MALARIA ASSOCIATED MALARIA ASSOCIATED RENAL FAILURERENAL FAILURE

Common in the tropics

Plasmodium falciparum

Renal tubules

Acute intravascular hemolysis

Heavy parasitic infection

INTRAVASCULAR INTRAVASCULAR HEMOLYSISHEMOLYSIS

Malarial infectionAntimalarial drugsG-6-P-D DeficiencyQuinine, Phosphates, Pyrimethamine

BLACKWATER FEVERBLACKWATER FEVER

HemoglobinemiaHemoglobinuriaExclude drug causationScanty parasitemiaRe-infection in non-immune immigrants Acute renal failureUncommon in Kenya

RENAL HISTOPATHOLOGY RENAL HISTOPATHOLOGY OF BLACKWATER FEVEROF BLACKWATER FEVER

Tubular AtrophyInterstitial Lymphocyte infiltrationFocal fibrosisIron pigments in fibroblasts and tubulesHeme casts in tubular lumen

CAUSES OF HEMOLYSIS IN CAUSES OF HEMOLYSIS IN FALCIPARUM MALARIAFALCIPARUM MALARIA

Impairment in physiologic deformityIncreased mechanical fragilityInterference with RBC ATPInterference with Na-K RBC ATPAltered charges on RBC surfaceImmunologic reactions

MALARIA ASSOCIATED MALARIA ASSOCIATED ACUTE RENAL FAILUREACUTE 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 MALARIA ASSOCIATED ACUTE RENAL FAILUREACUTE RENAL FAILURE

Occurs 4 - 7 days from onset of feverEarly onset hyperkalemiaHyperuricemia commonHigh urinary uric acid-creatinine ratioOliguria lasts a few days to several weeks

HISTOPATHOLOGY OF HISTOPATHOLOGY OF MARFMARF

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 GLOMERULONEPHRITIS IN FALCIPARUM MALARIAFALCIPARUM MALARIA

Manifestations include:– Mild proteinuria– Hematuria– Casts

Non-progressive,and reversibleARF and Hypertension rareResolves in 4 – 6 weeks after antimalarialsNephrotic syndrome is rare

HISTOPATHOLOGY OF HISTOPATHOLOGY OF GLOMERULONEPHRITISGLOMERULONEPHRITIS

Mild mononuclear cell infiltrationProminent mesangial proliferationIncreased mesangial matrixNormal glomerular capillariesImmune complex mediated

IMMUNOFLUORESCENCE IMMUNOFLUORESCENCE OF GLOMERULAR LESIONSOF GLOMERULAR LESIONSFine granular deposits of IgM and C3

– Capillary walls– Mesangium

Malarial antigens– Glomerular endothelium– Medullary capillaries

ELECTRON MICROSCOPY ELECTRON MICROSCOPY OF GLOMERULONEPHRITISOF GLOMERULONEPHRITISElectron dense depositsGranular, Fibrillar, and Amorphous materialSituated in

– Subendothelial, – Mesangial, – Paramesangial regions

PATHOGENESIS OF MARFPATHOGENESIS 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 MARFPATHOGENESIS 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 MARFPATHOGENESIS OF MARF

FeverCholestatic Jaundice

– Obstructive Jaundice and ARF– Tubulotoxicity of Bile acids– Severe oliguria in association with Jaundice

Rhabdomyolysis. Rare– Myoadenyl deaminase deficiency MAD

CYTOKINES IN MARFCYTOKINES IN MARF

Serum soluble CD14– Marker of inflammatory response – Elevated in complicated Malaria

TNFalfa. – Associated with tissue damage– Stimulates expression of adhesion molecules

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– Plasma leakage from intravascular compartments

CYTOKINES IN MARFCYTOKINES 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 HUMORAL FACTORS IN MARFMARF

Elevated catecholaminesIncreased plasma renin activitySIADHSInflammatory mediators

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

ELECTROLYTE IMBALANCEELECTROLYTE IMBALANCEIN MARFIN 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 IMBALANCEELECTROLYTE IMBALANCEIN MARFIN 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 MARFTREATMENT 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 MARFTREATMENT 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 MULTIORGAN FAILURE IN MARFMARF

Cerebral malariaHemodynamic shockRespiratory distressMARFHematological disordersDigestive disordersOften fatal

MARF AT KNHMARF 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 KNHMARF AT KNH

Onset phase 2.9 daysOliguria lasted 9.8 days5 patients not dialysed. 2 died4 patients had PD. 1 diedMean duration of PD 11 daysContinuous PD. 8 cycles dailyAll had heavy parasitemia. No BWF

MARF IN VIETNAMMARF IN VIETNAM (TANG ET AL) (TANG ET AL)

64 (MARF) vs 66 (Severe Malaria only)Clinically and biochemically, ATNAssociated cholestatic jaundice, & liver dysFatality associated with

– Anuria, Short duration of illness– Hyperparasitemia, Multisystem involvement

Recovery unrelated to parasitemia

MARF IN VIETNAMMARF IN VIETNAM (TANG ET AL) (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