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Tropical Acute Renal Failure

Dr. Omar Abboud, MD, FRCP

Consultant Nephrologist.Hamad Medial Corporation
Doha, Qatar


Acute Renal Failure (ARF) is defined as a sudden sustained decline in glomerular filtration rate (GFR) usually associated with Azotaemia and fall in urine output(1).

Tropical nephropathies causing ARF are broadly classified as infective or toxic. The infective nephropathies are associated with endemic microbial infections: bacterial, viral, fungal and parasitic. Toxic nephropathies include exposure to poisons of animal or plant origin.

Aetiologically there may be direct tissue invasion by the causative organism, remote cellular and humoral effects of bacterial antigens and endotoxins, and renal injury as a consequence of the acute systemic effects of the infection. The pathology of ARF caused by tropical nephropathies include glomerular, microvascular and tubulointerstitial lesions. The tubulointerstitial lesions include interstitial nephritis and toxic/ischaemic acute tubular necrosis (ATN). The pathogenesis of ARF is summarized as follows:

  1. Decreased blood supply to the glomerulus. A number of cytokines contribute to this including Tumour Necrosis Factor (TNF), Interleukin-1 (IL-1), Platelet Activating Factor (PAF) and Angiotensin II. The imbalance between the vasoconstricting effect of Endothelin (ET), and the vasodilator effect of nitric oxide (NO), are also contributory(2).
  2. Decreased GFR. This is produced by decrease in blood supply, decrease in glomerular permeability due to endothelial cell swelling, aggregation of neutrophils in glomerular capillaries and high tubular luminal pressure.
  3. Tubular damage. This occurs due to injury of the tubules by a complex cascade of interactive injury pathyways which ultimately lead to cell death(3). Among the factors leading to that is injury by free radicals due to excessive production of NO due to over production of the enzyme inducible Nitric Oxide Synthase (I-NOS) triggered by sepsis. Some injured but viable tubular cells get detached from their basement membrane and are shed in the tubular lumen together with the necrotic cells.
  4. Luminal Obstruction. This is caused by the shed tubules, the debri released by the injured cells and intraluminal protein casts(4).
  5. Backleak. Toxic tubular lumen contents leak back into the interstitium due to high luminal pressure and dysfunction of the damaged tubular cells. This further augments the tubular damage.

The principal acute infections reported to cause ARF are malaria, leptospirosis, tetanus, salmonellosis, shigellosis, and cholera. Schistosomiasis may cause ARF in both haematobium and mansoni infections.

Of those, the main infections causing ARF are malaria, leptospirosis and tetanus. ARF associated with salmonellosis, shigellosis and cholera is less common.

Hepatitis B and C viruses are associated with chronic renal disease. Dengue haemorrhagic fever can be associated with ARF.


ARF complicates malaria in 1 – 5% of the natives in endemic areas but in non-immune visitors the figure goes up to 30%(5) . It is mostly due to P. falciparum with P. vivax being the causative species in a minority of cases. The main features are oliguria and hypercatabolism in addition to the systemic effects of malaria. Mild proteinuria, <1gm/day, may occur but almost resolves completely after treatment. The urine sediment is usually negative. Hyperkalaemia is usually striking due to haemolysis, rhabdomyolysis and acidosis.

Histologically there is a mixture of ATN, interstitial nephritis and glomerulonephritis(6). ATN is the most consistent finding. The glomerular lesions show prominent mesangial proliferation with modest mesangial matrix expansion. Segmental necrosis may occur due to occlusion of the capillaries by erythrocyte rosettes. Immunofluorescence show finely granular IgM and C3 deposits along the capillary walls and in the mesangium(7).

Mortality depends on the urgency and facilities of treatment ranging from nil in well-equipped centers to as high as 45% when facilities are meager(8).

A study of prognosis from Yemen reported that out of 64 children (4.2 – 11.2 years) who required dialysis for ARF secondary to falciparum malaria, 28 (43.8%) died. The group that died had significantly high plasma creatinine and BP and low urine output(9).


Leptospirosis which is caused by several sero-types of Leptospira interrogans is a world wide disease. It is an uncommon cause of ARF in western countries(10),(11) but plays an important role in tropical countries : for example it accounts for 24% of all cases of ARF in South East Asia (12),(13).

Almost in all cases the disease involves the kidney causing ARF of variable degrees.

The ARF occurring with Liptospirosis is usually mild and non-oliguric, in 60% of the cases. Urinary abnormalities range from mild protienuria and haematuria to haemoglobinuria, granular and bile pigment casts. In severe cases of Liptospirosis, ARF can be marked with rapid deterioration of renal function and raised serum uric acid. Acidosis may be severe due to bicarbonate wastage because of failure of absorption by proximal tubules. Also hypokalaemia may occur due to inhibition of potassium reabsorption in the medullary thick limb of HenLe. In certain cases Haemolytic Uraemic Syndrome may occur (14),(15).

Leptosprios causes necrotizing vasculitis causing severe glomerulonephritis in some patients while in others there is mild mesangioproliferative glumerulonephritis with IgM immunofluorescence deposit. Interstitial nephritis also occurs with focal or diffuse mononuclear cell infiltration. The organism is rarely seen in the renal biopsy.

Treatment is mainly directed towards treating the disease, Penicillin being the drug of choice; some patients may require dialysis before recovery of renal function. Plasma exchange is advocated by some workers in patients with severe jaundice(16). Referring of ARF is almost invariable in patients who recover from the acute illness.


A number of mechanisms may lead to development of the ARF associated with tetanus, rhabdomyolysis(17) and autonomic nervous system over activity(18) being the most prominent. ARF due to tetanus is high in certain countries like Brazil(17), where ARF is seen in 34% of cases. It is usually mild and non-oliguric.


Abnormal renal function is reported in about 16% of patients(19) with salmonellosis. The main renal lesions are pyelonephritis, acute tubular necrosis and glomerulonephritis(20) which is exudative.

During the febrile phase haematuria and proteinuria, usually less than one gram, are common. The renal involvement is usually mild with full recovery within two weeks of typhoid treatment(21). A more severe illness mimicking post infections glomerulonephritis was reported from South Africa with generalized oedema and hypertension (22) . Renal biopsy showed mild to moderate mesangioproliferative glomerulonephritis with IgG and IgM deposits.


ATN may occur due to dehydation in severe infections. In a series reported by Bennish et al, out of 2018 patients ARF occurred in 26% of cases(23). Proliferative glomerulonephritis can occur. Shigellosis may also induce haemolytic uraemic syndrome (HUS) especially in children (24). In such cases there may be cortical necrosis and diffuse fibrous deposits in the glomeruli. Mortality may be high in those patients.


ARF occurency in cholera is similar to that of shigellosis, being due to fluid and electrolytes loss. Hypokalaemia can be severe. In addition to ATN, proximal tubular vacoulation can occur due to hypokalaemia and cortical necrosis was noted in some patients(25).


ARF in haematobium infection occurs due to acute obstructive uropathy, usually on top of chronic disease. With mansoni infection, ARF may occur with late disease as ATN due to severe variceal bleeding or as hepatorenal syndrome associated with hepatic dysfunction.

Dengue Haemorrhagic Fever

ARF occurs in 5% of patients with Dengue Haemorrhagic Fever. It is mainly due to ATN which is associated with interstitial oedema and mononuclear cell infiltration. Mesangioproliferative glomerulonephritis may be seen with IgG, IgM and C3 deposits. It is associated with mild proteinuria and abnormal urinary sediment.


  1. Nissenson, AR. Acute Renal Failure: definition and pathogenesis. Kidney Int. 1998;53 Suppl 66:S-7 –S-10.
  2. Thijs A, Thijs LG. Pathogenesis of renal failure in sepsis. Kidney Int. 1998;53 Suppl 66: S-34 –S-37.
  3. Rose BD. Pathophysiology of Renal Disease, 2nd Ed, McGraw-Hill, New York, 1987, pp 84-104.
  4. Myers BD, Moran SM. Hemodynamically mediated acute renal failure. N Eng J Med 1986; 314:97.
  5. Barsoum RS. Malarial acute renal failure. J Am Soc Nephrol 2000; 11 (11) : 2147-54.
  6. Barsoum R. Malarial nephropathies. Nephrol Dial Transplant 1998; 13:1588-97.
  7. Barsoum R, Sitprija V. Tropical Nephrology. In Diseases of the Kidney, 6th Ed., edited by Schrier RW, Gottaschalk CW, Boston, Little, Brown & Co. 1996, pp 2221-68.
  8. Trang TT, Phu NH, Vin H, et al. Acute renal failure in patients with severe falciparum malaria. Clin Infect Dis 1992; 15:874-80.
  9. Sheiban AK. Prognosis of malaria associated severe acute renal failure in children. Ren Fail 1999 Jan; 21(1) : 63-6.
  10. Kennedy ND, Pusey CD, Rainford DJ, et al. Leptospirosis and acute renal failure in clinical experience and a review of literature. Postgrad Med 1979; 55:176.
  11. O’Neill PG, Christie M, Cahill J, et al. Leptospirosis and renal failure. Clinical experience over a one year period. Ir J Med Sci 1982; 151:339.
  12. Sitprija V. Renal involvement in human leptospirosis. Br Med J (Clin Res) 1968;2:656.
  13. Lai KN, Aarnos I, Woodroffe AJ, et al. Renal lesions in Leptospirosis. Aust N Z M Med 1982; 12:276.
  14. Edwards CN, Nichilson GD, Everard Co. Thrombocytopenia In Leptospirosis. Am J Trop Med Hyg 1982; 31:827.
  15. Raoult D, Jeandel PL, Mailloux M, et al. Thrombocytopenia and renal failure in Leptospirosis. Am J Trop Med Hyg 1983; 32:1464.
  16. Pecchini F, Borghi M, Bodini U, et al. Acute renal failure in Leptospirosis : new trends in treatment. Clin Nephrol 1982; 18:164.
  17. Martinelli R. Matos CM, Roche H. Tetanus as a cause of acute renal failure : possible role of rhabdomyolysis. Rev Soc Bras Med Trop 1993 Jan-Mar; 26(1): 1-4.
  18. Daher EF, et al. Prospective study of tetanus-induced acute renal dysfunction: role of adrenergic overactivity. Am J Trop Med Hyg 1997 Nov; 57(5): 610-4.
  19. Khosla SN, Lochan R. Renal dysfunction in enteric fever. J Assoc Physicians India 1991 May; 38(5): 382-4.
  20. Parmar RC, et al. Nephritis and cerebellar ataxia. Rare presenting features of enteric fever. J Postgrad Med 2000 Jul-Sep; 46930: 184-6.
  21. Sitprija V, Pipatanagul V, Boonpucknavig, et al. Glomerulonephritis in typhoid fever. Ann Intern Med 1974; 81:210.
  22. Bouka I, Coovadia HM. Thyphoid glomerulonephritis. Br Med J (Clin Res) 1970; 2:710.
  23. Bennish ML, Harris JR, Wojyniak, et al. Death in Shigellosis : incidence and risk factors in hospitalized patients. J Infect Dis 1990; 161:500.
  24. Ashkenazi S. Role of bacterial cytotoxins in haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Ann rev Med 1993;44:11.
  25. De SN, Sengupta KP, Chanda NN. Renal changes including total cortical necrosis in cholera. Arch Pathol 1954; 57:505.