Serum creatinine biomarkers

In humans, serum creatinine is dependent on non renal factors independent of kidney function e.g. muscle mass, nutritional status, infection, volume of distribution. Also, serum creatinine is dependent on renal factors that are independent of function. For example, certain drugs like trimethoprim and cimetidine elevations in serum creatinine by altering the normal elimination pathways of creatinine. In addition, in humans, alterations in serum creatinine may lag several days behind actual changes in GFR. Earher detection of AKI with a kidney specific biomarker may be essential for early and successful treatment of AKI in humans. 

In humans, there seems to be a dose-dependent association between compound A exposure and the appearance of urinary biomarkers such as albumin, glucose, and the enzymes NAG or a-GST. These findings appear in studies when the compound A exposure exceeds 160 ppm/ hour [71-74], while they are absent in studies with lower compound A exposure [75-77]. In all studies associated with higher exposure of compound A, the urinary markers are transient, lasting 3-5 days with total normalization within one week. There is no correlation between serum creatinine and the urinary markers. 

Because control of renal function and blood pressure is multifactorial, the causal contribution of lead is difficult to isolate. A number of biomarkers (blood, tibial, and patella lead), and a variety of populafions differing by age, gender, race, and level of exposure are examined. Systohc and diastolic pressures are assessed separately and may be analyzed both as continuous or dichotomous variables. Kidney function is assessed by the serum creatinine concentration or empirical adjustments of the creatinine to estimate GFR. Large populations are required to achieve statistical significance amidst the noise of the multifactorial causality and the imprecision of outcome measures. Inconsistent results and weak correlations are, therefore, expected as smaller and smaller outcome effects are evaluated. 

Much research progress is also being made in safety biomarkers for renal tox-icities. Current clinical practice relies heavily on buildup of serum creatinine to determine whether the kidneys are functionally impaired. Since serum creatinine does not change until kidney function is reduced by over 50 percent, more sensitive biomarkers revealing subtle injury are needed.32... 

Biomarkers for decreased function include increases in urinary proteins and elevation of serum creatinine or 2-microglobulin. Biomarkers for renal cytotoxicity include increases in urinary excretion of antigens and enzymes located within renal tissues. Biomarkers for biochemical changes occurring within the kidneys include eicosanoids, fibronectin, kallikrein activity, and glycosaminoglycans in urine. 

Lead workers (N = 52) and controls (N = 44) Exposed mean = 64 p,g/dl control mean = 26 p,g/dl Renal biomarkers One-third of Pb workers had elevated serum creatinine versus 1/44 of controls Pinto de Almeida etal. (1987)... 

The influence of genotype on various biomarkers for renal function and cardiovascular effects from Pb exposure is apparent with interactions for serum creatinine, while the meta-analysis showed little effect of genotype on SBP or DBP. 

Commonly used soluble biomarkers include low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), triglycerides (TG), serum creatinine, and hepatocellular enzymes, as well as a host of other routine clinical laboratory measurements. 

A complete physical examination and laboratory analysis are needed to rule out secondary causes and to assess kyphosis and back pain. Laboratory testing may include complete blood count, liver function tests, creatinine, urea nitrogen, calcium, phosphorus, alkaline phosphatase, albumin, thyroid-stimulating hormone, free testosterone, 25-hydroxyvitamin D, and 24-hour urine concentrations of calcium and phosphorus. Urine or serum biomarkers (e.g., cross-linked N-telopeptides of type 1 collagen, osteocalcin) are sometimes used. 

Cystatin C is nearly completely metabolized by proximal renal tubular cells. As a consequence, under ordinary circumstances there is little to no detectable cystatin C present in the urine. Thus, a true clearance of cystatin C cannot be determined. However, in the presence of tubular damage, cystatin C may be detected in the urine [147,148] and may be more sensitive to early and mild changes of kidney function compared with creatinine [149,150]. In this regard, elevation in serum cystatin C consistent with AKI, defined by at least a 50% increase from baseline, was evident 1-2 days prior to changes in SCr [151]. Finally, in patients with AKI, elevated urinary cystatin C was highly predictive of subsequent need for acute renal replacement therapy and outperformed several other urinary biomarkers in some studies [152]., but not in others [152a]... 

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