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Polycystic kidney disease

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Polycystic kidney disease (PKD) is the most commonly inherited kidney disease and leads to chronic kidney disease (CKD) and typically results in renal failure.[1]

PKD is a progressive disease characterised by the development of multiple fluid-filled cysts in both kidneys that change the shape and size of the kidneys. It can also result in other complications such as hypertension, liver cysts, cardiovascular and cerebrovascular problems.[2] [3] Diagnosis is typically made on renal ultrasound taking renal function, age, and family history into account.[1]

There are two main types of PKD based on inheritance patterns: autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD).

ARPKD [3] [4] [7] [8]

  • Rare condition affecting ~1 in 20,000 to 40,000 people
  • Child of a person with ARPKD has a 25% chance of being affected
  • Most cases of ARPKD are due to PKHD1 gene mutations
  • Onset at birth or early childhood
  • Hepatic involvement is common, and end-stage renal disease typically develops in early childhood, often leading to death at a young age
  • Other ARPKD-related morbidities that may develop over time include systemic hypertension and complications of congenital hepatic fibrosis

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ADPKD [3] [9]

  • More prevalent – estimated to affect 1 in 500 to 1,000 people
  • Child of a person with ADPKD has a 50% chance of being affected
  • Multiple cysts in kidneys, liver, pancreas, and other organs
  • Affects females and males equally
  • Symptom onset usually in adulthood (3rd or 4th decade) but kidney cysts may be detected earlier
  • Most common genetic cause of kidney failure
  • Most common gene mutation is PKD1 (85% of cases)
  • ~ 15% of cases are due to PKD2 gene mutation - this presents with fewer kidney cysts and lower risk of progression to kidney failure
  • ~1% have GANAB gene mutations – milder disease but more associated liver disease
  • – 50% of cases will require dialysis or kidney transplantation by age 60
  • Increased risk of hypertension, cardiovascular events, and intracranial aneurysms

Prognostic markers - ADPKD

In ADPKD there can be a long period of stable or slowly declining kidney function, even in the presence of significant progression and expansion of the structural cystic kidney disease.[4] Prognostic indicators for rapid disease progression include younger age at diagnosis, the causative gene mutation, early onset hypertension and early onset haematuria.[5]

Studies have identified baseline *height-adjusted total kidney volume (htTKV) as an early predictor of the risk of CKD progression in ADPKD.[10] Baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD and other complications associated with ADPKD.[6]

Testing bodily fluids (for example blood or urine) for the presence of ADPKD biomarkers that can give prognostic information is also emerging.[4]

Treatment

Initial treatment includes lifestyle management, blood pressure control and managing associated complications such as kidney stones, urinary tract infections, hepatic complications and chronic pain.[1] Tolvaptan is currently the only approved medication for ADPKD that slows the progression of the condition and research is ongoing to explore other novel treatment options.[3] Renal replacement therapy, with dialysis or renal transplantation, is required for those who progress to end stage renal disease.

Underwriting considerations

ARPKD: Has a high mortality rate shortly after birth. For those that survive the neonatal period advances in renal replacement therapy have improved overall survival, however morbidity risk remains high and life expectancy is still significantly reduced.

ADPKD: Approximately 50% of those affected will develop chronic renal failure by the age of 60 and require renal dialysis or kidney transplantation. Some individuals will experience more rapid disease progression and earlier onset of end stage renal disease. Additional risks to consider are extra-renal complications, including increased risk of cardiovascular events and intracranial aneurysms.

Author

Dr Yvette Pheiffer

Medical Officer

Hannover Life Re of Australasia

April 2024

References

  1. KHA Fact sheet Polycystic Kidney Disease. March 2019. Available from https://kidney.org.au/uploads/resources/KHA-Factsheet-polycystic-kidney-disease-2019.pdf. Viewed on 1 March 2024
  2. National Institute of Diabetes and Digestive and Kidney diseases – What is Polycystic Kidney Disease. Available from https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/what-is-pkd. Viewed on 1 March 2024
  3. National Library of Medicine. Autosomal Dominant Polycystic Kidney Disease. Available from Autosomal Dominant Polycystic Kidney Disease - StatPearls - NCBI Bookshelf (nih.gov). Last update 18 October 2023. Viewed on 1 March 2024
  4. Liebau MC, Mekahli D, Perrone R, Soyfer B, Fedeles S. Polycystic Kidney Disease Drug Development: A Conference Report. Kidney Med. 2022;5(3):100596. Published 2022 Dec 27. Doi:10.1016/j.xkme.2022.100596
  5. Schrier RW, Brosnahan G, Cadnapaphornchai MA, et al. Predictors of autosomal dominant polycystic kidney disease progression. J Am Soc Nephrol. 2014;25(11):2399-2418. doi:10.1681/ASN.2013111184
  6. Perrone RD, Oberdhan D, Ouyang J, et al. OVERTURE: A Worldwide, Prospective, Observational Study of Disease Characteristics in Patients With ADPKD. Kidney Int Rep. 2023;8(5):989-1001. Published 2023 Feb 13. Doi:10.1016/j.ekir.2023.02.1073
  7. Dorval G, Boyer O, Couderc A, et al. Long-term kidney and liver outcome in 50 children with autosomal recessive polycystic kidney disease. Pediatr Nephrol. 2021;36(5):1165-1173. doi:10.1007/s00467-020-04808-9
  8. Bergmann C, Senderek J, Windelen E, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67(3):829-848. Doi:10.1111/j.1523-1755.2005.00148.x
  9. Chapman AB, Devuyst O, Eckardt KU, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015;88(1):17-27. doi:10.1038/ki.2015.59
  10. Irazabal MV, Rangel LJ, Bergstralh EJ, et al. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015;26(1):160-172. doi:10.1681/ASN.2013101138

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