PTFE grafts versus tunneled cuffed catheters for hemodialysis: which is the second choice when arteriovenous fistula is not feasible?

Vascular access-related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients' survival. An observational study was carried out with a 2-year follow-up. Eighty-seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients' mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan-Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log-rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan-Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log-rank test = 10.07, P < 0.01). The adjusted Cox regression analysis showed that patients with TCC had a 3.2 times higher risk of death than patients with PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation.

Importance of vascular calcification in kidney transplant recipients.

BACKGROUND: Kidney transplantation is the treatment of choice for chronic kidney disease (CKD), but in kidney transplant recipients (KTRs) cardiovascular events are the first cause of death with a functioning graft, ranging from 36 to 55%. The impact of vascular calcification (VC) on morbidity and mortality of KTRs is not appreciated enough nowadays. SUMMARY: This review summarizes 13 important studies on VC in KTRs, comparing the results with CKD and dialysis populations. We focused on VC evaluation and use of coronary artery calcification (CAC) and aorta calcification (AoC) scores. We also evaluated the influence of traditional and non-traditional progression risk factors. KEY MESSAGES: VC strongly predicts cardiovascular events and all-cause mortality in KTRs. VC assessment is important in KTRs and based essentially on multislice computed tomography or electron beam computed tomography recognition of lesions. Quantitative measurement of CAC and AoC scores is essential for a correct definition of the calcium burden before and after kidney transplant. Progression of CAC slows down but does not halt after kidney transplant. A variable association of both traditional and non-traditional risk factors is shown. There is a strong association between baseline CAC score and CAC progression. A significant improvement in secondary hyperparathyroidism after transplantation favorably affects the progression of CAC. Low 25(OH)D3 levels are an independent determinant of CAC progression. Diabetes is a risk factor for the presence of CAC in KTRs, but has not been independently associated with CAC progression. The data published on the use of immunosuppressive drugs as progression factors are few and inconclusive.

Emerging drugs for chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide health problem. Despite remarkable headway in slowing the progression of kidney diseases, the incidence of end-stage renal disease (ESRD) is increasing in all countries with a severe impact on patients and society. The high incidence of diabetes and hypertension, along with the aging population, may partially explain this growth. Currently, the mainstay of pharmacological treatment for CKD, aiming to slow progression to ESRD are ACE inhibitors and angiotensin II receptor blockers for their hemodynamic/antihypertensive and anti-inflammatory/antifibrotic action. However, novel drugs would be highly desirable to effectively slow the progressive renal function loss. AREAS COVERED: Through the search engines, PubMed and ClinicalTrial.gov, the scientific literature was reviewed in search of emerging drugs in Phase II or III trials, which appear to be the most promising for CKD treatment. EXPERT OPINION: The great expectations for new drugs for the management of CKD over the last decade have unfortunately not been met. Encouraging results from preliminary studies with specific agents need to be tempered with caution, given the absence of consistent and adequate data. To date, several agents that showed great promise in animal studies have been less effective in humans.

The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open-label comparative study.

This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open-label, 12-month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post-transplantation, 357 patients were randomized to receive standard-dose cyclosporine (sCsA, n = 179) or reduced-dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy-confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P < 0.001), and creatinine clearance (±SEM; Nankivell method) was significantly higher (57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min, P < 0.001) in patients receiving rCsA versus sCsA at 1 year, respectively. Patient and graft survival exceeded 98% in both groups. No significant differences in infection or malignancy were noted between groups. The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12-month patient and graft survival, a low incidence of BCAR, and improved renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long-term renal allograft outcomes.

Physical activity in solid organ transplant recipients: preliminary results of the Italian project.

BACKGROUND/AIMS: The role of physical activity in transplanted patients is often underestimated. We discuss the Italian National Transplant Centre experience, which started in 2008 studying transplanted patients involved in sports activities. The study was then developed through a model of cooperation between surgeons, sports physicians and exercise specialists. METHODS: A multicentre study was realized in 120 transplanted patients of which 60 treated with supervised physical activity (three sessions/week of aerobic and strengthening exercises) and 60 controls. We present the results of the first 26 patients (16 males, 10 females; 47.8 ± 10.0 years; 21 kidney, 5 liver transplanted; time from transplant 2.3 ± 1.4 years) who completed 12 months of supervised physical activity. RESULTS: Data showed an increase of peak aerobic power (t=4.535; P<0.01) and maximum workload (t=4.665; P<0.01) in the incremental cycling test. Maximum strength of knee extensors (t=2.933; P<0.05) and elbow flexors (t=2.450; P<0.05), and the power of lower limb (t=2.303; P<0.05) significantly increases. Health Related Quality of Life showed a significant improvement. Serum creatinine (1.4 ± 0.5 vs 1.3 ± 0.4 mg/dL) and proteinuria (0.10 ± 0.14 vs 0.08 ± 0.08 gr/dL) were stable. CONCLUSION: These preliminary results confirm the positive effects of supervised physical exercise. It can be considered as an input to promote other detailed exercise protocols.

Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

Prediction of three-year outcome of renal transplantation from optimal donors versus expanded criteria donors.

BACKGROUND/AIMS: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski's histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg's score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. METHODS: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0-1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). RESULTS: Karpinski scores 0-1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg's clinical score shows a good fit with medium-term outcome and Karpinski's score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski's score ≥7). CONCLUSIONS: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Effect of vitamin D receptor activator therapy on vitamin D receptor and osteocalcin expression in circulating endothelial progenitor cells of hemodialysis patients.

BACKGROUND: The effects of vitamin D receptor (VDR) and osteocalcin (OC) expression as well as VDR agonist (VDRA) therapy on circulating endothelial progenitor cells (EPCs) has not been elucidated yet. METHODS: We therefore analyzed EPCs in 30 healthy controls and 82 patients undergoing dialysis (no VDRA therapy: 28; oral calcitriol: 30, and intravenous paricalcitol, PCTA: 24). The percentage of EPCs (CD34+/CD133-/KDR+/CD45-) expressing VDR or OC, and VDR and OC expression defined by mean fluorescence intensity (MFI) were analyzed using flow cytometry. The in vitro effect of VDRAs was evaluated in EPCs isolated from each patient group. RESULTS: The percentage of VDR+ EPCs correlated positively with VDRA therapy and 25(OH)D, and negatively with diabetes, C-reactive protein, hemoglobin and osteopontin. VDR-MFI correlated positively with VDRA therapy, parathyroid hormone (PTH) and 25(OH)D, and negatively with diabetes and osteopontin. The percentage of OC+ EPCs correlated positively with the calcium score, PTH and phosphate, and negatively with 25(OH)D. OC-MFI correlated positively with calcium score, PTH, phosphate and hemoglobin, and negatively with albumin, 25(OH)D and osteopontin. Cell cultures from patients without VDRA therapy had the highest levels of calcium deposition and OC expression, which both significantly decreased following in vitro VDRA administration: in particular extracellular calcium deposition was only reduced by adding PCTA. CONCLUSIONS: Our data suggest that 25(OH)D serum levels and VDRA therapy influence VDR and OC expression on circulating EPCs. Since OC expression may contribute to vascular calcification, we hypothesize a putative protective role of VDRA therapy.

The relationship of NT-proBNP and dialysis parameters with outcome of incident haemodialysis patients: results from the membrane permeability outcome study.

BACKGROUND/AIMS: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. METHODS: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. RESULTS: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. CONCLUSIONS: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Thrombosis of tunneled-cuffed hemodialysis catheters: treatment with high-dose urokinase lock therapy.

Thrombosis-related malfunction of tunneled-cuffed central venous catheters (TCC) for hemodialysis (HD) currently leads to a high rate of untimely catheter removal. Urokinase (UK) therapy is used for TCC thrombosis/malfunction, but no consensus exists on the adequate dose to obtain thrombolysis. We selected 72 HD patients with TCC and a mean age and HD vintage of 74 years (range 65-87) and 36 months (range 12-61), respectively. All patients received warfarin therapy with a target international normalized ratio (INR) of 1.8-2.5. Coagulative assessment of the patients was obtained by checking the INR, activated partial thromboplastin time, fibrinogen, hemoglobin, and platelets. Sixty-five thrombotic events were recorded during a 3-year follow-up (median 0.3 events/patient/year). The patients selected were randomized into two groups according to a different thrombolytic therapy. Group A comprised 29 thrombotic events in 32 patients who received UK 25,000 IU in both arterial and venous lines of the TCC for each event. UK restored an adequate blood flow rate (BFR) for HD (≥ 250 mL/min) in 4/29 events (13.7%), whereas addition of 50,000 IU to both arterial and venous lines was required in 25/29 events (86.3%). For the same 25 events in the second HD session, a further 75,000 IU of UK was needed for each TCC lumen. Group B comprised 36 thrombotic events in 40 patients who received 100 000 IU of UK in the arterial and venous lumen of the TCC for each event. An adequate BFR was recovered in all events. In 12/36 events (33.3%), 100,000 IU UK for both lumens were needed in the second HD. In conclusion, group B patients obtained (i) a significantly better TCC patency than group A patients; (ii) a low UK administration in the following HD sessions; and (iii) no bleeding complications.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

Reduction of oxidative damage reflects a better kidney transplantation outcome.

BACKGROUND/AIMS: DNA fragmentation is one of the typical features of apoptosis, frequently induced by oxidative stress. Increased oxidative stress is known to be related to several pathological processes. In this study, we assessed oxidative damage in the early follow-up period after kidney transplantation measuring DNA oxidation and fragmentation of mononuclear cells and the circulating levels of inflammatory cytokines. METHODS: Blood samples from 30 kidney transplant recipients were collected before transplantation and after 2 days, 1 month and 6 months. Oxidative DNA fragmentation was measured by Comet Assay, whereas DNA oxidation was evaluated measuring 8-OHdG leukocyte levels. Serum IL-1ß, IL-4, IL-6, IL-8, IL-10, IFN-γ and TNF-α were assayed using a multiplex ELISA analysis. RESULTS: At 6 months after transplantation, a significant reduction in DNA fragmentation and IL-6 plasma levels was observed; DNA oxidation was higher in patients with a worse outcome, with delayed graft function and low nutritional status. We also found a correlation of IL-6 and IL-10 levels with DNA fragmentation and of IL-10 levels with DNA oxidation. CONCLUSION: Low levels of oxidation and apoptosis at 6 months after transplantation correlate with a better recovery of renal function in kidney allografts. The measurement of cytokine levels confirmed a reduction of inflammatory parameters within 6 months of follow-up.

Urinary neutrophil gelatinase-associated lipocalin at birth predicts early renal function in very low birth weight infants.

Preterm infants are exposed to conditions that can impair renal function. We evaluated the ability of serum and urinary neutrophil gelatinase-associated lipocalin (sNGAL and uNGAL) to predict renal function in the first weeks of life. From September 2008 to July 2009, infants weighing ≤1500 g at birth with no major congenital anomalies or sepsis were eligible. We measured sNGAL and uNGAL levels at birth. To evaluate renal function, we determined changes in serum creatinine (sCreat) and estimated GFR (eGFR) from birth to d 21. Forty neonates (mean GA, 27 ± 2 wk) completed the study. Renal function improved in 32 of 40 (80%) infants (normal renal function, NRF group) (sCreat, from 0.97 ± 0.2 to 0.53 ± 0.13 mg/dL; eGFR, from 15.3 ± 4.1 to 28.6 ± 7.9 mL/min), whereas renal function worsened in 8 of 40 (20%) infants (impaired renal function, IRF group) (sCreat, from 0.71 ± 0.27 to 0.98 ± 0.43 mg/dL; eGFR from 23 ± 14.7 to 16.4 ± 9.1 mL/min). The uNGAL/urinary creatinine (uCreat) ratio at birth was higher in the IRF group (31.05 ng/mg) than the NRF group (6.0 ng/mg), and uNGAL was significantly higher in IRF group, detecting IRF with a cutoff of 100 ng/mL. uNGAL levels at birth may have a predictive role in very LBW (VLBW) infants.

Effects of unfractioned heparin and low-molecular-weight heparin on osteoprotegerin and RANKL plasma levels in haemodialysis patients.

BACKGROUND: This randomized crossover study investigated the effects of unfractioned heparin (UFH) and low-molecular-weight heparin (LMWH) on intra- and post-dialytic blood levels of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL) and inflammatory cytokines. METHODS: Forty patients on haemodialysis for at least 12 months were selected. UFH or LMWH was randomly assigned and maintained for 1 month, and then, in the following month, each patient was switched to the other form of heparin. In the mid-week session, we determined the changes in anti-Xa activity, OPG, RANKL, IL-1ß, IL-6 and TNF-α values before heparin administration and after 15 min, 4, 8 and 24 h (T0, T1, T2, T3 and T4 respectively). Since these parameters at the various experimental times showed a non-normal distribution, log transformation was applied in order to run parametric ANOVA, with Bonferroni correction for multiple comparisons. RESULTS: The changes in anti-Xa activity over time were similar but not the same for the UFH and LMWH. A highly significant (P<0.001) increase in anti-Xa activity was detected at T1, regardless of the type of heparin, as confirmed in the comparison of T0 vs T1 using one-way ANOVA. Moreover, with both heparins, significant differences were found in the comparisons of anti-Xa activity at T1 vs T2 (both P<0.001) and at T2 vs T3 (P=0.0003 with UFH; P<0.001 with LMWH). Conversely, the difference in anti-Xa activity at T3 vs T4 was still significant with UFH (P=0.0186) but not significant with LMWH (P=0.728). When comparing anti-Xa activity at T4 vs T0, no significant differences were found either with UFH (P=0.1996) or with LMWH (P=0.7470), thus indicating that 24 h after heparin infusion, anti-Xa activity returned back to the pre-infusion values. When we analysed the changes in OPG levels over time, we found that the administration of heparin, regardless of the type, determined an increase in circulating OPG with a zenith at 15 min (T1), with a return back to the baseline levels within the 24th hour post-infusion. One-way ANOVA revealed significant differences in OPG blood levels at T0 vs T1 with both UFH (P=0.0112) and LMWH (P=0.0288), whereas no significant difference was observed in the comparisons of OPG levels at T1 vs T2, T2 vs T3, T3 vs T4 and T4 vs T0, either with UFH or with LMWH. The circulating levels of RANKL, IL-1ß, IL-6 and TNF-α at the different intra- and post-dialytic times did not show significant variations following heparin administration, either with UFH or with LMWH. One-way ANOVA performed on the log-transformed values of RANKL, IL-1ß, IL-6 and TNF-α at the various experimental times (T0 vs T1, T1 vs T2, T2 vs T2, T3 vs T4 and T4 vs T0) revealed no significant intra- and post-dialytic changes in their blood levels, thus confirming that heparin infusion did not affect their blood levels. CONCLUSIONS: These results suggest that heparin-regulated cyclic increases of OPG might play a role in the vascular pathology of haemodialysis patients.

Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. METHODS: One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. RESULTS: RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. CONCLUSIONS: This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

VDR expression on circulating endothelial progenitor cells in dialysis patients is modulated by 25(OH)D serum levels and calcitriol therapy.

BACKGROUND/AIMS: Vitamin D deficiency is associated with endothelial dysfunction in uremic patients, possibly by the impairment in the number and function of endothelial progenitor cells (EPCs). In 89 hemodialysis patients, we investigated the factors associated with the number of circulating EPCs (CD34+/CD133+/KDR+ and CD34+/CD133-/KDR+ cells), the presence of VDR and the determinants of VDR expression on EPCs, in particular in calcitriol therapy. METHODS: EPC counts, percentages of VDR-positive EPCs and VDR expression were assessed by flow cytometry. Cells isolated from a subgroup of patients were cultured to analyze colony-forming units, specific markers expression and a capillary-like structure formation. RESULTS/CONCLUSIONS: Our study demonstrates the presence of VDR on EPCs. In our dialysis patients, the parameters studied on both CD34+/CD133+/KDR+ and CD34+/CD133-/KDR+ cells, in particular VDR expression, seem to be influenced by uremia-related factors, including anemia, inflammation, diabetes, 25(OH)D serum levels and calcitriol therapy.

[Physical activity and renal transplantation]. / Attivita' fisica nei pazienti con trapianto di rene.

A sedentary lifestyle is an important risk factor leading to cardiovascular disease. Cardiovascular disease is particularly frequent in kidney transplant recipients, with a mortality rate of 38%. In this population, besides the classic risk factors (genetics, age, smoking, etc.) and disease-related factors (chronic renal failure, dialysis vintage) there are the side effects of immunosuppressive therapy such as diabetes and metabolic syndrome. Despite the general advice given on an appropriate lifestyle, most transplanted patients lead a sedentary life which may result in overweight. In this study the physiopathological effects of a sedentary lifestyle were analyzed with reference to the recent literature regarding the efficacy of physical activity in transplanted patients. Studies in the general population have demonstrated the beneficial effect of physical activity on the prevention of cardiovascular disease. There are only few studies within the kidney transplant population regarding regular physical activity and these studies were performed with heterogeneous protocols and different observation periods, and are therefore difficult to compare. Overall, positive results in terms of maximal aerobic capacity, muscle strength and perception of well-being have been obtained in the short and medium term (1 year). Further studies are necessary to verify the effect of physical activity on long-term patient and graft survival. In order to enhance physical activity in transplanted patients, local programs in collaboration with sports rehabilitation centers are to be recommended.

Tacrolimus combined with two different corticosteroid-free regimens compared with a standard triple regimen in renal transplantation: one year observational results.

Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up. Percentage of graft survival were 92.8%, 95.4%, and 95.9% (KM estimates 89.9%, 95.3%, 95.9%), percentage of surviving patients were 98.7%, 98.0%, and 100% (KM estimates 95.9%, 92.8%, and 100%). During months 7-12, graft loss occurred in 3 Tac/Bas, 2 Tac/MMF, and zero control patients, patient deaths in 1 Tac/Bas, 2 Tac/MMF, and zero control, and biopsy-proven acute rejection episodes in 4 Tac/Bas, 3 Tac/MMF, and zero control. Mean serum creatinine at month 12 was 141.9 +/- 69.6 microM, 144.0 +/- 82.1 microM, and 134.5 +/- 71.2 microM (ns). New-onset insulin use in previously non-diabetic patients at month 12 was 1/138, 6/127, and 4/126. Patient and graft survival as well as renal function at 12 months were not different between patient groups, despite considerably higher rates of acute rejection occurring within the first six months after transplantation in both steroid-free patient groups. Tac/Bas therapy might offer benefits in terms of a trend for a more favorable cardiovascular risk profile.

Risk for contrast nephropathy in patients undergoing coronarography.

Among the causes of in-hospital acute renal failure, contrast-induced nephropathy ranks third in prevalence. Although it represents a condition of renal impairment with spontaneous recovery, contrast nephropathy should always be considered, because it prolongs hospitalization and it may become a severe complication requiring dialysis. The purposes of this study are: (i) to determine if the application of the most effective contrast-induced nephropathy prevention strategies in the Cardiology Intensive Care Unit can prove to be successful in reducing nephropathy risk; and (ii) to identify which of the involved risk factors persist after the preventive treatment. We examined the patients who had a coronarography at the Bentivoglio hospital from April 2007 to April 2008 who required at least 3 days of permanence in hospital due to the presence of potential risk factors; 136 out of 784 patients were included. Among the selected patients, 21 (15.44%) developed a renal impairment compatible with contrast-induced nephropathy. The risk factors that seemed to display the best correlation with risk of contrast nephropathy were advanced age and an ventricular failure (ejection fraction <40%); however, the critical condition did not appear to be due to a single risk factor, but it resulted from the association of more contextual risk factors. Particularly, the concomitant presence of ventricular failure, anemia, diabetes, previous myocardial infarction and advanced age (>70 years) determined a threefold increased risk of contrast nephropathy. Our data suggest that the development of contrast nephropathy following coronarography is associated with worse renal function during hospitalization and at discharge.