Literature on acute HUS and the prognosis of individuals who develop HUS.
Post-diarrheal hemolytic uremic syndrome (D+HUS) is caused by Shiga toxin-producing E. coli (e.g., E. coli O157:H7) and is the most common cause of acute kidney failure during childhood. The syndrome is defined by the presence of thrombocytopenia, hemolytic anemia, and acute kidney failure.
Most patients require blood transfusions and dialysis, and life-threatening involvement of vital organs (especially the brain) results in a 3-5 percent mortality rate. Although patients who experience prolonged oligoanuria are at highest risk for eventual end stage renal disease (ESRD), life-long evaluation is recommended for all patients. Much can be done to maximize health and well-being in HUS survivors who are left with persistent kidney damage, and renal replacement therapy (dialysis, transplantation) is available for those who develop ESRD. Kidney transplantation is the goal for all patients, and even though it is fraught with complications, it offers improved survival, dialysis-free living, and greater well-being.
Literature on acute Hemolytic Uremic Syndrome and the prognosis of individuals who develop HUS
For help with terms used in these abstracts, see below, our Glossary of HUS Terms.
Hemolytic Uremic Syndrome is less common in adolescents and much more common in younger children. In one study (Siegler, Arch Pediatrics and Adolescent Medicine, 1997), adolescents accounted for 5.8% of the cases of HUS. While HUS is less common in adolescents, significant complications of HUS occur in teenagers as well as in younger children, and the incidence of complications is very similar to the incidence of complications that occurs in younger children. In an earlier study by Siegler, et al., (Journal of Pediatrics, 1991) 61 children were followed for a mean of 9.6 years following the acute episode of HUS. The risk of late complications was 39% of all children with a past history of Hemolytic Uremic Syndrome. The duration of oligo/anuria was found to be the best predictor of late complications. Among 34 children with oliguria, 15 (44%) had proteinuria at follow-up. In children who required dialysis, 52%, 41%, and 56% had proteinuria, decreased creatinine clearance or any renal sequelae, respectively. Abnormalities appeared after an interval of apparent recovery.
In the article by Perlstein, et al., oral protein loading in 17 children with a past history of Hemolytic Uremic Syndrome demonstrated that functional renal reserve was reduced in children with a past history of HUS who had normal renal function and normal blood pressure as compared to normal children. This study suggested that functional renal reserve in children with HUS might be reduced, although renal function and blood pressure are normal. The authors point out that the long-term significance of this finding is unknown and needs to be determined, but the study suggests that functional renal reserve may be reduced in spite of normal recovery and that children with HUS need long-term follow-up.
In the article by Gagnadouz, et al., 29 children were evaluated 15-25 years after the acute phase of Hemolytic Uremic Syndrome. Only 10 of the 29 children were normal, 12 had hypertension, 3 had chronic renal failure and 4 had end stage renal disease. Severe sequelae occurred in children with oligo/anuria for more than or equal to 7 days. The renal histology was the best predictor of long-term complications. Other studies by Caletti, et al., have also demonstrated that histologic finding of focal and segmental sclerosis and hyalinosis are observed several years following HUS. In that article, only a quarter of the children had normal renal function during long-term follow-up.
In the article by Milford, et al. (J Peds 1991), 40 children with Hemolytic Uremic Syndrome were studied to determine the risk of late complication. Of the 40 children, 17 required dialysis while 23 did not require dialysis. Of the 17 children who required dialysis, 6 had hypertension with or without chronic renal failure during follow up for an incidence of 35.5% of the 29 children who were considered to have recovered completely and demonstrated a normal urinalysis during follow up, 4 had proteinuria during later follow up for an incidence of 13%.
In the article by Fitzpatrick, et al. (British Medical Journal, 1991), 88 children were followed up 5.1 to 21 years (mean, 8.5 years) following the acute episode of HUS. Eleven of 74 children who required dialysis for less than 16 days had a reduced glomerular filtration rate (less than 80 ml/min/1.732) during follow up (14.8%) while one of 12 children (8.3%) who required dialysis for 1 to 5 days had a glomerular filtration rate less than 80 ml/min/1.732 during follow up.
In the article by Tonshoff, et al., (Nephron) 26% of patients with oliguria of less than 7 days had long-term renal complications. In the article by de Jong, 96 children with HUS were followed for 10 years. Seven of 29 children with oliguria of 7-14 days duration or anuria for less than 7 days had reduced GFR, proteinuria, or hypertension for an incidence of 24.1%.
In the article by O’Regan, et al., (Clinical Nephrology, 1989) eleven of thirty-seven children with a previous episode of Hemolytic Uremic Syndrome had a reduced glomerular filtration rate as measured by clearance of radioactive diethylene triamine pentaacetic acid (DTPA). The authors concluded that HUS might result in an appreciable deterioration of glomerular filtration rate (GFR) that is not detectable by routine laboratory tests.
Thus, children who appear to have recovered from HUS may develop late complications. A precise determination of the risk of late complications is not likely. It is important to note that the risks of long-term (more than 20 years) complications are unknown and are likely to be higher than risks at 10 years, as many of the above studies describe.
All persons who have experienced HUS should be formally evaluated by nephrologists—a kidney specialist—at a year following their acute illness. Kidneys injured by HUS may slowly recover function over at least a six-month period following the acute episode and perhaps longer. Even persons with “mild” HUS who did not require dialysis should be formally evaluated. Such an evaluation should include a routine physical, blood pressure measurement, and blood and urine analyses from which kidney filtration rate can be calculated.
Physicians doing follow-up on HUS patients will carefully look for indications of kidney injury. These will include whether there is an abnormal amount of protein in the urine that may signal a significant injury to the kidneys, or blood in the urine, which also can reflect kidney injury. As assessment of the HUS patient’s glomerular filtration rate—“GFR”—is essential to determining whether the kidneys are functioning in the range of normal for that person’s age, sex, and size. It is also important to establish a baseline GFR so that future assessment of kidney function can reflect any potential loss of filtering capacity over time.
Studies done to date on HUS outcomes have largely confirmed a positive correlation between more severe kidney involvement acutely; particularly the need for extended dialysis, and increased incidence of future renal complications. However, it has been shown in multiple studies that even moderate kidney compromise in the acute phase of HUS can result in long-term complications due to damage to the filtering units in the kidneys.
Medical follow-up is important because of the risk of deteriorating kidney function after one study of HUS patients noted that: “Of the 28 patients with a normal GFR at 1 year, 3 deteriorated into mild CRF [chronic renal failure] at 5 years.” The study’s authors went on to conclude:
We conclude that renal function at 1 year following HUS cannot be predicted with any certainty from the initial illness and should be formally assessed. However, renal function was within normal limits and remained stable between 1 and 5 years following HUS in most children. The results suggest that longer-term follow-up can probably be restricted to those with proteinuria, hypertension, and abnormal ultrasound and/or impaired GFR at 1 year. Small G, et. al., Hemolytic uremic syndrome: defining the need for long-term follow-up Clinical Nephrology 1999 Dec; 52(6) l352-6.
There is simply no way to precisely measure the extent of damage to the kidneys as a result of HUS. And there are still no studies that have followed HUS patients over their lifetimes. Thus, the best practice is to make sure that any child or young adult follows up with a kidney specialist until that physician is convinced that further follow-up is no longer necessary.