Topic Discussion: Use of immunotherapy in ESRD patients

Two recent studies from US now describe the use of immunotherapy in ESRD patients. Though both are case studies and series, this is encouraging data.

One study comes from Boston published in AJKD, with a database search leading to 18 patients: overall, six patients (32%) experienced irAEs and two (11%) experienced an irAE of grade 3/4 toxicity (pneumonitis, myocarditis).

Another study from New York published in Kidney 360, with a database search lead to 8 patients: only 2 patients (25%) experienced irAEs overall. A literature review done in that paper also found another 26 patients have previously been described in the literature, with the majority of them from  Italy and China.  Interestingly, 27% of these patients were on dialysis as a result of a rejected kidney transplant due to ICI therapy, and then continued to receive ICI. Over 80% of the patients had either partial or complete response to treatment. Aside from the kidney transplant rejection preceding dialysis, a minimal number of patients had a grade 2, 3, or 4 adverse immunotherapy related event (15%).  In the general population, between 40-60% of patients receiving ICIs experience irAEs at some point during therapy.

Again, due to smaller numbers, we cannot be sure the effects of ICI in ESRD patients but it appears that the rate of irAEs appears similar to general population. 

In the News: AKI in COVID-19 patients, a study and a story ( pics and words)

(Our fearless fellows during COVID-19)

As we tackle the world of COVID-19, at Northwell, we faced a lot of AKI related to COVID-19.
We were able to gather this data and publish a large 13 hospital dataset from US looking at AKI related to COVID-19. The data was just released in Kidney International today. This study is dedicated to all the patients and families we helped treat and our fearless warriors in this fight- our faculty, fellows, nurses, and all nephrology division staff at the two main campuses of North Shore University Hospital and LIJ at Northwell. Without their hard work, this study wouldn't be possible. We wanted to share some of our data here ( as a summary) with some personal faculty/fellows pics from the last 2 months of hard work.

1. When NY became the epicenter of COVID-19, nephrologist across NY noticed an alarming number of patients who developed AKI, at rates higher than reported in China. Our study reports the AKI rate and describes the presentation and risk factors of AKI in this population. We reviewed health records of patients hospitalized with COVID-19 between March1- April 5th, 2020, and followed up through April 12th. The data was from 13 hospitals. Our final cohort had 5449 patients.

2. Out of 5449 patients, 1993 (37%) developed AKI (stage 1-47%, stage 2- 22% and stage 3- 31%).
Up to 14% of all AKI patients required renal replacement therapy. At the time of this writing, among patients with AKI, 694 died (35%), 519 (26%) were discharged and 780 (39%) were still hospitalized.

3. AKI occurred early in the course of hospitalization, with 37% either arriving with AKI or developing within 24 hours of admission.

4. AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients.
276/285 (96.8%) of patients requiring RRT were on ventilators.

                                           (Our LIJ renal team with Dept of Medicine Chair)


5. We found that independent risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, Black race, hypertension, vasopressor medications and need for ventilation. In our study, baseline ACE-inhib use and BMI were not risk factors for AKI.

6. Around 66% of the patients had a urine Na of <35, suggestive of a prerenal state. In urinalysis, 46% had +ve blood and 42% had +ve protein. Unfortunately, we do not have accurate data on urethral catheters and baseline proteinuria.

                                            ( Our North Shore Inpatient rounding teams)

7.Why was our AKI rate higher (37%) than the study reported (5%) by Cheng et al?
We cannot completely explain this difference, but their patients had lower rates of comorbidities and ventilation needs than our patients. Our rates seem consistent with reports from US hospitals that are going to be published soon. In a recent preprint from Mt Sinai in NY- AKI rate was also 40%. Another US study also published at the same time from New Orleans found a rate of 28%.

8. We found a close temporal relationship between AKI and timing of intubation. It is possible that these patients developed ATN during systemic collapse. Since the 66% of AKI patients had urine Na of <35, they could have prerenal AKI.

9. Although not a primary purpose of this study, among the 285 on dialysis, 55% died, 42% still in the hospital and 3% were discharged.

                                            (Our North Shore Inpatient rounding teams)

10. It is important to note that because of early censoring and incomplete hospital disposition data, we cannot make definitive inferences about outcomes. We will do an update on full outcomes in 30 days. This study to define the rate of AKI, timing and risk factors.

11 The goal of this study was a broad description of AKI in COVID-19 patients. We believe that it is very important this information becomes available rapidly for clinicians. A full assessment of all patients’ outcomes will require a longer period of time to allow for disease processes to fully play out.

                                               (Our chief and associate chief in action)

12 What limitations do we have? 1. The cause of AKI were not fully elucidated. 2. Since this is an observational study, we will not be able to make causal inferences between exposures and AKI. 3. CKD could not be assessed given EHR data mining.

13 What are the strengths of the study? This is the largest cohort to date of hospitalized patients with COVID-19 with a focus on AKI. Our identification of AKI is consistent with guidelines, well-validated and automatically calculated in real-time for almost 1 year.

Cause of AKI- likely ischemic ATN( but AKI can come in various variants as noted on my prior post but a recent NEJM article also highlights potential involvement of ACE2 and renal tropism in AKI seen with COVID-19. In addition, there is an excellent CPC this week in NEJM on AKI with COVID-19.

Check out the above updates and tweetorial by first author Jia Ng, MD

I want to share our new paper “Acute kidney injury in patients hospitalized with COVID-19”. @kidney_int @hofstrakidney @hofstramed @jam_hirsch @danielwross4 @purvasharma821 @hiteshhshah Richard Barnett @gracezra1 @sfishbane @kdjhaveri https://t.co/XzvPa1vKtk

[THREAD] pic.twitter.com/Rq24N6XrLR

— Jia Hwei Ng, MD, MSCE (@jiahweing) May 14, 2020

The real heroes of our renal fight against COVID-19- our dialysis nurses and technicians!

Concept Map: AKI with COVID-19

Here is a concept map of early causes of AKI- what others and we have seen in NY. As you can see, tubular cause most likely but other compartments can be involved as well.

Perspective: Innovation during COVID-19

As our health system and NY and parts of US keeping getting hit with COVID-19, it is hard not to notice innovation happening rapidly.  Our health system is now cared for over 9,000 COVID inpatients and several doctors and nurses redeployed to help in this mission. What an heroic effort.

What has evolved as a result of pressured needed timely treatments?

1. Shortage of ventilators- use of CPAP machines
2. Offices closed -fastest adaption of Tele medicine in history of mankind. 
3. Shortage of health care workers- All physicians doing a transitional prelim year model- just amazing to see
4. Shortage of CRRT machines- resolving to use of acute PD in certain areas, some using prolonged intermittent renal replacement therapy)
5. QTc monitoring on the screen- so impressed!
6. Fastest trial designs and rapid approvals of treatment is unprecedented for treatment of this deadly virus.
7. Several health startup companies have risen and are trying to use their ways to help combat this virus. See this article in health transformer.

But few things have happened and I have seen it here as well
1. Less red tape with administration- fasted hiring approval I have seen to get someone on board- perhaps we should NOT go back to the old ways
2. Better and more meaningful meetings to get the job done
3. More modesty and acceptance of our strengths and flaws

Perspective: COVID-19: from the Trenches in NY on leadership, clinical care, teaching and research

In the last 3 weeks, our health system has been in the forefront of the entire COVID-19 pandemic in NYC. What I have learnt about leadership, medicine and nephrology is exponential in the last 3 weeks.

As soon as the cases started to rise, our department of medicine chairman started daily calls via Meetings that combined all department chairs, health system experts and division chairs to align the mission at stake. I cannot say how important this call is on setting the stage and the mood as a leader. It is important that all are on the same page and doing this with charisma and ease without panic. I was truly amazed at that. 

In nephrology, we quickly adapted a similar strategy on updated our fellows, faculty, staff on a twice a week basis on similar issues in nephrology.

Some of the issues in Nephrology that the world should consider:

1.       Deploy as many nephrologists in the inpatient setting (your volume will be increasing significantly).  I have not seen volume of AKI at this fold in years in practice.

2.       Re-deploy your fellows/trainees mostly inpatient and few for outpatient dialysis units.

3.       Remember, the other place where you will need help is outpatient dialysis units- beef up your medical directors and get help to them early as they will be 100% occupied- making schedule changes, creating extra shifts for PUIs and extra units/shifts for COVID-19 patients.

4.       Before you deploy to internal medicine help, help might be needed within nephrology itself- as we are in the front line as ESRD docs, inpatient volume increasing and transplant docs as patients with COVID and organ transplants also increase.

5.       Increasing supplies early on and not waiting till you hit peak- ordering more CRRT machines, fluids, cartridges is going to be key.. don’t wait

6.       Back up nursing and making sure you have a good balance between HD and ICU nursing and not stressing both with either HD orders and or CRRT orders.

7.       Anticoagulation might be extremely important in CRRT or citrate protocol( if possible) as clotting is not uncommon in this disease.

8.       Creating a simple but important criteria for need for dialysis in really sick patients and value of RRT in such cases

9.       Implementing and orchestrating (with a division champion) on tele medicine outpatient visits. This can help you fight the COVID fight by keeping your CKD/transplant patients out of the hospital. This is a very critical and important piece.

10.   Making all conferences tele for now but still doing them- education should NOT stop as we are still in the process of teaching along with caring for patients.

11.   Deploying some research strength to learning about COVID in this critical time and sharing information as quickly as possible to the world to allow for ongoing coordinate care.

12.   Separate inpatient and outpatient rounding docs every 2 weeks ( not to mix them) and give the inpatient docs a break.

13.   We also implemented more on call weekend docs for renal help and in addition, added a tele attending on call to help de burden calls on weekends.

14.   Rotation of clerical staff in the office to limit the number of folks in the office ( minimize exposure helps)

15.   Implementing dialysis tele health also helps (but should not replace seeing our ESRD patients). This might be best for our PD and home HD patients.

16.   Can’t stress enough is constant communication—with colleagues, fellows, nurses, staff about any changes. It eases the anxiety and plans for a smoother over a bumpy ride of this long winded ride we are in.

17.   While are in forced implementation of certain tactics due to COVID, perhaps some good tactics should be adopted for long term patient care as we overcome this pandemic. 

18.   The most important part- checking in your nurses, faculty and fellows – creating a group on WhatsApp or any app to share fun pics, old jokes and fun times together as a division. We are all in this together.. Let’s get over this hump…

Perspective of a Nephrologist amidst COVID-19 crisis in New York 2020

Just a month ago, I was on call at North Shore University Hospital in Manhasset and covering a census of >50 patients. It was a great mix of cases from AL amyloidosis, Anca vasculitis, Anti GBM, cardio renal syndromes, check pt inhibitor induced AIN, and several onconephrology electrolyte disorders.  In addition, our center had also just done their first heart-kidney transplant recently and it was an amazing feeling.

Fast forward, a month later, I am on call again and I sense a  census >60 and over 80% of those cases are COVID-19+ with either AKI or ESRD.  What just happened here????

As the pandemic knocked the doors of NY, the hospital I have worked for 10 years now had turned into a different place. In the last 3 weeks, all surgeries were cancelled, all non elective admissions postponed... outpatient clinics slowing down.. and what do I see now..

I walk in and I can't recognize people. The make up and gel that people used to have is replaced by N95s and surgical masks. Nice suits,dresses all gone and replaced by scrubs and surgical gowns.

CT ICU, NS ICU, SICU, CCU and transplant ICU - are now all medical ICU beds.
ER is overflowing with COVID-19 patients.
ICU has vented patients from ages 31-83y of age, both males and females.
CRRT machines being deployed at almost every floor.
Surgical floors converted to medical COVID-19 floors. Only 4-5 floors remain as non COVID floors in the hospital...
Hallways are empty, cafe empty since no family is allowed....

This transformation -- just in 3 weeks.  What a change.. Shock is an understatement.
What is more clear was the fear and anxiety in the eyes of the providers. People I used to see always joking around, making Trump Jokes, and laughing and smiling -- you could now sense fear in their voice.

Fatigue was evident in the nurses and ICU docs... but they were not giving up.
Renal consultations came every hour and it was all COVID-19 intubated patient in AKI, needing CRRT.  It was pre renal, ATN, AIN, who knows-- we were just trying to save whoever we could...
The fellow and I scared to enter rooms, no time to even take a bathroom break and not sure how to even eat at the cafeteria.

Sadness, fear and anxiety was evident everywhere....1/3 of admitted COVID-19 patients end up in ICU, staying longer and longer stays ( 2 weeks) on a ventilator.. and what happens after that.. renal failure, cardiac failure.

But....what also was evident and most inspiring to me was...

Never before seen- working together of teams of residents and attendings ever imagined.
One of the covid-19 ICUS was headed by a surgical intensivists, vascular surgery attending, medicine residents, and pulmonary team helping out-- what amazing team work..
Then comes the NSICU, another converted COVID-19 unit- intensivists out of their comfort zone providing amazing medical ICU care to these COVID patients.
Finally, pediatric ICU docs coming to help the adult ICU patients- working hand in hand with pulmonary fellows, medical residents, neurology residents... amazing amazing!!

Kudos to the hospital management, CEO, CMOs, and department chairs to get this together in 2 weeks and creating this team work environment.
While the hospital is now a COVID-19 hospital and increasing number of ICU beds, everyone has stepped up outside their comfort zone and created history at our institution.

There are some wins-some patients coming extubated and many getting discharged.. While we may loose many, we are also saving many lives.. Kudos to our ER, hospital medicine and ICU staff and amazing nurses and health care providers...
Consults have become real, people are not calling "non needed' consults
Note writing has been minimized... and communication has improved.

While there is fear in everyone's eyes, we also sensed and felt a sense of pride to battle this war with our invisible enemy...

One of my Nephrology friends said it perfectly  "This is literally a battle zone which we are dealing with. Quite honestly, for the most part could exhilarating.  You are living history. Nothing has prepared us for this. Soak it in.... Hopefully, 40 years from now, you will be telling your grandkids how you served on the front lines of the great 2020 pandemic.  You may never again have the opportunity to be involved in something more meaningful again."

Topic Discussion: COVID-19 and hemodialysis patients

As we all learn more and more about COVID-19, the burning question in many nephrologists is the risk to patients on dialysis mainly in-center HD? While we all are developing guidelines of how to triage and place patients on in-center HD who have symptoms of COVID-19, what is their risk of severe infection vs. death from this virus compared to the general population?

So far, while we are still learning about the Italian, South Korean, Japanese experience, the only pre published data is from Wuhan, China dialysis units. Ma et al describe their experience and it is quite interesting what they found.

Brief summary of the study

1. It is a single HD unit epidemic course of infected patients compared to non infected and staff that were effected.
2. Of 230 HD patients, 37 were infected( 37%) and 2 medical staff of 33 staff members. During that time frame, the HD center had 7 deaths, 6 were COVID-19 positive patients. This made the mortality of 3%( higher than usual for that dialysis unit)
3. Presumed cause of death was hyperkalemia and cardiac events and not pulmonary cause
4. 62% were men, mean age 66 years.
5. 59% patients had bilateral CT scan involvement, 41% had unilateral findings
6. Serum levels of all cytokines measured( Il-4,6,10, TNF .etc) were lower levels compared to non HD patients with COVID-19
7. In their discussion, they do mention that the deaths were due to under-dialysis and hyperkalemia given the fear of contracting the virus-- interesting analysis.
8. Interestingly, none of the 37 patients in their center were admitted to the ICU due to severe PNA
9. The authors think that the HD patients don't mount a severe immune response and don't have that cytokine storm as seen in healthy adults leading to the "itis" leading to less organ damage.

This study is a start. More data from S.Korea, USA, Japan and Italy might help us in better information to decide on the care of the HD patient with COVID-19

Recently also, there is a case report published on HD patient treated successfully with anti virals in China in Kidney Medicine