The majority of ADPKD patients will progress to end stage renal disease (ESRD) needing renal replacement therapy (RRT). The gold standard for RRT is currently renal transplant (RTx).
From the viewpoint of the transplant waiting list it might seem as if we are all in the same boat – we all face the same risks regardless of how we got there. But this is not necessarily so – there are several specific factors for ADPKD patients that warrant consideration aside from the GFR and antibody status ( the usual parameters that govern how soon you might be rescued).
Andrzej Kulesza and Longin Niemczyk have produced a review paper that looks at these differences, drawing on evidence from 80 separate studies. It was published in the Nephrology Section of the European Medical Journal in July 2015. Attention to the topic is justified by the numbers that suggest there are over 500,000 patients with ADPKD in the European Union, or 91 cases per million people.
ADPKD is now viewed as a systemic disease – that is one that has effects in multiple areas of the body – different organs, different systems will demonstrate abnormalities all linked to the underlying pathology. The underlying pathology in ADPKD is the abnormal polycystin proteins. These proteins take part in several physiological processes, some well understood but probably many others that have not yet been elucidated. So the Polish review paper relates to the current knowledge base and may probably have added factors as time goes forward.
They helpfully group these into two sections: pre-transplant and post-transplant.
Before renal transplant (RTx) the factors they suggest warrant extra attention are:
- Whether to remove the native kidneys
- Thoroughness of the cardiovascular assessment before surgery
- Liver cysts presenting additional complications
- Diverticular disease
1. Whether to remove the native kidneys
ADPKD is not an indication for removal of native kidneys per se. But pain, haematuria, infection and lack of space may lead to the decision to remove the polycystic kidneys. They reckon that only about 20% of patients with ADPKD will need a native nephrectomy (NN) and the guidelines suggest a kidney length above 21.5cm being a cut-off (or out) point. It has been shown that native kidneys actually diminish in size after RTx.
The timing of NN is still debated – before or during a transplant being the main decision. It does not affect graft survival either way. Some surgeons prefer to take one kidney only while others prefer bilateral nephrectomy. It does appear that a laparoscopic approach results in better healing and fewer complications. It seems pretty impressive that they can “deliver” such large kidneys through relatively small incisions.
2. Cardiovascular risks specific to ADPKD
This is actually quite a big topic in itself, but in a nutshell: because ADPKD predisposes to other vascular problems such as mitral valve abnormalities, intracranial aneurysms and hypertension, then a complete cardiovascular assessment pre-transplant should include screening for these problems. The presence of any extra cardiovascular abnormalities does not stop a transplant but does need to be managed.
3. Liver Cysts (PLD)
From 75-90% of patients with ADPKD will have liver cysts by the time they reach ESRD. On the whole the cysts do not affect liver function but in some cases their size leads to what is called “mass effect” or compression of surrounding organs. Some patients with PLD might benefit from surgical procedures to reduce liver size at the same time as or ahead of a kidney transplant
In addition, in PLD patients the serum carbohydrate antigen 19-9 (CA19-9) may be raised due to its secretion by the biliary epithelium that lines the liver cysts. In normal circumstances a raised CA19-9 is an indicator of inflammation or cancer – but it might not mean the same in ADPKD patients.
4. Diverticular Disease in ADPKD
This one surprised me a little – not that it is common in ADPKD, which is well documented, but that the recommendation is to consider removal of affected colon in patients with a past medical history that includes diverticulitis. An aside here, I once had severe diverticulitis with a diverticular abscess, and despite being pretty ill, once recovered I almost laughed when the surgeon suggested an elective colectomy to prevent further episodes, it seemed far too drastic! Maybe I should reconsider his advice.
After a transplant (RTx) the patient with ADPKD still needs extra factors to be taken into account in management plans. There is no apparent difference in acute rejection of the new kidney between ADPKD patients and non-ADPKD transplant patients. Nor is there any instance of development of cysts in the new kidneys. But the same four factors as above are relevant and there are differences for ADPKD patients relating to diabetes, infection and cancers developing after a transplant.
- Native kidneys after RTx
After RTx the native kidneys will continue to produce erythropoietin which induces higher haemoglobin levels compared with the post-transplant situation from other nephropathies. But this can also result in too many red blood cells (erythrocytosis), so needs particular monitoring.
The original kidneys can still be a source of cyst infection, pain and on occasion their size can impress the ureter from the transplant kidney. This increases to list of differentials when diagnosing post-transplant abdominal pain.
2. The cardiovascular system after RTx
The studies looking at this aspect have conflicting results and conclusions. It appears that while heart attacks and heart failure may occur less often post-ADPKD-transplant, there is an increase on post-transplant valve abnormalities, specifically mitral valve prolapse or regurgitation. An increase in the incidence of pericardial effusion has also been noted.
It is recommended that the ADPKD patient be screened regularly for the presence of aortic aneurysms after the transplant. Rarely the original kidneys can, by pressure on the veins of the pelvis, trigger post-transplant DVTs, which may occur more often when compared with other post-transplant patients.
3. The liver after RTx
In contrast to the shrinking of the native kidneys, the liver cysts will continue to enlarge after a renal transplant. This warrants additional observation and possible intervention.
4. Diverticular disease after RTx
After a renal transplant in ADPKD patients there is not only a higher incidence of diverticulitis but it also tends to be more serious with greater consequences. There are more instances of perforation of the diverticulae and this leads to higher mortality rates. Because of the immunosuppression the early signs may not be detected so it is advised that abdominal CT scans should be considered early for any low abdominal pain. This approach is supported by several case study descriptions of adverse outcomes in post-transplant patients with ADPKD.
5. New Onset Diabetes After Transplant (NODAT)
I have written about this in a previous post. This review paper concludes that there are more studies to suggest NODAT is more frequent in ADPKD patients. Five research papers demonstrate results where NODAT is twice as common in the ADPKD patients compared with other post-transplant patients. This contrasts with just 2 papers showing no differences in the incidence. Clearly it needs further analysis.
6. Infection and neoplasms after RTx
Infection is not more frequent in the ADPKD post-transplant patient. Anti-rejection immunosuppression is a risk factor for infection in any patient with a transplant regardless of the original cause of renal failure. Similarly for the overall incidence of new cancers occurring after transplants, though it does appear that new cancers in the ADPKD patient are more often skin cancers (basal and squamous cell cancers).
This review paper is a comprehensive account of the additional risks the ADPKD transplant patient might face. I found a few older papers looking at this area, in general concluding there were no special circumstances for the ADPKD patient undergoing a renal transplant above a non-ADPKD patient. It seems likely that with the passage of time more patients with ADPKD are reaching a transplant stage and having transplants so the differences have only recently become apparent.
To end on a high note, the paper’s conclusion is that
“RTx in ADPKD is currently associated with excellent results”
- ADPKD = Autosomal dominant polycystic kidney disease
- GFR = glomerular filtration rate (how well the kidneys are working – or not)
- antibody status = one way of matching kidneys for transplant
- ESRD = end stage renal disease (stage 5 / renal failure)
- RTx = renal transplant
- RRT = renal replacement therapy (dialysis or transplant)
- native kidneys = the ones you were born with
- NODAT = new onset diabetes after transplant
- PLD = polycystic liver disease
- DVT = deep vein thrombosis or clot in the veins of the leg
- neoplasm = cancer
- basal and squamous cell carcinoma = non-melanoma skin cancer growths
- epithelium = lining cells (e.g. biliary epithelium = cells lining bile ducts and PLD cysts)