This article provides comprehensive insights into autosomal dominant polycystic kidney disease (ADPKD), covering its genetic basis, clinical manifestations, diagnostic criteria, radiological evaluation, genetic testing, and treatment options, including the use of tolvaptan.

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Introduction

ADPKD (autosomal dominant polycystic kidney disease) is a genetic illness. It is a multisystem and progressive disease characterised by cyst formation, kidney enlargement, and other organ involvement (e.g., liver, pancreas, spleen). 

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Etiopathology

1. Because ADPKD is an autosomal dominant illness, it affects both men and women equally, and each offspring has a 50% chance of inheriting the disease.
2. ADPKD involves at least two genes. PKD1 accounts for most ADPKD cases and is located on 16p13.3. PKD2 accounts for 15% of ADPKD cases.
3. A common finding in pathogenesis is increased levels of cAMP in the kidney and the liver and vascular smooth muscle. cAMP exerts effects on cell proliferation in different cell types.

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Clinical evaluation

1. Renal size rises with age, and renal enlargement occurs in 100% of ADPKD patients. The severity of the structural abnormalities correlates with ADPKD symptoms such as pain, hematuria, hypertension, and renal impairment. Most clinical manifestations are directly related to the enlargement of renal cysts.
2. Acute renal pain is quite common as a result of cyst bleeding, infection, stone, and, in rare cases, malignancies. Visible hematuria may be the initial presenting symptom. Cyst haemorrhage is a frequent complication causing gross haematuria when the cyst communicates with the collecting system. It can manifest with fever, raising the possibility of cyst infection.
3. Urinary tract infection (UTI) is common in ADPKD. UTI presents as cystitis, acute pyelonephritis, cyst infection, and perinephric abscesses. Escherichia coli, Klebsiella and Proteus species, and other Enterobacteriaceae cause most infections.
4. Renal stone disease occurs in about 20% of patients with ADPKD. The majority of stones are made up of uric acid, calcium oxalate, or both. Stones in ADPKD can be difficult to detect on imaging due to cyst wall and parenchymal calcification. CT urography is helpful.
5. Hypertension is the most common manifestation of ADPKD. In hypertensive patients with ADPKD, microalbuminuria, proteinuria, and hematuria are more prevalent.
6. Renal function is normal in the vast majority of patients. When renal function begins to deteriorate, the kidneys are usually significantly enlarged. ESRD is not inevitable in ADPKD. Up to 77% of patients are alive with preserved renal function at age 50, and 52% at age 73. The volumes of the kidneys and cysts are the best indicators of renal functional deterioration.
7. Most simple hepatic cysts are solitary, and PLD should be suspected when there are four or more cysts in the hepatic parenchyma.
8. A ruptured cerebral aneurysm, resulting in a subarachnoid or intracerebral haemorrhage, is the most serious complication of PKD. Intracranial aneurysms occur in approximately 8 to 12 per cent of patients with ADPKD

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Diagnostic criteria

The diagnosis is made based on age and the number of cysts on ultrasonography of the kidney.

• 15-29 years old - two or more unilateral or bilateral cysts
• 30-39 years old- two or more cysts in each kidney
• 40-49 years old - two or more cysts in each kidney
• 60 years or above old - four or more cysts in each kidney

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Radiological evaluation

1. CT is more sensitive than ultrasonography and can detect as small as 0.5 cm cysts. CT may be useful in doubtful cases in children or complicated cases (e.g., kidney stone, suspected tumour).
2. MRI is more sensitive than ultrasound or CT scanning. It may be more helpful in distinguishing renal cell carcinoma from simple cysts. MRI is the best imaging method for monitoring kidney size following treatment to measure progress, and it is the criterion standard for determining renal volume in ADPKD clinical studies.
3. The primary imaging approach for diagnosing intracranial aneurysms (ICAs) is magnetic resonance angiography (MRA). It is used selectively rather than routinely.

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Genetic testing

1. Genetic testing may be performed. ADPKD, autosomal recessive polycystic kidney disease (ARPKD), and autosomal dominant polycystic liver disease (ADPLD) can all be distinguished via genetic testing. The presence of either PKD1 or PKD2 subtypes in ADPKD alters the prognosis and may aid in clinical management.
2. Young adults with negative ultrasonography findings who are being investigated as possible kidney donors are a primary indication for genetic screening.

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Treatment

Flank Pain

The following are the causes of flank pain that require treatment:

• Infections
• Stones
• Tumour

1. Opioid analgesics should be reserved for the management of acute pain.
2. Reassurance, lifestyle changes, and avoiding irritating activities may all be beneficial. Tricyclic antidepressants, which are well tolerated, are useful in chronic pain syndromes.
3. If a big cyst is thought to be causing the pain, cyst aspiration can be performed under ultrasound or CT guidance.
4. If many cysts are causing pain, laparoscopic or surgical cyst fenestration may help.

Cyst haemorrhage

1. Cyst haemorrhage episodes are self-limiting, and patients react well to conservative therapy, which includes bed rest, painkillers, and increased fluid intake to prevent clots from blocking the arteries.
2. Rarely, bleeding is more severe, leading to hemodynamic instability; this requires hospitalisation and transfusions.

Cyst and urinary tract infection

1. Immediate treatment of symptomatic cystitis and asymptomatic bacteriuria is indicated to prevent retrograde seeding of the renal parenchyma.
2. Agents of choice include trimethoprim-sulfamethoxazole and fluoroquinolones.
3. Infected cysts should be drained percutaneously or surgically if fever persists after 1 to 2 weeks of proper antimicrobial therapy.
4. Nephrectomy should be explored in the case of end-stage polycystic kidney disease.

Nephrolithiasis

Potassium citrate is the preferred treatment for stone-forming disorders, which include; 

• Uric, acid stones
• Hypo-citraconic calcium oxalate stones
• Distal acidification disorders

Hypertension

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), increase renal blood flow in ADPKD and are antihypertensives of choice.

Tolvaptan

1. Tolvaptan, a selective vasopressin V2-receptor antagonist, is approved for reducing kidney function decline in persons at risk of fast-progressing ADPKD in the United States and Europe.
2. During the 1-year REPRISE (Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD) experiment, tolvaptan treatment improved glomerular filtration rate (GFR).

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.