A case-control study indicates that coagulation imbalance is associated with arteriosclerosis and markers of endothelial dysfunction in kidney failure.

Endothelial dysfunction, one of many causes of arterial changes in end-stage kidney disease (kidney failure), is a likely link between early vascular aging and the risk of thrombosis or bleeding in this condition. To evaluate this, we compared links between arterial stiffness and endothelial/coagulation factors in 55 patients receiving hemodialysis therapy and 57 age-/sex-matched control individuals. Arterial stiffness was assessed from carotid-femoral pulse wave velocity, and coagulation status from the endogenous thrombin generating potential. Markers of endothelial dysfunction (von Willebrand factor, tissue factor pathway inhibitor), neutrophil extracellular traps and tissue factor-positive extracellular vesicles were higher in patients with kidney failure. Prothrombin fragments 1 and 2, and D-dimer markers of in vivo coagulation activation were also higher. However, in vitro in the presence of platelets, endogenous thrombin generating potential was lower and its downregulation by activated protein C impaired. Antiplatelet drugs did not affect these parameters. In multiple regression analysis, prothrombin fragments 1 and 2, D-dimer, factor VIII and monocyte-derived tissue factor-positive extracellular vesicles correlated with higher carotid-femoral pulse wave velocity. In patients with kidney failure, in vivo hypercoagulability occurred with reduced thrombin generation in platelet-rich plasma, likely explaining the opposing thrombotic and bleeding tendencies in patients with kidney failure. Importantly, arteriosclerosis is more closely related to a prothrombotic state. Thus, coagulation changes plus arterial stiffness highlight a major therapeutic challenge for anticoagulant and antiplatelet drug use.

Kidney graft dysfunction in simultaneous pancreas-kidney recipients after pancreas failure: analysis of early and late protocol biopsies.

BACKGROUND: Kidney graft survival in simultaneous pancreas-kidney (SPK) recipients is known to decrease after pancreas graft failure. METHODS: Sixty-three consecutive SPK recipients were retrospectively reviewed. Kidney graft function and proteinuria were evaluated at three months after the transplantation and at last follow-up. Histopathologic findings of protocol biopsies performed three months and one yr after transplantation were analyzed. RESULTS: Twelve patients lost the pancreas graft. Donors' characteristics were similar in patients with or without pancreas failure. After a median follow-up of 36 months, mean eGFR with a functional pancreas was 69.5 mL/min/1.73 m² vs. 56.3 mL/min/1.73 m² (p = 0.01) after pancreas loss. Patients who lost pancreas had a median proteinuria of 0.28 g vs. 0.13 g per 24 h (p = 0.02). Analysis of three-month protocol biopsies revealed more frequent isolated glomerulitis after pancreas failure (p = 0.0001), without peritubular capillaritis or C4d deposition. No donor-specific anti-HLA antibodies were detectable in these patients. Chronic tubulointerstitial changes were more frequent in patients with pancreas loss. There was no evidence of diabetic nephropathy recurrence. CONCLUSION: SPK recipients develop an early kidney graft dysfunction after pancreas failure. Histopathologic findings revealed frequent glomerulitis without antibody-mediated rejection and early chronic changes.

Two Years' Experience of Intensive Home Hemodialysis with the Physidia S3 System: Results from the RECAP Study.

The RECAP study reports results and outcomes (clinical performances, patient acceptance, cardiac outcomes, and technical survival) achieved with the S3 system used as an intensive home hemodialysis (HHD) platform over a three-year French multicenter study. Ninety-four dialysis patients issued from ten dialysis centers and treated more than 6 months (mean follow-up: 24 months) with S3 were included. A two-hour treatment time was maintained in 2/3 of patients to deliver 25 L of dialysis fluid, while 1/3 required up to 3 h to achieve 30 L. The additional convection volume produced by means of the SeCoHD tool (internal filtration backfiltration) was 3 L/session, and the net ultrafiltration produced to achieve dry weight was 1.4 L/session. On a weekly basis, an average 156 L of dialysate corresponding to 94 L of urea clearance when considering 85% dialysate saturation under low flow conditions was delivered. Such urea clearance was equivalent to 9.2 [8.0-13.0] mL/min weekly urea clearance and a standardized Kt/V of 2.5 [1.1-4.5]. The predialysis concentration of selected uremic markers remained remarkably stable over time. Fluid volume status and blood pressure were adequately controlled by means of a relatively low ultrafiltration rate (7.9 mL/h/kg). Technical survival on S3 was 72% and 58% at 1 and 2 years, respectively. The S3 system was easily handled and kept by patients at home, as indicated by technical survival. Patient perception was improved, while treatment burden was reduced. Cardiac features (assessed in a subset of patients) tended to improve over time. Intensive hemodialysis relying on the S3 system offers a very appealing option for home treatment with quite satisfactory results, as shown in the RECAP study throughout a two-year follow-up time, and offers the best bridging solution to kidney transplantation.

Preliminary results of transplantation with kidneys donated after cardiocirculatory determination of death: a French single-centre experience.

BACKGROUND: Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been re-introduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. METHODS: Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. RESULTS: From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 ± 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsy-proven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate ( Modification of Diet in Renal Disease formula) was 48 ± 16 mL/min/1.73 m(2) at 1 year and 48 ± 15 mL/min/1.73 m(2) at the last follow-up. CONCLUSIONS: DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.

Pulsatile perfusion preservation for expanded-criteria donors kidneys: Impact on delayed graft function rate.

PURPOSE: Expanded criteria donors (ECD) kidneys are a potential solution to organ shortage, but exhibit more delayed graft function (DGF). We conducted a prospective controlled study aiming to evaluate the impact of pulsatile perfusion preservation (PPP) on DGF rate. METHODS: Inclusion criteria were: 1) ECD definition (any brain-dead donor aged > 60 years or aged 50-60 years with at least 2 of the following: history of hypertension, terminal serum creatinin level = 1.5 mg/dL, death resulting from a cerebrovascular accident; 2) Donor prolonged circulatory arrest (> 20 mn); 3) previsible cold ischemia time longer than 24 hours. In each pair of kidneys, one organ was preserved with PPP and the other organ was preserved in static cold storage. RESULTS: From February 2007 to September 2009, a total of 22 donors (44 recipients) were included. Recipients were comparable in the two groups with respect to demographic and immunological data. The rate of DGF was significantly lower (9% vs. 31.8%, p = 0.021) in the PPP group. At 1, 3, and 12 months, renal function was comparable in the two groups. CONCLUSIONS: Pulsatile perfusion preservation significantly reduced DGF rate in ECD kidney transplantation.