Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a multisystem genetic disorder. It is most commonly caused by mutations in the PKD1 (85%, progress to ESRD earlier) or PKD2 (15%) genes. It is characterized by the progressive development and enlargement of numerous cysts in both kidneys, which eventually destroy the renal parenchyma, leading to end-stage renal disease (ESRD) typically by the 5th or 6th decade of life. The clinical presentation often involves hypertension, loin pain (due to cyst rupture or haemorrhage), and macroscopic haematuria. Notable extra-renal features include liver cysts (most common extra-renal site), berry aneurysms (subarachnoid haemorrhage risk), and mitral valve prolapse. Diagnosis is primarily via ultrasound using the Ravine/Modified Unified Criteria (age-dependent cyst count). Management aims to slow progression through strict BP control (target <130/80). Tolvaptan, a vasopressin V2-receptor antagonist, is recommended by NICE for patients with Stage 2/3 CKD and evidence of rapid progression, as it slows cyst growth and GFR decline.

The PKD1 and PKD2 genes encode polycystin-1 and polycystin-2, respectively. These proteins are located in the primary cilia of renal tubular epithelial cells and act as mechanoreceptors. Mutations lead to dysfunctional cilia and aberrant intracellular calcium signalling, causing increased cAMP levels. This triggers abnormal cell proliferation and fluid secretion into the tubular lumen, resulting in the formation of cysts. As these cysts expand from the tubules, they detach and compress surrounding healthy nephrons, leading to ischaemia, interstitial fibrosis, and progressive loss of renal function. Vasopressin (ADH) stimulates the production of cAMP, which is why V2-receptor antagonists like Tolvaptan are effective in slowing the disease process by inhibiting this pathway.

Patients are often asymptomatic until early adulthood. Common presentations include: 1. Hypertension (present in 90%). 2. Abdominal/Loin pain (can be acute if a cyst bleeds or chronic due to mass effect). 3. Macroscopic haematuria (cyst rupture into the collecting system). 4. Palpable, bilateral, knobbly kidneys on examination (ballottable). 5. Extra-renal features: Liver cysts (causing hepatomegaly but rarely liver failure), diverticular disease, and inguinal hernias. A critical complication is the rupture of a berry aneurysm (subarachnoid haemorrhage), which occurs more frequently in ADPKD. Cardiovascular disease is the leading cause of death. Progression to ESRD is common, requiring dialysis or transplantation. Autosomal Recessive PKD (ARPKD) is a different entity presenting in infancy with Potter sequence and liver fibrosis.

Bedside: BP measurement (critical); Urinalysis (haematuria, proteinuria). Bloods: U&Es (baseline eGFR), FBC. Imaging: Renal Ultrasound is first-line; for age 15-39, ≥3 cysts (total) confirms; age 40-59, ≥2 cysts in each kidney confirms. CT/MRI can be more sensitive for smaller cysts. Genetic testing: Map PKD1/PKD2 if diagnosis is unclear or for prenatal planning. Screening: MRA Brain only if there is a family history of SAH or high-risk occupation (e.g., pilot).

Conservative: High fluid intake (>3L/day) can suppress endogenous vasopressin. Low salt diet. Medical: 1. BP Control: ACE inhibitors or ARBs are first-line (Target <130/80). 2. Tolvaptan: NICE criteria include CKD stages 2-3 and evidence of rapid progression (e.g., total kidney volume increase). 3. Pain management: Analgesics; occasionally cyst aspiration or de-roofing for refractory pain. 4. Complications: Antibiotics for cyst infections (must cross cyst wall, e.g., Ciprofloxacin). Surgical: Nephrectomy may be needed if kidneys are massively enlarged and symptomatic or before transplantation. Renal Replacement Therapy (ESRD management).