Applicable People For Glomerular Filtration Rate Test

Jan 10, 2023

The main function of the kidney is to filter blood. The kidney filters about 100L of blood every day and produces 1~3L of urine. Therefore, the most important method to evaluate renal function is the glomerular filtration rate (GFR).

There are 2 main ways to assess GFR, they are:
(1) Estimated GFR (eGFR) based on endogenous biomarker levels (e is estimated).
(2) Measured GFR (mGFR) with exogenous biomarker levels as the reference for assessment (m is measurement).

eGFR
So, who are eGFR and mGFR suitable for? What are the precautions for interpreting eGFR and mGFR in clinical practice?

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On November 3, 2022, at the 2022 Kidney Week (Kidney Week) academic meeting held by the American Society of Nephrology (ASN), he gave a lecture on the best method for clinical measurement of GFR, and analyzed the applicable population of eGFR and mGFR examinations in detail.

 

Measurement of eGFR depends on the levels of endogenous biomarkers such as serum creatinine, cystatin C, and creatinine clearance.

01 Serum creatinine

Creatinine is an endogenous biomarker, which is produced by the body itself, and the daily secretion is basically constant, and it is excreted after being filtered by the glomerulus. Therefore, serum creatinine can be used as a reference for eGFR. Since the secretion of creatinine is closely related to age, gender, body shape, and living habits.

therefore
①Combined with other diseases, such as rhabdomyolysis;
②The muscle mass changes sharply, or is different from ordinary people, such as athletes and patients with a history of amputation;
③Extreme body weight (obesity, malnutrition)
④ Very young or very old patients;
⑤ long-term smokers,

Serum creatinine should not be used to estimate GFR.

02 Cystatin C

Cystatin C is a low molecular weight (13kDa) basic protein that is filtered and metabolized in the kidney. Cystatin C was less affected by age, sex, body size, and smoking habits than creatinine. Therefore, cystatin C can more accurately reflect GFR

03 Creatinine clearance

Creatinine clearance is suitable for people at extremes of size and age, people with bone disease, paralyzed or amputated people, and vegetarians. In addition, for people with GFR > 60ml/min/1.73㎡, creatinine clearance should be tested before using potential or definite nephrotoxic drugs.

04 eGFR formula

In addition to biomarkers, the applicable population of eGFR is closely related to the calculation formula of eGFR.

(1) CKD-EPI Cr (creatinine) formula, suitable for kidney transplant recipients and patients with advanced chronic kidney disease (CKD)
(2) The CKD-EPI CysC (cystatin C) formula is applicable to the renal function assessment of common kidney transplant donors.
(3) CKD-EPI Cr+CysC (creatinine+cystatin C) formula is applicable to all populations.

 

In addition to the CKD-EPI formula, the MDRD formula is also a common clinical eGFR formula, but there are certain errors between the two formulas. When the eGFR is 40~70ml/min/1.73㎡, the relative error of the two eGFR formulas is relatively high.

The relationship between these two formulas and mGFR has been studied. The results showed that for CKD and kidney transplant recipients, the MDRD formula was closer to mGFR at the age of 40-60, and the CKD-EPI formula was closer to mGFR at the age of 80-90; For patients, CKD-EPI is closer to mGFR.

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In short, no eGFR calculation formula is applicable to all populations, and physicians should pay attention to this when interpreting eGFR.

mGFR

The measurement of mGFR depends on the clearance of exogenous biomarkers, such as inulin clearance, iodopeptide clearance, and iohexol clearance.

01 Inulin clearance rate

Inulin clearance is the "gold standard" for GFR measurement. Inulin can be filtered by the glomerulus, and the renal tubules do not secrete or reabsorb it. At the same time, the body does not synthesize or metabolize inulin. In short, inulin met all the criteria for an exogenous biomarker, however, inulin clearance testing is less accessible and not available in all laboratories. In addition, the inspection of inulin clearance rate requires continuous infusion of inulin, and the inspection time is relatively long. On top of that, inulin tests are expensive and not covered by insurance.

02 Iohexol clearance rate

Iohexol is a reagent originally used in imaging examinations, but it can be used in the examination of mGFR. After intravenous or subcutaneous injection, it is only necessary to regularly collect plasma and urine to complete mGFR examination. Compared with inulin clearance, iohexol clearance is simple to operate and has higher accuracy (much higher than eGFR). However, the inspection of the clearance rate of iohexol still has many inconveniences.

 

For example, the entire examination lasts about 4 hours, and the patient needs to drink water continuously (3 to 4 cups per hour), empty the bladder before collecting urine (confirmed by imaging examination), and if necessary, the patient needs to insert a urinary catheter to drain urine.

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It is not difficult to find that compared with eGFR examination (only blood collection), mGFR examination takes a long time, costs more, and has lower accessibility.

So, which patients need mGFR examination?

In the last year, 4,109 patients at the Mayo Clinic underwent mGFR examinations, of which:
CKD patients accounted for 44% (n = 1829),
Patients with a history of kidney transplantation accounted for 43% (n = 1755),
Kidney transplant donors accounted for 13% (n = 525).


When evaluating the renal function of CKD patients with complex conditions and prescriptions, mGFR should be used for examination, and the situation of patients after kidney transplantation is also more complicated, so it is best to use mGFR to examine the renal function of the kidneys. For kidney transplant donors with perfect transplant matching results but abnormal eGFR, it is best to evaluate renal function by mGFR examination.

03 Cimetidine and mGFR

In view of the inconvenience of mGFR inspection, is there a simple mGFR inspection method?

 

A study found that after oral administration of cimetidine, the patient's serum creatinine clearance rate will decrease, and the relative error with the serum iohexol clearance rate is small, which can be used as a simple method for mGFR examination. A total of 168 patients were enrolled in the study, who underwent baseline creatinine clearance, serum iohexol clearance, renal iohexol clearance, and serum creatinine clearance after oral administration of cimetidine. The results of serum iohexol clearance test and renal iohexol clearance test showed that the GFR of serum iohexol clearance test was higher than that of renal iohexol clearance test, and the relative error between the two was about 16%.

 

After the patient took cimetidine, the serum creatinine clearance rate decreased by 19.8%, compared with the serum iohexol clearance rate test results, the relative error between the two was only 0.6%.

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However, the serum creatinine clearance rate after taking cimetidine was still higher than the renal iohexol clearance rate, and the relative error between the two was 17%.

 

In addition to eGFR and mGFR, proteinuria, microscopic hematuria (such as abnormal red blood cells), urine pH, imaging methods, and new biomarkers can all evaluate renal function. In clinical work, various indicators should be considered comprehensively to evaluate the renal function of patients in an all-round way.

 

Overall, many factors affect the levels of renal serum biomarkers, such as CKD status, transplanted kidney status, body weight, muscle mass, medications.

These factors can change the results of eGFR and mGFR

Therefore, the influence of factors such as patient history, physical condition, and eGFR formula on mGFR and eGFR should be correctly understood. Effective diagnosis, treatment and monitoring can only be carried out after an accurate and comprehensive assessment of the patient's renal function.


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