chronic kidney disease review

 New England Journal had a recent review of acute and chronic kidney disease (see ckd eGFR review nejm2022 in dropbox DOI: 10.1056/NEJMra2201153). There were several points that I think are useful in primary care.

 

Major points:

-- kidney disease definitions:

    -- AKI (acute kidney injury) is defined as serum creatinine increase by 0.3 mg/dL in 48 hours or by 50% in 7 days, or oliguria for >6hrs

    -- AKD (acute kidney disease) is defined as AKI, or GFR<60, or GFR decreased by 35% for <3 mo

    -- CKD (chronic kidney disease) is defined as GFR<60 for at least 3 months

-- major risk factors for chronic kidney disease: older age, diabetes, hypertension, and obesity

-- clinical evaluation:

    -- GFR reflects kidney function. the number of nephrons decline with age, but GFR may not decrease because of an increase in single-nephron GFR (the overall GFR being the product of the average single-nephron GFR times the number of functioning nephrons), thereby blunting the decline in GFR

    -- GFR evaluation: current guidelines recommend using the estimated GFR (eGFR)

        -- the initial measurement is typically by the creatinine

        -- but abnormalities should be followed with measurement of cystatin C

        -- things that affect creatinine level includes: muscle mass, diet, and drugs that interfere with tubular secretion (e.g. trimethoprim); it is also affected by age, sex, race and world region. Also exercise (not mentioned, but see next blog...) and high meat diet

        -- things that affect cystatin C: obesity, smoking, inflammation, and alterations in thyroid and glucocorticoid hormones, but not age, sex, race, and world region (and, not mentioned, neither exercise nor diet)

        -- so, the best calculation per the authors is by the eGFRcr-cys calculator, which combines both creatinine and cystatin c (for calculators: https://www.kidney.org/professionals/kdoqi/gfr_calculator )

 

    -- the other important part of kidney evaluation is albuminuria, which reflects renal damage. The easiest approach is the spot urine albumin/creatinine ratio, which if abnormal can be followed with a albumin excretion rate in a timed urine collection.

        -- of note, albuminuria presents a double issue:

            -- it reflects renal damage, having macromolecules in the tubular fluid

            -- but its presence also can accelerate tubular damage and progression of kidney disease (hence the importance of treating albuminuria itself)

    -- the major complication of CKD is cardiovascular disease, the main cause of death. And this risk is increased both with decreased GFR as well as microalbuminuria

    -- of course, one other complication of CKD is end-stage renal disease. There is a Kidney Failure Risk Equation to predict the two-year and five-year risks of kidney failure using the GFR, albumin-to-creatinine ratio, age, sex, as well as some electrolyte values to refine the estimate: see https://kidneyfailurerisk.com/

 

Commentary:

-- this review does present a pretty easy way to monitor renal function in those with chronic renal disease. It would be great, of course, if the laboratories with blood samples were able to automatically make these various calculations of eGFR. but, lacking that, the websites are pretty easy to use to make the eGFR calculations as well as calculating the risk of kidney failure

-- the guideline also reinforces the importance of measuring cystatin C in those with abnormalities of the creatinine. My experience with older people without much muscle mass, is that creatinine values are pretty unreliable by themselves. I have several patients in their 90s where their creatinine levels are in the 1.1-1.3 range, but they have stage IV renal disease by measuring cystatin C. As a result, I do typically check cystatin C levels in older, thin patients with low muscle mass, since it is important to know their renal prognosis, since increased renal dysfunction is such an important cardiovascular risk factor (leading to more aggressive control of hypertension, lipids, etc), and since many medications require renal dosing to avoid toxicity

-- one huge advantage of measuring cystatin C is that it eliminates the race-based formulas for creatinine (see http://gmodestmedblogs.blogspot.com/2021/10/eliminating-race-in-calculating-renal.html ). One point here is that not using race in creatinine-based eGFR measurements tends to underestimate actual GFR in Black persons by about 13%, which could affect clinical decision-making and also be a significant factor in their well-known poorer outcomes overall (fewer renal transplants, less aggressive care), along with the overall social inequities (including decreased access to health care) that lead to poorer outcomes

--unfortunately, one issue with cystatin C is the rather high cost for the test ($18.50 vs $5.10 for creatinine, per https://jamanetwork.com/journals/jama/fullarticle/2793291 ), which limits its real availability worldwide. My approach has been to do a simultaneous creatinine and cystatin C in those with abnormal creatinine levels, then typically use their relative values as a means to interpret the creatinine values in subsequent evaluations

-- the eGFR calculator URL mentioned above gives calculations according to creatinine, cystatin C, and both. Though these guidelines above suggest using the combination creatinine/cystatin C to offset the deficiencies of both of these measurements, the distortions noted above for creatinine are much more omnipresent than  those related to cystatin C, and for many older patients the cystatin-based one likely more truly reflect the true GFR (in fact, i think there is a strong argument that those at high risk for a falsely low creatinine to just get a cystatin C even if their creatinine appears to be "normal")

-- several studies have assessed urinary microalbumin levels as coronary risk factors and that serial measurements help predict cardiovascular mortality (see cad risk microalbumin amjcardiol 2012 in dropbox, or doi:10.1016/j.amjcard.2012.02.020), with some studies finding levels of 10 mg/g being associated with an increased CVD risk

-- other studies have confirmed the independent and additive role of lower eGFR and microalbuminuria in the risk of CAD

-- it also seems that lowering albumin excretion alone is associated with lower cardiovascular and renal outcomes (eg see https://diabetesjournals.org/care/article/44/4/1020/138601/Changes-in-Albuminuria-Predict-Cardiovascular-and )

 

So, simple guidelines on assessing renal function, stressing the importance of cystatin C measurement (which is now highlighted in pretty much all of the major renal society guidelines) as the best marker CKD. And this more accurate measure of renal function (especially in older people, those with low muscle mass, etc) is important for patient care: appropriate aggressive treatment of renal and cardiovascular risk factors, timely referral to nephrology for management of end-stage kidney disease, renal dosing of medications, etc

geoff

 

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