Methods Used in Economic Evaluations of Chronic Kidney Disease Testing — A Systematic Review

Background: The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. Aims: This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. Methods: Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. Results: The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. Conclusion: Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis

Death with functioning kidney transplant: an obituarial analysis

Death with a functioning kidney graft (DWFG) is now a major cause of graft loss after renal transplantation, occurring in up to 40% of cases. Its occurrence provides insight into the medical care of subjects with a functioning kidney transplant. In this study, we used the time to DWFG as an endpoint, to test whether improved medical care has contributed to better kidney transplant outcomes. We used single-center data from the Milwaukee Regional Medical Center and Froedtert Hospital, on kidney-only transplants from 1969 through 2005. A total of 3,157 kidney transplants were done at our center during this time. There were 714 deaths with functioning kidney. We also recorded the major causes of DWFG over the time period from 1969 through 2005 divided into 3 epochs. The data were analyzed as a serial collection of yearly obituaries. The time to DWFG has increased to 10 years despite a 20-year increase in the mean age of transplant recipients over the same time period. Better pre-transplant evaluation, improved treatments for hypertension and hyperlipidemia, improved management of acute myocardial infarction, superior immunosuppressive protocols and better prophylaxis and treatment of infectious diseases have all likely contributed to this trend

Pharmacokinetic role of protein binding of mycophenolic acid and its glucuronide metabolite in renal transplant recipients

Mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), is used to prevent graft rejection in renal transplant recipients. MPA is glucuronidated to the metabolite MPAG, which exhibits enterohepatic recirculation (EHC). MPA binds for 97% and MPAG binds for 82% to plasma proteins. Low plasma albumin concentrations, impaired renal function and coadministration of cyclosporine have been reported to be associated with increased clearance of MPA. The aim of the study was to develop a population pharmacokinetic model describing the relationship between MMF dose and total MPA (tMPA), unbound MPA (fMPA), total MPAG (tMPAG) and unbound MPAG (fMPAG). In this model the correlation between pharmacokinetic parameters and renal function, plasma albumin concentrations and cotreatment with cyclosporine was quantified. tMPA, fMPA, tMPAG and fMPAG concentration–time profiles of renal transplant recipients cotreated with cyclosporine (n = 48) and tacrolimus (n = 45) were analyzed using NONMEM. A 2- and 1-compartment model were used to describe the pharmacokinetics of fMPA and fMPAG. The central compartments of fMPA and fMPAG were connected with an albumin compartment allowing competitive binding (bMPA and bMPAG). tMPA and tMPAG were modeled as the sum of the bound and unbound concentrations. EHC was modeled by transport of fMPAG to a separate gallbladder compartment. This transport was decreased in case of cyclosporine cotreatment (P < 0.001). In the model, clearance of fMPAG decreased when creatinine clearance (CrCL) was reduced (P < 0.001), and albumin concentration was correlated with the maximum number of binding sites available for MPA and MPAG (P < 0.001). In patients with impaired renal function cotreated with cyclosporine the model adequately described that increasing fMPAG concentrations decreased tMPA AUC due to displacement of MPA from its binding sites. The accumulated MPAG could also be reconverted to MPA by the EHC, which caused increased tMPA AUC in patients cotreated with tacrolimus. Changes in CrCL had hardly any effect on fMPA exposure. A decrease in plasma albumin concentration from 0.6 to 0.4 mmol/l resulted in ca. 38% reduction of tMPA AUC, whereas no reduction in fMPA AUC was seen. In conclusion, a pharmacokinetic model has been developed which describes the relationship between dose and both total and free MPA exposure. The model adequately describes the influence of renal function, plasma albumin and cyclosporine co-medication on MPA exposure. Changes in protein binding due to altered renal function or plasma albumin concentrations influence tMPA exposure, whereas fMPA exposure is hardly affected

Test performance of faecal occult blood testing for the detection of bowel cancer in people with chronic kidney disease (DETECT) protocol

<p>Abstract</p> <p>Background</p> <p>Cancer is a major cause of mortality and morbidity in patients with chronic kidney disease (CKD). In patients without kidney disease, screening is a major strategy for reducing the risk of cancer and improving the health outcomes for those who developed cancers by detecting treatable cancers at an early stage. Among those with CKD, the effectiveness, the efficacy and patients' preferences for cancer screening are unknown.</p> <p>Methods/Design</p> <p>This work describes the protocol for the DETECT study examining the effectiveness, efficiency and patient's perspectives of colorectal cancer screening using immunochemical faecal occult blood testing (iFOBT) for people with CKD. The aims of the DETECT study are 1) to determine the test performance characteristics of iFOBT screening in individuals with CKD, 2) to estimate the incremental costs and health benefits of iFOBT screening in CKD compared to no screening and 3) to elicit patients' perspective for colorectal cancer screening in the CKD population. Three different study designs will be used to explore the uncertainties surrounding colorectal cancer screening in CKD. A diagnostic test accuracy study of iFOBT screening will be conducted across all stages of CKD in patients ages 35-70. Using individually collected direct healthcare costs and outcomes from the diagnostic test accuracy study, cost-utility and cost-effective analyses will be performed to estimate the costs and health benefits of iFOBT screening in CKD. Qualitative in-depth interviews will be undertaken in a subset of participants from the diagnostic test accuracy study to investigate the perspectives, experiences, attitudes and beliefs about colorectal cancer screening among individuals with CKD.</p> <p>Discussion</p> <p>The DETECT study will target the three major unknowns about early cancer detection in CKD. Findings from our study will provide accurate and definitive estimates of screening efficacy and efficiency for colorectal cancer, and will allow better service planning and budgeting for early cancer detection in this at-risk population.</p> <p>The DETECT study is also registered with the Australia New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12611000538943.aspx">ACTRN12611000538943</a></p

Effective peer-to-peer support for young people with end-stage renal disease: a mixed methods evaluation of Camp COOL

__Abstract__ __Background__ The Camp COOL programme aims to help young Dutch people with end-stage renal disease (ESRD) develop self-management skills. Fellow patients already treated in adult care (hereafter referred to as ‘buddies’) organise the day-to-day program, run the camp, counsel the attendees, and also participate in the activities. The attendees are young people who still have to transfer to adult care. This study aimed to explore the effects of this specific form of peer-to-peer support on the self-management of young people (16–25 years) with ESRD who participated in Camp COOL (CC) (hereafter referred to as ‘participants’). __Methods__ A mixed methods research design was employed. Semi-structured interviews (n = 19) with initiators/staff, participants, and healthcare professionals were conducted. These were combined with retrospective and pre-post surveys among participants (n = 62), and observations during two camp weeks. __Results__ Self-reported effects of participants were: increased self-confidence, more disease-related knowledge, feeling capable of being more responsible and open towards others, and daring to stand up for yourself. According to participants, being a buddy or having one positively affected them. Self-efficacy of attendees and independence of buddies increased, while attendees’ sense of social inclusion decreased (measured as domains of health-related quality of life). The buddy role was a pro-active combination of being supervisor, advisor, and leader. __Conclusions__ Camp COOL allowed young people to support each other in adjusting to everyday life with ESRD. Participating in the camp positively influenced self-management in this group. Peerto- peer support through buddies was much appreciated. Support from young adults was not only beneficial for adolescent attendees, but also for young adult buddies. Paediatric nephrologists are encouraged to refer patients to CC and to facilitate such initiatives. Together with nephrologists in adult care, they could take on a role in selecting buddies

Donor-recipient weight and sex mismatch and the risk of graft loss in renal transplantation.

Background and objectives Relatively smaller kidney donor to recipient size is proposed to result in higher graft loss due to nephron underdosing and hyperfiltration injury, but the potentially additive effect of sex and weight mismatch has not been explored in detail. The purpose of this study was to determine if concurrent donor and recipient absolute weight and sex mismatch was associated with graft loss in a cohort of deceased donor kidney transplant recipients. Design, setting, participants, and measurements The association of kidney donor and recipient absolute weight and sex difference with death-censored graft loss was explored using a cohort of United States deceased donor recipients between 2000-2014 through the Scientific Registry of Transplants Recipients (SRTR). Donor-recipient sex pairings (male donor-male recipient; female donor-female recipient; male donor-female recipient; female donor-male recipient) were further stratified by donor and recipient absolute weight difference (>30 kg or 10-30 kg (donor recipient) or Results 21,261 of 115,124 kidney transplant recipients developed death-censored graft failure, (median graft survival time was 3.8 years, Q1-Q3 0.0-14.8 years). After multivariable adjustment, the highest relative hazards for graft failure were observed for female recipients of male donor kidneys and male recipients of female donor kidneys in situations where the recipient was >30 kg larger than donor (HR 1.50 95% CI [1.32-1.70], HR 1.35 95% CI [1.25-1.45], respectively). Conclusions A concurrent mismatch in donor-recipient weight (donor<recipient) and donor-recipient sex is associated with a higher risk of death-censored graft loss in kidney transplantation.</p

Donor-recipient weight and sex mismatch and the risk of graft loss in renal transplantation.

Background and objectives Relatively smaller kidney donor to recipient size is proposed to result in higher graft loss due to nephron underdosing and hyperfiltration injury, but the potentially additive effect of sex and weight mismatch has not been explored in detail. The purpose of this study was to determine if concurrent donor and recipient absolute weight and sex mismatch was associated with graft loss in a cohort of deceased donor kidney transplant recipients. Design, setting, participants, and measurements The association of kidney donor and recipient absolute weight and sex difference with death-censored graft loss was explored using a cohort of United States deceased donor recipients between 2000-2014 through the Scientific Registry of Transplants Recipients (SRTR). Donor-recipient sex pairings (male donor-male recipient; female donor-female recipient; male donor-female recipient; female donor-male recipient) were further stratified by donor and recipient absolute weight difference (&gt;30 kg or 10-30 kg (donor &lt; recipient; donor &gt; recipient) or &lt;10 kg (donor = recipient)) resulting in 20 weight and sex pairings. Time to death-censored graft loss for each pairing was evaluated using multivariable Cox Proportional Hazards models adjusting for donor, immunological, surgical and recipient predictors of graft loss compared to the reference group of male donor-male recipients with no weight mismatch (&lt;10 kg difference). Results 21,261 of 115,124 kidney transplant recipients developed death-censored graft failure, (median graft survival time was 3.8 years, Q1-Q3 0.0-14.8 years). After multivariable adjustment, the highest relative hazards for graft failure were observed for female recipients of male donor kidneys and male recipients of female donor kidneys in situations where the recipient was &gt;30 kg larger than donor (HR 1.50 95% CI [1.32-1.70], HR 1.35 95% CI [1.25-1.45], respectively). Conclusions A concurrent mismatch in donor-recipient weight (donor</p