Evolution of kidney transplantation in the HIV-positive recipient

The presence of HIV has in the past been viewed as a relative contraindication to transplantation. This stance stemmed from concerns that immunosuppression would exacerbate an already immunocompromised patient and accelerate the disease process of AIDs. Additionally, there was an ethical concern in terms of giving a precious, limited resource to a group with what was in the past considered limited life expectancy.

However, the widespread introduction of HAART in the mid-90s has resulted in a marked decrease in morbidity and mortality in patients with HIV. As a result, people infected with HIV are living longer and dying less often from opportunistic infections and progression to AIDS, and more often from complications of traditional comorbidities such as coronary disease, diabetes, and chronic kidney disease. The incidence of ESRD continues to rise in those infected with HIV, and it is estimated that 1% of patients with ESRD are infected with HIV. In the United States, HIV nephropathy is the third most common cause of ESRD among blacks who are between the ages of 20 and 64.

As a result of this increasing incidence of disease and the improvement in management of HIV, many transplant centers have now eliminated HIV as a contraindication for transplantation. Several small studies have shown promising results, but there is really a lack of quality evidence in this field and it remains a controversial topic amongst nephrologists.

A recent publication in the NEJM has provided some stronger, encouraging data demonstrating that transplanting an HIV-positive recipient is feasible and offers good outcomes.

This study was a multicenter, non-randomized, prospective trial that was conducted at 19 U.S. transplant centers, which was designed to examine the safety and efficacy of kidney transplantation in ESRD patients who were also infected with HIV. The authors followed prospectively 150 HIV-positive recipients for up to 3 years after transplantation. Inclusion criteria were a CD4 count greater than 200 and undetectable viral load in the serum in the 16 weeks prior to transplantation. Patients were excluded if they had a history of PML, CNS lymphoma, or visceral kaposi’s sarcoma. They also were excluded if they did not meet center-specific transplant criteria. Primary outcomes were patient and allograft survival, and secondary outcomes were opportunistic complications, changes in CD4 counts, and detectable plasma HIV RNA levels. Refer to the paper for further details on their methods and post-transplant care.

The authors looked at patient and graft survival rates at years 1 and 3, and compared them to both the survival rates reported by the scientific registry of transplant recipients (SRTR) for all kidney transplant recipients, as well those older than 65. They conclude that patient survival rates in their population were similar to that of the general population, and that allograft survival rates were somewhere between that of the general population and the high risk elderly population. Significant opportunistic infections were minimal and there was no evidence of HIV progression during their follow period. Neoplasm rates were comparable to the general population, and there were no cases of PTLD. Interestingly, as has been previously described, they found their patients to have a very high rate of acute rejection which is much higher than the general population.

While this study does have its limitations, it provides some convincing evidence supporting kidney transplantation in HIV-infected patients. In a carefully selected population of HIV-infected patients with ESRD, it shows that kidney transplantation is a safe and feasible management option.

Justin Westervelt, MD

Shaken not stirred...

Not long ago while on call I received a midnight consult for hyperkalemia. The patient had a history notable for CLL, who was electively admitted to  for induction chemotherapy. Prior to this admission, he had received no previous chemotherapeutic agents. On arrival to the floor he was found to have a potassium of 6.5 mmol/L, and received IV insulin, kayexalate, and albuterol for medical management. Reportedly he had no EKG changes at that time. Despite this medical management, repeat labs that night demonstrated a K of 9.3 with ‘some hemolysis’, which prompted an urgent renal consult from an understandably concerned intern.

After waking up and clearing the cobwebs, I began lining up the usual suspects on my differential. Was this tumor lysis syndrome, ATN, or perhaps even a manifestation of his underlying CLL, causing either obstruction or direct infiltration of the renal parenchyma??

His evaluation however was not what I anticipated. He looked and felt well, having no complaints with the exception of the iatrogenic-induced hourly bowel movements he was having. He was euvolemic, normotensive, and overall had an unremarkable exam. I confirmed he had no concerning findings on EKG, and pertinent lab values are listed:

Wbc- 270,000, Hgb- 11.3 g/dL, plt- 99,000, uric acid- 6.7 mg/dL, LDH- 690 U/L, Creat.- 1.1 mg/dL, calcium- 8.5 mg/dL, Phosphorus- 4.8 mg/dL, Potassium- 9.3 mmol/L.

The story just wasn’t adding up, so I went to the literature and performed a search on CLL and hyperkalemia, and came across this interesting publication in AJKD…

First described in the 1950s, pseudohyperkalemia is defined as a spurious elevation of the serum potassium, occurring when potassium is released in vitro from cells in a collected blood sample. This may be seen in a variety of myeloproliferative disorders, typically those with marked leukocytosis or thrombocytosis, or as a result of improper collection technique (fist clenching during phlebotomy, a delay in the processing of the sample, or even the use of a pneumatic tube transport system). For a quick review look at Nate's prior post.

Pseudohyperkalemia in cases of leukemia is attributed to the fragility of the cell membrane causing lysis of cells and a falsely elevated potassium reading. This process can be exacerbated by the use of a pneumatic tubing system, as described in several case reports in the literature. In one particular instance, a femoral dialysis catheter was placed and the patient was initiated on hemodialysis with a potassium-free dialysate, resulting in a potassium level of 2.3.

In this patient, blood samples were obtained 45 minutes into dialysis and processed by several different methods.

1. vacutainer draw from a venous catheter into a heparin/lithium tube, pneumatic tube transport (the same as the initial sample).
2. venous sample draw into a heparinized arterial blood gas syringe (no lithium), ran in the ICU machine.
   
3. vacutainer draw from venous catheter into a heparin/lithium tube, walked to the laboratory
4. venous draw into a heparinized arterial blood gas syringe (no lithium), walked to the laboratory.
5. venous draw with a syringe (no vacutainer), poured gently into a heparin/lithium tube, and walked to the laboratory.

You can see that the primary factor responsible for the falsely elevated potassium in this case was the use of the pneumatic tubing system.

Repeated specimens sent the following day confirmed the diagnosis of pseudohyperkalemia, with a pneumatic tube-transported specimen demonstrating a potassium of 10.3 mmol/L and a specimen that was drawn at the same time and walked to the lab demonstrating a level of 5.1 mmol/L.

The take-home message- While psuedohyperkalemia is an unusual and rare occurrence, it is important to be aware of as practicing nephrologists. Missing this diagnosis certainly has clinical implications and can subject patients to unnecessary risk and harm, so always be aware of blood that has been shaken and stirred.

Justin Westervelt, MD

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