Product Development. Gel man Sciences Inc. Ann Arbor, MI 48106. Borek Janik. Antibioticsand p-Aminohippurate. To the Editor: p-Aminohippuric acid (PAll) has.
Tabie 1. Precisionof MagnesiumDetermination Serum controls Beckman 2
Urine controls
Beckman 3
Ortho 1#{149}
Ortho 2
Within run
mg/L b, mg/L CV, %
20.3
4.43 Between run A mg/L 20.9 b,mg/L 1.1 CV, % 5.26 n = 20 each. Ortho controls diluted threefold,
in preciand increased throughput (25 samples in 10 mm).This technique is useful for pediatric and stat determinations. L) volumes, sion, shorter
improvement
analytical
time,
Harold J. Kisner Thomas R. Koch Edward C. Knoblock Dept. of Pathol. Univ. of Maryland Sch. Hosp. 22 S. Greene St. Baltimore, MD 21201
of Med.
and
GeimanKit Modified To the Editor:
We agree
with the conclusions of Kumpel and Wood (1) that adenylate kinase (AK) activity should be suppressed in assays of creatine kinase isoenzymes. Accordingly, the reformulated CK Isozyme U.V. Reagent Set (P.N. 51914), which has been marketed by Gelman Sciences since February 1983, does contain 22 j.mol of diadenosine pentaphosphate and 8.4 mol of adenosine monophosphate per liter, to inhibit AK.
45.5 1.1
21.7
41.5
0.9
0.9 2.20
0.5 2.22
42.0 1.2 2.86
21.7 0.7 3.23
2.42 44.4 1.5 3.38
still indications for this relatively complicated test. In view of the side effects connected with continuous intravenous infusion and bladder catheterization, a single-injection technique is sometimes preferred (1). The patients being so evaluated are often vulnerable due to suspected or verified renal disease and sometimes are taking antibiotics. A recent patient examined at this hospital may deserve reporting as a reminder of the importance of drug interactions that may affect determination of PAll. PAH is usually assayed colorimetrically by use of the condensation product formed after reaction with an amino compound, nitrite (2) or p-dimethylaminobenzaldehyde (3). The latter procedure is used in this laboratory. The, patient, a two-month-old boy with right-sided hydronephrosis together with reflux, was given the PAll-clearance test (in connection with clearance of inulin), the single-injection technique being used. Thus only blood specimens were collected. Table 1 gives the results of PAH determinations in the patient’s serum. Absorbance before the injection of PAH was high, and remained so throughout the
Table 1. Determinationof PAH in Seruma
Reference
reagent improves identification of creatine kinase isoenzymes after electrophoresis. Clin Chem 29, 581 (1983). Letter.
Borek Janik Lab. Product Development Gel man Sciences Inc. Ann Arbor, MI 48106
Antibioticsand p-Aminohippurate To the Editor:
p-Aminohippuric acid (PAll) has classically been used in evaluation of renal plasma flow. This procedure has decreased in importance, but there are
lime, mln 0
A 0.115
5 10 15
0.571
B
0.001 0.527 0.284
20 30
0.441 0.411 0.381 0.311
45 60 75
0.241 0.216 0.179
0.054 0.039 0.026
0.189 0.144 0.091
90
0.154
0.021
105 120
0.134 0.120
0.014
150
0.103
0.006
180
0.094
0.009
0.004 #{149} The table shows results of determinations of the aminobenzene complex at 455 nm from the patient (A) and typical values obtained for another
patient, also
examined
with the single-injection
A standard solution containing 324 Mmol of PAH per liter correspondsto an absorbance of about 0.5. technique (.
methoxazole
to serum in vitro showed
that only sulfamethoxazole influenced assay of PAH. Trimethoprim had no effect, alone or in combination with sulfamethoxazole. Assay of p-aminobenzene derivatives by this technique is nonspecific; several other compounds are known (4) to influence it, most importantly sulfonamides. The medication being received by a patient who is to receive PAH-clearance studies should be made known to the analyst, to avoid interferences. References 1. Barratt TM, Chantler C. Clinical assessment of renal function. In Pediatric Nephrology. MI Rubin, TM Barratt, Eds., Williams & Wilkins Co., Baltimore, MD, 1975, pp 55-83. 2. Bratton AC, Marshall EK. A new cou-
pling component for sulfanilamide determination. J Biol Chem 128, 537-550 (1939). 3. Brim C. A rapid method for the determination ofparu-aminohippuric acid in kidney function tests. J Lab Clin Med 37, 955-958 (1951). 4. Richterich R. Klinische Chemie, Theorie und Praxis, 3rd ed., Karger, Base!, 1971, pp 338-344.
Karl-Eric
Karlmar
Dept. of Clin. Chem. I Karolinska Institutet Huddinge Univ. Hospital S-141 86 Huddinge, Sweden
Significance
of Hyperferritinuria
To the Editor:
Absorbance
1. Kumpel BM, Wood SM. Addition of diadenosine pentaphosphate to creatine kinase
test. We later learned that the patient had received sulfamethoxazole/trimethoprim (Bactrima; Roche) for treatment of a urinary-tract infection. Addition of trimethoprim or sulfa-
Ferritin, the major form in which iron is stored, is widely distributed in body tissues. Small amounts are being constantly released from the tissues into the circulation. In healthy subjects and in patients with iron deficiency or iron overload, the concentration of circulating ferritin is related to the available iron store (1). An abnormally low concentration of ferritin in serum is highly suggestive of iron deficiency; an above-normal concentration may result from various conditions such as iron overload, tissue damage, malignancy, or inflammation (2). Ferritin is also present in trace amounts in urine, originating most likely from renal tubular cells (3, 4). Correlations between urinary and serum ferritin have been reported, an observation that suggests that the concentrations of ferritin in urine and se-
CLINICALCHEMISTRY, Vol.29, No. 12, 1983 2121
lar cell damage, hyperferritinuria being indicative of iron overload or damage of renal tissue, or both.
rum have the same significance and that both reflect the body iron store (4, 5). In patients with chronic hemolytic anemia, however, high concentrations of ferritin in urine, inconsistent with the body iron store, may be observed as .a consequence of massive filtration of unbound hemoglobin through the gbmeruli and its subsequent uptake by the tubular cells (3). We have further investigated the significance of urinary ferritin by studying its relationship with serum ferritin and urinary retinol-binding protein (RBP), the latter being a sensitive and reliable index of renal tubular damage (6). We measured these proteins (7) in eight control subjects and in 69 patients with suspected or established renal damage, including three with transfusional iron overload. Analytical recovery of ferritin in urine averaged 102.8% (SD 11.1%), as tested by supplementing 10 control urmnes with 100 ig of ferritin per liter. The specificity of the ferritin assay in urine was also checked by chromatographing two urine samples on a Sephadex G-200 column and measuring ferritin in the fractions. Urinary ferritin co-eluted with purified spleen ferritin. Table 1 shows the concentration of ferritin in the urine of 77 subjects classified according to the concentration of ferritin in their serum and that of RBP in their urine. For the same range of serum ferritin, urinary ferntin tends, on the average, to increase in proportion to the extent of tubular dysfunction. Conversely, for the same range of urinary RBP, the concentration of ferritin in urine is, in general, related to that in serum. The few exceptions observed in these trends are probably ascribable to an inconsistency between the concentration of ferritin in serum and the iron store or between the total body iron store and that in the kidney. Furthermore, the urinary excretion of ferritin correlated significantly with serum ferritin (r = 0.51, n = 77,p10
24 (8) 168 (4)
170(5)
1. Porter RD, Cathcart-Rake WF, Wan SH, et al. Secretory activity and aryl acid content of serum, urine, and cerebrospinal fluid in normal and uremic man. JLab Clin Med 85, 723-733 (1975). 2. Schwertner HA, Hawthorne SB. Albumm-bound fluorescence in serum of pa. tients with chronic renal failure. Clin Chem
160 (3) 914 (2)
26, 3-
Table 1. Urinary Excretionof Ferrltina(pg/g Creatinine)as a Functionof Ferritinin Serum and Retinoi-BindingProteinin Urine Ferritin In serum, g/L 1000
Retinol-blndlng proteinIn urine, mg/g creatinine
