Renal Cystic Disease

Forfar & Arneil 7th Edition · Autosomal recessive polycystic kidney disease (ARPKD) · Autosomal dominant polycystic kidney disease (ADPKD) · Familial juvenile nephronophthisis (NPH) · Medullary sponge kidney · Tuberous sclerosis complex (TSC) · Renal cysts
📌 Key principles: ARPKD presents in infancy with enlarged kidneys, pulmonary hypoplasia, hepatic fibrosis. ADPKD presents in adults but can be detected in utero/childhood. Nephronophthisis: medullary cysts, salt wasting, CKD in childhood. Tuberous sclerosis: angiomyolipomas, renal cysts, seizures, hamartomas.

📖 Renal Cystic Disease: Core Concepts

🧬 ARPKD (PKHD1)
Infantile polycystic kidneys: enlarged, echogenic, multiple small cysts. Congenital hepatic fibrosis (portal hypertension, cholangitis). Pulmonary hypoplasia (if oligohydramnios). Hypertension, CKD progresses.
🧬 ADPKD (PKD1/PKD2)
Most common inherited kidney disease (1:400-1000). Presents in adulthood, but cysts can be detected in childhood. Hypertension, hematuria, progressive CKD. Extrarenal: liver cysts, berry aneurysms, mitral prolapse.
🌀 Nephronophthisis (NPHP1)
Autosomal recessive. Medullary cysts, tubular atrophy. Presents in childhood (5-15y) with polyuria, polydipsia, salt wasting, anaemia, CKD. Extrarenal: retinitis pigmentosa (Senior-Loken), liver fibrosis, cerebellar vermis hypoplasia.
🫘 Medullary sponge kidney
Benign, usually asymptomatic. Cystic dilation of collecting ducts in medulla. Calcifications, stones, hematuria. Sporadic, not progressive CKD.
🧠 Tuberous sclerosis complex (TSC1/TSC2)
Autosomal dominant. Renal angiomyolipomas (fat-containing tumours), renal cysts, hypertension, CKD. Also seizures, intellectual disability, cardiac rhabdomyomas, subependymal nodules.
📊 Key imaging/gene: ARPKD: large echogenic kidneys on US. ADPKD: cysts, family history, genetic testing (PKD1/PKD2). Nephronophthisis: small kidneys, medullary cysts (late), NPHP1 gene. Tuberous sclerosis: TSC1/TSC2 mutation, renal US for angiomyolipomas.

🔍 Clinical approach to renal cystic disease

1
Family history & age of presentation – ARPKD: infantile onset, often fatal. ADPKD: adult onset, family history AD. Nephronophthisis: childhood, AR, no family history common. Tuberous sclerosis: AD, seizures, skin lesions.
2
Renal ultrasound findings – ARPKD: large echogenic kidneys, poor corticomedullary differentiation, no large cysts. ADPKD: few to many cysts of varying size. Nephronophthisis: small kidneys, medullary cysts (late). Tuberous sclerosis: angiomyolipomas (echogenic), cysts.
3
Extrarenal manifestations – ARPKD: congenital hepatic fibrosis (portal hypertension, oesophageal varices). ADPKD: liver cysts, cerebral aneurysms, mitral valve prolapse. Nephronophthisis: retinitis pigmentosa (Senior-Loken), situs inversus, cerebellar ataxia. Tuberous sclerosis: seizures, hypopigmented macules, facial angiofibromas, cardiac rhabdomyomas.
4
Laboratory findings – Nephronophthisis: polyuria, salt wasting (hyponatraemia, hyperkalaemia?), normal or low BP, anaemia, CKD. ARPKD: hypertension, CKD, liver dysfunction (elevated transaminases).
5
Genetic testing – PKHD1 (ARPKD), PKD1/PKD2 (ADPKD), NPHP1 (nephronophthisis), TSC1/TSC2 (tuberous sclerosis).
6
Prognosis & monitoring – ARPKD: often ESRD in childhood. ADPKD: ESRD by 50-60y in many. Nephronophthisis: ESRD by 10-20y. Tuberous sclerosis: variable CKD, angiomyolipoma bleeding risk.
📌 Clinical pearl: In an infant with bilateral large echogenic kidneys and respiratory distress, think ARPKD. Look for oligohydramnios in utero. In a child with polyuria, salt wasting, and normal blood pressure, suspect nephronophthisis.

📋 Stepwise management of renal cystic diseases

1
ARPKD – neonatal management – Respiratory support (pulmonary hypoplasia). Manage hypertension (ACE inhibitors, CCB). Treat CKD. Portal hypertension: endoscopic variceal ligation, shunt, liver transplantation.
2
ADPKD – management – Control BP (ACE inhibitors/ARBs). Tolvaptan (vasopressin antagonist) slows cyst growth in adults. Monitor for cerebral aneurysms (family history). Renal replacement therapy (dialysis/transplant).
3
Nephronophthisis – management – Salt and water replacement (polyuria). Treat anaemia (erythropoietin). Manage CKD, prepare for transplant. Monitor for extrarenal features (eye, liver).
4
Tuberous sclerosis – renal management – Monitor angiomyolipomas for growth (US/MRI). Large or growing tumours: mTOR inhibitors (everolimus, sirolimus), embolisation, or partial nephrectomy. Manage hypertension, CKD.
5
Medullary sponge kidney – No specific treatment. Manage stones (hydration, analgesia). Treat UTIs.
6
Genetic counselling – ARPKD (25% recurrence), ADPKD (50%), nephronophthisis (25%), tuberous sclerosis (50% new mutation rate).
⚠️ Important extrarenal associations: Senior-Loken syndrome (nephronophthisis + retinitis pigmentosa). Caroli disease (ARPKD with congenital hepatic fibrosis).

🧠 Reflex prompts: renal cystic disease

👶 A neonate with large echogenic kidneys on prenatal US, oligohydramnios, and respiratory distress. Diagnosis?
Autosomal recessive polycystic kidney disease (ARPKD). Genetic testing PKHD1. Pulmonary hypoplasia common.
🩺 A 35-year-old mother is found to have ADPKD on screening. What should be offered to her children?
Renal ultrasound for cyst detection. Genetic counselling. BP monitoring. Avoid nephrotoxic drugs.
👧 A 10-year-old with polyuria, polydipsia, salt craving, normal BP, no proteinuria. Ultrasound shows small kidneys with medullary cysts. Diagnosis?
Nephronophthisis (juvenile type). Check NPHP1 gene. Manage electrolytes, prepare for CKD progression.
🩸 A child with tuberous sclerosis presents with hypertension. Renal ultrasound shows bilateral fat-containing tumours. Diagnosis?
Angiomyolipomas. Monitor for growth and bleeding. Consider everolimus.
🧠 A 6-year-old with seizures, hypopigmented macules, and renal cysts. Diagnosis?
Tuberous sclerosis complex (TSC). Genetic testing TSC1/TSC2. MRI brain for subependymal nodules.
🩺 An adolescent with haematuria, medullary calcifications on CT, and recurrent stones. Diagnosis?
Medullary sponge kidney (benign). Manage stones symptomatically. No progression to CKD.
🧬 A child with nephronophthisis and progressive vision loss. Diagnosis?
Senior-Loken syndrome (nephronophthisis + retinitis pigmentosa). Ophthalmology referral.
🩸 A child with ARPKD and portal hypertension. Most likely complication?
Oesophageal varices from congenital hepatic fibrosis. Upper GI endoscopy, beta-blockers, banding.
🔍 What is the gene for ARPKD?
PKHD1 (polycystic kidney and hepatic disease 1) on chromosome 6. Encodes fibrocystin.
💊 What medication slows cyst growth in ADPKD?
Tolvaptan (vasopressin V2 receptor antagonist). Approved for rapidly progressing ADPKD in adults.