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Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017The timing of investigations depends on the clinical condition of the patient and the rate and magnitude of change in serum creatinine.
In asymptomatic or mildly symptomatic patients, elevations in serum creatinine can be systematically evaluated. However, in severely ill patients with multiorgan involvement, an early kidney biopsy should be considered to expedite diagnosis and treatment.
If there is evidence of fluid overload or uremic signs and symptoms, treatment should be instigated in parallel with urgent investigations.
Initial assessment
Current serum creatinine values should be compared with previous serum creatinine values, if available, to distinguish acute from chronic changes. If previous values are not available, all values outside of the reference range should be treated as acute changes.
If the elevation in serum creatinine is acute, the magnitude and rate of rise in serum creatinine should be determined, as this provides clues as to the underlying cause and guides appropriate management:
The typical rise in serum creatinine in acute kidney injury (AKI) is 1 to 2 mg/dL/day (88 to 177 micromol/L/day).
Serum creatinine rises >1 to 2 mg/dL/day (>88 to 177 micromol/L/day) should prompt suspicion of rapidly progressive glomerulonephritis or rhabdomyolysis. Rises as high as 5 mg/dL/day (442 micromol/L/day) may be seen in rhabdomyolysis.
An acute increase in serum creatinine against the background of chronic kidney disease (CKD) may indicate progression of the underlying condition. However, other causes of elevated serum creatinine should be excluded first. Fluid balance issues, medications, contrast exposure, and worsening of comorbid conditions are the most common causes and may be reversible.
Acute kidney injury
There is considerable debate regarding the magnitude of serum creatinine increase that constitutes AKI.[38]
Consensus defines AKI as any of the following:[39][40][41]
Abrupt reduction in kidney function, defined as an absolute increase in serum creatinine of ≥0.3 mg/dL (≥26.5 micromol/L) within 48 hours.
An increase in serum creatinine to 1.5-fold from baseline within the last 7 days.
A reduction in urine output (documented oliguria of <0.5 mL/kg/hour for >6 hours).
AKI is staged as follows:
Stage 1: increase in serum creatinine >0.3 mg/dL (>26.5 micromol/L) or 150% to 200% of baseline values.
Stage 2: increase of 200% to 300% (two- to threefold) of baseline values.
Stage 3: >300% (threefold) increase in serum creatinine from baseline.
Use of serum creatinine to detect and assess the severity of AKI is limited. Serum levels are influenced by many factors, so the absolute level does not reflect the severity of the underlying kidney damage. Estimated glomerular filtration rate (eGFR) is based on the assumption of a steady-state creatinine concentration, but AKI is a nonsteady state.
Rises in serum creatinine after marked injury take 12-24 hours to occur and do not detect early-stage damage. In addition, creatinine kinetic studies have shown that the time to reach a 50% increase in serum creatinine is directly related to baseline kidney function and ranges from 4 hours (normal kidney function) to 27 hours (in stage 4 CKD).[42]
An alternative definition of AKI that incorporates absolute changes in serum creatinine over a 24- to 48-hour period has been proposed.[42]
Kinetic eGFR (KeGFR) is an estimation of creatinine clearance that is calculated from two serum creatinine concentration measurements taken at different timepoints. It has an emerging role in risk-stratifying patients with rapidly changing kidney function. Changes in KeGFR predict AKI and the need for kidney replacement therapy more accurately than the Modification of Diet in Renal Disease (MDRD) equation.[43] KeGFR calculator Opens in new window
Chronic kidney disease
Both international and UK guidelines define CKD as structural or functional abnormalities of the kidney for >3 months with implications for health indicated by at least one of the following:[44][45]
GFR <60 mL/minute/1.73 m² for ≥3 months, with or without kidney damage
Clinically important albuminuria (albumin excretion rate [AER] ≥30 mg/24 hours; albumin-to-creatinine ratio [ACR] ≥30 mg/g)
Urine sediment abnormalities
Persistent hematuria
Electrolyte and other abnormalities due to tubular disorders
Abnormalities detected by histology
Structural abnormalities detected by imaging
History of kidney transplantation
Kidney Disease: Improving Global Outcomes (KDIGO) and NICE (UK National Institute for Health and Care Excellence) guidelines classify CKD stages according to cause, GFR, and albuminuria (CGA).[44][45]
eGFR categories (where G denotes the GFR category) are:
G1: kidney damage with normal or increased GFR, ≥90 mL/minute/1.73 m²
G2: kidney damage with mild decrease in GFR, 60 to 89 mL/minute/1.73 m²
G3a: kidney damage with mild to moderate decrease in GFR, 45 to 59 mL/minute/1.73 m²
G3b: kidney damage with moderate to severe decrease in GFR, 30 to 44 mL/minute/1.73 m²
G4: kidney damage with severe decrease in GFR, 15 to 29 mL/minute/1.73 m²
G5: kidney failure, with GFR <15 mL/minute/1.73 m²
Albuminuria categories (where A denotes the ACR category) are:
A1 (normal to mildly increased): AER <30 mg/24 hours, ACR <30 mg/g
A2 (moderately increased): AER 30-300 mg/24 hours, ACR 30-300 mg/g
A3 (severely increased): AER >300 mg/24 hours, ACR >300 mg/g
For example, a person with an eGFR of 55 mL/minute/1.73 m² and an ACR of 350 mg/g has CKD G3aA3.
The diagnosis should be made following two measurements of eGFR at least 90 days apart.[44] Using a single screening test overestimated the prevalence of CKD by 25% in one primary care cohort study of people ages over 60 years.[46]
It is unclear whether estimation of GFR adds useful information to the serum creatinine measurement when determining CKD severity, or for guiding treatment. An increasing portion of serum creatinine is excreted by tubular secretion rather than glomerular filtration in advanced CKD, contributing to gross overestimation of GFR. Extrarenal secretion of serum creatinine is also increased, so the uptake of creatine generated by bacterial breakdown of creatinine in the gut, normally a negligible source of creatine, becomes significant.
History
Most of the underlying causes produce few or no specific symptoms. Assessment of current symptoms should include enquiry about symptoms of uremia.
Current symptoms
Symptoms of uremia are often vague. They include nausea, vomiting, fatigue, reduced appetite, muscle cramps, pruritus, and altered mental status. Uremia usually occurs in advanced AKI or in advanced CKD.
A history of trauma, severe vomiting, or diarrhea should prompt suspicion of volume depletion.
Joint pain, rash, progressive shortness of breath, hemoptysis, persistent sinusitis or otitis, scleritis or paresthesia should prompt suspicion of vasculitis.[47]
Fever and sore throat should prompt suspicion of streptococcal infection (causing glomerulonephritis).
Jaundice should prompt suspicion of hepatitis B or C infection, or hepatorenal syndrome.
Shortness of breath with peripheral edema may indicate heart failure.
Weight loss should prompt suspicion of an underlying malignancy.
Obstructive (voiding) and irritative (storage) symptoms should prompt suspicion of obstructive uropathy.
Severe loin pain with frank hematuria should prompt suspicion of acute kidney infarction or nephrolithiasis.
A history of polyuria, polydipsia, polyphagia, weakness, and/or weight loss should prompt suspicion of diabetic ketoacidosis.
Pregnancy should prompt suspicion of preeclampsia or exacerbation of underlying kidney disease.
Past medical history
CKD
Previous AKI
Other underlying conditions that may cause raised serum creatinine include hypertension (hypertensive nephropathy), diabetes (diabetic nephropathy), autoimmune diseases (vasculitis), cirrhosis (hepatorenal syndrome), lymphoproliferative disorders (cryoglobulinemia), paraproteinemias, and infections (postinfectious glomerulonephritis, cryoglobulinemia).
Surgical history
Recent surgery may indicate hypovolemia, ischemia of the kidney (due to clamping of arteries during cardiac surgery), or kidney transplant rejection.
Multiple cholesterol emboli syndrome can occur following arterial manipulation, vascular surgery, stent placement, or cardiac catheterization.
A small rise in serum creatinine following kidney donation or unilateral or partial nephrectomy is expected and should resolve.
Drug history
A thorough drug history is important, as the range of drugs known to cause elevated serum creatinine is extremely wide.
Cimetidine, gentamicin, fibric acid derivatives other than gemfibrozil, and trimethoprim inhibit creatinine secretion.
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers increase serum creatinine levels by 20% to 30% due to prerenal effects.[11]
Penicillamine, gold sodium thiomalate, nonsteroidal anti-inflammatory drugs (NSAIDs), captopril, mitomycin C, and cyclosporine can cause glomerulonephritis, as can heroin.
Many medications are known to cause acute interstitial nephritis.
Aminoglycosides, amphotericin-B, chemotherapeutic agents (e.g., cisplatin), NSAIDs, and radiocontrast media can cause acute tubular necrosis.
Some patients have an increase in serum creatinine within a few months after starting fenofibrate, an entity known as fenofibrate-associated creatinine increase.[48]
Nutrition history
Creatine is often taken as a supplement to boost muscle mass and increase athletic performance. Prolonged intake of creatine supplementation of >10 g/day may increase serum creatinine concentrations, but is unlikely to affect estimates of creatinine clearance.[4][5] The serum creatinine levels should return to baseline values upon discontinuing supplemental creatine.
A vegetarian diet is associated with decreased generation of creatinine, and ingestion of cooked meat causes a transient increase in serum creatinine.
Examination
The examination may be unremarkable in many patients, but is most useful to differentiate systemically ill patients (who require immediate treatment and early kidney biopsy) from other patients who can be investigated systematically.
Patients with shock appear ill, with decreased blood pressure, increase in heart rate, and increased respiratory rate with a possible decrease in oxygen saturations or reduced level of consciousness.
Uremic signs such as asterixis or altered mental status, and/or signs of fluid overload (e.g., pulmonary or peripheral edema), indicate severe kidney failure requiring immediate treatment. Early kidney biopsy to establish the cause should be considered in these patients.
The presence of rash should prompt suspicion of vasculitis or a microangiopathy. Ascites should prompt suspicion of cirrhosis. Jaundice should prompt suspicion of cirrhosis or hepatitis B or C infection. Peripheral edema should prompt suspicion of heart failure.
The appearance of cutaneous lesions, "thrash toes, blue toes", pancreatitis, stroke, ischemic bowel, or angina should prompt suspicion of multiple cholesterol emboli syndrome.
Investigations
Initial investigations include bloods and urinalysis, with specific further investigations guided by clinical features.
Blood tests
Blood urea nitrogen/serum creatinine ratio can help distinguish prerenal from renal causes. A ratio >20 suggests prerenal causes, whereas a ratio <10 suggests renal causes.
Urinalysis
Provides useful diagnostic clues:
Isolated proteinuria suggests nephrotic syndrome, diabetic nephropathy, or preeclampsia. Reagent strips should not be used to identify proteinuria in children and young people.[44] Incidental unexplained proteinuria in adults or children should prompt further investigation for CKD with a creatinine-based estimate of GFR and ACR.[44] ACR is preferred over protein:creatinine ratio (PCR) in patients with CKD because ACR has greater sensitivity for low levels of proteinuria.[44] An ACR of ≥30 mg/g is regarded as clinically important proteinuria, but should be confirmed in an early morning sample if it is <600 mg/mmol. An ACR of ≥600 mg/mmol does not need to be checked.[44]
Isolated proteinuria suggests nephrotic syndrome, diabetic nephropathy, or preeclampsia. Spot urine ACR quantifies proteinuria reasonably accurately, and much more easily than a 24-hour urine collection, and should always be ordered as a follow-up to urinalysis showing proteinuria.
Isolated hematuria suggests nephrolithiasis.
Proteinuria and hematuria without other abnormalities suggests acute interstitial nephritis.
Further urine tests include microscopy, specific gravity, osmolality, random urine sodium, and fractional excretion of sodium.
Normal or hyaline casts, specific gravity >1.020, osmolality >500 mOsm/kg H₂O, random urine sodium (UNa) <20 mEq/L, and a fractional excretion of sodium (FENa) <1% suggest prerenal pathology. FENa may be calculated using the following formula: (urine sodium x plasma creatinine)/(plasma sodium x urine creatinine) x 100. [ Fractional Excretion of Sodium Opens in new window ]
Hematuria, proteinuria, red blood cell casts, epithelial cell casts, waxy casts, granular casts, UNa >20 mEq/L, and FENa <1% suggest glomerulonephritis.
Muddy brown granular casts, epithelial cell casts, specific gravity approximately 1.010, UNa >20 mEq/L, and FENa >1% suggest acute tubular necrosis.
Myoglobin casts suggest rhabdomyolysis.
Eosinophiluria suggests atheroembolic disease (cholesterol emboli).
Crystals suggest a crystal-induced nephropathy. Examples include crystalluria in tumor lysis syndrome, calcium oxalate (ethylene glycol intoxication), medications (acyclovir, indinavir, sulfadiazine).
Other investigations are ordered depending on the clinical features and include the following.
Serum creatine kinase: elevated in rhabdomyolysis and multiple cholesterol emboli syndrome. Mild elevation is seen in patients taking creatine supplements.
Blood, urine, and sputum cultures if sepsis is suspected.
Complete blood count: may show anemia in cases of glomerulonephritis associated with systemic disease and patients with heart failure or acute hemorrhage; leukocytosis in infection or inflammatory states.
C-reactive protein or erythrocyte sedimentation rate: may be elevated in systemic inflammation, such as vasculitis.
Serology for underlying infections, including HIV, hepatitis B and C.
Vasculitis markers: antiglomerular basement membrane antibodies (positive in Goodpasture syndrome), antineutrophil cytoplasmic antibodies (positive in small-vessel vasculitis, e.g., granulomatosis with polyangiitis [formerly known as Wegener granulomatosis], polyarteritis nodosa) and antinuclear antibodies or anti-double-stranded DNA antibodies (positive in systemic lupus erythematosus).
Antistreptolysin O or antiDNAse antibodies should be ordered if poststreptococcal glomerulonephritis is suspected.
Antiphospholipase A2 receptor antibodies are highly sensitive and specific for idiopathic membranous glomerulonephritis.[49]
Complement titers are low in postinfectious glomerulonephritis, systemic lupus erythematosus, subacute bacterial endocarditis, cholesterol embolization, essential mixed cryoglobulinemia, and membranoproliferative glomerulonephritis.
Serum and urine protein electrophoresis should be ordered if paraproteinemia is suspected (electrophoresis shows a protein spike corresponding to the monoclonal protein).
Uric acid is elevated in tumor lysis syndrome.
HbA1c is useful to assess glycemic control in people with diabetes.
Coagulation studies: abnormalities can occur in septic shock and after trauma.
Liver function tests may be abnormal and placental growth factor levels low in women with pre-eclampsia.
Plasma aldosterone to renin ratio is <20 in renal artery stenosis.
ECG may show a cardiogenic cause of shock or evidence of left ventricular hypertrophy or underlying coronary artery disease in patients with hypertension or chronic heart failure.
Chest x-ray and echocardiogram are helpful in cases of chronic heart failure.
Imaging studies
The American College of Radiology provides guidelines for the selection of appropriate imaging modalities.[27][50][51]
Kidney Doppler ultrasound should be performed if renal artery stenosis or renal vein thrombosis is suspected.
Renal vein thrombosis can also be detected using magnetic resonance venography.
CT abdomen and pelvis with contrast and arteriography should be performed for major blunt trauma with suspected kidney infarction.
Kidney and urinary tract ultrasound should be performed if obstructive uropathy is suspected. If the suspected cause of obstructive uropathy is kidney stones, noncontrast CT is the preferred test.
Kidney biopsy
Kidney biopsy should be considered as an initial test in patients with uremic symptoms or multiorgan involvement; it provides a definitive diagnosis of underlying renal causes.
In all other patients, kidney biopsy is reserved for cases in which confirmation of the diagnosis is required after a systematic investigation is completed.
Laboratory measurement of creatinine
Serum creatinine is commonly measured by alkaline picrate (Jaffe reaction), enzymatic, and high-performance liquid chromatography (HPLC) methods. These methods are standardized to the isotope dilution mass spectrometry (IDMS) method.[52]
Point-of-care testing (POCT) is now commonly available in healthcare settings.
Isotope dilution mass spectrometry
IDMS is the diagnostic standard.
It is highly specific and offers the most accurate results for serum creatinine, but is available only in selected laboratories.
The Jaffe method
Commonly used but is subject to interference by a range of substances. Glucose and ketones can interfere with the assay, leading to an overestimation of serum creatinine in patients with diabetic ketoacidosis.[53]
Delayed sample receipt and centrifugation can lead to significant increases in measured creatinine using the Jaffe method.[54]
Guidelines recommend moving towards enzymatic methodology due to the poor specificity of Jaffe creatinine methods. Differences between Jaffe and enzymatic serum creatinine results can exceed the recommended 5% target, especially at concentrations <1.13 mg/dL (<100 micromol/L).[55]
High-performance liquid chromatography methods
Have better specificity than the Jaffe and enzymatic methods, and are less prone to interference. However, measurement errors can occur due to variability in calibration, and to random measurement errors.[52]
Combining HPLC with IDMS provides highly accurate results, but is not available in most centers.
Point-of-care testing enzyme-based serum creatinine measurement
Appears to be sufficiently accurate for clinical use in critically ill patients.[56]
Creatinine POCT can be used for screening patients at risk for contrast-induced acute kidney injury (CI-AKI) prior to contrast-enhanced diagnostic imaging.[57][58]
Dry blood spot on filter paper
An innovative method of creatinine measurement, especially useful for screening patients with CKD.
This method has a sensitivity of 96% and specificity of 55%.[59]
Estimated glomerular filtration rate and creatinine clearance
Using serum creatinine
The most accurate method for calculating GFR is by measuring the clearance of exogenous filtration markers, such as iothalamate, iohexol, or inulin. However, this is expensive and requires exposure to radiation and compliance with strict regulatory guidelines. In practice, creatinine clearance is therefore used to estimate GFR. Creatinine is freely filtered, has minimal tubular secretion and absorption, is simple and inexpensive to measure from random blood samples, and has relatively good accuracy. A rise in serum creatinine is used as a marker of reduced GFR. It varies inversely with GFR, but the relationship is not linear.
The use of serum creatinine as an indirect filtration marker is limited by the following factors:
Biologic variability
Bias and nonspecificity affecting creatinine measurement
Drug effects
Nutrition
Alterations in circulating serum creatinine produced by nonrenal disease states
Differences in GFR range and creatinine production in healthy people compared with people with CKD.
As a result of these confounding factors, there is a risk of overestimating the GFR, and the magnitude of the overestimation is not predictable.[60]
Cystatin C and serum creatinine
Cystatin C is an alternative marker of kidney function and is used as a confirmatory test for eGFR when more precise estimates for clinical decision making are required. Creatinine is mostly generated in skeletal muscles whereas cystatin C is produced by all nucleated cells. Cystatin C is fully catabolized in the proximal renal tubule following glomerular filtration and is not returned to blood. Unlike serum creatinine, serum cystatin C is less affected by gender, age, race, protein intake, and muscle mass but it is influenced by smoking, inflammation, adiposity, thyroid diseases, malignancy, and glucocorticoids.
Estimating eGFR using creatinine is appropriate for most patients, but if a more accurate eGFR is needed for clinical decision-making, cystatin C should be used. However, there can be substantial differences between creatinine-based and cystatin C-based eGFRs.[61] In these situations, calculating the eGFR using both serum creatinine and cystatin C is more accurate than using either biomarker alone, although there are insufficient data for accuracy of eGFRs calculated using creatinine, cystatin C or both biomarkers in many diseases and stages of CKD.
Although data are limited, one retrospective study reports that eGFR based on cystatin C can have a substantial effect on CKD staging. Compared with creatinine eGFR, cystatin C eGFR led to reclassification to a more advanced CKD stage in 27% of patients, a less advanced stage in 7%, and no change in 66% of patients.[62] Another retrospective study reported that eGFR based on cystatin C was lower than eGFR based on creatinine in 65% of cases.[63]
The EKFC cystatin C-based eGFR equation has the same mathematical form as the EKFC creatinine-based eGFR equation, but has a scaling factor for cystatin C that does not need to be adjusted for race or sex. In one cross-sectional analysis of patient data from multiple centers in Europe, US, and Africa, it was found to be more accurate in assessing GFR than any of the three CKD-EPI equations or the revised Lund-Malmo equation.[64]
KDIGO recommend that in adults at risk for CKD, the GFR category should be estimated from the combination of creatinine and cystatin C (creatinine and cystatin C - based estimated glomerular filtration rate [eGFRcr-cys]).[13]
Kinetic estimated glomerular filtration rate
eGFR is based on the assumption of a steady-state creatinine concentration. However, AKI is a nonsteady state and eGFR in this situation is unreliable.
KeGFR is an estimate of immediate biomarker clearance based on two serum creatinine measurements at different timepoints. It reflects dynamic changes in kidney function and can be determined from routine tests carried out in acutely ill patients.[65] KeGFR calculator Opens in new window KeGFR may be an important predictor of mortality. However, in one retrospective analysis, there was not a good correlation between AKI severity and the worst achieved KeGFR (<30 mL/min).[66]
KeGFR has also been shown to improve prediction of dialysis and recovery after kidney transplant.[67]
Equations for estimating glomerular filtration rate
Equations for estimating GFR from serum creatinine levels are mainly used for staging CKD and should not be used to interpret acute increases in serum creatinine. Correction factors for black people have generally been derived from studies in African-American people. UK guidelines and some US guidance do not recommend using correction factors for ethnicity.[44][68][69]
Available equations include:[53][64][69][70][71][72][73][74][75][76] [ Creatinine Clearance Estimate by Cockcroft-Gault Equation Opens in new window ] [ Glomerular Filtration Rate Estimate by the Abbreviated MDRD Study Equation Opens in new window ] [ Glomerular Filtration Rate Estimate by the IDMS-Traceable MDRD Study Equation Opens in new window ] [ Glomerular Filtration Rate Estimate by CKD-EPI Equation Opens in new window ] [ Glomerular Filtration Rate Estimation (eGFR) by CKD-EPI Equation with Creatinine and Cystatin C, without Race (2021) Opens in new window ] [ Glomerular Filtration Rate Estimation (eGFR) by CKD-EPI Equation with Cystatin C, without Race (2012) Opens in new window ] [ Glomerular Filtration Rate Estimation (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation with Creatinine, without Race (2021) Opens in new window ]
Cockcroft-Gault formula
Four-variable MDRD formula
IDMS-traceable 4-variable MDRD equation (MDRD-IDMS)
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation without race
Mayo Clinic equation
Lund-Malmo revised (LMR)
Full age spectrum (FAS) (can be used in children and adults of all ages)
Berlin initiative study 1 and 2 (BIS1, BIS2)
European Kidney Function Consortium equations
Mayo Clinic equation
Lund-1 equation without body weight measure
In a study of five equations (Cockcroft Gault, MDRD, CKD-EPI, LMR, European Kidney Function Consortium), the Cockcroft Gault equation generally had greater bias, imprecision and lower accuracy than the other equations except for in people age ≥65 years.[77] The Cockcroft-Gault, simplified MDRD, and CKD-EPI equations perform poorly in critically ill patients, and are not recommended in the intensive care unit setting.[78][79]
An evaluation of four different eGFR equations (CKD-EPI, LMR, FAS, BIS1) found that none was diagnostically superior in adults ages over 65 years with varying degrees of kidney impairment.[80]
Pitfalls in the use of serum creatinine and estimated glomerular filtration rate values
The rate of rise of serum creatinine (creatinine kinetics) is dependent on baseline GFR. In computer simulation models of creatinine kinetics, time to reach a 50% increase in serum creatinine was 10 hours when baseline GFR was normal versus >60 hours when GFR was <30 mL/min (CKD stage 4), contributing to a delay in the recognition of acute kidney injury by serum creatinine criteria.[42]
Creatinine kinetics is influenced by volume kinetics. Serum creatinine decreases by about 20% following crystalloid infusion and 40% following colloid infusion, and may take 4-12 hours to return to baseline. Uncorrected, this can lead to delay in the diagnosis of AKI.[81]
Acute changes in serum creatinine should be considered in the setting in which they take place. In patients with heart failure, various patterns of serum creatinine changes have been observed (bump, sustained increase, dip, sustained decrease, dip followed by bump, bump followed by dip, or no change). However, in one observational analysis, none of the patterns predicted diuretic responsiveness, death, or cardiovascular or renal rehospitalization.[82]
In certain conditions, elevated serum creatinine is not the primary concern. In heart failure (cardiorenal syndromes), patients with sustained decongestion and worsening kidney function had better outcomes than those with congestion and worsening kidney function.[83]
eGFR overestimates GFR in low GFR states (due to increased tubular secretion of creatinine).
eGFR is inaccurate in high GFR states (due to the lack of eGFR values above 60 mL/minute/1.73 m²).
Studies suggest that the Cockroft-Gault and MDRD formulas correctly assigned only 64% and 62% of patients, respectively, to their actual CKD classification GFR group. Based on National Health and Nutrition Examination Surveys (NHANES 1988-1994; 1999-2004) and population census data (2000), this suggests that around 10 million people (38%) may have been misclassified in the US.[84][85][86]
Serum creatinine and eGFR may not be equivalent in all clinical situations. In CI-AKI, an increase in serum creatinine, but not eGFR, was predictive for long-term mortality, with a threshold of 0.5 mg/dL (44.2 micromol/L) or more indicating worse prognosis.[87]
Prediction of kidney function is often inaccurate in individuals with class 2/3 obesity (BMI ≥35 kg/m²). Body cell mass GFR (BCM GFR) predicts creatinine clearance more accurately than traditional formulas in this patient population.[88]
The inclusion of race in eGFR algorithms results in higher reported eGFR in black patients (by a factor of approximately 1.2 in the MDRD and CKD-EPI equations).[72][89][90] eGFR algorithms that incorporate race may exacerbate health inequity by delaying specialist referral and kidney transplant evaluation in affected populations.[89]
UK guidelines recommend using the CKD-EPI equation to estimate GFR from serum creatinine in adults; and since 2021 they no longer recommend using correction factors for adults of African-Caribbean or African family origin.[44] A National Kidney Foundation and the American Society of Nephrology task force also recommends that correction factors for race should not be included when calculating CKD-EPI equations.[68]
The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recommends either the Lund-Malmo or the European Kidney Function Consortium (EKFC) equations, as they were developed and validated in European cohorts.[91] The EKFC eGFR equation involves adjusting to an individual's serum creatinine value based on median values in healthy populations across the age spectrum (from infants to older adults), sex, and race.[92][93]
There is ongoing controversy regarding the optimal method to estimate GFR for disease detection and monitoring. Comparisons of GFR estimation using the CKD-EPI equation and other creatinine-based equations in different populations show that these equations are not applicable to all populations and need to be individually validated prior to their routine use.[94][95][96][97]
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