Renal involvement with infective endocarditis
Riyad AbusrewilSupervisor John NelDepartment of nephrology
Mr RD , 35 years male. From Blue Downs presents with 2 months history of worsening dyspnoea , orthopnoea, PND , lower limbs oedema, fever and sweating.
He is known with rheumatic heart disease, had Mitral valve replacement in 1999.
Diagnosis of subacute infective endocarditis is base on Echocardiologic finding with a blood culture of Gram negative coccobacilli (Actinomycetomcomitams bacteria which is member of HACEK group) and fever >38 ͨ.
Clinically : he is in heart failure ( EF35%) with renal impairment on admission urea = 21 mmol/L & creatinine =145μmol/L
combination of Vancomycin 1 g+ Rifampicin 600 mg + Penicillin G, so initially Gentamicin was not given until day 5 when he was started on 80 mg BD dose.
Few days later : vancomycin trough becomes toxic: blood level of 30 μg/mL (10-20)urine dipstick = +1 protein, +4 blood, microscopy: dysmorphic RBCs,UPCR= 0.24 g/day , urine output > 2 L/daylow C3, C4 , negative HIV, HBV , HCV, RPR, ASOT, Anti-DNA
What is the cause of renal impairment?
Day 0 1 2 6 17 20 30Serum creatinine 145 136 87 124 154 247
Prerenal failure Acute tubular necrosis
Acute interstitial nephritis
Immune complex, or embolic
Congestive heart failureCardiac arrhythmiaseptic shockProlonged intraoperative hypotension
Ischemic ATN : prolonged hypoperfusion or NSAIDsNephrotoxic : Gentamicin , amphotericin , Radiocontrast
Mechanism of kidney injury
Drugs: vancomycin, methicillin, Rifampicin
Endocarditis associated glomerulonephritisRenal infarct and abscess
Kidney biopsy histopathologyUltrastructural appearance of periphery of glomerulus
Numerous subendothelial deposits
Occasional subepithelial deposits
Summary of renal biopsy• 64 glomeruli. 13 globally sclerosed.• Rest diffuse proliferative pattern with numerous
neutrophils• Immunofluorescence C3 +++ IgG + granular• EM Prominent deposits : Mesangial, subendothelial and
subepithelial• Fits well with ICGN associated with infective endocarditis
Nephrotoxic acute tubular necrosis• Drugs like gentamicin. Vancomycin and rifampicin • Lead to nephrotoxic ATN or acute interstitial nephritis• Dose dependant• Mechanism : vasoactive ( NSAIDs , radiocontrast) or
direct tubular damage (e.g. aminoglycoside)• NSAIDS prevents the production of prostaglandins
required to improve renal perfusion.• Radiocontrast: induce vasospasm and direct tubular
toxicity.• Aminoglycoside : more risk with elderly , female, Mg, Ca
& K deficiency, hypotensive patients
Acute interstitial nephritis• Not dose dependant
• Onset : first exposure up to several weeks, 3-5 days on second exposure.• Allergy: fever, skin rash and eosinophilia. Urine shows eosinophilia, WBC,
white cell casts and RBC
• Renal biopsy : interstitial oedema , interstitial infiltration of T – lymphocytes.
• Use of corticosteroids is warranted for cases that unlikely to recover e.g. NSAIDs
Embolic phenomena & abscesses
• Renal abscess as result of arterial emboli from vegetation on the heart valves. Especially with Staph aureus endocarditis.
• Renal infarcts can be asymptomatic or present as flank pain + haematuria
• Other embolic phenomenon : nail splinter haemorrhage, Osler’s nodes, Roth spots and Janeway lesions. other organ abscesses : spleen ,bowel, brain.
Endocarditis – associated GlomerulonephritisCirculating immune complexes can develop post-infectious GN
Urine dipstix : haematuria +/- proteinuriaUrine microscopy: dysmorphic RBCs, sometimes RBC castsHigh levels of immune complexes ( 90% cases) , RF +ve (10-70%)Low complement ( 90%)
Histology of kidney biopsy: focal proliferative GN & diffuse proliferative GN, increase cellularity in mesangium +/- Crescents
Treatment: appropriate antibiotic treatment of IEImmunosuppression using steroid in indicated in severe cases.Disease will not recover without infection control, ongoing nephritis may indicate need for urgent valve replacement
ESRF can occur with crescentic GN and occasionally with DPGNHaematuria and proteinuria can persist for months
Practical approachRenal pathology Onset of disease
Endocarditis associated At presentation, near peak of illness severity
Acute interstitial nephritis 3- 5 days
Aminoglycoside induced ATN Up to several weeks of drug administration
microscopy Urine osmolality BiochemistryPre-renal failure Bland urine Concentrated urine Very low Na
ATN Granular cast Dilute urine Normal Na
Glomerulonephritis Dysmorphic RBC, RBC cast
Heavy Proteinuria >3g/day
Parameter Prerenal ATN Acute interstitial N
IE associated
Onset At presentation
At presentation
During management
At presentation
Plasma U/Cr 1:10 1:20 1:20 1:20
Urine osmolality >450 <350
Urine microscopy
Normal / hyaline cast
Muddy granular or epithelial cast
WBC cast / eosinophilia
Dysmorphic RBC
Urine Na <20 >40
FeNa <1% >2%
Fraction of urea excretion
<35 % > 35%
Urine protein Norm / <1 g <2g/day <2g/day Absent to >2g/day
Recovery rate Rapid 48-72 hr Days -weeks
Differences between causes of renal failure
Thank youReference1. An insight into renal disease associated with infective
endocarditis; A.B Adeniyi, J.D.Nel. SA heart journal. vol.4.3.2007
2. Davidson’s principles and practice of medicine , 22nd edition.3. SAMF 11th edition