Kidney Transplantation in Sickle Cell Patients

Renal complications are a well-known cause of morbidity and mortality in Sickle Cell Disease (SCD). SCD is a genetic disorder resulting from the presence of a mutated form of haemoglobin, haemoglobin S (HbS), which causes red blood cells to develop a rigid, sickle-like shape under reduced oxygen conditions, leading to haemolysis and vaso-occlusion. SCD results in a range of renal complications, including various tubular and glomerular functional changes and potentially, gross anatomic alterations of the kidneys. Kidney injury as a result of sickle cell is known as Sickle Cell Nephropathy (SCN).

The underlying mechanisms that lead to SCN relate mainly to hypoxia (lack of oxygen) and ischaemia (lack of blood supply). Hypoxia and Ischaemia as a result of RBC sickling can lead to impairment of solute reabsorption and urinary concentrating ability. They can also lead to impairment of renal acidification and potassium secretion resulting in hyperkalaemia and in incomplete tubular acidosis.

There are very few studies specifically looking at progression to End Stage Renal Disease (ESRD) secondary to SCN. Prognosis is poor in ESRD even on dialysis. Kidney transplantation offers the best long-term outcome in such patients. SCD patients tend to be transfusion dependent and can potentially develop antibodies to HLA. As patient DJ has a long history of transfusion, his antibody history would need to be carefully reviewed with respect to his sibling donor’s HLA type.

An initial and final pre-transplant crossmatch test would be required. The initial crossmatch can be virtual if the sibling donor is fully HLA matched or if there are no DSAs. There is a ¼ chance his sibling could be fully matched. If there are a choice of compatible sibling donors, it may be useful to screen the donors for the APO-L1 gene. APOL1 encodes an apolipoprotein. A variant of the gene found commonly in persons of West African descent, confers resistance to sleeping sickness. Homozygosity for this variant has however been shown to increase kidney disease risk. Where there is a choice, kidney donation must be from a sibling who does not have the risk mutation of APO-L1.

Patients transplanted for SCN often receive peri-operative transfusions if anaemic or exchange transfusions if not. Post-transplant patients are also at higher risk of sickle cell crisis and therefore receive post-transplant exchange transfusions. Early and ongoing post-transplant DSA level monitoring is therefore required.

There is a significant risk of recurrence of SCN.

Kidney Transplantation in HIV Patients

Patients with HIV can be considered for kidney transplant if they meet all the normal criteria for kidney transplantation and in addition, they must be on a stable highly active anti-retroviral treatment (HAART) regimen and have viral suppression for at least 6 months with CD34 count greater than 200. Compliance with the immunosuppression regime is vital for successful transplantation. Stability on HAART is a good indicator. Phycological review may also be useful. The increased risk of transplant must have been explained to HIV patient which they must accept the risk.

All HIV positive patients must be discussed at MDT prior to listing. HIV patients are not suitable for some immunosuppression strategies such as ATG, therefore the MDT discussions should include the unacceptable mismatches strategy. Typically, all specificities with MFY greater than the positive cut off for the laboratory (~2000 MFI) must be listed as unacceptable.

At the time of a donor offer, the risks of transplant versus maintenance on dialysis are again carefully reviewed. Marginal kidneys may not be the best option for patients who are stable on dialysis.

A pre-transplant wet crossmatch is required for all HIV patients irrespective of DSA status. The crossmatch must include samples from as much of the patient history as possible to give a complete risk assessment.

Post-transplant, the HIV patients should be reviewed by the HIV team who should advise specifically on dosing of HAART. Regular post-transplant antibody monitoring is recommended, especially at times of suspected rejection.

Kidney Transplantation in Diabetic Patients

Diabetes is one of the most important causes of chronic kidney disease (CKD) and in patients with advanced diabetic kidney disease, kidney +/- pancreas transplant is the treatment of choice. The prognosis of diabetic patients with end stage kidney disease (ESRD) and without the possibility of live donor kidney transplant or early deceased donor transplant is poor. Therefore, for these patients all effort should be made to secure a live transplant, either directly or through the live donor sharing scheme (paired exchange).

There are no randomized controlled trails comparing forms of transplantation in type 1 diabetic patients with end stage kidney failure. Live donor kidney appears to have the best outcomes even over deceased donor SPK. Live donor is also preferable where the patient requires PAK.

Type 2 diabetic patients with end stage kidney failure should be offered a live donor transplant if they have a donor as outcomes are better than deceased donor transplant which is in turn better than dialysis.

Kidney Transplantation in Paediatric Patients

There are a number of additional factors which should be taken into account in paediatric kidney transplantation which may not always be considered in adult transplantation. The most obvious is that the patient will likely need a second transplant in their lifetime and so steps should be taken to reduce the risk of alloimmunisation from the first transplant. For instance if a paediatric patient was not being transplanted with kidney from one of their parents in the first transplant, the parental HLA mismatches could be listed as non-antibody defined unacceptable mismatches so that the patient could potentially be protected from forming HLA antibodies against those mismatches, making the parent acceptable future direct donors.