Here is the overview of HUS induced renal injury. A more complete picture can be seen at www.abouthus.com. Each kidney has between 700,000 to over a million filtering units called nephrons. The heart of each filter is a microscopic bundle of blood vessels called glomeruli. Blood goes into each glomerulus and waste products pass through a membrane into tubules which connect together and ultimately collect the urine and pass it out of the kidney. Below are a couple schematics.
If we zoom in on the microscopic glomerulus:
The glomerulus is the main filter of the nephron and is located within the Bowman’s capsule. The glomerulus resembles a twisted mass of tiny tubes through which the blood passes. The glomerulus is semipermeable, allowing water and soluble wastes to pass through and be excreted out of the Bowman’s capsule as urine. The filtered blood passes out of the glomerulus into the efferent arteriole to be returned through the medullary plexus to the intralobular vein. Meanwhile, the filtered water and aqueous wastes are passed out of the Bowman’s capsule into the proximal convoluted tubule.
In HUS the glomeruli can be permanently damaged due to loss of blood flow as tiny thrombi occlude those blood vessels. The toxins from E. coli O157:H7 also have a direct effect on the cells lining the blood vessels and tubules and can cause cell death. Once a filter is gone, it is gone forever. When a lot of filters are gone, the remaining ones work harder because there are fewer of them. If enough filters are lost, the remaining filters experience “hyperfiltration” which leads to enlargement, and over time, scarring which in turn leads to the loss of more filters. Once that process gets going the kidneys are doomed and will slowly lose their filtering ability. That is called end stage renal disease—ESRD. And that is the process we believe our clients face due to the loss of large numbers of nephrons during their severe HUS.
It is important to keep in mind that no one suggests any of the children involved in the UFG outbreak will face kidney failure in the near future. ESRD is a process that can take decades to play out. The demands on the kidneys increase through puberty and, for women, especially during pregnancy, adding another variable to issues of future renal health for girls who have suffered severe HUS.
Serious kidney injury usually manifests through reduced filter function, hypertension, and/or proteinuria. It is easy to get a rough estimate of kidney filter function by looking at the level of waste products, especially creatinine in the blood over time. There are also formulas to estimate filter function once you have a creatinine value. The key is whether filer function changes over time. Since the kidneys primarily regulate blood pressure, the development of hypertension after HUS signaled serious kidney injury and is considered a bad prognostic sign. So too is proteinuria which can be thought of as a signal that the kidneys are being overworked due to the loss of filtering units.
When enough filtering units are lost, the remaining filters have to work harder. This is called hyperfiltration. It is now understood that blood pressure in the remaining filters rises and over time this cause injury—scarring—of those filters and leads to progressive loss of filters. Proteinuria signals that injury. Ordinarily, the protein molecules are too big to pass through the walls of the microvessels within the glomerulii, the central part of the filtering units. But HUS can lead to structural damage to the walls of those microvessels allowing the protein moleculesto “leak” out and appear in the urine. That’s proteinuria. One particular type of protein called albumin is considered a particularly sensitive marker of kidney injury. When albumin appears in the urine in small amounts it is called microalbuminuria. Microalbuminuria is now recognized as a significant risk factor for future kidney injury (as well as heart disease). Dr. Siegler is one of the researchers whose studies have confirmed this.
So proteinuria, or microalbuminuria, is a sign of serious kidney injury and many studies have shown that the presence of those conditions is linked to progressive renal injury. That is why the nephrologists are always keen on knowing whether proteinuria persists over time after HUS. It is a bad sign for the future.
The literature of most interest to us consists of studies that have looked at HUS patients over time and tried to identify risk factors for long-term kidney disease. Remember though that HUS and its relationship to E. coli O157:H7 has only been recognized since 1982. Not surprisingly then, the studies that exist tend to be very limited by time. Further complicating the matter, most HUS victims are children and, of course, are treated by pediatric nephrologists. Those doctors are the ones with the HUS expertise. But when those kids grow up their care, if it is needed, passes to adult nephrologists. Thus, it is very tough to follow this population over time and the studies that have done looked at relatively large groups of HUS victims over time periods as long as even five years are few and far between.
But a consensus has developed about characteristics of during the acute course of HUS that bode ill for the future. And the single most important predictor of future problems is the duration of reduced (oliguria) or no urine (anuria) production (together oligoanuria as some patients will have days of no urine production and some of reduced urine production).