Expert Practice Guidelines for Autosomal Dominant Polycystic Kidney Disease

• ADPKD is a Mendelian autosomal dominant disorder where at-risk individuals have a 50% chance of inheriting the disease.Pre-symptomatic diagnosis of at-risk adults is most commonly performed by ultrasound due to its low cost and availability.¹
• The Ravine Pei Unified Criteria is used for diagnosis and exclusion.^2,3

• Genetic testing in ADPKD is seldom indicated for diagnosis but is useful for disease exclusion in at-risk persons age 40 and
  younger. Other considerations for genetic testing include PKD with no apparent family history, evaluation as a living-related
  organ donor, markedly asymmetric PKD, early and severe presentation or PKD with syndromic features and reproductive
  counseling.^4,5

Monitoring Disease Progression

• Kidney enlargement resulting from the expansion of cysts is continuous and quantifiable, and is associated with the decline of renal function.⁶
• Total Kidney Volume (TKV) is the most important prognostic biomarker for following ADPKD progression in the early stages of the disease. It is used to predict end-stage renal disease and implement appropriate treatment strategies in a timely fashion.^7,8
• TKV can be obtained from a variety of modalities but is most precise with MRI and CT scan. The Mayo Clinic Imaging Classification uses height-adjusted TKV and age to categorize typical ADPKD patients from 1A to 1E with those in classes 1C, 1D and 1E being considered rapid progressors.^6,9

Management

• Tolvaptan is FDA-approved (April 2018) to slow kidney function decline in adults at risk of rapidly progressing ADPKD.¹⁰
  
  • A Risk Evaluation Mitigation Strategy (REMS) exists for acute liver failure so continuous monitoring of liver function is recommended.¹¹

• Patients with ADPKD are at increased risk for hypertension, cardiovascular events and cardiovascular mortality. According to the HALT-PKD trials, blood pressure goals are <110/75 mmHg for early PKD (age 60, as long as patients are asymptomatic for hypotension) and 120-130/70-80 mmHg for advanced PKD (GFR <60).¹²
• Nutritional and lifestyle recommendations to mitigate renal/extrarenal manifestations and slow disease progression include moderate protein intake, low sodium intake, high water intake, low-to-moderate caffeine intake, no smoking and achieving a healthy weight and BMI.^13-17

1. Chebib FT, Torres VE, Am J Kidney Dis. 2016 May;67(5): 792–810. 2. Ravine D, et al. Lancet 1994 Apr;343(8901):824-827. 3. Pei Y, et al. JASN 2009 Jan;20(1):205-212. 4. Lanktree MB, et al. Nephrol Dial Transplant. 2019 Sept;34(9):1453–1460. 5. Lanktree MB, et al. CJASN 2020;16:790-799. 6. Grantham JJ, et al. N Engl J Med 2006;354:2122-2130. 7. Chapman AB, et al. Clin J Am Soc Nephrol. 2012 Mar;7(3):479–486. 8. Irazabal MV, Rangel LJ, Bergstralh EJ, et al. J Am Soc Nephrol. 2015;26(1):160-172. 9. https://www.mayo.edu/research/documents/pkd-center-adpkd-classification/doc-20094754 10. https://pkdcure.org/tolvaptan 11. Torres VE, Chapman AB, et al. CJASN 2021;16(1)48-58. 12. Schrier RW, et al. N Engl J Med 2014;371:2255-66. 13. Torres VE, et al. Kidney Int 2017;91:493-500. 14. Higashihara E, et al. Nephrol Dial Transplant 2014;29:1710-1719. 15. McKenzie KA, et al. BMC Nephrol 2018;19:378. 16. Orth SR, et al. Kidney Int 1998;54:926-931. 17. Nowak KL, et al. J Am Soc Nephrol 2018;29:571-578. 18. Chapman AB, et al. N Engl J Med 1992;327:916-920.