Over the next few days, his serum creatinine did not improve significantly and he underwent a renal biopsy. This showed nephrosclerosis, tubular atrophy and mild interstitial fibrosis with 10/15 glomeruli appearing completely normal. Immunofluorescence was also normal. The findings on renal biopsy did not correlate with his serum creatinine level.
In the Jaffé reaction, creatinine reacts with picric acid to form a colored complex. This forms the basis for the commonest methods for measuring serum creatinine. However, this test has well known limitations. Under normal circumstances, the Jaffé reaction overestimates the serum creatinine concentration by 10-20% because of the presence of endogenous chromogens. These chromogens include acetone and acetoacetate which, in the case of diabetic ketoacidosis, can lead to a significant overestimation of the serum creatinine. Similarly, certain drugs, including cephalosporins, flucytosine and barbiturates, can interfere with the assay.
Recently, more specific enzymatic assays have been developed which are thought to be less susceptible to falsely high readings. These involve measuring the generation of ammonia when creatinine is hydrolyzed.
In the case above, pseudohypercreatininemia was suspected because the biopsy results did not match the serum creatinine. The hospital was using an enzymatic method for measuring the creatinine concentration. When the patient’s serum cystatin C was checked, it was found to be only slightly elevated and his serum creatinine by the Jaffé method was only 1.0 mg/dl. This is the third reported case of pseudohypercreatininemia in a patient with WM where the enzymatic method was used to determine the serum creatinine. The mechanism for the false reading is uncertain but it may be related to increased turbidity or binding of the Ig to the enzyme.
This case shows the limitations of the test for serum creatinine but also demonstrates the importance of knowing which test is used in your own institution. And if you do see a patient with an isolated creatinine elevation, think of pseudohypercreatininemia as a cause.
Posted by Gearoid McMahon MD