Multicenter epidemiological study to assess the population of CKD patients in Greece: results from the PRESTAR study.

BACKGROUND: Chronic Kidney Disease (CKD) is a relatively common condition not only associated with increased morbidity and mortality but also fuelling End Stage Renal Disease (ESRD). Among developed nations, Greece has one of the highest ESRD incidence rates, yet there is limited understanding of the epidemiology of earlier stages of CKD. METHODS: Cross-sectional survey of pre-dialysis CKD outpatients in nephrology clinics in the National Health Care system between October 2009 and October 2010. Demographics, cause of CKD, blood pressure, level of renal function, duration of CKD and nephrology care, and specialty of referral physician were collected and analyzed. Different methods for estimating renal function (Cockroft-Gault [CG], CKD-Epi and MDRD) and staging CKD were assessed for agreement. RESULTS: A total of 1,501 patients in 9 centers were enrolled. Diabetic nephropathy was the most common nephrologist assigned cause of CKD (29.7%). In total, 36.5% of patients had self-referred to the nephrologist; patients with diabetes or serum creatinine above 220 µmol/l (eGFR<40 ml/min/1.73 m2) were more likely to have been referred by a physician. Agreement between MDRD and CKD-Epi, but not between CG, the other estimating equations, was excellent. There was substantial heterogeneity with respect to renal diagnoses, referral patterns and blood pressure among participating centers. CONCLUSIONS: In this first epidemiologic assessment of CKD in Greece, we documented delayed referral and high rates of self-referral among patients with CKD. eGFR reporting, currently offered by a limited number of laboratories, may facilitate detection of CKD at an earlier, more treatable stage.

Can dialysis modality influence quality of life in chronic hemodialysis patients? Low-flux hemodialysis versus high-flux hemodiafiltration: a cross-over study.

BACKGROUND: Hemodiafiltration with online preparation of the substitution [online high-flux hemodiafiltration (OHDF)] and hemodiafiltration with prepared bags of substitution (HDF) are important, recently widely used renal replacement therapies in patients with end-stage renal disease. However, there is little information on the comparative impacts of these modalities versus conventional low-flux hemodialysis (HD) on the quality of life (QoL) of HD patients. This study investigates the effect of dialysis modality on QoL in chronic HD patients. METHODS: In this prospective, randomized, cross-over, open label study, 24 patients were enrolled. Their age were 62 ± 13.34 years (mean ± SD), with the duration of dialysis of 31 ± 23.28 months (mean ± SD). Five of the patients were women. QoL was measured by the Short-Form Health Survey with 36 questions (SF-36) and subscale scores were calculated. Each patient received HD, OHDF, and HDF for 3 months, with the dialysis modality subsequently being altered. They completed the questionnaire of QoL at the end of each period. RESULTS: There were statistical significant differences in QoL for the total SF-36 [36.1 (26.7-45.7) and 40.7 (30.2-62.8)], for classic low-flux HD and high-flux hemodiafiltration, for bodily pain [45 (26.9-66.9) and 55 (35.6-87.5)], and for role limitations due to emotional functioning [0 (0-33.3) and 33.3 (0-100)], respectively. The scores did not differ significantly between the two types of hemodiafiltration. CONCLUSIONS: Our study indicates that QoL differs significantly among patients receiving low-flux HD and high-flux hemodiafiltration, on total SF-36, bodily pain, and role limitations due to emotional functioning. Convective modalities may offer better QoL than diffusive HD.

Exploring genomic structure differences and similarities between the Greek and European HapMap populations: implications for association studies.

Studies of the genomic structure of the Greek population and Southeastern Europe are limited, despite the central position of the area as a gateway for human migrations into Europe. HapMap has provided a unique tool for the analysis of human genetic variation. Europe is represented by the CEU (Northwestern Europe) and the TSI populations (Tuscan Italians from Southern Europe), which serve as reference for the design of genetic association studies. Furthermore, genetic association findings are often transferred to unstudied populations. Although initial studies support the fact that the CEU can, in general, be used as reference for the selection of tagging SNPs in European populations, this has not been extensively studied across Europe. We set out to explore the genomic structure of the Greek population (56 individuals) and compare it to the HapMap TSI and CEU populations. We studied 1112 SNPs (27 regions, 13 chromosomes). Although the HapMap European populations are, in general, a good reference for the Greek population, regions of population differentiation do exist and results should not be light-heartedly generalized. We conclude that, perhaps due to the individual evolutionary history of each genomic region, geographic proximity is not always a perfect guide for selecting a reference population for an unstudied population.

Calcific uremic arteriolopathy treated with cinacalcet, paricalcitol, and autologous growth factors.

BACKGROUND: Calcific uremic arteriolopathy is an uncommon cutaneous ischemic necrotizing disease, most commonly associated with renal disease and hyperparathyroidism, bearing a high mortality rate. OBJECTIVE AND METHOD: A case of a 57-year-old female renal patient with hyperparathyroidism who was successfully treated with combined paricalcitol and cinacalcet systemically, while autologous growth factors were locally applied, is herein presented. RESULT AND CONCLUSION: The combination of cinacalcet and paricalcitol is a reliable alternative to parathyroidectomy in patients with calcific uremic arteriolopathy and hyperparathyroidism. Meticulous débridement of necrotic tissues is essential and application of autologous growth factors promotes healing.

Effects of L-carnitine on oxidative stress responses in patients with renal disease.

PURPOSE: Hemodialyzed patients demonstrate elevated oxidative stress and reduced functional status. Exercise induces health benefits, but acute exertion up-regulates oxidative stress responses in patients undergoing hemodialysis. Therefore, the aim of the present study was to examine the effect of L-carnitine supplementation on i) exercise performance and ii) blood redox status both at rest and after exercise. METHODS: Twelve hemodialysis patients received either L-carnitine (20 mg kg(-1) i.v.) or placebo in a double-blind, placebo-controlled, counterbalanced, and crossover design for 8 wk. Participants performed an exercise test to exhaustion before and after supplementation. During the test, V˙O2, respiratory quotient, heart rate, and time to exhaustion were monitored. Blood samples, collected before and after exercise, were analyzed for lactate, malondialdehyde, protein carbonyls, reduced and oxidized glutathione, antioxidant capacity, catalase, and glutathione peroxidase activity. RESULTS: Blood carnitine increased by L-carnitine supplementation proportionately at rest and after exercise. L-carnitine supplementation increased time to fatigue (22%) and decreased postexercise lactate (37%), submaximal heart rate, and respiratory quotient but did not affect V˙O2peak. L-carnitine supplementation increased reduced/oxidized glutathione (2.7-fold at rest, 4-fold postexercise) and glutathione peroxidase activity (4.5% at rest, 10% postexercise) and decreased malondialdehyde (19% at rest and postexercise) and protein carbonyl (27% at rest, 40% postexercise) concentration. CONCLUSIONS: Data suggest that a 2-month L-carnitine supplementation may be effective in attenuating oxidative stress responses, enhancing antioxidant status, and improving performance of patients with end-stage renal disease.

Chromosome instability in patients with chronic renal failure.

OBJECTIVE: The aim of this study was to investigate the frequency of sister chromatid exchanges (SCEs), the presence of cytostaticity, cytotoxicity, and therefore, the possible genetic instability in patients with chronic renal failure (CRF) in human cultured peripheral blood lymphocytes. METHODS: Peripheral blood lymphocytes were cultured from 32 patients with CRF (average 55.2 years) and 18 healthy blood donors (average 44.6 years), and the SCE method was applied afterward. The increase in SCE frequency was evaluated as an immediate DNA damage index, while the reduction in the values of the proliferating rate indices was evaluated as a cytostatic index and the mitotic indices as a cytotoxic index was also measured. RESULTS: A significant increase in the SCE frequencies along with a significant reduction in mitotic indices was observed in patients with CRF compared with the controls. It is notable that there was no significant difference in SCE levels among patients with CRF and cancer, and patients with CRF alone. CONCLUSIONS: This study illustrates increased genetic instability in patients with CRF. These results could also be of a great importance in early diagnosis to prognosticate a possible generation of neoplasm in the future.

The serotonin transporter promoter polymorphism (5-HTTLPR) is associated with type 2 diabetes.

BACKGROUND: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene-linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with type 2 diabetes mellitus and obesity. METHODS: Study population consisted of 252 subjects diagnosed with Type 2 DM and 211 non-diabetic subjects, all Caucasians of Greek ethnic origin. Genomic DNA was extracted from peripheral blood and analyzed for 5-HTTLPR polymorphism with a novel PCR protocol. RESULTS: The frequency of SS and SL genotypes of HTTLPR was significantly higher in the diabetic group (77.0%) than in the non-diabetic group (61.6%) (P<0.001). The genetic risk of Type 2 DM for subjects carrying at least one S allele was increased compared to non-diabetic subjects (OR=2.08, 95% CI=1.39-3.12). When subjects were divided according to BMI status, the frequency of S allele carriers was similar in obese and non-obese subjects. CONCLUSIONS: The S allele of 5-HTTLPR is strongly associated with the presence of Type 2 DM. This association appears to be direct and not dependent on obesity status. Therefore, 5-HTTLPR LL genotype might be protective for development of Type 2 DM.

Rigorous Vibrio vulnificus soft tissue infection of the lower leg in a renal transplant patient managed by vacuum therapy and autologous growth factors.

BACKGROUND: Vibrio vulnificus is a gram-negative marine bacterium that grows well in coastal waters. It is an opportunistic pathogen that can cause serious life-threatening infections in patients with certain health conditions. Vibrio-induced wound infections in immunosuppressed patients are difficult to treat because the healing process may be significantly delayed. Reconstructive surgery may not be successful in early treatment as skin grafts are likely to fail, and there may be increased morbidity of donor sites of grafts or flaps. OBJECTIVE: Herein a case of septicemia and wound necrosis owing to V. vulnificus wound infection in a renal transplant patient is reported. METHOD: To conservatively yet adequately débride the wound bed, stimulate angiogenesis, and accelerate granulation, vacuum-assisted closure was employed. Granulation was further enhanced by autologous platelet concentrate spray, which has also been reported to increase the epithelialization rate. RESULT: Complete epithelialization of the wound was achieved 4 weeks after completion of treatment. CONCLUSION: Noninvasive advanced modalities may be employed to successfully treat infectious soft tissue deficits in immunocompromised patients.

Surgical revision of complicated false and true vascular access-related aneurysms.

PURPOSE: This prospective observational study examined the effect of revision surgery in patients who present solely with complicated arteriovenous access (AVA)-related aneurysms. METHODS: The demographics and comorbid conditions of 44 hemodialysis access patients who presented with complicated true or false AVA-related aneurysms and underwent revision surgery during a 7-year period were prospectively entered into our AVA database. Also recorded were AVA characteristics before and after revision. Arteriovenous access anatomy was evaluated preoperatively using color Doppler ultrasonography, and AVA adequacy was assessed in all patients postoperatively after the first needle puncture and every month thereafter. Postintervention access function and primary patency rates were analyzed. Patency was evaluated using the Kaplan-Meier method and compared between groups of patients with different AVA characteristics before and after revision using the log-rank test. RESULTS: The cases of initial AVA with complicated aneurysms comprised 16 radiocephalic, 8 brachiocephalic, 2 basilic vein transposition, and 18 prosthetic fistulas (7 and 11 of the lower and upper arm, respectively), of which 42 were dysfunctional and 2 had thrombosed early at presentation. Primary indications for revision were danger of aneurysm rupture in 26, duplication in graft aneurysm diameter in 18, painful aneurysm in 12, stenosis due to partial aneurysm thrombosis in 12, shortness of the potential cannulation area in 12, aneurysm enlargement in 4, infected aneurysm in 2, and completely thrombosed aneurysm in 2. The mean postintervention primary patencies were 93%, 82%, 57%, and 32% at 3, 6, 12, and 24 months, respectively. The outcomes was better in autogenous than prosthetic corrections, in true than false aneurysms, in patients with two or fewer than more than 2 previous AVAs on revised arms, and in forearm than upper-arm corrections (P = .0197, P = .004, P = .0022, and P = .0225, respectively). CONCLUSIONS: Surgical revision of complicated false and true AVA-related aneurysms reveals acceptable postintervention primary patency rates and therefore is justified. This outcome measure was superior in the following specific groups of corrections: autogenous were better than prosthetic, true aneurysms were better than false aneurysms, patients with one or two previous AVAs in the revised arm were better than those with more than two previous accesses in the revised arm, and finally, forearms were better than those in the upper arm.

The -759C/T polymorphism of the 5-HT2C receptor is associated with type 2 diabetes in male and female Caucasians.

OBJECTIVES: Type 2 diabetes mellitus and obesity constitute serious health problems. Studies reveal that the 5-HT2C receptor contributes substantially to the regulation of a wide variety of behavioral and physiological processes including feeding and glucose homeostasis. Our aim was to determine the possible association of the -759C/T polymorphism of the 5-HT2C receptor gene with type 2 diabetes and obesity in male and female individuals Caucasian origin. METHODS: The study population consisted of 151 patients diagnosed with type 2 diabetes and 164 nondiabetic patients, all of Greek origin. Genomic DNA was extracted from peripheral blood and analyzed for the -759C/T polymorphism of the 5-HT2C receptor gene using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of T allele of the -759C/T polymorphism of the 5-HT2C receptor was significantly lower in the diabetic group (12.6%) than in the nondiabetic group (23.3%) (P=0.003). The genetic risk of type 2 diabetes for patients not carrying the T allele was increased compared with nondiabetic patients (odds ratio (OR)=2.34, 95% confidence interval (CI)=1.36-4.02). The reduced frequency of T allele was present both in male [10% in patients with diabetes and 21.6% in patients without diabetes (P=0.041)] and female patients [14.1% in patients with diabetes and 24.3% in patients without diabetes (P=0.030)]. In contrast, the frequency of T allele was similar in obese (16.4%) and nonobese (17.1%) patients. CONCLUSIONS: Lower frequency of -759T allele of the 5- HT2C receptor gene was associated with type 2 diabetes but not with obesity in male and female Caucasians. Thus, this polymorphism might constitute a prognostic marker for diabetic risk.

Use of short PTFE segments (<6 cm) compares favorably with pure autologous repair in failing or thrombosed native arteriovenous fistulas.

OBJECTIVE: The re-establishment of patency in a stenosed or thrombosed native arteriovenous fistula (AVF) is fundamental to regaining adequate hemodialysis through the same cannulable vein. Many surgeons have been reluctant to use even small segments of synthetic grafts in AVF revisions because of a perception that these would lead to poor results; however, studies comparing various treatment options are scarce. This study compared the use of short (<6 cm) polytetrafluoroethylene (PTFE) segments with pure autologous repair in stenosed or thrombosed native fistulas. METHODS: The cumulative postintervention primary patency rates of two groups of hemodialysis patients receiving different surgical revision operations of their vascular accesses were prospectively compared. Group I (n = 30) comprised patients who presented with stenosed or thrombosed native fistulas and received short (2 to 6 cm) interposition PTFE grafts placed after the stenosed or thrombosed outflow vein segment was resected. These short PTFE grafts were not used for cannulation. Group II (n = 29) comprised patients who presented with dysfunctional or failed AVFs and underwent various types of pure autogenous corrections. AVF dysfunction or thrombosis was detected with clinical examination and color duplex ultrasound scanning. In all cases, on-table arteriography-fistulography was performed before surgical repair. Access adequacy was assessed in all patients postoperatively after the first puncture and every month thereafter (mean follow up 16.7 months). RESULTS: No statistically significant difference in patency was observed between the two groups. Postintervention cumulative patencies were 100%, 88%, and 82% for group I and 90%, 82%, and 71% for group II at 6, 12, and 18 months, respectively ( P = .8). CONCLUSIONS: Short (<6 cm) interposition PTFE segments used for the revision of failing or failed AVFs compare favorably to purely native repair and do not alter the autologous behavior of the initial access. These short PTFE revisions resulted in satisfactory midterm primary patency without further consumption of the venous capital by harvesting segments of vein from other locations and without compromising more proximal access sites. This practice is recommended and is justified as part of an aggressive access salvage policy addressed by many authors so far.

Hypotension in patients on chronic peritoneal dialysis: etiology, management, and outcome.

We retrospectively evaluated the phenomenon of arterial hypotension in peritoneal dialysis (PD) in a large cohort of 633 PD patients from two centers (Toronto Western Hospital, Toronto, Canada, and Division of Nephrology, Democritus University of Thrace, Greece), thus extending our previously reported experience for an additional 6 years (1995-2000). Together, the units had 81 hypotensive patients (12.8%), whose mean age was 63.8 +/- 14.2 years and whose mean duration of peritoneal dialysis was 49.3 +/- 30 months. Based on the underlying pathophysiology, the hypotensive PD patients were divided into four groups: (A) hypovolemia, 32 patients (39.5%); (B) congestive heart failure (CHF), 15 patients (18.5%); (C) receiving antihypertensive medications, 11 patients (13.6%); and (D) "unknown" etiology, 23 patients (28.4%). All patients in the hypovolemic and antihypertensive groups responded well to treatment (volume expansion and discontinuation of antihypertensive medication, respectively), but in the CHF and "unknown" groups, only 40% improved with the appropriate intervention. Patients in the latter two groups showed the poorest prognosis, with an approximate death rate of 65%. The hypovolemic group had better outcomes, which might reflect prompt response to fluid replacement in that group. We conclude that, in PD patients, careful use of antihypertensive medication, the right evaluation of target weight (especially in patients with cardiac failure), and judicious use of hypertonic exchanges may prevent the severe complication of arterial hypotension.