Kidney estimated 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. 

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. 

Rohn HA, Hall PM, Wei R. Inaccuracy of estimated creatinine clearance for prediction of iothalamate glomerular filtration rate. Am J Kidney Dis 1984 9 48-54. 

Aldactazide) microalbuminuria avoid spironolactone in patients with chronic kidney disease (estimated creatinine clearance < 30 mL/min) may cause hyperkalemia, especially in combination with an ACE inhibitor, angiotensin-receptor blocker or potassium supplements... 

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 influence of age on metabolic clearance is less clear than its influence on renal function. Metabolic clearance is more variable between individuals because of the genetic control and the influence of environmental factors on the metabolic capacity. The term metabolism also encompasses many different enzyme reactions that might be influenced to different extents by age, liver disease, or genetic variables. Unlike renal disease, in which creatinine clearance provides a reasonable estimate of kidney function, not one good indicator exists for the degree of liver function impairment with respect to drug metabolizing capacity. 

Pigure 24-9 Relationship between GFR measured using l-iothalamate clearance and estimates of creatinine clearance (CrC ) obtained using the (A) Cockcroft and Gault equation and (B) measured creatinine clearance. (From Coresh JJoto RD, Kirk KA,Whelton PK, Massry S, Jones C, et at. Creatinine clearance os a measure of GFR in screenees for the African-American study of kidney disease and hypertension pilot study. Am J Kidney D/s 1998 32 32-42.)... 

The kidneys receive about 20% of the cardiac output (blood flow) and filters approximately 125 ml of plasma per minute. As the patient loses kidney function, the quantity of plasma filtered per minute decreases with an accompanying decrease in clearance. The most useful estimation of creatinine clearance rate (CCr) is obtained using the following empirical formula based on the patient s age and serum creatinine level. 

The GFR can be estimated by clearance measurements of endogenous or exogenous small molecules (urea, creatinine, 2-MPT, inulin, cystatin C, iohexol, or iodixanol). An ideal marker of GFR should be primarily excreted by the kidneys, freely filtered by the glomerulus, and neither secreted nor reabsorbed by the tubule. It should also be supplied to the plasma at a constant rate and exhibit no or minimal protein binding. If these criteria are met, such as for inulin, the GFR is equivalent to the renal/urinary clearance of the substance, as defined earlier in this chapter. 

The anhydride of creatine is creatinine, in which form it is found in urine. Changes in the excretory function of the kidneys are reflected in plasma urea and creatinine concentrations. Glomerular filtration rate (GFR) and overall kidney function is conveniently estimated by metisuring creatinine clearance in the volume of urine excreted in 1 minute. Its value is about 125 ml/minute in healthy young men. It is usually a little less in young women and at 70 years of age it is about 75% of the value in youth. Kidney failure rarely produces symptoms until the GFR falls below 30 ml/minute. 

The clearance concept has been used in defining the pharmacokinetics of drugs since the mid-1970s. " The elearanee eoneept is based in physiology, where it is used as a measure of renal funetion (ereatinine elear-ance). Creatinine is formed from muscle breakdown at a constant rate, and thus a constant creatinine concentration in plasma results. The magnitude of this concentration is dependent on the elimination rate of ereatinine and the size of the muscle pool (formation rate). By measuring the plasma concentration and the renal excretion of ereatinine, renal clearance can be estimated and thereby kidney function indicated, as ereatinine is mainly filtered into the urine... 

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]. 

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. 

IMPAIRED RENAL CLEARANCE OF DRUGS If a drug is cleared primarily by the kidney, dose modification should be considered in patients with renal dysfunction. When renal clearance is diminished, the desired effect can be maintained either by decreasing the dose or lengthening the dose interval. Estimation of the glomerular filtration rate (GFR) based on serum creatinine, ideal body weight, and age provides an approximation of the renal clearance of many drugs. 

Specific functions of the kidney that can be assessed inclnde glomernlar filtration rate (GFR), which can be measured by quantifying the clearance of a substance that is freely filtered across the capillary wall and is neither reabsorbed nor secreted by the tubules. The optimal measurement of GFR is insnlin clearance (Arant et al., 1972). Clinically, however, GFR can be estimated by the clearance of endogenous creatinine. At serum levels of creatinine exceeding 2.0 mg/dL, changes in renal function can be monitored by the serum creatinine concentration. GFR is adequate for healthy term infants, bnt it does not approximate adult rates until about 3 years of age. Renal tubular reabsorption and urine acidification is less at birth and for several months thereafter than it is for adults. This function is adequate for healthy infants, but contributes to fluid and electrolyte abnormalities in infants who are ill or are fed an inappropriate diet (Goldsmith and Novello, 1992). 

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