Journal of The American Society of Nephrology最新文献

Background: The Medicare Secondary Payer Act (MSPA) requires that employer group health plans serve as the primary payer for individuals with end-stage renal disease (ESRD) for 30 months, with Medicare serving as the secondary payer. After 30 months, Medicare becomes the primary payer. The net fiscal consequences of this policy for the federal government are unknown.

Methods: We estimated the net federal fiscal effect of the MSPA for patients receiving dialysis and identified the private-to-Medicare spending ratio (R) at which the policy breaks even, accounting for the forgone tax revenue associated with tax-deductible private health care spending. We conducted an economic evaluation using published data on spending and utilization for ESRD, private-to-Medicare spending ratios for dialysis, dialysis chain financials, and federal tax parameters. Primary outcomes were expressed per privately insured dialysis patient-year, with a national aggregate calculated from incident ESRD counts.

Results: At current tax rates, the break-even spending ratio was R < 3.05. Using central price ratio estimates of R = 2.99, the MSPA reduced federal outlays by $2,217 per privately insured dialysis patient-year, or $28 million annually, relative to Medicare being the primary payer for dialysis patients without a coordination period. Ignoring the effect of the MSPA on tax revenue overstated the estimated savings from the MSPA by 4500%. Altering the MSPA so Medicare became the primary payer for dialysis treatments while retaining the coordination period for other services for dialysis patients would have increased federal savings to $29,981 per privately insured dialysis patient-year, or $378 million annually.

Conclusions: Under current prices and tax rates, the MSPA modestly reduced federal spending, while counterfactual policy changes would result in larger savings.

Background: Mutations in UMOD, encoding uromodulin, lead to Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD), a genetic cause of kidney failure. UMOD mutations have a common gain-of-toxic-function effect, causing mutant uromodulin retention in the endoplasmic reticulum (ER). This leads to ER stress, alteration of protein homeostasis and mitochondrial dynamics, defective autophagy and increased cell death. Calorie restriction exerts a beneficial role in diseases characterized by accumulation of pathogenic protein and inflammation, by modulating several pathways, including autophagy induction and suppression of inflammation and fibrosis. Given the relevance of these features in ADTKD, we investigated the effect of calorie restriction on disease onset and progression.

Methods: Transgenic mice expressing C147W uromodulin (TgUmodC147W) were subjected to a moderate (30%) calorie restriction regimen for 15 or 24 weeks, starting at different stages of disease progression.

Results: Calorie restriction restored autophagy, as shown by decreased P62 punctae and quenched mTOR activation specifically in mutant uromodulin expressing cells, and it recovered expression of key ER-phagy receptor genes, with a concomitant, striking reduction of mutant uromodulin ER retention. In pre-symptomatic TgUmodC147W mice, calorie restriction alleviated epithelial cell stress. This, likely along with a direct anti-inflammatory effect of calorie restriction, prevented inflammation and progressive decline of kidney function. At this early disease stage, calorie restriction ameliorated the already established kidney damage and reduced fibrosis, suggesting reversal of ADTKD phenotype. Calorie restriction was also effective in significantly delaying disease progression in TgUmodC147W mice with advanced disease and already compromised kidney function.

Conclusions: Calorie restriction enhanced autophagy and uromodulin degradation, counteracting the primary effect of UMOD mutations, and significantly ameliorated kidney disease onset and progression.