Cardiac Risk Assessment in Kidney Transplant Candidates: Clinical Usefulness of Different Guidelines.

Although cardiovascular (CV) assessment is recommended to minimize perioperative risk in all potential kidney transplant recipients, the utility and reliability of various assessment methods are not well established. In this study, we investigated the CV evaluations and outcomes of standardized CV assessment protocols (Lisbon and American Society of Transplantation [AST]) in potential kidney transplant recipients. Data were analyzed for 266 end-stage renal disease patients (mean age 45.4 ± 13 years, female-to-male ratio 126:140) accepted for kidney transplantation wait-listing. Patients were classified as low and high cardiac risk according to their first cardiac evaluation. Major cardiovascular events (CVEs) and deaths were recorded. At the end of follow-up (median 639 days), 72 (27.1%) patients underwent kidney transplantation. A total of 49 patients (18.4%) had CVEs and 42 (15.8%) patients died. Being over 45 years of age and having dialysis vintage over 1 year were found to be independent risk factors for CVEs. Forty-eight out of 60 high-risk patients evaluated with noninvasive tests had negative results. Twelve out of these 48 patients had a CVE in due course. Among 10 patients who underwent coronary angiography, 1 had a CVE and 1 died. The sensitivity and specificity of the AST guidelines (area under the curve = 0.647, P = .005, sensitivity 83%, specificity 54%) were higher than Lisbon. In conclusion, the predictive risk factors for CVEs were age over 45 years and dialysis vintage over a year. Our results also suggest that exercise electrocardiography and myocardial perfusion scintigraphy for cardiac evaluation are less sensitive in CVE prediction. We recommend clinicians to use the AST guidelines and to prioritize coronary angiography in pretransplant CV assessment.

Fatigue in systemic lupus erythematosus : Association with disease activity, quality of life and psychosocial factors.

OBJECTIVE: The aim of the study was to determine which disease-related factors and non-disease features can explain the presence of systemic lupus erythematosus (SLE)-related fatigue in Turkish patients. METHODS: This cross-sectional study was carried out with 99 SLE patients and 71 healthy controls. To assess fatigue and health-related quality of life (HRQoL) the participants were asked to complete two questionnaires: the short form-36 health survey (SF-36) and the multidimensional assessment of fatigue (MAF) scale. Anxiety and depression of participants were assessed by the hospital anxiety and depression scale (HADS). RESULTS: A total of 99 patients (female/male 95/4) and 71 controls (female/male 40/31) were studied. The mean age and standard deviation (±SD) of patients and controls were 43.3 ± 12.2 years and 43.2 ± 12.1 years, respectively. The mean (SD) disease duration was 7.8 ± 5.3 years and median SLE disease activity index (SLEDAI) score was 0 (range = 0-16). The level of fatigue was higher in patients compared to controls with mean MAF scores of 24.7 ± 12.2 and 12.8 ± 9.9 (p < 0.001), respectively. The HADS-D and HADS-A scores were also significantly higher in SLE patients (6.6 ± 4.3 vs. 3.6 ± 2.9, p < 0.001 and 7.2 ± 4 vs. 4.9 ± 4, p = 0.007, respectively). There were no significant associations between the MAF and SLEDAI scores (r = 0.05, p = 0.63) but MAF scores positively correlated with age, HADS-A and HADS-D scores and negatively correlated with physical component summary (PCS), mental component summary (MCS) and each domain of SF-36 except role emotional in SLE patients. CONCLUSION: Fatigue is an important factor influencing patient daily life independent from disease activity in our study. The SLE patients with severe fatigue should also be assessed for other possible underlying causes such as anxiety, depression and poor quality of life.

Donor Contraindications to Living Kidney Donation: A Single-Center Experience.

OBJECTIVE: Kidney transplantation is the treatment of choice in end-stage renal disease. In Turkey, the inadequate cadaveric donor supply has resulted in transplantation from living kidney donors (LKD) in 80% of transplant operations. LKD candidates undergo a thorough general medical evaluation and are approved to donate their kidneys only if no contraindication is found. In our study we aimed to investigate the reasons and rate of denial for living kidney donation in our center. METHODS: We included all LKD candidates who applied to our center between June 2012 to June 2014. Demographic data, rate of rejection, and the reasons for denial to organ donation were analyzed retrospectively. RESULTS: Of the 97 LKD candidates included in the study, 60 (62%) were unable to donate their kidneys. Among the reasons for denial were hypertension with target organ damage in 30% (n = 18), immunologic reasons in 23% (n = 14), impaired renal function in 20% (n = 12) cardiovascular reasons 13.3% (n = 8), diabetes mellitus in 10% (n = 6), malignity in 10% (n = 6), obesity (body mass index > 35 kg/m(2)) in 5% (n = 3), and miscellaneous in 18.3% (n = 11). There were >1 reasons in 13 candidates. CONCLUSIONS: The problems detected in donor candidates offer a possibility for early detection of disorders and increased awareness.

Association of BK Virus Titers With Lymphocyte Count in Renal Transplant Patients.

OBJECTIVES: Regular screening for the BK virus (BKV) is recommended for early intervention in renal transplant patients. Identification of predictors for the development of BK viremia would improve their monitoring. We performed a retrospective study investigating whether the lymphocyte count may be a predictor of BKV development in renal transplant patients. PATIENTS AND METHODS: We retrospectively analyzed 268 renal transplant patients who were followed in our clinic from January 2011 to August 2014. The viral loads of BKV in blood detected by quantitative real-time polymerase chain reaction test were performed according to relevant guidelines. We also retrospectively monitored lymphocyte count, creatinine, immunosuppressive drug doses, and tacrolimus/cyclosporine/mTor inhibitors levels during the same time as BKV screening. Demographic and other clinical data were extracted from patients' files. The calculation of correlation coefficients and receiver operating characteristics (ROC) curve analysis were performed. RESULTS: Overall, 16 patients (5.9%) who experienced BKV-DNA positivity were included the study. Mean age of patients was 38.2 ± 12.8 years. All patients received steroid and calcineurin inhibitors (CNIs). Mycophenolate mofetil/mycophenolic acid (MMF/MPA) was administered to 14 patients. BKV-DNA was found in 64 of the 88 (72.7%) plasma samples. The lymphocyte count on the first day of positive BKV-DNA test was significantly lower than in those with negative BKV-DNA results (1700/µl vs 2400/µl, respectively; P = .009). Its AUC of the ROC curve was 0.77 (P = .012). The optimal cutoff point for lymphocyte count was 1900/µl, and sensitivity and specificity for predict BKV positivity were 75% and 78.57%, respectively. We also found that lymphocyte count negatively correlated with the first detectable BKV titers (r = -0.438; P = .015). However, there is no relation between CNI/mTOR inhibitor levels, MMF/MPA doses, lymphocyte count, and all BKV-titers. CONCLUSIONS: Decreased lymphocyte count may be a predictor for preceding BKV viremia. Clinicians should be more careful in terms of the decreased lymphocyte count in case of BKV replication in renal transplant patients.

Fibroblast growth factor-23 levels are associated with uric acid but not carotid intima media thickness in renal transplant recipients.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD) patients. Fibroblast growth factor-23 (FGF-23) is associated with atherosclerosis and cardiovascular mortality in CKD patients and healthy subjects. However, data in renal transplant recipients (RTR) are scarce. We aimed to determine factors associated with FGF-23 and to explore its relationship to atherosclerosis. METHODS: Forty-six patients and 44 controls were included. FGF-23 was measured from plasma. Carotid intima media thickness (CIMT) was evaluated ultrasonographically. RESULTS: Patients had higher waist circumference (WC; 92.2 ± 14.9 vs 85.3 ± 11.0 cm; P < .05), glucose (99.8 ± 17.2 vs 90.3 ± 6.5 mg/dL; P < .01), creatinine (1.43 ± 0.6 vs 0.86 ± 0.1 mg/dL; P < .01), triglyceride (160.4 ± 58.9 vs 135.6 ± 59.8 mg/dL; P < .05), white blood cells (WBC; 7938.6 ± 2105.2 vs 6715.7 ± 1807.5 WBC/mm(3); P < .01), ferritin (217.0 ± 255.8 vs 108.3 ± 142.4 ng/mL; P < .05), uric acid (6.5 ± 1.6 vs 4.7 ± 1.3 mg/dL; P < .01), C-reactive protein (CRP; 8.2 ± 18.2 vs 5.3 ± 7.9 mg/L; P < .01), parathyroid hormone (PTH; 89.7 ± 59.2 vs 44.1 ± 16.7 pg/mL; P < .01), and alkaline phosphatase (ALP; 162.5 ± 86.6 vs 74.2 ± 21.9 U/L; P < .01). FGF-23 was higher in patients (11.7 ± 7.2 vs 9.6 ± 6.8 pg/mL; P < .05). CIMT was similar (0.58 ± 0.09 vs 0.57 ± 0.1 mm; P > .05). WC, creatinine, and uric acid were positively correlated with FGF-23, whereas albumin showed negative correlation. On multivariate analysis only creatinine and uric acid were determinants of FGF-23. CONCLUSION: FGF-23 levels are associated with uric acid in RTR. Larger studies are needed to confirm this finding.

Effects of spironolactone in an experimental model of chronic cyclosporine nephrotoxicity.

BACKGROUND: Cyclosporine (CsA)-associated nephrotoxicity is a long-term complication in transplant patients. Chronic CsA nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. The aim of this study was to investigate the effect of spironolactone on functional and structural alterations as well as on platelet-derived growth factor B (PDGF-B) and transforming growth factor (TGF) beta expression induced by CsA in a rat model of chronic CsA nephrotoxicity. MATERIALS AND METHODS: Twenty-four rats were divided into 3 groups. Group 1 (G1) received vehicle only (V); G2, CsA (15 mg/kg/d; CsA) by intraperitoneal (IP) injection; and G3, a similar CsA dosage + spironolactone (20 mg/kg/d; CsA + Ald.) by the oral route. At the end of 28 days, glomerular filtration rate (GFR) and blood CsA levels were measured as well as histopathological and immunohistochemical analyses performed on renal tissue. RESULTS: Mean CsA trough levels in G2 and G3 were both above 2000 ng/mL. In G2, GFR was lower than G1 and G3 (0.35 +/- 0.05, 1.64 +/- 0.24, and 1.20 +/- 0.25 mL/min, respectively; P < .001). There was a significantly increased number of arteriolopathic changes in G2 and G3 vs G1 (16% +/- 3.7%, 15% +/- 6.8%, 3% +/- 1.2%, respectively; P < .001). Interstitial fibrosis was significantly increased in G2 vs G1 and G3 (52%, 0%, 27%, respectively; P < .05). Marked by up-regulated PDGF-B and TGF beta expressions were observed in G2 vs G1 or G3: 100%, 0%, 37.5%, respectively, for PDGF-B (P < .001) and 87.5%, 0%, 12.5%, respectively, for TGF beta (P < .001). CONCLUSION: Our results suggested that chronic CsA nephrotoxicity may be mitigated by aldosterone receptor blockade which seemed to be associated with down-regulation of PDGF-B and TGF beta expression.

Renal protective effects of leukotriene receptor blockers in an experimental model of cyclosporine nephrotoxicity.

BACKGROUND: Chronic cyclosporine (CsA) nephrotoxicity is associated with renal fibrosis and hyaline arteriolopathy. Fibrogenic cytokines, such as transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF), play a pivotal role in CsA nephrotoxicity. Previous studies have demonstrated the possible role of leukotrienes (LT) in chronic CsA nephrotoxicity. The aim of this study was to examine the possible beneficial effects of LT blockers in attenuating the morphological and histochemical effects induced by CsA in a rat model of CsA nephrotoxicity. MATERIALS AND METHODS: Twenty-four male Wistar rats were divided into 3 groups (n = 8). The first group (G1) was treated with vehicle intraperitoneally (IP) for 60 days. The second group (G2) was treated with 15 mg/kg CsA IP for 60 days. The third group (G3) was treated with the same dose of CsA plus 4 mg/kg montelukast administered by oral gavage for 60 days. RESULTS: There was a statistically significant decrease in glomerular filtration rate (GFR) among G2 compared with G1 animals: 0.41 +/- 0.03 vs 1.63 +/- 0.12 mL/min (P < .001), or G3 hosts: 0.41 +/- 0.03 vs 0.95 +/- 0.05 mL/min (P < .005), respectively. The percentage of hyaline arteriolopathic changes was higher in G2 than G1 or G3: 81.66% +/- 8.2% vs 11.83% +/- 0.87% (P < .01) or 37.0% +/- 8.8% (P < .01), respectively. Fibrosis score was higher in G2 compared with G1 or G3: 1.5 +/- 0.04 vs 0.16 +/- 0.02 (P < .001) and 1.0 +/- 0.05 (P < .05), respectively. TGF-beta and VEGF immunoexpression were significantly increased in G2 compared with G1 (P < .05) or G3 (P < .05). CONCLUSIONS: Our study suggested that LT may play a critical role in the pathogenesis of chronic CsA nephrotoxicity; the administration of montelukast, a LT receptor blocker, may prevent CsA-induced nephrotoxicity.

Inhibition of the renin angiotensin system decreases fibrogenic cytokine expression in tacrolimus nephrotoxicity in rats.

The aim of our study was to investigate the influence of angiotensin-converting enzyme (ACE) inhibition and angiotensin II receptor blockage on the renal function by light microscopic and immunohistochemical findings in a rat model of tacrolimus nephrotoxicity. Thirty-two male Wistar rats were divided into four groups of eight: G1 = control group; G2-G3, G4 = Tacrolimus (Tac) 1 mg/kg/d intraperitoneally (ip); G3 (Tac + Q) = ip Tac and peroral quinapril 10 mg/kg; and G4 (Tac + V) = Tac and valsartan 40 mg/d. Serum blood urea nitrogen (BUN), creatinine, and creatinine clearance were measured before and at the end of the study period. Renal tissues were assessed for light microscopic findings of tacrolimus toxicity. Transforming growth factor-beta, VEGF, PDGF, BMP-7, and interleukin-6 (IL-6) expression were semiquantitatively scored after immunohistochemical staining. At the end of the study period serum BUN and creatinine levels were increased in all groups, but creatinine clearance was not significantly changed between the groups. Afferent arteriolopathy was significantly less pronounced in G3 versus G2 and G4. Interstial fibrosis was significantly less pronounced in G3 and G4 versus G2. TGF-beta, PDGF, and IL-6 expression were significantly increased in G2, G3, and G4 compared to G1, and in G2 compared to G3 and G4. BMP-7 expression was significantly decreased in G2, G3, and G4 compared to G1, whereas the differences between G2, G3, and G4 failed to reach statistical significance. In conclusion, the results of our study suggested that renin angiotensin inhibition down-regulates fibrogenic cytokine expression in rats displaying tacrolimus nephrotoxicity.

Transforming growth factor-beta1, vascular endothelial growth factor, and bone morphogenic protein-7 expression in tacrolimus-induced nephrotoxicity in rats.

The aim of our study was to investigate transforming growth factor (TGF)-beta1, vascular endothelial growth factor (VEGF), and bone morphogenic protein-7 (BMP-7) expression in the rat model of chronic tacrolimus (TAC) toxicity compared to healthy controls. Seventeen male Wistar rats were divided into two groups: group 1 animals were healthy controls and Group 2 animals were treated with TAC (1 mg/kg per day intraperitoneally for 8 weeks). At the end of the study period the animals were sacrificed following renal function studies including blood urea nitrogen (BUN), serum creatinine, and creatinine clearance, and renal tissues were examined by light microscopy for the findings of tacrolimus toxicity, specifically for afferent arteriolopathy and interstitial fibrosis. TGF-beta1, VEGF, and BMP-7 expression were assessed by semiquantitative scoring of the immunohistochemically stained specimens. Mean TAC levels were 5.53 +/- 2.38 ng/mL in group 2. BUN, creatinine levels, and creatinine clearance were 57.99 +/- 11.13 vs 39.49 +/- 5.64 mg/dL; 0.60 +/- 0.16 vs 0.65 +/- 0.09 mg/dL; 0.97 +/- 0.39 vs 1.17 +/- 0.32 mL/min in group 2 versus group 1. Only the BUN level was significantly higher in group 2 compared to group 1. Afferent arteriolopathy and interstitial fibrosis were significantly increased in group 2 compared to group 1. TGF-beta1 and VEGF expression was significantly increased while BMP-7 expression was significantly decreased in group 2 versus group 1. In conclusion, our findings suggest that TAC-induced nephrotoxicity is associated with increased TGF-beta1 and VEGF and decreased BMP-7 expression.

Cyclosporine-A induced nephrotoxicity is associated with decreased renal bone morphogenetic protein-7 expression in rats.

The aim of our study was to investigate bone morphogenetic protein-7 (BMP-7) expression in a rat model of chronic cyclosporine (CsA) toxicity compare with healthy controls, as well as the influence of treatment with the angiotensin-converting enzyme inhibitor (ACEI) quinapril. Twenty-four male Wistar rats were divided into groups of eight animals treated with CsA (15 mg/kg intraperitoneally) for 8 weeks (CsA group) without or with quinapril (10 mg/kg per day in the drinking water: CsA group + Q) for comparison with healthy controls (H group). The renal tissues were examined by light microscopy for CsA toxicity; specifically, tubulointerstitial damage and afferent arteriolopathy as well as BMP-7 expression were semiquantitatively scored by immunohistochemical staining. Mean CsA levels were 1982 ng/mL and 1968 ng/mL for the CsA and CsA + Q groups, respectively. At the end of the study period, the mean serum creatinine levels were 0.8 +/- 0.2 mg/dL, 1.6 +/- 0.8 mg/dL, and 1.4 +/- 0.8 mg/dL for the H, CsA, and CsA + Q groups, respectively. Interstitial fibrosis, tubular atrophy, and afferent arteriolar hyalinization were present in the CsA group and, to a lesser degree, in the CsA + Q group, compared with the H group. CsA-treated rats displayed significantly decreased BMP-7 expression compared with healthy controls (P <.0005). BMP-7 expression was higher among the CsA + Q group than the the group CsA group. In a rat model histologic changes characteristic of CsA-induced nephrotoxicity are associated with decreased expression of BMP-7, which seems to be at least partially restored by ACE inhibition.

Angiotension converting enzyme inhibition and calcium channel blockage improves cyclosporine induced glucose intolerance in rats.

The aim of this study was to evaluate the effects of quinapril, valsartan, and amlodipin on glucose tolerance in cyclosporine (CsA)-toxic rats. Among 40 male Wistar rats 32 were administered cyclosporine (CsA) (15 mg/kg) intraperitoneally for 6 weeks. Quinapril (10 mg/kg per day) (group Q), valsartan (40 mg/kg per day) (group V), and amlodipine (10mg/kg per day) (group A) were administered to individual sets of eight CsA-treated animals via the drinking water with the remaining untreated hosts followed as a control group (group C) and 8 healthy controls (group H). A Glucose-tolerance test was performed by administering oral glucose (2 g/kg) followed by blood samples obtained from the tail vein at baseline as well as 30,60,90, and 120 minutes after the glucose load. Glucose area under the curve (AUC) was calculated according to the trapezoidal rule. CsA levels were determined using an immunofluorescence method. Kruskal Wallis ANOVA test was used for statistical analysis. Median CsA levels were 1968 ng/mL, 1982 ng/mL, 1580 ng/mL, 1600 ng/mL; and glucose AUC, 232.4 +/- 130 mg/min per dL, 63.1 +/- 25 mg/min per dL, 115.0 +/- 90 mg/min per dL, 47.4 +/- 34 mg/min per dL 53.4 +/- 38 mg/min per dL for groups C,Q,V,A and H, respectively. Quinapril-treated and amilodipine-treated rats displayed a lower glucose AUC than group C (P <.01), which had higher glucose levels than healthy controls (P <.001). In summary, CsA treated rats show impaired glucose tolerance, which is improved by quinapril or amlodipine treatment. Angiotensin converting enzymes inhibitors and calcium channel blockers affect beta cell function rather than insulin sensitivity.

Causes of late leaks in peritoneal dialysis patients.

BACKGROUND/AIMS: Late dialysis leakage is an important complication of peritoneal dialysis. The aim of our study was to investigate the causes of late leaks in patients on peritoneal dialysis. METHODS: 25 patients (19 F: 6 M; mean age: 56 +/- 14) with and 25 patients (10 F : 15 M; mean age: 57 +/- 12) without dialysis leakage on maintenance peritoneal dialysis treatment were included in the study. Data on demographic characteristics including age, sex, body mass index, body surface area, primary renal disease and peritoneal dialysis characteristics including implantation technique of the catheter, site of the catheter, time from catheter implantation to initiation of peritoneal dialysis, daily total filling volumes, use of hypertonic solutions, membrane transport properties and total and peritoneal creatinine clearances were retrospectively collected for both groups. RESULTS: The number of female vs. male patients (76% vs. 40%, p < 0.05) and patients on CAPD vs. APD (68% vs. 56%, p < 0.05) were significantly higher in the group with dialysis leakage. Patients with leakage also had lower average transport properties (p < 0.05) and lower total creatinine clearances (p < 0.05). Other demographic and peritoneal dialysis characteristics were similar in both groups. CONCLUSIONS: Female gender and CAPD as opposed to male gender and APD are the risk factors involved in the development of late dialysis leaks. Peritoneal membrane transport characteristics as well as total creatinine clearance also seems to influence the development of complications.