Clinical chemistry measures

The most useful markers for changes in renal function and renal toxicity without special manipulation are clinical chemistry markers, including the newly identified set of seven identified by the Critical Path Initiative [5]. These can identify specific impaired function or toxicity (Table 7.7). 

Brush border alanine-aminopeptidase y-glutamyl-transferase trehalase 

Lysosomes p-glucuronidase N-acetyl-p-D-glucosaminidase acid phosphatese p-galactosidase 

Cytosol lactate dehydrogenase leucine aminopeptidase p-glucosidase fructose-1,6 biphosphatase (proximal tubule) pyruvate kinase (distal tubule) 

Proteinuria. In general, albuminuria leads to increases in the permeability of the glomerular capillary wall, whereas urinary release of low-molecular weight proteins (p-2-mg) suggest an impairment in tubular reabsorption. 

---

In some human studies where clinical chemistry measurements but no renal biopsies were performed, the only parameter of renal function shown to be affected was an increase in the levels of NAG in the urine. NAG is a lysosomal enzyme present in renal tubular cells that has been shown to be a sensitive indicator of early subclinical renal tubular disease. The mechanism by which lead affects the release of NAG from renal tubular cells is not known, but it is suggested that lead could attach to kidney cell membranes and alter membrane permeability (Chia et al. 1994). 

Weil, C.S. (1982). Statistical analysis and normality of selected hematologic and clinical chemistry measurements used in toxicologic studies. Arch. Toxicol. Suppl. 5 237-253. 

Walden CE, Knopp RH, Johnson JL, Heiss G, Wahl PW, 183. Hoover JJ. Effect of estrogen/progestin potency on clinical chemistry measures. The Lipid Research Clinics Program 184. Prevalence Study. Am J Epidemiol 1986 123(3) 517—31. 

Assessment of the present situation regarding quality of spectrophotometric measurements [5] suggested the need for basic principles to be followed to assure the required traceability. Lately, some efforts have been focused on elaborating traceability schemes for clinical chemistry measurements. The purpose of any traceability scheme is to provide comparability, compatibility and consistency between the huge numbers of chemical measurements needed everyday, universally in clinical laboratories. On the other hand, the quality accredita-... 

Estrogens in clinical chemistry Measurement of endogenous estrogens by immunoassays, LC-MS (ESI, APCI, APPI) and GC-MS. [15]... 

In some cases, drug exposure may be followed for the lifetime of the animal. In these situations clinical chemistry measurements can be made as well as pathological examination of post-mortem samples. Chronic studies can be carried out in animals at the same time that clinical trials are undertaken (see Chapter 14). 

Administration of clldlnlum for 1 yr at 5.0, 25, and 50 mg/kg In the diet of rats did not result In drug-related toxicity. Blood counts, clinical-chemistry measures, and results of gross and microscopic studies remained within normal limits (28). 

The main reasons for the current lack of comparability at working level include an insufficient awareness of uncertainty and source of error, a lack of high quality reference materials and no recognized system for intercomparison of traceable clinical chemistry measurements. In addition, the limit results were obtained in the absence of a reliable uncertainty budget and insufficient QA procedures. In fact, in the national area the introduction of adequate QA procedures is making its first steps. 

Figure 4-12 Design of amperometric enzyme electrode based on anodic detection of hydrogen peroxide generated from oxidase enzymatic reaction (e.g., glucose oxidase) (A), and expanded view of the sensing surface showing the different membranes and electrochemical process that yield the anodic current proportional to the substrate concentration in the sample (B). (From Meyerhoff N, New in vitro analytical approaches for clinical chemistry measurements in critical care. Clin Chem I990 36 I570.)...

Tris buffers are commonly used in clinical chemistry measurements. 

NAD is a common cofactor in clinical chemistry measurements. The reactions are monitored by measuring the NADH concentration. 

It is known that different rat strains differ in their metabolism—particularly in hepatic tissue reactions and therefore exposure to the test compound—so it should not be too surprising that clinical chemistry measurements may reflect these differences. When animal strains or suppliers are changed, new reference ranges should be established and compared with existing data. 

To interpret clinical chemistry measurements, we need to consider some of the variables in toxicological experiments. 

In general, the variations due to analytical components in clinical chemistry measurements usually are much less than variations due to the preanalytical factors. The... 

In rats orally administered 1.72, 3.43, or 6.86 g/kg of a freeze-dried noni fruit puree daily for 90 days, no histopathological changes or evidence of dose-related responses in hematological and clinical chemistry measurements, including liver function tests, were observed. Based on the results the NOAEL for freeze-dried noni fruit puree was determined as greater than 6.86 g/kg body weight, equivalent to approximately 90 ml/kg of noni fruit juice (West et al. 2009). 

Table 7.7 Clinical Chemistry Measures of Specific Renal Effects...

Until recently, only one toxicology study on CLA with an isomeric composition similar to most commercial preparations had been published (4). In this study, feeding CLA for 36 wk at a level of 1.5% w/w in the diet did not produce any toxicity in male Fischer 344 rats. The protocol for this study had a number of limitations including the use of a single dose level, single sex, no clinical chemistry measurements and... 

Meyerhoff, M. (1990) New in vitro analytical approaches for clinical chemistry measurements in critical care. Clin. Chem., 36,1567-1572. 

---