Funding Innovative Dialysis Technology in the United States: Home Dialysis and the ESRD Transitional Add-on Payment for New and Innovative Equipment and Supplies (TPNIES).

Innovative, patient-centered, and pragmatic dialysis technologies are urgently needed to accommodate the growing national interest in home dialysis use. To help achieve this goal, the US Centers for Medicare & Medicaid Services (CMS) are expanding reimbursement for eligible home dialysis machines through an existing payment mechanism, the transitional add-on payment for new and innovative equipment and supplies (TPNIES). This mechanism incentivizes the early adoption of innovative equipment into practice by reimbursing dialysis providers up to 26% of the total cost of approved home dialysis machines. Machines are evaluated for TPNIES eligibility using prespecified substantial clinical improvement (SCI) criteria that are derived from the Inpatient Prospective Payment System (for non-nephrology technologies). Although the SCI criteria may be suitable for some non-nephrology technologies, they have not been adapted to consider the unique and complex care inherent in home dialysis. Thus, many of the SCI criteria appear unsuitable for home dialysis machines. To better incentivize innovation, CMS should develop nephrology-specific transparent and pragmatic criteria for TPNIES. In this perspective, we provide an overview of the TPNIES payment mechanism, highlight areas of concern within the policy, and offer solutions for improving TPNIES that could better promote the adoption of new home dialysis machines.

Estimating Shortages in Capacity to Deliver Continuous Kidney Replacement Therapy During the COVID-19 Pandemic in the United States.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, New York encountered shortages in continuous kidney replacement therapy (CKRT) capacity for critically ill patients with acute kidney injury stage 3 requiring dialysis. To inform planning for current and future crises, we estimated CKRT demand and capacity during the initial wave of the US COVID-19 pandemic. STUDY DESIGN: We developed mathematical models to project nationwide and statewide CKRT demand and capacity. Data sources included the Institute for Health Metrics and Evaluation model, the Harvard Global Health Institute model, and published literature. SETTING & POPULATION: US patients hospitalized during the initial wave of the COVID-19 pandemic (February 6, 2020, to August 4, 2020). INTERVENTION: CKRT. OUTCOMES: CKRT demand and capacity at peak resource use; number of states projected to encounter CKRT shortages. MODEL, PERSPECTIVE, & TIMEFRAME: Health sector perspective with a 6-month time horizon. RESULTS: Under base-case model assumptions, there was a nationwide CKRT capacity of 7,032 machines, an estimated shortage of 1,088 (95% uncertainty interval, 910-1,568) machines, and shortages in 6 states at peak resource use. In sensitivity analyses, varying assumptions around: (1) the number of pre-COVID-19 surplus CKRT machines available and (2) the incidence of acute kidney injury stage 3 requiring dialysis requiring CKRT among hospitalized patients with COVID-19 resulted in projected shortages in 3 to 8 states (933-1,282 machines) and 4 to 8 states (945-1,723 machines), respectively. In the best- and worst-case scenarios, there were shortages in 3 and 26 states (614 and 4,540 machines). LIMITATIONS: Parameter estimates are influenced by assumptions made in the absence of published data for CKRT capacity and by the Institute for Health Metrics and Evaluation model's limitations. CONCLUSIONS: Several US states are projected to encounter CKRT shortages during the COVID-19 pandemic. These findings, although based on limited data for CKRT demand and capacity, suggest there being value during health care crises such as the COVID-19 pandemic in establishing an inpatient kidney replacement therapy national registry and maintaining a national stockpile of CKRT equipment.

Hepatitis C virus infection in kidney transplantation-changing paradigms with novel agents.

Hepatitis C virus (HCV) is a common cause of increased morbidity and mortality in kidney transplant patients. It is associated with posttransplant glomerulonephritis, chronic allograft nephropathy, and New Onset Diabetes after Transplant (NODAT). In the past, HCV was difficult to treat due to the presence of interferon alpha-based therapies that were difficult to tolerate and were associated with adverse side-effects, such as the risk of rejection. With the advent of oral directly acting antiviral therapies, the landscape for HCV and transplantation has changed. These agents are highly effective and well tolerated with minimal side-effects. Sustained viral response rates in excess of 90% are achieved with most current treatment regimens active against all HCV genotypes. These new agents may show an improvement in graft and patient survival while essentially eliminating the risk of acute rejection from the use of prior interferon-based HCV therapies. These agents may also result in an improvement in organ allocation for HCV donor/HCV recipient transplantation. This review is meant to discuss the epidemiology of HCV, the new oral direct-acting antiviral agents (DAAs) and future opportunities for research in the field of HCV related transplantation.

Breaking down the complement system: a review and update on novel therapies.

PURPOSE OF REVIEW: The complement system represents one of the more primitive forms of innate immunity. It has increasingly been found to contribute to pathologies in the native and transplanted kidney. We provide a concise review of the physiology of the complement cascade, and discuss current and upcoming complement-based therapies. RECENT FINDINGS: Current agents in clinical use either bind to complement components directly or prevent complement from binding to antibodies affixed to the endothelial surface. These include C1 esterase inhibitors, anti-C5 mAbs, anti-CD20 mAbs, and proteasome inhibitors. Treatment continues to show efficacy in the atypical hemolytic uremic syndrome and antibody-mediated rejection. Promising agents not currently available include CCX168, TP10, AMY-101, factor D inhibitors, coversin, and compstatin. Several new trials are targeting complement inhibition to treat antineutrophilic cystoplasmic antibody (ANCA)-associated vasculitis, C3 glomerulopathy, thrombotic microangiopathy, and IgA nephropathy. New agents for the treatment of the atypical hemolytic uremic syndrome are also in development. SUMMARY: Complement-based therapies are being considered for targeted therapy in the atypical hemolytic uremic syndrome and antibody-mediated rejection, C3 glomerulopathy, and ANCA-associated vasculitis. A few agents are currently in use as orphan drugs. A number of other drugs are in clinical trials and, overall, are showing promising preliminary results.

What is the optimal approach to a non- culprit stenosis after ST-elevation myocardial infarction - Conservative therapy or upfront revascularization? An updated meta-analysis of randomized trials.

BACKGROUND: Non-culprit percutaneous coronary intervention (PCI) during a ST-segment elevation myocardial infarction (STEMI) remains controversial. We performed a meta-analysis of the published literature comparing a strategy of complete revascularization (CR) with culprit or target vessel revascularization (TVR)-only after STEMI in patients with multi-vessel disease. METHODS: We searched PubMed/Medline, Cochrane, EMBASE, Web of Science, CINAHL, Scopus and Google-scholar databases from inception to March-2016 for clinical trials comparing CR with TVR during PCI for STEMI. Mantel-Haenszel risk ratio (MH-RR) with 95% confidence intervals (CI) for individual outcomes was calculated using random-effects model. RESULTS: A total of 7 randomized trials with 2004 patients were included in the final analysis. Mean follow-up was 25.4months. Major adverse cardiac events (MACE) (MH-RR: 0.58, 95% CI: 0.43-0.78, P<0.001), cardiac deaths (MH-RR: 0.42, 95% CI: 0.24-0.74, P=0.003) and repeat revascularization (MH-RR: 0.36, 95% CI: 0.27-0.48, P<0.001) were much lower in the CR group when compared to TVR. However, there was no significant difference in the risk of all-cause mortality (0.84, 95% CI: 0.57-1.25, P=0.394) or recurrent MI (MH-RR: 0.66, 95% CI: 0.34-1.26, P=0.205) between the two groups. CR appeared to be safe with no significant increase in adverse events including stroke rates (MH-RR: 2.19, 95% CI: 0.59-8.12, P=0.241), contrast induced nephropathy (MH-RR: 0.73, 95% CI: 0.34-1.57, P=0.423) or major bleeding episodes (MH-RR: 0.72, 95% CI: 0.34-1.54, P=0.399). CONCLUSIONS: CR strategy in STEMI patients with multivessel coronary artery disease is associated with reduction in MACE, cardiac mortality and need for repeat revascularization but with no decrease in the risk of subsequent MI or all-cause mortality. CR was safe however, with no increase in adverse events including stroke, stent thrombosis or contrast nephropathy when compared to TVR.

Is there a genetic predisposition to new-onset diabetes after kidney transplantation?

Kidney transplant recipients may develop new-onset diabetes after transplantation (NODAT) and transplant-associated hyperglycemia (TAH) (NODAT or new-onset impaired glucose tolerance-IGT). We studied 251 consecutive renal transplant South Asian recipients for incidence of NODAT and its risk factors between June 2004 and January 2009. Pre-transplant glucose tolerance test (GTT) identified non-diabetics (n = 102, IGT-24, NGT-78) for analysis. Baseline immunosuppression along with either cyclosporine (CsA) (n = 70) or tacrolimus (Tac) (n = 32) was given. Patients underwent GTT 20 days (mean) post-transplant to identify NODAT, normal (N) or IGT. TAH was observed in 40.2% of the patients (40% in CsA and 40.6% in Tac) (P = 0.5). NODAT developed in 13.7% of the patients (12.9% in CsA and 15.6% in Tac) (P = 0.5). Overall, Hepatitis C (P = 0.007), human leukocyte antigen (HLA) B52 (P = 0.03) and lack of HLA A28 (A68/69) (P = 0.03) were associated with TAH. In the Tac group, higher Day 1 dosage (P <0.001), HLA A1 (P = 0.04), B13 (P = 0.03) and lack of DR2 (P = 0.004) increased the risk of TAH. In the CsA group, HLA A10 (P = 0.03), failure of triglyceride (P = 0.001) or low-density lipoprotein (LDL) (P = 0.03) to lower or high-density lipoprotein to rise (P = 0.001), and higher post-transplant LDL (P <0.001) and cholesterol levels (P = 0.02) were associated with NODAT or TAH. Post-transplant fasting plasma glucose on Day 1 had sensitivity-54.5%, specificity-50.1%, positive predictive value-18.1% and negative predictive value-84.8% for detecting NODAT. In conclusion, there is a genetic predisposition to NODAT and TAH in South Asia as seen by the HLA associations, and a predisposition exists to the individual diabetogenic effects of Tac and CsA based on HLA type. This could lead to more careful selection of calcineurin inhibitors based on HLA types in the South Asian population.

Recurrent renal allograft dysfunction due to ureteric stenosis in a patient with the BK virus infection.

Diseases of the genitourinary tract in association with the BK virus (BKV) infection are increasing among renal allograft recipients. We herewith report a young, female renal transplant recipient who presented with allograft dysfunction secondary to proximal ureteric stenosis. The allograft function improved dramatically after correction and stenting of the stenosis. Our case suggests that screening for BKV infection should be an integral part of evaluation of allograft dysfunction.

Risk factors of chronic kidney disease influencing cardiac calcification.

We sought to determine the influence of risk factors of chronic kidney disease (CKD) on cardiac calcification. We studied the correlation between coronary artery calcium score (CACS) and the type and duration of dialysis as well as the presence of diabetes mellitus and hypertension. The relation between calcium score and mortality was also analyzed. Patients with CKD attending the outpatient department or admitted in our hospital were included. They were subjected to high-resolution computerized tomography of the thorax to determine their CACS. Serum levels of intact parathyroid hormone (iPTH), highly sensitive C-reactive protein (hCRP), homocysteine, calcium, phosphorus, and calcium × phosphorus product were measured. Out of the 50 patients studied, 39 were hypertensive (78%), 32 were diabetic (64.4%), 20 were on hemodialysis, and 13 were on continuous ambulatory peritoneal dialysis. The mean CACS was 388.6. Twenty-nine patients had high iPTH levels and 92.9% of them had calcium score >400 (P = 0.013). Twenty-eight patients had high hCRP and 85.7% of these patients had calcium score >400 (P = 0.048). Patients on dialysis for more than two years had higher calcium score >400 (P = 0.035). 43% of diabetics had calcium score >400 (P = 0.008). All the six patients who died had calcium score >400 (P = 0). There was statistically no significant association noted between hypertension, high calcium x phosphorus product, and high homocysteine levels, and high calcium score. Our study suggests that higher values of iPTH, hCRP, and longer duration on dialysis are associated with accelerated cardiac calcification. Calcification scores >400 are associated with increased mortality.

An important complication of a child with juvenile idiopathic arthritis: macrophage activation syndrome.

A 4-year-old girl, a known case of juvenile idiopathic arthritis for 2 years presented to us with high-grade fever and abdominal distension for 2 months. On examination, her temperature was 104 ° F and she was found to be pale with bilateral cervical lymphadenopathy of up to 3 × 3 cm in size. Her liver was enlarged with a firm consistency and a span of 12 cm. Her spleen was enlarged up to 3 cm along its long axis. The rest of her systemic examination was normal. Laboratory investigations revealed leucocytosis, anaemia and thrombocytopenia with a mildly elevated erythrocyte sedimentation rate. Serum ferritin was 16 500 ng/dL and lactate dehydrogenase was 2311 U/L. A bone marrow aspirate showed macrophages showing ingested nuclei. She was diagnosed as having macrophage activation syndrome and was initiated on intravenous methylprednisolone 300 mg daily for 3 days and was switched over to oral prednisolone 2 mg/kg/day. She is currently doing well on follow-up.

Progressive pulmonary hypertension: another criterion for expeditious renal transplantation.

The aim of this retrospective study was to compare the prevalence of pulmonary hypertension in a cohort of patients with end-stage renal disease (ESRD) prior to and following renal transplantation and to identify the possible risk factors. Of the 425 renal transplantations performed between 2001 and 2007, Doppler echocardiographic findings were available in 124. The echocardiographic data, collected both pre- and post-transplant, included the pulmonary artery pressure (PAP), ejection fraction and left ventricular hypertrophy. The data analyzed included age, gender, hypertension, diabetes, smoking status, along with blood urea, creatinine, glomerular filtration rate, hemoglobin, hemodialysis duration, urine albumin, arterio-venous access and body mass index (BMI). Chi-square test was used for discrete variables and ANOVA was used for continuous variables. Of the patients studied, males comprised 72%; the mean age was 43.3 ± 13.02 years; 87% were hypertensive, 30% were diabetic and 4% were smokers. Statistical analysis revealed a significant reduction of the PAP, irrespective of its severity, following renal transplantation (P <0.05). The PAP had no significant correlation with any of the parameters analyzed, with the exception of BMI (P <0.05). Our study suggests that the PAP gets reduced in patients with ESRD after renal transplantation.