Guideline sources The following summarized guidelines for the evaluation and management of autosomal dominant polycystic kidney disease (ADPKD) are prepared by our editorial team based on guidelines from the European Association for the Study of the Liver (EASL 2022), the United Kingdom Kidney Association (UKKA/BAPN 2019), the Ministry of Health, Labour and Welfare of Japan (MHLW/JSN 2016), and the Spanish Working Group on Inherited Kidney Diseases (SWG-IKD 2014). 1 2 3 4 Guidelines 1. Screening and diagnosis Indications for screening: As per UKKA 2019 guidelines, decide on screening for ADPKD in asymptomatic children and young individuals at risk of developing ADPKD jointly between health professionals and parents https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 1/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway or carers and, wherever possible, the young person. B Show 4 more As per SWG-IKD 2014 guidelines, obtain ultrasound as the preferred screening tool for relatives of an affected proband. B Show 5 more 2. Diagnostic investigations Diagnostic imaging: obtain CT in uncertain cases or in patients with suspicion of associated renal disease, such as stones or tumor. B Show 3 more Genetic testing: provide genetic counseling in all patients with ADPKD. B Show 5 more Evaluation for cyst infection: Consider diagnosing cyst infection based on the association of: fever > 38 C local pain in the flank CRP > 5 mg/dL. C Show 3 more Screening for polycystic liver disease: obtain abdominal ultrasound to screen for polycystic liver disease in all patients diagnosed with ADPKD. B Screening for intracranial aneurysm: As per JSN 2016 guidelines: Recognize that: the prevalence of unruptured intracranial aneurysms is higher in patients with ADPKD than in the general population ICH, either cerebral or aneurysmal subarachnoid hemorrhage, confers high risks for mortality and morbidity in patients with ADPKD. B Screen patients with ADPKD for intracranial aneurysms to improve prognosis. B As per SWG-IKD 2014 guidelines, screen for intracranial aneurysms in any of the following situations: family or past personal history of stroke or intracranial aneurysm symptoms suggestive of intracranial aneurysms job or hobby in which loss of consciousness may be lethal preparation for major elective surgery extreme anxiety regarding the risk of having intracranial aneurysms. B Show 3 more Screening for valvular heart disease: consider obtaining TTE only in patients with heart murmur to evaluate the severity of valvular disease. C https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 2/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway 3. Medical management General principles: assess cardiovascular risk and treat all modifiable cardiovascular risk factors according to the CKD guidelines. Show 2 more Tolvaptan: administer tolvaptan to slow the increase in total kidney volume and the decline in kidney function in patients with ADPKD with a relatively-good renal function with CrCl C60 mL/min by Cock-Croft equation and a total kidney volume 750 mL. B Antihypertensive therapy: As per JSN 2016 guidelines, initiate antihypertensive therapy to slow the deterioration of renal function and to improve the vital prognosis in patients with ADPKD complicated with hypertension. B As per SWG-IKD 2014 guidelines: Target clinic BP in patients with ADPKD similar to other patients with CKD. B Include RAAS inhibitors as the first option in the pharmacological regimens for hypertension. B Management of pain: obtain evaluation for the cause of chronic pain and correct it if possible. B Show 3 more Management of cyst bleeding: As per JSN 2016 guidelines, consider administering tranexamic acid if cystic hemorrhage does not improve by conservative treatment. C As per SWG-IKD 2014 guidelines, offer bed rest, analgesics and hydration to increase the urinary flow rate to 2-3 L/day for the treatment of patients with cyst bleeding. B Show 3 more Management of cyst infection: As per JSN 2016 guidelines, administer newer quinolones for the treatment of cyst infection in patients with ADPKD. B As per SWG-IKD 2014 guidelines, hospitalize patients with ADPKD with symptomatic cyst infection. B Show 4 more Management of kidney stones: Consider offering potassium citrate and urine alkalinization in patients with nephrolithiasis, if hypocitraturia is present. C Consider performing percutaneous nephrolithotomy and extracorporeal shock wave lithotripsy in an individualized setting. C 4. Nonpharmacologic interventions Lifestyle modifications: https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 3/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway Encourage lifestyle changes (maintenance of ideal body weight, regular aerobic exercise and a diet limited to a maximum intake of 6 g of salt daily) to prevent and to treat hypertension as in patients with essential hypertension. B Advise patients with large polycystic kidneys to avoid contact sports and situations carrying a high risk of abdominal trauma. B Water intake: As per JSN 2016 guidelines, advise 2.5-4 L/day of water intake in patients with ADPKD. B As per SWG-IKD 2014 guidelines, advise high free water intake (2-3 L/day) in patients with stages 1-3 CKD. B Dietary protein restriction: insufficient evidence to recommend for or against dietary protein restriction for inhibiting progression of renal dysfunction in patients with ADPKD. I 5. Therapeutic procedures Cyst aspiration: Do not aspirate renal cysts to improve renal function in patients with ADPKD. D Consider aspirating renal cysts for the management of disease-related chronic pain or abdominal distention, for diagnostic purposes and the treatment of infected cysts. C Transarterial embolization: Perform renal transarterial embolization in patients with end-stage renal disease to reduce the size of enlarged kidneys. B Perform hepatic transarterial embolization in patients with end-stage renal disease to reduce hepatomegaly. B Dialysis: As per JSN 2016 guidelines: Perform peritoneal dialysis in patients with ADPKD. B Consider performing peritoneal dialysis for the improvement of the vital prognosis and quality of life in patients with ADPKD. C As per SWG-IKD 2014 guidelines: Perform peritoneal dialysis or hemodialysis in most patients with end-stage renal disease. B Avoid administering heparin during hemodialysis in patients with recurrent gross hematuria. D 6. Surgical interventions Nephrectomy: as per JSN 2016 guidelines, perform unilateral or bilateral nephrectomy if native kidney enlargement seems sufficiently massive to jeopardize accommodation of the donor kidney. B Nephrectomy (SWGIKD): https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 4/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway Consider performing elective nephrectomy of native kidneys before renal transplantation if the kidney size prevents adequate placement of the graft. Take into account the experience of each center for timing (pretransplant or simultaneous with transplantation). C Consider performing native kidney nephrectomy for the treatment of complications, such as bleeding or persistent infection. C Kidney transplantation: as per JSN 2016 guidelines, consider performing solitary or simultaneous transplantation of the liver and the kidney for the improvement of the vital prognosis and quality of life in patients with autosomal dominant polycystic kidney. C Kidney transplantation (SWGIKD): perform transplantation as a RRT. Prefer preemptive renal transplantation from living donors. B 7. Specific circumstances Pregnant patients: counsel patients that pregnancy is not recommended in patients with ADPKD with stage 3-5 CKD, excluding transplanted patients. B Show 2 more Pediatric patients: insufficient evidence to recommend for or against screening for ADPKD in pediatric patients at risk due to ethical issues in the absence of a specific available treatment. Show 6 more Patients with cerebral aneurysm: As per JSN 2016 guidelines: Decide on treatment of a cerebral aneurysm by a comprehensive examination of factors such as location, shape, and size of the aneurysm, and general conditions, age, and medical history of the patient. B Consult with a neurosurgeon for decisions regarding treatment advisability and methods. B As per SWG-IKD 2014 guidelines, manage patients with unruptured intracranial aneurysms in collaboration with the neurosurgery department as follows: Situation Guidance Unruptured intracranial aneurysm 12 mm in diameter Treat Symptomatic unruptured intracranial aneurysm Enlarging unruptured intracranial aneurysm Unruptured intracranial aneurysm 7-12 mm in diameter and any of the following features Consider treating Unruptured intracranial aneurysm < 7 mm in diameter in anterior circulation without Do not treat https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 5/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway family history of subarachnoid hemorrhage and without daughter sac Asymptomatic cavernous internal carotid aneurysms. B Show 2 more Patients with polycystic liver disease: advise avoiding estrogens and drugs stimulating cyclic adenosine monophosphate accumulation (such as caffeine) in patients with moderate-to-severe polycystic liver disease. B Show 6 more 8. Patient education General counseling: provide information on ADPKD inheritance and potential benefits and harms of testing for ADPKD in parents or carers of children at risk of developing ADPKD. B 9. Preventative measures Prevention of kidney stones: Insufficient evidence to recommend any prophylactic medical treatment for urolithiasis in patients with ADPKD. I Consider offering standard prophylactic treatment in patients with metabolic disorder. C 10. Follow-up and surveillance Blood pressure monitoring: obtain ambulatory or home BP monitoring for early diagnosis of hypertension. B Follow-up: schedule follow-up visits according to the CKD stage. B Show 3 more References 1. Shigeo Horie, Toshio Mochizuki, Satoru Muto et al. Evidence-based clinical practice guidelines for polycystic kidney disease 2014. Clin Exp Nephrol. 2016 Aug;20 4 493 509. Open 2. Elisabet Ars, Carmen Bernis, Gloria Fraga et al. Spanish guidelines for the management of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv95 105. Open 3. European Association for the Study of the Live. EASL Clinical Practice Guidelines on the management of cystic liver diseases. EASL. 2022 Jun. Open https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 6/7 6/23/23, 3:16 AM Autosomal dominant polycystic kidney disease Pathway 4. Jan Dudley, Paul Winyard, Matko Marlais et al. Clinical practice guideline monitoring children and young people with, or at risk of developing autosomal dominant polycystic kidney disease ADPKD . BMC Nephrol. 2019 Apr 30;20 1 148. Open 5. Japanese Society of Nephrology. Essential points from Evidence-based Clinical Practice Guidelines for Chronic Kidney Disease 2018. Clin Exp Nephrol. 2019 Jan;23 1 1 15. Open https://web.pathway.md/diseases/recH4dmZ6H9uUUD67 7/7