Cystic Renal Diseases
Pathology · Renal · lean revision notes
Cystic Renal Diseases
A heterogeneous group of inherited and acquired disorders in which one or both kidneys develop epithelium-lined, fluid-filled cysts. They are a favourite NEET PG topic because they bridge molecular genetics, pathology, radiology and clinical medicine — the classic example being ADPKD with its berry-aneurysm and hepatic-cyst associations. This note organises the whole spectrum, then drills the high-yield discriminators.
Classification
Renal cysts range from trivial (simple cysts of ageing) to lethal (perinatal ARPKD). The most useful way to file them is by inheritance and age of presentation.
| Disease | Inheritance | Gene / locus | Typical age | Key association |
|---|---|---|---|---|
| Autosomal dominant PKD (ADPKD, "adult") | AD | PKD1 (16p13.3, polycystin-1) / PKD2 (4q, polycystin-2) | 30–50 yr (adult) | Berry (saccular) aneurysm, liver cysts, MVP |
| Autosomal recessive PKD (ARPKD, "infantile") | AR | PKHD1 (6p21, fibrocystin/polyductin) | Neonate / infant | Congenital hepatic fibrosis, Potter sequence |
| Medullary sponge kidney (MSK) | Mostly sporadic | — | Adult, often incidental | Nephrolithiasis, hypercalciuria |
| Medullary cystic kidney disease / Nephronophthisis complex | AD (MCKD) / AR (nephronophthisis) | NPHP genes / MUC1, UMOD | Childhood (NPHP) / adult (MCKD) | Salt wasting, commonest genetic cause of ESRD in children |
| Acquired cystic kidney disease (ACKD) | Acquired | — | Dialysis patients | Renal cell carcinoma (papillary type) |
| Simple cysts | Acquired | — | Older adults | Benign, incidental |
| Multicystic dysplastic kidney | Sporadic (non-genetic dysplasia) | — | Antenatal/neonate | Non-functioning, atretic ureter |
High-yield: "Dominant = aDult; Recessive = infant" — the single most repeated discriminator. ADPKD presents in adulthood despite being a congenital gene defect; ARPKD presents perinatally.
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Genetics & pathophysiology
- PKD1 on chromosome 16 encodes polycystin-1 — accounts for ~85% of cases; presents earlier and progresses faster (ESRD ~mid-50s).
- PKD2 on chromosome 4 encodes polycystin-2 (a calcium-permeable cation channel, TRPP2) — ~15%, milder, ESRD ~70s.
- Polycystin-1 and polycystin-2 form a complex localised to the primary cilium of tubular epithelial cells → ADPKD is a ciliopathy. Defective ciliary mechanosensation deranges intracellular Ca²⁺ and raises cAMP, driving fluid secretion and proliferation.
- Two-hit hypothesis: the germline mutation is one hit; a somatic "second hit" in the normal allele within a tubular cell initiates each cyst — explaining why only a fraction of nephrons become cystic and why cysts appear focally over decades.
Morphology
Both kidneys are massively enlarged (can exceed 4 kg each), with the external surface composed entirely of cysts; little intervening normal parenchyma. Cysts arise from any segment of the nephron (an important contrast with ARPKD's purely collecting-duct cysts).
Clinical features
- Flank/abdominal pain and a palpable abdominal mass; haematuria (cyst rupture or stones).
- Hypertension — early and very common (activation of intrarenal RAAS by cyst expansion).
- Progressive chronic kidney disease → ESRD in ~50% by age 60.
- Extra-renal manifestations (frequently tested):
- Hepatic cysts — the commonest extrarenal feature; rarely affect liver function.
- Berry (saccular) aneurysms of the circle of Willis → risk of subarachnoid haemorrhage; cluster in families.
- Mitral valve prolapse, aortic regurgitation.
- Colonic diverticulosis, abdominal wall and inguinal hernias.
- Cysts in pancreas, seminal vesicles, arachnoid.
High-yield: The classic NEET PG "genetics–pathology bridge" — Which condition is associated with berry aneurysm and subarachnoid haemorrhage? → ADPKD (PKD1). Also remember the reverse: a young patient with SAH + hypertension + bilateral flank masses = ADPKD.
High-yield: Commonest extrarenal manifestation = liver (hepatic) cysts; most dangerous = intracranial berry aneurysm.
Diagnosis
- Investigation of choice / screening = ultrasonography (cheap, no contrast, detects cysts ≥1 cm).
- Modified Ravine (Pei) ultrasound criteria for at-risk individuals (positive family history):
| Age | Number of cysts (combined, both kidneys) for diagnosis |
|---|---|
| 15–39 yr | ≥ 3 total |
| 40–59 yr | ≥ 2 in each kidney |
| ≥ 60 yr | ≥ 4 in each kidney |
- MRI is more sensitive and gives total kidney volume (TKV) — the best validated marker of disease progression and a guide to therapy.
- Genetic testing when imaging is equivocal, in young potential living-related donors, or when no family history.
Management
Approach: control BP → slow cyst growth → manage complications → renal replacement.
- Blood pressure control with an ACE inhibitor / ARB — first-line antihypertensive; target ≤110/75 in young patients with preserved function.
- Tolvaptan (a V2 vasopressin-receptor antagonist) — the disease-modifying drug of choice; lowers intracellular cAMP, slows TKV growth and eGFR decline in rapidly progressive disease. Monitor LFTs (hepatotoxicity) and expect aquaresis/polyuria.
- High fluid intake, sodium restriction; treat stones and infections.
- Dialysis / transplantation at ESRD.
- Screening for intracranial aneurysm with MR angiography in patients with a family history of SAH/aneurysm or a high-risk occupation.
High-yield: Tolvaptan = V2 antagonist = only approved drug to slow ADPKD progression. Antihypertensive of choice = ACE inhibitor/ARB.
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Genetics
- Single gene: PKHD1 on chromosome 6p, encoding fibrocystin (polyductin), a ciliary protein of collecting-duct and biliary epithelium.
Morphology — the classic exam picture
- Both kidneys are enlarged and smooth; on cut section, innumerable small cysts arranged radially, perpendicular to the cortical surface, giving a "sponge-like" / radial spoke-wheel pattern. Cysts arise exclusively from dilated collecting ducts (cylindrical, elongated, fusiform) — distinguishing it histologically from ADPKD's rounded cysts of any nephron segment.
Clinical features
- Presents in the neonate/infant. Severe forms cause Potter sequence in utero: oligohydramnios (poor fetal urine output) → pulmonary hypoplasia (the main cause of perinatal death), limb deformities, low-set ears, flattened facies.
- Massive flank masses, respiratory distress at birth.
- Survivors invariably develop congenital hepatic fibrosis → portal hypertension, hepatosplenomegaly, varices; bile-duct plate malformation may cause Caroli disease.
High-yield: ARPKD is always associated with congenital hepatic fibrosis; ADPKD is associated with liver cysts (not fibrosis). This liver distinction is a recurring single-best-answer.
High-yield: Perinatal death in ARPKD is from pulmonary hypoplasia (Potter sequence), not renal failure per se.
ADPKD vs ARPKD — the master comparison
| Feature | ADPKD (adult) | ARPKD (infantile) |
|---|---|---|
| Inheritance | Autosomal dominant | Autosomal recessive |
| Gene/protein | PKD1 (polycystin-1)/PKD2 (polycystin-2) | PKHD1 (fibrocystin) |
| Chromosome | 16 (PKD1), 4 (PKD2) | 6 |
| Age at presentation | 30–50 yr | Neonate/infant |
| Cyst origin | Any nephron segment, rounded | Collecting ducts only, radial/elongated |
| Kidney size | Hugely enlarged, bosselated | Enlarged, smooth |
| Liver | Cysts | Congenital hepatic fibrosis |
| Brain | Berry aneurysm, SAH | Not characteristic |
| Lungs | — | Pulmonary hypoplasia (Potter) |
| Prognosis | ESRD by 50s–70s | Often perinatal death; survivors → hepatic fibrosis |
Medullary Sponge Kidney (MSK)
- Multiple small cystic dilatations of the medullary and papillary collecting ducts — gives a "bunch of grapes" / "paintbrush" appearance on intravenous urography (the historic gold standard before CT urography).
- Usually sporadic, benign, incidental in adults; renal function is preserved.
- Complications driven by urinary stasis and hypercalciuria: recurrent calcium nephrolithiasis, nephrocalcinosis (medullary calcifications), and recurrent UTIs/haematuria.
- Management is supportive: hydration, treat stones; thiazides reduce hypercalciuria and recurrent stones; citrate supplementation.
High-yield: "Bunch of grapes / paintbrush appearance on IVU + recurrent calcium stones + normal renal function" = medullary sponge kidney.
Medullary Cystic Disease Complex (Nephronophthisis–MCKD)
A confusingly named group where cysts sit at the corticomedullary junction, but the dominant problem is tubulointerstitial fibrosis, not the cysts.
- Nephronophthisis (NPHP) — autosomal recessive, childhood onset; the commonest genetic cause of ESRD in children/young adults. Triad: polyuria/polydipsia (defective concentration), salt wasting, growth retardation/anaemia. May associate with retinitis pigmentosa (Senior–Løken syndrome).
- Medullary cystic kidney disease (MCKD) — autosomal dominant (UMOD/uromodulin, MUC1), adult onset, with hyperuricaemia and gout.
- Kidneys are typically normal-sized or small (a useful contrast: PKD enlarges kidneys, this group does not). Diagnosis by clinical picture + genetics; ultrasound may be normal.
High-yield: Nephronophthisis = commonest inherited cause of ESRD in children. Salt-losing nephropathy with small kidneys and corticomedullary cysts.
Acquired Cystic Kidney Disease (ACKD)
- Develops in patients with long-standing chronic kidney disease, especially on prolonged dialysis (kidneys are initially small/contracted, then develop multiple cysts).
- Major significance: a markedly increased risk of renal cell carcinoma (often papillary type, multifocal/bilateral) — these patients need surveillance imaging.
High-yield: Long-term dialysis patient develops new cysts and a solid mass → suspect RCC arising in acquired cystic disease.
Simple Cysts and the Bosniak Classification
Simple cysts are extremely common, increase with age, and are benign. The clinical challenge is separating benign from malignant cystic lesions on CT — the Bosniak classification stratifies malignancy risk.
| Bosniak category | Features | Malignancy risk | Management |
|---|---|---|---|
| I | Simple, thin wall, no septa, water density, no enhancement | Negligible | Reassure |
| II | Few hairline septa, fine calcification, <3 cm hyperdense | Minimal | No follow-up |
| IIF | Multiple thin septa, minimal thickening, "F" = follow-up | ~5% | Surveillance imaging |
| III | Thick/irregular walls or septa with enhancement | ~50% | Surgery/partial nephrectomy |
| IV | Clearly malignant: enhancing soft-tissue components | ~90% | Surgery |
High-yield: A cyst that enhances with contrast (categories III–IV) is malignant until proven otherwise.
Key Differentials & Discriminators
- Bilateral flank masses + hypertension + adult onset → ADPKD.
- Neonatal abdominal masses + oligohydramnios/pulmonary hypoplasia → ARPKD.
- Enlarged kidneys = ADPKD/ARPKD; normal/small kidneys with cysts = nephronophthisis–MCKD complex.
- Medullary cysts + stones, normal function = MSK; medullary cysts + ESRD = MCKD/NPHP.
- Unilateral, non-functioning, irregular cysts in a neonate with atretic ureter = multicystic dysplastic kidney (a developmental dysplasia, not inherited cystic disease).
- Cysts + angiomyolipomas + tubers → think tuberous sclerosis; cysts + clear-cell RCC + haemangioblastoma/phaeochromocytoma → von Hippel–Lindau.
Recently asked / exam angle
- Berry aneurysm / subarachnoid haemorrhage is most associated with which renal disease? → ADPKD (PKD1, chromosome 16) — repeatedly asked as the genetics–pathology bridge.
- Gene/chromosome match: PKD1 → chromosome 16/polycystin-1; PKD2 → chromosome 4/polycystin-2; PKHD1 → chromosome 6/fibrocystin.
- Most common extrarenal manifestation of ADPKD → hepatic cysts.
- Drug that slows ADPKD progression / mechanism → Tolvaptan, a V2 (vasopressin-2) receptor antagonist.
- ARPKD is associated with → congenital hepatic fibrosis; perinatal death from pulmonary hypoplasia.
- Cysts arise from collecting ducts in → ARPKD; from any nephron segment in → ADPKD.
- Commonest genetic cause of ESRD in children → nephronophthisis.
- Bunch-of-grapes / paintbrush on IVU → medullary sponge kidney.
- Dialysis patient + new cysts + RCC risk → acquired cystic kidney disease (papillary RCC).
- Enhancing renal cyst (Bosniak III/IV) → malignant, needs surgery.
- ADPKD is a disorder of which organelle? → primary cilium (ciliopathy).
Mnemonic — ADPKD extrarenal "BAD HELP": Berry aneurysm, Aortic regurgitation, Diverticulosis (colon), Hepatic cysts, Extra (pancreatic/seminal vesicle cysts), Liver cysts, Prolapse (mitral valve) + hernias.
Mnemonic — Potter sequence (ARPKD): POTTER = Pulmonary hypoplasia, Oligohydramnios, Twisted face (flat facies), Twisted skin/limbs, Extremity defects, Renal cause.
Rapid revision
- ADPKD = adult, AD, PKD1 (chr 16, polycystin-1, 85%) or PKD2 (chr 4, polycystin-2, milder).
- ARPKD = infant, AR, PKHD1 (chr 6, fibrocystin), collecting-duct cysts only.
- ADPKD → berry aneurysm + SAH; liver cysts; MVP; colonic diverticulosis.
- ARPKD → congenital hepatic fibrosis; perinatal death from pulmonary hypoplasia (Potter sequence).
- Investigation of choice for ADPKD screening = ultrasound; use modified Pei/Ravine criteria (≥3 cysts at 15–39 yr).
- ADPKD disease-modifying drug = tolvaptan (V2 antagonist); antihypertensive of choice = ACEi/ARB.
- ADPKD is a ciliopathy; pathogenesis follows the two-hit hypothesis.
- Medullary sponge kidney → bunch-of-grapes/paintbrush on IVU, calcium stones, normal renal function.
- Nephronophthisis (AR) = commonest genetic cause of ESRD in children; salt wasting, small kidneys.
- MCKD (AD) = uromodulin/UMOD, hyperuricaemia and gout.
- Acquired cystic disease (dialysis) → increased risk of papillary RCC.
- Bosniak III/IV = enhancing = malignant; tuberous sclerosis and VHL also cause renal cysts (with RCC/AML).