Serum creatinine derivatives

The search for more potent, selective and safe PPARa agonists has been challenging and only a limited number of compounds have progressed into the clinic. A number of phenoxyacetic acid derivatives and other diverse structures have emerged recently. Oral administration of LY-518674 (6) produced a 208% elevation in HDL and a 96% decrease in serum TG in apoA-I transgenic mice [38,39]. Recent clinical studies with compound 6 revealed a decrease in TG and an increase in HDL similar to fenofibrate. However, compound 6 also raised LDL-C in a dose-dependent fashion, and to a much higher level than seen with fenofibrate [28]. Both agents also raised serum creatinine levels above the upper limits of normal in 35-38% of patients [28]. 

This patient, who had autosomal dominant polycystic kidney disease (ADPKD), almost drowned and then developed ALPE. On July 20, 1990, he nearly drowned in the sea at 1500 hours, and was brought to our hospital by ambulance for dyspnea and severe loin pain at 1620 hours. On admission, metabolic acidosis was observed. His CRP, serum creatinine, CPK, amylase, and urinary protein levels were 1+, 1.5mg/dl, 116 U/l, 592IU/1 (derived from the salivary gland), and 2+, respectively. His body temperature was 37.7°C, and his blood pressure was 110/60 mmHg. His pulse and respiratory rate were 120/min and 22/min, respectively. Delayed CT 6h after the administration of contrast medium showed wedge-shaped contrast enhancement in the noncystic renal parenchyma (Fig. 34). On July 24, a bone scan with MDP revealed patchy lesions (Fig. 35). His serum creatinine level was 1.3 mg/dl, which had decreased to 1.0 mg/dl on July 27. The patient was then discharged. 

B-10) Creatinine as a test of renal function. Creatinine, which is derived from creatine phosphate, normally is excreted almost totally by the kidney. Blood levels of serum creatinine, as well as urea, are useful indices of renal function, their elevation often being a sign of renal insufficiency. 

The use of potentially nephrotoxic drugs requires close monitoring of renal function. The serum creatinine concentration is the most common method utilized to assess renal function but suffers from its lack of sensitivity. In patients with normal baseline renal function substantial renal injury can occur before there is a demonstrable rise in the serum creatinine concentration. A rise in the serum creatinine concentration that just exceeds the normal range may reflect as much as a 50% dechne in the GFR. The failure of the serum creatinine to accurately reflect the degree of renal injury is particularly evident in patients with decreased muscle mass or those with chronic liver failure. Creatinine is produced from the metabolism of creatine in skeletal muscle. In turn, creatine is derived from the liver. In the setting of chronic liver disease or malnourished patients with decreased muscle mass creatinine synthesis becomes impaired. As a result... 

Serum creatinine is an amino acid compound derived from the metabolism of creatine in skeletal muscle and from dietary meat intake [35]. The serum creatinine concentration (Scr) is a commonly used marker for the estimation of adequate renal function due to the fact that it is released into the plasma at a relatively constant rate, is freely filtered by the glomerulus, and is not metabolized nor reabsorbed by the kidney. Various reference ranges for the Scr take into consideration differences in age and gender (Table 5), but fail to consider other variables such as race, body weight and muscle mass. As a result, a Scr within the reference... 

Calculated Clearance. The mathematical relationship between plasma creatinine and GFR can be improved by correcting for the confounding variables that make that relationship nordinear. More than 25 different formulas have been derived that estimate GFR using plasma creatinine corrected for some or all of gender, body size, race, and age. These may produce a better estimate of GFR than serum creatinine alone. Indeed the National Kidney Foundation of the United States has recommended that such estimates should be used in preference to serum creatinine, and that either the Cockcroft and Gault or Modification of Diet in Renal Disease (MDRD) formula should be used in adults. The Schwartz and Counahan-Barratt formulas are recommended for use in children. 

Polycyclic compound 478, which forms stable complexes with urea, guanidine, amidines and their derivatives, is covered by patents (1991USP15030728, 1994USP5283333). These complexes were used in a biological investigation. Receptor betaine molecule 479 was constructed for diagnostic tests for blood (serum) creatinine and renal insufficiency. 

The acute renal failure is typical for acute tubular necrosis and is characterized by a urine sediment with granular pigmented casts, and benzidine positive urine often in the absence of significant hematuria. With rhabdomyolytic acute tubular necrosis the urinary sodium concentration and fractional excretion of sodium are not always increased as in classic acute tubular necrosis [99]. One half to two-thirds of patients have ohguria, which may last from hours to many weeks. During this phase of the acute renal failure, there is a very rapid rise in the serum creatinine (often > 2.0 mg/ dl/ day), and profound increases in the serum levels of a variety of solutes normally foimd in muscle or produced from muscle derived precursors. Thus, fhe levels of potassium, phosphate, and uric acid all rise dra-... 

A 30-year-old immunocompetent woman was given intravenous aciclovir 45 mg/kg/day for viral meningoencephahtis [17 ]. Acute renal insufficiency developed (serum creatinine 63 p.mol/1 on day 0, increasing to 385 p.mol/1 on day 12) urine analysis showed birefringent crystals, deemed typical of aciclovir-derived crystals on spectrophotometric examination. The renal dysfunction resolved after withdrawal of aciclovir and rehydration. 

Epoetin delta differs from the other erythropoietin derivatives in that it is produced in a human cell line using gene-activation technology. It has been approved in Europe but not in the USA for the treatment of anemia associated with chronic kidney disease. In patients with cancer and anemia who were given epoetin delta, possible treatment-related serious adverse events were hypertension, increased serum creatinine, and peripheral vascular disease [99 ]. There was a correlation with higher doses, suggesting that a dose of 150 lU/kg would be most appropriate to start with for this indication. 

P2.m. The cysteine proteinases are one of four major classes of endoproteinases that possess the ability to degrade intact glomerular basement membranes [144]. All nucleated cells produce cystatin at a stable rate. More than 99% is freely filtered by the glomerulus with little secretion or reabsorption. As a result, it has many of the ideal features for use as a marker of kidney function and eshmate of GFR. Serum cystatin C concentrations demonstrate a good inverse correlation with radionuclide derived measurements of GFR and has been shown in several studies to be superior to creatinine and comparable to iohexol clearances in estimating eGFR [145,146]. 

The PLS trials were preceded by a normalization stage (aU spectra were normalized to a common integrated intensity in the SCN absorption at 2060cm ). The second derivatives of the normalized spectra then served as the basis for the analyses. Scatterplots comparing the reference analytical levels to the IR-predicted albumin, total protein, glucose, cholesterol, tri ycerides, and urea are shown in Figure 12. The corresponding PLS models and their analytical accuracies are compiled in Table 4. Attempts to quantitate uric add and creatinine proved unsuccessful due to their relatively low serum concentrations. 

Klaus et al. (1991) presented a TLC method for the simultaneous analysis of uric acid, creatine, creatinine, and uric acid together with glucose in the urine and serum of patients with diabetes and other carbohydrate anomalies. The method requires no special sample preparation, and separations are done on amino-modified HPTLC precoated plates. Detection of all substances is achieved by simply heating the plates to give stable fluorescent derivatives. 

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