Tuesday, September 1, 2020

Topic Discussion: Gut Microbiota and UTIs

 


A Gut Microbiota – Urinary Tract Infection Connection

It is presumed that gut bacteria are the source for urinary tract infection, but is there any proof? If so, could changing the gut microbiota impact urinary tract infection?

Lee et al. evaluated this premise in a cohort of 168 kidney transplant recipients and profiled the gut microbiota serially using 16S rRNA deep sequencing. They reported that having higher gut abundance of E. coli was a risk factor for development of E. coli. They further performed strain analysis on matched fecal-urine specimens and found that the E. coli in the urine most closely resemble the E. coli in the gut from the same patients, supporting a gut origin of UTIs .

A follow up analysis identified that the gut abundances of two commensal bacteria, Faecalibacterium and Romboutsia, are associated with a decreased risk for UTIs

The data suggest the possibility that manipulation of the gut microbiota could alter the balance of commensal bacteria and pathogenic bacteria and could decrease the risk of UTIs, especially in patients with recurrent UTIs. Indeed, there is some recent evidence in case reports. In a case series by Tariq et al., patients with recurrent UTIs and recurrent C. difficile infections underwent fecal microbial transplantation for recurrent C. difficile infections and had a significant decrease in the number of UTIs after fecal microbial transplantation.

Whether gut microbial-based therapies can break the cycle of recurrent UTIs is still not known. Nevertheless, these therapies could be a novel approach to treating this common problem.


Image credit: http://www.sci-news.com/biology/gut-microbiota-manipulate-our-minds-05956.html

Thursday, August 20, 2020

Topic Discussion: ESRD patients and COVID-19


Kidneys And Covid-19: Renal Manifestations Of The Novel Coronavirus

While we saw several rising cases of AKI associated with COVID-19, the ESKD population was also vulnerable to this virus. With COVID-19, we didn't know if we would see worsening effects on ESRD or beneficial ( given a not so robust immune system in ESRD).  But the proximity and being in a closed dialysis unit did put most of them at risk. 

Studies from China and Europe on ESKD patients with COVID-19 were limited to small numbers and single centers. One of the first studies from US from CUMC was limited by less then 100 patients as well. It did show poor outcomes of 59 patients where 31% had died.


A Study from UK did discuss the concerns for an urban dialysis center ( on risk of hospitalizations). Of 1530 patients (median age 66 years; 58.2% men) receiving dialysis, 300 (19.6%) developed COVID-19 infection, creating a large demand for isolated outpatient dialysis and inpatient beds. An analysis that included 1219 patients attending satellite dialysis clinics found that older age was a risk factor for infection. COVID-19 infection was substantially more likely to occur among patients on in-center dialysis compared with those dialyzing at home. 

A study from the Bronx in NY also showed poor outcomes for hospitalized ESKD patients. Elevated inflammatory markers were associated with in hospital death.

Another UK study also found a high prevalence of seropositivity in the outpatient dialysis units. 

Alberici et al.describe their clinical experience with MHD patients cared for at 4 outpatient dialysis facilities that are part of the Brescia Renal COVID Task Force. In a period of 1 month, viral positivity was detected in 94 of their 643 ESRD HD patients (15%). Important findings in the study were the mild form of symptomatology at presentation, the high rate of overall mortality (29%), and emergence of usual risk factors for mortality and acute respiratory distress syndrome in SARS-CoV-2–positive HD patients. In addition, although certain patients were deemed more stable and were managed in the outpatient facility, 3 of those subsequently died, and a substantial portion had significant worsening of their symptoms.

Goicoechea et al. describe the clinical course and outcomes of 36 patients from 2 dialysis facilities caring for 282 patients that were admitted to a tertiary hospital in Madrid based on positive reverse transcription polymerase chain reaction for SARS-CoV-2. They report a mortality rate of 30.5%, and 33% of their patients required mechanical ventilation. 


At our health system of over 23 hospitals in NY, we decided to compare the outcomes of ESKD patients to non ESKD patients. The data was from 13 hospitals and our final cohort had 419 (4%) with ESKD and 10,063 (96%) without ESKD.This is the largest study to date.

What did we find:( similar tweetorial by first author Jia Ng)


1. Patients with ESKD were older, had a greater percentage self-identified as Black, and more comorbid conditions.

2. Patients with ESKD had a higher rate of in-hospital death than those without (31.7% vs 25.4%), odds ratio 1.38, 95% confidence interval 1.12 - 1.70). This increase rate remained after adjusting for demographic and comorbid conditions (adjusted odds ratio 1.37, 1.09 - 1.73).

3. Patients with ESKD had similar rates of mechanical ventilation as those without ESKD (89 [21.2%] vs 2076 [20.6%]). There was no difference in the odds of mechanical ventilation between the groups.

4. The odds of length of stay of seven or more days was higher in the group with compared to the group without ESKD in both the crude (1.62, 95%CI 1.27 - 2.06) and in the adjusted analysis (1.57, 95% 1.22 - 2.02)

5. We conducted stratified analyses to investigate the risk factors of death in the subgroups of ESKD and the non-ESKD separately, with the hypothesis that the risk factors of death and the magnitude of risk factors would differ between the two groups.

6. For patients without ESKD, the independent risk factors for in-hospital death increased age, male sex, cardiovascular disease, cancer, requiring ventilation, requiring vasoactive meds, high blood urea nitrogen, low albumin, high CRP and high ferritin.

7. The diagnosis of hypertension and use of an ACE inhibitor or ARB were associated with a lower risk of in-hospital death in the non-ESKD group.

8. Among patients with ESKD, independent risk factors for in-hospital death were increased age, requiring ventilation and lymphopenia, elevated BUN and high serum ferritin. Black race was associated with a significantly lower risk of death among patients with ESKD.

9. The protective effect of HTN in the non-EKSD group, and the protective effect of Black race in the ESKD group defy easy explanation. Perhaps APOL1 has some protective cardiac effect?

10. This is a large cohort of hospitalized patients with #COVID-19 comparing ESKD and non-ESKD in a diverse patient population. We had prespecified operational definitions for exposures, covariates and outcomes, as well as rigorous adjudication by two independent reviewers for ESKD exposure.

11. What limitations do we have?--Despite the larger size of this study compared to other reports, the ESKD sample may still have been relatively underpowered to find other statistically significant risk factors in mortality. Also there was inability to adjust for remdesivir and dexamethasone. As the evidence of these 2 drugs came after the surge of #COVID-19 cases in our health system, only a small proportion of patients received these drugs.

12. We had 11 PD patients in our admitted cohort. This was also published in a special report as well. Of 419 hospitalized patients with ESKD, 11 were on chronic PD therapy (2.6%). Among those 11, 3 patients required mechanical ventilation, 2 of whom died. Of the entire cohort, 9 of the 11 patients (82%) were discharged alive. While fever was a common presentation, more than half of our patients also presented with diarrhea. Interestingly, 3 patients were diagnosed with culture-negative peritonitis during their hospitalization. Seven patients reported positive SARS-CoV-2 exposure from a member of their household.

In conclusion, among patients hospitalized with COVID-19, those with ESKD had a higher rate of in-hospital death compared to those without ESKD. 

Two recent studies also show the outpatient HD infection and admission rates. A study published in AJKD from Canada showed from universal screening, 4.6% were infected. 


Another French study in KI showed a low incidence of infection of 3.3% in a large >40,000 dialysis patients. Older age, low albumin, and cardiac disease were risk factors for mortality. 


Taken together, the results suggest both a need for further research and the continued need for careful infection control procedures in the ESKD population at risk for #COVID-19.

Wednesday, August 5, 2020

Sunday, August 2, 2020

Topic Discussion: Pyelonephritis but no Urinary Tract Infection?

Pyelonephritis is defined as neutrophilic infiltration within the interstitium suggestive of a bacterial cause of urinary tract infection that might have migrated to the kidney. It rarely evolves into an abscess.

Can this exist without any signs of an urinary track infection? 
A study published in NDT looked prospectively of over 200 cases of acute pyelonephritis. 
What did they find?

Urinary culture was only positive in 31% of patients and blood cultures in 21%
92% did have CT findings of pyelonephritis. 
No differences were noted in patients with positive or negative CT findings in terms of fevers, and wbc counts, pyuria, urine cultures and symptoms. 

Why the negative urinalysis and urine culture? 

The low frequency of positive urine culture may be explained by previous antibiotic treatment, either self-prescribed or prescribed by the general practitioner, and by the possibility that infection was confined to the renal parenchyma. Could reflux disease explain some findings?While the association between acute pyelonephritis  and reflux has been extensively studied in children, the literature does not indicate when reflux must be searched in adults. The authors performed retrograde urethrocystography in the case of recurrent acute pyelonephritis or in the presence of urinary cavities dilation or urinary tract abnormalities: they found reflux in 20.9% of patients. 

In other words, the absence of infected urine does not rule out the diagnosis of acute pyelonephritis in common clinical practice. Renal abscesses are frequent and need to be looked for. Hence, it seems advisable to systematically perform CT or MRI, which have greater sensitivity than ultrasound in detecting them.

Sunday, July 19, 2020

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



Sunday, June 21, 2020

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

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!

Saturday, May 16, 2020

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. 

Thursday, May 14, 2020

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

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




Saturday, April 18, 2020

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.


Wednesday, April 15, 2020

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



Tuesday, April 7, 2020

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…



Sunday, March 29, 2020

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."


Wednesday, March 11, 2020

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

Wednesday, March 4, 2020

Topic Discussion: COVID-19 and the Kidney

Coronavirus disease 2019 (COVID-19) causes a severe acute respiratory syndrome. Similar to SARS outbreak, this virus has caused the 2019-2020 outbreak. It presents with a dry cough, fever, running nose, fatigue and shortness of breath. The elderly, hx of pulmonary disease, immunocompromised are at risk. Mortality rate is around 2-3% from ongoing outbreaks. 

How does this virus affect the Kidney. First and foremost, what is the data on transmission via dialysis units and infection in dialysis patients. Wuhan, China was where the outbreak occurred and started. In a single center study under open access review, 37 cases ( 16%) of HD patients were infected. 7 HD patients died and 6 had COVID-19 during this epidemic. The precaution measures taken by HD units prevented further cases. For some unclear reason, while HD patients were more likely to get this infection, the cases were milder than non HD counterparts. 


Here is the ASN suggestions for HD units for COVID-19 screening and precautions.


What about AKI? Is it common?  Again from Wuhan, in the month of the major outbreak in China, < 20 patients showed mild elevations in BUN and crt and trace albuminuria. 5 patients required CRRT. 
All patients that had CKD after this survived. Moreover, SARS-CoV-2 RNA in urine sediments was positive only in 3 patients from 48 cases without renal illness before, and one patient had a positive for SARS-CoV-2  from 5 cases with CKD. Interpretation Acute renal impairment was uncommon in COVID-19. SARS-CoV-2 infection does not significantly cause obvious acute renal injury, or aggravate CKD in the COVID-19 patients.

Interestingly, another center reported a different finding.  A large tertiary center in China studied 710 consecutive COVID19 patients, 89 (12.3%) of whom died in hospital. On admission, 44% of patients have proteinuria hematuria and 26.9% have hematuria, and the prevalence of elevated serum creatinine and blood urea nitrogen were 15.5% and 14.1% respectively. During the study period, AKI occurred in 3.2% patients. Kaplan-Meier analysis demonstrated that patients with kidney impairment have higher risk for in-hospital death. Cox proportional hazard regression confirmed that elevated serum creatinine, elevated urea nitrogen, AKI, proteinuria and hematuria was an independent risk factor for in-hospital death after adjusting for age, sex, disease severity, leukocyte count and lymphocyte count. Conclusion: The prevalence of kidney impairment (hematuria, proteinuria and kidney dysfunction) in hospitalized COVID-19 patients was high. After adjustment for confounders, kidney impairment indicators were associated with higher risk of in-hospital death. This was in strike contrast to the prior study.

Finally, hypokalemia was a common electrolyte finding in these patients. One would think GI cause as the cause, but GI symptoms were not associated with hypokalemia among 108 hypokalemia patients. Body temperature, CK, CK-MB, LDH, and CRP were significantly associated with the severity of hypokalemia. 93% of severe and critically ill patients had hypokalemia which was most common among elevated CK, CK-MB, LDH, and CRP. Urine K+ loss was the primary cause of hypokalemia.

Saturday, February 29, 2020

Nephrology Learning Bytes

A pathology report says in the IF section: LINEAR IgG staining
Usually the classic disease that is associated with that is

1) Anti GBM disease
But 2 other disorders can also have such staining

2) Fibrillary GN
3) Diabetic Nephropathy

Path image courtesy: Utah webpath

Sunday, February 2, 2020

Gender equality for invited speakers in Nephrology, comparing to other fields in medicine.

How does Nephrology do compared to other fields in Medicine in terms of female representation at academic conferences?

Here is a breakdown from articles all published in the last 2 years in medicine/surgery

In general medicine vs surgery,  in one study 181 conferences with 701 individual meetings were analyzed, including 100 medical and 81 surgical specialty conferences. The proportion of women ranged from 0% to 82.6% of all speakers. The mean (SD) proportion of female conference speakers for all meetings analyzed significantly increased from 24.6% (14.6%) for 40 meetings in 2007 to 34.1% (15.1%) for 181 meetings in 2017 (P < .001). The mean proportion of female speakers at medical specialty conferences was 9.8% higher (SE, 1.9%; P < .001) than the mean proportion of female speakers at surgical specialty conferences for all years analyzed. 

In dermatology, women spoke less than men at their main conferences. 
In Anesthesiology, when studied in Canada, the representation of women speakers at the their annual meeting was similar to the representation of women in the anesthesiology workforce in Canada over the study period. Gender representation varied widely by subspecialty symposia, subject area, and women were absent from nearly half of all symposia at the annual meetings.
In General Surgery, women remain in the minority of panelists and moderators at their main meetings, and approximately 1 in 5 panels are composed entirely of men. 
In Neurology, at Stroke conferences, women are less likely to be invited speakers.

In colo-rectal conferences, program representation of women was similar to meeting demographics, although with low numbers in some topics. An imbalance in the formality of speaker introductions between genders was observed. This introduction concern was also raised recently at ASCO(Oncology meetings)

Interestingly, at the Critical care conferences, Over the 7 years, Society of Critical Care Medicine had the highest representation of female (27% overall) and nursing/allied health professional (16-25%) speakers; notably, male physicians substantially outnumbered female physicians in all years (62-70% vs 10-19%, respectively)

In our analysis recently published in CJASN time series analyses showed that the proportion of women moderators increased significantly by 3.5% per year (p=0.009, CI 1.2% - 5.9 %), and women speakers increased by 2.3% per year (p=0.001, CI 1.3% - 3.3%). This is impressive and kudos to nephrology leadership and association. Comparing to other specialities outside of internal medicine and within internal medicine( nephrology clearly is leading the way in terms of gender equality in invited speakers are conferences). 


Tuesday, January 28, 2020

Concept map: Copeptin in Natremias



The above figure summarizes the best data on use of serum copeptin level for diagnosis of diabetes inspidus and primary polydipsia. Copeptin derives from the precursor protein of AVP and has been correlated well with AVP production

What about in cases of increased ADH- such as SIADH? Data on that is poor and only one large study of >200+ patients showed that in hypovolemic hyponatremia ( appropriate ADH), the copeptin levels were >84pmol/L ( spec 90%, sens 23%) and SIADH fell in the 10-30pmol/L categories( not helping much) and hypervolemic and diuretic induced fell in 30-65pmol/L category. Use of this test is currently not recommended in diagnosis of increased AVP production disorders. 

Finally in patients with nephrogenic syndrome of inappropriate anti diuresis, copeptin levels were are low or suppressed. 

This article is an excellent summary of the use of copeptin in Na related disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850413/ 


Monday, January 20, 2020

Topic Discussion: Hypertension and TMA- chicken or the egg?

A recent discussion on twitter and ASN Communities has sparked this age old battle if HTN related TMA exists? Some believe that TMA is the initial insult and that leads to endothelial damage and HTN is a symptom and not the disease. Some believe that HTN is the start - leading to sheer stress and endothelial damage and in severe cases-- TMA

Check out the amazing twitter discussion by TMA experts on this topic.
What i found was this amazing image
Image
As one can see in this image- with some data existing on this - that malignant HTN can lead to endothelial dysfunction and some complement activation but not as severe as aHUS.

So if HTN does cause TMA, how does one distinguish that from a complement mediated TMA or aHUS? What if we are missing a mutation or an antibody that we haven't discovered.

1) Kidney biopsy cannot distinguish HTN induced TMA from complement mediated TMA 2) C3 being low is more valuable for an over active complement cascade compared to C5b-9 as even HTN can cause that to be elevated
3)) Doing a fundus exam can help significantly- there is no value in genetic testing in grade 3/4 retinopathy and especially with DBP>130mm Hg 4) No value in genetic testing in those that have a good response to bp control and eventually stabilized kidney function.
5) Ongoing TMA despite bp control and recovering of renal function- likely is then not HTN mediated and additional complement testing should be done.

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