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Background and Purpose Laparoscopic donor nephrectomy (LDN) has been associated with delayed graft function compared with open donor nephrectomy (ODN). We have recently shown that the adverse effect of pneumoperitoneum (PP) on hemodynamics could be prevented by a new fluid regime. The aim of this study was to test the effect of this fluid regime on the kidney function of the donor and recipient after LDN and ODN.Patients and Methods We prospectively collected data of 51 donors undergoing ODN and 59 donors undergoing LDN as well as data from the corresponding recipients. All donors and recipients were treated with a standardized anesthesia and fluid regime. This fluid regime consisted of preoperative overnight hydration together with a bolus of colloid administered before induction of anesthesia and before introduction of PP. Follow-up was 2 years.Results Baseline characteristics of the two groups were comparable. Hemodynamics and urine output until nephrectomy were comparable between both groups. Donor kidney function did not differ after ODN and LDN. Estimated glomerular filtration rate, graft survival, and recipient survival did not differ between open and laparoscopically procured transplants. No adverse effects of the novel fluid regime (eg, pulmonary edema or additional oxygen supply) were observed in the donors.Conclusion In contrast to our earlier findings, the kidney function of the donor and recipient is comparable between ODN and LDN after introduction of a new fluid regime. [ABSTRACT FROM AUTHOR]

Background. Human leukocyte antigen (HLA)-identical living-related (LR) kidney transplant recipients often receive the standard regimen of immunosuppression. We wondered whether these patients should be exposed to the side effects of these drugs any longer. Safe tapering of immunosuppression should not result in rejection and high donor-directed T-cell responses. In the present study, we investigated the effect of tapering azathioprine (AZA) on T-cell reactivity.Methods. Fifteen HLA-identical LR kidney transplant recipients receiving a median of 150 mg/day AZA and 5–10 mg/day prednisone were tapered to a median of 50 mg/day AZA. Donor-, third-party and tetanus toxoid (TET)-reactivity were determined in interferon (IFN)-γ and interleukin (IL)-13 Elispot assays, which reflect the T-helper (Th)1 and T-helper (Th)2 response.Results. After the tapering of AZA, none of the patients developed acute rejection and the renal function remained stable, even at 1-year follow-up. The frequency of donor-specific IFN-γ and IL-13 producing cells (pc) was low. Tapering of AZA did not influence the frequency of both IFN-γ and IL-13 pc. Also, the reactivity against third-party cells and TET remained unchanged.Conclusions. The AZA-dose can be safely reduced in recipients of an HLA-identical LR kidney transplant without affecting kidney function and without increasing T-cell responses directed against donor or other antigens. [ABSTRACT FROM AUTHOR]

Background. Hypotension during haemodialysis results from an inadequate cardiovascular response to ultrafiltration-induced hypovolaemia. It has been suggested that plasma volume could be increased as a result of systemic vasoconstriction.Methods. We studied the effect of a norepinephrine (NOR) infusion (30 min), compared with no infusion, on relative blood volume (RBV) in six haemodialysis patients. During infusion we measured RBV, systolic blood pressure (SAP), heart rate (HR), stroke volume index (SI), total peripheral resistance (TPRI), ejection fraction (EF), inferior vena cava diameter (VCD) and core temperature.Results. At the end of the NOR infusion, we observed a significant increase in TPRI (47±47% vs 4±17%; P<0.01) and SAP (27±12% vs 0±8%; P<0.01). Norepinephrine-induced vasoconstriction resulted in a significant decrease in RBV (–9±3% vs 0±1%; P<0.01). No significant changes were seen in SI (–4±21% vs 0±8%), HR (–5±19% vs –4±5%), EF (7±14% vs –2±10%), VCD or temperature.Conclusions. We conclude that norepinephrine-induced vasoconstriction results in a decrease in RBV. This indicates that improved haemodynamic stability during haemodialysis through vasoconstriction can be accompanied by a decrease in RBV and that part of the variability in blood volume may be due to changes in arterial tone. Such changes must be taken into account if RBV measurements are used to improve the haemodynamic tolerance of dialysis. [ABSTRACT FROM AUTHOR]

Chemokines and their receptors have been implicated in the pathogenesis of different forms of heart failure (HF). We examined CC- and CXC-chemokine receptor expression in fresh peripheral blood leukocyte populations from 24 end-stage HF patients consisting of coronary artery disease (CAD; n = 6) and hypertrophic cardiomyopathy (HCM; n = 7) or idiopathic dilated cardiomyopathy (IDCM; n = 8) or valvular disease (VD; n = 3) and compared the data with 18 healthy controls. Levels of CCR1, 2, 3, 4, 5, and 7, and CXCR1, 2, 3, and 4 were measured by flow cytometry, and the expression profile was assessed as molecules of equivalent soluble fluorochrome units as well as frequency (percentage) of CD3+, CD4+, and CD8+ T cells and monocytes or granulocytes. Frequency of CD3+ CXCR4+, CD3+ CXCR1+, and CD3+ CXCR3+ cells was significantly increased in HF patients, whereas only CCR7 and CXCR4 expression levels were elevated on CD3+ cells. Both CD4+ CXCR4+ and CD8+ CXCR4+ cell frequencies were significantly increased irrespective of cardiac disease etiology. Elevated CCR7 expression was less pronounced on CD4+ than CD8+ cells in patients with CAD and IDCM. Expression of CXCR4 on CD8+ cells was upregulated substantially, regardless of the cause of disease. CD8+ CXCR1+ and CD8+ CXCR3+ but not CD4+ CXCR1+ or CD4+ CXCR3+ cells were increased in the HF patients with IDCM and CAD, respectively. Expression of CXCR1 or CXCR3 on both CD4+ and CD8+ cells did not differ in all the groups. For monocytes, frequency of CD14+ CCR1+ and CD14+ CCR2+ cells was significantly decreased in CAD patients, whereas, increase in CD14+ CXCR4+ cell frequency was accompanied with elevated CXCR4 expression. On granulocytes, CXCR1 and CXCR2 receptors were downregulated in all patients, compared with controls. Our results suggest that the altered expression profile of CC- and CXC-chemokine receptors on circulating leukocyte populations involves enhanced activation of the immune system, perhaps as part of the pathogenic mechanisms in HF. Modulation of the chemokine network could offer interesting novel therapeutic modalities for end-stage HF. [ABSTRACT FROM AUTHOR]

Background. LV systolic dysfunction in dialysis patients has been implicated in the genesis of dialysis hypotension. End-systolic elastance (Ees), a relatively load-independent parameter of myocardial contractility, was assessed by testing the acute left ventricular (LV) response to nitroglycerine (NTG) in hypotension-prone (HP) and hypotension-resistant (HR) patients.Methods. Routine measurement of ejection fraction (EF) was done before dialysis in 15 patients without significant valvular disease or symptoms of coronary heart disease. Continuous arterial pressure was measured by Finapres, with systolic blood pressure (SBP) as surrogate for LV end-systolic pressure. Simultaneously, LV area was measured using automated border detection. SBP and LV area data were combined online to create pressure–area loops in real time following intravenous NTG bolus. Ees was determined offline by beat-to-beat analysis of consecutive pressure–area loops.Results. SBP, at baseline 168 mmHg (128–188 mmHg), decreased to 127 mmHg (79–161 mmHg). End-systolic LV area, at baseline 6 cm2 (1–12 cm2), decreased to 4 cm2 (1–10 cm2). Ees in the HP group (11 mmHg cm−2; 7–22 mmHg cm−2) was not different from Ees in the HR group (9 mmHg cm−2; 4–16 mmHg cm−2). EF was 61% (45–73%). There was no correlation between Ees and EF.Conclusions. In this population of dialysis patients without clinically manifest heart disease, the HP and HR groups had a similar Ees. Therefore, these two types of dialysis patients were not distinguished by a difference in myocardial contractility. The results of this study argue against a role for reduced myocardial contractility in the genesis of intradialytic hypotension. [ABSTRACT FROM AUTHOR]

Background. The mechanisms underlying the immunodeficiency of chronic kidney disease (CKD) are incompletely understood. Recently, we described decreased numbers of myeloid (m) and plasmacytoid (p) dendritic cells (DCs), considered the most important antigen-presenting cells, in peripheral blood of patients on chronic intermittent haemodialysis (CIHD). In this study, we analysed whether this reduction resulted from CKD or from renal replacement therapy (RRT).Methods. Using flowcytometry, we quantified mDCs and pDCs in peripheral blood of patients maintained on CIHD (n = 37), continuous ambulatory peritoneal dialysis (CAPD; n = 29), and patients with CKD not receiving RRT (n = 37). Twenty-nine healthy volunteers served as controls.Results. Patients with CKD (n = 103) had lower pDC and mDC counts compared with volunteers: 4.2 vs 8.3 and 10.0 vs 13.8×106 cells/l, respectively (P ≤ 0.001). Within the CKD group, pDC counts did not differ between patients on CIHD, CAPD and those not receiving RRT (3.6 vs 5.0 vs 4.9×106 cells/l, respectively). In the latter group, pDC numbers correlated with the glomerular filtration rate (GFR; Spearman's r = 0.49; P<0.01). In contrast, mDC counts of patients on CIHD were lower compared with patients on CAPD (7.5 vs 10.1×106 cells/l; P = 0.039) and patients not receiving RRT (13.7×106 cells/l; P<0.001). Among non-dialyzing patients, no correlation existed between GFR and mDC numbers, which were comparable to those of volunteers, even when only non-dialyzing patients with a GFR below 15 ml/min were analysed.Conclusions. Circulating DC counts are decreased in patients with CKD; for pDCs, this reduction is primarily related to the loss of GFR, whereas the dialysis treatment appears to affect mDC numbers. [ABSTRACT FROM AUTHOR]

Background. Prevention of alloreactivity by rabbit anti-thymocyte globulins (rATG) may not only result from immunodepletion but also from the induction of T cells that control allogeneic immune responses. In the present prospective and controlled study, we investigated the effect of rATG on the frequency, function and phenotype of peripheral immunoregulatory CD4+ T cells in kidney transplant (KTx) patients. Methods. After transplantation, 16 patients received ATG-induction therapy and triple therapy consisting of tacrolimus, MMF and steroids. The control group (n = 18) received triple therapy only. By flow cytometry, T cells were analysed for CD25, FoxP3, CD127, CD45RO and CCR7. To study their suppressive capacities, CD25bright T cells were co-cultured with CD25−/dim effector T cells (Teff) in mixed lymphocyte reactions (MLR), stimulated with donor and third party (3P) antigens. Results. Pre-transplant levels of FoxP3+CD127−/low T cells were 6% of CD4+ T cells. One week post-ATG treatment, no measurable numbers of regulatory T cells were present (P P P P = 0.01 and P = 0.02 respectively), while the regulatory capacity of the CD25bright T cells, of which 90% consisted of FoxP3+CD127−/low T cells, remained unaffected. The CD25bright T cells suppressed the anti-donor (94%) and 3P responses (93%). Conclusion. Our findings show that rATG therapy does not spare peripheral immunoregulatory T cells in vivo, but after regeneration preserves their suppressive activity. [ABSTRACT FROM AUTHOR]

Background. After HLA-identical living-related (LR) kidney transplantation, only non-HLA antigen mismatches between donor and recipient may exist. We questioned whether donor-reactive responses against non-HLA antigens could be found after HLA-identical LR kidney transplantation, and wondered whether donor reactivity in the HLA-identical setting was different from the HLA-mismatched setting during immunological quiescence. Healthy individuals served as controls. Methods. Elispot assays were performed to determine the number of alloreactive IFN-γ-producing cells (pc), IL-10 pc, granzyme B (GrB) pc and IL-13 pc from peripheral blood mononuclear cells (PBMC) of HLA-identical, HLA-mismatched LR kidney transplant recipients and healthy individuals. Results. The frequency of alloreactive IFN-γ pc, IL-13 pc and GrB pc was higher in healthy individuals compared to both transplant patient groups. In the HLA-identical group, significantly higher numbers of donor-reactive IL-10 pc were found compared to their autologous control. These frequencies were also higher compared to the HLA-mismatched and healthy control group. The number of donor-reactive GrB pc was higher in the HLA-mismatched group than in the HLA-identical group. Donor-reactive IFN-γ pc and IL-13 pc were comparable in both transplant groups. Conclusions. In recipients of HLA-identical LR kidney transplant, high donor-reactive IL-10 pc, in combination with low donor-reactive IFN-γ pc, IL-13 pc and GrB pc, suggests active downregulation of reactivity against non-HLA molecules. [ABSTRACT FROM AUTHOR]