Friday, November 27, 2020

2020: What a year for Nephrology

As we enter the end of 2020( finally), we are starting to see some hope for the vaccines as a lifeline as we enter the rising COVID-19 surge.  For nephrology, 2020 has been a positive and negative year. 

Let's start with the negatives:
1. Covid19 led to development of more AKI than we had imagined and several of those patients dying as a result. Very few survived the RRT-related AKI
2. Our dialysis patients had a tough battle leading to an increased mortality
3. Many transplant centers were on hold and several on the wait list had a high mortality and so did some of our transplant patients.
4. All conferences and meetings were virtual( taking away the networking opportunity for many)
5. All fellowship interviews went virtual( hard to assess candidates candidly)
6. Research ( non covid19) came to a halt and or was interrupted 

But there is a silver lining to the COVID19 pandemic for nephrology:

1. Increased data and outcomes research on AKI as a result of the pandemic
2. Rise of HOME dialysis ( which was dormant for years) came more to the forefront( including acute PD)
3. Rise of the Nephrologists as front line COVID19 warriors leading to perhaps more applications this year
4. SGLT2i studies infiltrating NEJM multiple times making a mark on diabetic and non diabetic kidney disease
5. Novel therapeutics in autoimmune renal diseases are on a rise
6. Virtual conferences allowed for more quicker and swifter transfer of knowledge ( and more attendance)
7. Collaboration on research rose super fast with trials such as STOP-COVID
8. Gender and Ethnic diversity was evident in Kidney week this year and kept it's strength in 2020
9. More incentives and compensations increases for nephrologists will reign in 2021
10. Increase interest in subspecialization in Nephrology 

Wednesday, October 21, 2020

Let's STOP-COVID

In March 2020, as deaths from COVID-19 surged across the world, we orchestrated the largest nationwide study of critically ill patients with COVID-19 assembled to date in the United States. This grassroots, unfunded project was made possible with the help of over 400 collaborators across the US, including research coordinators, medical students, residents, fellows, and attendings across a variety of specialties. Together, we gathered detailed, patient-level data from over 5,000 patients with COVID-19 admitted to ICUs at 68 sites. This was the start of STOP-COVID (Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19).

All data were painstakingly extracted by manual chart review and entered into a centralized online database. Here is a snapshot of a few of our recent studies.

 *In the first manuscript, we examined risk factors for 28-day mortality among 2215 critically ill patients. We found that 784 (35.4%) patients died within 28 days, with wide interhospital variation in both treatments (e.g., proning) and outcomes (e.g., death). Factors associated with death included older age, male sex, morbid obesity, coronary artery disease, cancer, acute organ dysfunction, and, notably, admission to a hospital with fewer ICU beds. Admission to a hospital with <50 versus ≥100 ICU beds associated with a >3-fold increased risk of death in multivariable analyses. Results are published in JAMA Internal Medicine

 



*We utilized a ‘target trial emulation’ approach to test whether early use of tocilizumab decreases mortality in critically ill patients with COVID-19. Of 3924 patients included in our analysis, 433 (11%) were treated with tocilizumab in the first 2 days of ICU admission, and these patients had a 30% lower risk of death compared with those not treated with tocilizumab. The beneficial effect of tocilizumab on survival was consistent across categories of age, sex, and illness severity. Notably, we found that patients with a more rapid disease trajectory, defined as three days or fewer from symptom onset to ICU admission, appeared to benefit from tocilizumab to a greater extent than patients with a slower disease trajectory(60% lower risk of death). Results are published in JAMA Internal Medicine with an accompanying editorial.

 



*We studied risk factors for acute kidney injury treated with renal replacement therapy (AKI-RRT) in 3099 patients. We identified several patient-level risk factors for AKI-RRT, including chronic kidney disease, male sex, non-White race, and higher D-dimer. Among patients who survived to hospital discharge, one in three remained RRT-dependent at discharge, and one in six remained RRT dependent 60 days after ICU admission. Results are published in JASN 


*We investigated the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and CPR in 5019 patients. We found that 14% of patients had in-hospital cardiac arrest, of whom 57% received CPR. Patients who had in-hospital cardiac arrest were older, had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of ICU beds compared with those who did not have in-hospital cardiac arrest. Cardiac arrest was associated with poor survival, with only 12% surviving to hospital discharge, and even fewer (only 7%) surviving to hospital discharge with no more than mildly impaired neurologic function. Results are published in BMJ 


*We examined the clinical course of critically ill patients with COVID-19 with and without pre-existing kidney disease. Dialysis patients had a shorter time from symptom onset to ICU admission compared with other groups, and were more likely to present with altered mental status on admission. Half the patients with CKD died within 28 days of ICU admission versus 35% of patients without CKD, with dialysis patients having the highest risk of death. Results are published in AJKD.

 


*In a propensity score matched analysis, we examined the association between solid organ transplant (SOT) status with death and other clinical outcomes. Receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were similar between SOT recipients and non-recipients, as was the risk of 28-day mortality. Results are published in AJT.

Data collected by the STOP-COVID collaborators has provided valuable insight into the risk factors, outcomes, and treatment strategies for critically ill patients with COVID-19. This is just the beginning… more to come as we analyze more data.

Shruti Gupta, MD, MPH
David E Leaf, MD, MMsc

---------------------------------------------------------

( Full list of collaborators obtained from JAMA Internal Medicine website) 

The Study of the Treatment and Outcomes in Critically Ill Patients With COVID-19 (STOP-COVID) investigators include the following: Carl P. Walther (site principal investigator [PI]) and Samaya J. Anumudu (Baylor College of Medicine); Justin Arunthamakun (site PI), Kathleen F. Kopecky, Gregory P. Milligan, Peter A. McCullough, and Thuy-Duyen Nguyen, (Baylor University Medical Center); Shahzad Shaefi (site PI), Megan L. Krajewski, Sidharth Shankar, Ameeka Pannu, and Juan D. Valencia (Beth Israel Deaconess Medical Center); Sushrut S. Waikar (site PI) and Zoe A. Kibbelaar (Boston Medical Center); Ambarish M. Athavale (site PI), Peter Hart, Shristi Upadhyay, and Ishaan Vohra (Cook County Health); Adam Green (site PI), Jean-Sebastien Rachoin, Christa A. Schorr, and Lisa Shea (Cooper University Health Care); Daniel L. Edmonston (site PI) and Christopher L. Mosher (Duke University Medical Center); Alexandre M. Shehata (site PI), Zaza Cohen, Valerie Allusson, Gabriela Bambrick-Santoyo, Noor ul aain Bhatti, Bijal Mehta, and Aquino Williams (Hackensack Meridian Health Mountainside Medical Center); Samantha K. Brenner (site PI), Patricia Walters, Ronaldo C. Go, and Keith M. Rose (Hackensack Meridian Health Hackensack University Medical Center); Miguel A. Hernán (Harvard T.H. Chan School of Public Health); Rebecca Lisk, Amy M. Zhou, and Ethan C. Kim (Harvard University); Lili Chan (site PI), Kusum S. Mathews (site PI), Steven G. Coca, Deena R. Altman, Aparna Saha, Howard Soh, Huei Hsun Wen, Sonali Bose, Emily A. Leven, Jing G. Wang, Gohar Mosoyan, Girish N. Nadkarni, Pattharawin Pattharanitima, and Emily J. Gallagher (Icahn School of Medicine at Mount Sinai); Allon N. Friedman (site PI), John Guirguis, Rajat Kapoor, Christopher Meshberger, and Katherine J. Kelly (Indiana University School of Medicine/Indiana University Health); Chirag R. Parikh (site PI), Brian T. Garibaldi, Celia P. Corona-Villalobos, Yumeng Wen, Steven Menez, Rubab F. Malik, Carmen Elena Cervantes, and Samir C. Gautam (Johns Hopkins Hospital); Mary C. Mallappallil (site PI), Jie Ouyang, Sabu John, Ernie Yap, Yohannes Melaku, Ibrahim Mohamed, Siddhartha Bajracharya, Isha Puri, Mariah Thaxton, Jyotsna Bhattacharya, John Wagner, and Leon Boudourakis (Kings County Hospital Center); H. Bryant Nguyen (site PI) and Afshin Ahoubim (Loma Linda University); Kianoush Kashani (site PI) and Shahrzad Tehranian (Mayo Clinic, Rochester); Leslie F. Thomas (site PI) and Dheeraj Reddy Sirganagari (Mayo Clinic, Arizona); Pramod K. Guru (site PI) (Mayo Clinic, Florida); Yan Zhou (site PI), Paul A. Bergl, Jesus Rodriguez, Jatan A. Shah, and Mrigank S. Gupta (Medical College of Wisconsin); Princy N. Kumar (site PI), Deepa G. Lazarous, and Seble G. Kassaye (MedStar Georgetown University Hospital); Michal L. Melamed (site PI), Tanya S. Johns, Ryan Mocerino, Kalyan Prudhvi, Denzel Zhu, Rebecca V. Levy, Yorg Azzi, Molly Fisher, Milagros Yunes, Kaltrina Sedaliu, Ladan Golestaneh, Maureen Brogan, Neelja Kumar, Michael Chang, and Jyotsana Thakkar (Montefiore Medical Center/Albert Einstein College of Medicine); Ritesh Raichoudhury (site PI), Akshay Athreya, and Mohamed Farag (New York-Presbyterian Queens Hospital); Edward J. Schenck (site PI), Soo Jung Cho, Maria Plataki, Sergio L. Alvarez-Mulett, Luis G. Gomez-Escobar, Di Pan, Stefi Lee, Jamuna Krishnan, and William Whalen (New York-Presbyterian/Weill Cornell Medical Center); David M. Charytan (site PI), Ashley Macina, Sobaata Chaudhry, Benjamin Wu, and Frank Modersitzki (New York University Langone Hospital); Anand Srivastava (site PI), Alexander S. Leidner, Carlos Martinez, Jacqueline M. Kruser, Richard G. Wunderink, and Alexander J. Hodakowski (Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine); Juan Carlos Q. Velez (site PI), Eboni G. Price-Haywood, Luis A. Matute-Trochez, Anna E. Hasty, and Muner M. B. Mohamed (Ochsner Medical Center); Rupali S. Avasare (site PI) and David Zonies (site PI) (Oregon Health and Science University Hospital); David E. Leaf (site PI), Shruti Gupta (site PI), Meghan E. Sise, Erik T. Newman, Samah Abu Omar, Kapil K. Pokharel, Shreyak Sharma, Harkarandeep Singh, Simon Correa, Tanveer Shaukat, Omer Kamal, Wei Wang, Heather Yang, Jeffery O. Boateng, Meghan Lee, Ian A. Strohbehn, Jiahua Li, and Ariel L. Mueller (Partners Healthcare, Brigham and Women’s Hospital, Brigham and Women’s Faulkner Hospital, Massachusetts General Hospital, and Newton Wellesley Hospital); Roberta E. Redfern (site PI), Nicholas S. Cairl, Gabriel Naimy, Abeer Abu-Saif, Danyell Hall, and Laura Bickley (ProMedica Health System); Chris Rowan (site PI) and Farah Madhani-Lovely (site PI) (Renown Health); Vasil Peev (site PI), Jochen Reiser, John J. Byun, Andrew Vissing, Esha M. Kapania, Zoe Post, Nilam P. Patel, and Joy-Marie Hermes (Rush University Medical Center); Anne K. Sutherland (site PI), Amee Patrawalla, Diana G. Finkel, Barbara A. Danek, Sowminya Arikapudi, Jeffrey M. Paer, Peter Cangialosi, and Mark Liotta (Rutgers/New Jersey Medical School); Jared Radbel (site PI), Sonika Puri, Jag Sunderram, Matthew T. Scharf, Ayesha Ahmed, Ilya Berim, and Jayanth S. Vatson (Rutgers/Robert Wood Johnson Medical School); Shuchi Anand (site PI), Joseph E. Levitt, and Pablo Garcia (Stanford Healthcare, Stanford University School of Medicine); Suzanne M. Boyle (site PI), Rui Song, and Ali Arif (Temple University Hospital); Jingjing Zhang (site PI), Sang Hoon Woo, Xiaoying Deng, Goni Katz-Greenberg, and Katharine Senter (Thomas Jefferson Health); Moh’d A. Sharshir (site PI) and Vadym V. Rusnak (Tulane Medical Center); Muhammad Imran Ali, Terri Peters, and Kathy Hughes (United Health Services Hospitals); Anip Bansal (site PI), Amber S. Podoll, Michel Chonchol, Sunita Sharma, and Ellen L. Burnham (University of Colorado Anschutz Medical Campus); Arash Rashidi (site PI) and Rana Hejal (University Hospitals Cleveland Medical Center); Eric Judd (site PI), Laura Latta, and Ashita Tolwani (University of Alabama-Birmingham Hospital); Timothy E. Albertson (site PI) and Jason Y. Adams (University of California, Davis, Medical Center); Steven Y. Chang (site PI) and Rebecca M. Beutler (Ronald Reagan-UCLA [University of California, Los Angeles] Medical Center); Carl E. Schulze (Santa Monica-UCLA Medical Center); Etienne Macedo (site PI) and Harin Rhee (University of California, San Diego, Medical Center); Kathleen D. Liu (site PI) and Vasantha K. Jotwani (University of California, San Francisco, Medical Center); Jay L. Koyner (site PI) (University of Chicago Medical Center); Chintan V. Shah (site PI) (University of Florida Health–Gainesville); Vishal Jaikaransingh (site PI) (University of Florida Health–Jacksonville); Stephanie M. Toth-Manikowski (site PI), Min J. Joo (site PI), and James P. Lash (University of Illinois Hospital and Health Sciences System); Javier A. Neyra (site PI) and Nourhan Chaaban (University of Kentucky Medical Center); Rajany Dy (site PI), Alfredo Iardino, Elizabeth H. Au, and Jill H. Sharma (University Medical Center of Southern Nevada); Marie Anne Sosa (site PI), Sabrina Taldone, Gabriel Contreras, David De La Zerda, Alessia Fornoni, and Hayley B. Gershengorn (University of Miami Health System); Salim S. Hayek (site PI), Pennelope Blakely, Hanna Berlin, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O’Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Abbas Bitar, Jeff Leya, John P. Donnelly, and Andrew J. Admon (University of Michigan); Jennifer E. Flythe (site PI), Matthew J. Tugman, and Emily H. Chang (University of North Carolina School of Medicine); Brent R. Brown (site PI) (University of Oklahoma Health Sciences Center); Amanda K. Leonberg-Yoo (site PI), Ryan C. Spiardi, Todd A. Miano, Meaghan S. Roche, and Charles R. Vasquez (University of Pennsylvania Health System); Amar D. Bansal (site PI), Natalie C. Ernecoff, Sanjana Kapoor, Siddharth Verma, and Huiwen Chen (University of Pittsburgh Medical Center); Csaba P. Kovesdy (site PI), Miklos Z. Molnar (site PI), and Ambreen Azhar (University of Tennessee Health Science Center and Memphis Veterans Affairs Medical Center/Methodist University Hospital); S. Susan Hedayati (site PI), Mridula V. Nadamuni, Shani Shastri, and Duwayne L. Willett (The University of Texas Southwestern Medical Center and Parkland Health and Hospital System); Samuel A. P. Short (University of Vermont Larner College of Medicine); Amanda D. Renaghan (site PI) and Kyle B. Enfield (University of Virginia Health System); Pavan K. Bhatraju (site PI) and A. Bilal Malik (University of Washington Medical Center); Matthew W. Semler (Vanderbilt University Medical Center); Anitha Vijayan (site PI), Christina Mariyam Joy, Tingting Li, Seth Goldberg, and Patricia F. Kao (Washington University in St. Louis/Barnes Jewish Hospital); Greg L. Schumaker (site PI) (Wellforce Health System, Lowell General Hospital); Nitender Goyal (site PI), Anthony J. Faugno, Greg L. Schumaker, Caroline M. Hsu, Asma Tariq, Leah Meyer, Ravi K. Kshirsagar, Aju Jose, and Daniel E. Weiner (Wellforce Health System, Tufts Medical Center); Marta Christov (site PI), Jennifer Griffiths, Sanjeev Gupta, and Aromma Kapoor (Westchester Medical Center); and Perry Wilson (site PI), Tanima Arora, and Ugochukwu Ugwuowo (Yale School of Medicine).

Sunday, October 18, 2020

Concept Map: Glomerular Diseases with Immunotherapy

 A recent systematic review discussed GNs cases seen with immune checkpoint inhibitors. This concept map( part of the paper) is displayed here.

https://www.kireports.org/article/S2468-0249(20)31640-5/fulltext



The above review was done before the listed two articles were published 

Even after addition of the above cases, vasculitis would still be the most common and podocytopathies following that. C3 GN would be the third most common. 



Detective Nephron: Next Venture

 

Check out the next venture of Detective Nephron in the Oct 2020 issue of Kidney News. 

https://www.kidneynews.org/kidney-news/fellows-corner/detective-nephron/detective-nephron-october-november-2020



Wednesday, September 23, 2020

Topic Discussion: Outcomes of AKI in COVID-19

 As COVID19 surged the NY area, March-May 2020 is when the AKI surge happened at most northeast hospitals. Initial reports from us and others showed that the incidence of AKI was high- close to 40%. 

At that time, almost 39% of patients were still admitted. Now there are 99% discharged allowing for complete outcome analysis. Here is our data on the outcomes of AKI in AJKD when all have been discharged. 













The aim of this study was to investigate in-hospital death and kidney outcomes among hospitalized patients with COVID-19 and AKI.  We reviewed health records of 9657 patients hospitalized with #COVID-19 between March1- April 27th, 2020, and followed up to the day of discharge/death. The data was from 13 hospitals. To investigate the impact of AKI on in-hospital death, we performed cox regression using AKI as a time-varying exposure and in-hospital death as the outcome.

In the cohort 40% of patients developed AKI (incidence rate of 38.3 per 1000 patient-days). Those who developed AKI had higher proportion with DM, heart disease, chronic kidney disease and had a more severe illness. The death rate was much higher in the AKI requiring dialysis( 6.4 times more) compared to AKI not requiring dialysis (3.4 times more) compared to no AKI. 

What matters to us is what happens to patients who survived? - how many had CKD, how many were sent on dialysis?  The big finding-- Among patients with AKI non-dialysis requiring who had survived, 74% had kidney recovery at the time of discharge. For patients with AKI-on dialysis and survived, 67% had kidney recovery at discharge. For the remainder who did not have kidney recovery, 91.7% remained on dialysis at the time of discharge.  Among those with AKI-on dialysis who survived, the presence of chronic kidney disease was the only independent risk factor associated with need for dialysis at discharge. 60 and 90 day outcomes are lacking and will be eventually useful. 

Regardless of need for dialysis or kidney recovery at discharge, hospitalized COVID-19 patients who experienced any form of AKI should be followed closely post-discharge to assess ongoing kidney function.  Our 13 hospital sites were all in metropolitan NY during the early part of the pandemic; is the major limitation.  

So in patients hospitalized with #COVID-19, those with AKI was associated with higher risk of death, particularly among those who needed dialysis. Most surviving patients with AKI had kidney recovery upon discharge.

Another recent study from a NY metro area showed similar findings in JASN.  Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 36% patients who had not recovered kidney function at discharge did so on posthospital follow-up.

Finally, a research letter in CJASN showed some outcomes data from yet another NY center. Patients with AKI had higher mortality than patients without AKI (40% versus 8%).  Among the patients with AKI, 48% recovered to their baseline kidney function. Among the 52% who did not recover to their baseline kidney function, 43 received dialysis, among which 34 were dialysis dependent and 26 died (60%), and 111 did not receive dialysis, among which 80 (72%) died.  



Sunday, September 20, 2020

Consult Rounds: Hyponatremia from Anti depressants

 As nephrologists we often get called on SIADH from medications. Anti depressants a class of agents that we do consider to cause hyponatremia. Which ones are more likely vs others has always been interesting to know? A study from Denmark has a detailed look into this matter. 

The odds of developing hyponatremia in one large study was the highest in clomipramine, followed by nortriptyline, citalopram, paroxetine, duloxetine, venlafaxine, sertraline and amitriptyline. It had the least odds of association with mirtazapine, mianserin and escitalopram. The development was highest in the first 2 weeks of starting treatment( with the highest incidence of hyponatremia in the first 2 weeks in citalopram and lowest in mianserin. 

So, SSRI had the most association, SNRIs had slightly lower and non adrenergic specific serotogenic antidepressants had the least association. 









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…



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