09:43 AM

#527 - Cystatin C, A-Fib Update, Having An Awepique Year

Take 3 – Practical Practice Pointers©

A Question From a Colleague

1)  Should We Use Cystatin C for Diagnosing Chronic Kidney Disease


We have focused a lot recently on the new “kidney health measure” – a combination of the calculated estimated glomerular filtration rate (eGFR) and the measured urine albumin-creatinine ratio (uACR) – to diagnose/monitor chronic kidney disease (CKD).

Cystatin C – measured from the serum – has been around for a while as an alternate way to measure kidney function. The 2012 “Kidney Disease: Improving Global Outcomes” (KDIGO) guideline recommends the use of cystatin C when additional confirmation is needed to diagnose CKD, in the case of a patient with low muscle mass (which limits the amount of circulating creatinine) or in someone with a borderline calculated eGFR for whom we are worried about adjusting the dose of a renally-cleared medication. Cystatin C is not perfect on its own – it can be incorrect in the presence of acute kidney injury, with certain patient characteristics (abnormal thyroid function, heterophilic antibodies that interfere with testing and corticosteroid use) and higher GFR levels. The ultimate recommendation of the 2012 KDIGO guideline was for a cystatin C-based eGFR calculation (rather than cystatin C levels alone) as the best way to use cystatin C when needed.

A NEJM study from 2021 used data from 23 studies to derive a combined creatinine/cystatin C calculation with the intent to remove race from the traditional eGFR equation (which has been done in most institutions at this point). The equation was then validated using data from 12 other studies. The results show that the combined creatinine/cystatin C calculation revealed only a minor difference between black and non-black patients and was more accurate compared to measured 24-hour creatinine clearance that the traditional equation.

A recent opinion piece from the National Kidney Foundation appeared to set the stage for the routine recommendation of this new combined creatinine/cystatin C-based eGFR calculation in the new KDIGO guidelines, scheduled for 2023. However, these guidelines have not yet been published.

John’s Comments:

Cystatin C appears promising as a way to develop more accurate GFR estimation equations but has not hit the routine guidelines yet. Avoid checking cystatin C by itself or using it regularly for now – there may still be problems with lab availability and insurance coverage. Focus instead on better completion of the existing kidney health measure and look for the soon-to-be published revisions of the KDIGO CKD guideline.


  • Chapter 1: Definition and classification of CKD. Kidney International Supplements. 2013;3(1):19-62. Link
  • Inker LA, Eneanya ND, Coresh J, et al. New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race. New England Journal of Medicine. 2021;385(19):1737-1749. Link


From the Family of Cardiology Societies and the Guidelines

2)  Diagnosis/Management of Atrial Fibrillation (AF) in 2024


Atrial fibrillation (AF) is the most sustained common cardiac arrhythmia, and its incidence and prevalence are increasing in the US due to multiple reasons, including an  aging of the population, rising tide of obesity, increasing detection, and increasing survival with AF and other forms of CVD.   AF is associated with a 1.5- to 2-fold increased risk of death as well as a 2.4-fold risk of stroke, 1.5-fold risk of cognitive impairment or dementia, 1.5-fold risk of MI, 2-fold risk of sudden cardiac death, 5-fold risk of heart failure (HF), 1.6-fold risk of chronic kidney disease (CKD), and 1.3-fold risk of peripheral artery disease (PAD).  In Medicare beneficiaries, the most frequent outcome in the 5 years after AF diagnosis was death (19% at 1 year and 49% at 5 years), followed by HF (13.7%) and new-onset stroke (7.1%).

The American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) recently updated their 2019 guideline for preventing and optimally managing AF.   Selected messages include (some categorized by Strength of Recommendation/Level of Evidence):

  • Although photoplethysmography monitors (smartphone cameras/smartwatches) may indicate the need to obtain an electrocardiographic tracing, they are not sufficiently reliable to establish an AF diagnosis.
  • New Staging of atrial fibrillation (AF): The previous classification of AF was based only on arrhythmia duration and tended to emphasize therapeutic interventions. The new classification, using stages, recognizes AF as a disease continuum that requires a variety of strategies at the different stages, from prevention, lifestyle and risk factor modification, screening, and therapy.
    • Stage 1: At risk for AF due to the presence of risk factors: Modifiable = Obesity, DM, poor fitness, HTN, alcohol, OSA (smoking not RF but cessation advised)
    • Stage 2: Pre-AF – evidence of structural or electrical findings predisposing to A
    • Stage 3: AF, including paroxysmal (3A), persistent - > 7 days (3B), long-standing persistent - > 12 months (3C), successful AF ablation (3D)
    • Stage 4: Permanent AF
  • Lifestyle and risk factor modification is a pillar of AF management to prevent onset, progression, and adverse outcomes (1/B-NR).  Specific pillars include assessing and treating stroke risk, optimizing modifiable risk factors, and minimizing AF burden (frequency and duration) through rhythm and rate control.
  • For newly diagnosed AF, initial w/u should include cardiac ECHO, EKG, BMP, CBC, TSH, and other labs as clinically indicated based on risk factors or findings (1/B-NR).
  • For newly diagnosed AF,  protocolized testing for ischemia, acute coronary syndrome (ACS) or PE are not indicated unless there are specific signs/symptoms.
  • Caffeine cessation for those with AF not recommended.
  • Those with AF should be evaluated yearly with a CHA2DS2-VASc score (1/B-NR).  For those with intermediate risk (equal to score of 1 in men or 2 in women) who remain uncertain about the benefit of anticoagulation, consider factors that may modify their risk of stroke to help inform the decision (2a/C-LD).  Anticoagulation is a reasonable option in these patients (2a/A).
  • For those deemed at high risk for stroke, bleeding risk scores should not be used in isolation to determine eligibility for anticoagulation, but instead to identify and modify bleeding risk factors and to inform medical decision-making.
  • For those with an estimated annual risk of stroke or thromboembolic events > 2% (score > 2 for men and > 3 for women), selection of anticoagulation therapy to reduce risk of stroke should be based on the risk regardless of the AF pattern (1/B-R).  DOACs are recommended over warfarin except for those with mechanical heart valves or moderate to severe rheumatic mitral stenosis (1/A).
  • Reevaluation of the need for and choice of therapy should be done at periodic intervals to reassess stroke and bleeding risk, net clinical benefit, and dosing (1/B-R).
  • Aspirin with or without clopidogrel is not recommended as an alternative to anticoagulation unless other indication for antiplatelet therapy (Harm/B-R).
  • For those with AF without risk factors for stroke, aspirin monotherapy is of no benefit.
  • For patients with AF and stable peripheral artery disease (PAD), monotherapy oral anticoagulation is reasonable over dual therapy (anticoagulation plus aspirin or P2Y12 inhibitor) to reduce the risk of bleeding (2a/B-NR).
  • For those with AF at elevated risk for stroke and with CKD stage 3 or greater, consult the guideline for specific guidance.
  • Shared decision-making (SDM) is recommended to discuss rhythm- versus rate-control strategies (1/B-NR).
  • In those with reduced LV function and persistent (or high burden) AF, a trial of rhythm control should be recommended (1/B-R).
  • In symptomatic AF, rhythm control can be useful to improve symptoms (2a/BR).
  • For AF < 1 year, rhythm control has been shown to reduce hospitalizations, stroke, and mortality (2a/B-R).
  • Rhythm control can reduce likelihood of AF progression (2a/B-NR).
  • For AF duration > 48 hours, a 3-week duration of therapeutic anti-coagulation or imaging evaluation to exclude intracardiac thrombus is recommended before elective cardioversion (1/B-R).  Anticoagulation should be continued for at least 4 weeks after cardioversion (1/B-RM).
  • For those who are hemodynamically stable, pharmacological cardioversion is a reasonable alternative to electrical cardioversion (2a/C-LD)
  • Catheter ablation is a useful first-line therapy for those with symptomatic AF (1/A).
  • For athletes who develop AF, catheter ablation is a reasonable strategy for rhythm control (2a/B-NR).

Mark’s Comments:

There’s a lot in this 156-page guideline and I’ve attempted to summarize some highlights relevant to our work providing primary medical care.  The sections on anticoagulation with CKD stage 3 or greater and the one on peri- and post-operative anticoagulation management are quite detailed and should be remembered as a future reference when managing patients with AF in these contexts.


  • Joglar J, et al.  2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.  Circulation. 2024;149:e1–e156.  Link

From PeerRxMed ( www.PeerRxMed.org )

3) Word Up!  It’s Looking to be an Awepique Year …

"The real voyage of discovery consists not in seeking new landscapes, but in having new eyes." - Marcel Proust


As I shared in last week's blog, I believe words matter, which is why one of my New Year’s rituals is to pick my “word for the year.”   This is a word that represents a personal and/or professional aspiration that will serve as an inspiration, motivation, guide, anchor, or “theme” for the upcoming year.   Mine has traditionally been a self-created word, as I have found that for me most existing words either don’t adequately capture what I’m seeking or have become overlaid with so much baggage or “cliché” that they’ve lost their impact for me.  The Merriam-Webster Dictionary’s “word for the year” for 2023, "authentic", would be one such example.

For me, the concept of choosing a personal word for the year is more than a trend; it's a psychological anchor.  It helps in focusing my thoughts and actions, aligning them with core values and goals.  For anyone, such a practice can lead to increased self-awareness, motivation, and a sense of purpose. It's a way to simplify aspirations into a single, powerful concept that can easily be recalled and reflected upon daily.

My 2024 word is “awe pique,” which is a blend of awepique (stimulate), and “epique” (French for “epic”).  I define awepique as: “The quality or state of regularly experiencing a profound sense of wonder and reverence for everyday moments, combined with a feeling of being gently prodded or nudged towards recognizing the extraordinary in the ordinary, leaving one to know that each moment of this life is part of an incredible poetic journey.” 

The word awepique will be a “lens” that will encourage me to explore and appreciate the richness of everyday life, to “catch” myself in those moments when I am deviating from this path (driving in traffic and the EMR specifically tend to do this for me), and to remember and recognize the wonderment in the small details and routine experiences of life.  I intend that my leading a more awepique life will open me to new levels of awareness and presence, and ultimately a greater sense of both elation and peace.  There will be playfulness as well.  In order to lead an awepique life, other words that will accompany me for the year include my practice for the year (“awelchemy”), my journey (an “awedessy”), and my attitude along the way (“awedacity”).   

How about you?  What might be the word or words to help you frame your year – or perhaps for you it’s a picture, quote, song, or poem (or all of the above!).  Consider picking one or more and sharing their meaning for you with those close to you, including your PeerRx partner.  I’ve found that doing so is great fun, can provide you insights into your psyche, and by inviting others into the conversation, can supercharge your intention by providing some encouragement and accountability around it.  When you look back one year from now, what will have defined your 2024?  That journey begins right now, so “Word Up” ….


Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org