Katarzyna Madziarska

Mycophenolate mofetil severely depresses antibody response to CMV infection in early posttransplant period

Estimation of anti-CMV-IgG and anti-CMV-IgM is considered a relatively inexpensive screening tool of CMV status. The aim of study was to estimate how the immunosuppressive protocol influence serum anti-CMV IgG and IgM concentration in renal graft recipients and to estimate the adequacy of anti-CMV-IgG concentration and anti-CMV-IgM index as screening parameters of active CMV disease in patients receiving different immunosuppression. The study group consisted of 33 patients with clinical signs of CMV disease who received one of three types of immunosuppression: (1) azathioprine (Aza) + cyclosporine (CyA) + prednisone (Pr), 20 patients; (2) mycophenolate mofetil (MMF) + CyA + Pr, eight patients; tacrolimus (Tac) + MMF, five patients. Patients were enrolled when the pp65-antigen (pp65) of PBL was positive within 1 to 5 months after transplant (75 patients tested). The IgM-i in the Aza + CyA + Pr group was higher than in MMF + CyA + Pr group (2.73 + 1.8 vs 1.08 +/- 1.07, P =.021). The IgM-i in the Aza + CyA + Pr group was higher than in Tac + MMF (2.73 +/- 1.8 vs 0.78 +/- 0.69; P =.014). There was no difference in IgM-i between MMF + CyA + Pr and Tac + MMF. There was no difference in relative increase of IgG-c among all groups but there was a difference in relative increase of IgM-i between Aza + CyA + Pr and MMF + CyA + Pr groups (6.7 +/- 9.4 vs 2.3 +/- 5.9; P =.007) and between Aza + CyA + Pr and MMF + Tac groups (6.7 +/- 9.4 vs 0.6 +/- 0.54; P =.003). Immunosuppressive protocols including MMF exert an inhibitory influence on B-cell response and synthesis of anti-CMV-IgM. It makes the anti-CMV-IgM index an inadequate rough screening diagnostic parameter of active CMV disease.

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

BACKGROUND Post-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). METHODS Three 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. RESULTS In 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). CONCLUSIONS Treatment 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.

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 85.9 ± 2.05 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 20.80 ± 19.45 months. The mean time of AVF use was 15.9 ± 20.2 months. Until present, 38% have been dialyzed using AVF for 31.0 ± 18.8 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.

Arteriovenous fistula reconstruction in patients with kidney allograft failure

Abstract: Background:  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.

Advanced age of renal transplant recipients correlates with increased plasma concentrations of interleukin-6, chemokine ligand 2 (CCL2), and matrix metalloproteinase 2, and urine concentrations of CCL2 and tissue inhibitor of metalloproteinase 1.

BACKGROUND Advanced age of renal transplant recipients (RTRs) has a negative impact on kidney allograft survival through impaired extracellular matrix degradation by the matrix metalloproteinases/tissue inhibitors of metalloproteinases (MMPs/TIMPs) system. Moreover, older RTRs are at risk of smoldering inflammation, known as inflammaging. AIM The aim of the study was to assess the impact of a RTRs age on plasma and urine concentrations of interleukin 6 (IL-6), chemokine ligand 2 (CCL2), and the MMPs/TIMPs system. MATERIAL AND METHODS One hundred fifty adult RTRs (8.7% ≥ 65 years) and 37 adult healthy volunteers (10.8% ≥ 65 years) were enrolled in the study. The studied factors (IL-6, CCL2, MMP-2, MMP-9, TIMP-1 and TIMP-2) were quantified in plasma and urine with enzyme-linked immunosorbent assay. The Mann-Whitney U test and Spearmans (rs) rank correlation were applied, and differences with a P < .05 were considered statistically significant. RESULTS There was a weak but significant positive correlation between increasing RTRs age and plasma IL-6 (rs = 0.18, P = .028), CCL2 (rs = 0.27, P = .001), and MMP-2 (rs = 0.20, P = .017), as well as urine CCL2 (rs = 0.16, P = 0.050) and TIMP-1 (rs = 0.20, P = .014) concentrations. CONCLUSIONS Advancing age of RTRs correlates with increasing plasma IL-6 and CCL2 concentrations, reflecting smoldering inflammation (known as inflammaging) and alterations in MMPs/TIMPs profiles, especially with increased plasma MMP-2 and urine TIMP-1 concentrations.

Superficialization of the radial artery – an alternative secondary vascular access

Purpose The standard approach in patients with a clotted arteriovenous fistula (AVF) on the forearm is the creation of another vascular access on the arm using the patients own vessels or a prosthetic graft. Here we propose another option as secondary angioaccess for chronic hemodialysis (HD): superficialization of the radial artery. Methods Indications for the procedure were 1) long-standing forearm AVF that has irreversibly clotted and/or central vein stenosis resistant to angioplasty; 2) patients who have no other prospect for forearm or even brachial AVF. The procedure was undertaken in 7 chronic HD patients dialyzed by forearm AVF for 27±26 months. Results In one case the superficialization was abandoned intra-operatively due to small diameter of the artery (<4 mm). Five of 6 elevated arteries were patent and the follow-up period ranges from 11 to 15 (median 12) months. In 1 male patient with prothrombin G20210a mutation the artery clotted after 13 months of usage. Conclusions Superficialized radial artery was successfully used for hemodialysis over one year. The only prerequisite for safe repeated puncture is a patent and enlarged radial artery. Due to avoidance of arteriovenous shunt this access type may be particularly suitable for patients with cardiac failure.

Balloon Dilatation for Removal of an Irretrievable Permanent Hemodialysis Catheter: The Safest Approach.

Long-term hemodialysis catheter dwell time in the central vein predisposes to fibrin sheath development, which subsequently causes catheter malfunction or occlusion. In very rare cases, the catheter can be overgrown with fibrin and rigidly connected with the vein or heart structures. This makes its removal almost impossible and dangerous because of the possibility of serious complications, namely vein and heart wall perforation, bleeding, or catheter abruption in deep tissues. We describe two cases in which standard retrieval of long-term catheters was not possible. Balloon dilatation of catheter lumens was successfully used to increase the catheter diameter with simultaneous tearing of the fibrin sheath surrounding it. This allowed the catheter to be set free safely. Based on this experience, we present recent literature and our point of view.

The effect of high-tone external muscle stimulation on symptoms and electrophysiological parameters of uremic peripheral neuropathy.

OBJECTIVE AND DESIGN Peripheral neuropathy is a devastating uremic complication that causes debilitating pain and movement limitation. The aim of the study was to assess the influence of high-tone external muscle stimulation (HTEMS) therapy on clinical and electrophysiologycal parameters in hemodialysis patients with uremic peripheral neuropathy. PATIENTS AND INTERVENTIONS The study group consisted of 28 chronic hemodialysis patients (mean age 71.6 ± 8.6 y, median 74 y) on maintenance dialysis for 3 - 187 months (median 31 months). Eight persons (28.9%) were diabetics. All of them exhibited overt peripheral neuropathy and had undergone pharmacological therapy without improvement. All subjects were treated with HTEMS for 1 h during a hemodialysis session, 3 times weekly for 12 weeks. The dialysis parameters (duration of the session, blood and dialysate flow) were constant during the treatment period. Electrophysiological evaluation before and after intervention included assessment of sensory nerves (ulnar nerve, sural nerve) and motor nerves (ulnar nerve, peroneal nerve). The examined nerve conduction parameters were conduction velocity, amplitude, distal latency and F-wave latency. RESULTS In the questionnaire 18 persons (64%) reported improvement of general well-being after HTEMS therapy, 17 persons (61%) felt an increase of physical capacity, and 16 persons (57%) experienced a decreased feeling of cold feet. The electrophysiological findings were obtained in 19 patients who completed the examination before and after the course of HTEMS. A significant improvement was noted in the motor conduction velocity of the ulnar nerve; respective values were 48.53 ± 6.14 vs. 51.50 ± 5.51 m/s, p = 0.03. CONCLUSION The study demonstrated for the first time that the subjective amelioration of uremic peripheral neuropathy by HTEMS treatment is associated with significant improvement in an objective electrophysiological parameter, motor conduction velocity of the ulnar nerve.