Relevant Physical Signs

  • Blood pressure: hypertension
  • Conjunctival pallor: anaemia complicating chronic kidney disease
  • Plethora: increased erythropoietin production
  • Pupillary reflexes: compression from berry aneurysms (classically a posterior communicating artery aneurysm) result in dilation of the ipsilateral pupil. Mydriasis typically occurs before ophthalmoplegia in surgical third nerve palsies because the parasympathetic fibres run along the outer surface of the nerve
  • Fundus examination:
    • Hypertensive retinopathy
    • Retinal haemangioblastomas – von Hippel Lindau
    • Retinal hamartoma – tuberous sclerosis
  • Mitral valve prolapse and aortic regurgitation due to systemic collagen defect (approximately 20% of patients)
  • Bilateral ballotable masses which do not move with inspiration
    • Able to get above the masses
    • Overlying percussion note is resonant
    • Usually non-tender
    • Usually no associated renal bruit
  • Hepatosplenomegaly: hepatic cysts occur in up to 70% of patients with polycystic kidney disease, and may result in palpable hepatomegaly. Splenic cysts occur in up to 5% of patients
  • Nephrectomy scars: cyst haemorrhage, traumatic injury, recurrent infections, cyst rupture
  • Abdominal wall herniae
  • Evidence of ongoing renal replacement therapy
    • Arteriovenous fistula
    • Tenckhoff catheter
    • Tunneled dialysis catheter
    • Renal transplant: usually in the iliac fossae
  • Fluid status
    • Jugular venous pulse, neck veins
    • Pedal oedema
    • Pulmonary oedema
  • Evidence of uraemia
    • Pruritus
    • Uraemic flap
    • Encephalopathy
    • Nausea / vomiting
    • Uraemic rub – pericarditis
    • Bleeding due to platelet dysfunction
  • Neurological deficits
    • Old strokes (increased vascular morbidity in patients with ESRD)
    • Signs of space-occupying lesions
      • von Hippel Lindau disease: usually haemangioblastomas, most commonly in the cerebellum / spinal cord
    • Skin:
      • Hypopigmented macules (ash leaf spots) – tuberous sclerosis
      • Angiofibromas, usually on malar region – tuberous sclerosis
      • Shagreen patches, areas of leathery, orange peel-like skin – tuberous sclerosis
      • Forehead plaques – tuberous sclerosis
      • Ungual or peri-ungual fibromas – tuberous sclerosis

Differential Diagnosis

  • Polycystic kidney disease
    • Autosomal dominant most common mode of inheritance
    • Rarely, may be autosomal recessive
    • Mutations in either polycystin 1 (85% of cases) on chromosome 16 or polycystin 2 on chromosome 4. PKD1 is associated with earlier progression to ESRF
    • Diagnostic (Ravine’s) criteria:
      • Ultrasound of kidneys recommended from age of 20
        • Age 20-40: at least 3 unilateral or bilateral renal cysts
        • Age 40-60: at least 2 cysts in each kidney
        • Age >60: at least 4 cysts in each kidney
      • Positive family history
    • Renal manifestations
      • Causes progressive decline in renal function due to enlarging cysts
      • Measured total kidney volume is the strongest predictor for development of renal insufficiency
      • Typically progresses to end-stage renal failure between 40-60 years of age
      • Haematuria
        • Associated with more rapid progression of disease
        • Causes: infection, cyst rupture, nephrolithiasis, haemorrhage into cyst (usually presents with pain as most cysts do not communicate with duct)
        • Generally self-limiting within 1 week
        • Management: bed rest, hydration, analgesia
      • Nephrolithiasis (up to 25% of patients)
    • Cerebral aneurysms: approximately 5% in young adults, up to 20% in >60
      • Larger aneurysms, poorly-controlled hypertension increase rupture risk
    • Cysts in liver and pancreas (do not usually cause limitation of function)
    • Cardiac manifestations
      • Hypertension ± hypertensive heart disease
      • Increased frequency of mitral valve prolapse, aortic regurgitation
    • Gastrointestinal: abdominal wall herniae and colonic diverticulae
    • Investigations
      • Full blood count: anaemia / polycythaemia
      • Renal function
      • Calcium and phosphate: secondary / tertiary hyperparathyroidism
      • Urine protein creatinine ratio
      • Renal ultrasound for cyst number and size
      • Magnetic resonance angiogram for cerebral aneurysms
      • Echocardiography if murmurs detected clinically
    • Management
      • Patient education on disease course, complications
      • Control of blood pressure (<130/80)
        • ACE inhibitors / ARBs are preferred agent
      • Control of other cardiovascular risk factors
      • Avoidance of nephrotoxic drugs
      • Attempt at least 3L of fluid intake per day (suppresses ADH secretion)
      • Renal replacement therapy
      • Screening for cerebral aneurysms, especially in patients with positive family or personal history of sub-arachnoid haemorrhage, and prior to major surgery (e.g. renal transplantation).
        • Screening interval: every 5 years
      • Screening of first degree-relatives should be done from the age of 20, using renal ultrasound scans
      • Screening of first degree-relatives for hypertension
      • Avoid contact sports / situations where risk of abdominal trauma is high
      • Indications for nephrectomy:
        • Recurrent infection
        • Uncontrolled haemorrhage
        • Suspected malignancy
        • Symptomatic mass effect
        • Extension of polycystic kidney into transplant site
  • Tuberous sclerosis
    • Autosomal dominant
    • Two genes: TSC1 on chromosome 9 (harmatin), TSC2 on chromosome 16 (tuberin)
    • Main renal manifestation is angiomyolipoma (benign); on CT high fat content of angiomyolipomas appear black
    • Often, angiomyolipomas are multiple and bilateral
    • Main complication is bleeding
    • End-stage renal failure may result from:
      • Multiple angiomyolipomas reducing renal mass
      • Segmental glomerulosclerosis
    • Incidence of RCC slightly higher compared to general population
    • Dermatological manifestations: ungual fibromas, ash-leaf patches, shagreen patches, forehead plaques, facial angiofibromas
    • CNS manifestations: hamartomas, subependymal giant cell tumours
      • Frequently causes epilepsy (80-90% of patients)
      • May impair cognitive development / function
    • Cardiac: cardiac rhabdomyomas; usually asymptomatic, may cause stenosis
    • Pulmonary: lymphangiomyomatosis (LAM); cystic lung disease, almost indistinguishable from diffuse interstitial fibrosis. Usually presents with dyspnea or pneumothorax.
  • Von Hippel Lindau syndrome
    • Autosomal dominant
    • VHL gene on chromosome 3
    • Type 1 and type 2; type 2 associated with phaeochromocytoma
    • Bilateral, multifocal renal cell carcinoma in approximately 70% of patients
    • RCC median age of occurrence is 45 years
    • Nephron-sparing surgery, percutaneous radiofrequency ablation, cryoablation to maintain renal function
    • Haemangioblastomas: close monitoring, surgery / RT if progressing in size and causing symptoms
    • Retinal haemangioblastomas: amenable to laser photocoagulation / cryotherapy
    • Surveillance:
      • Annual retinal screen
      • Annual plasma / urinary metanephrines
      • Annual abdominal ultrasound from the age of 8
      • Audiology
      • Biannual MRI with contrast of abdomen, brain and cervical spine
    • Multiple simple cysts
    • Bilateral hydronephrosis
    • Amyloidosis

Summary

  • Sir, this patient has polycystic kidney disease. I say this because in the abdomen, there is a fullness in the flanks with bilateral ballotable enlarged kidneys. These have a nodular surface, and are non-tender. They measure ____ and ____ in bipolar length; there is no overlying bruit. There is associated hepatomegaly extending ____ cm below the costal margin, which implies co-existent cysts in the liver. There are no stigmata of chronic liver disease, such as jaundice, ascites, spider naevi or gynaecomastia. The spleen is not palpable.
  • His polycystic kidney disease has been complicated by renal failure. There is evidence of a previous tunneled dialysis catheter in the left / right sub-clavicular region. In addition, there is a functional arteriovenous fistula on the right / left arm, with good overlying thrill and bruit. There are needling marks / overlying dressings to suggest recent needling.
  • There do not appear to be complications of renal failure such as fluid overload or symptomatic uraemia. The patient is anaemic, with conjunctival pallor.
  • I would like to complete my examination by examining:
    • The cardiovascular symptom for signs of mitral valve prolapse / aortic regurgitation
    • The cranial nerves for signs of intracranial aneurysms
    • The blood pressure and temperature chart
    • Fundoscopy for evidence of hypertensive retinopathy
    • The urine, if possible, for haematuria / proteinuria
    • A digital rectal examination for the presence of blood, as diverticular disease is a known association
    • Asking for a family history
  • Investigations
    • FBC – anaemia, signs of infection
    • Renal function, calcium and phosphate – renal bone disease
    • Chest radiograph: fluid overload
    • Ultrasound kidneys
    • MRA if high risk
    • Genetic testing: for potential donors with no cysts on US
  • The management of this patient requires a multi-disciplinary approach:
    • Patient education and screening of family members
    • Aggressive control of BP and CVRF
    • Avoidance of nephrotoxic medication
    • A nephrologist for monitoring of renal function
    • Magnetic resonance angiography if there is a personal / family history of aneurysm
    • Antibiotics for urinary tract infections / cyst infections
    • Nephrectomy