The CKD Insider - April & May Recap

Welcome to the Chronic Kidney Disease Insider Newsletter. If you are living with chronic kidney disease (CKD) on dialysis, have had a kidney transplant or are helping care for someone who is, this newsletter was created for you! The content is meant to keep you and/or a family member up to date on the latest information to help you manage your health now and in the near future in consultation with your physician.

In this month’s CKD Insider : COVID-19 & vaccine immune responses, kidney transplant rejection testing, FDA approval for medicine for CKD, and the Fun Tip of the Day!

Note: Both NKF and ASN recommend getting vaccinated. Any level of protection a SARS-CoV-2 vaccine can provide is better than no protection against COVID-19.

SARS-CoV-2 Vaccine Immune Response

Research evaluating the immune response following SARS-CoV-2 vaccination for people with chronic kidney disease, on dialysis, or living with a kidney transplant and discussions on how to improve protection against COVID-19 are actively be pursued globally. A few of these studies are highlighted below along with NKF recommendations.

For people on hemodialysis:
Recent publications found that a substantial antibody immune response was seen in people undergoing hemodialysis following both SARS-CoV-2 mRNA vaccine doses, however the response was lower than people without CKD.

What this means for you: Per NKF continue to mask and practice physical distancing after you are fully vaccinated.

References: Humoral response to the Pfizer BNT162b2 vaccine in patients undergoing maintenance hemodialysis, Antibody Response to mRNA-1273 SARS-CoV-2 Vaccine in Hemodialysis Patients with and without Prior COVID-19, Humoral response of mRNA-1273 SARS-CoV-2 vaccine in peritoneal dialysis patients

For kidney transplant recipients: 2 recent studies show impaired antibody responses:
1) Johns Hopkins University School of Medicine in Maryland recently published their follow up study to the original publication looking at the antibody response of organ transplant recipients after the first dose of SARS-CoV-2 mRNA vaccines. This follow up publication looks at the antibody response of 658 organ transplant recipients who had not been diagnosed with COVID-19 prior to their vaccination and who had both doses of the SARS-CoV-2 mRNA vaccines. The breakdown is below for your reference.

658 organ transplant recipients (322 people with kidney transplants were included)

54% of transplant recipients overall had an in increase in antibody levels, however they were still well below what is typically seen in people with healthy immune systems per the authors.
Median sampling days after dose 1 was 21 days and after dose 2 was 29 days

15% (98 people) had a measurable response after both dose 1 and dose 2
39% (259 people) had no response after dose 1, but had a response after dose 2
46% (301 people) had no response after dose 1 or dose 2

Breaking this data down further : poor antibody response associates with anti-metabolite immunosuppression therapy.
473 of the participants received antimetabolite therapy (mycophenolate mofetil,mycophenolic acid, or azathioprine):

43% had an antibody response (combined response data from below: 8% + 35%)

8% (38 people) had an antibody response after both dose 1 and dose 2
35% (167 people) had no antibody after dose 1, but had a response after dose 2
57% (268 people) had no antibody response after dose 1 or dose 2

185 of the participants did not receive antimetabolites:

82% had an antibody response (combined response data from below: 32% + 50%)

32% (60 people) had an antibody response after both dose 1 and dose 2
50% (92 people) had no antibody response after dose 1 but had a response after dose 2
18% (33 people) had no antibody response after dose 1 or dose 2

2) Columbia University Medical Center in New York did a smaller kidney transplant focused study looking at the response of 28 kidney transplant recipients following administration of 2 doses of SARS-CoV-2 mRNA vaccines.

The antibody response was not that the same as what was seen in the SARS-CoV-2 vaccines clinical trials, which excluded immunocompromised people.
People taking belatacept and mycophenolate had the least antibody response, which is consistent with data from previous influenza studies.
The authors state they are unable to draw conclusions about vaccine efficacy at this time due to multiple reasons including the small study size, not encompassing all vaccines available globally, and not including evaluation of other immune mechanisms in addition to antibodies (there is ongoing research in the global research community looking at other immune mechanisms).

References: Antibody Response to 2-Dose SARS-CoV-2 mRNA Vaccine Series in Solid Organ Transplant Recipients, Postvaccine Anti–SARS-CoV-2 Spike Protein Antibody Development in Kidney Transplant Recipients

What this means for you:

Per the authors of these studies and the NKF - Continue practicing strict COVID-19 safety precautions after vaccination and follow the CDC COVID-19 safety guidelines.
Bottom line: At this time it is safer to be cautious and act as though you have not been vaccinated and take the appropriate precautions including practicing physically distancing and continuing to wear a mask. New studies will be completed and new treatment regimens will be evaluated for use from these ongoing studies - so hold on awhile longer!

Advocacy Alert

Help support living kidney donors
One third of all kidney transplants are from living kidney donors. These same people who are providing a precious gift to the recipient often have challenges with life insurance benefits, they can either be rejected or are offered higher premiums because of their status as an organ donor.

The NKF is urging congress to enact the living donor protection act Living Donor Protection Act (S. 377/H.R. 1255) across all the states in the United States. You can join this movement by signing up here http://advocacy.kidney.org/ldpa/.

Test to Predict Kidney Transplant Rejection in Adults Works for Children

What it is: There are multiple test types to determine if a transplanted kidney is going to be rejected. One test method uses next generation sequencing to determine the amount of the transplant donor’s DNA in the blood of the recipient. This donor–derived cell free DNA (dd-cfDNA) test has been used in adults to get an earlier indication for kidney rejection than common kidney function tests such as serum creatinine. A recent study looking at 67 pediatric kidney transplant recipients found that AlloSure® dd-cfDNA test was “highly predictive of histological rejection and superior to other indicators such as graft dysfunction or antibody positivity alone”, meaning this test was also useful to nephrologists when evaluating if their pediatric transplant recipients kidney is being rejected.

What this means for you: If you have a child in your life that has a kidney transplant, consult with your nephrologist to determine if this test will be useful for them to detect kidney rejection. The earlier kidney rejection can be detected the more options your nephrologist will have to help preserve the kidneys function for as long as possible.

Reference: Donor-derived cell-free DNA (dd-cfDNA) for detection of allograft rejection in pediatric kidney transplants, Cedars-Sinai Pioneers Successful Pediatric Use of Test Developed for Adults

NY State Department of Health has approved 2 new non- invasive kidney rejection tests

What it is: Eurofins company has received NYS Clinical Laboratory Evaluation Program (CLEP) approval for two kidney rejection tests. The 1st test, Viracor TRAC® (Transplant Allograft Rejection Check) uses the same dd-cfDNA method described above. The 2nd test is the TruGraf® Blood Gene Expression Test which uses DNA microarray technology to measure changes in the expression of genes in the blood as an indicator of early rejection.

What this means for you: With NY CLEP approval, both of these tests are now available to patients in New York and in all 50 states. Clinical laboratories that test patient samples originating in NY must be approved by CLEP to ensure test accuracy and reliability for the state’s residents. Check with your nephrologist to determine if these tests would be a useful tool when evaluating the health of your transplanted kidney.

Outdoor Activities

Are you hearing about how businesses are opening up to larger groups of vaccinated people and wishing you could join the fun?

Here are some ideas that let you still adhere to COVID-19 safety precautions and feel as if you are at a larger public event!

Check these out in your local area:

1. Drive in or lawn chair movie theaters - If there aren't any in your area create your own night at the movies in your backyard or a friends backyard.

2. Outdoor music concerts - If nothing is available in your area get some musically inclined friends or their kids together to do an outdoor musical jam session at someone's house.

3. Outdoor sports games - Baseball, football or soccer minor league & even high school games can be just as entertaining as watching a professional game in person and depending on where you are can continue throughout the year. Go check out a game and be a part of the crowd from a distance.

What it is: The U.S. Food and Drug Administration approved AstraZeneca’s Farxiga (dapagliflozin) oral tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death and hospitalization for heart failure in adults with chronic kidney disease who are at risk of disease progression.

What this means for you: This treatment is another option to help slow progression of kidney function decline. Speak to your nephrologist and learn if this treatment can work for you.

Study details: FDA based its decision on a multicenter, double-blind study (n=4,304 patients), which evaluated the efficacy of Farxiga to improve kidney outcomes and reduce cardiovascular death in patients with chronic kidney disease. This new approval in chronic kidney disease was based on results of the DAPA-CKD trial that was stopped early in March 2020 due to efficacy of the treatment.

FDA notice regarding other CKD groups: “Farxiga was not studied, nor is expected to be effective, in treating chronic kidney disease among patients with autosomal dominant or recessive polycystic (characterized by multiple cysts) kidney disease or among patients who require or have recently used immunosuppressive therapy to treat kidney disease. Patients should not use Farxiga if they have a history of serious hypersensitivity reactions to the medication or if they are on dialysis treatment.” While Farxiga was originally approved in 2014 to improve glycemic control in adults with type 2 diabetes in addition to diet and exercise, the FDA notes that “Serious, life-threatening cases of Fournier’s Gangrene have occurred in patients with diabetes taking Farxiga. Patients should consider a lower dose of insulin or insulin secretagogue to reduce the risk of hypoglycemia (low blood sugar) if they are also taking Farxiga.”.

Reference: FDA Approves Treatment for Chronic Kidney Disease. Approval is First to Cover Many Causes of Disease