Calculating glomerular filtration rate in a young man with a large muscle mass

Serum creatinine level, the most commonly used measure of kidney function in clinical practice, varies with factors other than kidney function. These include age, sex, muscle mass, and dietary protein intake. Glomerular filtration rate (GFR) is therefore widely accepted as a better marker. Numerous equations using the serum creatinine level have been developed to calculate estimated GFR (eGFR) (Box 2). Recently, automated reporting of eGFR using the MDRD (modification of diet in renal disease) formula has been introduced, but limitations exist, especially with extremes of body size. Our patient illustrates the difficulties of calculating GFR for a person with a large muscle mass, with different methods giving widely varying results.

The recently published CARI (Caring for Australasians with renal impairment) guidelines recommend that serum creatinine level alone should not be used to measure kidney function, because of the multitude of factors other than renal function that can affect this marker.1,2 Serum creatinine is derived from the metabolism of creatine in muscle and the generation of creatinine tends to be proportional to muscle mass.

In adults, the abbreviated (4-variable) MDRD, the 6-variable MDRD, and the Cockcroft–Gault equations generally provide reliable eGFRs. The Cockcroft–Gault formula is probably the most widely recognised formula for conversion of serum creatinine level, although with reductions below 60 mL/min it becomes increasingly inaccurate compared with the MDRD formula.

Recently, the abbreviated MDRD formula has been used in the automated laboratory reporting of eGFR in Australia, given extensive validation with no correction needed for body surface area. It is important to note that the different units for GFR measurements (mL/min for Cockcroft–Gault versus mL/min/1.73 m2 for MDRD) can create some discrepancy in their comparison (see Box 1).

MDRD and Cockcroft–Gault equations are essentially rescaled serum creatinine levels with the same pitfalls as using the serum creatinine level itself. They are based on statistical models predicting averages, and our patient was not average. Therefore, clinical judgement is always required with eGFR, and the clinician has the advantage of being able to consider dietary history and physical examination — factors not considered in these equations.

Previously, 24-hour urine collections to assess creatinine clearance were commonly used. These are inconvenient, inaccurate because of inadequate collection techniques, and, with severe renal impairment, creatinine clearance overestimates GFR. With worsening impairment there is an increase in tubular creatinine secretion, ranging from 10% to 50%, and therefore variations may alter the relationship between serum creatinine level and GFR.3

Nuclear medicine scans provide validated direct measures of GFR and are useful in circumstances of extremes of body size or age, high or low dietary intake of creatinine or creatine supplements, and patients with muscle disease or atrophy. They determine renal clearance of exogenous filtration markers, most commonly DTPA (diethylenetriaminepentaacetate), and provide acceptably accurate measurements, although it is recognised that they may overestimate GFR.1,2 The disadvantages of radionucleotide GFR measurement relate to safety with the use of radiolabelled compounds and the cost.

In our patient, different methods of GFR measurement provided a range from 4.96 to 13.51 mL/min/1.73 m2, depending on the equation or the investigation used. The CARI guidelines suggest that dialysis should be commenced when GFR falls below 10 mL/min/1.73 m2, if associated with symptomatic uraemia or malnutrition, or below 6 mL/min/1.73 m2, if asymptomatic.4 Initiation of dialysis in our patient, with risks of temporary dialysis access, was weighed against the decision to wait for a renal transplant, given that the patient was initially relatively asymptomatic. The best option for renal replacement therapy is kidney transplantation where appropriate, and the patient’s mother had volunteered as a potential donor. The commencement of dialysis is sometimes a difficult decision and clinicians need to recognise the inaccuracies with eGFR measurement. Symptoms, treatment options and rate of GFR decline are among a multitude of factors that must be taken into account in the decision to initiate dialysis.

Having illustrated some of the limitations in determining renal function using eGFR, we strongly advocate routine automated reporting in clinical practice. eGFR is extremely useful for identifying patients at risk of progressive chronic kidney disease and correlates well with complications, including an increased risk of cardiovascular morbidity and mortality. An educational program is underway, involving distributed written material and short courses organised by Kidney Health Australia, to ensure that information is available to help health professionals interpret eGFR values. It should be appreciated that there are specific clinical settings in which eGFR is not appropriate and GFR should be measured directly through other methods.