A Novel—And Cost-Effective—Approach to End-Stage Renal Disease

End-stage renal disease (ESRD), also called end-stage kidney disease, occurs when chronic kidney disease—the gradual loss of kidney function—reaches an advanced state. Until a few years ago, patients with ESRD had few treatment options: they could undergo hemodialysis, peritoneal dialysis, or they could wait for kidney transplantation from a live or deceased donor.

Recent data show about 500,000 patients received dialysis for ESRD in 2016; of these, 3.8% received a kidney transplant. While a live donor is an option for some patients, the majority will be placed on a waiting list to receive an organ from a deceased donor, said Peter P Reese, MD, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, PA.

“[A]ny patient should consider living kidney donor transplantation the best option, because there is no waiting time,” Dr Reese told First Report Managed Care in an email interview. “But most patients are not lucky enough to have a living donor.”

Those who wait on a transplant list could be facing years on dialysis—as long as up to 5 years in areas like Philadelphia and Baltimore—a “very expensive and a terrible burden for patients,” Dr Reese said.

The associated costs to keep patients on dialysis while on a transplant waitlist varies, but is approaching $90,000 per year, according to data from the United States Renal Data System.

The shortage of kidneys for donation and the risks and costs associated with dialysis have caused payers and providers to look at novel ways of lowering the wait time for kidney transplantation in patients with ESRD.

In the 10% to 15% of patients with ESRD on dialysis who are also seropositive for hepatitis C (HCV), there has been success in transplanting HCV-positive kidneys with good outcomes. However, until recently, there has been little study of non–HCV-infected patients receiving transplants from HCV-infected donors.

With the advent of direct-acting antiviral drugs as a curative treatment for HCV, these patients may now be able to accept kidneys from donors who are HCV-positive. Although the transplantation process causes them to be infected with HCV in the short term, they can be treated with an 8- to 12-week course of direct-acting antivirals with a high rate of sustained virologic response. Furthermore, adverse event rates are comparable to patients receiving a healthy organ. Dr Reese said this strategy is not only clinically beneficial but also cost-effective.

“Despite the high cost of direct-acting antiviral drugs, transplantation with an organ from an HCV-infected donor kidney can save money for payers provided that it shortens time on dialysis,” Dr Reese explained.

Increase In HCV-Infected Donors

Between 2010 and 2015, the acute rate of infection for HCV has increased by nearly three-fold. “This increase is associated with increases in injection drug use,” Mark H Eckman, MD, MS, from the University of Cincinnati Medical Center Department of Internal Medicine in Cincinnati, told First Report Managed Care in an email interview. “The largest increases in HCV are among persons less than 40 years of age.”

S Russel Spjut, PharmD, formulary management pharmacist at MagellanRx Management in
Salt Lake City, UT, and First Report Managed Care editorial board member, said that because many of the drugs used by illicit intravenous drug users are opioids, the current opioid crisis is contributing to more HCV infections. An increase in opioid-related deaths my be contibuting to greater availability of HCV-positive organs as a result. Dr Reese said he has noticed a trend of more HCV-positive organ donors, up to an approximate 25% rate of HCV-positive donors in some areas of the United States. Many of these organ donors do not know they are infected with HCV.

“Many of these donors are young and otherwise in good health,” Dr Reese said. “Their families were interested in making some small good out of a family tragedy through organ donation. But, often, no one would accept the organs for transplantation. I think that situation is gradually changing.”

Historically, many HCV-positive kidneys were—and continue to be—discarded by transplant teams due to the perception that they are not useable. A recent study cited that, since 1995, 3562 kidneys have been discarded in the United States, with a discard rate of 53.6% compared with 22.4% for HCV-negative kidneys.

“Prior to the donation of kidneys from an HCV-positive donor, almost all treatment centers would deem organs from these donors as ineligible for transplant,” Dr Spjut said. “This of course limited the number of available organs and potential yearly transplants meaning donors had to wait longer for a kidney resulting in longer dialysis duration and potentially death.”

Concerns About HCV-Positive Donation

The potential acceptance of using HCV-infected kidneys for transplant in patients with ESRD could provide much needed relief for a transplant community that has been plagued by long wait times.

Organ transplantation has its own associated costs and risks. With HCV-positive organ donation, these concerns are compounded by costs of immunosuppressive drugs, the cost of HCV antiviral drugs, and other associated direct costs of HCV treatment. Patients can develop cirrhosis or glomerulonephritis, and treatment with interferon can cause organ rejection. Some clinicians have raised concerns that immunosuppression after transplant may impede curative treatment for HCV. There is also a slightly increased mortality rate among transplant patients receiving HCV-positive kidneys during the first month; however, researchers have noted the prognosis for these patients is good.

“Although there have been concerns about other complications following transplantation with HCV-infected kidneys, recent studies have shown high rates of sustained virologic response (ie, cure) with minimal adverse events or graft rejection,” Dr Eckman said.

Further, he noted that ESRD patients who are HCV-positive will incur treatment costs of antiviral drugs regardless of whether they receive an HCV-infected kidney.

In 2017, experts met at the American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation and issued a series of recommendations of care for these patients. The recommendations included placing patients who receive HCV-positive organs on a prospective registry with clinical trials for follow-up, as well as having organ procurement organizations work with transplant physicians to help with shared decision-making in treatment of these patients. The consensus committee pointed out the cost of collaborating with these teams would likely be offset by the increase in the number of available organs.

“The transplant community should recognize kidneys from HCV-infected donors are very valuable and should be used as much as possible to bring transplant to more people,” Dr Reese, who was a member of the committee, said.

Cost-Effectiveness Of HCV-Positive Donation

Dr Eckman and his colleagues recently performed a large, retrospective cohort study to analyze the cost-effectiveness of implanting HCV-infected kidneys into HCV-positive patients. They employed a 75-state Markov transition model that simulated HCV treatment followed by kidney transplantation as well as transplantation of an HCV-infected kidney followed by HCV treatment using data from 1814 HCV-infected patients in the United Network for Organ Sharing. The findings were published in Annals of Internal Medicine.

The investigators noted the median wait time for receiving an HCV-infected kidney was 231 days compared with 771 days for an uninfected kidney; mean dialysis time was 2.7 years in patients receiving an infected kidney compared with 4.7 years in the group receiving a healthy kidney.

The researchers found that early transplantation resulted in an average gain of 0.5 quality-adjusted life-years and a lifetime cost savings of approximately $42,000. Patients who waited on dialysis for a healthy kidney had a 34.5% increased risk of dying of chronic kidney disease compared with 29% of patients who received HCV-infected kidneys and antiviral treatment.

While Dr Eckman acknowledged a small increase in the annual mortality rate of patients from liver disease in the early transplant group, he attributed the risk to asymptomatic liver inflammation from HCV, which can lead to fibrosis and liver-related death over a period of several years.

“Other than the temporary decreased quality of life associated with the 8- or 12-week course of treatment for HCV, there is no reason to think that quality of life among the large majority of patients cured of their HCV infection after transplant would be any different than that of other kidney transplant recipients,” Dr Eckman told First Report Managed Care.

A recent presentation by Richard K Sterling and colleagues at Digestive Disease Week 2018 (June 2-5, 2018; Washington, DC) analyzed the cost-effectiveness of transplanting HCV-positive kidneys into HCV-negative recipients over a 5-year period compared with waiting for an HCV-negative kidney while on dialysis.

Using a decision-tree model, the researchers evaluated years of life, pre- and post-care direct expenditures for transplantation, immunosuppressive therapy, costs for 12 weeks of direct-acting antiviral drugs, and associated medication costs and dialysis while waiting for transplant.

Dr Sterling and colleagues found that recipients who underwent transplantation followed by antiviral treatment had an expected 4.6 years of life and a total cost of $154,000 compared with 3.6 years of life and a $257,000 cost for recipients who waited for an HCV-negative kidney. This strategy remained cost-effective after adjusting for factors such as probability of transplant survival, wait time on dialysis, probability of receiving a transplant by waiting on dialysis, and the cost and cure rate of antiretroviral treatment.

“By getting these patients a kidney as soon as it is available, the cost avoidance of the monthly treatments can almost offset the entire HCV treatment cost,” Dr Spjut commented. “From a patient perspective, they are also more likely to die from the renal disease than the HCV infection in the short term, so getting them a kidney improves their chance at lengthening their life.”

Viability Of HCV-Positive Transplantation

In a recent open-label, nonrandomized trial, published in Annals of Internal Medicine, Dr Reese and his colleagues tested the viability of HCV-positive kidney transplantation in a cohort of patients. They analyzed data from 20 HCV-negative patients from the THINKER and EXPANDER trials who were transplant candidates and received an HCV-positive kidney donation. Participants were 56.3 years old on average, 70% male, and 40% black.

All patients received treatment to cure HCV after transplantation. Although physical component and mental component scores had decreased at 4 weeks, they returned to pretransplant and baseline values, respectively, and remained stable by 12 months. At 6 months, participants in the THINKER trial had estimated glomerular filtration rates similar to participants who received an HCV-negative kidney.

“[I]t appears as if patients are very likely to be cured—perhaps because the infection is acute and the virus is not well established in the recipient,” Dr Reese told First Report Managed Care. “We need larger studies to look at other potential complications of HCV after kidney transplant, such as immunological risks—one recipient developed an unusual condition called focal segmental glomerulo-sclerosis—rejection, vascular disease, or diabetes.”

Continued Decrease in Cost of Treating HCV

When sofosbuvir (Sovaldi; Gilead Sciences) debuted on the market, it cost $84,000. Since then, costs have continued to decrease: combination elbasvir/grazoprevir has a cost of $52,131, and combination glecaprevir/pibrentasvir has a cost of $24,490 for a 12-week course. This cost decrease has greatly increased the viability of gaining payer support for the transplantation approach. Using the annual treatment costs of a patient on dialysis and noting that the average wait time for a patient on dialysis, HCV treatment alone can pay for itself within a year, Dr Spjut said.

“While rebate rates for competitor products are not disclosed, we can infer that they likely bring the net cost of most HCV treatment courses within that range as well,” he added.

“For now, we need clinical trials,” explained Dr Reese. “In the future, I also very much hope that Medicare and other insurance companies will create payment pathways for HCV medications after transplant. That is a necessary step for this form of transplantation to one day become standard of care.”

“In the future, only with insurance support can transplant centers offer HCV-infected organs to their patients and have confidence that their patients will be able to be cured of HCV after transplant,” Dr Reese concluded.