|Year : 1998 | Volume
| Issue : 3 | Page : 247-260
|Acute Renal Failure in the Tropics
V Sakhuja, K Sud
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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|How to cite this article:|
Sakhuja V, Sud K. Acute Renal Failure in the Tropics. Saudi J Kidney Dis Transpl 1998;9:247-60
| Introduction|| |
Health problems in the tropics are related to the warm climate, overcrowding and socio-economic factors. The latter includes widespread poverty, inadequate hygienic conditions and abundance of animal and insect vectors in the immediate vicinity. Although most of these disease may be only of 'historical interest' to physicians outside the tropics, a working knowledge of these illnesses is imperative, since increasing opportunities for travel could make them more likely to be encountered.
Although reliable statistics on the prevalence of acute renal failure (ARF) amongst different tropical countries are not available, statistics based on referrals to dialysis units suggest that the condition is more common in the tropics. Kaufman recently reported a 0.1% incidence of community acquired intrinsic ARF from the US  . This contrasts with data from our institute, a large referral hospital in North India, where 1.5% of all hospital admissions were referred to the Nephrology services for management of moderate or severe ARF  . Factors responsible for this higher incidence include hot climate (resulting in peripheral vasodilatation) in conjunction with excessive sweating. Predisposing to hypovolemic insults and poor nutritional status increasing susceptibility to infections. Certain cultural practices e.g. consumption of fresh water grass carp by the Chinese or eating raw djenkol beans in Southeast Asia could also account for this higher incidence. A high prevalence of glucose 6 phosphate dehydrogenase (G6PD) enzyme deficiency in certain ethnic groups pre-disposes them to hemolysis when exposed to certain drugs and infections.
Amongst the other important differences is the younger age of patients developing ARF in the tropics. In the West, the median age of patients has increased from 41.3 years in the 1950s to 6 years in the 1980s  . On the other hand, the average patient dialyzed for ARF in the tropical countries is younger and is in the 4 th decade of life ,, . Hemodialysis facilities are not widely available in the underdeveloped countries of the tropics and even peritoneal dialysis (PD) is available only in the major townships. Therefore, it is quite common to see patients presenting with serve and lifethreatening complications of renal failure requiring emergency management including dialysis. Finally, it is not uncommon to see patients in the tropics with common and treatable diseases presenting with major complications including renal failure simply because of poverty, ignorance and inadequate access to medical care.
In recent years, improvements in socioeconomic conditions, rapid industrialization, expanding medical facilities and developments in the preventive aspects have led to near eradication of ARF due to infections and obstetrical accidents. ARF in the western societies is now largely a consequence of traffic and industrial accidents, cardiovascular surgery, drugs, multi-organ failure and renal transplant rejection  . This sharp decline in the incidence of community acquired ARF in the developed countries contrasts with hospitals in tropical countries which continue to cater to ARF associated with diarrheal diseases, obstetrical accidents, toxins and infections specific and unique to their respective regions, The patterns of ARF encountered in the tropics have, however, shown changes similar to those in the west, though at a much slower pace  . Amongst the medical causes of ARF, etiological factors leading to ARF in tropical countries are very different from those seen in the developed world. Diarrheal diseases, intravascular hemolysis due to G6PD deficiency, copper sulfate poisoning, snake bites and insect stings together constitute over 40% of all causes of ARF in India and these causes are rarely encountered in the west , .
| Infections|| |
Poor socio-economic conditions and lack of clean water supply are two important factors responsible for the wide prevalence of diarrheal diseases in the tropical developing countries where diarrheal diseases in children account for 5-10 million deaths/ year  . Though not exclusive to children, more than 40% of patients suffering from diarrhea are in the pediatric age group  . Diarrheal diseases are responsible for most cases of ARF in children in India , . The incidence increases with the onset of summer months, with maximum frequency during the rainy season. Over the last decade, early use of oral rehydration therapy and a possible improvement in the standards of living have resulted in an impressive decline of ARF related to diarrheal diseases from 23% in the late 1960s to <10% in the last few years at our center  .
Renal failure is usually of the oliguric type and patients often have metabolic acidosis out of proportion to the degree of failure as a result of loss of bicarbonate in the diarrheal fluid. In addition, hypokalemia many occur due to loss of large amounts of potassium leading to paralytic ileus. Although acute tubular necrosis (ATN) is the commonest histological lesion, acute cortical necrosis (ACN) can occasionally occur  Oral dehydration is advised in patients with mild to moderate dehydration provided they are not vomiting. The recommended solution by the World Health Organization contains 20 gm glucose, 3.5 gm sodium chloride, 2.5 gm sodium bicarbonate and 1.5 gm of potassium chloride dissolved in 1 liter of clean pre-boiled water. Intravenous dehydration with Ringer's lactate in necessary in patients with severe dehydration, persistent vomiting or paralytic ileus. Hypokalemia may worsen following correction of metabolic acidosis and may require massive amounts of potassium to prevent life threatening cardiac dysrrhythmias. Children with established ARF are treated by PD as pediatric hemodialysis facilities are not available in most tropical countries. Femoral vein catheters can be used for peritoneal access as a cheaper substitute for pediatric PD catheters which may not be universally available and are expensive  . Since commercially available PD fluid does not contain any potassium, replacement of potassium should be guided by frequent serum potassium estimations during dialysis.
Malaria remains one of the major public health problems in the tropics. It affects 103 endemic countries with a population of 2.5 billion, causing 1-3 million deaths per year  . Although the incidence of Plamsmodium falciparum infection is declining in the west, the past decade has seen a resurgence of this infection in India. Heavy parasitemia with P.falciparum is associated with various systemic complications like cerebral involvement, ARF, cholestatic jaundice, non-cardiogenic pulmonary edema, shock and disseminated intravascular coagulation (DIC). Non-immune visitors to an endemic area renal failure than the local residents, who acquire varying degrees of immunity.
The overall prevalence of ARF in falciparum malaria is less than 1%, but could go up to 60% in patients with heavy parasitemia , . ARF is usually seen by the end of first week and is non-oliguric in 50-75% of cases  . Because of hemolysis and hypercatabolism, hyperkalemia is an early feature. A host of other electrolyte abnormalities i.e., hyponatremia, hyperkalemia hypokalemia, respiratory alkalosis, hypocalcemia, hypophosphatemia even in the absence of renal failure have also been described  . Although there is no sign or symptom that is pathognomonic of falciparum malaria, the diagnosis should be suspected in any patients from the tropics with fever and one or more of the common manifestations, i.e., altered sensorium, ARF, anemia and jaundice. Hepatosplenomegaly may be an additional finding. Patients may have a conjugated or unconjugated hyperbilirubinemia and the alkaline phosphatase may rise out of proportion to the rise in transaminases. The diagnosis can be established by the demonstration of a sexual forms of the parasite in peripheral blood smears stained with Giemsa stain. On renal histology, findings of ATN predominantly affecting the distal tubules, are often seen. Tubular cells may contain hemosiderin granules. Hemoglobin casts may be seen in the lumina of the distal and collecting tubules of patients with intravascular hemolysis. In patients with heavy parasitemia, the peritubular capillaries may be packed with parasitized erythrocytes. The glomeruli are usually normal but at times exhibit a mesangial hyperplasis and increase in mesangial matrix  . ARF develops because of the unique properties of the parasite which produces hemorrheologic changes leading to renal ischemia. After entry into the erythrocytes, the growing parasite progressively consumes and degrades intracellular proteins and alters the red cell membrane changing its transport properties, making the red blood cells (RBCs) more spherical and less deformable.
The parasite also induces formation of membrane protuberances or "knobs" on the erythrocyte surface, P. falciparum infected cells adhere to the vascular endothelium and uninfected RBCs to form rosettes, interfering in the microcirculatory flow and tissue metabolism. Acute hemolysis may play a role in the pathogenesis of ARF in G6PD deficient patients. Although mild hemolysis may occur due to heavy parasitemia per se, a variety of infections and drugs such as primaquin and aspirin can induce severe hemolysis in such patients with even mild parasitemia. Other factors incriminated include increased plasma viscosity and rarely rhabdomyolysis  .
Severe falciparum malaria is a medical emergency. As chloroquine resistance is common in India, quinine is the mainstay of treatment. Although usual therapeutic doses of quinine in patients with renal failure result in higher plasma concentrations, these are not associated with extra toxicity. Moreover, higher plasma levels in the first 48 hours are life saving. After the first two days, the dose of quinine should be decreased by 30-50% in patients with GFR between 10-50 ml/min and by 7.5% in those with GFR <10 ml/min. quinine is removed by hemodialysis and therefore needs supplementation after the dialytic procedure. Administration of tetracycline or pyrimethamine/ sulfadoxin is recommended in addition to quinine. However, in patients with renal failure, tetracycline is best avoided, as it may precipitate acidosis and increase catabolism. Instead, doxycycline is safe and effective in a dose of 100 mg/day for 7 days. Treatment of renal failure does not differ from that due to other causes. Fluid should be administered cautiously in the absence of signs of frank dehydration because a delayed response to water load may precipitate pulmonary edema in these patients with the syndrome of inappropriate antidiuretic hormone (SIADH) secretion and increased vascular permeability in the lungs. PD is less effective than hemodialysis because of impaired peritoneal microcirculation due to infected erythrocytes and vasoconstriction. Exchange blood transfusion has been recommended in patients with parasite count exceeding 10% or hyperbilirubinemia more than 25 mg/dl  . Patients with high levels of parasitemia, involvement of multiple organs and previously unimmunized subjects carry a poor prognosis. The mortality varies between 10-40%.
Leptospirosis, reported from many parts of India, Southeast Asia, South America and Africa occurs in a wide range of animal hosts such as rats, mice, gerbils, hedgehogs, foxes, dogs, domestic cattle, sheep, pigs and rabbits. These animals develop a carrier state and shed leptospira in urine for months to years and the leptospira can survive in nature for several weeks. Human infection occurs either by direct contact with the urine or tissue of an infected animal or indirectly through contaminated water, soil or vegetation  . Although leptospirosis can occur all through the year, there is a sharp increase in its incidence during or soon after the rainy season and following floods.
Clinical manifestations appear between 7-13 days following exposure and are typically biphasic in character. During the initial or leptospiremic phase, patients develop high fever with chills, headache, severe muscle aches and tenderness. Other clinical features include anorexia, nausea, vomiting, cough, chest pain and disturbances of sensorium. This phase lasts for 4-9 days. The second or immune phase appears after a relatively asymptomatic period of 1-3 days. Fever and earlier symptoms reappear and patients may develop atypical pneumonia, aseptic meningoencephalitis or myocarditis. However, the most characteristic feature of this phase is involvement of the liver and kidneys. Patients develop marked tenderness in the right hypochondrium, heptomegaly and progressively jaundice. Hemorrhagic manifestations include epistaxis, hemoptysis, gastrointestinal bleeding, hemorrhagic pneumonitis and bleeding into the adrenal glands. Thrombocytopenia may be encountered in 40% of cases. Urinalysis reveals transient proteinuria and hyaline and granular casts. Hypokalemia, secondary to a high urinary potassium excretion is observed in 45% of cases. Conjugated hyperbilirubinemia with serum bilirubin values up to 50-60 mg/dL may occur. In contrast to viral hepatitis, the aspartate transminase levels show only a mild rise  . ARF occurs in 20-85% of cases and is oliguric in 40-60% , . Renal failure and other organ involvement generally improve by the end of second week. Renal biopsy reveals interstitial edema and infiltration with mononuclear cells and a few eosinophils. This finding is observed even in the absence of renal failure. Patients with renal failure also show evidence of ATN primarily affecting the proximal tubules. Transient glomerular lesions like milemesangial proliferation may also be observed.
Diagnosis is based on a positive culture or serology. The organisms can be isolated from blood during the first phase or from urine later. The growth of the organism may take up to four weeks in fletcher's or Stuart's semisolid media. Serologic methods are useful in detecting antibodies in the second phase and reaching a quick diagnosis. A single titer of > 1:400 or a four-fold rise is taken as significant. The macroscopic agglutination test or the slide test can be used as a screening test. The more specific microscopic agglutination test is complex and requires maintenance of live leptospira cultures  . Recently an IgM specific dot-ELISA has been found to be specific in diagnosing leptospirosis in endemic areas  .
Leptospirosis is a self-limiting disease and mild cases recover spontaneously. It has been suggested that antibodies, unless given early in the course of diseases, do not alter the course. However, trials using penicillin (1.5 million units intravenously every six hours for seven days) or doxycycline (100 mg orally twice daily for seven days) have shown shortening of duration of fever and hospital stay and amelioration of leptospiruria , . The prognosis depends upon the virulence of the organism and general condition of the patients. With increasing availability of dialysis, deaths usually secondary to internal hemorrhage or myocarditis. Mortality increase with increasing age and with the development of jaundice.
Hemolytic Uremic Syndrome
Hemolytic uremic syndrome (HUS) is one of the commonest causes of ARF in children in most tropical countries and the endemic form of this condition is seen infrequently in adults. In India, HUS is responsible for 35-41% of all cases of ARF in children , . In western countries, the most common organism responsible is verotoxin producing E.coli (0157:H7). On the other hand, the organisms isolated from patients of HUS in the tropical countries include Shigella dysenteriae e serotype I and less commonly Salmonella More Details, Klebsiella, nonverotoxin producing strains of E. coli, Shigella flexneri, Proteus and Pseudomonas. This syndrome is seen mainly in preschool children and affects males and females with equal frequency. Renal failure is preceded by a diarrheal prodrome in 70-81% of patients , . After an asymptomatic period ranging from 3-20 days, patients develop renal failure which is usually oliguric. In addition to pallor, mild icterus and hypertension, neurological involvement including visual disturbances, irritability, seizures and drowsiness may be seen.
The diagnosis is established by the demonstration of a microangiopathic hemolytic anemia with fragmented erythrocytes and thrombocytopenia. The degree of anemia or thrombocytopenia does not correlate with the severity of renal failure. These hematological abnormalities may be absent in patients who present late. Urinalysis shows proteinuria up to 1-2 gms a day with microscopic hematuria. Nephrotic range proteinuria and a secondary membranoproliferative glomerulonephritis have been described. Treatment is mainly supportive and includes volume replacement and control of hypertension and dialysis. Specific therapies to limit vascular injury include plasma infusions or plasmapheresis. HUS in tropical countries is associated with a poor outcome with a mortality rate of about 60%. Up to 40% of patients may develop patchy or diffuse CAN  . Out of those who show recovery of renal function during the acute phase, a significant proportion are left with proteinuria, hypertension and residual renal dysfunction.
Renal mucormycosis is a rate cause of ARF caused by zygomycetes fungi. It produces organ involvement through vascular invasion and thrombosis resulting in infarction and necrosis of the affected organ. The major clinical forms are the rhinocerebral, pulmonary, gastrointestinal and disseminated forms. Recently primary renal mucormycosis involving major renal vessels has been described  . This condition should be suspected if the patients has high fever, lumbar pain, hematuria and pyuria. Most patients have bilateral renal involvement and present with anuric ARF. Ultrasound and CT scan reveal enlarged kidneys with evidence of perirenal collection and/or intrarenal abscesses. In addition, a contrast CT scan shows characteristic absence of renal perfusion  . A define diagnosis requires demonstration of mucor hyphae in the material obtained by renal biopsy or at surgery. The only definitive treatment is extensive debridement including bilateral nephrectomy and systemic anti-fungal therapy with amphotericin B. Bilateral renal mucormycosis carriers an extremely poor prognosis and the outcome is usually fatal.
Melioidosis encompasses a broad spectrum of disease processes caused by Pseudomonas pseudomallei and is encountered in Southeast Asia, Central and South America, the Caribbean Islands, Madagaskar, Australia and Guam. ARF was observed in up to 61% of patients with acute septicaemic melioidosis  . Renal histology shows ATN and less commonly interstitial nephritis and micro-abscesses. Presentation is with progressive fever, productive cough and marked tachypnea.
Renal failure is generally of oliguric and hypercatabolic picture. When renal failure is accompanied by multi-organ dysfunction, the mortality rate approaches 90%. The diagnosis is established by demonstration of the organism in exudates material with methylene blue or Gram stain  . Treatment requires a prolonged course of parentenal ceftazidime  .
ARF has been reported rarely in patients with lepromatous leprosy  . In patients with kala azar, a disease encountered in the tropical regions of East-Africa, Mediterranean area, Latin American and India, ARF due to acute interstitial nephritis has been described rarely  . Typhoid, an acute systemicrfebile illness caused by Salmonella species and widely seen in the Indian subcontinent, Egypt, Indonesia, South Africa and Latin America, can rarely cause ARF due to intravascular hemolysis (in the presence of G6PD deficiency), myoglobinuria or hemolytic uremic syndrome  .
| Animal Toxins|| |
Snake-bite is an environmental health hazard to inhabitants of rural areas in the tropics. The approximately 450 venomous species are specified into four families.
i. Viperidae, which includes Russell's viper, Echis carinatus (saw scaled viper), puff adder, pit viper and rattlesnakes,
ii. Elapidae, which includes kraits, cobras mambas and coral snakes,
iii. Colubridae, of which boomslang is a prominent species and
iv. Hydrophidae or the sea snakes.
The venom of elapid snake is mainly neurotoxic and renal involvement is unusual. ARF had been reported following bites by viperidae and hydrophidae snakes with majority of the cases of ARF seen following viper bites. The incidence of ARF following Echis carinatus or Russell's viper bite varies from 13-32% in hospitalized patients , .
The severity of symptoms depends upon the does of venom injected and may vary from mild local symptoms to extensive systemic manifestations. Intense local pain and swelling appear within a few minutes. A blister forms around the bite and extravasation of blood leads to ecchymosis. Bleeding, seen in as many as 65% of cases, may occur from the local site or the patient may develop hematemesis, melena and hematuria. Development of myonecrosis after sea-snake bites may give rise to severe muscle pain and weakness. Renal failure occurs within a few hours to as late as 96 hours after the bite and is oligoanuric in up to 94% of patients  . Renal biopsy shows ATN in 70-80% of patients with varying degrees of interstitial edema and inflammatory cell infiltration. Other lesions described include CAN (in 20-25%), acute interstitial nephritis, nercotising arteritis of interlobular arteries and occasionally crescentic glomerulonephritis. Factors that lead to renal failure include direct nephrotoxicity of venom, hypovolemia, intravascular hemolysis, myoglobinuria, and microangiopathic hemolytic anemia with or without DIC  .
Early administration of antivenin is vital in patients with evidence of systemic envenomation as it may prevent hematological abnormalities and renal complications. In countries where only the monovalent antivenin is available, difficulty in identification of the offending snake and nonavailability of the specific antivenin impose serious limitations in its usage. Newer immunodiagnostic techniques are at times helpful in easy and rapid identification of the venom antigen. Only polyvalent antivenin is available in most tropical countries, therefore precise identification of the snake species is not essential. Antivenin administration must be continued till effects of systemic envenomation disappear. A simple way to monitor this is by frequent measurement of whole blood clotting time. Other therapeutic measures include replacement of blood loss with fresh blood, administration of tetanus immunoglobulin and treatment of local infection if any. The mortality rate is up to 30%  .
Bee, Wasp and Hornet Stings and Spider Bites
Honey bees, yellow jackets hornets and paper wasps are commonly found in most tropical countries. Local allergic reaction or rarely, anaphylactic shock usually follows an isolated sting by these insects. However, multiple stings result in inoculation of a large does of the venom and can lead to systemic symptoms like vomiting diarrhea, hypotension, loss of consciousness and occasionally ARF 936). Although patients who develop renal failure have generally received multiple stings, a single Sicarius spider bite or bite of the common brown spider (Loxosceles recluse) may introduce enough venom to produce renal failure, especially in children. Although ARF in bee or hornet stings is secondary to hemolysis and rhabdomyolysis, a direct nephtrotoxic role of these venoms has been postulated  . Venom of the spiders can also cause DIC and renal failure. Renal biopsy invariably reveals ATN and renal recovery is the rule provided the patient survives the acute complications.
Isolated instances of ARF have been reported following stings by scorption, jelly fish and giant centipede bite. ARF in these cases is mostly due to intravascular hemolysis and/or DIC.
Raw Carp Bile
The raw gallbladder or bile of freshwater grass carps (Ctenopaharyngodon idellus)is used to improve failing vision and rheumatism in rural areas of Taiwan, South China, Hong Kong, Japan and South Korea. Raw gallbladder of Indian carp (Labeo rohita) has also been used as a traditional remedy for various ailments in certain parts of India  . Symptoms occur within minutes to up to 12 hours following ingestion and include abdominal pain, nausea, vomiting, watery diarrhea and hepatocellular jaundice. ARF usually occurs within 48 hours after ingestion and is oliguric in 54%  . Hypotension and hemolysis may be responsible for the development of ARF. A direct nephrotoxic effect and hepatic injury could be additional factors , . The kidney reveals ATN with interstitial edema. The duration of renal failure ranges from two to three weeks and recovery is complete with supportive treatment.
| Plan Toxins|| |
Callilepis Laureola (Impila) Poisoning
Callilepis laureola is a herb with tuberous rootstock, which grows in South Africa, Zambia, Zaire, Zimbabwe and neighbouring countries. Impila poisoning is one of the commonest causes of ARF in the black population of South Africa  An extract of the tubers is used either orally or given as an enema as a traditional remedy for various illness. The clinical manifestations include abdominal pain, vomiting and hypoglycemia  . Patients with severe poisoning may show deranged liver functions. Renal histological lesions are those of ATN. Interstitial edema with dense interstitial infiltration is common. The precise mechanism of renal failure is not clear and direct nephrotoxicity is a possibility. Mortality rte may be more than 50% in children and treatment is largely supportive  .
Djenkol Bean Poisoning
The djenkol (jering) trees grow in Indonesia, Malaysia, Southern Thailand and Myanmar. Considered a local delicacy, djenkol beans are consumed raw or in fried or roasted form. Raw djenkol beans consumed in large amounts can cause poisoning especially if associated with a low fluid intake. The bean contains djenkolic acid, a sulphur-rich aminoacid, which precipitates as needle-like crystals in concentrated and acidic urine causing intratubular obstruction. The crystals may also act as nidus for stone formation. A large variation has been noted in individual susceptibility to the toxic effects. The symptoms of poisoning (djenkolism), which may occur immediately after ingestion or as late as 36 hours, include dysuria, lumbar and lower abdominal pain, hypertension, hematuria, and oligoanuria. Urinalysis shows presence of needle-like crystals of djenkolic acid. Djenkolism can be prevented by pretreatment of the beans by boiling or consumption of small amounts of the raw bean with liberal fluid intake. High fluid intake and alkalinization of urine helps in dissolving the crystals  . The majority of victims recover within a few days.
ARF has been observed following accidental ingestion of mushrooms of the families Amanita, Galerina and Cortinarius. The toxic symptoms consist of abdominal pain, nausea, vomiting, and diarrhea developing a few hours after ingestion followed by hypotension, hepatocellulaar jaundice, fever, alteration in consciousness and renal failure. Although direct nephrotoxicity has been implicated, volume depletion and hepatic failure are more important factors contributing to renal injury  . Renal pathological changes are compatible with ATN. Mortality rate exceeds 50 per cent in patients with severe renal failure. Treatment is supportive.
The marking-nut tree, Semecarpus anacardium, found in tropical and subtropical forests has an irritant black sap, which produces painful blisters, eruption and sloughing of skin resulting in deep ulcerations. Accompanying symptoms include fever, dysuria, and hematuria. Nephro-toxicity is due to the phenolic substance in the sap and anuric renal failure may occur due to CAN  .
| Pigment Induced ARF|| |
Intravascular Hemolysis and G6PD Deficiency
Acute intravascular hemolysis is an uncommon cause of renal failure in the west occasionally occurring after incompatible blood transfusion. However, acute hemolysis in G6PD deficient individuals is a frequent cause of ARF in some ethnic populations of the tropical countries. In India, G6PD deficiency is a common cause of clinically significant is a common cause of clinically significant intravascular hemolysis producing ARF in about 5-10% of cases  . The incidence of inherited G6PD deficiency varies from 2.2% to 15% in various ethnic groups in India. 13% in Saudi Arabia, 15% in East Africa, 22.5% in Ghana, 20% in Nigeria, 0.4% in Ashkenazee Jews, 20% in oriental Jews, 62% in Kurdish Jews and 2% in the Chinese. As the gene for G6PD deficiency is located on the X-chromosome, all males, (hemizygotes) inherit the abnormal gene from their mothers who act as the carriers (hetrozygotes). Because of inactivation of one of the two X-chromosomes, the heteroxygote female carriers remain asymptomatic as they have two populations of RBCs: normal and those deficient in G6PD. G6PD is a key enzyme in the hexose-monophosphte shunt responsible for regeneration of reduced glutathione which protects the sulphydryl (SH) group of the hemoglobin and erythrocyte membrane from oxidation. The hemoglobin in G6PD-deficient subjects gets precipitated if the RBCs are subjected to an oxidant stress, resulting in hemolysis. The equivalent of 100 ml of erythrocytes, when lysed and released into in to human circulation can lead to ARF.
Hemolysis triggered within hours of exposure to drugs, toxins or certain infections. Commonly incriminated drugs include primaquin, sulphonamides, acetyl salicylic acid, nitrofurantoin, nalidixic acid and furazolidine. Accidental ingestion of naphthalene balls, fava beans and severe metabolic acidosis of any etiology can also precipitate hemolytic episodes. Common infections known to cause hemolysis include viral hepatitis, rickettsia, typhoid and urinary tract infection. Clinical manifestations include abrupt passage of dark (cola) colored urine and a sudden drop in hemoglobin. Since the younger population of RBCs is relatively resistant to the oxidant stress injury, the hemolytic crisis is usually self-limiting. Renal failure usually develops within 24 hours of the hemolytic crisis and is oliguric in the vast majority . Estimation of G6PD level in the erythrocytes by fluorescent sot test is usually confirmatory. Since the defect primarily occurs in older RBCs, a false negative test may be seen during a hemolytic episode when the larger proportion is constituted by younger erythrocytes  . It may therefore be necessary to repeat the after the patient has recovered from the acute episode. In patients with intravascular hemolysis, maintenance of a high urine output by increasing fluid intake as well as rendering the urine alkaline early in the course may prevent renal damage. Severe life threatening hyperkalemia may be present early in course of renal failure and may necessitate immediate and frequent dialysis.
Copper Sulfate Poisoning
The extensive use of copper sulfate in leather industry, its low cost and easy availability were the main reasons for its widespread use as a mode of suicide amongst the poor socio-economic groups in India. The incidence of ARF following copper sulfate ingestion has shown a significant decline in the last decade  . Another form of copper sulfate poisoning after ingestion of "holy water" given by spiritual leaders was reported from Nigeria  . Within 15-30 minutes of ingestion, patients develop a metallic taste in mouth, salivation, epigastric burning, nausea and repeated vomiting. Patients may also develop diarrhea, hematemesis and malena. In severe poisoning, jaundice, hypotension, convulsions and come may develop  . Acute pancreatitis, myoglobinuria and methemoglobinemia have also been reported. Renal failure is seen in 20-25% of cases and is invariably oliguric. Death may occur in the acute phase from gastrointestinal bleeding, hepatic or renal failure Hypovolemia secondary to fluid loss along with direct nephrotoxicity and severe hemolysis caused by copper appear to be the main pathogenetic factors for development of renal failure. Renal histology usually shows ATN involving the proximal tubules with interstitial edema. Once the diagnosis has been established, gastric lavage should be done using 1% potassium ferrocyanide solution which leads to formation of insoluble cupric ferrocyanide. Egg white or milk can be administrated as an antidote. Emesis should not be induced. An upper GI endoscopy is necessary to determine the degree and extent of ulceration. Volume deficit should be corrected with crystalloid and patients with hemolysis should receive blood transfusions. The hyperkalemia is often severe and sustained because of the ongoing hemolysis and requires early and frequent dialysis.
In the tropics the common causes of nontraumatic rhabdomyolysis producing myoglobinuric ARF include eclampsia, prolonged labor, poisoning with mercuric chloride or zinc phosphide, status epilepticus, viral myositis, burns, electrical injury and status asthmaticus  . The diagnosis is established by the demonstration of myoglobin in urine and elevated levels of creatine phosphokinase and aldolase in the serum. Other characteristic features include hypocalcemia and hyperuricemia during the oliguric phase and hypercalcemia during the diuretic phase. The pathogenesis of myoglobinuric ARF is similar to that following intravascular hemolysis and renal histology invariably shows ATN.
| Miscellaneous Medical Causes|| |
Heat stroke occurs when body's thermal regulation is unable to dissipate adequate amount of heat resulting in a rise in the core temperature. This condition is observed in summer months in tropical areas with high ambient temperatures and relatively high humidity. The characteristic features are hyperpyrexia, hyperventilation, nausea, vomiting, cramps, dehydration, ataxia, incoherent speech, followed by loss of consciousness, hypotension and vascular collapse. As the syndrome progress, oliguric renal failure may develop. Laboratory data show hemo-concentration, hypernatremia, hypocalcemia and elevated transminases, aldolase and creatine phosphokinase levels. In severe cases hemolysis, myoglobinuria and DIC may be seen  . Presence of multi-organ failure indicates a poor prognosis. The pathogenesis of ARF is multi factorial with hypovolemoa, hypotension and DIC playing major roles. The pathology shows ATN. Management consists of rapid cooling by any method with continuous temperature monitoring. The patient should be placed in a cool room/icewater bath or given ice water sponging.
Rapidly progressive and post-infectious glomerulonephritis constitute about 10% of all cases of ARF seen in the tropics  . The incidence of ARF associated with the postinfectious form of glomerulonephritis has declined in the western countries to about one tenth of what was seen in the 1950s  . However, it continuous to be a significant cause of ARF, especially in the pediatric population in the tropical countries.
| Surgical ARF in the Tropics|| |
The incidence of surgical ARF in our center has increased from 11% of all cases of ARF in the 1960s to around 30% in the 1980s and 90s  . Whereas roadside and industrial trauma, drugs and complicated cardiac, vascular and abdominal surgery are the leading causes of surgical ARF in the developed countries, ARF due to obstructive uropathy constitutes a major cause of surgical ARF in certain tropical areas. Trauma and operative complications contribute to only 2-5% of cases of community-acquired ARF in the tropics. Postoperative renal failure accounted for 24% of hospital acquired ARF and factors related to surgery were identified as the major cause in 18%  .
| Obstetric ARF in the Tropics|| |
Improvements in obstetrical care have led to a virtual disappearance of ARF related to pregnancy in the advanced countries. Even in some of the developing countries like India, the incidence of obstetric ARF has shown a decline from 22% (of all ARF) in 1960s to 8% in 1990s  . On the other hand, in Ethiopia, septic abortion is the underlying cause of ARF in 52% of all patients  and in Argentina and Nigeria, gynecologic and obstetric complications still account for 32% and 25% of cases of ARF respectively , . This high incidence is due to the prevalence of unsafe home deliveries and abortions conducted by untrained personnel. Obstetrical ARF has a bimodal occurrence with the first peak between 8-16 weeks of gestation in association with septic abortions. Preeclampsia, eclampsia, abruption-placentae, post partum hemorrhage and puerperal sepsis account for the second peak, which is seen after 34 weeks. More than 85% of patients are oliguric and as many as 32% may be totally anuric at presentation  . Pathogenetic factors that predispose to ARF include enhanced vascular reactivity to catecholamines and angiotensin, renal ischemia due to hypotensive effect of hemorrhage, overwhelming infection, increased production of fibrin and DIC. The majority of cases of obstetric renal failure show histological changes of ATN. However, ACN was seen in 19% of cases of ARF in early pregnancy and in 38% during late pregnancy  .
| Acute Cortical Necrosis in the Tropics|| |
Acute renal cortical necrosis is the most catastrophic of all types of ARF. With improvement in medical care, this entity has virtually disappeared from the western world. In India, the incidence of CAN in patients dialyzed for ARF has also declined from 7.1% in 1983 to 3.8% in 1994 (13, 48). In the large series reported from India, obstetrical causes accounted for CAN in 56% of patients. Other causes included snake bites (14.2%), hemolytic uremic syndrome (11.5%) and gastroenteritis (4.4%). The pathogenesis of CAN remains unclear  . The hypotheses postulated include i) endothelin induced vasospasm of small vessels ii) toxic capillary endothelial damage iii) endotoxin induced generalised Schwartzmann phenomenon and iv) hypercoagulable state.
The condition should be suspected in a patients with any of above predisposing conditions with a prolonged period of oligoanuria. The oligo-anuric phase may extend for weeks to months and patients with diffuse cortical necrosis may never enter a diuretic phase. Recovery of renal function, if any, is extremely slow and depends upon the amount of viable cortical tissue. In our study, only 17% patients could be taken off dialysis by the end of three months  . The rest either died or remained dialysis dependent. Even in patients who achieve partial functional recovery, the renal function invariably deteriorates with the passage of time and ultimately culminates in ESRD. The gold standard for establishing the diagnosis has been renal histology. Histology shows a variable degree of necrosis of all elements of renal parenchyma, especially in the cortical region. A small amount of cortical tissue in the subcapsular and juxtamedullary region may be spared in patients with diffuse CAN. Detection of cortical tramtrack or egg-shell calcification on plan Xray of abdomen or ultrasonography is helpful but is seen in only a minority. In recent years, CT scan has emerged as a good non-invasive modality for early diagnosis of CAN , . The characteristic finding is the presence of hypo-attenuating subcapsular rim of renal cortex following contrast injection. In addition, a noncontrast CT scan is more sensitive in picking up the cortical calcifications. It must be emphasized that a needle biopsy can miss a patchy cortical necrosis and presence of a 'diffuse' ACN on biopsy could overestimate the extent of lesions because of sampling error. Therefore, it is important to take the clinical course of the patients into consideration before deciding on the probability of reversibility or otherwise of the renal failure. A prolonged period of dialytic support while waiting for any evidence of renal functional recovery should therefore be attempted in all patients.
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Department of Nephrology, Postgraduate Institute of Medical Education & Research , Chandigarh
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