The FDA and CDC yesterday announced that the latest romaine lettuce E. coli outbreak was over. Industry groups crowed that romaine is now safe to eat and they attested to doing more in the future to prevent another outbreak while at the same time discounting the cause of the last one.
For some these outbreaks are never really over.
Carolyn Graham is a 74-year-old woman residing in Loomis, California with her husband Kenneth. Carolyn was food poisoned after eating contaminated romaine lettuce in a meal she purchased with cash and consumed from a local restaurant in April 2018.
Carolyn began to experience symptoms consistent with E. coli infection on April 14, 2018. An exposure on April 11 is consistent with an incubation period that can averages 3 to 4 days for Shiga toxin-producing E. coli (STEC). A stool specimen collected on April 15, 2018 tested positive for STEC at Kaiser Regional Laboratory in Berkley, California. This specimen was further tested at the California Department of Public Health Laboratory, where it was found to genetically match the Yuma, Arizona romaine outbreak strain (PFGE pattern: EXHX01.0047/ EXHA26.0626).
Given Carolyn’s confirmed infection with STEC O157, her exposure to romaine lettuce within the STEC incubation period, and the genetic evidence connecting her infection to the outbreak, Carolyn was identified as a confirmed case in the Yuma, Arizona romaine E. coli outbreak (Outbreak ID: 1804MLEXH-1) by the California Department of Public Health.
Carolyn first noticed that something was amiss with her health when, on April 14, 2018, she began to suffer from severe diarrhea early in the day. By 11:30 PM that night, there was blood in her diarrhea: “… I begin bleeding and the bleeding continued throughout the night.” She did not wait for the night to end before making the decision to seek medical attention. At around 3:30-4 AM, Carolyn called the Kaiser Hospital advice nurse, because she found herself unable to move without feeling blood escape from her rectum. Carolyn was instructed to go immediately to the hospital.
Kaiser Hospital – Roseville, California
It was just past 6 AM on Sunday, April 15, 2018 by the time Carolyn arrived at the Kaiser Hospital located in Roseville, California, where Jessica Holley Derkacs, MD evaluated her in the emergency department. In triage, Carolyn described the onset of lower abdominal pain and diarrhea a little over 24 hours earlier. She noticed her stools looked brownish at first and later turned frankly bloody. She told the nurse that she had tried taking Imodium without relief. Carolyn answered questions about possible exposures, explaining that she had not taken any antibiotics recently, but she had been on Aleve since January for a pinched nerve, taking it a few times a week. She was not on blood thinners and had never had these kinds of symptoms before.
Carolyn was horrified when she experienced an episode of incontinent stool in the bed while she was waiting to see the doctor. The nurse helped Carolyn clean herself up and gave her “pull-ups” to put on, replacing the linens on her bed and providing a clean gown.
On exam, Dr. Derkacs found Carolyn afebrile, but her abdomen was tender in the right upper to mid quadrant, and her bowel sounds were hyperactive. The doctor did identify external hemorrhoids, but these were not bleeding, and she did not identify any anal fissures. Carolyn’s stool was guaiac positive for occult blood. She told the doctor that her last colonoscopy was in 2013, and she was noted to have hemorrhoids and diverticulosis at that time.
Dr. Derkacs started Carolyn on intravenous fluids and sent blood, urine, and stool samples to the lab for analysis. She kept under Carolyn observation in the ER for several hours on IV fluids, as well as clear liquids by mouth. Carolyn required supplemental oxygen to keep her blood oxygen saturation above 92%. She continued to pass “odiferous bloody diarrhea stool (no formed stool at all)” while in the ER.
When Carolyn’s lab results began filtering in, they were significant for an elevated white blood cell count of 17.2; however, she was not anemic (hemoglobin 12.4, hematocrit 38.0) and her renal function was normal (BUN and creatinine 18 and 0.76). Her stool was negative for toxigenic C. difficile. Dr. Derkacs discussed Carolyn’s case with the on-call gastroenterologist, who suspected she had infectious colitis and advised culturing her stool. He recommended avoiding antibiotics until the culture results were back. He saw no indication for colonoscopy at that time.
Dr. Derkacs initially planned to let Carolyn go home after a period of observation; however, when she passed another stool that consisted mostly of bright red, nonclotting blood, she called the hospitalist service to admit her.
Admitted for rectal bleeding – Hospital Day 0
It was just past noon on April 15, 2018 when Pamela Mercado, DO formally admitted Carolyn to the observation unit for a principal diagnosis of “rectal bleeding.” She was kept under contact isolation out of concern for an infectious process. Dr. Mercado planned to trend Carolyn’s blood counts and discharge her from the hospital later that day if her hemoglobin remained stable. If Carolyn exhibited worsening bleeding, Dr. Mercado wanted to bring gastroenterology in for consultation and possible endoscopy.
Later that afternoon, Carolyn was admitted to the medical/surgical unit when her bloody diarrhea increased in frequency to every 20-30 minutes, and her abdominal cramping worsened. In addition, her white count was increased to 20K. Dr. Mercado requested a CT scan.
CT Imaging consistent with pancolitis
Radiologist James Smith, MD took Carolyn for a contrast-enhanced CT of her abdomen and pelvis at 4 PM, during which he observed diffuse wall thickening throughout the entire length of her colon, which appeared edematous. Dr. Smith identified scattered diverticuli without diverticulitis. Her small bowel appeared to be unaffected. He diagnosed Carolyn with inflammatory versus infectious colitis, but he did not think this looked like mesenteric ischemia. He saw no free fluid or gas to suggest perforation.
Initiation of IV antibiotics (Rocephin and Flagyl)
At 6:31 PM, Nidhi Shukla, MD was the hospitalist overseeing Carolyn’s care and received the results of the CT scan. She discussed the CT differential diagnoses of inflammatory vs. infectious colitis with the on-call gastroenterologist, who recommended starting antibiotics if Carolyn spiked a fever or had worsening pain. When the nursing staff alerted her at 7:26 PM of an increase in Carolyn’s abdominal pain, Dr. Shukla conferred with infectious disease, who advised that Carolyn be started on IV ceftriaxone and metronidazole (Rocephin 1 gram IV daily, Flagyl 500 mg IV three times daily). Dr. Shukla implemented the antibiotic infusion and gave Carolyn oral narcotics (Norco) for pain.
Hospital Day 1
On Monday, April 16, 2018 at 4:39 PM, hospitalist Shanin Zanganeh, MD came in to see Carolyn in the afternoon and observed that there had been no change in her symptoms. Her white count was higher at 25.7K, but she was not running a fever. She had little urinary output, but she was losing a great deal of fluid through her diarrhea. Dr. Zanganeh consulted with gastroenterology, who planned to consult in the morning and assess the need for endoscopy.
Hospital Day 2 – GI consultation – IV antibiotics changed to azithromycin
At 11:32 AM on April 17, 2018, gastroenterologist Christopher Romberg, MD came in for a consultation. He assigned Carolyn the diagnosis of acute colitis, “most likely community acquired.” He called the bacteriology lab (“bacti”) and was told the GI Pathogen PCR results should be ready later that afternoon. Dr. Romberg stopped Carolyn’s ceftriaxone and metronidazole and changed her to IV azithromycin. He planned to perform a sigmoidoscopy later that day if she had not improved. He called “bacti” again later in the day and the stool results were still not available. He deferred the sigmoidoscopy but continued the IV azithromycin.
Hospital Day 3 – Altered mental status, anemia, anuria, thrombocytopenia
On April 18, 2018, the nursing staff alerted the hospitalist service at 11:17 AM, when Carolyn became hypotensive and tachycardic. Her blood pressure was 92/42 and she was noted to have only 1 mL of urine output in the prior 24 hours. Her white cell count increased to 28, and she was anemic with a hemoglobin of 10.6 and hematocrit 32.3%. Her platelet count fell to 112K. Carolyn was feeling so weak, she had to ask her husband to move her covers when she felt cold. She was able to move all her extremities but exhibited weak grip strength. She was noted to be confused, “… as she was asking her husband to remove the bathroom door.” Carolyn also reported visual disturbances with “narrow” vision. The nursing staff alerted the rapid response team (RRT) so they would be aware of Carolyn’s potentially unstable status.
Hospitalist Dr. Driscoll thought Carolyn’s leukocytosis fit with C. difficile, but her stool sample tested negative.
Dr. Romberg went forward with a flexible sigmoidoscopy that afternoon, citing Carolyn’s failure to respond to the IV antibiotics. During the exam, he observed patchy colitis from the rectum “… to the extent examined.” These areas exhibited patchy submucosal hemorrhages but no visible ulcerations. Dr. Romberg did not think Carolyn had inflammatory bowel disease; he thought the visual appearance of her colon was most consistent with moderate ischemic colitis. He suggested a viral etiology and continued her IV azithromycin. Because Carolyn’s abdomen was extremely tender to examination, he recommended a surgical consultation if her she began to exhibit peritoneal signs.
Confirmation of E. coli O157 DNA by PCR, Shiga toxin 2 positive
Just before 4 PM, the hospital laboratory called a critical value to the floor, reporting that Carolyn’s stool had tested positive for E. coli O157 DNA by PCR testing, as well as positive for Shiga toxin 2 gene. The lab report carried a cautionary warning:
Patients with E. coli O157:H7 infection are at risk of developing hemolytic-uremic syndrome (HUS). Antibiotic treatment and/ or loperamide in the setting of shiga toxin positivity is contraindicated in most cases. E. coli O157:H7 is a reportable disease.
Hospital Day 4 – continued anuria, leukocytosis, thrombocytopenia, acute renal failure
On April 19, 2018, Carolyn’s morning labs had worsened significantly, with a white blood cell count up to 32.5K, and a hemoglobin and hematocrit down to 10.9 and 33.5. Her platelets were down to of 111K. Her urinalysis was significant for moderate hemoglobin, proteinuria, and leukocyte esterase. Carolyn’s renal function was also markedly abnormal, with a BUN and creatinine of 50 and 4.53. In addition, her LDH was elevated at 1548. Carolyn had produced no urine overnight, and nephrology was asked to consult. A Foley catheter was inserted to more accurately measure her output.
Nephrology consultation – possible HUS, altered mental status
At 11 AM, Tuan Anh Nguyen, MD came in for nephrology at the request of Dr. Driscoll. He reviewed the onset and progression of Carolyn’s diarrhea illness, including her serial lab results and imaging. He noted the negative stool test for toxigenic C. difficile, but positive PCR testing for E. coli O157 and Shiga toxin 2. He observed the WBC spikes, thrombocytopenia, elevated LDH, and abnormal renal function. He saw that Carolyn had been anuric for two days and exhibited signs of fluid overload. She had puffy hands, and her husband reported she was having hallucinations and exhibiting mild delirium. On the plus side, her diarrhea was improving.
Dr. Nguyen assessed Carolyn with “acute kidney injury secondary to ‘multifactorial,’” possibly from acute tubular necrosis (ATN) related to colitis, “… in the setting of lisinopril and contrast-induced injury vs. HUS due to E. coli.” He did not think Carolyn needed hemodialysis at this point, but he discussed with her husband and family that they would need to monitor her closely and he could not rule that out. He wanted to get a hematology consultation for HUS and an assessment of whether apheresis would be recommended. “If apheresis is recommended, she will need an apheresis catheter by IR, and nephrology would be the one to coordinate and perform apheresis.” Particularly in light of Carolyn’s altered mental status, Dr. Nguyen advised avoiding morphine given her acute kidney injury, “due to buildup of metabolites.” He also wanted to avoid the use of nephrotoxins, such as IV contrast, aminoglycoside antibiotics, Fleets enemas, and NSAIDs, and requested that her care team renally adjust all medications for her current eGFR. He requested the insertion of a Foley catheter so Carolyn’s fluid intake and output could be carefully monitored.
Hospital Day 5 – negative head CT
Shortly after midnight on April 20, 2018, the nursing staff placed an urgent call to the rapid response team (RRT) when Carolyn was found moaning loudly, exhibiting increasing confusion, expressive aphasia, and the inability to respond about where she was hurting. Dr. Driscoll responded as well and ordered brain imaging, Tylenol IV, and Dilaudid for pain. Nakiye Yegul, MD performed an urgent head CT urgently, no evidence of an acute intracranial process.
Hematology consultation – diagnosis HUS – CNS involvement
Dinesh Kotak, MD came in for a hematology consultation later than morning and reviewed Carolyn’s clinical presentation, including her abnormal lab results so far. He noted that she had exhibited gradually worsening CNS symptoms over the prior couple of days. “These started with hallucinations; patient has had periods where she is lucid and remembers her family.” Dr. Kotak reviewed a peripheral blood smear that showed 3-4 schistocytes per high power field, with normal appearing platelets but occasionally nucleated red blood cells. Her thrombocytopenia had worsened slightly, with a current platelet count of 91K. Dr. Kotak explained to the family that Carolyn now met the criteria for a diagnosis of hemolytic uremic syndrome (HUS), and the primary treatment for that condition was supportive care only. However, given the severity of Carolyn’s CNS symptoms, Dr. Kotak consulted with a regional expert (“Dr. Bradley”) about her case, who recommended treating Carolyn with one dose of eculizumab (Soliris). Dr. Kotak discussed the need for pre-medication with vaccination, as well as antibiotic coverage for meningococcus per infectious disease. Dr. Kotak deferred to infectious disease for how to treat that.
Nephrologist Dr. Nguyen conferred with Dr. Kotak after his consultation regarding apheresis therapy, and Dr. Kotak advised against it. He cited his discussion with the regional expert and medical literature review, who had recommended the single dose of Soliris based on limited case studies with patients who had exhibited a rapid CNS decline. They would have to request the drug from another medical center and planned to do one hemodialysis treatment before giving Carolyn the Soliris, “… so that the drug is not cleared off.” He advised discontinuing Carolyn’s bicarbonate drip, and Dr. Nguyen did so. After conferring with Dr. Kotak, Dr. Nguyen discussed with Carolyn’s husband and daughter the indication to proceed with renal replacement therapy (hemodialysis versus other methods), which he hoped would be a temporary measure.
Hemodialysis No. 1
At 2 PM, Benedict Hsu, MD performed the insertion of a dual lumen 19 cm right internal jugular tunneled dialysis catheter under fluoroscopic guidance. Both lumens were functioning normally at the conclusion of the procedure. The catheter was then flushed with heparin as recommended by the manufacturer, secured in place, and a sterile dressing was applied. Carolyn tolerated the procedure without difficulty or immediate complications. Dr. Nguyen put a request in to Davita to implement the inpatient hemodialysis procedure. Gary Miller, RN started Carolyn’s hemodialysis at 7:26 PM, ending at 10:26 PM, with a net fluid removal of 1900 mL
Only later, Carolyn talked with her family to piece together what was happening to her during this period of time:
A dialysis port was inserted and my first dialysis started that evening. I had a CT Head/Brain scan to make sure I hadn’t had a stroke. I started a new, rare and expensive, cancer medication to block the E coli. Kaiser Hospital had to find medication. I had no urine output. I did not recognize my family.
Hospital Day 6 – Soliris administered – continued altered mental status
At 1:30 AM on April 21, 2018, Carolyn received a second peripheral IV line to accommodate the administration of eculizumab, which was administered at 1:50 AM. She tolerated the medication without complications. Hospitalist Lifang Zhang, MD implemented a renal dose (500 mg) of intravenous azithromycin for coverage of meningococcus at 2:40 AM. She had originally intended to use oral Penicillin VK, but Carolyn was too sleepy and so she chose the IV azithromycin instead. When she was more alert, Dr. Zhang wrote orders to go back to giving her Pen VK orally twice a day.
Carolyn continued to exhibit a great deal of confusion that morning, so much so that the rapid response team was again called when she began moaning loudly around 5 AM. Dr. Zhang responded to the call as well and ordered the administration of IV Tylenol, as she did not want to give Carolyn and more Dilaudid because of her altered state of consciousness.
Lisa Law, MD came in for hematology around 10 AM and saw Carolyn along with hospitalist Dr. Driscoll. Her husband and granddaughter were at the bedside, and the doctors discussed how Carolyn was doing. Her morning labs showed a slight decrease in her white count to 29.0, with significant hemolytic anemia (hemoglobin 8.2, hematocrit 24.8) and thrombocytopenia (platelets 80K), and abnormal renal function (creatinine 4.46). She did not have a fever and her blood pressure was stable, although she was tachycardic with a pulse of 105. According to her husband and the nursing staff, Carolyn’s mental status was improved, and she was able to answer questions appropriately that morning. She stated her diarrhea had decreased, as had her abdominal pain. Dr. Law did not think her anemia warranted a blood transfusion at that point and they could follow her blood counts for now, as well as a daily LDH. If Carolyn showed no clinical improvement over the next few days, she wanted her to have another dose of eculizumab in one week after the first dose.
Hospital Day 7 – Hemodialysis No. 2 – anuric, continued hemolysis
On April 22, 2018, Dr. Law returned to see Carolyn, finding her mental status worse than it was the day before. Her husband stated that she was not talking and appeared to be more confused, although her eyes were open and she was moving her arms and legs. Her LDH had increased slightly to 1520, her anemia was worse (hemoglobin 8.5, hematocrit 26.3), although her platelets were stable (82K). Her serum creatinine was higher at 6.26. Carolyn had not produced any urine whatsoever in the prior 24 hours. Dr. Nguyen came in for nephrology and made the same observations as Dr. Law, and initiated Carolyn’s second hemodialysis treatment at 12:30 PM. She also received a dose of EPO to stimulate red blood cell production. Carolyn’s doctors continued her diagnoses of “colitis,” “severe sepsis,” and “hemolytic uremic syndrome.” Dr. Driscoll noted that she was much calmer later that afternoon, but she was not in peaceful sleep, “startling” whenever anyone touched her.
Hospital Day 8 – Hemodialysis No. 3 – continued encephalopathy
The following morning, Jignesh Kantibhai Patel, MD was in for nephrology and noted that Carolyn was still anuric with “negligible” urine production. Her mental status remained altered and she was still non-verbal, although her husband thought she was more alert. Dr. Patel looked at her morning labs and observed improvement in her renal function, with a BUN and creatinine of 41 and 4.91, so he did not think her poor mental status was consistent with “uremic confusion.” She was still very anemic but not at a level that required a blood transfusion. Carolyn underwent her third hemodialysis treatment beginning at 2:41 PM, along with another dose of EPO.
Carolyn later recalled what a difficult time this was for her:
It was a rough night. I started a new pain medication that I received every 3 hours. I was still unconscious and I couldn’t seem to move anything, except for my arms, which caused me to scream in pain.
Hospital Day 9 – still anuric, but no hemodialysis today
On April 24, 2018, Dr. Kotak came in for hematology and was happy to see Carolyn speaking with her husband and responding appropriately to questions, albeit in monosyllables. Her granddaughter was at her bedside when the doctors came to see her, and she told them that she had noticed her grandma had difficulty speaking about three days earlier.
Carolyn’s morning labs exhibited slight improvement in her renal function (BUN 34, creatinine 4.27), but she was still not producing any urine; however, Dr. Patel did not think she needed hemodialysis that day.
Hospital Day 10 – Hemodialysis No. 4
On April 25, 2018, hospitalist Irina Badalyan visited Carolyn in the morning. She still carried the diagnosis of severe sepsis with “acute organ dysfunction,” accompanied by leukocytosis with a white count of 21.8; she remained afebrile and was hemodynamically stable, however. Infectious disease specialist Dr. Fontanilla weighed in on her care plan and recommended that she be given meningococcal prophylaxis as long as she still required monoclonal antibody treatment (eculizumab). When she discovered that Carolyn had been given only a Meningococcal B vaccine on the 24th and not the Meningococcal A, C, Y, W vaccine (“apparently there is a shortage”), she recommended they get the vaccine from an outside pharmacy and give it immediately. Dr. Fontanilla approved the use of oral amoxicillin for antibiotic prophylaxis at this point. Carolyn’s blood count had dipped almost down to transfusion levels, with a hemoglobin of 7.2 and hematocrit 21.9, and the plan was to transfuse her with packed red blood cells (PRBCs) if her hemoglobin went below 7.0.
Carolyn’s renal function panel continued to exhibit markedly abnormal values on the 25th, with a BUN and creatinine of 31 and 4.58, and she was still anuric. She underwent her fourth hemodialysis treatment, along with another dose of EPO. Carolyn also received the appropriate meningococcal vaccine that afternoon.
Today was my fourth day of dialysis. I started to remember some things, and I am trying to talk, but I have difficulty forming words. I worked with the speech therapist. I received a phone call from Lynnette at Placer County Health Department and she spoke with my husband, explaining that that the E. coli strain I had contracted had been traced to a restaurant in Rocklin, California that served Yuma romaine lettuce.
Hospital Day 11 – transfusion PRBCs
On April 26, 2018, Carolyn was noted to have an increase in her rectal bleeding. Her anemia worsened to a hemoglobin of 6.9, and she required a transfusion of PRBCs. Dr. Patel visited her during rounds that morning with her sister and daughter at the bedside. Carolyn was more alert and talkative. Dr. Patel noted that she was tolerating hemodialysis with ultrafiltration. He discussed her minimal urine output and the likelihood of plans for outpatient hemodialysis. Dr. Patel also spoke with Carolyn’s husband in the hallway and explained that, as part of discharge planning, they needed to start looking for an outpatient dialysis spot. He was hoping she might be ready to go outpatient dialysis as early as the following week. Meanwhile, her next dialysis was planned for the 27th.
Hospital Day 12 – Hemodialysis No. 5 – continued anuria
On April 27, 2018, Carolyn’s blood count was improved, reflecting the blood transfusion the day before, with a hemoglobin and hematocrit of 8.3 and 25.4, and her white count had also improved at 17.9. Her platelets were in normal range. Her BUN and creatinine remained markedly abnormal at 42 and 5.80.
Carolyn was more alert and began working with physical therapy to get her ambulatory and increase her stamina, in anticipation of a safe transition to either her home or a skilled nursing facility. Per Dr. Fontanilla, Carolyn was also going to be on antibiotic prophylaxis against meningococcus for a total of three months of amoxicillin treatment. She underwent her fifth hemodialysis that evening, and nephrologist was working on arranging outpatient hemodialysis, as she was still anuric.
Carolyn recalls coming out of the fog of her altered mental status:
After being admitted to my hospital room, I don’t have any recall of the events that took place while in the hospital until April 26 or 27.
Hospital Day 13-14 – Hemodialysis No. 6 – discharged to SNF
On April 28, 2018, Dr. Patel came in for nephrology and noted that Carolyn was alert and conversant. She was beginning to make a little urine, so he approved the removal of her Foley catheter. He had arranged outpatient dialysis for her (“FMC Secret Ravine”), and so he hoped to discharge her the following day after her treatment.
Carolyn’s morning labs on the 29th showed improvement of her anemia and her white count was coming down towards normal range; however, her renal function remained markedly abnormal (BUN 37, creatinine 5.38). She underwent her sixth hemodialysis treatment that morning. Afterwards, Irina Badalyan, MD discharged Carolyn from the hospital, transferring her to the care of a skilled nursing facility. The nursing facility was instructed to continue her antibiotic therapy with oral amoxicillin and three times weekly hemodialysis.
Kindred Siena Skilled Nursing & Rehabilitation – Generations Healthcare
On April 29, 2018, Sreehar Javagal, MD admitted Carolyn to Siena Skilled Nursing and Rehabilitation, where she was slated to receive both occupational and physical therapy, as well as continued hemodialysis. Carolyn remained at Siena until May 11, 2018. Her first dialysis treatment after her arrival at Siena (Hemodialysis No. 7) was administered at the Davita Auburn Dialysis Clinic on Wednesday, May 2, 2018, and she returned there for repeat HD once more that week on Friday, and again on Monday and Wednesday the following week (Hemodialysis Nos. 8, 9 and 10).
On Friday, May 11, 2018, Dr. Javagal reviewed Carolyn’s progress over the prior ten days. She had progress in PT to where she was ambulating over 200 feet with minimal assistance. Despite receiving dialysis treatments three times a week, her serum creatinine had not fallen below 5.0. Her anemia was stable above 7.0 g/dL, but that was just above transfusion threshold and Dr. Javagal thought she would need to continue on EPO with her dialysis. Her platelets were stable in normal range. Carolyn had not exhibited any confusion or other signs of altered mental status during her stay, and Dr. Javagal thought she was ready to go home. She had another dialysis treatment at Davita that day and was discharged from the skilled nursing facility later that afternoon.
Carolyn recalls her stay at the SNF:
I spent 12 days at Sienna Skilled Nursing facility in Auburn, CA. I worked with occupational and physical therapists for a couple of hours every day to learn how to use a walker, dress myself, get in and out of bed, use the bathroom with help, at first, and then, without help near the end of my stay. They also worked on trying to get my mental facilities back. At that time, I was having a hard time figuring out how to use my cell phone, the controls on the bed, and adding and subtracting numbers. I had dialysis three times a week, at Davita Dialysis Center, Auburn, CA while I stayed at the skilled nursing facility.
Fairwood Medical Clinic – Secret Ravine Dialysis Clinic
On Monday, May 14, 2018, Carolyn presented to FMC Secret Ravine outpatient dialysis clinic to resume hemodialysis.
Over the next few weeks, Carolyn continued with regular outpatient hemodialysis, EPO therapy, and serial lab tests to watch her renal function.
Carolyn recalls resuming dialysis in Roseville:
I started dialysis at Secret Ravine Parkway, Roseville, CA- 3 times a week for 3 hours of treatment. Blood tests were done every Monday. They also gave me protein shots and iron supplements to help build up my hemoglobin, which was very low. My labs slowing started improving every week.
Kaiser Riverside Outpatient Clinic – recurrent diarrhea
On May 17, 2018, Carolyn presented to Kaiser Riverside Clinic, where Cindy Loh, MD evaluated her in follow-up of her hospitalization for STEC HUS. Carolyn was still on three days of hemodialysis every week. Since she left the Kaiser SNF, Carolyn reported that she had experienced recurrent diarrhea. It did not contain blood, but she had abdominal cramping and fecal urgency when it occurred. She did not have any fevers, chills, nausea or vomiting. She was taking Lasix for lower extremity swelling and wondered if it was causing her diarrhea. Dr. Loh did not think that the Lasix was the cause and wanted Carolyn to start taking probiotics.
Carolyn told Dr. Loh that she was still taking the amoxicillin prescribed when she was discharged from the hospital. Dr. Loh reviewed her labs and saw that Carolyn still exhibited abnormal renal function, with a serum creatinine of 4.5 the day before this visit. She sent blood work to the lab, as well as a urinalysis with culture if indicated.
Fairwood Medical Clinic – Secret Ravine – continued HD
On June 12, 2018, Christopher McConnell, RN, the Kaiser Renal Care Coordinator, documented a phone call with Dr. Yuan discussing Carolyn’s dialysis clinic lab work and progress. Dr. Yuan was satisfied that Carolyn was showing signs of renal recovery and probably no longer required hemodialysis. He wrote orders for her to return to the FMC Secret Ravine Clinic on Saturday, June 16, 2018 for HD catheter care and another blood draw to check her renal function and complete blood count, and he would base his final HD orders on those results.
Kaiser General Surgery – HD catheter removal
On June 24, 2018, Carolyn presented to Kaiser General Surgery outpatient clinic for removal of her hemodialysis catheter. Matthew Kurowski, PA-C performed the procedure under local anesthesia in the clinic, under the supervision of Joshua Kehoe, MD. There were no complications of the procedure. Carolyn’s blood was drawn that day, and the Kaiser lab returned results showing an improvement in her serum creatinine to 1.89, and she was no longer anemic, with a hemoglobin and hematocrit of 11.4 and 37.5.
Kaiser Roseville Nephrology Clinic
On July 10, 2018, Carolyn presented to Kaiser’s outpatient nephrology clinic in Roseville, where Tuan Anh Nguyen, MD saw her in follow-up of her STEC HUS acute renal failure status post dialysis. Dr. Nguyen reviewed the onset and progression of Carolyn’s diarrhea illness, which had been diagnosed as Shiga toxin related E. coli O157 HUS, complicated by acute renal failure that required renal replacement therapy until June. He noted that she had received one dose of Soliris in the hospital and was still taking amoxicillin for meningococcal prophylaxis. Carolyn reported that she was feeling much better and was even playing golf. Her appetite was back to normal. She was having some ankle swelling, but she had no shortness of breath, cough, or other pulmonary symptoms. She no longer had diarrhea or loose stools.
Dr. Nguyen diagnosed Carolyn with “AKI due to HUS, was on HD, now off, still improving.” He advised her to avoid NSAIDs, herbal supplements and other nephrotoxins. He wanted to repeat her renal function labs in a month, then every two months.
On August 5, 2018, Carolyn had her blood drawn, which returned lab results showing a serum creatinine of 1.71, eGFR 29, parathyroid hormone 85 (RR 10-65 pg/mL), and hemoglobin and hematocrit of 13.1 and 40.8. A recheck on October 4th showed further improvement in her renal function to a BUN and creatinine of 22 and 1.22, the latter of which was still slightly elevated.
Dr. Nguyen telephoned Carolyn on October 31, 2018 to discuss her lab results, explaining that her renal function panel placed her in the category of CKD-3.  He reassured her that she was gradually improving and he expected that to continue. He advised her to avoid medications such as NSAIDs, herbal supplements, aminoglycoside antibiotics, and any other medications or substances that were nephrotoxic. He also advised her to stay well hydrated. She had improved sufficiently to where he did not think she needed lab testing as frequently, and they could go to every six months for retesting.
Carolyn reflects on her recovery from her E. coli HUS infection:
In conclusion, I am grateful that my kidneys are functioning better, and that I no longer have to be on dialysis. I know I still have a ways to go, as I continue to have problems with my memory, with confusion, and some difficulty with walking up and down the stairs/steps. I will forever be grateful to my family for their love and support throughout this terrible ordeal. They were at the hospital day and night, working with the nurses and doctors. I am positive that without my family’s care and participation in my recovery, my ordeal and continuing recovery would have been more difficult and the results more dire.
Providing a prognosis for a patient’s renal outcome who has suffered HUS due to E. coli O157:H7 is often imprecise, but Carolyn’s 4-week history of anuria and 2 months of dialysis dependence suggest she is likely to undergo progressive chronic kidney disease. Her 5-month follow-up with an eGFR of 51 ml/min/1.73m2 with proteinuria make it highly likely she will require kidney replacement therapy in the next 8-13 years. The duration of her initial kidney failure and associated significant renal impairment (eGFR 51 ml/ min/1.73 m with proteinuria) following recovery suggests she will likely require renal replacement therapy and in view of her age it will be some form of dialysis since her age will preclude transplantation.
Carolyn’s proteinuria and renal impairment make it highly likely that she will undergo rapid renal decline (losing 3-5ml/ min/year ). Over the next 5-8 years she will develop symptoms of fatigue and will require erythropoietin therapy and judicious use of phosphate binders and dietary salt restriction plus or minus antihypertensive therapy. Her quality of life will be gradually reduced as her CKD advances and if she requires hemodialysis her quality of life will be about 50% of normal and her life expectancy will be shortened due to her underlying CKD. The only other concern is her prior CNS involvement due to HUS means she requires sensitive psychometric testing re cognitive dysfunction which can potentially have a significant impact on her quality of life.
 Reference ranges for this lab: WBC 3.7-11.1K, hemoglobin 11.5-15.0 g/dL, hematocrit 34.0-46.0%, BUN 7-27 mg/dL, creatinine <1.11 mg/dL, LDH <270 U/L
 Plasmapheresis is performed by two fundamentally different techniques: centrifugation or filtration. With centrifugation apheresis, whole blood is spun so that the four major blood components are separated out into layers by their different densities. With filtration plasmapheresis, whole blood passes through a filter to separate the plasma components from the larger cellular components of red blood cells, white blood cells, and platelets. Nguyen, Trung C et al. “The role of plasmapheresis in critical illness” Critical care clinics vol. 28,3 (2012): 453-68, vii.
 Severe complications due to Shigatoxin-associated hemolytic uremic syndrome (STEC-HUS) currently present a serious challenge since no specific treatment for this condition is available. Eculizumab, a terminal complement inhibitor, has been used especially in STEC-HUS patients with severe neurological involvement, but the efficacy remains undetermined. Keenswijk, Werner, et al. “Is Eculizumab Efficacious in Shigatoxin-Associated Hemolytic Uremic Syndrome? A Narrative Review of Current Evidence.” European Journal of Pediatrics, vol. 177, no. 3, 2017, pp. 311–318., doi:10.1007/s00431-017-3077-7.
 Eculizumab recipients are at 1,000 to 2000 times greater risk for getting meningococcal disease compared to otherwise healthy individuals in the United States. https://www.cdc.gov/meningococcal/clinical/eculizumab.html
 In HUS, lactate dehydrogenase (LDH) level is commonly elevated. Serial measurements of LDH help track the approximate level of hemolytic activity. Gillespie, Robert, MD. “Pediatric Hemolytic Uremic Syndrome Workup.” Pediatric Hemolytic Uremic Syndrome Workup: Laboratory Studies, Imaging Studies, Other Tests. Medscape, 13 June 2016. Web. 31 Jan. 2017.
 Erythropoietin (also known as EPO) is a growth factor that stimulates the production of red blood cells. Most of the cells in the blood are red blood cells, whose main function is to carry oxygen throughout the body. https://www.themmrf.org/multiple-myeloma-knowledge-center/myeloma-treatments-guide/growth-factors/erythropeietin/
 Ultrafiltration refers to filtration of a colloidal substance in which the dispersed particles, but not the liquid, are held back. During hemodialysis treatments, water and sodium are not ordinarily removed by diffusion but rather through the process of ultrafiltration. Venes, Donald. Taber’s Cyclopedic Medical Dictionary (Taber’s Cyclopedic Medical Dictionary (Thumb Index Version)) (Page 2407). F.A. Davis Company. Kindle Edition.
 A person with stage 3 chronic kidney disease (CKD) has moderate kidney damage. This stage is broken up into two: a decrease in glomerular filtration rate (GFR) for Stage 3A is 45-59 mL/min and a decrease in GFR for Stage 3B is 30-44 mL/min. As kidney function declines waste products can build up in the blood causing a condition known as “uremia.” In stage 3 a person is more likely to develop complications of kidney disease such as high blood pressure, anemia (a shortage of red blood cells) and/or early bone disease. Reference: https://www.davita.com/kidney-disease/overview/stages-of-kidney-disease/stage-3-of-chronic-kidney-disease/e/4749