Friday, April 14, 2017

Jaundice and Renal Failure

In patients with combined renal and liver dysfunction it is important to differentiate between renal impairment that is secondary to liver disease i.e. hepatorenal syndrome, and conditions where an insult directly affects both the liver and kidney.  
I recently saw a 20-something year old student who was a regular kayaker in local rivers.  He had a 5 day history of myalgia, fever and headache with no vomiting or diarrhoea.  He took paracetamol (acetaminophen) and ibuprofen within recommended limits for his symptoms.  In the 24 hours prior to his admission he developed jaundice and noticed decreased urinary output. On arrival to hospital he was jaundiced but examination was otherwise unremarkable.  There were no signs of chronic liver disease and the liver was not palpable.  He was hemodynamically stable.  Blood tests showed a raised (conjugated) bilirubin at 453umol/L (25 mg/dL), ALT within normal limits and mildly elevated ALP at 162U/L.  He had an acute kidney injury with creatinine 427umol/L (4.83 mg/dL), potassium 3.4mmol/L.  He was anemic and thrombocytopenic with a neutrophilia, and blood film showed toxic granulation, with no red cell fragments.  An ultrasound of his liver was unremarkable and his kidneys were at the upper limit of normal size with no hydronephrosis. For 36 hours he was anuric despite fluid resuscitation, and required a short period of CRRT.  After this time he began passing urine and his creatinine spontaneously fell, although bilirubin remained elevated.  He was treated empirically with ceftriaxone and doxycycline for leptospirosis, and six days later urine PCR and serum IgM came back positive for leptospirosis.  
Photo from ACG Case Reports Journal

Leptosporosis is a zoonosis usually transmitted to humans through rodent urine in water.  The majority of cases cause a self-limiting febrile illness, but in its severe form - Weil’s syndrome – patients can develop jaundice, renal failure, pulmonary haemorrhage and aseptic meningitis.  Renal impairment in leptospirosis can be secondary to a number of different mechanisms including sepsis/critical illness, a direct nephrotoxic effect to the renal tubule by the leptospira toxin, tubulointerstitial nephritis, rhabdomyolysis and hyperbilirubinemia.  Patients often maintain good urine output despite renal injury, and tubular dysfunction means most patients are hypo- or normokalemic even if oliguric.  Another characteristic finding is enlarged kidneys with normal parenchymal echogenicity on ultrasound.  
Included in our initial differential was that his renal impairment was secondary to hyperbilirubinemia.  Bilirubin causes renal impairment again through a range of mechanisms including direct toxicity to the nephron, bile acid casts causing tubular obstruction, and hypoperfusion from vasodilation.  Renal biopsy can show pigmented bile casts within the tubules and tubular hypertrophy (see image).  Electron microscopy can show bile acid accumulation within lysosomes and dilated mitochondrial cristae.  In those with normal baseline renal function and short-lived hyperbilirubinemia changes are often mild and reversible, but irreversible damage can occur in those with underlying renal impairment.  
Early clues for leptospirosis in this case include hypokalemia despite being oligoanuric, enlarged kidneys on ultrasound and of course his social history.  

Post by Ailish Nimmo


Yazied Chothia said...

Nice case. Another mechanism for the hypokalemia in those with liver disease is bile acids inhibit the 11-beta-HSDH enzyme in basolateral membrane of the CCD resulting in stimulation of the cytosolic aldosterone receptor by cortisol and subsequent insertion of ENaC.

LEE JUN said...

Where I work (Malaysia)
our Leptospirosis patients are usually
Oil Palm Plantation workers
Rice mill workers
Construction site workers
Armed forces personel who have been in the jungle for training
Anyone who has been swimming in the river
Any where there are rats, poor sanitation, no access to clean drinking water

Leptospira carrier is the rat.

Other clinical signs of Leptospira are
(1) Red eyes
(2) muscle tenderness-especially calves, thigh
(3) Blood tests-Thrombocytopaenia

Other differentials we must exclude
Malaria falciparum
Dengue Shock Syndrome