11/21/2023 0 Comments 1964 perfect dark romAs a result, serum inulin concentrations are often lower than expected, which in turn leads to an overestimation of GFR, frequently exceeding urinary inulin clearance by ∼5–10 ml min −1. Furthermore, animal and human studies demonstrate that complete equilibration of inulin in body fluids, necessary for accurate GFR calculation, can take several hours to achieve. While this method gives reproducible results, it is hard to achieve a constant plasma inulin concentration, and small changes in inulin concentration can significantly affect the calculated GFR. The GFR (in millilitres per minute) may be calculated by dividing the rate of the infusion (in milligrams per minute) by the plasma concentration (in milligrams per millilitre). This method was based on the concept that inulin is exclusively eliminated via the renal pathway and therefore, in steady state, the rate of excretion equals the rate of infusion. Methodological limitations are associated with the use of this method, however, not least due to the strictly timed urine collections, which are not only challenging for both patient and clinician but may even necessitate urinary catheterization.Įarle and Berliner (1946) described an alternative infusion technique avoiding the need for timed urine collections. Once steady state is achieved, repeated timed urine and blood samples are collected, and GFR can be derived from the concentration of inulin in plasma ( P), urine ( U) and the urine flow rate ( V) using the formula: GFR = UV/ P. The classic method of urinary clearance involves fasting subjects prior to administration of a priming dose of inulin followed by a continuous intravenous infusion. Inulin is freely filtered at the glomerulus and is not reabsorbed, synthesized or metabolized by the tubules. Urinary clearance of inulin, a 5200 Da inert polymer of fructose derived from plant tubers, is considered the ‘gold standard’ measurement of GFR. A number of exogenous and endogenous filtration markers (creatinine and cystatin C) have been studied and will be discussed in more detail. Additionally, filtration markers must be able to achieve a stable plasma concentration without being reabsorbed, secreted or metabolized by the kidney. An ideal filtration marker is one that is physiologically inert, with a low molecular weight allowing free filtration at the glomerulus, is not bound to plasma proteins and does not itself alter renal function. Glomerular filtration rate cannot be measured directly in humans but instead can be determined by plasma clearance of a filtration marker into the urine. Interindividual variation exists, however, depending on body mass, protein intake, exercise and diurnal variation. Kidney function is proportional to kidney size which, in turn, is proportional to body surface area and so adjustment is necessary when comparing GFR with normal values. A normal GFR is ∼130 ml min −1 1.73 m −2 in males and ∼120 ml min −1 1.73 m −2 in females. Glomerular filtration rate is considered the best overall measurement of kidney function and correlates well with disturbance in renal function. International adoption of this system has facilitated both clinicians and researchers in the identification, diagnosis and management of CKD, and aided large-scale epidemiological studies examining the prevalence of CKD and the implications of severity with respect to clinical outcome. Proteinuria, included within the classification as a marker of kidney damage, has been identified as an independent risk factor for CKD progression, cardiovascular disease and overall mortality. Chronic kidney disease is categorized into five stages based on the estimated GFR (eGFR Table 1). Kidney damage itself is defined as structural or functional abnormalities of the kidney manifest by either pathological abnormalities or markers of kidney damage, e.g. Criteria outlined by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) define chronic kidney disease as kidney damage present for more than 3 months with or without a decrease in glomerular filtration rate (GFR), or a reduction in GFR for more than 3 months with or without kidney damage. In the USA, there are around 19 million adults with CKD and it is estimated that more than 2 million people will require dialysis or transplantation by the year 2030. Chronic kidney disease has been described as a worldwide public health problem, with a prevalence of ∼12% in the USA and Europe. Chronic kidney disease (CKD) is common and associated with an increased mortality, frequently as a result of kidney failure and cardiovascular disease.
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