MALARIA ASSOCIATED

RENAL FAILURE
Common in the tropics
Plasmodium falciparum
Renal tubules
Acute intravascular hemolysis
Heavy parasitic infection

INTRAVASCULAR
HEMOLYSIS
Malarial

infection
Antimalarial drugs
G-6-P-D Deficiency
Quinine, Phosphates, Pyrimethamine

BLACKWATER FEVER
Hemoglobinemia
Hemoglobinuria
Exclude

drug causation
Scanty parasitemia
Re-infection in non-immune immigrants
Acute renal failure
Uncommon in Kenya

RENAL HISTOPATHOLOGY
OF BLACKWATER FEVER
Tubular Atrophy
Interstitial

Lymphocyte infiltration
Focal fibrosis
Iron pigments in fibroblasts and tubules
Heme casts in tubular lumen

CAUSES OF HEMOLYSIS IN
FALCIPARUM MALARIA
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
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
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
Distal

tubules, Necrosis, Degeneration

Proximal tubules
Cloudy swelling and Vacuolisation
Hemoglobin in lumen
Hemosiderin in Lumen

Oedematous

interstitium
Tubular degeneration
Regeneration of epithelial cells
Dilatation of tubules
Features of acute tubular necrosis

GLOMERULONEPHRITIS IN
FALCIPARUM MALARIA
Manifestations

include:

Mild proteinuria
Hematuria
Casts

Non-progressive,and

reversible
ARF and Hypertension rare
Resolves in 4 6 weeks after antimalarials
Nephrotic syndrome is rare

HISTOPATHOLOGY OF
GLOMERULONEPHRITIS
Mild

mononuclear cell infiltration

Prominent mesangial proliferation
Increased mesangial matrix
Normal glomerular capillaries
Immune complex mediated

IMMUNOFLUORESCENCE
OF GLOMERULAR LESIONS
Fine

granular deposits of IgM and C3

Capillary walls
Mesangium

Malarial

antigens

Glomerular endothelium
Medullary capillaries

ELECTRON MICROSCOPY
OF GLOMERULONEPHRITIS
Electron

dense deposits
Granular, Fibrillar, and Amorphous material
Situated in
Subendothelial,
Mesangial,
Paramesangial regions

PATHOGENESIS OF MARF
Hypovolemia

Release of Kinins, Kallikreins, Histamine

Increased capillary permeability
Insensible fluid loss
Renin Angiotensin System stimulation
Increased catecholamine secretion
Hyperviscosity

Decreased RBC deformability

Elevated fibrinogen

Causes

renal ischemia and MARF

PATHOGENESIS OF MARF
INTRAVASCULAR

COAGULATION
Fibrin degradation products
Prolonged pro-thrombin time
Thrombocytopenia
Decreased platelet life span
Platelet agglutination
Splenic pooling

Alteration

in coagulation factors
Low grade regional intra-vascular coagulation
Stasis and Inflammation

Hemolysis

and MARF

PATHOGENESIS OF MARF
Fever
Cholestatic

Jaundice

Obstructive Jaundice and ARF

Tubulotoxicity of Bile acids
Severe oliguria in association with Jaundice

Rhabdomyolysis.

Rare

Myoadenyl deaminase deficiency MAD

CYTOKINES IN MARF
Serum

soluble CD14

Marker of inflammatory response

Elevated in complicated Malaria

TNFalfa.
Associated with tissue damage
Stimulates expression of adhesion molecules

IL-1,

ELAM 1 and ICAM-1

Facilitates thrombospondin secretion

IL-6, IL-8

Acute phase reactions

Expression of adhesion molecules
Release of vasoactive mediators
Plasma leakage from intravascular compartments

CYTOKINES IN MARF
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
Elevated

catecholamines
Increased plasma renin activity
SIADHS
Inflammatory mediators

Kinins, Prosaglandins,
Histamine, Serotinin
Nitric Oxide, Endothelin,
Complement, Superoxidase

ELECTROLYTE IMBALANCE
IN MARF
Hyponatremia

67% in heavy parasitemia

Dilutional
Water retention in renal failure
Resetting of osmoreceptors
SIADH due to fever
Delayed response to water load
Caution with IV fluids
Pulmonary edema a hazard

ELECTROLYTE IMBALANCE
IN MARF
Hypernatremia.

Rare

Pure water depletion

Cerebral edema

Blunted thirst
Inadequate provision of water

Hypokalemia

in uncomplicated malaria
Hyperkalemia
Hypocalcemia with severe infection
Hypophosphatemia wih severe infection

TREATMENT OF MARF
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

Artemesin

derivatives. Potent

Inhibit adherence properties

Reduce parasite count remarkably

Exchange

transfusion

TREATMENT OF MARF
Dialysis

in hypercatabolic states
Hemodialysis or Hemofiltraion
Peritoneal dialysis less preferable

Impaired peritoneal microcirculation

Parasitised erythocytes
Vasoconstriction
Reduced solute transport
Improved efficiency as parasitemia declines
Continuous PD beneficial

MULTIORGAN FAILURE IN
MARF
Cerebral

malaria
Hemodynamic shock
Respiratory distress
MARF
Hematological disorders
Digestive disorders
Often fatal

MARF AT KNH
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
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)
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

Recovery

unrelated to parasitemia

MARF IN VIETNAM
(TANG ET AL)
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