Kim Zuber, DNP

Jane Davis, DNP (left) and Kim Zuber, PA-C (right)
Credit: Self

Atrial fibrillation (AF) is linked to an increase in embolic strokes and thus most patients with AF will be prescribed anticoagulants to decrease this incidence.

AF is frequent in chronic kidney disease (CKD) with estimates ranging from 16-21% in non-dialysis patient and up to 40% in dialysis patients.1 AF is associated with both worse cardiac and kidney outcomes with an increased risk of CKD progression.

 The incidence of stroke in End Stage Kidney Disease (ESRD) is 7-9 times greater than in the general population and 3-fold more deadly.

For many years, warfarin was the drug of choice to decrease strokes in all populations but serum monitoring requirements, diet restrictions and narrow therapeutic window led to multiple complications. With the introduction of the direct oral anticoagulant (DOACs) medications, the complication rate in AF was significantly decreased.

As is true for most drug trials, patients with severe CKD (defined as an eGFR 

25 ml/min) were excluded from the DOAC trials.

 This is not unexpected; kidney patients have multiple comorbidities and are treated with multiple medications.

These comorbidities and medications add a level of complexity to the evaluation of adverse events during a drug trial. Yet, for a population where close to half of the population has AF, we do not have answers about the use of DOACs.

As there is no guidance from the pivotal DOAC trials for the CKD and ESRD patients, the kidney community has undertaken the collection of data from real world use of DOACs. We know that acute kidney injury (AKI) is significantly lower with the use of DOACs vs warfarin.

This is true for all stages of CKD, even in the elderly.

Using a meta-analysis approach, we have seen that DOACs have a better safety and effectiveness profile than warfarin.

 For this reason, the Kidney Disease Improving Global Outcomes (KDIGO) expert workgroup has developed recommendations for use of DOACs in CKD.

Adapted from KDIGO Controversies Conference

Legend: KDIGO-Kidney Disease Improving Global Outcomes, SCr-serum creatinine, eGFR-estimated glomerular filtration rate, bid-twice a day, qd-once a day. 

Yet, there is still a population that KDIGO recommendations did not address: the ESRD patient.

In the kidney failure patient, the incidence of AF is 40% and the stroke and sudden cardiac death are common.

 While cardiology defers to nephrology when treating ESRD, nephrology is divided on optimal treatment for this population. Most trials are retrospective and observational. However, recently randomized, controlled trials have been conducted.

With the most recent trial data available, the consensus is that warfarin is the most dangerous for this population whether it is used for AF prophylaxis or treatment for recurrent thromboembolism.

 Warfarin increases the incidence of bleeding without decreasing mortality. Two other large trials looking at DOAC vs warfarin both showed a better safety profile for apixaban but there were significant episodes of bleeding in the dialysis population.

 For this reason, the recently closed preliminary trial of three separate trial arms, which examine apixaban, warfarin, and no treatment, respectively, is being closely watched.

This Canadian/Australian trial included 151 participants and is a pilot to evaluate if we should 

 be treating the dialysis population with anticoagulants. The trial was completed in late December 2022. Results are pending.

If, as expected, the no treatment arm has a similar outcome profile with less bleeding complications, we will have to reassess our mantra of 

 while we stop treating the AF patient on dialysis with anticoagulants. A definite relearn for all of us.

Wanner C, Herzog CA, Turakhia MP; Conference Steering Committee. Chronic kidney disease and arrhythmias: highlights from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. 

Bobot M, Suissa L, Hak JF, et al. Kidney disease and stroke: epidemiology and potential mechanisms of susceptibility. 

Garlo KG, Steele DJR, Nigwekar SU, et al. Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney Disease. 

Harel Z, McArthur E, Jeyakumar N, et al. The Risk of Acute Kidney Injury with Oral Anticoagulants in Elderly Adults with Atrial Fibrillation. 

Malhotra K, Ishfaq MF, Goyal N, et al. Oral anticoagulation in patients with chronic kidney disease: A systematic review and meta-analysis. 

Wetmore JB, Herzog CA, Yan H, et al. Apixaban versus Warfarin for Treatment of Venous Thromboembolism in Patients Receiving Long-Term Dialysis. 

Mavrakanas TA. Should Oral Anticoagulation Be Used in ESKD Patients on Hemodialysis with Atrial Fibrillation?: COMMENTARY. 

Pokorney SD, Chertow GM, Al-Khalidi HR, et al for the RENAL-AF Investigators. Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial. 

Reinecke H, Engelbertz C, Bauersachs R, et al. A Randomized Controlled Trial Comparing Apixaban With the Vitamin K Antagonist Phenprocoumon in Patients on Chronic Hemodialysis: The AXADIA-AFNET 8 Study. 

Strategies for the management of atrial fibrillation in patients receiving dialysis (Safe-D) ClinicalTrials.gov identifier NCT03987711

Articles

Kim Zuber, PA-C, and Jane Davis, DNP, offer insight into the use of DOACs in people with atrial fibrillation and chronic kidney disease. 

Using DOACs in People with Chronic Kidney Disease, with Kim Zuber, PA-C, and Jane Davis, DNP

Expert guidelines for evaluation, testing and management of hepatitis C (HCV) in chronic kidney disease (CKD) have gone through 2 major iterations in the last decade. The first discussion of how to treat the CKD patient was published in 2008.

 In 2018, the introduction of new oral direct acting antiviral (DAA) therapies necessitated a new guideline.

However, Kidney Disease Improving Global Outcomes (KDIGO), the nephrology ‘gold standard’, has decided that an update is needed with new DAA protocols and the increasing use of HCV+ organ transplants.

 There is no update on who to screen nor how to screen, no update on transmission in dialysis units but there are changes in how to treat HCV in CKD (Chapter 2) and how to manage HCV in kidney transplant patients. (Chapter 4).

KDIGO recommends treating all patients with CKD, Stage 1 through Stage 5D (on dialysis), with DAA therapy (Figure 1) Of course, as is standard for all HCV protocols, patients should be tested for hepatitis B prior to treatment.

Hepatitis C treatment Regimen by CKD Stage

Source: Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease

Treatment is condensed in the figure with the caveat that the order of treatments in the figure does not indicate a ranking or preferential order. Note is made that sofosbuvir is safe for all stages of CKD.

The biggest change in the guidelines is in the kidney transplant patient. While there have been concerns of drug-drug interactions with the medications used for immunosuppression, recent trials have shown the DAA medications are safe in this population. We know that if left untreated, HCV will decrease patient survival after kidney transplant. For patients who are HCV+, the timing of treatment depends on the transplant plan and the level of liver fibrosis (

high liver fibrosis means a liver/kidney transplant is recommended, rather than kidney only

). If the HCV+ patient has a living donor and is expected to be transplanted quickly (defined as less than 24 weeks), then the recommendation is to treat with DAA therapy after the transplant. If the wait time for the living donor is less than 24 weeks, the recommendation is to treat as soon as possible with a DAA.

If the patient does not have a living donor and a deceased donor HCV+ kidney is used, then treatment is after transplant. Transplant with HCV+ kidneys is encouraged by KDIGO due to the excellent outcomes with these organs. Treatment for HCV+ should occur as soon as possible post-transplant with DAA therapy. However, due to the more frequent relapse rate, treatment should be for the full 12 weeks no matter which protocol is used.

KDIGO’s new guidelines for the treatment of CKD patients place a special emphasis on the kidney transplant patient. As more and more of our patients are transplanted with HCV+ organs, experience with DAA regimens has shown them to be a safe and effective treatment in all stages of CKD. Dialysis is a bridge to transplant for patients able to qualify and tolerate transplant surgery. Survival on dialysis is limited and survival with a transplant is statistically much better. HCV+ organs will allow better long-term survival in kidney failure patients and the use of these organs is encouraged by the entire nephrology community.

Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease. 

Gordon CE, Balk EM, Francis JM. Summary of the 2018 Kidney Disease Improving Global Outcomes (KDIGO) Guideline on hepatitis C in chronic kidney disease. 

Kidney Disease: Improving Global Outcomes (KDIGO) Hepatitis C Work Group. KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease. 

Kim Zuber, PA-C, and Jane Davis, DNP, provide perspective on guideline recommendations for the management of hepatitis C in people with chronic kidney disease from the Kidney Disease Improving Global Outcomes. 