Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR

Individuals who test positive for anti-HCV IgG antibody, but who have negative blood HCV RNA
PCR are generally considered to have been infected with HCV but to have cleared the the virus
spontaneously. However, due to the general conservative approach of living donor kidney
transplant programs, these individuals are not considered potential live kidney donors,
despite being considered at extremely low risk for HCV transmission to the recipient. This
reluctance stems from past experiences with post-transplant HCV complications, both hepatic
(e.g. cirrhosis) and extra-hepatic (e.g. transplant glomerulonephritis) and from the fact
that the historical mainstay of HCV treatment, interferon, was poorly tolerated, had low cure
rates, and caused transplant rejection. Now, however, highly effective novel therapeutics may
transform the way transplant physicians and patients think about HCV-positive donated
kidneys.

With these new agents, the current cure rates for HCV now exceed 95%. A recent report
demonstrated high cure rates even in the liver transplant setting, suggesting that
immunosuppression does not impede eradication and that interactions between HCV and
transplant drugs can be successfully managed. Thus, while the risk of transmission of
infection from anti-HCV antibody positive, HCV PCR-negative is not known, if transmission
were to occur, treatment is now possible, to the point where transplant professionals are
beginning to advocate using anti-HCV Ab positive individuals as donors for HCV-negative
recipients. A group in Barcelona reported transplantation of a live donor kidney from a donor
treated with an anti-HCV regimen that achieved a sustained virological response to her spouse
with no transmission of infection.

The main area of concern seems to be what is described as "occult HCV infection"- the
presence of HCV RNA in peripheral blood mononuclear cells and organ tissue by ultrasensitive
assays in the absence of detectable RNA in the serum. However, this entity is itself
controversial, and its significance is uncertain, with inadequately described risk of
transmission. If HCV were transmitted and successfully treated, another concern is the
potential residual risks of viral complications, even though these have not been evident in
any previous trials. Finally, a major concern is financial, as HCV treatment currently costs
more than $80,000 for a 3-month regimen. However, chronic hemodialysis costs upwards of
$100,000 per year when all costs are considered, while kidney transplantation costs only
about $20,000 per year after the first year. Thus, over time, even after treatment for CMV
infection, if it is required, kidney transplantation would result in an overall cost savings
to the health care system.

Given the unknown, though generally considered very low risk of transmission of HCV from an
antibody-positive, PCR-negative individual, combined with the wide availability of effective
treatment for HCV infection, it is felt that the recipient is not exposed to a high risk of
infection in such a transplant. Furthermore, this small risk needs to be weighed against the
risk of staying on dialysis, which carries a mortality rate of 6.5-7.4 times that of the
general population and 4.6-5.9 times that of the renal transplant population. The case
becomes even more compelling when considering patients with a high risk of deterioration if
they continue dialysis (elderly, diabetics, and those with cardiovascular disease),
disadvantageous blood types, and those with broad sensitization, with extremely limited
compatible donor options. Given the proven survival benefit of kidney transplantation in
patients with chronic HCV, there is ample reason to believe that providing HCV positive
kidneys and HCV therapy (if indeed required) to HCV negative recipients will lead to better
outcomes than those associated with remaining on dialysis.

Inclusion Criteria:

Donor inclusion criteria:

- The donor candidate must be anti-HCV positive by ELISA and HCV RNA negative by PCR,
with both tests repeated for confirmation, as per standard protocol.

- The donor must be evaluated and cleared by Hepatology, which is currently the standard
of care for HCV seropositive individuals.

- The donor must meet criteria for living kidney donation and be approved by the UF
Health Shands Kidney Transplant Medical Review Board.

Recipient inclusion criteria:

- The recipient may be HCV antibody negative or anti-HCV antibody positive but HCV RNA
negative by PCR.

- The recipient must meet the criteria for kidney transplantation and be approved by the
UF Health Kidney Transplant Program Medical Review Board.