Potential Mechanisms Involved in Chronic Kidney Disease of Unclear Etiology.

BACKGROUND AND OBJECTIVES: The etiology of chronic kidney disease of unclear etiology, also known as Mesoamerican nephropathy, remains unclear. We investigated potential etiologies for Mesoamerican nephropathy in an immigrant dialysis population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Migrants with Mesoamerican nephropathy kidney failure (n=52) were identified by exclusion of known causes of kidney disease and compared using a cross-sectional survey with demographically similar patients with kidney failure from other causes (n=63) and age/sex/place of origin-matched healthy participants (n=16). Survey results were extended to the bench; C57BL/6 mice (n=73) received 10-15 weekly intraperitoneal injections of paraquat (a reactive oxygen species-generating herbicide) or vehicle. Kidney function, histology, and expression of organic cation transporter-2 (proximal tubule entry for paraquat) and multidrug and toxin extrusion 1 (extrusion pathway) were examined. Kidney biopsies from Nicaraguan patients with acute Mesoamerican nephropathy were stained for the above transporters and compared with patients with tubulointerstitial nephritis and without Mesoamerican nephropathy. RESULTS: Patients with Mesoamerican nephropathy and kidney failure were young agricultural workers, almost exclusively men; the majority were from Mexico and El Salvador; and they had prior exposures to agrochemicals, including paraquat (27%). After adjustment for age/sex, exposure to any agrochemical or paraquat was associated with Mesoamerican nephropathy kidney failure (odds ratio, 4.86; 95% confidence interval, 1.82 to 12.96; P=0.002 and odds ratio, 12.25; 95% confidence interval, 1.51 to 99.36; P=0.02, respectively). Adjusted for age/sex and other covariates, 1 year of agrochemical exposure was associated with Mesoamerican nephropathy kidney failure (odds ratio, 1.23; 95% confidence interval, 1.04 to 1.44; P=0.02). Compared with 16 matched healthy controls, Mesoamerican nephropathy kidney failure was significantly associated with exposure to paraquat and agrochemicals. Paraquat-treated male mice developed kidney failure and tubulointerstitial nephritis consistent with Mesoamerican nephropathy. Organic cation transporter-2 expression was higher in male kidneys versus female kidneys. Paraquat treatment increased organic cation transporter-2 expression and decreased multidrug and toxin extrusion 1 expression in male kidneys; similar results were observed in the kidneys of Nicaraguan patients with Mesoamerican nephropathy. CONCLUSIONS: Exposure to agrochemicals is associated with Mesoamerican nephropathy, and chronic exposure of mice to paraquat, a prototypical oxidant, induced kidney failure similar to Mesoamerican nephropathy.

Dose of Continuous Renal Replacement Therapy in Critically Ill Patients: A Bona Fide Quality Indicator.

Acute kidney injury (AKI) is common in critically ill patients, and renal replacement therapy (RRT) constitutes an important aspect of acute management during critical illness. Continuous RRT (CRRT) is frequently utilized in intensive care unit settings, particularly in patients with severe AKI, fluid overload, and hemodynamic instability. The main goal of CRRT is to timely optimize solute control, acid-base, and volume status. Total effluent dose of CRRT is a deliverable that depends on multiple factors and therefore should be systematically monitored (prescribed vs. delivered) and iteratively adjusted in a sustainable mode. In this manuscript, we review current evidence of CRRT dosing and provide recommendations for its implementation as a quality indicator of CRRT delivery.

Pre-ESKD Nephrology Care and Employment at the Start of Dialysis.

INTRODUCTION: Employment is associated with an improved sense of well-being and quality of life in patients with kidney disease. Earlier nephrology referral and longer duration of pre-end-stage kidney disease (ESKD) nephrology care are associated with improved health outcomes in patients with advanced kidney disease who initiate dialysis. It is unknown if pre-ESKD nephrology care helps patients stay employed leading up to dialysis initiation. METHODS: We used the US ESKD registry to identify adults aged 18-54 years who initiated dialysis between 2007 and 2014. Analyses were restricted to patients who reported being employed 6 months prior to ESKD. We used multivariable regression models with estimated average marginal effects to examine the independent association between ≥6 months of pre-ESKD nephrology care and employment at dialysis initiation. To reduce bias, we conducted an instrumental variable (IV) analysis based on geographic variation in pre-ESKD care. RESULTS: Of 75,700 patients included in study cohort, 49% reported receiving pre-ESKD nephrology care for ≥6 months, and 62% were employed at dialysis initiation. Although geographic variation in pre-ESKD nephrology care was strongly associated with the likelihood that working-aged patients in our analytic cohort received pre-ESKD care, the receipt of pre-ESKD nephrology care was not significantly associated with employment at dialysis initiation; estimated probability: 5%; 95% confidence interval (CI) -6% to 14%. CONCLUSIONS: Pre-ESKD nephrology care 6 months prior to initiation of dialysis is not associated with the likelihood of remaining employed at the initiation of dialysis. Although nephrology care has potential to help patients remain employed, this benefit is not manifested in current practice.

Physician reimbursement for outpatient dialysis care: Past, present, and future.

Ever since Medicare began covering nearly every patient with end-stage renal disease in the United States, reimbursement for dialysis services has deviated from traditional fee-for-service. The method of reimbursing physicians for outpatient dialysis care has undergone a series of reforms in an effort to improve the overall quality of dialysis care and to control healthcare costs-changes that we are still seeing today. In 2004, the Centers for Medicare and Medicaid Services (CMS) changed the Monthly Capitation Payment (MCP) for physician reimbursement to the tiered fee-for-service system that is used today. This most recent reform encouraged more frequent face-to-face visits to patients receiving dialysis. While the quantity of visits increased in response to the change in reimbursement, the quality of care did not meaningfully improve, the policy may have had unintended negative health consequences and may have led to increases in wasteful physician and advanced practitioner effort. There are several promising opportunities to reform economic incentives around physician dialysis care that could improve the quality and value of care. These include new pay-for-performance initiatives, implementing incentives for high-quality care within fully capitated payment models, and reforming the MCP itself to link payment to high-value dialysis services.

A historical perspective of how public policy shaped dialysis care delivery in the United States.

Broadly defined public policy has been said to be whatever "governments choose to do or not to do" As applied to healthcare, public policy can be traced back to the 4000-year-old Code of Hammurabi. As it applies to dialysis care its history is barely 50 years old since national coverage for end-stage renal disease (ESRD) was legislated as Public Law 92-603 in 1972. As with most healthcare policy changes, it was a result of medical progress which had changed renal function replacement by dialysis from its rudimentary beginnings during the Second World War into an experimental acute life-saving procedure in the 1950s and to an established life-sustaining treatment for the otherwise fatal disease of uremia in the 1960s that was limited by its costs. Since 1973, the Medicare ESRD Program has saved the lives of thousands of individuals, a compassionate achievement that has come at increasing costs which have exceeded all estimates and evaded containment. Apart from cost containment, policy changes in dialysis care have been directed at improving its safety and adequacy. Some of the results of these changes are evident as one compares the outcomes and complications of dialysis encountered in the 1970s to those in the present; others, particularly those related to vascular access and hospitalization rates have improved modestly. This article recounts the historical background in which national coverage for dialysis care was developed, legislated and has evolved over the past 50 years.