Topic Discussion: COVID and Kidneys- the biopsy experience

As we expand our understanding of COVID-19 related AKI, in the last few weeks, more studies are emerging on what might be the main kidney biopsy findings with COVID related AKI.
We have now established the incidence being around 30-40% in the US.

What is exactly going on in the kidney? Is the virus attacking the kidney or is the renal disease a consequence of "being sick" and or  "inflammatory state".

This figure from an article in JASN summarizes the potential way the SARS-Cov2 might be effecting the kidney



Two recent biopsy series from Columbia and Northwell Nephrology showed the variety of pathology reported in COVID-19



In addition, an autopsy series (specific) to the kidneys showed ATN only.  Finally, in KI, a series of anti GBM were reported in UK related to COVID-19

All recent papers added interesting few things to the ongoing literature.

1. ATN is by far the most common presentation for AKI( if not pre renal)- even in transplanted kidney. Pigment nephropathy from myoglobin or hemoglobin is rare. Vitamin C overdose induced oxalate nephropathy is rare.
2. Podocytopathies( MCD and cGN) are the most common glomerular findings
3. Other glomerular diseases are a varied amount( TMA, ANCA, Membranous GN, anti GBM)
4. The virus was not found in the kidney with immunohistochemistry in all 3 studies.

Does the kidney get infected?- time will tell.. data is mixed

10 Years of Nephrology Social Media

10 years and a few months ago, I wrote the first nephronpower post. It was simple and about a historical event in nephrology. My inspiration was the Late Nate Hellman from Renal Fellow Network. What has transpired since then is truly amazing for the field of Nephrology.

Few of us started blogging at National conferences, some of us tweeting like a storm. Finally, the academic community noticed this and soon ASN, NKF and all wanted tweets and blogs of their events. The first landmark paper summarizing some of this was in AJKD in 2011.

Following that, was the birth of AJKDblog or then called eAJKD. This allowed for more collaboration and more social media to flourish in nephrology and leading to the ultimate- Nephmadness ( mastermind game by the Topf Sparks team) in 2013.

After 2013, nothing was stopping nephrology to take the lead in social media.
From NephJC to tweetorials to whatsApp to creation of NSMC-- happening so fast and furious!

Nephrologists quickly stormed the social media world to lead and show how it's done!
In NDT is a brief tutorial for how to be social media savvy.

Academic journals- AJKDBlog
Journal club- NephJC
Well ironed blogs- Renal Fellow Network
Online Successfully run interactive game for over 7 years- Nephmadness
Online academy of educators for future social media wannabees- NSMC
Every fellowship program trying to have a twitter account and social media presence.

What else can you ask for?
All this is summarized in recent issue in Seminars in Nephrology by guest editor Joel Topf and includes all various aspects of the social media
Here is a nice tweetorial by Chan on the entire issue

Seminars in Nephrology has an entire issue devoted to social media in the discipline of nephrology.

The mastermind @kidney_boy highlights the contents here:https://t.co/1XhYQLpEyS pic.twitter.com/OQs757SxmI

— Teresa Chan (@TChanMD) June 20, 2020

Introduction to social media
Tweet or not to tweet
Twitter based journal clubs
Tweetorials
Podcasting
Newsletters
Visual abstracts
Slack
Semi-private Apps ( WhatsApp)
FOAM quality 
NSMC

Congratulation to the nephrology community to being leaders in education via social media in medicine!

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…