Hemolytic uremic syndrome : study of prognostic factors as seen on the Indian scene.
Hemolytic uremic syndrome (HUS) is characterised by micro-angiopathic hemolytic anaemia and acute renal failure (ARF). The syndrome was first described by Gasser et al in 1955 and following this initial report, a number of paediatric cases were reported with a similar clinical picture. For long, this was considered a specific form of childhood renal disease. It was only in 1966 that a similar clinical picture was described by Waddell and Matz in adults. In children, HUS is a reasonably clear cut clinicopathologic entity, whereas in adults it is a much more heterogenous condition and the clinical syndrome can occur in a number of different situation. We present here our clinical experience of both childhood and adult HUS with emphasis on aetiology, clinical features, complications and prognostic factors.
Forty three cases of HUS admitted to the dialysis unit of the King Edward the VIIth Memorial Hospital, Bombay from January 1981 to December 1984 have been studied, of which 16 were males and 27 were females. Since the aetiology and clinical presentation of childhood HUS differ from that of adult HUS, the cases were broadly divided into 2 groups. Group A comprised those aged 10 years or less and Group B included those aged more than 10 years. The age of 10 years was chosen because most cases of childhood HUS have been reported in infants and children less than ten years of age.
Each patient was subjected to a detailed history and clinical examination. Routine urine analysis and urine culture were done in every case. Hematological investigations done were hemoglobin, white cell count, platelet count, reticulocyte count, peripheral smear for erythrocyte morphology and detailed coagulogram. Renal investigations included blood urea nitrogen, plasma creatinine, plasma electrolytes, bicarbonate, total protein and serum albumin. Ultrasonography was done to assess the kidney size whenever possible. Wherever indicated, a sigmoidoscopic examination was done to look for pseudomembranous colitis. Apart from aggressive supportive treatment, all the patient3 received dialysis. Peritoneal dialysis was preferred in children, while in adults the choice of dialysis depended upon the clinical status of the patient.
[Table - 1] shows the aetiology in two groups. In group A the syndrome was most often preceded by a gastro-intestinal illness (85.5%), while in group B it occurred in association with pregnancy in 8 (47.1%), gastro-enteritis in 6 (35.3%) and septicemia in 3 (17.6%).
The most frequent presenting features were oligo-anuria (97.7%) and a bleeding tendency (88.4%)-most often manifesting as gastro-intestinal bleeding. Gastro-intestinal symptoms like loose motions (72.1%) and neurologic manifestations such as altered sensorium (67.4%) and convulsions were also commonly observed. The common findings on physical examination were pallor, ecchymotic patches around venipuncture sites, congestive heart failure (37.2%), acidosis (58.1%) and hypertension (14%).
Infection was a frequent complication in both groups and contributed to morbidity and mortality in these patients. Nineteen patients developed respiratory tract infection and five had confirmed urinary tract infection. Peritoneal infection following dialysis was noted in 2 patients. Another important complication encountered was pseudomembranous colitis confirmed by sigmoidoscopy in all and by autopsy in some cases; this was seen mainly in group A cases and was found to correlate with an extremely poor prognosis.
Thirty patients had an oliguric presentation while thirteen were anuric. Among the oliguric patients, 12 survived (40%), while only two (15.4%) of the anuric patients survived. The improvement in survival rates when dialysis was instituted early is shown in [Table - 2].
[Table - 1] shows survival in relation to different aetiological factors. The survival was worst in those developing HUS secondary to septicemia. Survival in group A was 34.6% and group B was 29.4%.
Kaplan and Drummond have emphasized that HUS can occur in response to various causative factors. The exact triggering mechanism, however, are still unknown. As for the pathogenesis, the central feature in the great majority of cases is vascular endothelial damage confined principally to the glomerular capillaries and renal arterioles, although in some cases vascular endothelial changes are found in other organs.
In children, there is usually a prodrome of vomiting and diarrhoea as was seen in 88.5% of our group A cases, while in adults, the syndrome can occur under various circumstances. In our study, among seventeen cases in group B, eight. developed HUS in association with pregnancy, six following a gastro-intestinal illness and three secondary to septicemia.
The most frequent presenting complaints are diarrhoea, bleeding manifestations (especially gastro-intestinal) and oligo-anuria., A similar presentation was noted in our study. Neurological problems are also common and these were in the form of altered sensorium, convulsions and hemiparesis. Pallor, ecchymotic patches and congestive heart failure,, are prominent clinical findings. Hypertension has been reported to occur in 30 to 60% of patients., However, in our study it was seen in only 6 cases (14%).
Infection is one of the most serious complications of ARF constituting a leading cause of death. This was seen in both our groups, most common being chest and urinary tract infection. The incidence of urinary tract infection may be even higher than what we observed since, urine bacteriological studies were not possible in anuric patients. Seven (26.9%) of Group A patients developed pseudomembranous colitis, manifesting with persistent loose motions, paralytic ileus and marked gaseous abdominal distension. Marked abdominal distension rendered peritoneal dialysis ineffective in these children and hemodialysis could not be performed because of problems of vascular access. Ultimately all these children succumbed suggesting a poor prognosis associated with this complication. Morel-Maroger has observed prominent gastro-intestinal involvement quite often in case of HUS. However, he has made this observation in older children, whereas we have noted this in children aged less than two years. We could not determine the relationship between pseudomembranous colitis and prior antibiotic therapy (6 cases were on ampicillin when referred to our unit) or whether it was a complication of the syndrome itself. Peritonitis is a known complication of peritoneal dialysis. In our study, the two patients who had peritonitis died of complications other than peritonitis.
The major determinant of outcome in HUS, is the severity of renal involvement. Anuria suggests severe renal injury and carries an ominous prognostic significance. In our study, the survival was 40% in oliguric patients and only 15.4% in anuric patients.
When dialysis was instituted early, the survival rate was better [Table - 2]. Kaplan et al too, in their series of 67 patients, reported a 20% mortality in those who received early dialysis and 91% mortality in those who received dialysis late in the course of their illness.
Apart from the severity of renal injury, it is the underlying causative factor which, to a great extent, determines the final outcome. In this study, the survival was 34.5% in cases of HUS following gastro-intestinal illness and 37.5% in cases associated with pregnancy. None of the cases of HUS secondary to septicemia, which in itself carries a poor prognosis, survived.
In our study, the survival rates of 34.6% and 29.4% respectively in groups A and B are much lower than those reported in western countries. A study by Bhuyan et al, also reported higher mortality rate in childhood HUS. A higher mortality in our study is attributable to delayed dialysis therapy due to late referrals.
Thus, it is evident that for an improved prognosis in HUS, an early institution of dialysis would go a long way in achieving this aim.