Moon phases and moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation.

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.

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.

Immunosuppression in pancreas transplantation: the Euro SPK trials and beyond.

The Immunosuppression in Pancreas Transplantation was historically based on the fact that the pancreas is an extremely immunogenic organ. Quadruple drug therapy with polyclonal or monoclonal antibodies induction was the mainstay therapy since the introduction of Cyclosporine A. In the modern era of Immunosuppression, Mycophenolate Mofetil replaced Azathioprine while Tacrolimus-another potent calcineurin inhibitor-had-and still has-a difficult challenge to replaced Cyclosporine A, due to its potential diabetogenic effect. Thanks to the first two EuroSPK studies which prospectively tried to answer several questions in that field. But, the future challenge will be in understanding the impact of innate immunity and ischemic reperfusion injuries on the long-term graft function. Hopefully, new drugs will be available and tested to block unspecific deleterious reactions to attenuate the proinflammatory response. It will be the aim of the third Euro SPK Study.

Impaired glucose tolerance in pancreas grafted diabetic patients is due to insulin secretory defects.

INTRODUCTION: Pancreas transplantation in diabetic patients can sustain insulin independence for years. The aim of the study was to measure the incidence of an impaired or diabetic glucose tolerance in patients after successful transplantation and analyse insulin resistance and insulin secretion. METHODS: 174 Type 1 diabetic recipients of simultaneous pancreas/kidney (SPK) transplants were investigated early (three months) and 95 patients late (five years) after transplantation using an oral glucose tolerance test combined with an iv arginine load. RESULTS: Although mean fasting blood glucose and HbA1c levels were within the normal range, only 65% of the patients displayed a normal glucose tolerance (NGT), whereas 25% had an impaired (IGT) and 10% showed a diabetic glucose tolerance (DGT). Fasting blood glucose and HbA1c values were significantly lower in patients with NGT compared to graft recipients with IGT or DGT, either three months or five years after SPK. Indicators of insulin resistance (fasting insulin, HOMA-IR, Matsuda/de Fronzo Index) were elevated in all graft recipients, but no differences were found between groups. In contrast insulin secretion was significantly reduced in patients with IGT and DGT early and late after transplantation. SUMMARY: Insulin resistance is a common feature after pancreas transplantation. However, either three months or five years after SPK abnormal glucose tolerance was mainly due to a reduced glucose- and arginine-induced secretory response of insulin.

The janus face of immunosuppression - de novo malignancy after renal transplantation: the experience of the Transplantation Center Munich.

After decades of successful organ transplantation clinicians continue to be troubled by the increasing incidence of cancers under maintenance immunosuppression. In this study, we examined rates of malignancies in 2419 renal transplant recipients transplanted in our institution between 1978 and 2005. In renal transplant recipients the cumulative incidence of cancer after 25 years was 49.3% for all tumors and 39.7% excluding non-melanoma skin cancers, compared with 21% for a normal sex- and age-matched population. The most frequent tumors observed were non-melanoma skin cancers (20.5%), kidney cancers (12.0%), and cancers of the pharynx, larynx, or oral cavity (8.2%). The general increase of cancer risk was 4.3-fold. Independent risk factors for the development of a tumor were male gender, older recipient age, the presence of preformed antibodies before transplantation, and the time on immunosuppression. Interestingly, the use of IL-2-receptor antagonists significantly reduced the tumor risk of transplant recipients. The tumor risk between immunosuppressive drugs typically used for maintenance immunosuppression was not significantly different. However, mammalian target of rapamycin (mTOR) inhibitor-based immunosuppressive protocols showed a clear tendency for lower malignancy rates. De novo malignancies following renal transplantation represent a serious problem endangering the prognosis of otherwise successfully transplanted patients. Future studies will have to address whether optimized immunosuppressive regimens including mTOR-inhibitors are capable of reducing the incidence or preventing the development of posttransplant malignancies.

Cholesterol atheroembolic disease in kidney allografts--case report and review of the literature.

Cholesterol atheroembolic renal disease is a rare cause of renal allograft dysfunction. Two recipients of cadaveric kidney transplantats from the same donor are discussed with presumed graft failure due to cholesterol emboli of donor origin. A review of the literature summarizes the reported cases in renal transplant recipients. While cholesterol embolization of presumed donor origin seems to have a poor renal outcome, cholesterol emboli originating in the recipient have a more favorable prognosis. As donors and recipients of increasing age or prominent atherosclerosis are accepted for transplantation, cholesterol atheroembolic renal disease may become more prevalent and should be considered in patients with renal allograft dysfunction.

Simultaneous pancreas-kidney transplantation: analysis of rejection.

UNLABELLED: The 3-year data concerning the occurrence of rejection episodes (RE) are reported herein. PATIENTS AND METHODS: Two hundred five simultaneous pancreas-kidney (SPK) transplantations were performed from May 1998 to September 2000, including 103 patients randomly assigned to tacrolimus (Tac) and 102 to cyclosporine microemulsion (CsA-ME). All patients received concomitant rATG induction therapy, mycophenolate mofetil (MMF), and short-term corticosteroids. RESULTS: After a follow-up of 3 years, acute rejection episodes occurred in 41 patients receiving tacrolimus and in 51 patients receiving CsA ME. The majority of first rejection episodes in both groups occurred during the first 6 months (93% and 90%, respectively) and in most cases were treated with corticosteroids (88% and 90%). Actuarial rejection-free graft survival was not significantly different between the two groups (54% and 44% at 3 years posttransplant). In a multivariate analysis, HLA compatibility (P = .003) and graft vessel extension (P = .0005) had a significant influence on rejection-free survival. Rejection influenced pancreatic graft survival (P = .01) and pancreatic graft loss owing to rejection influenced patient survival (P = .02). In the intent-to-treat analysis of early rejection, first moderate-to-severe episodes (1 of 40 versus 12 of 47; P = .004) and refractory episodes (2 of 40 versus 10 of 47; P = .03) were significantly lower with tacrolimus than with CsA ME. Pancreatic graft survival was worse among late rejectors (53%) than nonrejectors (86%; P = .002). In addition, serum creatinine was highest in late rejectors. In conclusion, Tac-based immunosuppressive therapy shows advantages over CsA ME in terms of the severity of acute rejection episodes among patients undergoing SPK transplantation.

[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%.

Contrast-enhanced MR angiography in patients after kidney transplantation.

The aim of this study was to investigate the value of a contrast-enhanced 3D MR angiography in detecting postoperative vascular complications after kidney transplantation in comparison with digital subtraction angiography (DSA). Forty-one patients who underwent a kidney transplantation were examined with MR angiography and DSA. Contrast-enhanced MR angiography was performed as a dynamic measurement with one precontrast and three postcontrast measurements. Maximum intensity projection reconstructions were performed for all postcontrast data sets after DSA. The results were evaluated by two independent observers who were unaware of the DSA results. Twenty-three hemodynamically significant arterial stenoses were identified with DSA in the iliac arteries ( n=7), the renal allograft arteries ( n=12), and in their first branches ( n=4). For a patient-based analysis the sensitivity and specificity, respectively, for observer 1 were 100 and 97%, and for observer 2, 100 and 93%. Respective data were 100 and 100% after a consensus evaluation by two observers. Complications involving the renal veins were detected in 2 cases and perfusion defects of the kidney parenchyma were detected in 4 cases. Contrast-enhanced MR angiography is a reliable method in identifying postoperative arterial stenoses after kidney transplantation. In addition, dynamic MR angiography can be helpful in detecting venous complications and perfusion defects in kidney allografts.

[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.

Hyperimmunoglobulin prophylaxis, monitoring and preemptive ganciclovir treatment eliminate the risk of CMV infection to improve patient and renal allograft survival.

This study was designed to investigate whether the introduction of ganciclovir to clinical use for anti-CMV treatment changes the risk of CMV infection in renal transplant patients. A total of 1545 cases who had received cadaveric renal transplants were divided into two groups: group 1 (n = 721) was made up of patients who received their transplants within 6 years before the introduction (1991) of ganciclovir and group 2 (n = 824), of individuals transplanted thereafter. Patient and graft survival of CMV D+/R- patients was uni- and multivariately compared with non-CMV D+/R- patients. In CMV D+/R- patients in group 1, survival was significantly lower, and their relative risk for graft loss was 1.32-fold (P = 0.0483) that of non-CMV D+/R- patients. In group 2 patient and graft survival was identical regardless of whether the patients were at risk for CMV infection or not. The risk of CMV infection can be eliminated by hyperimmunoglobulin prophylaxis, CMV monitoring and preemptive ganciclovir treatment in renal transplant patients.

Mycophenolate mofetil-based, cyclosporine-free induction and maintenance immunosuppression: first-3-months analysis of efficacy and safety in two cohorts of renal allograft recipients.

BACKGROUND: The currently used macrolide immunosuppressants, i.e., cyclosporine and tacrolimus, exert considerable nephrotoxicity. We aimed to avoid the nephrotoxic effects by applying a cyclosporine-free regimen for the induction as well as for the maintenance treatment of renal allograft recipients using mycophenolate mofetil (MMF) as the primary immunosuppressant. METHODS: Thirteen patients were converted from cyclosporine (CsA) to MMF monotherapy. For 4 weeks, MMF (2 g/day) was added to the CsA treatment, before CsA was tapered by weekly steps of 25 mg/day and without "safeguard treatment" with additional immunosuppressants. In a second approach, 12 patients older than 50 years, and receiving a renal graft from a donor older than 50 years, were treated primarily with MMF combined with steroids and an induction therapy using antithymocyte globulin, and without the addition of CsA. RESULTS: Thirteen long-term renal transplant patients could be converted from CsA to MMF monotherapy. Conversion resulted in an immediate and long-lasting improvement of their median creatinine values by 20%. No serious adverse events occurred. In the second cohort of 12 patients, MMF was used as the primary immunosuppressant. All patients are alive and no grafts were lost after 4 months (n= 12) and after 6 months (n=7). The median creatinine values achieved after 4 and 6 months were 1.16+/-0.25 and 1.30+/-0.21 mg/dl, respectively. One patient was converted to CsA because of a reversible rejection episode (8.3%), and another patient was converted because of cytomegalovirus disease. Major complications consisted of wound-healing disturbances (16.6%) and cytomegalovirus infections (41.6%). CONCLUSION: MMF monotherapy can be safely applied as long-term maintenance immunosuppression with improvement of renal function. Steroids are not required as an adjunct to MMF. MMF monotherapy, in the absence of drug-related nephrotoxicity, is particularly beneficial for grafts derived from marginal donors, such as donors of advanced age.

Aggressive treatment of the first acute rejection episode using first-line anti-lymphocytic preparation reduces further acute rejection episodes after human kidney transplantation.

The detrimental effect of acute rejection episodes on long-term outcome of renal allografts in cyclosporin-treated patients is well established, although has not been seen by all investigators. To analyse the possibility that aggressive treatment of the first episode may ameliorate this detrimental effect, we performed an open label, randomised prospective trial in cyclosporin-based, immunosuppressed recipients of postmortem renal allografts in order to compare two different treatment protocols during primary acute rejection episodes: (1) group 1 of 25 patients received 3 x 250 mg methylprednisolone (MP) i.v.; (2) group 2 of 25 patients received 7 x anti-thymocyte globulin (ATG)-Fresenius i.v. (4 mg/kg body weight). During a period of 4 years, the following clinical observations were made: (1) The incidence of an acute re-rejection episode was significantly reduced in the ATG-treated study group (16%) compared to the MP-treated study group (72%); (2) The severity of the first acute rejection episode (intensity of renal dysfunction measured in terms of 10-day creatinine area under curve) showed no significant difference between the groups (37 mg x 10-d/dl to 58 mg x 10-d/dl); and (3) The half-lives of allografts in both groups have not shown any significant differences so far. In conclusion, aggressive treatment of the first rejection episode of renal allografts with the use of ATG reduced the incidence of re-rejection episodes which, however, are not reflected so far by improvement of the 4-year survival rate of these allografts. Since it could be observed that re-rejection is an even worse predictor for chronic transplant failure, a better long-term outcome of renal allografts in ATG-treated patients may be expected during a longer observation period. The incidence of a third episode was also reduced in the ATG-treated group (0%) compared to the MP-treated group (12%).

[Prolonged post-anesthesia recovery in hemodialysis-induced hypothyroidism]. / Prolongierte Aufwachphase bei dialyseinduzierter Hypothyreose.

We report about a 30-year-old female patient with terminal renal failure, undergoing allogenic renal-transplantation after two and a half years on hemodialysis. Besides, the preoperative examination seemed normal. The intraoperative phase was uneventful, except a transfusion-requiring blood-loss of 2000 ml, and the graft started diuresis immediately after reperfusion. Postoperatively the duration of the non-depolarising muscle-relaxant atracurium was prolonged for more than one hour and a deep sedation, caused by the premedication-benzodiazepine Dipotassiumchlorazepat, was seen. Unless antagonisation, the patient was unconscious for some hours. Laboratory evaluation showed peripheral hypothyroidism with normal pituitary activity: T(3)0.8 ng/ml, T(4)3.9 micrograms/dl und TSH 0.67 microU/ml. Under temporary substitution with L-Thyroxine 50 micrograms, the patient recovered quickly an could be demitted after 10 days. Further controls showed euthyroidism. 14 month later, she underwent an antirefluxive surgical procedure, at excellent graft-function. Anesthesia was uneventful that time.