Laurent Weekers

Polyomavirus in renal transplantation: a hot problem.

Polyomavirus BK has emerged as an important complication after kidney transplantation. Although, BK nephropathy develops in only 1% to 5% of renal transplant recipients, its prognosis when present is very poor. The most accepted risk factor is the level of immunosuppressive treatment, but the serostatus of donor and recipient and the absence of human leukocyte antigen C7 in donor and/or recipient influence the BK virus (BKV) reactivation. The gold standard in diagnosing BKV nephropathy (BKVN) continues to be biopsy with use of immunohistochemistry for large T antigens. Urinary decoy cells and blood BKV DNA polymerase chain reaction are used in the screening, but their positive predictive values are poor. However, their use as predictors of the evolution of BKVN is more valuable. The reduction of immunosuppressive therapy currently represents the first-line treatment for BKVN. Cidofovir and leflunomide can be used when BKVN continues to progress. In the event of graft loss, retransplantation is possible with a low risk of recurrence when the infection is no longer active.

Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher (eGFR <45 mL/min)

Diabetes mellitus is becoming increasingly prevalent and is considered a rapidly growing concern for healthcare systems. Besides the cardiovascular complications, diabetes mellitus is associated with chronic kidney disease (CKD). CKD in patients with diabetes can be caused by true diabetic nephropathy, but can also be caused indirectly by diabetes, e.g. due to polyneuropathic bladder dysfunction, increased incidence of relapsing urinary tract infections or macrovascular angiopathy. However, many patients who develop CKD due to a cause other than diabetes will develop ormay already have diabetes mellitus. Finally, many drugs that are used for management of CKDs, e.g. corticosteroids or calcineurin inhibitors, can cause diabetes. Despite the strong interplay between diabetes and CKD, the management of patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) remains problematic. Many guidance-providing documents have been produced on the management of patients with diabetes to prevent or delay the progression to CKD, mostly defined as the presence of microand macro-albuminuria. However, none of these documents specifically deal with the management of patients with CKD stage 3b or higher (eGFR <45 mL/min). There is a paucity of well-designed, prospective studies in this population, as many studies exclude either patients with diabetes, or with CKD stage 3b or higher (eGFR <45 mL/min), or both. This limits the evidence base to these approaches. In addition, due to some new developments in this area, the advisory board of ERBP decided that a guideline on the management of patients with diabetes and CKD stage 3b or higher (eGFR <45 mL/min) was needed and timely:

Outcome of the living kidney donor

Renal transplantation from living kidney donors is still relatively marginal in most of the European countries. However, this source of kidney grafts may help to overcome in part the organ donor shortage of cadaveric donors. The living donor strategy implies correct and objective information about donation risks and completely free acceptance of the living candidate of the donation. In this paper, we reviewed the consequences of kidney donation on the living donor health, considering very short term (linked to the surgery), short term (effect of nephrectomy on glomerular filtration rate) and long term (risk of mortality, chronic kidney disease, proteinuria and hypertension) consequences of kidney donation.

Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study

BACKGROUND The role of cholecalciferol supplementation in end-stage renal disease (ESRD) patients has been questioned. The objective of this randomized double-blinded study is to assess whether cholecalciferol therapy can increase serum 25-hydroxyvitamin D [25(OH)D] levels in haemodialysed patients and the safety implications of this therapy on certain biological parameters and vascular calcifications score. METHODS Forty-three haemodialysis patients were randomized to receive placebo or cholecalciferol (25,000 IU) therapy every 2 weeks. The biological parameters, serum calcium, phosphorus, 25(OH)D and parathormone (PTH) levels, were monitored monthly for 12 consecutive months. Vascular calcifications were assessed by lateral X-ray radiography. RESULTS At baseline, the mean serum 25(OH)D levels were low and similar in both groups. Thirty patients (16 treated and 14 placebo) completed the study: 11 patients died (5 placebo and 6 treated), 1 patient dropped out and 1 patient was transplanted (both from the placebo group). After 1 year, the percentage of 25(OH)D deficient patients was significantly lower in the treated group. None of the patients developed hypercalcaemia. The PTH levels tended to increase over the study period under placebo and to decrease in the cholecalciferol group. The median changes in PTH levels from baseline to 1 year were statistically different between the two groups [+80 (-58 to 153) and -115 (-192 to 81) under placebo and cholecalciferol treatment, respectively, P=0.02].The calcification scores increased equivalently in both groups (+2.3 per year). CONCLUSIONS Cholecalciferol is effective and safe, and does not negatively affect calcium, phosphorus, PTH levels and vascular calcifications. Additional studies are needed to compare the impacts of nutritional and active vitamin D agents on vascular calcification and mortality.

Mesenchymal Stromal Cell Therapy in Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) represents a worldwide public health issue of increasing incidence. IRI may virtually affect all organs and tissues and is associated with significant morbidity and mortality. Particularly, the duration of blood supply deprivation has been recognized as a critical factor in stroke, hemorrhagic shock, or myocardial infarction, as well as in solid organ transplantation (SOT). Pathophysiologically, IRI causes multiple cellular and tissular metabolic and architectural changes. Furthermore, the reperfusion of ischemic tissues induces both local and systemic inflammation. In the particular field of SOT, IRI is an unavoidable event, which conditions both short- and long-term outcomes of graft function and survival. Clinically, the treatment of patients with IRI mostly relies on supportive maneuvers since no specific target-oriented therapy has been validated thus far. In the present review, we summarize the current literature on mesenchymal stromal cells (MSC) and their potential use as cell therapy in IRI. MSC have demonstrated immunomodulatory, anti-inflammatory, and tissue repair properties in rodent studies and in preliminary clinical trials, which may open novel avenues in the management of IRI and SOT.

Mesenchymal stromal cell therapy in conditions of renal ischaemia/reperfusion

Acute kidney injury (AKI) represents a worldwide public health issue of increasing incidence, with a significant morbi-mortality. AKI treatment mostly relies on supportive manoeuvres in the absence of specific target-oriented therapy. The pathophysiology of AKI commonly involves ischaemia/reperfusion (I/R) events, which cause both immune and metabolic consequences in renal tissue. Similarly, at the time of kidney transplantation (KT), I/R is an unavoidable event which contributes to early graft dysfunction and enhanced graft immunogenicity. Mesenchymal stromal cells (MSCs) represent a heterogeneous population of adult, fibroblast-like multi-potent cells characterized by their ability to differentiate into tissues of mesodermal lineages. Because MSC have demonstrated immunomodulatory, anti-inflammatory and tissue repair properties, MSC administration at the time of I/R and/or at later times has been hypothesized to attenuate AKI severity and to accelerate the regeneration process. Furthermore, MSC in KT could help prevent both I/R injury and acute rejection, thereby increasing graft function and survival. In this review, summarizing the encouraging observations in animal models and in pilot clinical trials, we outline the benefit of MSC therapy in AKI and KT, and envisage their putative role in renal ischaemic conditioning.

Results of Kidney Transplantation From Donors After Cardiac Death

Confronting the organ donor shortage, many transplant centers around the world increasingly use donors after cardiac death (DCD). Over the past 20 years, follow-up studies in kidney recipients comparing DCD and donors after brain death (DBD) have shown comparable long-term graft function and survival. As a consequence, DCD programs should be continued and expanded, for these donors constitute a potential solution to the imbalance between the numbers of end-stage kidney disease patients on waiting lists versus available kidney grafts. DCD kidneys do not necessarily signify suboptimal grafts; they may merit to be allocated the same as DBD grafts.

Results of kidney transplantation from controlled donors after cardio‐circulatory death: a single center experience

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio‐circulatory death (DCD). Primary end‐points were graft and patient survival, and post‐transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end‐points. This is a retrospective mono‐center review of a consecutive series of 59 DCD‐KT performed between 2005 and 2010. Overall graft survival was 96.6%, 94.6%, and 90.7% at 3 months, 1 and 3 years, respectively. Main cause of graft loss was patient’s death with a functioning graft. No primary nonfunction grafts. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 45.6% of all DCD‐KT. DGF significantly increased postoperative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index ≥30 was the only donor factor that was found to significantly increase the risk of DGF (P < 0.05). Despite a higher rate of DGF, controlled DCD‐KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid‐term results to those procured after brain death.

Delayed graft function does not harm the future of donation-after-cardiac death in kidney transplantation.

INTRODUCTION Delayed graft function (DGF) occurs more frequently in kidney transplants from donation after cardiac death (DCD) than from donation after brain death (DBD). We investigated the effect of DGF on posttransplantation outcomes among grafts from controlled DCD kidneys. PATIENTS AND METHODS This single-center retrospective study recruited 80 controlled DCD kidneys transplanted from January 2005 to December 2011. Mean patient follow-up was 28.5 months. RESULTS There were no primary nonfunction grafts; the DGF rate was 35.5%. Overall graft survival rates between groups with versus without DGF were 92.4% and 95.2% at 1 year, 92.4% and 87.1% at 3 years, and 84.7% and 87.1% at 5 years, respectively (P = not significant (NS)). Patients with versus without DGF showed the same survival rates at the corresponding time 92.4% vs 97.2%, 92.4% vs 93.9%, and 84.7% vs 93.9% (P = NS). Estimated glomerular filtration rate was significantly lower in the DGF compared with the non-DGF group at hospital discharge (29 vs 42 mL/min; P = .00) and at 6 months posttransplantation (46 vs 52 mL/min; P = .04), but the difference disappeared thereafter: 47 vs 52 mL/min at 1 year, 50 vs 48 mL/min at 3 years, and 54 vs 53 mL/min at 5 years (P = NS). DGF did not increase the risk of an acute rejection episode (29.6% vs 30.6%; P = NS) or rate of surgical complications (33.3% vs 26.5%; P = NS). However, DGF prolonged significantly the length of hospitalization in the DGF versus the non- DGF group (18.9 vs 13 days; P = .00). Donor body mass index (BMI) ≥ 30 kg/m(2), recipient BMI ≥30 kg/m(2), and pretransplantation dialysis duration increased the risk of DGF upon multivariate logistic regression analysis. CONCLUSIONS Apart from the longer hospital stay, DGF had no deleterious impact on the future of kidney allografts from controlled DCD, which showed comparable graft and patient survivals, renal function, rejection rates, and surgical complications as a group without DGF. Therefore, DGF should no longer be considered to be a medical barrier to the use of kidney grafts from controlled DCD.

Contribution of Donors After Cardiac Death to the Deceased Donor Pool: 2002 to 2009 University of Liege Experience

OBJECTIVE In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.