The quality of life in end stage renal disease care

Abstract The improved prognosis and survival statistics of both renal transplantation and dialysis have focused attention on the quality of life offered by these treatments. Using a standardized questionnaire, we assessed the quality of life of 612 patients undergoing renal replacement therapy at our center. Of these patients, 359 had been transplanted and 253 patients were on dialysis. Concerning the sociodemographic data, only the time on specific treatment was longer in dialysis patients than in transplanted patients (49.2 versus 55.6 months, P < 0.05). Most complaints were more common in dialysis patients than in transplanted patients. Only the side effects of medication were seen more in transplanted patients ( P < 0.005). Life satisfaction was higher in transplanted patients than in dialysis patients. Dialysis patients were more anxious ( P < 0.05) and more depressed ( P < 0.001) than transplanted patients. Transplanted patients also felt that they had more social support than did dialysis patients. Overall life quality was almost equal between patients on hemodialysis and patients on peritoneal dialysis, and between patients on the waiting list for transplantation and those not on the waiting list. Despite a significantly better quality of life after renal transplantation, the percentage of patients working remained unchanged. (57.5% versus 57.8%, P = n.s.). We conclude that despite an improved quality of life after renal transplantation, these patients are economically not more productive than patients on dialysis.     

Cyclosporine C2 levels in de novo renal allograft recipients: a German multicenter prospective observational study

This ongoing multicenter prospective observational study was undertaken in de novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2-hour postdose (C2) level monitoring at defined times so as to assess the risk for an acute rejection episode or allograft dysfunction. The renal transplant recipients (n = 159) were enrolled at 11 German centers. The 6-month posttransplant data from 138 patients were evaluable for this interim analysis. Mean C2 levels (ng/mL), which were measured by liquid chromatography-tandem mass spectrometry at a central laboratory, were: days 3 to 5: 873.1 +/- 391.9; days 7 to 10: 939.1 +/- 422.8; days 14 to 28: 1116.3 +/- 497.6; 3 months: 905.0 +/- 316.8; and after 6 months: 787.0 +/- 276.5. To identify patients at higher risk for acute rejection or allograft dysfunction, we calculated the relative CsA absorption capacity (C2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean values on days 3 to 5: 284.4 +/- 115.1; days 7 to 10: 306.7 +/- 134.8; days 14 to 28: 382.5 +/- 164.7; month 3: 501.5 +/- 168.8; month 6: 512.7 +/- 176.5. Three groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs < 200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350). A between-group comparison of absorption level at 6 months posttransplant revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault formula-based mean glomerular filtration rates of 23.8% and 54.7 +/- 19.0 mL/min, 22.6% and 59.5 +/- 20.7 mL/min, and 17.6% and 67.7 +/- 23.5, respectively. In conclusion, mean C2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA-Abs increasing continuously over the first 6 posttransplant months. High CsA absorbers show a propensity toward good allograft function and lower acute rejection rates at 6 months after renal transplantation.     

Pharmacokinetics of the immunosuppressant everolimus in maintenance renal transplant patients

The novel macrocyclic immunosuppressant everolimus has been approved for use in renal and heart transplantation. The objective of this randomized, double-blind, placebo-controlled, dose-escalating Phase 1 study was to evaluate the pharmacokinetic profile of different dosing regimens of everolimus. Fifty-four subjects were randomized for 4-weeks treatment with everolimus (n = 44) or placebo (n = 10). Steady state was reached by day 4 of multiple dosing with evidence for dose-proportionality over the dose range tested. Systemic accumulation was 1.6- to 2.2-fold with multiple dosing. Steady-state predose trough concentrations were well correlated with AUC (r = 0.87, p < 0.001). Within-subject coefficients of variation for the tablet formulation ranged from 10-19% and between-subject coefficients from 34-60% for Cmax and AUC. There was no effect of common demographic parameters (age, sex, weight) on variability in steady-state exposure. These results support the clinical use of everolimus in renal transplantation.     

Differences in reporting of acute rejections between American and European publications of large immunosuppressive trials impair comparability of study results

This study examined the use of different definitions for acute rejection in recent large multicenter trials performed in America and Europe in order to assess whether systematic differences exist between both scientific cultures. We systematically selected recent publications on multicenter randomized controlled trials, investigating immunosuppressive regimens in de novo kidney transplant recipients. Publications included were classified according to the type of acute rejection reported: group 1 reported no or only one type of rejection rate (biopsy-proven or treated); group 2 reported information on both treated and biopsy-proven rates. Other potential factors (journal's impact-factor, study size) were compared within the subgroups. To determine the rates of treated but not biopsy-proven acute rejections, additional analyses were performed within subgroup 2. The reviewed publications were 24/44 (54.5%) European (E) and 20/44 (45.5%) American (A) origin. Eighteen of 44 publications reported no or only one type of rejection rate (group 1); 26 publications reported treated as well as biopsy-proven rates (group 2). Significantly more European publications reported both treated and biopsy-proven rates (E: 18/24 [75.0%] vs A: 8/20 [40.0%]; P = .019). Group 1 American papers were published in higher-ranked journals than European ones. The rate of blindly treated rejections did not differ significantly (A: 6.13% [range 0% to 12.8%] vs E: 8.43% [range 0% to 16.9%]) and the proportion of blindly treated rejections was slightly lower in American studies (A: 18.5% vs E: 26.5%). Our systematic review showed large discrepancies with a trend to report biopsy-proven rejection rates only in recent years.     

Quality of life of living kidney donors in Germany: a survey with the Validated Short Form-36 and Giessen Subjective Complaints List-24 questionnaires

BACKGROUND: Most studies evaluating the impact of kidney donation on donors' quality of life (QOL) have limitations such as small cohort size, unmatched references, use of nonstandardized and nonvalidated questionnaires, or low response rates. METHODS: We performed a study on donors' QOL that was designed to avoid these limitations. All available living renal donors in our department in the last 18 years were included in the study. QOL was assessed with two validated, standardized questionnaires (Short Form-36, Giessen Subjective Complaints List [Giessener Beschwerdebogen]-24) and compared with gender- and age-matched references. In addition, specific questions relating to kidney donation were asked. RESULTS: The response rate (89.8%) is one of the highest reported for studies on QOL of living kidney donors. Most donors had an equal or better QOL than the healthy population. Donors' willingness to donate again (93.4%) or recommend living-donor kidney transplantation (92.4%) was high, irrespective of complications. A small number of donors experienced financial drawbacks or occupational disadvantages. Donors aged 31 to 40 years were found to be at risk of QOL deterioration after organ donation. Donor and recipient complications had a significant impact on donors' QOL. One third of the donors found that the psychologic care preceding and after kidney donation was insufficient. CONCLUSIONS: Our findings support the practice of living-donor kidney transplantation as a good means to meet the persisting organ shortage. Further effort must be put into minimizing donor and recipient complications. The specific demands of younger donors should be further elucidated. In addition to medical follow-up, living kidney donors should also be offered lifelong psychologic counseling.     

Pharmacokinetics of intravenous, single-dose tiotropium in subjects with different degrees of renal impairment

Tiotropium, a new potent anticholinergic bronchodilator, is excreted mainly by the kidney. To investigate the pharmacokinetics of tiotropium in renal impairment, the authors evaluated the pharmacokinetics and safety after administration of a single dose of intravenous tiotropium 4.8 microg, given as an infusion over 15 minutes in subjects with normal renal function and a wide range of renal impairment based on measured creatinine clearance (normal: > 80 mL/min, n = 6; mild impairment: > 50-80 mL/min, n = 5; moderate impairment: 30-50 mL/min, n = 7; severe impairment: < 30 mL/min, n =6). As expected for a drug excreted predominantly in unchanged form by the kidneys, tiotropium plasma concentrations increased as renal impairment worsened, with mean values of 55.5 (16.2 percent geometric coefficient of variation [%gCV]), 77.1 (20.1 %gCV), 101 (29.8 %gCV), and 108 (27.3 %gCV) pgh/mL for AUC(0-4h) in the normal renal function and the mild, moderate, and severe renal impairment groups, respectively. The percentage of tiotropium dose excreted unchanged in the urine decreased from 60.1% of dose (17.7 %gCV) to 59.3% (14.4 %gCV), 39.9% (34.5 %gCV), and 37.4% (10.2 %gCV) in the normal renal function and the mild, moderate, and severe renal impairment groups, respectively. Plasma protein binding of tiotropium did not significantly change in the renal-impaired subjects. Two subjects with normal renal function experienced headache 10 hours after the infusion, which was mild and transient. No adverse events occurred in subjects with renal impairment. There were no clinically relevant changes in blood pressure, pulse rate, 12-lead ECG, physical examination, hematology, or clinical chemistry, compared with baseline values, in any subject after intravenous administration of tiotropium. Tiotropium should only be used in patients with moderate to severe renal insufficiency if the potential benefit outweighs the potential risks.     

Recessions lower (some) mortality rates: evidence from Germany

In his article with the provocative title "Are Recessions Good for Your Health?", Ruhm (J. Health Econ. 21(4) (2000) 659) has found robust and consistent evidence that the total mortality rate, age-specific mortality rates as well as most specific mortality causes are pro-cyclical. His finding that high unemployment rates are associated with lower mortality and vice versa stands in stark contrast to Brenner's earlier work, who found the opposite effect, possibly after a time lag. Ruhm controls for state-specific effects in a panel of US states over the period 1972-1991, whereas Brenner's work is based on time-series analysis. Extending and improving upon Ruhm's original analysis, we analyse the effect of state unemployment and economic growth rates on mortality in the states of Germany over the period 1980-2000, both in a static and a dynamic econometric model. Controlling for state-specific effects, we find evidence that aggregate mortality rates for all age groups taken together as well as most specific age groups are lower in recessions. The same is true for mortality from cardiovascular diseases, pneumonia and influenza, motor vehicle accidents and suicides, but not for necessarily for other specific mortality causes. In particular, there is never a statistically significant effect on homicides, other external effects and malignant neoplasms. There are also few differences apparent between the effect on male and female mortality. If we do not control for state-specific effects, then we often arrive at the opposite result with higher unemployment being associated with higher mortality. This suggests that a failure to control for time-invariant state-specific effects leads to omitted variable bias, which would erroneously suggest that mortality rates move counter-cyclically. Overall, we can confirm Ruhm's main finding for another country: recessions lower some, but not all, mortality rates in the case of Germany.