Burak Sayin

Pulmonary Hypertension in Patients With End-Stage Renal Disease Undergoing Renal Transplantation

INTRODUCTION Pulmonary hypertension (PHT) has been reported to occur in a considerable proportion of patients with end-stage renal disease (ESRD). It is a progressive condition of the pulmonary circulation that poses prognostic importance. In this study, we sought to investigate the prevalence and the predictors of PHT among ESRD patients undergoing renal transplantation. PATIENTS AND METHODS We retrospectively evaluated the records, clinical and demographic data as well as laboratory results of 500 adult patients who underwent renal transplantation at our institution. A comprehensive Doppler echocardiographic examination was performed in all patients as part of the preoperative assessment. Systolic pulmonary artery pressure (SPAP) was calculated using Bernoulli equation; a value of >30 mm Hg was accepted as PHT. RESULTS The mean age of the study population was 31.6 +/- 10.2 years. The mean duration of dialysis was 40 months; 432 patients (86.4%) were on hemodialysis (HD) and 68 (13.6%) on peritoneal dialysis (PD). PHT was detected in 85 (17%) patients with a mean SPAP of 46.7 +/- 8.7 mm Hg (range = 35-75 mm Hg). The mean age, sex, and laboratory variables were similar between patients with versus without PHT (P > .05 for all). The mean duration of dialysis therapy was longer in the PHT group than those subjects with normal SPAP (50.8 vs 38.5 months; P = .008). Concerning the type of dialysis, the ratio of patients having PHT was higher in the HD compared with the PD group (18.8% vs 5.9%; P = .008). The prevalence of chronic obstructive pulmonary artery disease, asthma, smoking, hypertension, and diabetes mellitus did not differ between patients with versus without PHT (P > .05 for all). CONCLUSION The findings of this study revealed that PHT was a common clinical condition among patients with ESRD evaluated for renal transplantation. The time on renal replacement therapy particularly HD as the treatment was associated with greater prevalences. Since it may be of prognostic importance in patients undergoing renal transplantation, a careful preoperative assessment including a comprehensive Doppler echocardiographic examination is needed to identify PHT.

Conversion to Sirolimus for Chronic Allograft Nephropathy and Calcineurin Inhibitor Toxicity and the Adverse Effects of Sirolimus After Conversion

BACKGROUND Chronic allograft nephropathy and calcineurin inhibitor toxicity may cause graft loss. After kidney transplantation, especially among those patients with chronic allograft nephropathy, sirolimus may be a good alternative to calcineurin inhibitors. Unlike calcineurin inhibitors, sirolimus is devoid of significant nephrotoxicity, but approximately 30% to 50% of patients on sirolimus therapy display mild or severe adverse effects. We sought to report our experience with sirolimus conversion among patients with chronic allograft nephropathy as well as the mild versus severe adverse effects that limit the drugs use. MATERIALS AND METHODS We analyzed the outcomes of 88 patients (64 men and 24 women) of overall mean age of 35.9 +/- 9.9 years (range, 21-59 years) who had undergone kidney transplantation. Immunosuppressive therapy had been converted from a calcineurin inhibitor to sirolimus because of biopsy-proven chronic allograft nephropathy, calcineurin inhibitor toxicity, or presence of malignancy. We excluded patients with prior acute rejection episodes. Subjects were divided into two groups with respect to their creatinine levels: Group A < 2 mg/dL and Group B >or= 2 mg/dL. After conversion to sirolimus, possible adverse effects of sirolimus were evaluated at the follow-up inset. Each patient underwent a physical examination, and estimation of serum lipid and electrolyte levels as well as hemoglobin concentration. RESULTS At the time of conversion of the 88 renal transplant patients, their mean duration after grafting was 48 +/- 15 months (range, 4-296). The prior treatment consisted of a calcineurin inhibitor, prednisolone, and mycophenolate mofetil. After conversion, the calcineurin inhibitor was stopped and sirolimus was begun. The 48 Group 2 patients (34 men, 14 women) of overall mean posttransplant time of 22.7 +/- 14.6 months who underwent conversion displayed a mean serum creatinine increase to 3.2 +/- 1.4 mg/dL, including 17 subjects who underwent rejection. The 40 Group 1 patients (30 men, 10 women) with a mean overall posttransplant period of 67.6 +/- 49.9 months showed an fall in serum creatinine level to 1.4 +/- 0.5 mg/dL among only 3 patients. While 5/88 patients showed no increase in proteinuria (5.6%); 83 (94.4%) did experience it. Proteinuria increased from a mean of 192 +/- 316 to 449 +/- 422 mg/d. Only three patients displayed heavy proteinuria (>3 g/d); sirolimus was discontinued for this reason. Proteinuria was well controlled in the other patients with angiotensin-converting enzyme and/or angiotensin II receptor inhibitor agents. After sirolimus conversion, serum cholesterol levels increased from 187 +/- 42 to 214 +/- 52 mg/dL, and serum triglyceride levels increased from 161 +/- 61 to 194 +/- 102 mg/dL. All but four patients responded to statin therapy, with serum lipid levels falling to acceptable levels. Another four patients developed unilateral lower extremity edema with sirolimus discontinued for this reason. One patient displayed generalized arthralgia. CONCLUSION Chronic allograft nephropathy or calcineurin inhibitor toxicity can lead to loss of graft kidney function. Calcineurin inhibitor toxicity can lead to chronic allograft nephropathy. Patients with a low baseline serum creatinine level who undergo sirolimus conversion showed stabilized kidney function. Late conversion of patients with a serum creatinine above 2 mg/dL face a risk of graft failure. Sirolimus displayed a limited incidence of serious adverse effects; mild or moderate adverse effects, such as hyperlipidemia and proteinuria, were easily controlled with countermeasure therapy.

Is there a link between hyperuricemia, morning blood pressure surge, and non-dipping blood pressure pattern in metabolic syndrome patients?

Background: Hypertensive patients usually have a blunted nocturnal decrease, or even increase, in blood pressure during sleep. There is also a tendency for increased occurrence of cardiovascular events between 6 and 12 am due to increased morning blood pressure surge (MBPS). Co-occurrence of metabolic syndrome (MetS) and hypertension is also a common problem. Hyperuricemia might trigger the development of hypertension, chronic renal failure, and insulin resistance. In this study, we aimed to determine whether there is a relationship between hyperuricemia, MetS, nocturnal blood pressure changes, and MBPS. Method: A total of 81 newly diagnosed hypertensive MetS patients were included in this study. Ambulatory blood pressure monitoring of patients was done and patients’ height, weight, and waist and hip circumferences were recorded. Fasting blood glucose (FBG), lipid profile, creatinine, potassium, uric acid, hematocrit levels were studied. Results: Non-dipper (ie, those whose blood pressure did not drop overnight) patients had higher waist–hip ratios (WHR) (P = 0.003), uric acid (P = 0.0001), FBG (P = 0.001), total and low-density lipoprotein cholesterol levels (P = 0.0001). Risk analysis revealed that hyperuricemia was a risk factor for non-dipping pattern (P < 0.0001, odds ratio = 8.1, 95% confidence interval = 1.9–33.7). Patients in the highest quadrant for uric acid levels had higher FBG (P = 0.001), low-density lipoprotein cholesterol (P = 0.017), WHR (P = 0.01), MBPS (P = 0.003), and night diastolic blood pressure compared with lowest quadrant patients (P = 0.013). Uric acid levels were also positively correlated with night ambulatory blood pressure (ABP) (r = 0.268, P =0.05), night diastolic blood pressure (r =0.3, P =0.05), and MBPS (r =0.3, P =0.05). Conclusion: Evaluation of hypertensive patients should also include an assessment of uric acid level and anthropometric measurements such as abdominal obesity. Hyperuricemia seems to be closely related to undesired blood pressure patterns and this may signal to the clinician that an appropriate therapeutic approach is required.

Comparison of preemptive kidney transplant recipients with nonpreemptive kidney recipients in single center: 5 years of follow-up.

Background For suitable patients with end-stage renal disease, kidney transplantation (KT) is the best renal replacement therapy, resulting in lower morbidity and mortality rates and improved quality of life. Preemptive kidney transplantation (PKT) is defined as transplantation performed before initiation of maintenance dialysis and reported to be associated with superior outcomes of graft and patient survival. In our study, we aimed to compare the 5-year outcomes of PKT and nonpreemptive kidney transplantation (NPKT) patients who received KT in our center, to define the differences according to complications, comorbidities, adverse effects, clinical symptoms, periodical laboratory parameters, rejection episodes, graft, and patient survival. Methods One hundred kidney transplantation (37 PKT, 63 NPKT) recipients were included in our study. All patients were evaluated for adverse effects, complications, comorbidities, clinical symptoms, monthly laboratory parameters, acute rejection episodes, graft, and patient survival. Results Acute rejection episodes were found to be significantly correlated with graft loss in both groups (P = 0.02 and P = 0.01, respectively). Hypertension after transplantation was diagnosed by ambulatory blood pressure measurement in 74 of 100 patients. Twenty-five of 37 (67.6%) of Group 1 (PKT) recipients had hypertension while 54 of 63 (85.4%) of Group 2 (NPKT) had hypertension. The incidence of hypertension between two groups was statistically significant (P = 0.03), but this finding was not correlated to graft survival (P = 0.07). Some patients had serious infections, requiring hospitalization, and were treated immediately. Infection rates between the two groups were 10.8% for Group 1 patients and 31.7% for Group 2 patients and were statistically significant (P = 0.02). Infection, requiring hospitalization, was found to be statistically correlated to graft loss in only NPKT patients (P = 0.00). Conclusion While the comparison of PKT and graft and patient survival with NPKT is poorer than we expected, lower morbidity rates of hypertension and infection are similar with recent data. Avoidance of dialysis-associated comorbidities, diminished immune response, and cardiovascular complications are the main benefits of PKT.

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

BACKGROUND Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. METHODS Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. RESULTS The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CONCLUSIONS CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Reliability of bioelectrical impedance analysis in the evaluation of the nutritional status of hemodialysis patients - a comparison with Mini Nutritional Assessment.

INTRODUCTION Protein-energy wasting (PEW) is a strong predictive factor for morbidity and mortality in patients who have end-stage renal disease (ESRD). Mini Nutritional Assessment (MNA) is an important and confirmed tool to evaluate PEW that has been recommended by many guidelines. Bioelectrical impedance analysis (BIA) is a noninvasive technique for assessing body composition. The aim of the present study was to analyze the reliability of BIA in malnutrition diagnosis by comparing it with standard MNA in a group of 100 ESRD patients. METHODS One hundred ESRD patients who were medically stable and under dialysis treatment for at least 6 months were enrolled to the study. Monthly assessed serum creatinine, albumin, C-reactive protein (CRP), and lipid profiles from the last 6 months prior to the study were retrospectively collected. A standard Full-MNA and body composition analyses were applied to all patients. Body compositions were analyzed with the BIA technique using the Body Composition Analyzer (Tanita BC-420 MA; Tanita, Tokyo, Japan). Patients were classified into three groups according to MNA scores as PEW (n = 15, score <17), moderate PEW or risk group (n = 49, score 17-23.5), and well-nourished (n = 36, score ≥ 24) patients. RESULTS Mean duration of maintenance hemodialysis treatment was significantly shorter in the PEW group compared to both of the other groups described (P = .015). Well-nourished and risk groups had lower CRP and higher albumin levels compared to PEW patients; however, these values were statistically similar in these two groups (P = .018, .01, respectively). According to BIA findings, well-nourished patients had the highest fat ratio, fat mass, muscle mass, visceral fat mass, and fat-free mass compared to both moderate the PEW/risk and the PEW groups (P < .05). Risk group patients also had higher muscle mass, visceral fat mass, and fat-free mass values compared to the PEW group (P < .05). A correlation analysis revealed that MNA scores were positively correlated with albumin (P = .005), creatinine (P = .049), fat mass (P = .045), muscle mass (P = .001), visceral fat ratio (P = .007), and BMI (P = .047) and in negative correlation with CRP (r = -0.357, P = .0001) levels. CONCLUSIONS We recommend BIA as a complementary diagnostic tool to evaluate nutritional status of ESRD along with MNA, anthropometric measures, and classical biochemical markers.

Comparison of Tissue Doppler Echocardiography Parameters in Patients With End-Stage Renal Disease and Renal Transplant Recipients

BACKGROUND Tissue Doppler echocardiography has been introduced as a useful tool to assess systolic myocardial function. In this study we sought to compare patients with end-stage renal disease (ESRD), with renal transplantations and control subjects with regard to tissue Doppler parameters. METHODS Thirty recipients with functional grafts of overall mean age 36 +/- 7 years included 24 men. An equal number of patients with ESRD of overall mean age 35 +/- 7 years included 20 men. A third cohort was comprised of 20 age- and gender matched control subjects. Tissue Doppler imaging from the septal and lateral mitral annulus of the left ventricle and free wall of the right ventricle was performed from a 4-chamber view. RESULTS Mean systolic and diastolic blood pressures were similar among the groups during imaging. Peak systolic velocity (S wave) at the septal annulus was similar in control subjects and recipients. S waves were significantly lower among ESRD patients compared with recipients (10.3 +/- 2.1 vs 12.0 +/- 2.5 cm/s, P = .04, respectively). Isovolumic contraction velocity of the septum and the right ventricular wall were significantly lower in ESRD patients than recipients or controls: 10.2 +/- 2.6 vs 12.5 +/- 2.8 vs 11.4 +/- 1.8 cm/s for septal wall (P = .008) and 13.9 +/- 3.6 vs 17.9 +/- 5.1 vs 16.8 +/- 5.8, for right ventricle (P = .01). CONCLUSION Systolic indices of tissue Doppler echocardiography in recipients demonstrated similar values as control subjects and increased values compared with ESRD patients. These results suggested improvement in systolic myocardial function following renal transplantation.

High-Grade Proteinuria as a Cardiovascular Risk Factor in Renal Transplant Recipients

BACKGROUND Proteinuria is a marker of graft damage and is closely associated with a higher risk of morbidity, mortality, and cardiovascular disease in kidney transplant recipients (KTRs). Arterial stiffness is a well-known predictor of vascular calcification and systemic arteriosclerosis. In our study, we aimed to investigate the association between proteinuria and graft/patient survival and to determine whether proteinuria may be a predictor for cardiovascular disease in our KTR population. METHODS Ninety KTRs (31 women; age, 38.7 ± 11 years, with 45.9 ± 9.6 months post-transplantation period) with normal graft functions in the 3 to 5 years of the post-transplantation period were enrolled. All patients were evaluated for their standard clinical (age, sex, and duration of hemodialysis) parameters. High-grade proteinuria was defined as proteinuria >500 mg/day in the 24-hour urine collection. All patients were evaluated by means of pulse-wave velocity (PWV) measurement at the initiation of the study. RESULTS Patients were divided into 2 groups: group 1 (high-grade proteinuria) patients with ≥500 mg/24 hours (n = 30) and group 2 (low-grade proteinuria) patients with <500 mg/24 hours (n = 60). High-grade proteinuria was correlated with higher PWV measurements and lower estimated glomerular filtration levels. Proteinuria appears to precede the elevation of serum creatinine and thus may be a useful marker of renal injury and may also be a contributing factor on deterioration of the graft. CONCLUSIONS High-grade (>500 mg/day) proteinuria in KTRs is strongly associated with poor graft survival and increased risk of cardiovascular events. In our study, we proved the significant difference between high-grade and low-grade proteinuric patients, and we suggest 500 mg/day as the threshold of proteinuria in KTR population.

Early Conversion to mTOR Inhibitors Prevents Kidney Function Better Than Late Conversion

Introduction Mammalian target of rapamycin (mTOR) inhibitors are the major alternative immunosuppressive treatment to prevent the adverse effects of calcineurin inhibitor (CNI) based immunosuppressive regimen in kidney transplant (KT) recipients but the timing of conversion to mTOR inhibitors is still a controversial clinical decision. In our study, we aimed to compare the effects of early and late conversion to mTOR inhibitors in our KT recipient population to contribute the data of timing of mTOR inhibitor initiation in patients who were planned to use CNI-free immunosuppressive regimens. Materials and Methods 108 kidney recipients who were converted to mTOR inhibitor based immunosuppressive regimen from CNI-based immunosuppressive regimen were enrolled to our study according to their conversion time. KT recipients who were converted to mTOR inhibitor regimen in the first 12 months after KT were in the early conversion group (Group 1) and KT recipients who were converted to mTOR inhibitor regimen after the first year following KT were in the late conversion group (Group 2). The demographic, clinical and laboratory values of the patients were recorded and patients in both groups were followed-up for 24 months after conversion. Group 1 and Group 2 were compared according to their basic laboratory values, clinical situation and also graft kidney function. Results 32 patients who were converted to mTOR inhibitor based therapy in the first year after KT (Group 1) were compared to 76 patients who were converted to mTOR inhibitor therapy after the first year (Group 2). After 2 years of follow-up of all patients after conversion; serum creatinine levels and 24 hours proteinuria were significantly lower and creatinine clearance and serum high-density lipoprotein levels were significantly higher in the early conversion group compared to late conversion group. Other laboratory values showed no significant difference between two groups. No graft loss was obtained in the 2 years follow-up. Conclusion CNI-based immunosuppressive regimens after KT are still the first choice in the very early period but long-term results are controversial. Until recently, the major adverse effects of CNIs that result with conversion to mTOR inhibitors are malignancy, chronic allograft nephropathy, viral infections and metabolic disturbances. Current studies showed that, early conversion to mTOR inhibitor-based regimens are clearly associated with preserving short and long graft kidney function in the KT recipients. In our study, we determined the early conversion in the first year after KT showed better results compared to late conversion. We suggest that elective conversion to mTOR inhibitors in patients with stable kidney function rather than salvage conversion in patients with worsening kidney function would help maintaining graft kidney and patient survival.

Shear Wave Elastography Findings of Achilles Tendons in Patients on Chronic Hemodialysis and Patients with renal Transplantation

Introduction Achilles tendon which was comprised of tendinous parts of gastrocnemius and soleus muscles is the strongest and the largest tendon in the human body. Chronic renal disease is related to reduced physical activity, exercise capacity. Spontaneous rupture of achilles tendon have been reported in patients with chronic renal disease and degeneratif changes, recurrent microtraumas, hypoxia, chronic acidosis are predisposing factors. The aim of the study is to assess the degeneration of achilles tendon by shear wave elastography to compare the elastographic findings of Achilles tendons in patients on chronic hemodialysis, patients with renal transplantation and healthy adults. Materials and Methods Twenty-five patients who were on chronic hemodialysis at least 5 years, twenty-five renal transplant patients and twenty-five healthy controls were included in this study. The thickness and shear wave velocity (SWV) of the middle thirds of the achilles tendons were measured bilaterally. Results The mean SWV of right achilles was 3,67 cm/sn left achilles was 3,64 cm/sn in hemodialysis group. The mean SWV of right achilles was 4,29 cm/sn left achilles was 4,25 cm/sn in renal transplant group. The mean SWV of right achilles was 6,68 cm/sn left achilles was 6,59 cm/sn in control group. There was a statistically significant difference between the SWVs of hemodialysis group, renal transplant group and control group (p<0,005). Conclusion The achilles tendons in patients with chronic renal failure were softer than in patients with renal transplantation and control group. Chronic tendinopathy cause softening and weakening of the tendon. In the renal transplant group stiffness of the achilles tendon was increased with respect to hemodialysis group but still softer than the control group which could be explained by the positive clinical effect of renal transplantation. In conclusion shear wave elastography is an objective, easy, noninvasive, method that can asssess tendinopathy.