Transcript MALARIA ASSOCIATED RENAL FAILURE

MALARIA ASSOCIATED
RENAL FAILURE
Common in the tropics
Plasmodium falciparum
Renal tubules
Acute intravascular hemolysis
Heavy parasitic infection
INTRAVASCULAR
HEMOLYSIS
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Malarial infection
 Antimalarial drugs
 G-6-P-D Deficiency
 Quinine, Phosphates, Pyrimethamine
BLACKWATER FEVER
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Hemoglobinemia
 Hemoglobinuria
 Exclude drug causation
 Scanty parasitemia
 Re-infection in non-immune immigrants
 Acute renal failure
 Uncommon in Kenya
RENAL HISTOPATHOLOGY
OF BLACKWATER FEVER
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Tubular Atrophy
 Interstitial Lymphocyte infiltration
 Focal fibrosis
 Iron pigments in fibroblasts and tubules
 Heme casts in tubular lumen
CAUSES OF HEMOLYSIS IN
FALCIPARUM MALARIA
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Impairment in physiologic deformity
 Increased mechanical fragility
 Interference with RBC ATP
 Interference with Na-K RBC ATP
 Altered charges on RBC surface
 Immunologic reactions
MALARIA ASSOCIATED
ACUTE RENAL FAILURE
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Common cause of MARF
Heavy parasitemia
1% to 4% develop ARF
60% in Malignant malaria
Usually oliguric
Catabolic State
Cholestatic Jaundice
Rarely hepatocellular
Lasts a few days to several weeks
MALARIA ASSOCIATED
ACUTE RENAL FAILURE
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Occurs 4 - 7 days from onset of fever
 Early onset hyperkalemia
 Hyperuricemia common
 High urinary uric acid-creatinine ratio
 Oliguria lasts a few days to several weeks
HISTOPATHOLOGY OF
MARF
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Distal tubules, Necrosis, Degeneration
 Proximal tubules
– Cloudy swelling and Vacuolisation
– Hemoglobin in lumen
– Hemosiderin in Lumen
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Oedematous interstitium
Tubular degeneration
Regeneration of epithelial cells
Dilatation of tubules
Features of acute tubular necrosis
GLOMERULONEPHRITIS IN
FALCIPARUM MALARIA
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Manifestations include:
– Mild proteinuria
– Hematuria
– Casts
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Non-progressive,and reversible
 ARF and Hypertension rare
 Resolves in 4 – 6 weeks after antimalarials
 Nephrotic syndrome is rare
HISTOPATHOLOGY OF
GLOMERULONEPHRITIS
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Mild mononuclear cell infiltration
 Prominent mesangial proliferation
 Increased mesangial matrix
 Normal glomerular capillaries
 Immune complex mediated
IMMUNOFLUORESCENCE
OF GLOMERULAR LESIONS
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Fine granular deposits of IgM and C3
– Capillary walls
– Mesangium
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Malarial antigens
– Glomerular endothelium
– Medullary capillaries
ELECTRON MICROSCOPY
OF GLOMERULONEPHRITIS
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Electron dense deposits
 Granular, Fibrillar, and Amorphous material
 Situated in
– Subendothelial,
– Mesangial,
– Paramesangial regions
PATHOGENESIS OF MARF
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Hypovolemia
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Release of Kinins, Kallikreins, Histamine
Increased capillary permeability
Insensible fluid loss
Renin Angiotensin System stimulation
Increased catecholamine secretion
Hyperviscosity
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Decreased RBC deformability
Elevated fibrinogen
Causes renal ischemia and MARF
PATHOGENESIS OF MARF
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INTRAVASCULAR COAGULATION
Fibrin degradation products
Prolonged pro-thrombin time
Thrombocytopenia
Decreased platelet life span
– Platelet agglutination
– Splenic pooling
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Alteration in coagulation factors
 Low grade regional intra-vascular coagulation
– Stasis and Inflammation
PATHOGENESIS OF MARF
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Fever
 Cholestatic Jaundice
– Obstructive Jaundice and ARF
– Tubulotoxicity of Bile acids
– Severe oliguria in association with Jaundice
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Rhabdomyolysis. Rare
– Myoadenyl deaminase deficiency MAD
CYTOKINES IN MARF
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Serum soluble CD14
– Marker of inflammatory response
– Elevated in complicated Malaria
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TNFalfa.
– Associated with tissue damage
– Stimulates expression of adhesion molecules
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ELAM 1 and ICAM-1
Facilitates thrombospondin secretion
IL-1, IL-6, IL-8
– Acute phase reactions
– Expression of adhesion molecules
– Release of vasoactive mediators
CYTOKINES IN MARF
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GPI. Glycosilphosphatidylinositol
– Elevated in MARF
– Glycolipid substances
– Acts like an endotoxin
– Can induce TNF and IL-1
– Cause hypoglycemia and pyrexia
HUMORAL FACTORS IN
MARF
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Elevated catecholamines
 Increased plasma renin activity
 SIADHS
 Inflammatory mediators
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Kinins, Prosaglandins,
Histamine, Serotinin
Nitric Oxide, Endothelin,
Complement, Superoxidase
ELECTROLYTE IMBALANCE
IN MARF
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Hyponatremia
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67% in heavy parasitemia
Dilutional
Water retention in renal failure
Resetting of osmoreceptors
SIADH due to fever
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Delayed response to water load
Caution with IV fluids
Pulmonary edema a hazard
ELECTROLYTE IMBALANCE
IN MARF
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Hypernatremia. Rare
– Pure water depletion
– Cerebral edema
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Blunted thirst
Inadequate provision of water
Hypokalemia in uncomplicated malaria
 Hyperkalemia
 Hypocalcemia with severe infection
 Hypophosphatemia wih severe infection
TREATMENT OF MARF
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Antimalarial therapy essential
 Quinine.
– Normal doses in MARF for first 24 to 48 hours
– Thereafter reduce dose to 10 mg/kg 12 hourly
– Or 24 hourly for 7
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Artemesin derivatives. Potent
– Inhibit adherence properties
– Reduce parasite count remarkably
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Exchange transfusion
TREATMENT OF MARF
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Dialysis in hypercatabolic states
 Hemodialysis or Hemofiltraion
 Peritoneal dialysis less preferable
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Impaired peritoneal microcirculation
Parasitised erythocytes
Vasoconstriction
Reduced solute transport
Improved efficiency as parasitemia declines
Continuous PD beneficial
MULTIORGAN FAILURE IN
MARF
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Cerebral malaria
 Hemodynamic shock
 Respiratory distress
 MARF
 Hematological disorders
 Digestive disorders
 Often fatal
MARF AT KNH
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Were et al
47 Patients with ARF
21 (45%) with medical causes
9 (19%) developed MARF
Overall mortality 40.4%
MARF mortality 33.3%
Cholestatic Jaundice in 4 patients
All patients with MARF were oliguric
MARF AT KNH
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Onset phase 2.9 days
 Oliguria lasted 9.8 days
 5 patients not dialysed. 2 died
 4 patients had PD. 1 died
 Mean duration of PD 11 days
 Continuous PD. 8 cycles daily
 All had heavy parasitemia. No BWF
MARF IN VIETNAM
(TANG ET AL)
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64 (MARF) vs 66 (Severe Malaria only)
 Clinically and biochemically, ATN
 Associated cholestatic jaundice, & liver dys
 Fatality associated with
– Anuria, Short duration of illness
– Hyperparasitemia, Multisystem involvement
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Recovery unrelated to parasitemia
MARF IN VIETNAM
(TANG ET AL)
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Recovery unrelated to hemoglobinuria
Oliguria 4 days (0-19)
Normal biochemistry 17 days (11-23)
Treated by PD
Mortality decreased from 75% to 26%
Good condition initially
Complications develop rapidly
Treat as ATN with circulatory shock
Early diagnosis and dialysis mandatory