What are the Expected Short and Long-term Outcomes for Patients with Hemolytic Uremic Syndrome?
The natural history (or, clinical course) of hemolytic uremic syndrome (HUS) improved remarkably with the advent of dialysis and intensive care facilities for children. In the 1950s, there was a forty-percent death rate with HUS; however, now, in developed countries, only 3% to 5% die as a result of HUS.
Patients today rarely die directly from the acute renal failure. When death occurs, it is almost due to our inability to prevent, recognize, and effectively treat life-threatening extra renal organ injury. Although brain damage is the most common cause of death, severe multi-organ damage (renal cortical necrosis, bowel necrosis and stroke) is common in fatal cases.
Although those surviving HUS usually escape immediate serious complications (sequelae), about three-to-five percent are left with long-term damage to organs other than the kidneys, especially to the pancreas or brain. An equal number are left with severe kidney damage and, thus, require chronic dialysis and kidney transplant, either from the start or after only a few years.
A larger number of HUS patients will develop future complications, including hypertension, proteinuria, low glomerular filtration rate (GFR). Development of future sequelae correlates best with the presence and duration of oliguria or anuria. For example, one or more sequelae, albeit, usually mild, are seen in about a third of those with no recorded oliguria or anuria. Thereafter, the prevalence of one or more sequelae increases to 80% in those with more than ten days of oliguria, and 90% if oliguria exceeded 15 days. Finally, two-thirds of those with anuria that lasted greater than 5 days have one or more sequelae, and almost all of those with anuria exceeding 10 days have sequelae.
High blood pressure is later found in approximately 10% of those with no oligoanuria, but rises to approximately 33% percent in those whose oliguria that exceeds 15 days, and 66% in those whose anuria persists for more than 15 days.
Most concerning with regard to the risk of future complications is the combination of both low glomerular filtration rate (GFR) and proteinuria, both being signs of impaired renal function and ongoing hyperfiltration injury. This combination occurs in less than 10% of patients, but increases to about 15% in those with more than 10 days of oliguria, and 40% if oliguria lasts for more than 15 days. Those with anuria (no urine production) of more than 5 days duration exhibit both low GFR and proteinuria almost 20% of the time. It rises to 33% in those with more than 10 days of anuria, and to 66% in those whose anuria persists for more than 15 days. Overall, this subset of patients (who have both proteinuria and low GFR) is most likely heading toward end-stage renal disease because of ongoing hyperfiltration injury.
Initially, hyperfiltration may manifest only as microalbuminuria (albumin in the urine). If more severe, there is usually also overt proteinuria (protein in the urine). Hyperfiltration occurs when more than half of the nephrons have been destroyed, for example, as might happen during the acute phase of HUS. The remaining nephrons become hypertrophic (enlarged) in an attempt to compensate for the reduced number of nephrons. The enlarged nephrons usually compensate well for a number of years, but then eventually become “overworked”. The “cry for help” of the overworked nephrons comes in the form of microalbuminuria. For this reason, albumin in the urine is a convenient urinary marker that can be used to estimate “hyperfiltration injury”—with higher amounts of albumin indicating the greater the injury. Microalbuminuria may precede, by a number of years, the emergence of overt proteinuria, a sign of more severe injury.
To make matters even worse, starting at about age 30, as part of the normal aging process, the number of nephrons slowly decreases. Medications—like angiotensin enzyme inhibitors and angiotensin receptor blockers—can reduce hyperfiltration injury and, thus, slow the progressive loss of nephrons. Eventually, however, when more than 90% of the nephrons have been destroyed, end-stage renal disease (ESRD) ensues.
We do not know the life-time risk of ESRD, because an accurate estimate will require lifelong tracking of a large group (cohort) of survivors. It is therefore recommended that all patients be evaluated several times during the first year. This evaluation includes blood pressure and serum-creatinine measurements, and a first morning urine specimen for a complete urinalysis and microalbuminuria determination. Evaluations should be conducted yearly for the first decade, and every two years for the second decade; more frequently if abnormalities are found. Careful monitoring during any pregnancies is important since there may be an increased risk of toxemia (pre-eclampsia and eclampsia) of pregnancy. Thereafter, until we have life-long prognostic information, it seems prudent to recommend evaluations every five years for life.