0.98 ⫾ 0.64/1.02 ⫾ 0.71/0.95 ⫾ 0.67 20.61 ⫾ 5.18 13.2 36.2 11.2 4.1 14.2 21.1 90 10 1.7 ⫾ 0.9
Graft Function
CKD was present in 90% of patients and eGFR by the abbreviated MDRD equation yielded a mean value of 54 ⫾ 26 mL/min/1.73 m2; 75% of patients were CKD stages 2 and 3 (31% and 44%). The 24-hour mean protein excretion was 480 ⫾ 1500 mg/d. Upon multivariate analysis, graft function was related to donor age (relative risk [RR] 1.23; 95% confidence interval [CI] 1.1–1.43; P ⬍ .01) and proteinuria (RR 1.02; 95% CI 1.01–1.2; P ⬍ .01). Sixty percent of patients had ⬍150 mg/d; 30%, between 150 mg and 1 g/d; and 10%, ⬎1 g/d of proteinuria. ACE inhibitor (ACEI) or angiotensin II receptor blocker (ARB) treatment was more frequent among proteinuric patients (P ⬍ .05). Hypertension
The mean blood pressure was 133 ⫾ 16/81 ⫾ 9 mm Hg. The proportion of patients on antihypertensive therapy was 75%, and on ACEI or ARB, 26%. The percentages of patients with blood pressures lower than 140 or 90 mm Hg and lower than 130 or 80 mm Hg were 68%/78% and 50%/38%, respectively. Hypertension and uncontrolled hypertension were prevalent, increasing significantly with CKD stage (P ⬍ .05). Lipid Parameters
The mean cholesterol, LDL, HDL, and triglycerides were 195 ⫾ 41, 115 ⫾ 32, 51 ⫾ 17, and 137 ⫾ 75 mg/dL, respectively. The proportion of patients on statin treatment was 49.7%. The percentages of patients with cholesterol ⬍200 mg/dL, LDL ⬍100 mg/dL, and triglycerides ⬍200 mg/dL were 59%, 29%, and 86%, respectively. Among the patients on statin treatment, the proportions with cholesterol ⬍200 mg/dL and LDL ⬍100 mg/dL were 55% and 49%, respectively. There was no relationship between suboptimal control and CKD stage.
Diabetes Mellitus
Among diabetic patients, the mean glycosylated hemoglobin was 6.8% with 35% showing levels ⬎7%. There was no relationship between suboptimal control and CKD stage. Obesity
The proportions of patients with body mass indices between 25 and 30, 30 and 35, and ⬎35 kg/m2 were 35%, 15%, and 4%, respectively. Anemia
The mean hemoglobin decreased as the CKD stage increased. Anemia (Hb ⬍ 11 g/dL) was present in 5.4%, increasing significantly from stage 1 to 5: namely, 3%, 12%, 19%, 30%, and 50%, respectively (P ⬍ .001). Likewise, the use of erythropoietin increased significantly as the CKD stage increased (P ⬍ .001). Upon multivariate analysis, serum hemoglobin correlated with donor age (RR 1.1; 95% CI 1.01–1.3; P ⬍ .01), gender (RR 1.03; 95% CI 1.01–1.4; P ⬍ .01), and eGFR (RR 1.5; 95% CI 1.3–2; P ⬍ .01). Finally, only 15% of patients were on anti-aggregant treatment. DISCUSSION
The findings of this study may have an impact on the management of renal transplant recipients. We observed a high prevalence of CKD, hypertension, dyslipidemia, uncontrolled diabetes, and obesity among renal transplant patients. Suboptimal control was frequent with multifactorial reasons for failure to achieve management target, in these patients. Epidemiological and interventional studies in the general population have identified several risk factors for cardiovascular disease, including age, hypertension, diabetes, and dyslipidemia.4 These risk factors are also valid in renal transplant patients.5 The risk-modification strategies useful in the general population are likely also to be effective in transplant patients. Besides, the rates of adverse effects are manageable and the therapeutic index of most interventions is favorable. We often do not pay attention to the potential of these factors in renal transplant recipients, mainly because we are too focused on the renal allograft compared with other accompanying comorbid diseases.6 REFERENCES 1. Chapman JR, O’Connell PJ, Nankivell BJ: Chronic renal allograft dysfunction. J Am Soc Nephrol 16:3015, 2005 2. Kasiske BL, Guijarro C, Massy ZA, et al: Cardiovascular disease after renal transplantation. J Am Soc Nephrol 7:158, 1996 3. Karthikeyan V, Karpinski J, Nair RC, et al: The burden of chronic kidney disease in renal transplant recipients. Am J Transplant 4:262, 2003 4. Levey AS, Beto JA, Coronado BE, et al: Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 32:853, 1998 5. Fernández-Fresnedo G, Rodrigo E, Valero R, et al: Traditional cardiovascular risk factors as clinical markers after kidney transplantation. Transplant Rev 20:88, 2006 6. Ojo AO, Hanson JA, Wolfe RA, et al: Long-term survival in renal transplant recipients with graft function. Kidney Int 57:307, 2000