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. 









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