“Lettuce” make it clear that lettuce from California and Arizona have been problematic over the last 20 years. We – Government, Industry and Consumers need to do more. Watch the trailer and was the full documentary streaming August 2.

Here is what Canada Health Officials just posted about importing (or not) lettuce from California. If poisoning US citizens doesn’t do the trick and change grower/processor behavior, perhaps the Canadians setting standards (that the US doesn’t even do) will make a difference. Here are the rules from our Northern brothers and sisters:

1. Introduction

Romaine lettuce imported from the United States (U.S.) have been associated with several outbreaks of foodborne E. coliO157:H7 illnesses in Canada and the U.S. Food safety investigations from U.S. authorities have identified a recurring geographical area as the source of the outbreaks. This area encompasses the California Salinas Valley counties of Santa Cruz, Santa Clara, San Benito, and Monterey.

To decrease the risk associated with E. coli O157:H7 in romaine lettuce, the Canadian Food Inspection Agency (CFIA) is implementing temporary Safe Food for Canadians (SFC) licence conditions for the importation of romaine lettuce originating from the U.S. Between September 28 and December 20, 2023, importers of romaine lettuce and/or salad mixes containing romaine lettuce from the U.S. must:

• declare that the product does not originate from counties of Santa Cruz, Santa Clara, San Benito and Monterey in the Salinas Valley, California, U.S., or
• submit an attestation form and Certificates of Analysis for each shipment to demonstrate that the romaine lettuce does not contain detectable levels of E. coli O157:H7

The complete details on the temporary SFC licence conditions and other existing import requirements are outlined in this document.

The temporary SFC licence conditions are in addition to other existing import requirements.

2. Requirements at time of import

If importers and the products they import comply with other Canadian legislation, the CFIA will allow the importation of romaine lettuce and/or salad mixes containing romaine lettuce from the U.S. if they comply with the temporary SFC licence conditions and other import requirements, as follows:

• the importer provides a Proof of Origin indicating the state and county where the romaine lettuce was harvested if the romaine lettuce is from outside of the California counties of Santa Cruz, Santa Clara, San Benito and Monterey
• romaine lettuce and/or salad mixes containing romaine lettuce from the California counties of Santa Clara, Santa Cruz, San Benito and Monterey is accompanied by an attestation (using form Importer’s Attestation for Romaine Lettuce Products from the Salinas Valley, California, United States (CFIA/ACIA 5961; 2023/06)) that sampling was conducted according to the temporary SFC licence conditions and by the Certificate of Analysis demonstrating that the product does not contain detectable levels of E. coli O157:H7
• if a Proof of Origin of the romaine lettuce is not available, the attestation and Certificate of Analysis must be provided
• romaine lettuce grown in California has been handled by a certified member of the California Leafy Greens Marketing Agreement (LGMA)
  • California LGMA Certified Members List
• romaine lettuce grown in Arizona has been handled by a shipper that is a certified member of the Arizona LGMA
  • Arizona LGMA Certified Members List

3. Temporary SFC licence conditions

Temporary licence conditions pursuant to section 20 (3) of the Safe Food for Canadians Act will be in effect for the period from September 28 to December 20, 2023.

During this period, the conditions for import will require importers of leafy greens to provide proof that romaine lettuce and/or salad mixes containing romaine lettuce do not originate from counties of Santa Cruz, Santa Clara, San Benito, and Monterey in the Salinas Valley of California, U.S.

Alternatively, importers who import romaine lettuce and/or salad mixes containing romaine lettuce from the counties of Santa Cruz, Santa Clara, San Benito, and Monterey in the Salinas Valley of California, U.S., or who import such products without a valid Proof of Origin, must conform with the following:

1. the licence holder’s preventive control plan includes a written procedure describing how the sampling and testing requirement outlined below is implemented
2. each shipment is accompanied by an attestation by the importer, in the form provided by the CFIA (CFIA/ACIA 5961), attesting that: they have an official Certificate of Analysis for each romaine-lettuce product in the shipment; sampling and testing was conducted according to the temporary SFC licence conditions (points d., e., and f. below); and E. coliO157:H7 was not detected
3. each shipment is accompanied by the Certificates of Analysis issued for the romaine products in the shipment
4. the imported product was sampled and tested for E. coli O157:H7 according to 1 of the 2 sampling options described below and the testing conditions outlined in points e. and f. below:

Option 1: Finished-product sampling

4. sampling and testing is conducted after all post processing and handling steps are completed, but before the product is imported into Canada
5. a sampling lot is 1 type of romaine-lettuce product and a size no larger than the equivalent of 1 truckload of product (no more than 20,400 kilograms/45,000 pounds)
6. for each sampling lot, the minimum sampling and testing requirement is a total sample weight of 1,500 g consisting of 60 individual random sample units of 25 g each

Option 2: Pre-harvest sampling

4. sampling of romaine lettuce in the field is conducted no more than 7 days before harvest
5. a sampling lot is a 2 acre field or less of homogeneous romaine lettuce crop that has been exposed to homogeneous agricultural conditions
6. for each sampling lot, the minimum sampling and testing requirement is a total sample weight of 1,500 g consisting of 60 individual random sample units (grab specimens) of 25 g each
7. this sampling option can be used for romaine lettuce that will be field-packed at the time of harvest

This option is also acceptable for romaine lettuce destined for further processing before export (for example, chopped or mixed with other products) if the product is to be processed in separate batches, and a link can be established and documented between the Certificate of Analysis of the product sampled in the field and the finished product at the time of import

5. testing with both screening and confirmation methodologies must be performed in a laboratory accredited by an accreditation body that is a signatory to the International Laboratory Accreditation Cooperation (ILAC) Mutual Recognition Agreement (MRA) as conforming to the requirements of ISO/IEC 17025:2017 for specific tests

The chosen method must be on the laboratory’s scope of accreditation

The “application” section of the method chosen must be appropriate for the intended purpose, including that it is intended for testing romaine lettuce, leafy greens, or fresh fruits and vegetables

6. a presumptive positive result from a screening method is treated as a positive result for E. coli O157:H7 unless a confirmation test is performed on the original enrichment broth within 24 hours of the first test and produces a negative result (that is, not detected)

The confirmation test is a cultural method that is compatible with the screening method

4. Guidance on the temporary SFC licence conditions

a. Scope

The temporary SFC licence conditions apply to all U.S. import shipments of romaine lettuce and/or salad mixes containing romaine lettuce, sold in bags, in bulk, or combined with other food items, in a fresh state. It applies to all varieties of mature and baby romaine.

b. Proof of Origin

Shipments of romaine lettuce and/or salad mixes containing romaine lettuce from the U.S. but outside the California counties of Santa Clara, Santa Cruz, San Benito, and Monterey, must be accompanied by a declaration from the exporter on an official company letterhead which includes:

• the signature of the exporter
• the date the letter was signed by the exporter
• the state and county where the romaine lettuce was harvested

c. Certificate of Analysis

A Certificate of Analysis issued by the laboratory that conducted the test must be provided for each romaine product in an import shipment, demonstrating that the test result for E. coli O157:H7 is negative. The Certificate of Analysis must identify:

• the date of sample collection
• the certificate number
• the laboratory that analysed the sample
• the client
• a product description
• the methodology
• the sample weight and number of units
• the test result
• the test date

d. Sampling

The sampling level is based on International Commission on Microbiological Specifications for Foods (ICMSF) recommendations for E. coli O157:H7. The 2 sampling options are considered of similar value in achieving the required sampling level. The sample units must be collected aseptically and be representative of the lot being tested.

For option 2, additional guidance on how to take representative samples from a field is available on the California LGMAwebsite (see Appendix C).

Examples of appropriate sampling for option 1: Finished-product sampling

When to sample:

• field packaged romaine hearts can be sampled after cooling and just before they are loaded into a transport truck destined for Canada
• bulk romaine lettuce can be sampled just before it is loaded into a transport truck destined for Canada
• mixed salad sold in bags can be sampled during the packaging process at the processing facility or before it is loaded into a transport truck destined for Canada

Sampling lots:

• Example 1 – A shipment of 800 cartons of pre-packaged romaine hearts, 50 cartons of wrapped iceberg lettuce and 169 cartons of mixed bagged salad containing romaine lettuce:
  • this shipment should be considered 2 sampling lots

1 sampling lot is 800 cartons of pre-packaged romaine hearts

the other sampling lot is 169 cartons of mixed bagged salad containing romaine lettuce

• when romaine-lettuce products in a shipment have different bar codes or Price Look-Up (PLU) codes, they should be treated as separate sampling lots
• Example 2 – A shipment of bulk romaine lettuce with a weight of 14,000 kilograms

The shipment will be delivered to numerous clients in Canada after import to Canada:

• this shipment should be considered 1 sampling lot
• Example 3 – An importer purchases 1,500 cartons of pre-packaged romaine hearts weighing less than 20,400 kilograms

This product will be shipped to Canada in 4 shipments headed to various distribution centers in Canada:

• this product can be considered 1 sampling lot
• the importer’s preventive control plan must include a system for tracking all shipments that are associated with the Certificate of Analysis

All packages, cases or containers in the sampling lot must be equally represented in the sample. For example, a shipment of 800 cartons should have no more than 1 piece taken in a carton, and the 60 cartons sampled should be selected from various parts of the shipment. A shipment of 10 cartons should be sampled by collecting 6 pieces per carton. Product sampled during the packaging process should be sampled at the beginning, middle and end of the lot.

Examples of appropriate sampling for option 2: Pre-harvest sampling

When to sample:

• sampling is conducted as close as possible to harvest day, but not more than 7 days before harvest
• if the 7-day window is exceeded, the sampling lot can be re-sampled before harvest or the finished product can be sampled later according to option 1: Finished-product sampling

Sampling lots:

• Example 1 – A 3-acre plot of romaine lettuce intended for packaged romaine hearts:
  • 2 sampling lots must be taken as the field size from which the romaine lettuce was harvested exceeds the maximum 2-acre sampling size
• Example 2 – A shipment of bulk romaine lettuce with a weight of 14,000 kilograms
  • The bulk romaine is from 2 farms:
    • this shipment should originate from at least 2 pre-harvest sampling lots (at least 1 from each farm)
    • the number of sampling lots from each farm depends on field size from which romaine lettuce was harvested (maximum 2-acre sampling size)
• Example 3 – A shipment of 169 cartons of mixed bagged salad containing romaine lettuce:
  • this shipment could originate from 1 pre-harvest sampling lot provided all of the romaine lettuce was harvested from 1 homogeneous field not exceeding 2 acres
  • the product must be processed in batches separate from other product with a clear break between production lots
  • a link must be established and documented between the Certificate of Analysis of the product sampled in the field and the finished product at the time of import
  • if the processing facility handles tested and untested products (or products not tested according to the temporary SFC licence conditions), the break between production lots requires a full sanitation of the production line
• Example 4 – Pre-harvest sampling and testing is conducted on a sampling block that is subsequently harvested over multiple days:
  • the gap between the sampling date and the last harvest date must not exceed 7 days

5. Legislative authority

The licence conditions are based on the following legislative authority.

Section 20(3) of the Safe Food for Canadians Act states: “The Minister may make a registration or licence subject to any additional conditions that the Minister considers appropriate.”

The import requirements are based on the following legislative authority.

Section 8 of the Safe Food for Canadians Regulations and Section 4 of the Food and Drugs Act.

Section 8(1) of the Safe Food for Canadians Regulations states:

“Any food that is sent or conveyed from 1 province to another or that is imported or exported

1. must not be contaminated
2. must be edible
3. must not consist in whole or in part of any filthy, putrid, disgusting, rotten, decomposed or diseased animal or vegetable substance; and
4. must have been manufactured, prepared, stored, packaged and labelled under sanitary conditions”

Section 4 of the Food and Drugs Act states: “No person shall sell an article of food that:

1. has in or on it any poisonous or harmful substance;
2. is unfit for human consumption;
3. consists in whole or in part of any filthy, putrid, disgusting, rotten, decomposed or diseased animal or vegetable substance;
4. is adulterated; or
5. was manufactured, prepared, preserved, packaged or stored under unsanitary conditions.”

Failure to comply with the temporary licence conditions and import requirements may result in enforcement action taken by the CFIA.

Acute hemolytic uremic syndrome (HUS).

Post-diarrheal hemolytic uremic syndrome (D+HUS) is a severe, life-threatening complication that occurs in about 10 percent of those infected with E. coli O157:H7 or other Shiga toxin-producing (Stx) E. coli (STEC).

The cascade of events leading to HUS begins with ingestion of Stx-producing E. coli (e.g., E. coli O157: H7) in contaminated food, beverages, animal to person, or person-to-person transmission. The bacteria rapidly multiply in the gut, causing inflammation and diarrhea (colitis) as they tightly bind to cells that line the large intestine. This snug attachment becomes a route for the toxin to travel from the gut into the bloodstream, where it attaches to weak receptors on white blood cells (WBCs). From there, WBCs carry the toxin to the kidneys and other organs. 

To induce toxicity in target cells, Shiga toxins must first bind to specific receptors on their surface (Gb3 receptors). Organ injury is primarily a function of Gb3 receptor location and density. They are found on epithelial, endothelial, mesangial, and glomerular cells of the kidney, as well as microvascular endothelial cells of the brain and intestine. Because this attachment causes these organs to be susceptible to the toxicity of Shiga toxins, this distribution explains the involvement of the gut, kidney, and brain in STEC-associated hemolytic uremic syndrome (HUS).^[1]

Within the target organ, Shiga toxins disrupt the cellular machinery, resulting in cell injury and/or death. Within the intestine, infectious bacterial lesions cause derangements in the intestinal lining, disrupting the structure of the villi, affecting absorption in the gut, and eventually leading to watery diarrhea. Damage to the intestinal endothelium also causes mucosal/submucosal edema and, hemorrhage, introducing blood into the diarrhea.

Within the circulatory system, Shiga toxins are directly involved in platelet activation and aggregation (clot formation). The thrombotic microangiopathy that characterizes hemolytic uremic syndrome (HUS) occurs when platelet microthrombi (tiny clots) form in the walls of small blood vessels (arterioles and capillaries) causing platelet consumption. This pathologic reduction in platelets is called thrombocytopenia and is one of the hallmarks of HUS.^[2]Within the microvasculature of the kidney these clots disturb blood flow to the organ, causing acute kidney injury and kidney failure.

How hemolytic uremic syndrome (HUS) causes permanent kidney damage.

The kidney is the main target organ in STEC-mediated HUS. The nephron is the functional unit of the kidney. Each kidney contains approximately 1.2 million nephrons. At the heart of each nephron is a microscopic bundle of blood vessels called the glomerulus. The glomerulus represents the initial location of the renal filtration of blood.^[3] Blood enters the glomerulus through the afferent arteriole at the vascular pole, undergoes filtration in the glomerular capillaries, and exits the glomerulus through the efferent arteriole at the vascular pole.

Bowman’s capsule surrounds the glomerular capillary loops and participates in the filtration of blood from the glomerular capillaries. Bowman’s capsule also has a structural function and creates a urinary space through which filtrate can enter the nephron and pass to the proximal convoluted tubule. Liquid and solutes of the blood must pass through multiple layers to move from the glomerular capillaries into Bowman’s space to ultimately become filtrate within the nephron’s lumen. This ends the first stage in the production of urine.

In the rare event that the results of renal biopsies are known, microthrombi have been identified in the glomerular capillaries, resulting in extensive endothelial damage and, frequently, death of the nephron.^[4] Severe cases develop acute cortical necrosis affecting most cells in the renal cortex. Damage to tubular cells results in electrolyte disturbances, acidosis and decreased urine production. 

As seen in other kidney diseases, in STEC-HUS patients the progression to CKD is the consequence of renal mass reduction due to the loss of nephrons during the acute stage. Hyperfiltration,^[5] or abnormally elevated glomerular filtration rate (GFR), followed by significant and persistent albuminuria is the first marker of glomerular hypertension; however, it could appear several years later, especially in patients who have had a mild disease not requiring dialysis.^[6]This is analogous to running a car 24 hours a day—it would be taxing on the vehicle, wearing it out faster. In the kidneys, it can lead to early nephron cell death.

Loss of the filtration units of the kidney—the nephrons—is permanent. 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. 

Studies have shown a correlation between an increased number of days of anuria (lack of urination) or oliguria (decreased urination) and worse prognosis.^[7] Patients who have been anuric/oliguric and required dialysis are at the highest risk for late complications; however, even those who were not dialyzed are not spared. Research has consistently shown that these patients commonly progress to chronic kidney disease within 5 years.

Acute Kidney Injury (AKI) is the term that has recently replaced the term ARF. AKI is defined as an abrupt (within hours) decrease in kidney function, which encompasses both injury (structural damage) and impairment (loss of function).^[8] There are usually no symptoms until kidney function is at least moderately to severely impaired. When present, signs and symptoms of serious kidney injury reflect reduced filter function leading to buildup of toxic wastes, and may include high blood pressure, protein in the urine, swelling of the lower extremities, loss of appetite, nausea/vomiting, sleepiness, confusion, and difficulty thinking. 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 using the creatinine value. The key is whether filter function changes over time. Since one of the primary functions of the kidneys is to regulate blood pressure, the development of hypertension after HUS also signals serious kidney injury and is considered a bad prognostic sign. So too is proteinuria—the passage of protein molecules in the urine—which is a sign that the glomeruli have been damaged, and the remaining filters are hyperfiltrating—i.e., they are being overworked due to the loss of filtering capacity related to nephron loss.

If enough filters are lost either due to injuries suffered during the acute HUS illness, or later in life due to the process of hyperfiltration, a patient will reach end stage renal disease (“ESRD”). ESRD, truly a worst-case scenario for someone who has survived the acute HUS illness, is a very painful 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.

Long-term consequences of hemolytic uremic syndrome (HUS).

Multiple studies have demonstrated that children with HUS who have apparently recovered will develop hypertension, urinary abnormalities and/or renal insufficiency during long-term follow-up. One of the best predictors is the duration of anuria and/or oliguria.

Milford, et al, (J Pediatrics, 1991) studied the importance of proteinuria at one year following the acute episode of HUS in 40 children. They found that a poor prognosis defined as hypertension, decreased renal function or end stage renal disease was strongly associated with proteinuria at the one year follow up.

Perlstein et al, (Arch Dis Child, 1991) reported results of oral protein loading in 17 children with a history of HUS; they demonstrated that functional renal reserve was reduced in children with a history of HUS who had normal renal function and normal blood pressure as compared to normal children. This study suggests that functional renal reserve in children with HUS is 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 despite normal recovery and that children with HUS need long term follow-up.

In the article by Gagnadouz, et al, (Clinical Nephrology, 1996) 29 children were evaluated 15-25 years after the acute phase of HUS. Only 10 of the 29 children were normal, 12 had hypertension, 3 had chronic renal failure and 4 had end stage renal disease (65.5%). Severe sequelae occurred in children with oligo/anuria for more than or equal to 7 days.

Other studies (Caletti, et al, Pediatric Nephrology, 1996) have demonstrated that histological finding of focal and segmental sclerosis and hyalinosis are observed several years following HUS. In that article, only 25% of the children had normal renal function during long-term follow-up.

Similarly, Moghal, et al. (Journal of Pediatrics, 1998) performed kidney biopsies in children with persistent proteinuria three to seven years following the acute episode of HUS. Global glomerulosclerosis was noted in six of the seven patients and two had segmental sclerosis as well. In addition, tubular atrophy and interstitial fibrosis was seen in all but one. Finally, the glomeruli in the children with HUS were significantly larger than those in normal children. These are finding that are typically found in individual with reduced nephron number and are consistent with changes of hyperperfusion and hyperfiltration is surviving nephrons. Hyperfiltration is a process that frequently leads to progressive renal damage and the development of end stage renal failure.

In 1997 Spizzirri, et al, (Pediatr Nephrol, 1997), reported that 69.2% of children with 11 or more days of anuria and 38.4% of children with 1-10 days of anuria had chronic sequelae. In addition, of patients with proteinuria at the 1-year follow-up, 86% had renal abnormalities at the end of the follow-up. The authors suggested that children with residual proteinuria with or without hypertension would probably develop progressive chronic renal failure.

In 2002, Blahova, et al, reported that long term follow up of 18 children who had HUS 10 or more years previously, only 6 children were normal while the other 12 children had either residual renal symptoms, chronic renal insufficiency, or renal failure (66.6%). Many of the children with residual renal symptoms or chronic renal insufficiency/renal failure had appeared to have recovered normally at earlier checkups.

 Lou-Meda, et al, reported that 14 patients with microabluminuria and no overt proteinuria at 6 to 18 months after the acute phase of HUS, on long term follow up three had a decreased glomerular filtration (GFR), one had overt proteinuria, and four had hypertension. Eight of the 14 patients had at least one sequelae for an incidence of 57.1%. Six children had overt proteinuria and at the most recent follow up, two had hypertension, four and a low renal function and two had continued proteinuria; four (66.6%) had at least one renal sequale.

Recently, Oakes, et al, determined the risk of later complications in children who had HUS several years earlier; they found that the incidence of late complications increased markedly in those with more than 5 days of anuria or 10 days of oliguria. Among children with greater than 10 days of oliguria 63.3% had a low glomerular filtration rate, 33.3% had hypertension and 88.7% had at least one long term complication.

In the manuscript by Vaterrodt, et.al, the investigators noted that in a retrospective single center study, clinical and laboratory data of the acute phase and 1-10 year follow up visits were  analyzed.   The authors conclude that although renal outcomes has improved over the investigated decades, patients with HUS still had a high risk of permanent renal damage and that these findings underline the importance of a consequent long-term follow-up in HUS patients.  

In summary, many children who have recovered normal renal function following the acute episode of HUS have a high risk for the development of late complications from their acute episode of HUS. The risk is substantially lower in children who did not require dialysis and in children who were not oliguria or anuric while the risk is the highest in children who had oligo/anuria for more than 7 days. In one study, all children with oligo/anuria for 14 days had residual renal disease (100%).

As previously mentioned some children who did not require dialysis had late complication of HUS.  One third of the children in the study by Alconcher, et. al. (Pediat Neph, 2023 evolved into CKD after a median of 5 years.  In addition CKD appeared in some patients 15 years after the acute episode.   In addition, these investigators reinforced that all non-dialyzed should be followed into adulthood.  

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.

Long-term side effects of hemolytic uremic syndrome (HUS).

Adolescents and young adults with chronic kidney disease face several complications from their chronic kidney disease (Andreoli SP, Acute and Chronic Renal Failure in Children, 2009) including alterations in calcium and phosphate balance and renal osteodystrophy (softening of the bones, weak bones and bone pain), anemia (low blood count and lack of energy), hypertension (high blood pressure) as well as other complications.

Renal osteodystrophy (softening of the bones) is an important complication of chronic renal failure. Bone disease is nearly universal in patients with chronic renal failure; in some patients’ symptoms are minor to absent while others may develop bone pain, skeletal deformities and slipped epiphyses (abnormal shaped bones and abnormal hip bones) and have a propensity for fractures with minor trauma. Treatment of the bone disease associated with chronic renal failure includes control of serum phosphorus and calcium levels with restriction of phosphorus in the diet, supplementation of calcium, the need to take phosphorus binders and the need to take medications for bone disease.

Anemia (low blood cell count that leads to a lack of energy) is a very common complication of chronic renal failure. The kidneys make a hormone that tells the bone marrow to make red blood cells and this hormone is not produced in sufficient amounts in children with chronic renal failure. Thus, children with chronic renal failure gradually become anemic while their chronic renal failure is slowly progressing. The anemia of chronic renal failure is treated with human recombinant erythropoietin (a shot given under the skin one to three times a week or once every few weeks with a longer acting human recombinant erythropoietin).

Renal replacement therapy can be in the form of dialysis (peritoneal dialysis or hemodialysis) or renal transplantation. The average waiting time for a deceased donor kidney for children aged 0-17 years is approximately 275-300 days while the average waiting time for patient’s aged 18-44 years is approximately 700 days (United States Renal Data Systems, Table 7.8, 2005).

Following transplantation, a patient will need to take immunosuppressive medications for the remainder of his/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 liability, cataracts, decreased growth, osteomalacia and osteonecrosis (softening of the bones and bone pain), hypertension, acne and difficulty in controlling glucose levels.

Cyclosporine and/or tacrolimus are also commonly used as immunosuppressive medications following transplantation. Side effects of these drugs include hirsutism (increased hair growth), gum hypertrophy, interstitial fibrosis in the kidney (damage to the kidney), as well as other complications. Meclophenalate is also commonly used after transplantation (sometimes imuran is used); each of these drugs can cause a low white blood cell count and increased susceptibility to infection. Many other immunosuppressive medications and other medications (anti-hypertensive agents, anti-acids, etc.) are prescribed in the postoperative period.

Lifelong immunosuppression as used in patients with kidney transplants is associated with several complications including an increased susceptibility to infection, accelerated atherosclerosis (hardening of the arteries) and increased incidence of malignancy (cancer) and chronic rejection of the kidney.

A patient may need more than one kidney transplant during his/her life. United States Renal Data Systems (USRDS) report that the half-life (time at which 50% of the kidneys are still functioning and 50% have stopped functioning) is 10.5 years for a deceased transplant in children aged 0-17 years and 15.5 years for a living related transplant in children 0-17 years. Similar data for a transplant at age 18 to 44 years is 10.1 years and 16.0 years for a deceased donor and a living related donor, respectively. Thus, depending upon age when the patient receives his/her first transplant he/she may need 1-2 transplants. The life expectancy of a person with a kidney transplant is significantly less than the general population and the life expectancy of person on dialysis a markedly less than the general population.

If a child needs a second kidney transplant after loss of his/her first transplant, he/she will need dialysis until a subsequent transplant can be performed. He/She can be on peritoneal dialysis or on hemodialysis. Peritoneal dialysis has been a major modality of therapy for chronic renal failure for several years. Continuous Ambulatory Peritoneal Dialysis (CAPD) and automated peritoneal dialysis also called Continuous Cycling Peritoneal Dialysis (CCPD) are the most common form of dialysis therapy used in children with chronic renal failure. In this form of dialysis, a catheter is placed in the peritoneal cavity (area around the stomach); dialysate (fluid to clean the blood) is placed into the abdomen and changed 4 to 6 times a day. Parents and adolescents can perform CAPD/CCPD at home. Peritonitis (infection of the fluid) is major complication of peritoneal dialysis.

E. coli O157:H7 and other shiga-toxin producing E. coli are very dangerous bacteria – especially to children. The acute phase – even for those who do not progress to hemolytic uremic syndrome (HUS) – can be a painful and frightening experience. For those who progress to HUS, the risk of death is real. HUS has a mortality rate of 1-3%. And, even if the child survives, it may well be left with chronic health problems for the remainder of his/her life.

Additional Resources

Hemolytic Uremic Syndrome (HUS) chris edits 7.31.23.pptx from Bill Marler

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^[1]           Chan, Y.S., Ng, T.B. Shiga toxins: From structure and mechanism to applications. (2016). Appl Microbiol Biotechnol 100, 1597–1610. https://doi.org/10.1007/s00253-015-7236-3

^[2]           HUS is thrombotic microangiopathy characterized by the presence of a triad of symptoms: thrombocytopenia, acute renal impairment, and microangiopathic hemolytic anemia. Bhandari, J., & Sedhai, Y. R. Hemolytic uremic syndrome (HUS). (2020). State University of New York. https://www.researchgate.net/publication/341925697

^[3]           Falkson SR, Bordoni B. Anatomy, Abdomen and Pelvis, Bowman Capsule. In: StatPearls. StatPearls Publishing, Treasure Island (FL); 2022. PMID: 32119361. https://europepmc.org/article/NBK/nbk554474

^[4]           Renal biopsies are not routinely carried out as HUS diagnoses are usually clinically derived and patients are usually thrombocytopenic. Obrig, T. G., & Karpman, D. (2012). Shiga toxin pathogenesis: kidney complications and renal failure. Ricin and Shiga Toxins: Pathogenesis, Immunity, Vaccines and Therapeutics, 105-136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779650/

^[5]           Helal, I., Fick-Brosnahan, G. M., Reed-Gitomer, B., & Schrier, R. W. (2012). Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nature Reviews Nephrology, 8(5), 293-300.

^[6]           Alconcher, L. F., Lucarelli, L. I., & Bronfen, S. (2023). Long-term kidney outcomes in non-dialyzed children with Shiga-toxin Escherichia coli associated hemolytic uremic syndrome. Pediatric Nephrology, 38(7), 2131-2136. https://link.springer.com/article/10.1007/s00467-022-05851-4

^[7]           Pundzienė, B., Dobilienė, D., Čerkauskienė, R., Mitkienė, R., Medzevičienė, A., Darškuvienė, E., Jankauskienė, A. (2015). Long-term follow-up of children with typical hemolytic uremic syndrome. (2015). Medicina 51(3)146-151. https://doi.org/10.1016/j.medici.2015.06.004

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