Calcineurin inhibitor-free immunosuppressive strategy in elderly recipients of renal allografts from deceased donors: 1-year results from a prospective single center trial.

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.

Comparative evaluation of oxidative and antioxidative capacity during high-flux hemodialysis using two different membranes.

AIM: In patients with end-stage renal disease (ESRD) cardiovascular morbidity and mortality are increased. Apart from traditional and uremia-specific factors oxidative stress has been implicated as a main risk factor. This study investigated the influence of two different high-flux hemodialysis membranes on parameters of oxidative stress during a dialysis session. PATIENTS AND METHODS: 14 stable ESRD patients were enrolled in the study and randomly assigned to high-flux hemodialysis using either a polyamide membrane (Polyflux 14; PA group) or a new polysulfone membrane (Diacap Polysulfone HI PS 15; PS group). All patients received 6 treatments with the same membrane. During the 5th treatment parameters of dialysis efficiency, biocompatibility (cell counts, complement C3a, thrombin-antithrombin complex) and oxidative stress (lipid peroxides, total antioxidative capacity) were measured. RESULTS: Parameters of dialysis efficiency and biocompatibility were similar in both treatment groups. At the beginning of the dialysis session both groups showed a low to moderate level of oxidative stress and a reduced total antioxidative capacity as compared to healthy controls. Both parameters deteriorated significantly during the extracorporeal procedure with a similar magnitude in both membrane groups. No correlation between oxidative or antioxidative capacity and parameters of biocompatibility or dialysis efficiency could be found. CONCLUSIONS: Dialysis with synthetic high-flux membranes induces a temporary deterioration of oxidative stress parameters in ESRD patients despite good dialysis efficiency and biocompatibility.

[Development, state of the art and perspectives of transplantation medicine, exemplified by kidney transplantation]. / Trotz grosser Fortschritte bei der Nierentransplantation: Warum steht nur jeder fünfte Dialysepatient auf der Warteliste?

In particular the knowledge of the immunological aspects of organ rejection represented a giant step forward in the field of transplantation medicine. However, despite the fact that, in the absence of a contraindication, every dialysis-requiring preterminal/terminal renal insufficiency is an indication for transplantation, fewer than 20% of 50,000 candidate patients in Germany are earmarked for a new kidney. Furthermore, the fate of the patients on the waiting list is determined in particular by the dearth of donor organs. As a rule, the source of a transplantable kidney continues to be a brain-dead donor. If, however, no such organ is likely to be available in the foreseeable future, a kidney from a living donor is an alternative option. The proportion of organs from living donors in Germany is currently between 10 and 20%.

[Living donors in kidney transplantation. Renaissance by non-related donors?]. / Lebendspende bei Nierentransplantation. Renaissance durch nicht verwandte Spender?

Renal Transplantation is hampered worldwide by the continuing lack of cadaveric organs. The discrepancy between the number of patients on the waiting list and the number of organs available is further compounded by the still unresolved problem of chronic transplant failure. Against this background, the arguments for increasing acceptance of the use of kidneys from living donors, both related and unrelated, are discussed. Initial reports on appreciably improved transplant survival rates of organs from unrelated living donors (85% survival after 3 years [19]) have since been confirmed by more recent studies. Our own results, in part obtained during a prospective study involving 103 patients (53 related, 50 unrelated) done between October 1994 and April 1999, with strict psychological care/evaluation prior to and after transplantation, revealed a four-year transplant survival rate of 98% in both groups. So far, the higher rejection rate of 34% in unrelated, vs. 13.2% in related, donors has not led to any earlier chronic dysfunction of the transplant. The expanded use of living kidney donors is not only ethically justifiable, but also improves the outcome.

[Contrast enhanced MR angiography in the preoperative evaluation of living kidney donors]. / Die kontrastverstärkte MR-Angiographie in der präoperativen Diagnostik von Lebendnierenspendern.

PURPOSE: To compare Gadolinium-enhanced MR angiography with conventional DSA in the preoperative evaluation of living kidney donors. MATERIAL AND METHODS: 27 potential living kidney donors were examined with contrast-enhanced MR angiography after conventional angiography. The MR angiograms were evaluated for the number of renal arteries, the presence of early arterial branching and vascular pathologies by two independent readers. The results were compared with those of selective conventional angiography and intraoperative findings. RESULTS: Conventional angiography detected 14 accessory renal arteries. Reader A detected 13 of 14 accessory arteries with no false positive result (sensitivity 93%, specificity 100%). Reader B detected 11 of 14 accessory vessels with one false positive finding (sensitivity 79%, specificity 98%). Early arterial branching was detected by both readers in 9 of 12 vessels with no false positive result (sensitivity 75%, specificity 100%). None of the patients had additional vascular pathology. DISCUSSION: Gadolinium-enhanced MR angiography is a non-invasive alternative to conventional angiography in the preoperative evaluation of living kidney donors. In order to achieve high accuracy in detecting accessory renal arteries and early arterial branching extensive experience with the method and the specific preoperative needs is required. Selective conventional angiography is still superior in detecting very small accessory vessels and early arterial branching.

Clinical and biochemical findings in uremic patients with and without restless legs syndrome.

The restless legs syndrome (RLS) is one of the most common and unpleasant complaints of uremic patients. The pathophysiology of the RLS is still unclear. Various factors, including anemia and iron deficiency, are proposed to play a major role. We determined the prevalence of RLS in all stable hemodialysis patients under long-term treatment in two dialysis centers (n = 136) and compared the clinical and biochemical findings of patients with RLS and without RLS. Twenty-three percent of all patients investigated fulfilled the diagnostic criteria of RLS according to the International Restless Legs Syndrome Study Group. There were no statistical differences between the two groups regarding age, duration of uremia and need for dialysis, time on dialysis per week, hemoglobin, hematocrit, erythrocytes, s-ferritin, s-transferrin, s-iron, calcium, and standard biochemical indices, except for intact parathyroid hormone (iPTH) levels. Uremic patients with RLS showed significantly lower iPTH (P < 0.01) concentrations. In addition, the RLS group received a significantly higher number and dosage of psychopharmacological drugs, (ie, L-DOPA), than patients without RLS. These biochemical findings suggest that neither the severity of anemia nor that of iron deficiency has to be considered a major pathophysiological factor in established RLS. The significantly lower iPTH secretion in uremic patients with RLS, however, is a new finding, and further investigations will be necessary to determine whether this result is of any clinical significance to this group of patients. The significantly higher number of psychopharmacological drugs prescribed to uremic patients with RLS may be related to the symptoms of RLS.

Renal transplantation: progress and prospects.

Despite encouraging and improving results, organ transplantation is still hampered by a shortage of organs, chronic transplant loss, and a changed patient population. Liberal inclusion criteria for dialysis and/or renal transplantation and the increasing unwillingness to donate organs in some countries had led to a growing imbalance between the numbers of transplantations performed and patients on waiting lists. Until now, poorly understood chronic transplant dysfunction is responsible for a still unchanged graft loss of approximately 5% per year. The patient population has changed to include more multimorbidity and an increasing number of risk factors (age, diabetes mellitus, former [failed] transplantations, or preexisting cardiovascular diseases). The recommendation for a against dialysis or transplantation has become increasingly difficult for the responsible physician. Newly developed immunosuppressant drugs, an increasing consideration regarding living organ donation, or xenotransplantation in the future may solve this dilemma. New reflections and considerations about the ethical background of transplantation medicine are necessary.