Kidney creatinine clearance

Carboplatin displays less nephro-, oto- and neurotoxicity. However, myelosuppression is more frequent, and as the drug is exclusively cleared through the kidney, adjustment of dose for creatinine clearance must be accomplished. 

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

Creatinine clearance < 60 mL/min/1.73 m2 (stages III-V chronic kidney disease), diabetes mellitus (with renal insufficiency), hypertension, chronic heart failure, cirrhosis, nephrosis, age >75 yr, cholesterol emboli syndrome, multiple myeloma (questionable)... 

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. 

O Equations to estimate creatinine clearance that incorporate a single creatinine concentration (e.g., Cockcroft-Gault) may underestimate or overestimate kidney function depending on whether acute renal failure is worsening or resolving. 

Several equations have been developed to assess unstable kidney function. The Jelliffe equation (Table 22-1) estimates creatinine clearance by considering the change in serum creatinine over a specified time period.11 While it is more mathematically difficult to calculate, it better estimates creatinine clearance in patients with rapidly changing kidney function compared to an equation that only includes a single creatinine concentration. 

Assess kidney function by evaluating a patient s signs and symptoms, laboratory test results, and urinary indices. Calculate a patient s creatinine clearance to evaluate the severity of kidney disease. 

The therapeutic dose of acamprosate is 666 mg orally three times daily, and it is supplied as a 333 mg tablet. It can be started at the full dose in most patients without titration. It differs from disulfiram and naltrexone in that it is excreted by the kidneys without liver metabolism. Consequently, it is contraindicated in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/minute), and dose reduction is necessary when the creatinine clearance is between 30 and 50 mL/minute. The most common side effects are gastrointestinal and include nausea and diarrhea. Rates of suicidal thoughts were also increased in patients treated for 1 year with acamprosate (2.4%) versus placebo (0.8%). If necessary the total daily dose maybe decreased by 1 to 3 tablets (333-999 mg) per day to alleviate side effects. 

Although determination of creatinine clearance rate is a standard clinical procedure, it is difficult to carry out mainly because accurate collection of total urine output over a 24-hour period is required. It can never be certain that this requirement has been met. Since creatinine is produced continuously in muscle and is cleared by the kidney, renal failure is characterized by elevated serum creatinine levels. The degree of elevation is directly related to the degree of renal failure—if it is assumed that the production of creatinine in the muscle mass is constant and that renal function is stable. When these assumptions are valid, there is a direct relationship between serum creatinine level and kanamycin half-life, as shown in Fig. 9. The equation of the line in Fig. 9 is... 

The most common adverse effects involve the GI system (gastritis, bleeding, and perforation), kidneys (renal papillary necrosis, reduced creatinine clearance [CLcr]), cardiovascular system (sodium and fluid retention, increased blood pressure), and CNS (impaired cognitive function, headache, dizziness). 

Methotrexate is an antimetabolite drug that is excreted primarily by the kidney. It is contraindicated in significant renal impairment and in hepatic impairment. It is nephrotoxic and accumulation may occur in renal impairment. Dose should be reduced in renal impairment that is not severe and drug should be avoided if creatinine clearance is less than 20 mL/minute. 

P743 was tested on a validated multiple-insult rat model [35] involving transient renal ischemia, dehydration, uninephrectomy and selective injection of a high dose (about 1.8 gl kg ) into the single remaining kidney and was found to have only minimal effects on GFR (evaluated by the endogenous creatinine clearance) and induced moderate enzymuria (NAG release into the final urine) or proteinuria. The effects observed were lower than those of the HOCA diatri-zoate [25]. 

Adverse reactions to gold, especially dermatitis, can occur at plasma gold levels as low as 1 /ug/ml but impaired creatinine clearance, which is indicative of severe kidney damage, is rarely seen at plasma gold levels less than 4 [ig/ml (L14). The clinical value of plasma gold measurements must still be considered unsettled, despite the optimism of many investigators. 

Renal function impairment Because daptomycin is eliminated primarily by the kidney, a dosage modification is recommended for patients with creatinine clearance (Ccr) less than 30 mL/min, including patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (CARD). When possible, administer daptomycin following hemodialysis on hemodialysis days. 

In fact elderly people have a reduced creatinine clearance, often balanced by the decline in creatinine input with a resulting normal serum creatinine. This is clinically important because drugs which are cleared through the kidneys need to be given in scaled down amounts to prevent cumulation and possible toxicity - e.g., gentamicin and other parenteral aminoglycosides, digoxin. 

Diabetic nephropathy prevention of kidney failure PO 25 mg 3 times a day Dosage in renal impairment Creatinine clearance 10-50 ml/min. 75% of normal dosage. Creatinine clearance less than 10 ml/min. 50% of normal dosage. 

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. 

Digoxin is not extensively metabolized in humans almost two thirds is excreted unchanged by the kidneys. Its renal clearance is proportional to creatinine clearance and the half-life is 36-40 hours in patients with normal renal function. Equations and nomograms are available for adjusting digoxin dosage in patients with renal impairment. 

Penicillin is rapidly excreted by the kidneys small amounts are excreted by other routes. About 10% of renal excretion is by glomerular filtration and 90% by tubular secretion. The normal half-life of penicillin G is approximately 30 minutes in renal failure, it may be as long as 10 hours. Ampicillin and the extended-spectrum penicillins are secreted more slowly than penicillin G and have half-lives of 1 hour. For penicillins that are cleared by the kidney, the dose must be adjusted according to renal function, with approximately one fourth to one third the normal dose being administered if creatinine clearance is 10 mL/min or less (Table 43-1). 

Because the kidney is the major organ for clearance of drugs from the body, the age-related decline of renal functional capacity is very important. The decline in creatinine clearance occurs in about two thirds of the population. It is important to note that this decline is not reflected in an equivalent rise in serum creatinine because the production of creatinine is... 

Tacrolimus + sirolimus, tacrolimus + mycophenolate mofetil, and ciclosporin + sirolimus have been compared in recipients of their first kidney transplant (52). One-year patient and graft survival did not differ. Ciclosporin + sirolimus was associated with increased serum creatinine concentrations, reduced creatinine clearance, more frequent protocol discontinuation, more antihyperlipidemic drug therapy, and a higher incidence of post-transplant diabetes mellitus. 

Renal Effects. Occupational exposure to silver metal dust has been associated with increased excretion of a particular renal enzyme (N-acetyl-p-D glucosaminidase), and with decreased creatinine clearance (Rosenman et al. 1987). Both of these effects are diagnostic of marginally impaired renal function. However, the workers in this study were also exposed to cadmium, which was detected in the urine of 5 of the 27 workers studied. Cadmium is known to be nephrotoxic differentiation of the effects of the two metals in the kidney is not possible with the data presented. Therefore, no conclusion can be drawn regarding renal effects of silver based on this study. 

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. 

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