ESRD in Guatemala and a Model for Preventive Strategies: Outlook of the Guatemalan Foundation for Children with Kidney Diseases

The rapidly growing burden of chronic renal failure (CRF) is a major public health problem that will stretch the health care system of all countries, especially those that are not yet industrialized. It is estimated that only 35% of Guatemalan patients with end stage renal disease (ESRD) would be diagnosed and treated, and unlike many developed countries, the age of presentation in 60% of the patients is before the forth decade. Therefore, the cost of death and disability due to a CRF in this young population is particularly profound, resulting in reduced productivity and economic growth of the country. It is also estimated that 400 pediatric cases develop progressive kidney disorder (neurogenic bladder, reflux nephropathy, chronic glomerulonephritis) annually, which, if left untreated, could result in ESRD in adulthood. This reality justifies initiatives such as FUNDANIER (Foundation for Children with Kidney Diseases), whose mission is to offer comprehensive nephrological treatment to children and adolescents and enable health care providers to prevent ESRD by early identification, diagnosis, and timely referral of children with risk factors. Efforts should be taken to better involve pediatricians and pediatric nephrologists in the fight against the burden of CRF.     

Treatment strategies for insulin-dependent diabetics with ESRD: a cost-effectiveness decision analysis model

Clinical decision analysis has become an important tool for evaluating specific clinical scenarios and exploring public health policy issues. A decision analysis model that incorporates patient preferences regarding various outcomes, as well as cost, may be particularly informative in patients with type I diabetes and end-stage renal disease (ESRD). Such a model that includes pancreas transplantation as a treatment choice has not been performed and is presented in this study. The decision tree consisted of a choice between four possible treatment strategies: dialysis, kidney-alone transplant from a cadaver (KA-CAD) or living donor (KA-LD), and simultaneous pancreas-kidney (SPK) transplant. The analysis was based on a 5-year model, and the measures of outcome used in the model were cost and cost adjusted for quality of life. The measure of preference for quality of life was obtained using the "Standard Reference Gamble" method in 17 SPK transplant recipients who underwent transplantation between January, 1992 and June, 1996 at our center. The measures for various outcome states (mean +/- 1 SD) were dialysis-free/insulin-free = 1, dialysis-free/insulin-dependent = 0.6 (0.4 to 0.8), dialysis-dependent/insulin-free = 0.5 (0.36 to 0.64), dialysis-dependent/insulin-dependent = 0.4 (0.21 to 0.59), and death = 0. The expected 5-year costs for each of the treatment strategies in the model were dialysis, $216,068; KA-CAD transplant, $214,678; KA-LD transplant, $210,872; and SPK transplant, $241,207. The expected cost per quality-adjusted year for each of the treatment strategies in the model were dialysis, $317,746; KA-CAD transplant, $156,042; KA-LD transplant, $123,923; and SPK transplant, $102,422. SPK transplantation remained the optimal strategy after varying survival probabilities, costs, and utilities over plausible ranges by means of one-way sensitivity analysis. In conclusion, according to the 5-year cost-utility model presented in this study, SPK transplantation is the most cost-effective treatment strategy for a patient with type I diabetes and ESRD. From a policy standpoint, looking at the cost alone of pancreas transplantation is deceiving. In these patients, who may view various outcome states differently, it would be important to take into account cost adjusted for quality of life when evaluating this procedure.     

Funding ESRD care through charity: the paradigm of the National Kidney Foundation of Singapore.

Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized dialysis care and comprehensive rehabilitative services to approximately 60% of all ESRD patients in the country, whose activities are funded entirely by charitable public donations. Unique to the NKF-S model are the considerations of the donor as an "investor" in the health care of NKF-S dialysis patients, the personal responsibility of the dialysis patient as a recipient of this "investment" to play an active role in achieving good clinical and rehabilitative outcomes, and the fostering of community-based support systems to facilitate patient rehabilitation such as partnerships with employers willing to employ dialysis patients. The success of the system is shown by its clinical outcomes, which approximate those observed in the United States. We believe that several aspects of the NKF-S model for ESRD care may be implemented in other communities, particularly in countries that have yet to develop financially and clinically mature dialysis programs.     

Middle molecules and small-molecular-weight proteins in ESRD: properties and strategies for their removal

Molecular weight has traditionally been the parameter most commonly used to classify uremic toxins, with a value of approximately 500 Da frequently used as a demarcation point below which the molecular weights of small nitrogenous waste products fall. This toxin group, the most extensively studied from a clinical perspective, is characterized by a high degree of water solubility and the absence of protein binding. However, uremia is mediated by the retention of a plethora of other compounds having characteristics that differ significantly from those of the previously mentioned group. As opposed to the relative homogeneity of the nitrogenous metabolite class, other uremic toxins collectively are a very heterogeneous group, not only with respect to molecular weight but also other characteristics, such as protein binding and hydrophobicity. A recently proposed classification scheme by the European Uraemic Toxin Work Group subdivides the remainder of molecules into 2 categories: protein-bound solutes and middle molecules. For the latter group, the Work Group proposes a molecular weight range (500-60,000 Da) that incorporates many toxins identified since the original middle molecule hypothesis, for which the upper molecular weight limit was approximately 2,000 Da. In fact, low-molecular-weight peptides and proteins (LMWPs) comprise nearly the entire middle molecule category in the new scheme. The purpose of this article is to provide an overview of the middle molecule class of uremic toxins, with the focus on LMWPs. A brief review of LMWP metabolism under conditions of normal (and in a few cases, abnormal) renal function will be presented. The physical characteristics of several LMWPs will also be presented, including molecular weight, conformation, and charge. Specific LMWPs to be covered will include beta 2-microglobulin, complement proteins (C3a and Factor D), leptin, and proinflammatory cytokines. The article will also include a discussion of the treatment-related factors influencing dialytic removal of middle molecules. Once these factors, which include membrane characteristics, protein-membrane interactions, and solute removal mechanisms, are discussed, an overview of the different therapeutic strategies used to enhance clearance of these compounds is provided.     

Association of Body Mass Index with Patient-Centered Outcomes in Children with ESRD

Obesity is associated with less access to transplantation among adults with ESRD. To examine the association between body mass index at ESRD onset and survival and transplantation in children, we performed a retrospective analysis of children ages 2–19 years old beginning RRT from 1995 to 2011 using the US Renal Data System. Among 13,172 children, prevalence of obesity increased from 14% to 18%, whereas prevalence of underweight decreased from 12% to 9% during this period. Over a median follow-up of 7.0 years, 10,004 children had at least one kidney transplant, and 1675 deaths occurred. Risk of death was higher in obese (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.03 to 1.32) and underweight (HR, 1.26; 95% CI, 1.09 to 1.47) children than children with normal body mass indices. Obese and underweight children were less likely to receive a kidney transplant (HR, 0.92; 95% CI, 0.87 to 0.97; HR, 0.83; 95% CI, 0.78 to 0.89, respectively). Obese children had lower odds of receiving a living donor transplant (odds ratio, 0.85; 95% CI, 0.74 to 0.98) if the transplant occurred within 18 months of ESRD onset. Adjustment for transplant in a time–dependent Cox model attenuated the higher risk of death in obese but not underweight children (HR, 1.09; 95% CI, 0.96 to 1.24). Lower rates of kidney transplantation may, therefore, mediate the higher risk of death in obese children with ESRD. The increasing prevalence of obesity among children starting RRT may impede kidney transplantation, especially from living donors.     

Promoting quality of care for ESRD patients: the role of the ESRD Networks

The 18 End Stage Renal Disease (ESRD) Networks were established by Congress to oversee the care of Medicare beneficiaries with ESRD, serving as HCFA's primary quality improvement (QI) agents. The Networks play a critical role in the ESRD surveillance system by collecting, analyzing and disseminating data from dialysis clinics regarding the occurrence of ESRD, and the processes of care and outcomes of ESRD patients. In addition, under the direction of volunteer Medical Review Boards, the Networks propose, design and implement regional QI activities targeting specific areas in the delivery of ESRD care, and provide technical assistance to foster QI at the facility level. In this article, we discuss the ESRD Network system and review the scope of QI activities through which the Networks accomplish their mission.     

Complications in colorectal surgery: risk factors and preventive strategies

Backround  

Open or laparoscopic colorectal surgery comprises of many different types of procedures for various diseases. Depending upon the operation and modifiable and non-modifiable risk factors the intra- and postoperative morbidity and mortality rate vary. In general, surgical complications can be divided into intraoperative and postoperative complications and usually occur while the patient is still in the hospital.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.     

Projecting the United States ESRD population: issues regarding treatment of patients with ESRD

In 2001, there were 406,081 patients who received treatment for end-stage renal disease (ESRD), increasing by 4.2% since 2000. The number of patients with ESRD has grown consistently over the past decade, with the greatest rate of growth occurring among patients older than 75 years of age, and patients with comorbidities such as diabetes mellitus and hypertension. Current projections indicate that the population of patients with ESRD may reach more than 2 million by 2030. The overall mortality rate has fallen by 10% since 1988, with the greatest decline among patients incident to dialysis, and an increase among patients receiving dialysis for greater than five years. While the rate of hospitalization for ESRD patients has remained relatively constant, recent improvements in mortality are temporally associated with a greater proportion of patients achieving adequate benchmarks of care in dialytic processes, such as anemia correction and dose of dialysis. The ESRD program consumes 6.4% of the Medicare budget. On a per-patient per month basis, Medicare costs have risen between 1991 and 2001. While payments fell slightly during 1998 and 1999 because of changes in Medicare policies, more recent years have seen an upswing in total expenditures, presumably related to use of injectables not included in the composite rate. Continued growth in the number of new patients reaching ESRD, as well as improved mortality rates of ESRD patients, are both contributing to the current rise and projected epidemic of ESRD over the next 25 years. The current public health strategy of identification of patients with early kidney disease to slow their progression to ESRD, in addition to aggressive treatment strategies to minimize the morbidity and mortality of patients with ESRD, is essential toward affecting the growth and health of this population.