Polycystic Kidney Disease (PKD)

Polycystic kidney disease is an inherited disorder in which fluid-filled cysts arise from renal tubules, detach from them, and grow independently. The cysts do not replace functioning tissue so much as compress and distort it — kidneys that may eventually weigh several kilograms each still contain nephrons, progressively strangled by the expanding cysts and the interstitial fibrosis that accompanies them.

It is a ciliopathy. The polycystin proteins sit in the primary cilium of the tubular epithelial cell, where they sense luminal flow and regulate intracellular calcium. When they fail, calcium falls, cyclic AMP rises, and the cell switches from a quiescent absorptive phenotype to a proliferative, fluid-secreting one. That single mechanistic switch explains both the cyst growth and why vasopressin — which raises tubular cAMP — accelerates the disease, and therefore why hydration status and vasopressin antagonism matter therapeutically.

Autosomal dominant PKD (ADPKD) is much the commoner form, affecting roughly 1 in 1,000 and accounting for most cases. Mutations in PKD1 (about 78%, more severe, end-stage disease around age 55) or PKD2 (about 15%, milder, around age 75). A family history is usual but up to a quarter arise de novo. Crucially, it is a systemic disorder, not a renal one — cysts occur in liver, pancreas and seminal vesicles, and vascular involvement produces intracranial aneurysm, mitral valve prolapse and abdominal wall hernia.

Autosomal recessive PKD (ARPKD) is rare, caused by PKHD1 mutations, and presents in infancy or in utero with massively enlarged kidneys and congenital hepatic fibrosis. Severe cases cause oligohydramnios and pulmonary hypoplasia.

Progression is driven by total kidney volume, which rises steadily for decades before creatinine moves at all — the reason renal function looks deceptively normal until late.

Most people are asymptomatic for decades, and diagnosis is frequently incidental or made through family screening.

Pain is the commonest symptom: a chronic dull flank or back ache from the mass and stretch of enlarging kidneys, punctuated by acute episodes from cyst haemorrhage, cyst infection, or passage of a stone. Visible haematuria affects around half at some point, usually from cyst rupture into the collecting system, and is typically self-limiting.

Hypertension is the most important early sign — it appears before renal function declines, affects most patients by middle age, and is driven by cyst compression of the renal vasculature activating the renin-angiotensin system. Controlling it is the single most effective intervention for slowing progression and reducing cardiovascular risk.

Other features include recurrent urinary infection and cyst infection, nephrolithiasis in around 20%, a palpable abdominal mass, early loss of urinary concentrating ability causing nocturia, and eventually the symptoms of chronic kidney disease. Liver cysts are common, usually asymptomatic, and more numerous in women.

Intracranial aneurysm is the complication that changes management: prevalence is around 8%, rising to 20% where there is a family history of aneurysm or subarachnoid haemorrhage. Rupture is catastrophic, and screening with MR angiography is offered to those with a family history, a high-risk occupation, or before major surgery. A sudden severe headache in a patient with ADPKD must be treated as subarachnoid haemorrhage until proven otherwise.

Cyst infection is difficult to treat because most antibiotics penetrate cysts poorly — lipid-soluble agents such as fluoroquinolones and trimethoprim-sulfamethoxazole are preferred. End-stage renal disease requiring dialysis or transplantation is the eventual outcome in the majority with PKD1.

Ultrasound is the first-line investigation and is usually sufficient where there is a family history. Age-adjusted criteria apply, because cysts accumulate over time: in an at-risk individual aged 15–39, three or more cysts in total; aged 40–59, two or more in each kidney. Fewer than two cysts by age 40 effectively excludes the diagnosis.

MRI is more sensitive and is used to measure total kidney volume, which is the best available predictor of progression and is now used to select patients for disease-modifying treatment. Genetic testing is reserved for equivocal cases, for potential living related donors, and for reproductive counselling.

Assessment should also cover blood pressure, eGFR, urinalysis for protein and blood, and liver function. Screening an asymptomatic at-risk young person raises real questions about insurance and psychological impact, and warrants discussion before testing rather than after.

Hypertension and cardiovascular disease dominate the long-term picture, and left ventricular hypertrophy is common. Chronic kidney disease brings anemia, mineral and bone disorder, and hyperkalaemia. Polycystic liver disease can become symptomatic through mass effect, particularly in women after multiple pregnancies or estrogen exposure. Colonic diverticulosis, abdominal wall and inguinal hernia, and mitral valve prolapse all occur at increased frequency. Because ADPKD is autosomal dominant, each child of an affected parent has a 50% risk, so family screening and genetic counselling are part of managing the patient in front of you.