An observational study of the effectiveness of darbepoetin alpha administered in dialysis patients once every 2 weeks for 12 months.

AIMS: Erythropoiesis-stimulating agents (ESAs) are recommended for managing renal anemia. ALTERNATE is an observational study in European and Australian dialysis patients evaluating darbepoetin a (DA) once every 2 weeks (Q2W) in clinical practice. METHODS: Adult dialysis patients initiating treatment with DA Q2W were eligible regardless of previous/current ESA use. Data were collected 6 months before and 12 months after Q2W initiation. The primary endpoint was hemoglobin (Hb) concentration 12 months after initiation. RESULTS: A total of 6,112 patients were enrolled; 6,104 were eligible (87% hemodialysis, 12% peritoneal dialysis). Before initiation, 77.3%, 8.8%, and 7.8% of patients were receiving DA, epoetin beta, and epoetin alpha, respectively; 6% were ESA naïve. Mean (95% CI) Hb (g/dl) was 11.68 (11.63-11.72) 6 months before initiation, 12.00 (11.97-12.04) at initiation, and 11.62 (11.58-11.66) 12 months after initiation. Geometric mean (95% CI) weekly ESA dose (µg/wk) was 27.27 (26.62-27.93) immediately before initiation, 23.69 (23.28 - 24.10) at initiation, and 26.80 (26.12-27.49) 12 months after initiation. At month 12, 77.3% of patients were receiving DA Q2W. CONCLUSIONS: This large observational study demonstrates that Hb concentrations can be effectively maintained over 12 months in a general dialysis population with DA Q2W without an increase in ESA dose.

Senescence rates in patients with end-stage renal disease: a critical appraisal of the Gompertz model.

The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274 221; follow-up=594 767 person-years), for European patients with a functioning kidney transplant (n=61 286; follow-up=345 024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmic mortality curve for patients on dialysis compared with both patients with a functioning kidney transplant and the general population (P<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded the highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation.

Preservation of renal function after heart transplantation: initial single-center experience with sirolimus.

BACKGROUND: Long-term survivors of heart transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin-inhibitors. Sirolimus is increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity. METHODS: Between November 2002 and November 2003, 9 adult heart transplant candidates with moderate to severe chronic renal disease were switched from cyclosporine to sirolimus. The conversion scheme consisted of an immediate stop of cyclosporine and an 8-mg loading dose of sirolimus, followed by 3 mg/d; after 1 week, the sirolimus dose was adjusted to maintain trough levels between 5 and 15 microg/L. The majority of patients were on corticosteroids, and on either azathioprine or mycophenolate mofetil. At conversion, the mean serum creatinine level was 2.11 (+/-0.4) mg/dL and the mean glomerular filtration rate (GFR) was 32 (+/-7) mL/min/1.73 m(2). Prior to conversion, the renal dysfunction was predominantly stable. RESULTS: After conversion, there were 7 dropouts (75%) due to several side effects related to sirolimus: edema (n = 2), general discomfort (n = 2), delayed wound healing (n = 1), cardiac thrombus (n = 1), and diarrhea (n = 1). The median treatment time with Sirolimus, therefore, was only 4.0 months. While on sirolimus, the renal function of all patients remained unchanged or showed even some improvement. Retrospective nephrological review revealed severe renal artery stenoses in 2 patients and serious generalized abdominal and renal atheromatosis in 7 patients. No cardiac dysfunction was seen. CONCLUSION: Conversion from cyclosporine to sirolimus was problematic due to sirolimus side effects, occurring at any time after the switch. One should also question whether chronic kidney disease after heart transplantation is routinely caused by the administration of calcineurin-inhibitors, in view of the generalized renal and abdominal atheromatosis.

Iso-risk curves as a tool for clinical decision-making: donor factors and medical urgency in cardiac transplantation.

UNLABELLED: BACKGROUND; No significant improvement of overall graft survival in cardiac transplantation has occurred during the past decade, notwithstanding the identification of several prognostic donor and recipient risk factors. By translating multivariate results into iso-risk curves plots, stratified for medical urgency, we attempt to present results in a more practical manner, to be used as guidelines at the time of donor heart offer and of allocation. METHODS: We analyzed all first heart-only transplants performed in adults and carried out between January 1, 1997, and June 30, 1998 (N = 1120). Before transplant, 687 patients were at home, 233 on hospital wards, and 200 on the intensive care unit. The overall Cox model yielded 5 independent factors associated with 1-year graft outcome: donor age, donor:recipient weight ratio, medical urgency, end-stage heart disease, and transplant country. We used the significant donor variables of donor age and donor:recipient weight ratio for the iso-risk curves; we calculated relative risks for all combinations of donor age and donor:recipient weight ratio. We obtained iso-risk curves by linking equal relative risks. RESULTS: All iso-risk curves showed that with older donor age, the donor:recipient weight ratio must be higher to obtain the same relative risk for all 3 medical urgency groups. The more urgent the heart transplant candidate, the higher the course of the iso-risk curve for all donor ages. CONCLUSIONS: Iso-risk curve is an elegant tool for presenting multivariate analyses in a more practical and patient-oriented manner. The more understandable prognostic factors become the more likely we are to achieve better results in cardiac transplantation and to use more optimally donor hearts. As an example, we have demonstrated the interaction between donor age, donor:recipient size ratio, and medical urgency.

Effect of receiving a heart transplant: analysis of a national cohort entered on to a waiting list, stratified by heart failure severity. Comparative Outcome and Clinical Profiles in Transplantation (COCPIT) Study Group.

OBJECTIVE: To determine whether there is a survival benefit associated with cardiac transplantation in Germany. DESIGN: Prospective observational cohort study. SETTING: All 889 adult patients listed for a first heart transplant in Germany in 1997. MAIN OUTCOME MEASURE: Mortality, stratified by heart failure severity. RESULTS: Within 1 year after listing, patients with a predicted high risk had the highest global death rate (51% v 32% and 29% for medium and low risk patients respectively; P<0.0001), had the highest risk of dying on the waiting list (32% v 20% and 20%; P=0.0003), and were more likely to receive a transplant (48% v 45% and 41%; P=0.01). Differences between the risk groups in outcome after transplantation did not reach significance (P=0.2). Transplantation was not associated with a reduction in mortality risk for the total cohort, but it did provide a survival benefit for the high risk group. CONCLUSION: Cardiac transplantation in Germany is currently associated with a survival benefit only in patients with a predicted high risk of dying on the waiting list. Patients with a predicted low or medium risk have no reduction in mortality risk associated with transplantation; they should be managed with organ saving approaches rather than transplantation.

Demand, supply and allocation in Eurotransplant.

The main problem in organ transplantation is the continuing shortage of organ donors. Despite all efforts no major significant increases in organ availability are observed during the year 1996 in the participating Eurotransplant counties, while the demand i.e. the waiting lists are still increasing. Shortage of organs will also have its effects and constraints on the distribution i.e. the allocation of scarce organs. To meet the demand of the renal transplantation programs a special kidney allocation system was designed based upon many simulation studies. Already a few months after implementation of the new system very promising results were observed i.e. the discrepancies between the different countries in terms of kidney procurement and transplantation frequencies disappeared. Furthermore, twice as much long waiting kidney patients have been transplanted as previously and the percentage of well matched HLA donor-recipient combinations remained surprisingly high, nearly 24%.