Wacław Weyde

IL-18 is involved in vascular injury in end-stage renal disease patients.

BACKGROUNDnThe role of interleukin (IL)-6 and IL-18 in induction of the inflammatory reaction underlying arteriosclerosis, and protective effect of an anti-inflammatory cytokine IL-10 in this process, have been confirmed by experimental and clinical observations. A systemic inflammatory reaction marker, C-reactive protein (CRP), is known to be associated with the induction of IL-6 and IL-18 release. The chronic inflammatory state associated with renal insufficiency contributes to acceleration of arteriosclerosis, reflected by decreased elasticity which can be measured with aortal pulse wave velocity (PWV). It is well known that chronic kidney disease (CKD) is associated with the chronic inflammatory process, as evidenced by increase in CRP and IL-6 level. It also results in a drop of fetuin-A concentration which is the calcification inhibitor negatively regulated by inflammation. Part of the derangements associated with the progressive renal failure is also the rise of activated monocyte pool, which among others produces IL-18. The aim of the present study was to evaluate, through measurements of CRP, fetuin-A and aortal pulse wave velocity (aoPWV), whether IL-6 and IL-18 affect the arterial wall of CKD patients as a part of general inflammatory process or locally, through their effect on the arterial lesion development. Materials and methods. The study was performed in a group of 102 patients with stage V CKD (73 treated with haemodialysis and 29 treated with continuous ambulatory peritoneal dialysis) (CKD5 group) and in 30 healthy controls. We measured serum high-sensitivity C-reactive protein (hs-CRP), fetuin-A, IL-6, IL-18, IL-10 (ELISA) and others (haemoglobin level, white blood cell count, serum calcium, phosphate, calcium-phosphate product, albumin, fibrinogen, cholesterol, high-density lipoprotein (HDL), triglycerides and parathormone). ECG-gated carotid and femoral artery waveforms were recorded and analysed.nnnRESULTSnSerum levels of hs-CRP, IL-6, IL-10 and IL-18 were higher and fetuin-A levels were lower in the CKD5 group than in controls [6.4 (0.6-22.3) mg/dl versus 2.5 (0.5-5.2) mg/dl; 8.29 pg/ml (0.96-74.48)] versus 2.78 (7.91-0.77) pg/ml; 6.5 (3.7-29.7) pg/ml versus 4.1 (3.8-7.2) pg/ml; 254.4 (468.8-47.5) pg/ml versus 89.3 (91.3-27.5) pg/ml]. The aoPWV was higher in the CKD5 group patients than in the control group (9.4 +/- 1.75 m/s versus 7.76 +/- 1.67 m/s; P < 0.05, respectively). Serum fetuin-A level was negatively associated with hs-CRP and IL-6 but not with IL-18 or IL-10. The aoPWV positively correlated with hs-CRP (r = 0.246; P < 0.05), IL-6 and IL-18 (r = 0.220; P < 0.05) and negatively correlated with fetuin-A (r = -0.204; P < 0.05). No relationship between IL-10 and aoPWV was found. In a multiple regression analysis model respecting inflammatory markers the influence of hs-CRP, IL-18 and fetuin-A on aoPWV remained significant.nnnCONCLUSIONSnThe novel observations in the present study are the data indicating that the distinctive contribution of IL-18, but not IL-6, to the arteriosclerosis occurrence in CKD patients, is independent from CRP, fetuin A or other factors involved in the general inflammatory process.

Outcome of Autogenous Fistula Construction in Hemodialyzed Patients Over 75 Years of Age

Background: There are controversies regarding the feasibility of autogenous vascular access creation in elderly hemodialysis (HD) patients. The aim of this retrospective study was to evaluate the results of creating different types of autogenous arteriovenous fistulas (AVFs) in a consecutive series of HD patients over 75 years of age. Methods: The analysis was performed in 131 patients (65 females, 66 males, average age 79.1 ± 3.6 years) in whom the creation of an autogenous AVF was considered within a 6-year period (February 1998 to February 2004). Among them, 26.7%were diabetics, 66.3% had hypertension, 30.7% were smokers, and 35.6% were obese. Patient survival and primary and secondary AVF patency were assessed. Results: The survival rates for patients were 94, 88, 66, and 45% at 6 months and at 1, 3, and 5 years, respectively. Successful autogenous AVF formation was finally achieved in 107 patients (81.6%): in 99 patients in the forearm and in 8in the upper arm. A Kaplan-Meier analysis showed primary AVF patency rates of: 74 ± 4.3% (± SE) at 1 month; 70 ± 4.7% at 6 months; 59 ± 4.9% at 1 year; 59 ± 4.9% at 2 years; 59± 4.9% at 3 years; 59 ± 4.9% at 4 years, and 58 ± 4.9% at 5 years. The secondary patency rates were: 95 ± 2.0; 92 ± 2.2; 84 ± 3.3; 79 ± 4.0; 72 ± 4.3; 71 ± 4.4, and 69 ± 4.5% in the corresponding periods, respectively. All postoperative complications in 10 patients were treated surgically, if applicable, without endovascular techniques. Conclusions: By exploiting all suitable types of autogenous AVF it is possible to establish the best form of vascular access even in the majority of elderly patients.

The increased risk of post-transplant diabetes mellitus in peritoneal dialysis-treated kidney allograft recipients

BACKGROUNDnPost-transplant diabetes mellitus (PTDM) is a common metabolic complication in kidney allograft recipients, significantly contributing to the elevated cardiovascular morbidity after renal transplantation and increased risk of chronic transplant dysfunction. The aim of the present investigation was to evaluate the factors influencing PTDM development. Under particular consideration were the elements, existing before the transplantation, especially the modality of dialysis treatment significance, i.e. haemodialysis (HD) versus peritoneal dialysis (PD).nnnMETHODSnThree hundred and seventy-seven consecutive outpatients who underwent renal transplantation (RTx) in our institution between January 2003 and December 2005 were analysed. PTDM was diagnosed according to the current American Diabetic Association/World Health Organization criteria. Statistical inference was conducted by means of univariate methods (one factor versus PTDM) and multivariate methods in frames of generalized linear model.nnnRESULTSnIn the study group, 72 patients (23.4%) developed PTDM after RTx (55 HD and 17 PD patients). PTDM incidence at 3, 6 and 12 months was 15.9%, 22.1% and 23.4%, respectively. The mean interval from transplantation to the onset of PTDM was 3.08 ± 2.73 months. In univariate analysis, the factors associated with the elevated risk of PTDM appearance were older recipient age, positive family history of diabetes, hypertensive nephropathy as end-stage renal disease cause, higher body mass index at transplantation, treatment by PD, and the graft from an older donor. In multivariate verification, statistical significance remained: older recipient age (P < 0.001), positive family history of diabetes (P = 0.002), and treatment by PD (P = 0.007).nnnCONCLUSIONSnTreatment by PD appears to be a possible novel factor, not yet reported, which may increase the risk of PTDM development.

A program of physical rehabilitation during hemodialysis sessions improves the fitness of dialysis patients.

Aim: The aim of the present study was to evaluate the influence of cycle exercise during hemodialysis (HD) on patients’ physical proficiency, muscle strength, quality of life and selected laboratory parameters. Patients and Methods: In a group of 29 (15 female, 14 male) HD patients (age 64.2 ± 13.1 years), 3 months of cycle training during dialysis sessions was performed. The following data were analyzed: strength of lower extremities (six-minute walk test, isokinetic knee extension, flexion peak torque), nutrition parameters (albumin, BMI), inflammation intensity (CRP, IL-6), and quality of life (SF-36v2). Results: In the six-minute walk test, the increase in walk velocity was 4% (3.56 km/h before and 3.73 km/h after cycle training; p < 0.01). At angular velocity (AV) of 60°/s, extension peak torque in the knee joint rose by 7% and at AV of 300°/s by 4% (p = 0.04). Flexion peak torque at AV of 180°/s increased by 13% (p = 0.0005). The program does not influence nutrition or inflammation parameters. No complications directly related to exercise were observed. Conclusion: Cycle exercise during dialysis is safe even in older HD patients with multiple comorbidities. It results in a significant increase in general patient walking ability and in a gain in lower extremity muscle strength.

A new technique for autogenous brachiobasilic upper arm transposition for vascular access for hemodialysis.

Purpose Conventional brachiobasilic fistula creation consists of the mobilization and preparation of the brachial part of the basilic vein along its whole length, the vein transposition on the anterior surface of the arm and anastomosis using the brachial artery. In case of late thrombosis, the reparation of such a fistula is almost impossible. Methods To avoid total vein clotting in the case of thrombosis we decided to prepare only a short part of the vein in our method and not to mobilize the other part of the vein. The brachiobasilic fistula with our modification was performed as a two-stage procedure in 18 patients (8 females and 10 males), aged from 37–78 yrs (60 ± 13.6 yrs). Results In two patients early thrombosis occurred. The reparation procedure was not performed in two patients (the first patient died due to pneumonia; the second patient did not give his permission for further intervention). In 16 patients brachiobasilic fistula creation was successful. Late thrombotic complications occurred in three patients (in the 3rd, 8th and 12th months). A new successful fistula, a few centimeters proximally to the original one, was performed in 2 patients 24hr and in 1 patient 48hr after fistula clotting. On the following day after the procedure the fistula was ready to be used. The primary, assisted primary and cumulative secondary patency rates after 12 months of follow-up were 74, 89 and 100%, respectively. Conclusion In comparison with standard brachiobasilic techniques our method offers the possibility of a reparation procedure in the case of late thrombosis, which could improve the long-term patency of brachiobasilic fistulas. However, a prospective controlled study is necessary to establish if this new technique is superior to the traditional surgical procedure.

Creation of arteriovenous fistulae for hemodialysis in octogenarians.

Elderly patients, defined as octogenarians and nonagenarians, are an increasing population entering renal replacement therapy. Advanced age appears as an exclusive factor negatively influencing dialysis practice. Elderly patients are referred late for the initiation of hemodialysis and more likely are offered catheters rather than arteriovenous fistulae (AVF), which increase mortality and negatively affect quality of life. We present our approach to the creation of vascular access for hemodialysis in this demanding population. In 2006–2012, 39 patients aged 85.9u2009±u20092.05 with end‐stage renal disease, mainly resulting from ischemic nephropathy, were admitted to the Department of Nephrology to establish permanent vascular access for hemodialysis: preferably AVF. Temporary dialysis catheters were implanted in uremic emergency to bridge the time to fistula creation/maturation. AVF was attempted in 87.2% of the patients. Primary AVF function was achieved in 54% of the patients. Cumulative proportional survival of AVF at months 12 and 24 was 81.5%. Ninety‐four percent of AVF were localized on the forearm: 74% in the distal and 20% in the proximal part. Mean duration of hemodialysis therapy was 20.80u2009±u200919.45 months. The mean time of AVF use was 15.9u2009±u200920.2 months. Until present, 38% have been dialyzed using AVF for 31.0u2009±u200918.8 months. Five patients died with functioning fistula. Eight patients initiated hemodialysis therapy with fistula. During further observation, the use of AVF increased to 62%. Elderly patients should not be denied creation of AVF as a rule. The outcome of AVF benefits more from acknowledging individual vascular conditions rather than age of the patient.

Increased Aortic Wall Stiffness Associated with Low Circulating Fetuin A and High C-Reactive Protein in Predialysis Patients

Background/Aims: Vascular calcification and arterial stiffening are cardiovascular risk factors among chronic kidney disease (CKD) patients. The aim of the study was to analyze relationships between inflammatory markers, fetuin A and arterial wall stiffness in CKD patients in the predialysis period and on maintenance dialysis. Methods: Serum C-reactive protein (hs-CRP), fetuin A, interleukin 6 (IL-6) and other classical markers of atherosclerosis were measured in a group of 155 CKD patients (77 on hemodialysis, HD, 29 on peritoneal dialysis, 49 in CKD stage 5 in the predialysis period) and in 30 healthy volunteers. The aortic pulse wave velocity (aoPWV) was recorded using a tonometric method. Results: The aoPWV, serum hs-CRP and IL-6 were higher and fetuin A levels were lower in all CKD groups than in controls. In multiple regression analysis, the age appeared as the strongest, independent factor increasing arterial wall stiffness in all investigated groups, including controls, whereas the association of aoPWV with IL-6 and fetuin A remained significant only in HD patients. Conclusions: Aortic wall stiffness is higher in CKD patients than in controls, and it already develops in the predialysis period. Age is the principal determinant of arterial wall stiffness also in CKD patients. The acceleration of arterial wall stiffness in CKD is associated with additional factors, i.e. fetuin A deficiency and higher CRP and IL-6.

Arteriovenous fistula reconstruction in patients with kidney allograft failure

Abstract:u2002Background:u2002 Kidney recipients with failing allograft function face the vascular access problem again before returning to hemodialysis. An autologous arteriovenous fistula (AVF), according to the recent Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, is the optimal vascular access and the use of prosthetic grafts and catheters should be limited. The objective of this study was to assess the feasibility of AVF reconstruction in patients reentering hemodialysis after kidney allograft failure.

Impact of Donor-Dependent Genetic Factors on Long-Term Renal Graft Function

Our aim was to study the association of donor genetic features with long-term graft function as well as the impact of donor age, gender compatibility, cold ischemia time (CIT), and delayed graft function (DGF). We observed the outcomes of 125 kidney recipients for a minimum of 12 months (mean, 30.9 +/- 13.0 months). Grafts were obtained from 89 donors who underwent profiling for AHSG 1/2, MMP9 -1562C/T, IL6 -174G/C, IL1beta 3954C/T, MTHFR 677C/T, MTHFR 1298A/C, NOS3 -786C/T, and PAI1 4G/5G single-nucleotide polymorphisms (SNPs) using sequence-specific probe (SSP) polymerase chain reaction (PCR) and MPO -463G/A and CRP -390C/T/A with restriction fragment length polymorphism (RFLP) analysis. NOS3 IVa/b VNTR polymorphism was genotyped by gel electrophoresis of the respective PCR-generated DNA fragment. The presence of the aa eNOS genotype was connected with worse graft function. The aa genotype was also linked to acute rejection episodes. The lowest values of glomerular filtration rate (GFR) were displayed by recipients of grafts from donors with homozygotic PAI1 gene 5G polymorphism, linking paradoxically with lower PAI-1 synthesis suggesting that the intensity of proteolysis led to increased alloantigen specificity stimulating alloresponses. Graft function depended significantly on donor age with an influence of gender matching. GFR showed a significant dependence on DGF. Genetic features of the donor influenced long-term graft function. Variant eNOS gene polymorphism, which produced decreased eNOS activity, was linked to worse remote graft function. A similar negative impact was observed in the case of donor PAI1 polymorphism, with the functional consequence of lower gene product synthesis.

Elderly dialysis patients: analysis of factors affecting long-term survival in 4-year prospective observation.

PurposeTo assess factors influencing the long-term survival of elderly dialysis patients.MethodsThe study group consisted of 51 prevalent dialysis patients aged over 70xa0years (32 F and 19xa0M, all caucasians), who had been on a chronic hemodialysis (27) or peritoneal dialysis program (24) for at least 2xa0months; median age was 77xa0years, median time on dialysis before inclusion was 16xa0months, and median residual diuresis was 600xa0ml. The patients were prospectively followed up to 4xa0years, and an analysis of factors affecting survival was performed.ResultsThirteen patients from the initial cohort of 51 (25.5xa0%) survived the whole 48-month observation period: 10 HD patients (37xa0%) and 3 PD patients (12.5xa0%). Annual mortality rate was 28.2xa0%: 37.4xa0% on PD vs. 20.9xa0% on HD. The dialysis modality had a significant impact on patients’ survival (pxa0=xa00.049; Cox F-test). The independent mortality risk factors in the Cox proportional hazard regression model were higher plasma pro-atrial natriuretic peptide (pro-ANP) (pxa0=xa00.006), lower residual diuresis (pxa0=xa00.048), and lower systolic blood pressure (BP) value (pxa0=xa00.039).ConclusionsParamount for the survival of the elderly on dialysis is adequate extracellular volume control. Residual renal function is a protective factor for the survival of elderly HD patients. This observation is novel, not previously reported in an elderly dialysis population.