A. Akgul

Early Assessment of Renal Resistance Index and Long-Term Renal Function in Renal Transplant Recipients

Background. The effect of the intrarenal arterial resistance index (RI) on long-term renal functions is not well known. We examined the predictive value of intrarenal RI on long-term allograft outcomes. Methods. We retrospectively investigated 121 stable renal transplant recipients, followed for a mean of 63.21 ± 19.9 months after renal transplant. Patients with complications during the first six months after transplant were not included. Color Doppler ultrasonography was done to calculate the intrarenal RI within the first four weeks after transplant. Results. Older recipient age, high pulse pressure, active smoking, and proteinuria were associated with a higher intrarenal RI. Multivariate analyses revealed that renal RI and donor age were independent predictors of allograft outcome. Kaplan-Meier estimates of cumulative graft survival were significantly worse in patients who had an RI of 0.7 or more than they were in patients who had an RI of less than 0.7 (p = .005). Development of chronic allograft nephropathy (CAN) was significantly higher in patients who had an RI of 0.7 or more (p = .02). Conclusions. Renal RI determined within the first month after renal transplant predicts long-term allograft function and development of CAN in renal transplant recipients.

Metabolic Syndrome Is Related to Long-Term Graft Function in Renal Transplant Recipients

The metabolic syndrome (MS) is a known cardiovascular risk factor in the general population and a common problem among renal transplant recipients. This study investigated whether MS after renal transplantation affected long-term graft function. We included 112 transplants at our center between 2000 and 2002. We excluded patients with the presence of pretransplant diabetes or nonstable renal function at 1 year after transplantation. We evaluated parameters such as demographic features, medications, smoking history, body mass index, daily proteinuria, blood pressure, number of HLA mismatches, number of acute rejection episodes, delayed graft function, and laboratory parameters. Patients were followed for a mean of 69.86 +/- 21.94 months. The prevalence of MS was determined using the National Cholesterol Education Program-Adult Treatment Panel III criteria. At 1 year after transplant, 28.6% of subjects had MS, whereas only 10.7% had MS before transplantation. Among 27.7% of patients graft failure had occurred during the follow-up; MS was more frequent among these individuals compared with those displaying stable renal function (51.6% vs 19.8%; P = .002). Older donor age, delayed graft function, acute rejection episodes, smoking history, MS, proteinuria, serum creatinine level, and C-reactive protein were associated with graft failure. Upon multivariate Cox regression analysis, patients with MS at 1 year after transplantation showed an increased risk for graft failure (relative risk, 0.22; 95% confidence interval, 0.06-0.75; P = .016). Older donor age and proteinuria level were other independent risk factors for graft failure. The MS was a prominent risk factor for graft failure. Because MS is a cluster of modifiable risk factors, early identification of patients at risk and intervention in due time may improve graft survival.

Factors related to silent myocardial damage in hemodialysis patients.

Background. Both traditional and non-traditional risk factors play a role for the development of cardiovascular disease in hemodialysis patients. However, a specific relationship between these risk factors and silent myocardial damage is unknown. Methods. Demographic, anthropometric, clinical, and laboratory data were collected. Silent myocardial damage was defined by elevated cardiac troponin I values above cutoff values. Results. In total, 113 hemodialysis patients were included. Cardiac troponin I concentrations were below cutoff value (<2.3 ng/mL) in 103 (91.2%) patients (Group 1), whereas 10 (8.8%) patients had elevated concentrations (Group 2). Group 1 patients had higher levels of hemoglobin (p = 0.002) and high-density lipoprotein cholesterol (p = 0.002) and lower C-reactive protein (p = 0.003) and tumor necrosis factor-α (p = 0.005) levels, as well as less incidence of left ventricular hypertrophy (p = 0.045), when compared to Group 2 patients. Diabetes mellitus (Beta = +0.160, p = 0.021), left ventricular hypertrophy (Beta = +0.247, p < 0.0001), uncontrolled blood pressure (Beta = +0.170, p = 0.016), normalized protein equivalent of total nitrogen appearance (Beta = −0.230, p = 0.001), hemoglobin (Beta = −0.302, p < 0.0001), and tumor necrosis factor-α (Beta = +0.506, p < 0.0001) were found to be independently associated with cardiac troponin I levels in multiple linear regression analysis. Conclusions. Both traditional and non-traditional risk factors are related with silent myocardial damage, which is considered to an antecedent of major cardiovascular events. Hemodialysis patients, even when asymptomatic, must be closely followed up for the presence of these risk factors.

Posttransplant proteinuria is associated with higher risk of cardiovascular disease and graft failure in renal transplant patients.

In this study, we sought to determine whether proteinuria after renal transplantation was associated with cardiovascular disease (CVD), patient survival, and long-term allograft survival. One hundred twenty-six patients included 102 males and 24 females of mean age 30.7 +/- 8.9 years. Their mean follow-up was 63.21 +/- 19.9 months. All patients were evaluated for CVD, namely, ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. Proteinuria was defined as urinary protein >or=500 mg/d which persisted for >6 months after transplantation. We retrospectively examined pre- and posttransplant data, including sex, age at transplantation, smoking, pretransplant dialysis duration, donor status, number of acute rejection episodes, body mass index, systolic and diastolic blood pressure levels, lipid profile and other biochemical parameters, immunosuppressive regimens, as well as pulse steroid dose. Proteinuria was significantly associated with CVD (P = .001; RR = 6.43; confidence interval [CI] 2.15-19.22). Patients with proteinuria showed significantly lower graft survival rates than those without proteinuria (58.62% vs 80.41%; P = .02). The mean time to appearance of proteinuria was 14.1 +/- 11.4 months (range, 1-36 months). There was no significant association between proteinuria and patient survival. Patients with persistent proteinuria displayed a greater number of acute rejection episodes (1.20 +/- 1.17 vs 0.62 +/- 0.85; P = .004) and higher pulse steroid dosages (4380.0 +/- 3123.4 vs 2800.0 +/- 2766.7; P = .022). In conclusion, persistent proteinuria is a strong risk factor for CVD among renal transplant patients. Therefore, an etiologic search and antiproteinuric strategy should be considered routinely to improve patient and graft outcomes.

Relationship of Renal Resistive Index and Cardiovascular Disease in Renal Transplant Recipients

BACKGROUND Cardiovascular disease is the primary cause of death in renal transplant recipients, and elevated renal allograft resistive index (RI) has been associated with patient survival. OBJECTIVE To evaluate the predictive value of intrarenal RI on atherosclerotic disease. PATIENTS AND METHODS Ninety-seven patients who had undergone renal transplantation between 1999 and 2001 and had stable renal function were included in the study. Patients with renal artery stenosis, urinary tract obstruction, clinical symptoms of acute rejection, or chronic allograft nephropathy were excluded. Clinical and laboratory information was obtained from the medical records and included demographic data, medications used, body mass index, blood pressure, and laboratory values. Intrarenal RI and carotid intima-media thickness (IMT) were determined using Doppler ultrasonography. RESULTS At linear regression analysis, RI was significantly correlated with recipient age, C-reactive protein concentration, systolic blood pressure, pulse pressure, body mass index, smoking, and carotid IMT. At multivariate linear regression analysis, only pulse pressure was an independent predictor of intrarenal RI. CONCLUSION Intrarenal RI is associated with traditional cardiovascular risk factors and carotid IMT. Elevated intrarenal graft RI may be predictive of cardiovascular disease in renal transplant recipients without complications.

Low Total Plasma Homocysteine Level in Relation to Malnutrition, Inflammation, and Outcome in Hemodialysis Patients

OBJECTIVE We examined the association between nutritional status and total plasma homocysteine (tHcy) level, cardiovascular disease (CVD), and mortality in hemodialysis (HD) patients. DESIGN This prospective study consisted of 124 HD patients. A number of baseline parameters were measured, including tHcy level and laboratory markers of nutrition and inflammation. A CVD history and a malnutrition-inflammation score (MIS) were determined in all patients. The follow-up period was 2 years. RESULTS Forty-nine patients (39.8%) had a history of CVD. During follow-up, 11 (8.8%) deaths occurred, and of these 7 deaths were attributable to CVD. A low tHcy level and an increased MIS were associated with CVD and mortality. The rates of CVD and mortality were also higher in the lowest tHcy level tertiles. In addition, tHcy level was positively correlated with albumin and creatinine, and was negatively correlated with C-reactive protein, MIS, and comorbidity. The survival rates in Kaplan-Meier survival analysis tests were significantly lower in patients with the highest MIS (log rank, 22.3; P < .001). Patients with higher tHcy levels had significantly longer survival rates (log rank, 9.7; P = .007). CONCLUSIONS Because of the strong association of tHcy levels with malnutrition- inflammation, the presence of these factors should be considered when tHcy is evaluated as a risk factor of outcomes in HD patients.

Effect of protein‐energy malnutrition on erythropoietin requirement in maintenance hemodialysis patients

Possible interactions between inflammatory and nutritional markers and their impact on recombinant human erythropoietin (rHuEPO) hyporesponsiveness are not well understood. We investigated the role of nutritional status in rHuEPO requirement in maintenance hemodialysis (MHD) patients without evidence of inflammation. This cross‐sectional study included 88 MHD patients. The associations between required rHuEPO dose and malnutrition‐inflammation score (MIS) and several laboratory values known to be related to nutrition and/or inflammation were analyzed. Anthropometric measures including body mass index, triceps skinfold thickness, and midarm circumferences were also measured. Twenty‐three patients with serum C‐reactive protein levels >10 mg/L were excluded from the analysis. The remaining 65 patients (male/female, 41/24; age 49.1±11.4 years; dialysis duration 99.7±63.0 months) were studied. These patients had moderate malnutrition and the average MIS was 7.4 (range 3–17). The average weekly dose of administered rHuEPO was 69.1±63.1 U/kg. Malnutrition‐inflammation score had a positive correlation with the serum concentration of tumor necrosis factor‐α, whereas it had a negative correlation with anthropometric measures, total iron‐binding capacity, prealbumin, phosphorus, creatinine, and triglyceride. According to Pearsons correlation analysis, significant relationships of increased MIS with increased required rHuEPO dose and rHuEPO responsiveness index (EPO divided by hematocrit) were observed (p=0.008, r=−0.326; p=0.017, r=−0.306, respectively). Recombinant human erythropoietin dose requirement is correlated with MIS and adverse nutritional status in MHD patients without evidence of inflammation. Further research should focus on reversing the undergoing microinflammation for a better outcome in dialysis patients.