Topic Discussion: Use of immunotherapy in ESRD patients

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

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

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

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

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

(Our fearless fellows during COVID-19)

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

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

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

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

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

                                           (Our LIJ renal team with Dept of Medicine Chair)


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

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

                                            ( Our North Shore Inpatient rounding teams)

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

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

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

                                            (Our North Shore Inpatient rounding teams)

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

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

                                               (Our chief and associate chief in action)

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

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

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

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

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

[THREAD] pic.twitter.com/Rq24N6XrLR

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

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