Forerunners, contrarians and dissenters advance science and nephrological practice. That is why in this section a doctor always tells about how they do something different from others. In this first episode: internist-nephrologist Arjan van Zuilen of UMC Utrecht about kidney transplantation in HIV patients.
Is there a standard procedure for this treatment in the Netherlands?
“For a long time, a kidney transplant was contraindicated for HIV, but that has changed since life-saving therapies have been introduced. The procedure is fine, but you have to pay extra attention to a number of things. In particular, the adverse effects of immune suppression on HIV infection and vice versa. For example, the HIV drug ritonavir was widely used to boost antiretriviral combination therapy (cART). Ritonavir inhibits the major metabolizing enzyme CY3A4. As a result, it increases the plasma levels of tacrolimus. But after a transplant, a patient is also often given tacrolimus to reduce the risk of rejection. This therefore requires a carefully defined drug policy: you want to prevent rejection, but you do want an optimal antiretroviral regimen.”
What do you do differently?
“We see people with HIV who have an indication for kidney transplant together at a combined consultation hour with the transplant nephrologist and the infectious disease specialist. We also consult with the virologist and the hospital pharmacist. If required by the medication regimen, the patient is given a small test dose of tacrolimus before the transplant and we measure plasma levels in the blood during hospitalisation. This allows us to make a good predictive estimate of the dose required after transplantation.”
Why are you doing it differently?
“We know that tacrolimus is poorly cleared by some of the HIV medications, such as ritonavir. Where we can use a trough level in the blood values in HIV-negative patients, this is a lot more complex when using ritonavir: that level barely drops. So we have to arrive very precisely at a slightly higher mirror, which then lasts for a long time. That is why we conducted a study into the correct dosage.1 Where other patients have to take 4 mg tacrolimus twice a day, for example, these patients who take ritonavir often receive a strongly reduced dose of, for example, only 0.5 mg once a week. ”
What are the benefits of your approach for patients and healthcare professionals?
“Thanks to our expertise, we now fulfill a regional function. The biggest benefit for patients is that the two biggest concerns – a flare-up of HIV or organ rejection – have hardly occurred in our country. While the chance of rejection is lurking because the drug interaction requires precision. Incidentally, flare-ups of the disease almost never occur due to transplantation, but rather because someone does not take the medication properly.”
Would you recommend other centers to adopt this approach?
“Certainly, and I think that is already happening in other academic centres. In addition, things have changed over time. For example, current HIV medication has fewer interactions with immunosuppressant drugs. In addition, there used to be a number of factors that increased the risk of kidney failure with HIV. In the acute phase, HIV could lead to kidney filter inflammation and kidney failure due to undetected or improperly treated HIV. However, with early recognition, this complication hardly occurs, as do co-infections that can cause kidney damage.
Finally, there were certain HIV medications that could increase the risk of kidney damage. Tenofovir, which is used in combination therapy, was particularly notorious. But that drug now has a variant that gives much less of this toxicity. In short, with a timely diagnosis, optimal treatment and an eye for side effects, the chance of a kidney transplant is very small these days. However, because they get older, HIV patients have a higher risk of cardiovascular disease, which can lead to kidney failure.”
Should there be more research into, for example, the optimal treatment strategy?
“I do not think so. Firstly, the number of patients is limited: I think we have treated 15 in the last 15 years. Our studies on this topic, and those of others, mainly date from 2009 to 2013 and are often case reports and observational studies. The group is therefore too small to set up a line of research into the optimal treatment strategy. Moreover, as stated, current HIV medication has fewer interactions.
A question that is much more topical and relevant is: can an HIV patient donate or receive a kidney from another HIV-infected person? Or can an HIV-negative recipient receive a kidney from an HIV-positive person? The first is possible: in 2008 this happened for the first time in South Africa. In 2019, the first HIV-positive living kidney donation was even performed. It is also possible in the Netherlands, but the procedure does take a lot of time. For example, you need to know whether the HIV is under control at the donor. If someone has a resistant form, you want to avoid ‘transplanting’ that form. You have to know that in advance, otherwise the recipient will end up in the rain: he will need different HIV medication, for example. And that can cause a lot of hassle: because we naturally have to think carefully about the combination with immunosuppressants in advance, you don’t want to have to set that again after the transplant. Then you often have to make worse compromises for 2 types of medication that someone has to use for the rest of their life.”
Do you see a place in (national) guidelines for your approach?
“I see more in a local protocol with do’s and don’ts. And perhaps most important is the consultation with the right specialists about the strategy to ensure that the transplant proceeds as safely as possible. We have consultations in advance, but we also sit around the table every 3 months to evaluate patients. Even after years, we still check how patients are doing. We also sometimes receive a request for advice, for example if there is a shortage of a certain HIV drug, to think about a good alternative. Finally, I think that as nephrologists we can now think along with colleagues who set up heart or lung transplants for HIV patients: we already have experience and know the pitfalls.”
Reference:
Maarseveen E van, Zuilen A van, Mudrikova T. Outcomes of Kidney Transplantation in HIV-Infected Recipients. N Engl J Med. 2011;364:683.
2023-07-07 08:48:15
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