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