Outcomes
What is the Expected Short and Long-term Outcome?
The natural history (clinical course) of D+HUS improved remarkably with the advent of kidney dialysis and intensive care facilities for children. What was originally (in the 1950’s) a 40% death rate is now only 3 to 5% in developed countries. Patients today rarely die directly from the acute renal failure, and when death occurs, it is almost always due to our inability to prevent, recognize and effectively treat life threatening extra renal organ injury. Although brain damage is the single most common cause of death, severe multiorgan damage (e.g., renal cortical necrosis, bowel necrosis and stroke) is common in fatal cases.
Survivors usually escape immediate serious sequelae, but about 3-5% percent are left with long-term extra-renal damage, especially of the pancreas or brain. An equal number are left with severe kidney damage, and require chronic dialysis and kidney transplant from the start or after only a few years. A much larger number will develop future sequelae (hypertension, proteinuria, low glomerular filtration rate [GFR]) that correlate best with the presence and duration of oliguria and anuria. For example, one or more sequelae (e.g., proteinuria, low GFR, hypertension), 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 10 days of oliguria and 90% if oliguria exceeds 15 days. Two-thirds of those with anuria greater than five days duration have one or more sequelae, and essentially, 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 about 33% in those whose oliguria exceeds 15 days, and 66% in those whose anuria persists for more than 15 days.
Most concerning is the combination of both low glomerular filtration rate (GFR) and proteinuria, that is, the presence of both below normal kidney function and proteinuria, signs of impared renal function as well as ongoing hyperfiltration injury. This combination occurs in less than 10% of patients until oliguria or anuria persists for more than 10 or five days, respectively. Thereafter, it increases to about 15% in those with greater than 10 days of oliguria, and 40% if oliguria lasts for more than 15 days. Those with anuria of greater than five 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.
This subset is most likely heading toward ESRD because of ongoing hyperfiltration injury. This occurs when more than 50% 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 renal population. They usually work well for a number of years, but eventually become “overworked”. Their “cry for help” is in the form of microalbuminuria. This convenient urinary marker can be used to estimate “hyperfiltration injury”; the higher the value the greater the injury. Microalbuminuria may precede the emergence of overt proteinuria (a sign of more severe hyperfiltration injury) by a number of years. Moreover, starting at about age 30, as part of the aging process, the number of nephrons slowly decreases. This nephron obsolescence places additional strain on the already damaged kidneys. Medications (angiotensin enzyme inhibitors and angiotensin receptor blockers) can reduce hyperfiltration injury and thus slow the progressive loss of nephrons, but eventually, 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; this will require life long tracking of a large group (cohort) of survivors. It is therefore recommended that all patients be evaluated several times during the first year to include 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.