Levofloxacin based non-rifampicin anti-tuberculous therapy: An effective alternative in renal transplant recipients in resource limited setting.

INTRODUCTION: Rifampicin is one of the most effective components of anti-tuberculous therapy (ATT). Since rifampicin is a hepatic enzyme (CYP3A4) inducer, in a post-renal transplant recipient, the dose of calcineurin inhibitors needs to be up-regulated and frequently monitored. In resource-limited (low- and lower-middle-income countries) setting this is not always feasible. Therefore, we evaluated a non-rifampicin-based ATT using levofloxacin in kidney transplant recipients. METHODS: We retrospectively studied the medical records of renal transplant recipients diagnosed with tuberculosis in our institute between 2014 and 2017. After a brief discussion with patients regarding the nature and course of ATT, those who opted for a non-rifampicin based therapy due to financial constraints were included in the study and followed for a minimum of 6 months period after the completion of ATT. RESULTS: Out of the 550 renal transplant recipients, 67 (12.2%) developed tuberculosis after a median period of 24 (1-228) months following transplantation, of them, 64 patients opted for non-rifampicin-based ATT. The mean age was 37.6 years. Only 25% were given anti-thymocyte globulin based induction, while the majority (56; 87.5%) of them were on tacrolimus-based triple-drug maintenance therapy. Extrapulmonary tuberculosis was noted in 33% of cases, while 12 (18.7%) had disseminated disease. The median duration of treatment was 12 months and the cure rate of 93.7% (n = 60) was achieved at the end of therapy. CONCLUSION: Levofloxacin based ATT appears to be a safe and effective alternative of rifampicin in kidney transplant recipients who cannot afford heightened tacrolimus dosage.

Equity-Efficiency Trade-offs Associated With Alternative Approaches to Deceased Donor Kidney Allocation: A Patient-level Simulation.

BACKGROUND: The number of patients waiting to receive a kidney transplant outstrips the supply of donor organs. We sought to quantify trade-offs associated with different approaches to deceased donor kidney allocation in terms of quality-adjusted life years (QALYs), costs, and access to transplantation. METHODS: An individual patient simulation model was developed to compare 5 different approaches to kidney allocation, including the 2006 UK National Kidney Allocation Scheme (NKAS) and a QALY maximization approach designed to maximize health gains from a limited supply of donor organs. We used various sources of patient-level data to develop multivariable regression models to predict survival, health state utilities, and costs. We simulated the allocation of kidneys from 2200 deceased donors to a waiting list of 5500 patients and produced estimates of total lifetime costs and QALYs for each allocation scheme. RESULTS: Among patients who received a transplant, the QALY maximization approach generated 48 045 QALYs and cost £681 million, while the 2006 NKAS generated 44 040 QALYs and cost £625 million. When also taking into consideration outcomes for patients who were not prioritized to receive a transplant, the 2006 NKAS produced higher total QALYs and costs and an incremental cost-effectiveness ratio of £110 741/QALY compared with the QALY maximization approach. CONCLUSIONS: Compared with the 2006 NKAS, a QALY maximization approach makes more efficient use of deceased donor kidneys but reduces access to transplantation for older patients and results in greater inequity in the distribution of health gains between patients who receive a transplant and patients who remain on the waiting list.

Comparing Simultaneous Liver-Kidney Transplant Strategies: A Modified Cost-Effectiveness Analysis.

BACKGROUND: The proportion of patients with kidney failure at time of liver transplantation is at a historic high in the United States. The optimal timing of kidney transplantation with respect to the liver transplant is unknown. METHODS: We used a modified cost-effectiveness analysis to compare 4 strategies: the old system ("pre-OPTN"), the new Organ Procurement Transplant Network (OPTN) system since August 10, 2017 ("OPTN"), and 2 strategies which restrict simultaneous liver-kidney transplants ("safety net" and "stringent"). We measured "cost" by deployment of deceased donor kidneys (DDKs) to liver transplant recipients and effectiveness by life years (LYs) and quality-adjusted life years (QALYs) in liver transplant recipients. We validated our model against Scientific Registry for Transplant Recipients data. RESULTS: The OPTN, safety net and stringent strategies were on the efficiency frontier. By rank order, OPTN > safety net > stringent strategy in terms of LY, QALY, and DDK deployment. The pre-OPTN system was dominated, or outperformed, by all alternative strategies. The incremental LY per DDK between the strategies ranged from 1.30 to 1.85. The incremental QALY per DDK ranged from 1.11 to 2.03. CONCLUSIONS: These estimates quantify the "organ"-effectiveness of various kidney allocation strategies for liver transplant candidates. The OPTN system will likely deliver better liver transplant outcomes at the expense of more frequent deployment of DDKs to liver transplant recipients.

Caring for Migrants and Refugees With End-Stage Kidney Disease in Europe.

With the number of migrants and refugees increasing globally, the nephrology community is increasingly confronted with issues relating to the management of end-stage kidney disease in this population, including medical, logistical, financial, and moral-ethical questions. Beginning with data for the state of affairs regarding refugees in Europe and grounded in moral reasoning theory, this Policy Forum Perspective contends that to improve care for this specific population, there is a need for: (1) clear demarcations of responsibilities across the societal (macro), local (meso), and individual (micro) levels, such that individual providers are aware of available resources and able to provide essential medical care while societies and local communities determine the general approach to dialysis care for refugees; (2) additional data and evidence to facilitate decision making based on facts rather than emotions; and (3) better information and education in a broad sense (cultural sensitivity, legal rights and obligations, and medical knowledge) to address specific needs in this population. Although the nephrology community cannot leverage a change in the geopolitical framework, we are in a position to generate accurate data describing the dimensions of care of refugee or migrant patients with end-stage kidney disease to advocate for a holistic approach to treatment for this unique patient population.

Immunosuppressive agents in adult kidney transplantation in the National Health Service: a model-based economic evaluation.

BACKGROUND: Immunosuppression is required in kidney transplantation to prevent rejection and prolong graft survival. We conducted an economic evaluation to support England's National Institute for Health and Care Excellence in developing updated guidance on the use of immunosuppression, incorporating new immunosuppressive agents, and addressing changes in pricing and the evidence base. METHODS: A discrete-time state transition model was developed to simulate adult kidney transplant patients over their lifetime. A total of 16 different regimens were modelled to assess the cost-effectiveness of basiliximab and rabbit anti-thymocyte globulin (rabbit ATG) as induction agents (with no antibody induction as a comparator) and immediate-release tacrolimus, prolonged-release tacrolimus, mycophenolate mofetil, mycophenolate sodium, sirolimus, everolimus and belatacept as maintenance agents (with ciclosporin and azathioprine as comparators). Graft survival was extrapolated from acute rejection rates, graft function and post-transplant diabetes rates, all estimated at 12 months post-transplantation. National Health Service (NHS) and personal social services costs were included. Cost-effectiveness thresholds of £20 000 and £30 000 per quality-adjusted life year were used. RESULTS: Basiliximab was predicted to be more effective and less costly than rabbit ATG and induction without antibodies. Immediate-release tacrolimus and mycophenolate mofetil were cost-effective as maintenance therapies. Other therapies were either more expensive and less effective or would only be cost-effective if a threshold in excess of £100 000 per quality-adjusted life year were used. CONCLUSIONS: A regimen comprising induction with basiliximab, followed by maintenance therapy with immediate-release tacrolimus and mycophenolate mofetil, is likely to be effective for uncomplicated adult kidney transplant patients and a cost-effective use of NHS resources.

Healthcare costs in chronic kidney disease and renal replacement therapy: a population-based cohort study in Sweden.

OBJECTIVE: To compare healthcare costs in chronic kidney disease (CKD) stage 4 or 5 not on dialysis (estimated glomerular filtration rate <30 mL/min/1.73m2), peritoneal dialysis, haemodialysis and in transplanted patients with matched general population comparators. DESIGN: Population-based cohort study. SETTING: Swedish national healthcare system. PARTICIPANTS: Prevalent adult patients with CKD 4 or 5 (n=1046, mean age 68 years), on peritoneal dialysis (n=101; 64 years), on haemodialysis (n=460; 65 years) and with renal transplants (n=825; 52 years) were identified in Stockholm County clinical quality registers for renal disease on 1 January 2010. 5 general population comparators from the same county were matched to each patient by age, sex and index year. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual healthcare costs in 2009 incurred through inpatient and hospital-based outpatient care and dispensed prescription drugs ascertained from nationwide healthcare registers. Secondary outcomes were annual number of hospital days and outpatient care visits. RESULTS: Patients on haemodialysis had the highest mean annual cost (€87 600), which was 1.49 (95% CI 1.38 to 1.60) times that observed in peritoneal dialysis (€58 600). The mean annual cost was considerably lower in transplanted patients (€15 500) and in the CKD group (€9600). In patients on haemodialysis, outpatient care costs made up more than two-thirds (€62 500) of the total, while costs related to fluids ($29 900) was the largest cost component in patients on peritoneal dialysis (51%). Compared with their matched general population comparators, the mean annual cost (95% CI) in patients on haemodialysis, peritoneal dialysis, transplanted patients and patients with CKD was 45 (39 to 51), 29 (22 to 37), 11 (10 to 13) and 4.0 (3.6 to 4.5) times higher, respectively. CONCLUSIONS: The mean annual costs were ∼50% higher in patients on haemodialysis than in those on peritoneal dialysis. Compared with the general population, costs were substantially elevated in all groups, from 4-fold in patients with CKD to 11, 29 and 45 times higher in transplanted patients and patients on peritoneal dialysis and haemodialysis, respectively.

[Analysis of contractual incentives for kidney transplants in Brazil using the principal-agent model]. / Análise dos incentivos contratuais de transplantes de rins no Brasil pelo modelo agente-principal.

The aim of this article was to analyze contractual incentives for kidney transplants in Brazil based on the principal-agent model. The approach assumes that the Brazilian Ministry of Health is the principal and the public hospitals accredited by the National Transplant System are the agent. The Ministry of Health's welfare depends on measures taken by hospitals in kidney uptake. Hospitals allocate administrative, financial, and management efforts to conduct measures in kidney donation, removal, uptake, and transplantation. Hospitals may choose the levels of effort that are consistent with the payments and incentives received in relation to transplantation costs. The solution to this type of problem lies in structuring an optimal incentives contract, which requires aligning the interests of both parties involved in the transplantation system.

Cost comparison of kidney transplant versus dialysis in Brazil.

This study aimed to compare the direct medical costs of renal transplantation and renal replacement therapies, specifically hemodialysis and peritoneal dialysis, from the perspective of the Brazilian Unified National Health System (SUS). Renal replacement therapies costs were based on data published in the literature. Cost items for kidney transplant were identified in a private hospital based on procedure codes used for charging the SUS, and other items were taken from the literature. In the four years covered by the study, cadaver kidney transplant generated per-patient savings of BRL 37,000 and BRL 74,000 compared to hemodialysis and peritoneal dialysis, respectively. Savings were even greater with living donor kidney transplant: BRL 46,000 and BRL 82,000 compared to hemodialysis and peritoneal dialysis, respectively. This result, together with survival and quality-of-life analyses, characterizes kidney transplant as the best clinical and financial alternative, thus supporting public policies for organ transplants in Brazil.

Uma comparação dos custos do transplante renal em relação às diálises no Brasil / Cost comparison of kidney transplant versus dialysis in Brazil / Una comparación de los costes del trasplante renal en relación con las diálisis en Brasil

Resumo: O objetivo do presente estudo foi comparar os custos médicos diretos do transplante renal e das terapias renais substitutivas, especificamente a hemodiálise e a diálise peritoneal, sob a perspectiva do Sistema Único de Saúde (SUS). Os custos das terapias renais substitutivas foram extraídos de informações publicadas na literatura. Os itens de custo previstos do transplante renal foram identificados em um hospital privado mediante coleta dos códigos dos procedimentos utilizados para a cobrança do SUS e os demais itens extraídos da literatura. O resultado desta pesquisa indica que, no período dos quatro anos coberto por este estudo, o transplante renal de doador falecido gera uma economia, por paciente, de R$ 37 mil e R$ 74 mil em relação à hemodiálise e à diálise peritoneal, respectivamente. Quanto ao transplante renal de doador vivo, as economias são ainda maiores: R$ 46 mil e R$ 82 mil em relação à hemodiálise e à diálise peritoneal, respectivamente. Este resultado, aliado a análises de sobrevida e qualidade de vida, pode caracterizar o transplante renal como a melhor alternativa do ponto de vista financeiro e clínico, auxiliando na formulação de políticas públicas relacionadas com os transplantes de órgãos no Brasil.

Abstract: This study aimed to compare the direct medical costs of renal transplantation and renal replacement therapies, specifically hemodialysis and peritoneal dialysis, from the perspective of the Brazilian Unified National Health System (SUS). Renal replacement therapies costs were based on data published in the literature. Cost items for kidney transplant were identified in a private hospital based on procedure codes used for charging the SUS, and other items were taken from the literature. In the four years covered by the study, cadaver kidney transplant generated per-patient savings of BRL 37,000 and BRL 74,000 compared to hemodialysis and peritoneal dialysis, respectively. Savings were even greater with living donor kidney transplant: BRL 46,000 and BRL 82,000 compared to hemodialysis and peritoneal dialysis, respectively. This result, together with survival and quality-of-life analyses, characterizes kidney transplant as the best clinical and financial alternative, thus supporting public policies for organ transplants in Brazil.

Resumen: El objetivo del presente estudio fue comparar los costes médicos directos del trasplante renal y de las terapias renales substitutivas, específicamente la hemodiálisis y la diálisis peritoneal, bajo la perspectiva del Sistema Único de Salud (SUS). Los costes de las terapias renales substitutivas se extrajeron de información publicada en la literatura. Los ítems de coste previstos del trasplante renal se identificaron en un hospital privado, a partir de la recogida de códigos de procedimientos utilizados para el cobro del SUS y los demás ítems extraídos de la literatura. El resultado de esta investigación indica que, en el período de los 4 años cubierto por este estudio, el trasplante renal del donante fallecido genera un ahorro, por paciente, de R$ 37 mil y R$ 74 mil en relación al hemodiálisis y al diálisis peritoneal, respectivamente. En cuanto al trasplante renal del donante vivo, los ahorros son incluso mayores: R$ 46 mil y R$ 82 mil, en relación a la hemodiálisis y a la diálisis peritoneal, respectivamente. Este resultado, junto con análisis de supervivencia y calidad de vida, puede caracterizar el trasplante renal como la mejor alternativa desde el punto de vista financiero y clínico, auxiliando en la formulación de políticas públicas relacionadas con los trasplantes de órganos en Brasil.

Análise dos incentivos contratuais de transplantes de rins no Brasil pelo modelo agente-principal / Analysis of contractual incentives for kidney transplants in Brazil using the principal-agent model / Análisis de los incentivos contractuales de trasplantes de riñón en Brasil mediante el modelo agente-principal

Resumo: O objetivo do artigo foi analisar os incentivos contratuais de transplantes renais no Brasil com base no modelo agente-principal. A abordagem assume que o Ministério da Saúde seja o principal e os hospitais públicos credenciados pelo Sistema Nacional de Transplantes sejam o agente. O bem- estar do Ministério da Saúde depende das ações tomadas pelos hospitais captadores desse órgão. Os hospitais alocam esforços administrativos, financeiros e gerenciais para realizar as ações de doação, remoção, captação e transplante de rim. Os hospitais podem escolher os níveis de esforços que são compatíveis com os pagamentos e incentivos recebidos referentes ao custeio de transplantes. A solução para esse tipo de problema está na estruturação de um contrato ótimo de incentivos, no qual se requer um alinhamento de interesses de ambas as partes envolvidas nesse sistema de transplantes.

Abstract: The aim of this article was to analyze contractual incentives for kidney transplants in Brazil based on the principal-agent model. The approach assumes that the Brazilian Ministry of Health is the principal and the public hospitals accredited by the National Transplant System are the agent. The Ministry of Health's welfare depends on measures taken by hospitals in kidney uptake. Hospitals allocate administrative, financial, and management efforts to conduct measures in kidney donation, removal, uptake, and transplantation. Hospitals may choose the levels of effort that are consistent with the payments and incentives received in relation to transplantation costs. The solution to this type of problem lies in structuring an optimal incentives contract, which requires aligning the interests of both parties involved in the transplantation system.

Resumen: El objetivo del artículo fue analizar los incentivos contractuales de trasplantes renales en Brasil, a partir del modelo agente-principal. Este enfoque asume que el Ministerio de Salud sea el principal y los hospitales públicos, autorizados por el Sistema Nacional de Trasplantes, sean los agentes. El bienestar del Ministerio de Salud depende de las acciones tomadas por los hospitales receptores de este órgano. Los hospitales proporcionan los esfuerzos administrativos, financieros y de gestión para realizar las acciones de donación, extirpación, recepción y trasplante de riñón. Los hospitales pueden escoger los niveles de esfuerzos que son compatibles con los pagos e incentivos recibidos, referentes al costeo de trasplantes. La solución para este tipo de problema está en la estructuración de un contrato óptimo de incentivos, en el que se requiera un alineamiento de intereses de ambas partes involucradas en este sistema de trasplantes.

Evaluation of clinical and safety outcomes associated with conversion from brand-name to generic tacrolimus in transplant recipients enrolled in an integrated health care system.

STUDY OBJECTIVE: To evaluate clinical and safety outcomes among transplant recipients whose tacrolimus was converted from the brand-name formulation to a generic formulation. DESIGN: Retrospective analysis. DATA SOURCE: Clinical databases and electronic records from a large, integrated health care system in California. PATIENTS: A total of 234 clinically stable, adult transplant recipients (renal, liver, and heart) whose tacrolimus was converted from the brand-name formulation to a generic formulation between October 1, 2010, and December 31, 2010, according to a physician-approved protocol. MEASUREMENTS AND MAIN RESULTS: For each patient, pre- and postconversion tacrolimus trough concentrations and serum creatinine concentrations were analyzed. Data were also collected on the percentage of patients who required dosage titration, drug cost savings, and rates of reversion to brand-name tacrolimus, biopsy-proved acute allograft rejections, and mortality. No significant differences were noted in mean ± SD pre- and postconversion tacrolimus trough levels (6.74 ± 1.61 vs 6.96 ± 2.31 ng/ml, p=0.137) or serum creatinine concentrations (1.33 ± 0.48 vs 1.36 ± 0.82 mg/dl, p=0.302). The mean ± SD percent change in tacrolimus trough concentration was 5.63 ± 32.95%. Thirty-six patients (15.4%) required dosage titration. Six patients (2.6%) reverted back to brand-name tacrolimus. No deaths or acute rejections occurred. Use of the generic product saved each patient an average of $45/month in drug acquisition cost and $26/prescription copayment. CONCLUSION: Clinical experience as well as research data show that use of generic tacrolimus results in trough concentrations that are comparable to the brand-name drug. Given the lack of adverse events reported and the cost savings recognized, conversion from brand-name tacrolimus to generic tacrolimus should be encouraged. Since dosage titration may be required, close therapeutic drug monitoring is recommended.

More than 1,000 kidney transplants in a single year by the "Hospital do Rim" Group in Sao Paulo - Brazil.

We describe the organization of a high-volume Brazilian kidney transplant program that performed 7,833 transplants in 12 years fulfilling government expectations without compromising the care of the patients. The annual number of kidney transplants increased from 428 in 1999 to 1,048 in 2010. In our Organ Procurement Organization (6.1 million inhabitants) brain death notifications increased from 196 to 468 in 2010 and 35% became actual donors. There are 5,011 patients on the waiting list and recipient selection is based on HLA matching. A significant proportion of the recipients is of black ethnicity and had been for long time on dialysis. Over 700 first appointments for living donation are done every year. After the transplant, the majority of patients are followed locally (200-250 appointments per day). The transplant outcome among living-donor recipients is comparable to large registries but inferior outcome have been observed among recipients of deceased donor organs, though consistent improvement has been seen in more recent years. We also discuss issues related to local regulations and solutions to improve efficiency and outcomes.

National Kidney Registry: 213 transplants in three years.

Since its establishment in 2008, the National Kidney Registry has facilitated 213 kidney transplants between unrelated living donors and recipients at 28 transplant centers. Rapid innovations in matching strategies, advanced computer technologies, good communication and an evolving understanding of the processes at participating transplant centers and histocompatibility laboratories are among the factors driving the success of the NKR. Virtual cross match accuracy has improved from 43% to 91% as a result of changes to the HLA typing requirements for potential donors and improved mechanisms to list unacceptable HLA antigens for sensitized patients. A uniform financial agreement among participating centers eliminated a major roadblock to facilitate unbalanced donor kidney exchanges among centers. The NKR transplanted 64% of the patients registered since 2008 and the average waiting time for those transplanted in 2010 was 11 months.

The databases: renal replacement therapy since 1989--the European Renal Association and European Dialysis and Transplant Association (ERA-EDTA).

Chronic kidney disease is now considered a public health priority, and the prevalence of this disease is approximately 10% in both North American and European countries. Such a phenomenon raises concern about the future increased incidence of ESRD. A recent analysis in the European Renal Association-European Dialysis and Transplant Association Registry shows that the incidence rates in Northern European countries have stabilized at approximately 110 per million people, a phenomenon that is associated with a parallel stabilization in the incidence of ESRD caused by diabetes. Such a stabilization has occurred in the face of an increasing prevalence of diabetes and hypertension in the general population, suggesting that this improvement may be the result of better prevention. Genetic factors, competing risks with other diseases, and other medical factors explain only in part the variability in the incidence of renal replacement therapy in European countries. Health care financing priorities have an obvious influence on the outcome of ESRD. Nonmedical factors seem to be of importance at least equal to that of medical factors. In this respect, Dialysis Outcomes and Practice Patterns Study Europe has revealed relevant differences in clinical policies that are related to ESRD treatment among European countries.

Chronic kidney disease, transplantation practices and transplantation law in Pakistan: opportunity for a global meditation.

The majority of countries have enacted edicts to regulate organ transplantation due to mounting recognition of its intricacies and increasing level of global disquiet. Frail national economy and status of health care infrastructure restricts access of the local population to both dialysis and transplantation in Pakistan. There is a surge in kidney transplantation activities, however. I have reported the enormity of organ crime in Pakistan. The number of commercial renal transplants range from 3000 to 4500. Foreign nationals share the marketplace. There are current attempts from the government to stop organ trade by strictly enforcing a recently sanctioned law on organ transplantation. Scarcity of comprehensive reliable data has hampered plausible assessments and indispensable modifications to facilitate designs for the future health care. Alternatives to organ transplantation will augment the choice of treatment modalities for a proliferating end-stage renal disease (ESRD) population. The whole array of existing therapeutic modalities for ESRD has to be utilized. Promoting a fresh culture of organ donation by strengthening of the family institution may be another objective.

End-stage renal disease in Indonesia: treatment development.

The number of cases of chronic kidney disease is growing rapidly, especially in the developing world. At a certain level of renal function, progression of chronic kidney disease to endstage renal disease (ESRD) is inevitable. ESRD has become a major health problem because it is a devastating medical condition, and the cost of treatment is a huge economic burden. This article presents data collected from 13 nephrology centers in response to specifically designed questionnaires. These centers were divided into 7 groups on the basis of geographic location. Previous data had given the impression that the incidence and prevalence of ESRD had increased, and the results of this study support these previous data. Since a national registry of ESRD has just been developed for Indonesia and we can present only limited data in this study, the numbers in this article underestimate the true incidence and prevalence rates. Although hemodialysis facilities have been developed rapidly, further development is still required. Continuous ambulatory peritoneal dialysis as an alternative renal replacement therapy (RRT) is only now being introduced. Kidney transplantation programs expand very slowly. RRT still imposes a high cost of treatment for ESRD; therefore, these treatments are unaffordable for most patients. Recently, government health insurance has covered financially strained families requiring RRT. Since the cost of RRT for ESRD has significantly increased over time, the management approach should be shifted from treatment to prevention.

End-stage renal disease and economic incentives: the International Study of Health Care Organization and Financing (ISHCOF).

End-stage renal disease (ESRD) is a debilitating, costly, and increasingly common condition. Little is known about how different financing approaches affect ESRD outcomes and delivery of care. This paper presents results from a comparative review of 12 countries with alternative models of incentives and benefits, collected under the International Study of Health Care Organization and Financing, a substudy within the Dialysis Outcomes and Practice Patterns Study. Variation in spending per ESRD patient is relatively small, but correlated with overall per capita health care spending. Remaining differences in costs and outcomes do not seem strongly linked to differences in incentives.