Kidneys using creatinin

Therapeutic uses Thiazide diuretics decrease blood pressure in both the supine and standing positions postural hypotension is rarely observed, except in elderly, volume-depleted patients. These agents counteract the sodium and water retention observed with other agents used in the treatment of hypertension (for example, hydralazine). Thiazides are therefore useful in combination therapy with a variety of other antihypertensive agents including (3-blockers and ACE inhibitors. Thiazide diuretics are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function (creatinine clearance less than 50 mls/min). Loop diuretics may be required in these patients. 

Renal function is an indication of the physiological state of the kidney glomerular filtration rate (GFR) describes the flow rate of Altered fluid through the kidney, while creatinine clearance rate (Ccr) is the volume of blood plasma that is cleared of creatinine per unit time, and is a useful measure for approximating the GFR. Most clinical tests use the plasma concentrations of the waste substances of creatinine and urea, as well as electrolytes, to determine renal function. The nephron is the functional unit of the kidney (Figure 10.1) it consists of two parts ... 

Intravenous cidofovir is well tolerated. The major treatment-limiting toxicity of this drug is irreversible nephrotoxicity (Plosker and Noble, 1999). Intravenous pre-hydration with normal saline and administration of oral probenecid must be used with each cidofovir infusion to lessen the effects on the kidney. Serum creatinine and urine protein must be monitored with each infusion and adjusted accordingly. Other adverse effects associated with its use are neutropenia and peripheral neuropathy (Plosker and Noble, 1999). 

For the diagnosis of kidney function, creatinine determinations in serum are increasing in popularity over urea measurements, since the creatinine level is not affected by a high protein diet or by metabolic rate, as is the case for urea. Enzymatic methods use either creatinine amido-hydrolase (EC 3.5.2.10) or creatinine iminohydrolase (EC 3.5.4.21) ... 

The most commonly used criteria for the diagnosis of Balkan nephropathy are those proposed by Danilovic et al [99]. They include (1) farmers in the endemic villages, (2) familial history positive for endemic nephropathy, (3) mild proteinuria, (3) low specific gravity of the urine, (4) anemia, early occurrence, normochromic or hypochromic, (5) retention of nitrous compounds in the blood (urea > 50 mg/dl, creatinine > 1.5 mg/dl), (6) symmetrically shrunken kidneys. Using these criteria, Danilovic classified patients into the following groups ... 

Nitrogen compounds commonly determined are creatinine, urea, and uric acid. Creatinine is an end product of the energy process occurring within the muscles, and is thus related to muscle mass. Creatinine in urine is commonly used as an indicator and correction factor of dilution in urine. Creatinine in serum is an indicator of the filtration capacity of the kidney. Urea is the end product of the nitrogen luea cycle, starting with carbon dioxide and ammonia, and is the bulk compoimd of urine. The production of uric acid is associated with the disease gout. In some cases, it appears that the excess of uric acid is a consequence of impaired renal excretion of this substance. 

Saline laxatives containing magnesium, potassium, or phosphates should be used cautiously in persons with reduced kidney function. Monitor appropriate serum electrolyte concentrations in patients with unstable renal function evidenced by changing serum creatinine or creatinine clearance. 

Baseline serum creatinine, hematology profiles, and serum transaminases with repeat levels at 6- to 12-month intervals are useful in identifying specific toxicities to the kidney, liver, GI tract, or bone marrow. 

In the muscle, phosphocreatine and creatine undergo cyclisation to form creatinine (Figure 8.20(b)). Since creatinine cannot be metabohsed, it is released from muscle and is then excreted in the urine. This biochemical process is useful in clinical practice, since creatinine production is spontaneous and is remarkably constant 1.7% of the phosphocreatine and creatine in muscle cyclises each day, so that its concentration in blood provides an indication of the glomerular filtration rate, and hence provides an indication of the function (i.e. the health) of the kidney. 

Uric acid is the end product of the purine metabolism. When uric acid excretion via the kidneys is disturbed, gout can develop (see p. 190). Creatinine is derived from the muscle metabolism, where it arises spontaneously and irreversibly by cyclization of creatine and creatine phosphate (see p. 336). Since the amount of creatinine an individual excretes per day is constant (it is directly proportional to muscle mass), creatinine as an endogenous substance can be used to measure the glomerular filtration rate. The amount of amino acids excreted in free form is strongly dependent on the diet and on the ef ciency of liver function. Amino acid derivatives are also found in the urine (e.g., hippu-rate, a detoxification product of benzoic acid). 

Abnormal clearance may be anticipated when there is major impairment of the function of the kidney, liver, or heart. Creatinine clearance is a useful quantitative indicator of renal function. Conversely, drug clearance may be a useful indicator of the functional consequences of heart, kidney, or liver failure, often with greater precision than clinical findings or other laboratory tests. For example, when renal function is changing rapidly, estimation of the clearance of aminoglycoside antibiotics may be a more accurate indicator of glomerular filtration than serum creatinine. 

The hemodialyzer, also known as the artificial kidney, is a device that is used outside the body to remove the so-called the uremic toxins, such as urea and creatinine, from the blood of patients with kidney disease. While it is a crude device compared to the exquisite human kidney, many patients who are unable to receive a kidney transplant can survive for long periods with the use of this device. 

Degradation Creatine and creatine phosphate spontaneously cyclize at a slow, but constant, rate to form creatinine, which is excreted in the urine. The amount of creatinine excreted is proportional to the total creatine phosphate content of the body, and thus can be used to estimate muscle mass. When muscle mass decreases for any reason (for example, from paralysis or muscular dystrophy), the creatinine content of the urine falls. In addition, any rise in blood creatinine is a sensitive indicator of kidney malfunction, because creatinine is normally rapidly removed from the blood and excreted. A typical adult male excretes about 15 mmol of creatinine per day. The constancy of this excretion is sometimes used to test the reliability of collected 24-hour urine samples—too little creatinine in the submitted sample may indicate an incomplete sample. 

Dofetilide is 100% bioavailable. Verapamil increases peak plasma dofetilide concentration by increasing intestinal blood flow. Eighty percent of an oral dose is eliminated by the kidneys unchanged the remainder is eliminated by the kidneys as inactive metabolites. Inhibitors of the renal cation secretion mechanism, eg, cimetidine, prolong the half-life of dofetilide. Since the QT-prolonging effects and risks of ventricular proarrhythmia are directly related to plasma concentration, dofetilide dose must be based on the estimated creatinine clearance. Treatment with dofetilide should be initiated in hospital after baseline measurement of the QTc and serum electrolytes. A baseline QTC of > 450 ms (500 ms in the presence of an intraventricular conduction delay), bradycardia of < 50 beats/min, and hypokalemia are relative contraindications to its use. 

While renal contribution to overall metabolism is less than hepatic contribution, renal metabolism is of clinical importance. The kidney, in particular the renal cortex, contains many of the same metabolic enzymes found in the liver, including CYPs. Serum creatinine and creatinine clearance are the typical methods used to assess renal function, although 24-hour urine collection can also be used. These are reliable indicators of renal clearance. 

The ratio of renal clearance of digoxin to creatinine clearance decreased with the coadministration of clarithromycin (0.64 and 0.73), and was restored (1.30) after administration of clarithromycin had stopped (326). The role of P-gp efflux in this interaction was confirmed using an in vitro kidney epithelial cell line (326). The administration of itraconazole, a P-gp inhibitor, with digoxin resulted in an increased trough concentration and a decrease in the amount of renal clearance, possibly by an inhibition of the renal tubular secretion of digoxin via P-gp (329). The P-gp modulator verapamil has also been shown to decrease the renal clearance of digoxin (330). 

Renal dysfunction Poor kidney function (10% or less of normal) causes accumulation of antibiotics that are ordinarily eliminated by this route. This may lead to serious adverse effects unless controlled by adjusting the dose or the dosage schedule of the antibiotic. Although serum creatinine levels are sometimes used as an index of renal function for adjustment of drug regimens, direct monitoring of serum levels of some antibiotics is preferred... 

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