10 unanswered questions in CKD, nephrology and transplantation
There are many. So the ones described below are just a start. Nonetheless we will now describe 10 unanswered questions in CKD, nephrology and transplantation.
CKD
1. What are the toxins in CKD?
This perhaps the simplest but most important question in nephrology. Disappointingly [“yes, very”, CKDEx Ed], we still do not know what the toxins are; or why and how they make you unwell. We use surrogates for the toxins, like urea and creatinine. But these are just ‘marker molecules’ and are not toxic themselves.
2. Why don’t we have good biomarkers in CKD? The Biomarker Dilemma
At present, the diagnosis of some causes of chronic kidney disease (CKD) is based on a renal (kidney) biopsy. This procedure invasive but safe(ish). However it is unpleasant, time consuming, and may not affect treatment. And it often fails to predict the course of the disease reliably.
It also cannot be done repeatedly; so cannot be be used to monitor a disease or the efficacy of treatment.
Hence we need new specific reliable biomarkers (not just non-specific GFR/creatinine) that can diagnose and monitor specific causes of CKD; tell us and the patient if the treatment is working, and give a reliable prognosis (outlook).
3. Why are sexual problems in CKD not addressed?
Many patients with advanced CKD have sexual problems (e.g. erectile dysfunction, dry vagina or lack of libido) – and we don’t know why. Sexuality and sexual happiness is part of life but few renal health professionals ask the patients about it (care about it?). They are happier to discuss Hb, GFR, BP or skin-fold thickness [“safer ground” Ed]. More work needs to be done about this important problem.
4. Do dietary restrictions work in CKD?
They are still routinely prescribed, especially regarding sodium, potassium, phosphate and protein. There was (and is) little evidence that long-term restriction of such substances is a. possible and b. affects hard end-points (dialysis, death etc).
We need simple controlled trials to examine their efficacy. Comparing people that clearly know they are on a beneficial diet, to others that clearly know they are not, is not good science. Patients that volunteer for such research are also the converted. Such studies are very hard to do, which is why there are so few [“aww .. another little excuse, Ed”]. They need to be done.
5. What are CKD symptoms due to? What causes them? What is the best way to treat them? We know little about some of the most intractable and unpleasant symptoms of advanced CKD (e.g. itching, pain and tiredness). We need to know what causes them, and therefore have better treatment strategies. Itching is especially an area where there is a lack of knowledge of causation – and effective treatments are poor. For example, Gabapentin is commonly used, but to little effect.
Dialysis
6. Which is better: peritoneal dialysis or haemodialysis?
This is a simple question but we still do not know the answer. Both types of dialysis provide about 5 ml/min of GFR (averaged over the week). This is simply not enough to make the majority of patients feel well. We need ways of increasing the dialysis dose without putting a increased burden on the patient’s quality of life.
7. When should dialysis be started?
This is another simple question but we still do not know the answer. The pros and cons of an early start to dialysis is debated on CKDEx here: when to start dialysis.
8. Is there evidence of better outcomes with more dialysis?
There is little evidence that more dialysis leads to better outcomes. And so, this is another simple question but we still do not know the answer. It is assumed that ‘more dialysis is better’. There is little evidence for this belief.
The few controlled trials have shown little (or no) evidence for higher dialysis doses. Why? We don’t know. Perhaps it is because increasing (dialysis delivered) GFR to 7 ml/min (averaged over the week) is not significantly more than the ‘normal’ 5 ml/min.
9. Does dialysis make you live longer? Does it work at all?
This is another basic – and very important – question in nephrology. But we still do not know the answer. There is alot of doubt that dialysis prolongs life in the frail elderly with Stage 5 CKD.
Hence there is a controlled trial of dialysis in the frail elderly going on in the UK at present. It should report in 2-3 years time. The UK and the world needs to know the answer.
Renal transplantation
10. How do we reduce chronic transplant dysfunction and loss of kidneys? – apart from controlling blood pressure and minimising nephrotoxic drugs, there are few specific therapies to prolong the life of a kidney transplant.
Summary
We have described 10 unanswered questions in CKD, nephrology and transplantation. There are many more. We hope you have found it interesting. It is disappointing the answers to such fundamental questions are still unknown. Why not try to answer one of them?
Other resources
10 (more) unanswered questions in CKD, nephrology and transplantation (linked article)
10 unanswered questions in kidney transplantation (another linked article)
What we know and don’t know about women and CKD (Piccoli, 2018)
Levin, 2022 emphasises that interventional studies of the value of specific diets in individuals with CKD are few.
Last Reviewed on 17 April 2024