35615.jpgWith over 3,100 ill in over a dozen European countries and the United States and 33 dead, this E. coli O104:H4 outbreak should be a sobering reminder of the power of bacteria and the need to deal with effectively with them as the public health threat that they are. But, that discussion will continue to be had in posts over the coming weeks and months.

However, long after the 33 (and there will be more deaths) are buried, and long after most of the 3,100 are back in there normal routine, some 800 people who suffered Hemolytic uremic syndrome (HUS), a complication of an E. coli O104:H4 infection, will be reminded of this outbreak everyday for the remainder of their lives.

I have been reading a lot of German newspapers (in translation) lately and was struck by this passage and quote this morning – “Karl Lauterbach, health spokesman for the opposition Social Democrats, has warned that some of those who have fallen ill in the E.coli epidemic could face severe health problems.” He went on to say:

“Around 100 patients have suffered such terrible kidney damage that they will require a transplant or have to undergo dialysis for the rest of their lives,” he told the Bild am Sonntag newspaper.

That is stunning – 100 people loosing their kidneys because they ate a salad with sprouts? And, the remaining 700 needing to be monitored for the rest of their lives wondering if or when their kidneys too might fail? So, what are this 700 and the very unlucky 100 facing?

Acute renal failure is one of the signature elements of HUS. Many of those who develop HUS must receive dialysis to survive. Most of those that survive the acute phase of HUS regain enough renal function to abandon dialysis, at least for a time.

One of the most disheartening aspects of the syndrome, however, is the irreversible damage done to the kidneys during the acute stage. The damage sustained in the short term then places the patient at risk for long-term renal complications, including end stage renal disease (ESRD). That damage to the kidney is referred to as a “hyperfiltration injury.”

Hyperfiltration injury is a term used to describe chronic, progressive damage in kidneys that have already sustained a severe acute injury (such as in HUS) that results in the destruction of a substantial percentage of nephrons. Nephrons are the functional units of the kidney and are comprised of glomeruli connected to renal tubules.

The remaining functional glomeruli attempt to adapt to their reduced number by enlarging (hypertrophy) and by hyper- filtrating (i.e., the remaining glomeruli work extra hard) in an attempt to meet the needs of the body. For a time, they are usually able to compensate, but they are being “over worked”, and their “cry for help” is manifested by the spillage of protein (albumin) in the urine (proteinuria).

As time passes, the hyperfiltration injury causes progressive loss of the remaining glomeruli due to fibrosis (scar tissue formation). And, in time, once the remaining functional nephron population drops below 10 percent, the person’s survival requires initiation of “renal replacement therapy”.

10170.jpgThe use of an angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) is usually helpful in slowing the fibrotic process, but no known treatment can stop it. ESRD, also known as stage 5-kidney disease, eventually occurs.

Many such victims will suffer from myriad physical complications before, during, and after kidney transplantation, including: (1) alterations in calcium and phosphate balance, known as renal osteodystrophy, that cause the bones to become weak and soft, resulting in bone pain and susceptibility to fracture; (2) anemia —which is characterized by a low red blood cell count and consequent lack of energy; (3) growth failure caused by the damaged kidney’s inability to properly regulate the calcium necessary for bone growth; and (4) high blood pressure, which, among other things, stresses the heart and can lead to coronary artery disease, heart attack, and stroke.

Following transplantation, the victim will require immunosuppressive medications for the rest of her life to prevent rejection of the transplanted kidney. Medications used to prevent rejection have considerable side effects. Corticosteroids are commonly used following transplantation. The side effects of corticosteroids are Cushingnoid features (fat deposition around the cheeks and abdomen and back), weight gain, emotional instability, cataracts, decreased growth, osteomalacia and osteonecrosis (softening of the bones and bone pain), hypertension, acne, and difficulty in controlling glucose levels. The steroid side effects, particularly the effects on appearance, are difficult for children, particularly teenagers, and non-compliance with the treatment regimen is a problem with teenagers due to unsightly side effects.

Clearly, the physical impediments to leading a normal life for victims of severe HUS are many. The economic losses that frequently result in such cases are correspondingly staggering. Prevention seems to be a much better strategy.