Assessment of Kidney Function
Fizza Abbas
Steven Cheng
General Principles
Assessing kidney function is a critical step in the recognition and monitoring of acute and chronic kidney disease (CKD).
Kidney function is most commonly approximated by the glomerular filtration rate (GFR). This provides a quantitative measurement of the kidney’s ability to filter and clear solute from the body.
Equally important is the quality of the filtrate that is produced by the kidneys. This can be assessed by examining the content of the urinary filtrate, which reflects renal tubular function and the integrity of the filtration barrier.
Clinicians need to understand the assumptions and pitfalls regarding the various measurements of kidney function in order to use and interpret them appropriately.
The amount of fluid that is processed by the kidney is reflected by the GFR.
GFR is defined as the sum of the filtration rates of all functional nephrons.
The normal GFR is ∼125 mL/min/1.73 m2 in men and 100 mL/min/1.73 m2 in women.
Changes in the overall filtering capacity of the kidney will result in parallel changes in GFR. For example, diseased kidneys with significantly impaired filtering capacity will have a reduced GFR.
The content or composition of the urinary filtrate is also highly regulated. An intact nephron has an effective filtration barrier and tight control over solute concentration in the urine.
Abnormal urinary findings can suggest damage to specific sites in the nephron.
Proteinuria and hematuria, for example, may reflect impaired glomerular architecture, thus compromising the filtration barrier.
Diagnosis
Differential Diagnosis
Renal dysfunction, identified by a reduction in GFR, an abnormality in urine content, and/or direct tissue evaluation with biopsy, can be categorized in the following ways:
Acute kidney disease versus CKD: The acuity of the renal disease is important for both diagnostic and prognostic purposes. Establishing a time course for the loss of renal function helps the clinician to narrow the differential diagnosis to processes that acutely injure the kidney or those that cause a more gradual, insidious loss of function. It also provides important information about the likelihood of renal recovery, since most CKD processes cause irreversible damage.
Localization of renal injury: With intrinsic renal injury, the underlying process should be localized to vascular, glomerular, tubular, or interstitial compartments. This can be done using the clinical context, serologic tests, and urinary findings, as discussed later in this textbook. Localization of the injury helps the clinician to narrow the differential diagnosis and provide treatment targeted to specific lesions.
Stage of disease: In both acute and chronic renal diseases, it is important to identify the severity or stage of the disease process. The rise in creatinine and fall in urine output can be used to stratify the stage of acute kidney injury, while the estimated GFR and degree of urine protein excretion can be used to stratify CKD. These staging criteria are described in later chapters of this textbook.
Diagnostic Testing
Estimating GFR
Serum markers, such as creatinine and blood urea nitrogen, are commonly used to track changes in GFR. They are inexpensive and convenient tools, but their limitations and shortcomings must be understood.
When used in isolation, serum markers can provide only general information about trends in renal function.
Levels of these markers rise when there is poor renal clearance and fall when clearance improves.
Levels need to be interpreted in the patient’s clinical context, with particular attention to historical laboratory values, in order to provide meaningful information about the acuity or severity of renal impairment.
Certain patient characteristics and drug effects can alter the serum levels of markers without changing true renal function.
A slightly elevated serum creatinine level in an extremely muscular individual may reflect a higher degree of creatinine generation rather than an impairment in renal function.
Conversely, a normal serum creatinine may overestimate true renal function if a patient is extremely small or cachectic, since these individuals generate less creatinine than average.
Drugs such as cimetidine and trimethoprim inhibit tubular secretion of creatinine and can thus lead to elevations in serum creatinine without impairing GFR.
Comorbidities such as upper GI bleeding or steroid use can cause blood urea nitrogen levels to increase.
It is also important to recognize that the relationship between the change in creatinine and the change in renal function is nonlinear. For example, a change in creatinine from 1.0 to 1.4 mg/dL represents a greater decline in kidney function than a change from 3.0 to 3.4 mg/dL, even though there is a 0.4 mg/dL difference in both examples.
The most commonly used markers are summarized in Table 1-1 below. Of these, serum creatinine is utilized most frequently in day-to-day clinical practice.
Equation-based estimates of GFR incorporate serum markers and patient-dependent variables such as race and gender into mathematical models that approximate GFR in the steady state. A variety of online calculators are available for each equation, as the math is not always easy to do mentally. These equations provide useful quantitative approximations of GFR, but, like serum markers, their limitations need to be appreciated.
All estimates of GFR are only valid in the steady state. In acute kidney injury, when creatinine levels are fluctuating or gradually reaching a plateau level, GFR cannot be approximated with these equations.
The Cockcroft–Gault equation is the oldest of the three equations and has several limitations attributable to the discrepancy between weight and muscle mass. However, this equation continues to be important since it was used in most drug dosing studies to approximate renal function.
The MDRD equation was initially derived in a nonhospitalized, nondiabetic population.1 It loses accuracy when applied to obese patients and can underestimate GFR in patients with normal renal function.
TABLE 1-1 SERUM MARKERS OF RENAL FUNCTION
Serum Marker
What It Measures
Use and Limitations
Creatinine
Accumulation of a muscle-derived metabolite that is predominantly cleared by glomerular filtration.
A reduction in GFR results in a rise in serum creatinine. However:
- Creatinine is highly dependent on muscle mass. Individuals at the extremes of muscle mass may have physiologic values that are lower or higher than the reference ranges.
- Dietary intake and drugs that inhibit tubular secretion (notably cimetidine and trimethoprim) may falsely elevate creatinine levels.
Blood urea nitrogen (BUN)
Accumulation of urea, a product of protein metabolism.
Although BUN may rise in renal disease, an elevated BUN is not specific for renal impairment. Increased generation (upper GI bleed, steroid use) and renal reabsorption (volume contraction) are common confounders.
Cystatin C
Cystatin C is generated at a steady rate by nucleated cells. It is filtered at the glomerulus and metabolized (but not reabsorbed) in the tubules.
Equations that utilize cystatin C in combination with creatinine may be more accurate in estimating GFR than those that utilize creatinine alone.
- Creatinine is highly dependent on muscle mass. Individuals at the extremes of muscle mass may have physiologic values that are lower or higher than the reference ranges.
The CKD-EPI equation performs better than either the Cockcroft–Gault or MDRD equations when estimating GFR in patients with a true GFR >60 mL/min/1.73 m2.2 As such, it is often preferred in the general population.
See summary of equations to calculate renal function in Table 1-2.
Timed collections are used to directly calculate clearance. Clearance describes the quantity of fluid that is completely cleared of a marker over a definite period of time. When a marker is removed exclusively by renal filtration, clearance = GFR.
Inulin was considered the classic gold standard marker for such measurements. Inulin is cleared by glomerular filtration and is neither reabsorbed nor secreted by the renal tubules. Other substances with similar properties (iothalamate, ethylenediaminetetraacetic acid, and iohexal) are now used more commonly to obtain precise measurements of GFR. Although these methods are useful in obtaining a very accurate GFR measurement, they are neither cost-effective nor convenient for most purposes and are used only in specific situations that require more precision than estimates from creatinine clearance (CrCl).Related posts:
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