The conference brought together a multidisciplinary group of experts with the aim of identifying gaps in knowledge about the condition and inform the direction of future research.
The first few paragraphs paint a grim picture using words like “relentless” and “continuous destruction”, “major burden” and “reduced quality of life”. It also points out that ADPKD is a systemic disorder, that is one with effects on other parts of the body, not just the kidneys.
The subsequent paper is divided into sections: Genetics, Diagnosis, Monitoring, Management, End Stage Renal Disease, Other Complications, and Patient Support. I have used bullet points to improve clarity. I have highlighted some aspects of particular interest – clearly there is a personal element in that!
- PKD1 was discovered in 1994, PKD2 in 1996
- No evidence of a third PKD gene.
- European families appear to have 85% PKD1 and 15% PKD2
- Canada/US studies suggest more have PKD2, (26% or 36% respectively)
- An “at-risk” individual is one where a first degree relative is diagnosed with the condition. A first degree relative is a parent or sibling.
- Screening at-risk children is not currently recommended.
- Screening at-risk adults is recommended because of the benefits of knowing and managing the condition.
- Ultrasound is the most cost effective diagnostic tool but it should be noted that the rules for confirming a diagnosis are significantly different from the rules for excluding a diagnosis.
- It is now possible to perform direct tests to look for the actual genes, where previously the genetic tests involved looking for marker genes alongside the affected gene, a less accurate method. But while sequencing of the PKD1 and PKD2 can be used for molecular diagnosis, the process to look for PKD1 mutations is technically challenging: the PKD1 gene is large and complex.
- Currently most patients do not have genetic testing. It is increasingly used in unusual cases and some situations where reproductive decisions are required. The availability and costs vary between countries.
- Total Kidney Volume (TKV) is an accurate measure of progress, and can be related to pain, blood pressure and loss of kidney function.
- Average TKV increase in ADPKD patients is 5-6%per year.
- TKV can be measured by US, CT or MRI.
US is less precise, CT entails radiation exposure, but MRI is costly.
However MRI can be used without gadolinium enhancement and accurately measures total cyst volume not just total kidney volume.
- It would help to have internationally standardised radiology reports giving kidney measurements of length, width and depth.
- GFR = glomerular filtration rate
- GFR is usually estimated using an equation; this estimate is sufficiently accurate to use for clinical management in patients. The actual GFR can be measured directly, mGFR, and may be more appropriate for trials and research, but is expensive and invasive.
- ADPKD patients are at higher risk of high blood pressure and cardiovascular events.
- BP targets should be individualised for the patient.
- First line drugs = act on the renin-angiotensin system (RAAS) along with a sodium-restricted diet.
- Second line treatment of high blood pressure should be selected for the individual because the usual add-on drugs (calcium channel blockers and diuretics) may not be the most suitable in ADPKD patients.
- Children with a family history of ADPKD should have their BP measured every 3 years from the age of 5 onwards.
- The HALT PKD trial justified the use of an ACEinhibitor as first line treatment of hypertension and concluded that using a lower BP target for ADPKD patients was protective of kidney function.
- Patients are advised to increase their water intake to suppress endogenous (the body’s own production) arginine vasopressin as it has a harmful role in ADPKD.
- Three classes of drug are looking promising: vasopressin V2 receptor antagonists (eg tolvaptan), somatostatin analogues (eg ocreotide) and HMG-CoA reductive inhibitors (eg pravastatin).
- Regarding bleeding of the cysts one potential approach might be to temporarily stop the anti hypertensives while the cyst is bleeding to avoid kidney damage.
- Kidney stones are common in ADPKD and potassium citrate is the treatment of choice. Using shock wave therapy to break up the stones is not damaging to the ADPKD kidneys.
- Infected cysts are hard to diagnose accurately. If antibiotics are used, then fat soluble ones such as fluoroquinolones (“*floxacins”) or trimethoprim should be first choice.
Effective treatment is indicated by no fever and two negative urine or blood cultures.
- Kidney pain is the most common feature for ADPKD patients and may become chronic, perhaps due to sensitising of the nerve pathways. There are many approaches to treating chronic renal pain.
- Pregnancy may increase risks of hypertension and liver cysts and some of the blood pressure drugs are not suitable. Counselling is advised for all ADPKD patients of reproductive potential.
- Pre-emptive living kidney transplantation is the optimal choice of end stage renal disease.
- Dialysis is the alternative treatment with both forms suitable, but some issues regarding peritoneal dialysis (space, diverticulae, hernias).
- Nephrectomy comes with associated morbidity but might be indicated by recurrent stones, infection or intractable pain.
- Anaemia is less severe in ADPKD patients compared with others in ESRD.
- Post transplant risks include diabetes, GI complications, strokes and infections.
- Intracranial aneurysms occur in 9-12% of ADPKD patients compared with 2-3%general population. The average age of rupture of an ICA is 41 years compared to 51 in general.
- Liver cysts concur in more than 80% of adults with ADPKD. One fifth of these patients suffer from compression symptoms and some have infected cysts.
- All patients should have access to a specialist nephrologist.
- Issues to be discussed include screening family, reproductive choices, lifestyle modifications, exercise, diet, and psychological support.
- Anxiety and depression are common – more than 60% patients with ADPKD experience one or both.
- The approach of insurance companies and the workplace is inconsistent and requires standardised recommendations.
- PKD centres of excellence with multidisciplinary approaches would be beneficial.
The full report will be available on the KDIGO website. Currently the papers in the journals require either a subscription or payment per view – It is likely that my link to the paper above may require you to make a payment and for this I am sorry – when all academic papers are freely available the web will be serving its function!