Polycystic Kidney Disease Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited cause of End-Stage Renal Failure (ESRF) in our population, accounting for a significant portion of our dialysis and transplant workload.
High-Yield Definition: ADPKD is a multisystemic, progressive genetic disorder characterised by the extensive formation and enlargement of cysts in both kidneys, which ultimately destroy the renal parenchyma. It frequently involves extra-renal cysts, most commonly in the liver.
Clinical One-Liner: This is the patient with bilateral, massive, ballotable kidneys, early-onset hypertension, and a strong family history of "kidney failure," who will eventually progress to ESRF.
II. Etiology & Risk Factors
Etiology:
ADPKD is a genetic disorder with autosomal dominant inheritance.
PKD1 gene mutation (Chromosome 16): ~85% of cases. Encodes Polycystin-1. More severe, with an earlier onset of ESRF (median age ~55 years).
PKD2 gene mutation (Chromosome 4): ~15% of cases. Encodes Polycystin-2. Milder phenotype, later ESRF onset (median age ~75 years).
De novo mutations (no family history) occur in ~10% of cases.
Risk Factors for Rapid Progression (This is what you screen for):
PKD1 genotype (if known).
Male sex.
Early onset of hypertension (age < 35).
First episode of gross haematuria before age 30.
Large Total Kidney Volume (TKV) on imaging relative to age.
(Note: Autosomal Recessive PKD (ARPKD) is a separate, severe paediatric condition caused by PKHD1 gene mutations, presenting in utero or in infancy with renal and hepatic fibrosis.)
III. Quick Pathophysiology
The PKD1 or PKD2 gene mutations lead to defective polycystin proteins in the primary cilium of renal tubular epithelial cells. This cilium normally acts as a flow sensor.
Defect -> Dysfunctional signalling -> Increased intracellular cAMP -> Abnormal cell proliferation, fluid secretion, and matrix production -> Cysts form from the tubule -> Cysts detach, enlarge, and compress surrounding normal parenchyma -> Leads to parenchymal ischaemia, fibrosis, and activation of the Renin-Angiotensin System (RAS) -> Results in hypertension and progressive CKD.
IV. Classification
Genetic: By mutation (PKD1 vs. PKD2).
Imaging (Mayo Clinic Classification): This is the key prognostic tool used in practice. It classifies patients by Total Kidney Volume (TKV) adjusted for height and plotted against age (derived from CT or MRI).
Class 1A (Slowest) to 1E (Fastest): This classification, along with eGFR, determines who is a "rapid progressor" and thus eligible for specific therapies like Tolvaptan.
V. Clinical Assessment
🚩 Red Flags & Immediate Actions
Severe, sudden flank pain + fever: Suspect infected cyst or haemorrhagic cyst.
Action: Full septic workup, blood & urine cultures, IV antibiotics (must have good cyst penetration, e.g., Ciprofloxacin), and urgent imaging (CT).
Sudden, severe "thunderclap" headache: Suspect ruptured intracranial aneurysm (ICA).
Action: Immediate non-contrast CT Brain. Escalate to your senior and the neurosurgical team.
Gross haematuria with haemodynamic instability: Suspect significant cyst rupture/haemorrhage.
Action: Secure two large-bore IV lines, send GXM, monitor vitals, and correct coagulopathy.
History
Key Diagnostic Clues:
Positive family history: Ask for "kidney disease," "dialysis," or "sudden brain bleeds" in multiple family members.
Hypertension diagnosed at a young age (e.g., < 40).
Awareness of having "cysts" in the kidney or liver.
Symptom Breakdown:
Common (>50%):
Hypertension (often the first manifestation).
Abdominal/flank pain (a dull ache from mass effect of large kidneys; sharp, severe pain suggests acute complication like rupture, infection, or stone).
Less Common (10-50%):
Gross haematuria.
Recurrent UTIs or cyst infections.
Nephrolithiasis (uric acid or calcium oxalate stones).
Rare (<10%):
Symptoms from massive hepatomegaly (early satiety, dyspnoea).
Symptoms of ESRF (uraemia, fluid overload).
Pertinent Negatives: Absence of family history (consider de novo mutation or misattributed paternity), absence of hypertension (unusual in established disease).
Physical Examination (OSCE Approach)
General Inspection: Usually looks well until late-stage CKD (uraemic appearance, cachexia).
Vitals: Hypertension is the cardinal sign. Fever suggests infection.
Disease-Specific Examination (Abdomen):
Inspection: May have abdominal distension ("bat-wing" flanks).
Palpation: This is the classic finding. Bilateral, firm, irregular masses in the flanks that are ballotable. These are the enlarged kidneys. The liver may also be palpable and nodular (polycystic liver disease).
Pertinent Negatives: Non-palpable kidneys (common in early-stage disease).
Examination for Differentials: Listen for renal bruits (renal artery stenosis), check for peripheral oedema (nephrotic syndrome or heart failure).
Differentiating Disease Stage
Early / Mild: Often asymptomatic or only has mild hypertension. Kidneys not yet palpable. eGFR is normal or near-normal.
Intermediate / Moderate: Palpable kidneys, worsening hypertension, declining eGFR (CKD Stage 3-4), recurrent pain or haematuria.
Late / Severe: Massive kidneys, CKD Stage 5 (ESRF), uraemic symptoms, complications (e.g., abdominal hernias, diverticulosis).
Clinical Pearl
In any young patient (<40) diagnosed with hypertension, your abdominal examination is not complete until you have attempted to ballot the kidneys.
VI. Diagnostic Workflow
Differential Diagnosis
Multiple Simple Cysts:
Points For: Cysts on ultrasound.
Points Against: No family history, kidneys are not enlarged, cysts are few and scattered, no progression to CKD.
Differentiate: Strict ultrasound diagnostic criteria (e.g., Ravine criteria).
Bilateral Hydronephrosis:
Points For: Bilateral flank masses/fullness.
Points Against: Ultrasound shows a dilated collecting system, not discrete parenchymal cysts. An obstructive cause is usually found.
Differentiate: Ultrasound is definitive.
Acquired Cystic Kidney Disease (ACKD):
Points For: Bilateral renal cysts.
Points Against: Occurs in patients with long-standing ESRF from another cause (e.g., DM, HTN), especially those on long-term dialysis. Kidneys are typically small or normal-sized, not enlarged.
Differentiate: Clinical context and kidney size.
Investigations Plan
Bedside / Initial:
UFEME: Check for haematuria (micro or gross), proteinuria (a prognostic marker), and pyuria (suggests infection).
BP Measurement: Often elevated.
First-Line Labs & Imaging:
Labs: RP/eGFR (for baseline function and staging), FBC, LFTs (to check for polycystic liver involvement).
Imaging: Ultrasound Abdomen / KUB. This is the primary diagnostic tool. Diagnostic criteria depend on age and number of cysts (e.g., for age 15-39, >=3 cysts in one or both kidneys).
Confirmatory / Gold Standard:
CT or MRI Abdomen: Not needed for diagnosis if US is clear, but essential for prognostication. These are used to calculate Total Kidney Volume (TKV) for the Mayo Classification. Also superior for evaluating complications (e.g., complex cysts, stones, haemorrhage).
Genetic Testing (PKD1, PKD2): Not routine. Reserved for atypical cases, young potential kidney donors, or for family planning.
VII. Staging & Severity Assessment
CKD Staging (KDIGO): Staged 1-5 based on eGFR and albuminuria.
Prognostic Staging (Mayo Clinic): As described in Section IV. This is what we use to decide who to treat with disease-modifying therapy.
Impact: Patients identified as "rapid progressors" (e.g., Class 1C-1E, or documented rapid eGFR decline >2.5-5 mL/min/year) are candidates for Tolvaptan.
VIII. Management Plan
A. Principle of Management
Aggressive blood pressure control.
Slowing cyst growth and CKD progression.
Managing symptoms and complications.
Timely preparation for Renal Replacement Therapy (RRT).
B. Immediate Stabilisation (For Acute Complications)
Infected Cyst: Sepsis protocol. Start broad-spectrum IV antibiotics with good cyst penetration (e.g., IV Ciprofloxacin or Ceftriaxone).
Ruptured ICA (SAH): ABCDE, secure airway, control BP (target SBP <160), urgent neurosurgical consult for coiling/clipping.
Gross Haematuria (Severe): Bed rest, hydration, analgesia. Usually self-limiting. Transfuse only if haemodynamically unstable or severely anaemic.
C. Definitive Treatment (The Ward Round Plan)
Blood Pressure Control (The #1 Priority):
Target: Strictly <130/80 mmHg. In younger patients (18-50y) with eGFR >60, aim for <110/75 mmHg if tolerated (based on HALT-PKD trial).
First-Line: ACE-Inhibitors or ARBs. They are preferred for RAS blockade.
Slowing Progression (Disease-Modifying Therapy):
Tolvaptan (Vasopressin V2-Receptor Antagonist):
Indication: Adult patients (e.g., <55 years) with CKD Stage 2-4 and evidence of rapid progression (e.g., Mayo Class 1C-1E).
MOA: Blocks vasopressin, reduces intracellular cAMP, and thus inhibits cyst cell proliferation and fluid secretion.
Side Effects: Significant aquaresis (polyuria, nocturia, thirst). Requires patient compliance to drink >3-4L/day.
Monitoring: Requires monthly LFT monitoring for the first 18 months due to risk of idiosyncratic hepatotoxicity. This is a strict requirement.
Lifestyle Modification:
High Fluid Intake: Aim for >3 L/day. This physiologically suppresses vasopressin.
Low Salt Diet: <2 g/day to help with BP control.
Avoid: NSAIDs (nephrotoxic), high caffeine intake (may increase cAMP).
Management of Complications:
Pain: First-line is Paracetamol. Avoid NSAIDs.
Cyst Infection: Requires prolonged antibiotics (4-6 weeks), often PO fluoroquinolone or trimethoprim-sulfamethoxazole, as they penetrate cysts.
Nephrolithiasis: Standard management (hydration, pain relief), but surgical access (e.g., PCNL) is more complex due to distorted anatomy.
D. Long-Term & Discharge Plan
Regular nephrology clinic follow-up (3-12 monthly depending on CKD stage) to monitor BP, eGFR, and proteinuria.
Periodic imaging (US or MRI) to monitor TKV.
Family Screening: Offer screening (usually with US) to all first-degree relatives >18 years old.
RRT Planning: Initiate education on haemodialysis, peritoneal dialysis, and kidney transplantation when eGFR approaches <20-25 mL/min/1.73m².
IX. Complications
Renal / Immediate:
Cyst haemorrhage (haematuria, pain).
Cyst infection (fever, pain).
Nephrolithiasis.
Renal / Long-Term:
Progressive CKD leading to ESRF.
Hypertension.
Extra-Renal (Very High-Yield):
Intracranial "Berry" Aneurysms (ICA): ~10% prevalence (up to 25% if positive family hx of rupture).
Action: Screen with MRA if patient is high-risk (family hx of rupture, previous rupture, high-risk profession).
Polycystic Liver Disease (PLD): Very common, especially in women. Usually asymptomatic but can become massive, causing mass effect.
Valvular Heart Disease: Mitral Valve Prolapse (MVP) and Aortic Regurgitation are most common.
Hernias: Inguinal, umbilical, or incisional (due to increased intra-abdominal pressure).
Colonic Diverticulosis.
X. Prognosis
Variable, depending on genotype and risk factors.
Median age of ESRF is ~55 years for PKD1 and ~75 years for PKD2.
Top poor prognostic factors: PKD1 mutation, large TKV, early-onset HTN, male sex.
Tolvaptan has been shown to slow eGFR decline by ~1-1.5 mL/min/year in rapid progressors.
XI. How to Present to Your Senior
S: "Dr, I am calling about Mr. Tan, a 42-year-old gentleman in bed 10, a known ADPKD patient (CKD Stage 3), who presented with 1 day of high-grade fever and severe left flank pain."
B: "His baseline creatinine is 180. He has no other new urinary symptoms. He missed his last clinic follow-up."
A: "On examination, he is febrile at 38.7°C, tachycardic at 110, but his BP is stable at 145/90. His abdomen is tender in the left flank with his known palpable kidneys. I strongly suspect an infected renal cyst."
R: "I have sent blood and urine cultures, FBC, and RP. His WBC is 15. I would like to start IV Ciprofloxacin 400mg BD and request an urgent CT abdomen to confirm the infected cyst and rule out a perinephric collection."
XII. Summary & Further Reading
Top 3 Takeaways
ADPKD is the main inherited cause of ESRF. Suspect it in any young hypertensive patient, especially with a family history or palpable kidneys.
Management hinges on two pillars: strict BP control (ACEi/ARB first) and, in select rapid progressors, Tolvaptan to slow cyst growth (watch the LFTs).
This is a multisystem disease. Always think of and screen for extra-renal manifestations, especially intracranial aneurysms.
Key Resources
International Guideline: KDIGO 2024 Clinical Practice Guideline for the Management of ADPKD. (This is the new global standard).
UpToDate: "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management"
Amboss: "Autosomal dominant polycystic kidney disease"
