Peritoneal Dialysis: Prospects and Challenges

<正>There are 3 kinds of Renal Replacement Therapy:hemodialysis,peritoneal dialysis and kidney transplantation.Although a kidney transplant would be the best solution,organ donations are limited and the transplanted organs can be rejected by the body.Hemodialysis is a widely recognized and near-universally available treatment method,however,the patient must make at least 3 weekly visits to a hospital to undergo treatment,with each session lasting on average around 4 hours.Consequently this can have an impact on the patients'life,including work and travel.Since the clinical populariza-     

Langzeitüberleben bei chronischer Niereninsuffizienz

Patients with end-stage renal disease require renal replacement therapy with either dialysis or kidney transplantation. Survival and quality of life (QoL) after transplantation are superior to chronic dialysis. Early living donor kidney transplantation is best for patient and graft survival. Preemptive living-related kidney transplantation therefore is the best medical treatment option for these patients. Patients with end-stage renal disease suffer from multiple physical and psychological complaints. The prevalence of depressive disorders is 20-25% in this population. Studies on QoL in children after kidney transplantation show a reduced physical QoL, but an overall good psychological QoL. Alarming results of numerous studies are the high non-adherence rates in adolescents. Especially exercise interventions during dialysis and after kidney transplantation show promising results. Whether QoL of patients will improve with new approaches to immunosuppressive therapy remains to be evaluated in future studies.     

Pretransplant obesity: a weighty issue affecting transplant candidacy and outcomes.

Because of the global increase in prevalence of obesity, many more overweight and obese individuals are undergoing evaluation for transplantation than in the past. Although obesity seems to provide a survival benefit in dialysis patients, obesity has traditionally been considered a contraindication for transplantation of most organs. It is theorized that obesity will contribute to worse transplant outcomes, including lower rates of graft and patient survival and higher rates of delayed graft function and infection. This review evaluates the available literature evaluating outcomes of obese patients with end-stage organ failure who undergo transplantation. Obesity seems to be associated with increased rates of wound infection after transplantation. However, other adverse transplant outcomes related to obesity seem to be dependent on the type of organ being transplanted and the degree of obesity. For example, a body mass index (BMI) of 30 kg/m(2) may reduce short-term survival in lung transplant recipients; however, obesity does not seem to confer an adverse effect on short- or long-term survival in liver transplant patients until a much higher BMI is reached (such as 35 or 40 kg/m(2)). Each transplant center must determine weight guidelines and criteria for identifying the level of obesity as a contraindication for transplantation. This must be based on organ type, each center's transplant and complication statistics, and available donor pools. Guidelines must also consider the morbidity and mortality risks of the obese patient with organ failure who does not receive a transplant.     

The role of heterogeneity of patients’ preferences in kidney transplantation

We elicit time and risk preferences for kidney transplantation from the entire population of patients of the largest Italian transplant centre using a discrete choice experiment (DCE). We measure patients’ willingness-to-wait (WTW) for receiving a kidney with one-year longer expected graft survival, or a low risk of complication. Using a mixed logit in WTW-space model, we find heterogeneity in patients’ preferences. Our model allows WTW to vary with patients’ age and duration of dialysis. The results suggest that WTW correlates with age and duration of dialysis, and that accounting for patients’ preferences in the design of kidney allocation protocols could increase their welfare. The implication for transplant practice is that eliciting patients’ preferences could help in the allocation of “non-ideal” kidneys.     

A joint model for longitudinal and time-to-event data to better assess the specific role of donor and recipient factors on long-term kidney transplantation outcomes

In renal transplantation, serum creatinine (SCr) is the main biomarker routinely measured to assess patient’s health, with chronic increases being strongly associated with long-term graft failure risk (death with a functioning graft or return to dialysis). Joint modeling may be useful to identify the specific role of risk factors on chronic evolution of kidney transplant recipients: some can be related to the SCr evolution, finally leading to graft failure, whereas others can be associated with graft failure without any modification of SCr. Sample data for 2749 patients transplanted between 2000 and 2013 with a functioning kidney at 1-year post-transplantation were obtained from the DIVAT cohort. A shared random effect joint model for longitudinal SCr values and time to graft failure was performed. We show that graft failure risk depended on both the current value and slope of the SCr. Deceased donor graft patient seemed to have a higher SCr increase, similar to patient with diabetes history, while no significant association of these two features with graft failure risk was found. Patient with a second graft was at higher risk of graft failure, independent of changes in SCr values. Anti-HLA immunization was associated with both processes simultaneously. Joint models for repeated and time-to-event data bring new opportunities to improve the epidemiological knowledge of chronic diseases. For instance in renal transplantation, several features should receive additional attention as we demonstrated their correlation with graft failure risk was independent of the SCr evolution.     

Damon or Pandora?

Americans have recently had thrust into their faces multiple media borne medical and social ethics dilemmas ranging from Dr. Kevorkian's euthanizing a patient on national television to payments by managed care providers for experimental medical treatments,to the nationally telecast situation which this paper will attempt to address. The case at hand concerns a minor in need of a repeat(third) kidney transplant who has been offered a kidney by her father. He also provided a kidney for her second kidney transplant some years ago. The teenage girl went into her current kidney failure/organ rejection state because, feeling well, she stopped taking her antirejection medications. Her father appears to understand the consequences of this offer and is willing nonetheless to donate his remaining kidney to his daughter. His ex-wife and daughter want the kidney and will take it knowing what it will do to him. Of additional interest is that he is incarcerated as a prisoner for a crime for which he will be eligible for parole in the not distant future. This means that although altruistically self-induced, the State will become financially responsible for his medical care and dialysis treatments. This paper will attempt to analyze the competing issues presented by this dilemma and address the underlying conflict between the parameters patient autonomy, parental beneficence and the deontologically based responsibilities of the state and of the health care team. This revised version was published online in July 2006 with corrections to the Cover Date.     

The relationship between social networks and pathways to kidney transplant parity: evidence from black Americans in Chicago

Research has shown that black dialysis patients in the United States are significantly less likely than their white peers to be evaluated and listed for a kidney transplant. Extrapolating from social-network theory, I hypothesize that a lack of access to social contacts with information about kidney transplantation may hinder information transaction regarding the benefits of, and pathway to, transplantation. In 2007–2008, the following research questions were addressed in an investigation in Chicago, USA: (1) What is the role of social networks in providing information about kidney transplantation to black hemodialysis patients? (2) What is the relationship between social networks and a patient’s likelihood of being seen at a kidney transplant center? From a stratified sample of dialysis units in the area, a purposive sample of 228 black patients was surveyed while they received treatment about their social networks and kidney transplant status. It was found that the odds of black hemodialysis patients being seen at a kidney transplant center increase with income, and patients who have people in their social network with information about kidney transplant were significantly more likely to be seen at a kidney transplant center. Specifically, black dialysis patients who get informational social support from their dialysis team and social networks were significantly more likely to be seen at kidney transplant centers. I conclude that considering black dialysis patients’ social milieu can be complementary to the existing research regarding this public health crisis.     

Clinical study on 53 cases of cadaveric kidney transplantation at Osaka City University Hospital

BACKGROUND: In this study, we examined the effects of nonimmunological factors on cadaver kidney transplant. METHODS: Fifty-three cadaver kidney transplant recipients were studied. They were divided into two groups, Group I ( donor age<60, n=38 ) and Group II ( donor age > or = 60, n=15). These patients were studied to determine whether donor age and recipient Body Mass Index (BMI) affected transplant outcome. RESULTS: The 3 and 5-year overall graft / patient survival was 80.6 / 100% and 72.7 97.3%, respectively. The best S-Cr after transplantation was significantly (p<0.05) lower in Group I compared to Group II. The 1, 5 and 8-year graft survival was significantly (p<0.05) better in Group I. In the low BMI patients of Group II, 5-year graft survival was significantly (p<0.01) better than high BMI patients. DISCUSSION: An aged cadaver donor was a risk factor for decreased posttransplant renal functions and lower graft survival. However, if a recipient with a low BMI can be selected, the outcome of cadaver kidney transplants from aged donors may be improved.     

Quality of life in renal transplant patients: impact of a functioning graft

Objective measures to evaluate quality of life are gaining importance as an adjuvant in assessing therapeutic interventions. The study purpose was to compare quality of life in renal transplant patients with functioning graft and those who restarted dialysis after graft loss. Quality of life was measured using the World Health Organization Quality of Life questionnaire (WHOQOL-Bref). One hundred and thirty two patients were interviewed, and divided into two groups: group I, 100 patients on regular follow-up in outpatient clinics and stable graft functioning; and group II, 32 patients who restarted dialysis after graft loss. The WHOQOL-Bref showed better quality of life in those renal transplant patients with a functioning graft, especially regarding the physical and psychological domains assessed in the general questions. There were no differences between the groups in the social relationship and environmental domains. WHOQOL-Bref is an efficient tool and can be useful for better approaching these patients, not only on a medical basis.     

Projecting Long-Term Graft and Patient Survival after Transplantation

ObjectiveIn spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates, increasing long-term graft survival rates remains a major challenge. The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in randomized trials.MethodsWe developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft. Health states included functioning graft stratified by level of renal function, failed graft, functioning regraft, and death. Transitions between health states were predicted using statistical models that accounted for renal function, acute rejection, and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival. Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System. The model was populated with data from a 3-year, randomized phase III trial comparing belatacept to cyclosporine.ResultsThe decision model was well calibrated with data from the United States Renal Data System. Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon.ConclusionsThis is the first long-term follow-up model of renal transplant patients to be based on renal function, acute rejection, and new-onset diabetes. It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications.     

How can we achieve global equity in provision of renal replacement therapy?

There is a significant emerging burden of chronic and end-stage kidney disease in low- and middle-income countries, driven by population ageing and the global epidemic of type 2 diabetes. Sufferers of end-stage kidney disease require ongoing dialysis or kidney transplantation to survive; however, in many low- and middle-income countries, treatment options are strictly limited or unaffordable. Low numbers of maintenance dialysis patients and transplant recipients reflect profound economic and service provision challenges for health-care systems in low- and middle-income countries in sustaining renal replacement therapy programmes. Underdeveloped organ donor and transplant programmes, health system and financing issues, ethical regulation of transplantation and the cost of pharmaceuticals commonly pose additional barriers to the delivery of efficient and cost-effective renal replacement therapy. Development of locally appropriate transplant programmes, effective use of nongovernmental sources of funding, service planning and cost containment, use of generic drugs and local manufacture of dialysis consumables have the potential to make life-saving renal replacement therapy available to many more in need. Select low- and middle-income countries demonstrate more equitable provision of renal replacement therapy is possible outside high-income countries. For other low- and middle-income countries, education, the development of good public policy and a supportive international environment are critical. Prevention of end-stage kidney disease, ideally as part of an integrated approach to chronic vascular diseases, must also be a key objective.     

Unequal access to cadaveric kidney transplantation in California based on insurance status.

OBJECTIVE: To assess the impact of insurance status on access to kidney transplantation among California dialysis patients. STUDY SETTING: California Medicare and Medicaid dialysis populations. STUDY DESIGN: All California ESRD dialysis patients under age 65 eligible for Medicare or Medicaid in 1991 (n = 9,102) took part in this cohort analytic study. DATA COLLECTION: Medicare and California Medicaid Program data were matched to the Organ Procurement and Transplantation Network Kidney Wait List files. PRINCIPAL FINDINGS: Only 31.4 percent of California Medicaid dialysis patients were placed on the kidney transplant waiting list compared to 38.8 percent and 45.0 percent of dually eligible Medicate/Medicaid and Medicare patients, respectively. Compared to the Medicaid population, Medicare enrollees were more likely to be placed on the kidney transplant waiting list (adjusted Relative Risk [RR] = 2.10, Confidence Interval [CI] 1.68, 2.62) as were dually eligible patients (RR = 1.54, CI 1.24, 1.91). Once on the waiting list, however, Medicare enrollment did not influence the adjusted median waiting time to acquire a first cadaveric transplant (p > .05). CONCLUSIONS: California dialysis patients excluded from Medicare coverage, who are disproportionately minority, female, and poor, are much less likely to enter the U.S. transplant system. We hypothesize that patient concerns with potential subsequent loss of insurance coverage as well as cultural and educational barriers are possible explanatory factors. Once in the system, however, insurance status does not influence receipt of a cadaveric renal transplant.     

Predictors of weight gain and cardiovascular risk in a cohort of racially diverse kidney transplant recipients

OBJECTIVE: Renal transplantation is associated with an increased risk of atherosclerotic cardiovascular disease and marked racial and ethnic disparities in graft and patient survival. We characterized differences in racial and ethnic susceptibility to weight gain, diabetes, and alterations in circulating lipid levels and isolated independent predictors of those changes in a diverse population of kidney transplant recipients. METHODS: The data for this analysis were drawn from a prospectively collected database of 506 renal transplant recipients obtained between 1983 and 1998. Univariate and multivariate analyses characterized differences in outcomes and predictors of cardiovascular risk by race and ethnicity. RESULTS: In all recipients, coronary artery disease was the most common cause of death, and African-American recipients had the shortest graft survival and the highest percentage of deaths. At 1 y post-transplantation, 39% of African-American recipients were obese (body mass index > 30), and the odds ratios for post-transplant diabetes were 3.5 and 5 times greater in non-white and obese recipients, respectively. CONCLUSIONS: Multiple regression analysis confirmed the predominant independent effect of African American race or ethnicity on weight gain; however, hypercholesterolemia was independent of race or ethnicity and predicted by cyclosporine treatment and post-transplant diabetes. Therefore, kidney transplantation represents a state of accelerated atherogenic risk induced in part by the metabolic effects of immunosuppressive medications and compounded by marked racial and ethnic disparities in weight gain and diabetes risk.     

他克莫司个体内高变异度与肾移植受者移植结局的关系探讨

目的探讨他克莫司(tacrolimus，Tac)个体内变异度(intra-patient variability，IPV)是否与肾移植受者慢性移植物失功密切相关。 方法选取2009年1月至2016年12月在四川大学华西医院肾移植中心进行肾移植且在术后长期随访的肾移植受者共1167人，用移植后7~12月期间的Tac全血浓度计算得到Tac IPV。设定的结局(含终点)包括：(1)移植物衰竭，再移植，(再)开始透析，或肾小球滤过率(glomerular filtration rate，eGFR)≤15 ml/min，活检证实的急性排斥反应(biopsy-proven acute rejection，BPAR)；(2)组织学确定的移植肾小球病；(3)移植后12个月到最后一次随访期间，血清肌酐浓度加倍；(4)最后一次随访。分析不同IPV组肾移植受者肾脏功能差异，生存时间差异以及出现慢性移植物失功的情况。 结果纳入研究的1167位患者中，有79(6.8%)位到达了移植物失功的终点。肾移植受者移植后7~12月Tac IPV平均值为25.7%；高IPV组移植后第15个月血清肌酐显著高于低IPV组(P<0.05)，第15、21、24个月eGFR显著低于低IPV组(P<0.05)。多因素Cox回归分析结果显示：Tac IPV对肾移植预后的预测有一定作用，但并不显著(P=0.051，Harzards ratio：1.015，95%CI：1.000-1.031)。而受者的年龄、性别、移植后6 h的移植物功能，是移植物存活的独立预测因子。 结论高Tac IPV与肾移植受者移植物失功有一定临床相关性，同时高Tac IPV是预测肾移植受者移植后两年内肾脏功能的重要实验室指标。     

Chronic kidney disease in human immunodeficiency virus infection

The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV-uninfected transplant recipients. However, high rates of acute and chronic rejection have been observed among HIV-infected kidney transplant recipients. The Infectious Diseases Society of America (IDSA) published guidelines in 2005, recommending that all individuals be assessed for kidney disease at the time of diagnosis of HIV infection with a screening urinalysis for proteinuria and a calculated estimate of renal function. Therefore any patient with persistent proteinuria, persistent haematuria or glomerular filtration rate < 60 mL/min per 1.73 m(2) should be referred to an institution where a specialist can evaluate this patient for further investigations. An integrated plan to reduce the progression to kidney failure together with lifestyle measures, focusing also on high risk groups with effective management at all levels of chronic kidney disease remains essential.     

Concentrations of free amino acids and other blood components in a lymphoma patient during intensive hemodialysis

L‐Asparaginase is used as a therapeutic enzyme to selectively destroy asparagine‐dependent cancer cells. This study explores alternate means for depriving cancer tissues of L‐asparagine and other specific amino acids or vital substrates required by normal and cancer cells. Hemodialysis, employing an artificial kidney, was used to remove free amino acids from the blood of a patient with lymphoblastic lymphosarcoma. Approximately 1200 mg, the equivalent of the patient's total amino acid pool, was removed every 100 minutes while the patient was on the artificial kidney. Despite this impressive clearance capacity, the dialyzer was not able to completely overcome the endogenous amino acid influx of the patient. The combined data indicate that hemodialysis is theoretically capable of removing specific amino acids to a therapeutic level, but that the clearance efficiency of the artificial kidney must be significantly increased or the endogenous amino acid influx must be effectively blocked before hemodialysis can be successfully applied to cancer patients. An unexpected finding was that the malignant lymphocyte population was strikingly increased during dialysis but returned to the original levels when dialysis was temporarily discontinued. The presence of a nonprotein inhibiting factor capable of suppressing an increase in the peripheral malignant lymphocyte population could be an explanation. This postulated factor behaved during dialysis as though its molecular weight was relatively low, possibly less than 500.     

Patients' decisions for treatment of end-stage renal disease and their implications for access to transplantation

Gaining access to kidney transplantation is a complex process that involves treatment decisions made by patients. Despite several advantages of kidney transplantation, some patients choose to remain on hemodialysis for treatment of end-stage renal disease. The present study was undertaken to describe the sociocultural factors influencing patients' decisions to remain on dialysis compared to those who sought a transplant. The study also examined whether African Americans made decisions different from European Americans which would offer insights into one of many factors resulting in them receiving disproportionately fewer kidney transplants. Using a qualitative approach supplemented by a quantitative approach, interviews employing open-ended questions and a card sort technique were conducted with 79 hemodialysis patients. Patients who preferred to remain on dialysis were significantly older and more likely to be unmarried and Protestant. The relationship between treatment decisions and ethnicity was inconclusive due to multiple, interrelated covariates. The three most common reasons patients reported for remaining on dialysis included: doing well on dialysis, fear of being "cut on" from a transplant, and knowing other patients whose kidney transplant failed. This study identified sociocultural and ethnomedical beliefs and values about the body and transplantation that inform patients' treatment decisions. This study also generated data that illuminate the complexity of patients' decisions and how these affect patients' preferences regarding transplantation. The results emphasize the need for policy makers to recognize patients' decisions when accounting for alleged difficulties in gaining access to transplantation.     

Interactions between inflammation, oxidative stress, and endothelial dysfunction in end-stage renal disease.

Despite a rapid improvement in dialysis technology during the last 20 years, the mortality rate is still very high in patients with end-stage renal disease (ESRD), and the death rate is comparable with that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. The high cardiovascular mortality rate suggests that ESRD patients are subjected to a process of accelerated atherogenesis. Because factors proven to contribute to atherosclerosis in the general population, such as dyslipidemia, smoking, diabetes mellitus, and hypertension are highly prevalent in ESRD patients, it is reasonable to assume that such risk factors also apply to these patients. However, as it has been shown that the high cardiovascular risk in ESRD is incompletely accounted for by traditional risk factors, it may be speculated that nontraditional risk factors, seemingly more difficult to reconcile, also contribute. Among several putative nontraditional risk factors, chronic inflammation has attracted a lot of interest recently because it seems to be associated to both increased vascular oxidative stress and endothelial dysfunction, both of which are important predictors of cardiovascular events in nonrenal patient groups.     

Incidence, timing and site of infections among pancreas transplant recipients

The incidence, timing and site of infections among the different categories of pancreas transplant recipients were investigated. Patients were divided into three groups: pancreas transplant alone (PTA), pancreas after kidney transplant (PAK), or simultaneous pancreas and kidney (SPK) transplants. Length of follow-up, time to death, pancreas graft survival, incidence, timing and site of bacterial infections were noted. Our study showed that at least 75% of pancreas transplant recipients experienced at least one infection (range from 77.8% in the PTA group to 86.7% in the PAK group). The SPK group presented the highest rate of infections with 35.1 infections per 1000/patient-days. Symptomatic urinary tract infections were the most common cause of infection in all patients. The incidence of infections was higher during the first month after transplantation, except for the SPK transplant group, where infections occurred over a longer time period.