Fibromyalgia and its clinical relevance in renal transplant recipients.

OBJECTIVE: Recent evidence suggests that fibromyalgia syndrome (FS) is associated with inflammation and endothelial dysfunction. Our aim was to determine the prevalence of FS in renal transplant recipients and to identify possible links between FS and clinical and laboratory parameters. METHODS: Ninety-nine kidney transplant recipients with normal graft functions (37.15 ± 10.83 years old, 67 male) were enrolled in the study. All subjects completed the Fibromyalgia Impact Questionnaire (FIQ). The biochemical and clinical parameters in the 1st post-transplantation year were retrospectively recorded. Cardiovascular parameters, including body composition analyses (Tanita), ambulatory blood pressure monitoring data, and pulse-wave velocity, were cross-sectionally analyzed. RESULTS: Mean FIQ score for the whole group was 21.4 ± 14.7. Eight patients had FIQ score >50, and these patients had significantly higher left ventricular mass index than patients with lower FIQ score (P = .048). Patients were divided according to their physical impairment score (PIS): PIS ≥5 (n = 50) and PIS <5 (n = 49). Patients with higher PIS had significantly higher serum creatinine (P = .047) and lower eGFR values (P = .008) than patients with lower PIS. Patients were also evaluated with the use of the stiffness score (SS): patients with (n = 41) and without (n = 58) stiffness. Patients with stiffness had significantly higher office systolic (P = .027) and diastolic (P = .044) blood pressure, body mass index (P = .033), and sagittal abdominal diameter (P = .05) than patients without stiffness. Decline in estimated glomerular filtration rate levels were significantly higher in patients with higher FIQ (7.6% vs 9.4%; P = .0001) than in other patients. CONCLUSIONS: FS in renal transplant recipients was strongly associated with hypertension, arterial stiffness, obesity, and renal allograft dysfunction.

Post-transplant Hyperuricemia as a Cardiovascular Risk Factor.

PURPOSE: Uric acid is known to impair endothelial cell function and to stimulate the development of renal interstitial fibrosis. The aim of this study was to evaluate the association between first-year hyperuricemia with graft dysfunction and the development of cardiovascular risk disorders in renal transplant recipients. METHODS: One hundred kidney transplant recipients (31 female, 45.9 ± 9.6 post-transplantation months) with normal graft functions were enrolled. The clinical biochemical parameters in the first post-transplantation year were retrospectively recorded and searched for the predictive value in yearly determined graft function and association with cross-sectionally analyzed cardiovascular parameters, including body composition analyses, ambulatory blood pressure monitoring data, and pulse wave velocity. Hyperuricemia was defined as an uric acid level of ≥ 6.5 mg/dL that persisted for at least 2 consecutive tests. RESULTS: One year after transplantation, 37% of subjects had hyperuricemia. According to cross-sectional data, sagittal abdominal diameter (P = .002) and hip circumferences (P = .013) were significantly higher in hyperuricemic patients than in normouricemic ones. Hyperuricemic patients had higher fat (P = .014) and muscle mass (P = .016) than normouremic patients. Hyperuricemic patients had significantly higher mean systolic BP (P = .044) than normouremic patients. Hyperuricemic patients had significantly higher pulse wave velocity levels (P = .0001) and left ventricular mass index (P = .044) than normouremic patients. The yearly decline in estimated glomerular filtration rate levels was significantly higher in hyperuricemic patients (P = .0001) than in normouricemic ones. CONCLUSION: Post-transplantation hyperuricemia is associated with hypertension, arterial stiffness, and dyslipidemia; it should be accepted not only as a marker for renal allograft dysfunction but also as a cardiovascular risk factor in renal transplant recipients.

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.

Can dental pulp calcification serve as a diagnostic marker for carotid artery calcification in patients with renal diseases?

OBJECTIVES: The aim of this study was to determine the relationship between the presence of pulp calcification and carotid artery calcification on dental panoramic radiographs in end-stage renal disease (ESRD) patients on haemodialysis and renal transplant recipients. METHODS: A total of 60 nephrology patients (29 haemodialysis patients and 31 renal transplant recipients) participated in this study. For all patients, both panoramic and periapical radiographs were evaluated twice by three examiners to determine the presence or absence of narrowing of the dental pulps and pulp stones in pulp chambers and canals. The kappa coefficient was used for intervariable agreement, and interexaminer reliability was evaluated by the intraclass correlation coefficient. Panoramic radiographs were also evaluated to determine carotid calcification. Ultrasound examination confirmed radiographic findings of carotid calcification on panoramic radiographs. RESULTS: Carotid calcifications were detected in 11 patients (6 haemodialysis patients and 5 transplant recipients). 48 patients (22 haemodialysis patients, 26 transplanted recipients) had dental pulp narrowing, and 8 patients (5 haemodialysis patients, 3 transplant recipients) had pulp stones. There was no statistical relation between pulp narrowing and carotid artery calcification (CAC) in the haemodialysis patient group and renal transplant recipients. There was also no statistical relation between pulp stones and CAC in haemodialysis patients and renal transplant recipients. CONCLUSION: In our study, no relationship was found between the presence of pulpal calcification and CAC in ESRD patients on haemodialysis and renal transplant recipients. Therefore, the presence of pulp calcification does not seem to serve as a diagnostic marker for carotid atherosclerosis.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis.

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 +/- 0.5. Fifty patients (60.3%) had GI value >or= 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = -0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.

The role of proinflammatory cytokine gene polymorphisms for development of insulin resistance after renal transplantation.

BACKGROUND: Insulin resistance, a frequent prediabetic metabolic complication after renal transplantation, is generally linked to immunosuppressive drugs including corticosteroids, cyclosporine (CsA) or tacrolimus, as well as to age, cadaveric donors and ethnic factors. Cytokines are known to be inflammation modulatory substances that contribute to metabolic derangements after transplantation. The present study investigated the effects of cytokine gene polymorphisms on insulin resistance in renal transplant recipients. PATIENTS AND METHODS: Sixty-one renal transplant recipients (37 men, 24 women; mean age: 39.3 +/- 10.8 years) who attended regular clinical visits without a known history of diabetes were enrolled in the study. All patients were on a regimen of steroid, CsA, and mycophenolate mofetil. Venous blood samples were collected for biochemical analyses after an overnight fast at 08:00 pm. CsA trough levels, C-reactive protein, and fibrinogen were also estimated. Additional 10 mL of blood was withdrawn into an ethylenediamine tetraacetic acid-containing tube to determine cytokine genotypes (tumor necrosis factor-alpha [TNF-alpha] -238 G/A, transforming growth factor-beta [TGF-beta] codon 10 -869 T/C). Insulin resistance was calculated by the homeostasis model assessment (HOMA) method using the values of fasting blood glucose (FBG) and insulin levels. Anthropometric indices as well as body height, weight, waist and hip circumferences were measured simultaneously to calculate body mass index (kg/m2) and waist-to-hip ratio. Impaired fasting glucose (IFG) was described as an FBG > or = 110 but < 126 mg/dL. RESULTS: IFG was detected in 27.9% of this study group. The HOMA index was significantly higher among patients with IFG compared with normal FBG (NoGT) (6.3 +/- 4.5 vs 3.7 +/- 1.5; P = .01). Neither FBG and insulin nor HOMA values correlated with antrophometric, metabolic, or inflammatory parameters. Cytokine genotype allele frequencies, age, sex, immunosuppressive and antihypertensive drug type and doses, CsA trough levels, and donor source (cadaveric/living) were similar for patients with IFG and NoGT. Mutant allele carrier genotypes (AA + GA) for TNF-alpha -238 G/A showed higher fasting insulin (14.0 +/- 7.9 vs 34.1 +/- 17.7 microIU/mL; P = .04) and HOMA (4.01 +/- 2.01 vs 7.95 +/- 5.44; P = .002) levels than GG homozygote subjects. FBG, HOMA, and other metabolic and anthropometric indices were similar between TGF-beta codon 10 -869 T/C genotypes. The daily dose of steroid (mg/d) and A allele frequency for TNF-alpha -238 G/A genotype were significant predictors of HOMA index in linear regression analysis. CONCLUSION: The present study revealed that beside the daily dose of steroids, TNF-alpha -238 G/A genotype may contribute to insulin resistance in renal transplant recipients. Further investigations may highlight the effects of cytokine gene heterogenity on insulin resistance in those patients.

The prevalence of carotid artery calcification on the panoramic radiographs of patients with renal disease.

OBJECTIVES: To determine the prevalence of carotid calcification on dental panoramic radiographs in end-stage renal disease (ESRD) patients on haemodialysis and renal transplant recipients. METHODS: Panoramic radiographs of 69 adult patients with renal disease (34 with haemodialysis and 35 with renal transplantations) (age range 17-74 years; mean age 39.45 years) and 50 controls (age-match, free of systemic disease) were examined on panoramic radiographs for any unusual radiopacity adjacent to or just below the intervertebral space between C3 and C4. Patients with such calcifications were referred to ultrasound examination. Using Chi-squared tests, calcification prevalence rates were statistically compared. RESULTS: The statistical difference between renal disease patients and control group was significant (chi2 = 17.91, P < 0.001). On comparison of haemodialysis patients and renal transplant recipients with controls, statistical difference (P=0.007) was found to be significant. CONCLUSION: Carotid artery calcification was higher in haemodialysis patients and renal transplant recipients. These patients with such calcifications should be referred for further evaluation and treatment of carotid arteries, coronary arteries and vascular risk factors.

Prediction of renal allograft function with early Doppler ultrasonography.

INTRODUCTION: Doppler ultrasonography (USG) is an useful, noninvasive diagnostic tool for the management and follow-up of the transplanted kidney. However, it is believed that the value of Doppler USG is limited to discrimination of acute rejection episodes. We tested whether early Doppler USG findings were predictive of 1-month and 1-year allograft functions in noncomplicated renal transplant recipients (RTRs). PATIENTS AND METHODS: Resistive index (RI) and pulsatile index (PI) values obtained by doppler USG within the first week of transplantation were correlated with allograft function at 1 month and 1 year in 45 (10 women, 35 men, mean age: 27 years) noncomplicated cases. Patients with complications during the first posttransplant year were not included. RESULTS: There was a negative correlation between both RI and PI with creatinine clearance values at 1 month and at 1 year posttransplant. There was a significant decline in allograft function among cases with either RI > or = 0.7 or PI > or = 1.1. Patients with impaired allograft function have higher RI and PI values. CONCLUSION: Renal allograft survival is influenced by many factors. However, no reliable simple parameter has been identified to predict long-term outcome. Doppler USG performed during the early transplantation period with calculation of RI and PI may have a predictive value to forecast early and long-term outcomes of noncomplicated kidney transplants.

Septic arthritis caused by Nocardia asteroides in a renal transplant recipient.

Although articular complications are common following renal transplantation, septic arthritis is not frequent. Previous bacterial infection in an another site is a consistent finding and the knee is the most often affected joint. We present a 30-year-old female renal transplant recipient with recurrent pulmonary infiltrates preceding septic arthritis of her left knee. Cultures of the aspirated synovial fluid yielded a gram-positive, rod-shaped bacterium later identified as Nocardia asteroides. The patient was treated with oral trimethoprim-sulfamethoxazole without any side effect. Nocardia is a rare but serious cause of infection in renal transplant recipients but there is no well-known predisposing factor. Recently mycophenolate mofetil has been implicated as a factor associated with Nocardia infections. Prolonged courses of treatment with sulphonamides are recommended.