4.15: Renal Disease, Creatinine Analysis

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A 48 year old black male was brought to the emergency room, semicomatose. His initial blood chemistries were as follows: pH 7.25, PCO₂ 21, PO₂ 94, bicarbonate 18, base deficit 17 mmol/L, glucose 6857 mg/L (glucose oxidase), BUN 190 mg/L (enzymatic, urease/GLDH), creatinine (alkaline picrate) 21 mg/L (check upon repeat), ketones large (> 1600 mg/L), electrolytes within normal range.

The patient was treated intravenously with isotonic saline, insulin, potassium, chloride, and 50 g/L dextrose. The patient improved rapidly, and his blood glucose decreased. Twenty-four hours after entering the hospital, the following results were obtained on a renal profile: glucose 2050 mg/L, BUN 180 mg/L, creatinine 9.5 mg/L, electrolytes within normal range, ketones negative.

The physician in charge of the patient does not believe the patient was in renal failure. Since the creatinine result is now only slightly elevated while the BUN result is within the reference range, the physician questions the initial creatinine value.

QUESTION

What is the reason for the discrepancy in creatinine values?

Questions to Consider

How do serum urea and creatinine concentrations change in renal failure? In dehydration?
What methods are available for the measurement of creatinine?
Are there any advantages or disadvantages for the measurement of creatinine by the alkaline picrate reaction versus the enzymatic methods?
How is BUN measured? Are there any major interferants of BUN assays?

Answer

The reason for the apparently discrepant results for creatinine was the presence of large amounts of ketones which give a strong positive interference in the end-point alkaline picrate reaction. The second specimen, which was free of ketones following therapy, did not have interference from ketones and reflected true renal status as did the BUN results in both specimens.

Answers to Questions to Consider

In renal failure, both serum urea and creatinine become elevated usually in a parallel manner (Chapter 26). In dehydration, the urea may be elevated without proportional changes in creatinine (Chapter 26).
The most popular method of measuring creatinine is the alkaline picrate method. When performed without prior adsorption to, and elution from, fuller’s earth, this method is not very specific; ketones, proteins, and many other compounds also react with the reagent (See Method Creatinine CD-ROM). The alkaline picrate method can be performed as an end-point or kinetic procedure.

Some methods for the routine measurement of creatinine (See Method Creatinine CD-ROM) employ enzyme reagents. The creatinine amidohydrolase reaction uses three additional coupled reactions, eventually measuring the conversion of NADH to NAD⁺. The creatinine iminohydrolase reaction generates NH₃ which is monitored by employing the GLDH reaction and the conversion of NADPH to NADP⁺. Both of these enzymatic assays require enzyme reagents of high purity. The latter coupled reaction sequence is especially sensitive to the presence of endogenous ammonia.
The reasons for the widespread use of the alkaline picrate method have been its low cost and the lack of a suitable alternative. The alkaline picrate method has relatively poor specificity, because of positive interferences from ketones and protein, and negative interferences from bilirubin and hemoglobin (See Method Creatinine CD-ROM). The use of fuller’s earth to remove these interferences is not practical when employing automated analyses.

The more recently developed enzymatic methods have better specificity than the alkaline picrate procedure. The only major interferent is ammonia in the creatinine iminohydrolase method. The primary disadvantages of the enzymatic methods have been their high cost and the difficulty of securing pure enzyme reagents.
BUN can be measured by diacetyl monoxime or, more frequently, by a urease reaction. The urease reaction can be monitored by conductimetric means or by measuring the NH3 formed by a GLDH reaction (See Method Urea CD-ROM). None of these methods have significant interference by protein or ketones.