The long road from the kidney bazaar: a commentary on Pakistan’s progress towards self-sufficiency in organ transplantation

The dark history of transplant tourism in Pakistan demonstrates the hazards of unregulated cross-border markets in human organs. Trading on existing national and international social inequities, ‘transplant tourism’ offers dubious benefits for transplant recipients and attractive profits to those facilitating the industry at the expense of the world’s poor. The impact of Pakistan’s 2007 Transplantation of Human Organs and Tissue Ordinance and the sustained efforts of transplant professionals and societal groups led by the Sindh Institute of Urology and Transplantation, show that organ trading can be effectively discouraged and equitable programs of organ procurement and transplantation pursued despite multiple challenges. In this paper, the factors that have contributed to Pakistan’s progress towards self-sufficiency in organ transplantation are identified and discussed. The case of Pakistan highlights the need for countries to protect their own organ and tissue providers who may be vulnerable in the global healthcare market. Pakistan provides an excellent example for other countries in the region and throughout the world to consider when regulating their own transplantation programs and considering the pursuit of national self-sufficiency.

Heuristic approaches for multi-criteria optimisation in kidney exchange programs

The Kidney Exchange Problem (KEP) is an optimisation problem that was first discussed in Rapaport (1986) but has only more recently been the subject of much work by combinatorial optimisation re-searchers. This has been in parallel with its increased prevalence in the medical community. In the basic formulation of a KEP, each instance of the problem features a directed graph D = (V,A) . Each node i ∈ V represents an incompatible pair wherein the patient needs to trade kidneys with the patient of another incompatible pair. The goal is to find an optimal set of cycles such that as many patients as possible receive a transplant. The problem is further complicated by the imposition of a cycle-size constraint, usually considered to be 3 or 4. Kidney exchange programs around the world implement different algorithms to solve the allocation problem by matching up kidneys from potential donors to patients. In some systems all transplants are considered equally desirable, whereas in others, ranking criteria such as the age of the patient or distance they will need to travel are applied, hence the multi-criteria nature of the KEP. To address the multi-criteria aspect of the KEP, in this paper we propose a two-stage approach for the kidney exchange optimisation problem. In the first stage the goal is to find the optimal number of exchanges, and in the second stage the goal is to maximise the weighted sum of the kidney matches, subject to the added constraint that the number of exchanges must remain optimal. The idea can potentially be extended to multiple-objectives, by repeating the process in multiple runs. In our preliminary numerical experiments, we first find the maximum number of kidney matches by using an existing open source exact algorithm of Anderson et al. (2015). The solution will then be used as an initial solution for the stage two optimisation problem, wherein two heuristic methods, steepest ascent and random ascent, are implemented in obtaining good quality solutions to the objective of maximizing total weight of exchanges. The neighbourhood is obtained by two-swaps. It is our intention in the future to implement a varying neighbourhood scheme within the same two heuristic framework, or within other meta-heuristic framework.

Deficiency in apoptosis-inducing factor recapitulates chronic kidney disease via aberrant mitochondrial homeostasis

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with dual roles in redox signaling and programmed cell death. Deficiency in AIF is known to result in defective oxidative phosphorylation (OXPHOS), via loss of complex I activity and assembly in other tissues. Because the kidney relies on OXPHOS for metabolic homeostasis, we hypothesized that a decrease in AIF would result in chronic kidney disease (CKD). Here, we report that partial knockdown of Aif in mice recapitulates many features of CKD, in association with a compensatory increase in the mitochondrial ATP pool via a shift toward mitochondrial fusion, excess mitochondrial reactive oxygen species production, and Nox4 upregulation. However, despite a 50% lower AIF protein content in the kidney cortex, there was no loss of complex I activity or assembly. When diabetes was superimposed onto Aif knockdown, there were extensive changes in mitochondrial function and networking, which augmented the renal lesion. Studies in patients with diabetic nephropathy showed a decrease in AIF within the renal tubular compartment and lower AIFM1 renal cortical gene expression, which correlated with declining glomerular filtration rate. Lentiviral overexpression of Aif1m rescued glucose-induced disruption of mitochondrial respiration in human primary proximal tubule cells. These studies demonstrate that AIF deficiency is a risk factor for the development of diabetic kidney disease.

The transplant team's support of kidney transplant recipients to take their prescribed medications: a collective responsibility.

AIMS AND OBJECTIVES: To obtain an understanding of how health professionals support the kidney transplant patient to take their medications as prescribed long term. BACKGROUND: Kidney transplantation requires stringent adherence to complex medication regimens to prevent graft rejection and to maintain general well-being. Medication nonadherence is common in kidney transplantation, emerging in the first few months post-transplantation, leading to poor patient outcomes. DESIGN: Exploratory qualitative design. METHODS: Five focus groups were conducted with a total of seven renal nurse transplant coordinators, two renal transplant nurse unit managers, seven nephrologists, seven pharmacists, four social workers, and one consumer representative representing all five hospitals offering adult kidney transplantation in Victoria, Australia in 2014. The views of two general practitioners who were unable to attend the focus groups were incorporated into the data set. All data underwent thematic analysis. RESULTS: Analysis revealed that adherence was a collective responsibility involving the whole of the transplant team and the patient via education blitz in hospital, identifying and managing nonadherence, promotion of self-advocacy, and the partnership between the patient and health professional. Patients were directed how to take their complex medications to be self-empowered, yet the partnership between the patient and health professional limited the patient's voice. CONCLUSION: Although medication adherence was a collective responsibility, communication was often one-way chiefly as a result of staffing and time constraints, hindering effective partnerships necessary for medication adherence. Expert skills in communication and adherence counselling are necessary to identify barriers affecting medication adherence. Patients need to be systematically screened, prepared and supported long-term within an accommodating healthcare system for the reality of caring for their transplanted kidney. RELEVANCE TO CLINICAL PRACTICE: Kidney transplant recipients require systematic preparation and quality long-term follow-up to adhere to their prescribed medications.

Stressors and coping resources of Australian kidney transplant recipients related to medication taking: a qualitative study

AIM: To understand the stressors related to life post-kidney transplantation, with a focus on medication adherence, and the coping resources people use to deal with these stressors. BACKGROUND: Although kidney transplantation offers enhanced quality and years of life for patients, the management of a kidney transplant post-surgery is a complex process. DESIGN: A descriptive exploratory study. METHOD: Participants were recruited from five kidney transplant units in Victoria, Australia. From March to May 2014, patients who had either maintained their kidney transplant for ≥ 8 months or had experienced a kidney graft loss due to medication non-adherence were interviewed. All audio-recordings of interviews were transcribed verbatim and underwent Ritchie and Spencer's framework analysis. RESULTS: Participants consisted of fifteen men and ten women aged 26 - 72 years old. All identified themes were categorised into: 1) Causes of distress and 2) Coping resources. Post-kidney transplantation, causes of distress included the regimented routine necessary for graft maintenance, and the everlasting fear of potential graft rejection, contracting infections and developing cancer. Coping resources utilised to manage the stressors were firstly, a shift in perspective about how easy it was to manage a kidney transplant than to be dialysis-dependent and secondly, receiving external help from fellow patients, family members and healthcare professionals in addition to utilising electronic reminders. CONCLUSION: An individual well-equipped with coping resources is able to deal with stressors better. It is recommended that changes, such as providing regular reminders about the lifestyle benefits of kidney transplantation, creating opportunities for patients to share their experiences and promoting the utilisation of a reminder alarm to take medications, will reduce the stress of managing a kidney transplant.

The role of religion and spirituality in coping with kidney disease and haemodialysis in Thailand

BACKGROUND: People with chronic kidney disease (CKD) face various problems including psychological, socioeconomic and physical effects associated with CKD and its treatment. They need to develop strategies to help them cope with CKD and life challenges. Religion and spirituality are important coping strategies, but their role in helping people cope with CKD and haemodialysis (HD) in Thailand is relatively unknown.

AIMS: To investigate the role of religion and spirituality in coping with CKD and its treatment in Thailand.

DESIGN: An exploratory, qualitative approach was undertaken using semistructured individual interviews.
METHOD: Purposive sampling was used to recruit participants. Face-to-face, in-depth individual interviews using open questions were conducted during January and February 2012. Interviews were audio-recorded and transcribed verbatim. Data were analysed using the framework method of qualitative data analysis.

FINDINGS: Twenty people receiving HD participated: age range 23-77 years, mean 53.7 (±16.38 SD). Ten were women. Participants reported use of religious and spiritual practices to cope with CKD and its treatment, including religious and spiritual explanations for developing CKD, karmic disease, making merit, reading Dharma books, praying and chanting to save life and making a vow to Pran-Boon.

CONCLUSION: Religion and spirituality provide powerful coping strategies that can help Thai people with CKD overcome the associated distress and difficulties. Religion and spirituality cannot be separated in Thai culture because Thai people are both religious and spiritual.

Sulfate transporters involved in sulfate secretion in the kidney are localized in the renal proximal tubule II of the elephant fish (Callorhinchus milii)

Most vertebrates, including cartilaginous fishes, maintain their plasma SO4 (2-) concentration ([SO4 (2-)]) within a narrow range of 0.2-1 mM. As seawater has a [SO4 (2-)] about 40 times higher than that of the plasma, SO4 (2-) excretion is the major role of kidneys in marine teleost fishes. It has been suggested that cartilaginous fishes also excrete excess SO4 (2-) via the kidney. However, little is known about the underlying mechanisms for SO4 (2-) transport in cartilaginous fish, largely due to the extraordinarily elaborate four-loop configuration of the nephron, which consists of at least 10 morphologically distinguishable segments. In the present study, we determined cDNA sequences from the kidney of holocephalan elephant fish (Callorhinchus milii) that encoded solute carrier family 26 member 1 (Slc26a1) and member 6 (Slc26a6), which are SO4 (2-) transporters that are expressed in mammalian and teleost kidneys. Elephant fish Slc26a1 (cmSlc26a1) and cmSlc26a6 mRNAs were coexpressed in the proximal II (PII) segment of the nephron, which comprises the second loop in the sinus zone. Functional analyses using Xenopus oocytes and the results of immunohistochemistry revealed that cmSlc26a1 is a basolaterally located electroneutral SO4 (2-) transporter, while cmSlc26a6 is an apically located, electrogenic Cl(-)/SO4 (2-) exchanger. In addition, we found that both cmSlc26a1 and cmSlc26a6 were abundantly expressed in the kidney of embryos; SO4 (2-) was concentrated in a bladder-like structure of elephant fish embryos. Our results demonstrated that the PII segment of the nephron contributes to the secretion of excess SO4 (2-) by the kidney of elephant fish. Possible mechanisms for SO4 (2-) secretion in the PII segment are discussed.

The complexity in the implementation process of empowerment-based chronic kidney care: a case study

Background: This study is part of an interactive improvement intervention aimed to facilitate empowerment-based chronic kidney care using data from persons with CKD and their family members. There are many challenges to implementing empowerment-based care, and it is therefore necessary to study the implementation process. The aim of this study was to generate knowledge regarding the implementation process of an improvement intervention of empowerment for those who require chronic kidney care. Methods: A prospective single qualitative case study was chosen to follow the process of the implementation over a two year period. Twelve health care professionals were selected based on their various role(s) in the implementation of the improvement intervention. Data collection comprised of digitally recorded project group meetings, field notes of the meetings, and individual interviews before and after the improvement project. These multiple data were analyzed using qualitative latent content analysis. Results: Two facilitator themes emerged: Moving spirit and Encouragement. The healthcare professionals described a willingness to individualize care and to increase their professional development in the field of chronic kidney care. The implementation process was strongly reinforced by both the researchers working interactively with the staff, and the project group. One theme emerged as a barrier: the Limitations of the organization. Changes in the organization hindered the implementation of the intervention throughout the study period, and the lack of interplay in the organization most impeded the process. Conclusions: The findings indicated the complexity of maintaining a sustainable and lasting implementation over a period of two years. Implementing empowerment-based care was found to be facilitated by the cooperation between all involved healthcare professionals. Furthermore, long-term improvement interventions need strong encouragement from all levels of the organization to maintain engagement, even when it is initiated by the health care professionals themselves.

Methodology used in studies reporting chronic kidney disease prevalence : a systematic literature review

BACKGROUND: Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. METHODS: For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. RESULTS: We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. CONCLUSIONS: The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

Urinary osteopontin predicts incident chronic kidney disease, while plasma osteopontin predicts cardiovascular death in elderly men

Background and objectives The matricellular protein osteopontin is involved in the pathogenesis of both kidney and cardiovascular disease. However, whether circulating and urinary osteopontin levels are associated with the risk of these diseases is less studied. Design, setting, participants and measurements A community-based cohort of elderly (Uppsala Longitudinal Study of Adult Men [ULSAM; n=741; mean age: 77 years]) was used to study the associations between plasma and urinary osteopontin, incident chronic kidney disease, and the risk of cardiovascular death during a median of 8 years of follow-up. Results There was no significant cross-sectional correlation between plasma and urinary osteopontin (Spearman rho=0.07, p=0.13). Higher urinary, but not plasma osteopontin, was associated with incident chronic kidney disease in multivariable models adjusted for age, cardiovascular risk factors, baseline glomerular filtration rate (GFR), urinary albumin/creatinine ratio, and inflammatory markers interleukin 6 and high sensitivity C-reactive protein (Odds ratio for 1-standard deviation (SD) of urinary osteopontin, 1.42, 95% CI (1.00-2.02), p=0.048). Conversely, plasma osteopontin, but not urinary osteopontin, was independently associated with cardiovascular death (multivariable hazard ratio per SD increase, 1.35, 95% CI (1.14-1.58), p<0.001, and 1.00, 95% CI (0.79-1.26), p=0.99, respectively). The addition of plasma osteopontin to a model with established cardiovascular risk factors significantly increased the C-statistics for the prediction of cardiovascular death (p<0.002). Conclusions Higher urinary osteopontin specifically predicts incident chronic kidney disease while plasma osteopontin specifically predicts cardiovascular death. Our data put forward osteopontin as an important factor in the detrimental interplay between the kidney and the cardiovascular system. The clinical implications, and why plasma and urinary osteopontin mirror different pathologies, remains to be established.

Risk, regulation, and financial incentives for living kidney donation

In his comprehensive review of the hazards of existing,largely unregulated markets in human kidneys, Koplin(2014) argues that advocates of regulated markets mayunderestimate the potential physical, psychosocial andfinancial harms risked by vendors. He acknowledges, however,that market proponents will likely be undeterred incalling for “trials” or “pilot studies” of financial incentivesin developed countries on the grounds that the experienceof international black markets is of limited predictive valuein anticipating the outcomes of regulated markets. We contendthat there is good evidence to support the concernthat living vendors would be at higher risk of adversehealth outcomes compared to altruistic donors in the contextof a regulated market. This has important implicationsnot only for the informed consent of prospective vendors,but also for the potential regulations that would berequired to mitigate these risks. We argue here that pilotstudies would be at the very least premature until suchtime as market proponents have sufficiently engaged withpotential harms to prospective kidney vendors.

The effect of holiday haemodialysis treatments on patient mood, adverse symptoms and subjective wellbeing using the Big Red Kidney Bus

BACKGROUND AND AIMS: People with end-stage kidney disease receiving haemodialysis are restricted to holidays where dialysis services are readily available. Holiday dialysis in regional, rural and remote areas is particularly challenging. The aims of this study were to (1) evaluate the wellbeing of those who received dialysis in a holiday haemodialysis bus, and (2) to measure patient wellbeing with that of a comparable cohort of haemodialysis patients. METHODS: A three machine haemodialysis bus, the Big Red Kidney Bus, was built to enable people, their families and carers to take holidays across a range of tourist destinations in Victoria, Australia. Measures included pre-post subjective wellbeing, dialysis symptoms and mood questionnaires complemented by post semi-structured telephone interviews. RESULTS: Participating holidaymakers were positive about the haemodialysis bus service and the standard of care experienced. They reported decreased dialysis side effects of fatigue, muscle cramp, and dry skin. The overall number of reported symptoms decreased and the perceived level of bother associated with symptoms also decreased. No changes in subjective wellbeing and mood were detected. Mean Personal Wellbeing Index scores were significantly higher than in a comparative haemodialysis sample. CONCLUSION: The Big Red Kidney Bus provided a safe and feasible holiday dialysis service. Holidaymakers' wellbeing was reflected by the decreased dialysis patient side effects.

Protect your body, your temple : Do You Know Your Kidney Count?

These bookmarks state: Your kidney count is a number that your doctor can tell you that could save your life. Your kidney count should be 90 or above. In South Carolina, 1 in 8 people has kidney disease. More than 70 percent of South Carolinians on dialysis are African-American. If you have diabetes or high blood pressure, you are at risk for kidney disease. Kidney disease can be prevented or delayed.

Índice del perfil del donante renal (KDPI) como factor pronóstico del trasplante

La enfermedad renal crónica ha aumentado a nivel mundial y nacional, mientras que el número de donantes viene en descenso, y los pacientes en lista de espera aumentan. Los donantes cadavéricos son una opción para estos pacientes, y han sido utilizados en últimos años para aumentar los órganos disponibles. La evaluación de la calidad de estos es importante para optimizar su uso. Estudio analítico tipo cohorte retrospectiva, cálculo de KDPI en donantes cadavéricos, seguimiento función renal creatinina sérica 1 mes, 3 meses, 6 meses y un año. Correlación supervivencia del injerto, función renal, KDPI y EPTS. Análisis de supervivencia y regresión logística con variables del donante, receptor y acto quirúrgico.