Postgraduate nephrology level. How to recognise and diagnose. Principles plus more detail on a couple of important examples. 60 mins.
Neil Turner, Professor of Nephrology. Prepared for the UK Renal Association’s Advanced Nephrology Course. This page includes extra content beyond this 50 min lecture.
Rare kidney diseases, an approach. 50 mins. Text alternative (to follow)
When you don’t know | When you do | Fabry disease | Other conditions | Other resources
What to use when you don’t know the diagnosis
Try these: Links show sample search “gout kidney disease genetic”:
- Dr Google – ‘oldest and best’ (estab. 1997). Can be remarkably effective.
- scholar.google – intellectual Google, links to papers etc.
- PubMed – one of the astonishingly good free resources from NCBI (US). They’ve changed the world of science and medicine. Publicly funded for the benefit of the world by US taxes in a foresightful, liberating move – ” thanks Obama*” (*actually 1988, the Reagan era; read the noble history of PubMed). Register and log in automatically each time you visit for additional features.
- OMIM – Online Mendelian Inheritance in Man, one of many alternatives on the PubMed drop-down menu.
- Professor Wikipedia – particularly good on genes and genetics. Usual cautions apply. Have you thought about editing it? New fascination every day on the Wikipedia main page.
When you do know the diagnosis:
- Rare Kidney diseases UKKA (UK Kidney Association) (previously at rarerenal.org). Diseases listed there have a UK expert group and a Registry that updates test results automatically. UK-relevant info about how to get testing done, management pathways. Register your patients on Radar, become your local link?
- Gene Reviews (NCBI) many of these are outstanding, better than many text books. There are exceptions, and not all diseases are covered.
- Gene Cards are technical but useful.
- For patients, Genetics Home Reference (NIH) has good concise explanations, but tends to be quite dry. For professionals, often provides a good intro to complex topics.
- There may be good professional or patient sites on specific conditions, and some of these can be exceptional.
See for instance this Fabry example:
(Anderson-) Fabry Disease
Alpha-galactosidase deficiency leads to accumulation of glycoshpingolipid in lysosomes, primarily of endothelial cells. An important disease to diagnose, as now treatable by enzyme replacement, and a good example of the issues in managing lysosomal disorders, metabolic diseases, etc. Info in the video at the head of this page or Fabry video here (from 8-26 mins)
Further info
- Gene Reviews (NCBI) on Fabry is comprehensive and very good. Written from the Royal Free. Includes thoughtful recommendations for treatment and monitoring. Guarded on long term impact of treatment.
- uKidney talk – Fabry – what every nephrologist should know (Michael West, Daniel Bichet)
- Wikipedia on Fabry is concise but good.
- Gene Card on the GLA gene is technical but useful; the database of mutations is for those with genetic experience or knowledge.
- For patients: two companies that market recombinant enzyme have produced patient info sites: fabrycommunity.com (Genzyme) and focusonfabry.co.uk (Shire)
- Genetics Home Reference (NIH) has good concise explanations, quite dry.
UK management guidelines were published in 2012 from the now-defunct NHS Specialist Services, but were very heavy on screening organs where treatment wouldn’t be altered much – updating is said to be pending, but there is useful info in Gene Reviews (NCBI) on Fabry. There are UK centres for Fabry Disease in London (Royal Free/UCL, GOSH), Salford, Birmingham (QE and BCH), Cambridge, and Edinburgh/Glasgow. They will no doubt have their own preferences.
Fabry is usually cared for by specialists in Metabolic Medicine in the UK. Most come from a Chemical Pathology background and don’t have inpatient beds. The patients have diseases in many systems and local management is essential too. Some have significant or end stage renal disease. Nephrologists may be key providers and coordinators of care for many. They could play a role in many other conditions too, maybe. ( Metabolic Medicine curriculum)
Some other conditions
Just a few of potentially, well, hundreds. These ones included as nephrologists will meet them from time to time, or because examiners like them.
| Tuberous sclerosis | Autosomal dominant disease (TSC1 and 2 encoding hamartin, tuberin) causing lumps in brain, kidneys, skin (adenoma sebaceum), and in women, lung. Kidneys predominantly may become replaced, or develop large angiomyolipomas. They may have some cysts, or in a minority masses of cysts because of contiguous genes PKD1/TSC2. Viewing images in Radiopaedia is recommended. There is a very good Wikipedia page on Tuberous Sclerosis and for an advanced view, the Gene Review on TS is the place to go. The molecular basis of TS is uncontrolled activation of mTOR. So inhibitors of mTOR (sirolimus, everolimus etc) seem a natural therapeutic avenue. |
| Alport Syndrome | and related basement membrane conditions are considered briefly on Genetic Kidney Diseases (as is PKD) linked below. Along with a pointer to more PG-level detail. |
| LCAT deficiency | Very rare autosomal recessive disorder causes loss of lecithin-cholesterol acyl transferase. Leads to accumulation of lipid deposits in cornea, glomerulus, and low HDL; cloudy cornea (fish eyes) and progressive proteinuric kidney disease seems common in complete deficiency. The best intro to this fascinating but complex disorder is Genetics Home Reference, GHR on LCAT deficiency and also read GHR on partial LCAT deficiency which gives more molecular background. Autoimmune-caused enzyme deficiency has also been reported. Kidneypathology.com gives an unusually good summary. |
| Methylmalonic acidaemia | Also known as methylmalonic aciduria. In addition to the metabolic manifestations, causes interstitial renal disease, which often leads to ESRF and transplantation. There’s a good Gene Review on MMA |
| Nail patella syndrome | Autosomal dominant condition in which mutations in the transcription factor LMX1B cause a series of features with considerable variation even within families. The characteristic nail and skeletal abnormalities are sometimes accompanied by proteinuric renal disease which may lead to ESRF; but LMX1B mutations are now being identified in patients with familial renal disease but without the characteristic non-renal features. The Gene Review on NPS is typically good, led by Liverpool geneticist Elizabeth Sweeney, who has contributed patient and professional info at NPS UK. |
| Von Hippel Lindau | A complex topic and the Genetics Home Reference (GHR) page on VHL is a good intro. There is a very good Gene Review on VHL. The pathogenesis involves HIF (Hypoxia-inducible factor), manipulation of which is now being attempted in order to raise Epo levels in renal anaemia. |
Additional resources
- Rare Kidney diseases UKKA (UK Kidney Association) (previously at rarerenal.org) – provides info on clinical pathways and how to get advice for the UK. It oversees the renal rare disease registries (Radar).
- bit.ly/otcn4 has good info on these conditions, mostly in Section 15 on Genetic Disease. But it’s not free, and we have to declare an interest, low-level financial as well as ensuring that the content is excellent. (The Oxford Textbook of Clinical Nephrology – eUpdates annually)
Finally some recommended resources on other things
- Genetic kidney diseases and other resources on medcal-renal
- Alport and basement membrane disorders (PG level) – more to follow, but as a starter, here is a 27 min talk on Alport treatment 2022 (should we add SGLT2i – surely yes; but what else?).
- Our patient info and unit protocols are at edren.org
- Radiopaedia has thousands of radiological images for your free re-use with attribution
This page written by Neil Turner @neilturn and first posted here December 2020, updated Jan 2022.
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