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    10 views21 pages

    Correlacion 2 - Pruebas de Funcion Renal

    Uploaded by

    jenny paola londoño londoño

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    © All Rights Reserved
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    of 21
    Assessment of Renal Function Lesley A. Inker, Li Fan, and Andrew S. Levey GLOMERULAR FILTRATION RATE Glomerular filtration rate (GFR) isa product ofthe average filtration rate of each nephron the filtering unit of the kidneys, multiplied by ‘the numberof nephrons in both kidney The normal level for GFRis approximately 130 milimin/.73 mfr men ad 120 ml/nin/ 73 m for women, with considerable varation among individual according ‘wo age, gender, body size, physical activity, diet, pharmacotherapy, and physiologic states such as pregnancy. To standardize he function ofthe kidney for differences in kidney sie, which is proportional to body size, GER is adjusted for body surface area (BSA), computed fom height and weight and is expressed pe 1.73 m? BSA, the mean [BSA of young men and women. Even after adjustment for BSA, GFR ispproximately8% highern young men than in women and declines with age; the mean rate of decline is approximately 0.75 ml/min/yt aller age 40 years, but the variation is wide, and the sources of varia tion are poorly understood. During pregnancy, GFR increases by about 50% in the first trimester and returs to normal immediately after delivery. GFR has a diurnal variation and is 10% lower a mi night compared with the afternoon. Within an individual, GFR is relatively constant over time but varies considerably among people, «even after adjustment forthe known variables. Reductions in GFR may result from a desine inthe nephron number or in the single-nephron (SN) GER. from physiologic of hemodynamicalterations. An incteasein NGFR causedby increased slomerular capillary pressure or glomerular hypertrophy can com pensate fora decrease in nephron number therefore the level of GER may not reflec the loss of nephrons. Asa result there may be sub- stantial kidney damage before GFR decreases. MEASUREMENT OF THE GLOMERULAR FILTRATION RATE The GFR cannot be measured directly. Instead, i is measured as the urinary clearance ofan ideal filtration marker. Concept of Clearance Clearance ofa substance is defined asthe volume of plasma cleared ofa marker by excretion per unit of time. The clearance of substance 1x (G) cam be calculated as C, = AYP, where A, is the amount of + Climinated from the pass , isthe averape plasma concentration, tnd Gis expressed in units of volume pet ime. Clearance does not fepresent ant acual volume; rather itis a virtual volume of plasma thats completely cleared ofthe substance per unit of time. The value for clearance is related tothe eficiency of elimination: the greater the rate of elimination, the higher the earance, Clearance of sub tance x isthe sum of te urinary and extrarenal cearance: for substances tha ae eliminated by renal and extrarenal outs, plasma Clearance exceeds urinary clearance. 30 Urinary Clearance ‘The amount of substance x excreted in the urine can be calculated asthe product ofthe urinary low rate (V) and the urinary concentra, tion (U). "Therefore urinary clearance is defined as follows: C= (UVP, Urinary excretion of a substance depends on filtration, tubular secretion, and tubular reabsorption, Substances that are filtered but ‘not secreted or reabsorbed by the ubules are ideal filtration markers, because their urinary clearance can be used as a measure of GFR For substances that are filtered and secreted, urinary clearance exceeds GFR: and for substances that are filtered and reabsorbed, urinary clearance is less than GER “Measurement of urinary clearance requires a timed urine collec tion for measurement of urine volume, as well as urine and plasma concentrations of the filtration marker. Special care must be taken to avoid incomplete urine collections, which will limit the accuracy of the clearance calculation, Plasma Clearance Interest in measurement of plasma clearance continues because it avoids the need fora timed urine collection. GER is caleuated from plasma clearance (C, after a bolus intravenous injection ofan exog «enous filtration marker, with the clearance (C,) computed from the amount of the marker administered (A,) divided by the average plasma concentration (P.), which can be computed from the area under the curve of plasma concentration versus time. CAC, ‘The decline in plasma levels is secondary to the immediate disap pearance of the marker from the plasma into its volume of distribu: tion (fast component) and to renal excretion (slow component), Plasma clearance is best estimated by use of a two-compartment ‘model that requires blood sampling early (usually two or theee time Points until 60 minutes) and late (one to three time points from 120 minutes onward). As with urinary clearance, plasma clearance of 4 substance depends on filtration, tubular secretion, and tubular rea sorption, but in addition, extrarenal elimination, Exogenous Filtration Markers Inulin an uncharged polymer of fructose with molecular weight of approximately 5000 daltons (d), was the first substance described as. an ideal filtration marker and remains the reference (gold standard) against which other markers are evaluated. The clase protocol {0 inulin clearance requite a continuous intravenous {IV} infin 1 achieve a steady state and bladder catheterization with: multiple timed urine collections. Because this technique is cumbersome, and inulin measurement requires a dificult chemical aay this method thas not een used widely in clinical practice and remains research See cea Sica Cc Contiaous!V Gold standard ‘nfson totholamate Bolus 1V Can be administered as | Injection or radioactive compound with Sbestaneous laine 125 (= ag the tracer | injection rin nonradioactive form, with 2353) using HPLC methods In | Faaloactve form, potent problem of tyro uptake Sf" othalamate is secreted, leading te everetimation orarn STcOTPA Bolus IV injection Dissociation of "Tc leads to plasma protein binding and Underestimation of GPR |S@-EDTA Bolus Vinoction 108 lower clearance than inulin BolusIV injection Low incidence of adverse effets, Comparable to inl: expensive and dificult to perform wey lobes! Table 3-1 Exogenous filtration markers for estimation of glomerular Firat rate. CrED12, Chromium 51 abeed ethenecarenetetsace Tesod, GFR glomerar tration ral, HPLG highpefomance hqud Sramatograpty, 1, intravencus, "TeDTAA technetum 9Om-isbeled Sethenetnaminepentaaceve 26 tool Alternative exogenous substances include fothalamate,iohexol, ‘etaylenediaminetetraacetic acid, and diethylenetriaminepentaacetic ‘acid often chelated to radioisotopes fr ease of detection (Table 3-1 ‘Aiterative protocols to assess clearance have also been validated, {acluding subcutaneous injection and spontaneous bladder empty ing, There are advantages to alternative exogenous filtration markers and methods, but also limitations. Understanding the strengths and limitations of each alternative marker and each clearance method wil facilitate interpretation of measured GFR! Endogenous Filtration Markers Endogenous filtration markers are substances generated inthe body ata relatively constant rate and eliminated largely by glomerular filtration. Therefore, the serum level correlates highly with measured GGFR after accounting for factors other than GER tha influence the fon-GFR determinants. Currently identified endogenous filtration ‘markers include low- molecular-weight metabolites and serum pro: teins. Filtered metabolites may undergo reabsorption or secret which contribute to their urinary excretion, Comparison to urinary ‘learance of exogenous filtration markers enables inferences about the renal handling of endogenous filtration markers. By contrast, filtered serum proteins are reabsorbed and degraded within the "ubule with minimal appearance inthe urine. For filtration markers excreted in the urine, urinary clearance can be computed from 3 "ied urine collection and single measurement of serum concen: lation. the serum level is not constant during the urine collection, 4 in acute kidney disease or when residual kidney function is ‘sessed in dialysis patient, tis necessary to obtain additional blood ‘amples during the urine collection to estimate the average serum Creatinine is the most frequently used endogenous filtration ‘marker in clinical practice. Urea was widely used in the past, and. ‘rmtatin € presently shows great promise (/sble 2 Relationship of GFR and Non-GFR Determinants to Serum Levels Une GFRAP-TRVTS. o-E= GFR«P-TR+ TS rR (asta 18-6] Figure 3-1 Relationship of glomerular filtration rate and non-GFR determinants to serum fvels. @ Generation E exafenal elimination. Ppa TR bila reaesorpticn, TS, tubule secretion. (Modied from reference 1) Estimated Glomerular Filtration Rate from Plasma Levels Figure 3-1 shows the relationship of plasma concentration of sub: stance x to its generation (G,) by cells and dietary intake urinary excretion (U, x V), and extrarenal elimination (E,) by gut and liver. ‘The plasma level i related tothe reciprocal ofthe level of GFR, but itis also influenced by generation, tabular secretion and reabsorp tion, and extrarenal elimination, collectively termed non-GFR deter ‘minants ofthe plasma level! In the steady state, a constant plasma level of substance xis main tained because generation is equal to urinary excretion and extrare ‘al elimination, Estimating equations incorporate demographic and clinical variables as surrogates forthe non-GFR determinants and provide a more accurate estimate of GFR than the reciprocal of the plasina level alone. Estimating equations are derived from regression ff measured GFR on measured values of the filtration marker and ‘observed values ofthe demographic and clinical variables. Estimated GER (eGFR) may der from measured GER in a patient ifa discrep ancy exists between the true and average values forthe relationship Of the surrogate to the non-GFR determinants of the filtration marker. Other sources of errors include measurement error in the filtration marker (eg falure to calibrate assay for filtration marker to assay used in development of equation), measurement cero in ‘GFR in development ofthe equation, and regression to the mean, In principe, ll these errors a likely to be greater at higher values for GER. CREATININE Metabolism and Excretion Creatinine sa 113-d end product of muscle catabolism. Advantages of creatinine inclade its ease of measurement and the low cost and Widespread availabilty of asays, Disadvantages include the large ‘number of non-GFR determinants, leading to a wide range of GFR fara given serum creatinine level (See Table 3-2). For example, a serum creatinine level of 1.5 mg/dl (132 mol) may correspond to 44 GER from approximately 20 10 90 ml/min/1.73 m ‘Creatinine is derived by the metabolism of phosphocreatine in muscle as well a from dietary meat intake or creatine supplements. Creatinine generation is proportional to muscle mass, which can be ‘estimated from age, gender, race, and body size. Table 33 lists factors that can alfect creatinine generation.” (Creatinine is released into the circulation ata constant rate during ‘normal physiologic conditions. Ics aot protein bound and is freely Equations for Estimating Glomerular Filtration Rate Cockroft-Gault Formula’ 72xS,(mg/dl) 0.814 «5, (amol/) a Male (140 Age) Weight or 140 - Age) « Weight (tin) = 140 Age) < Weight (140 - Age) « Weight Sk 72x5,(mgid) Colin) = "ogi 5, (umoll) Female ~ Age) x Weight x! or — Age) x Weight 0.85 | omirmin) = 140— Age x Weight «0.85 etm = = Age) weihts085 | [MRD Study Equation for Use with Standardized Serum Creatinine (Four-ariable Equation)" {GER (mlmins1.731m) = 175 x Standardized (mgt ™™ x Age" 0.742 (if female) «1.210 ff black) | Age * 0.742 (if female) 1.210 i black) {GFR (ml/mins1.731) = 30,849 Standardized S,(umol (CKD-EPI Equation for Use with Standardized Serum Creatinine” {GER (miminv1.73m*) = 141i (Sy x, 1 xan, x, 91% 0,993 «1.018 (if Female)1.187 (if black) ‘here « i 0.7 for females and 0:9 for males, «is 0.329 for females and -0.411 for males, min indicates the minimum of Sx oF 1, ‘and max indiates the maximum of Se or 1 Female 144 (54 10.792 (0.993) «1.157 (if black) 144(5, 10.7)" Male 14t«(5, 10.9)" 1415, 10.9) ‘CKO-EPI Equation for Use with Standardized Serum Cystatn C™ (GFR (nl/mins1 731m?) =133 mis, 0.8, 11° 120 5 Estimated GFR (rliin/.73 m8) 50. 40 1-Py 8 10 15 15-29 20-59 weGFR, GFF ACGFR. fa ty e089 90-120 >120) timated GFR (mimint.73 m?) SOT Sein sce th es ac a a wm shoe Ge ace ice lone (eGFR.), that using cystatin Clone (@GFR,,), and the combed ceatnne- lesion ede. Leukocytes Urinary neutrophils range from 7 to 15 yim in diameter and are the ‘Most frequently found leukocytes in the rine. Neutrophils are iden ifcd by theie granular cytoplasm and lobulated nucleus (Fig. 4-1. © tn mot patients neutrophils indicate lower oF wpe unary ‘act infection, but they may also result from urine contamination ‘auc by geil secretion, especialy in Young women. Varble ‘mumbers of neutrophils are often, but not always, found in acute Invest nephis. Newtopbis canbe found in low umber in chron itn neh and in proerave GN, inermagled with high umber of rtroete™ edna wich on be ented ony bythe seo stains (eg Hane et nce coped mir of tf adey nce nephrte Curenty, However coeop enw erp Petes they tay be pet In vere Opes of GN. prov Girne pyeoneprtis urinary schiaceott and Galena Embolam ce Chapter 6) =" Tjmployes wie Weniiction slo equi wing ofthe sample may nde ce cellar ton neal loge rep tnt Hwee ining poets inte rine cant replace mre ‘ale dagos ole such a eal py Lymphocyte ae ao {ype finding inpatients wth yh "lcrophag ar mononuceted o mune calls of var ables (191995 im in deter and varie apes ga ter Fg. 4-1, D),vcualae phagocyte (when cola cons Decterel dee al ragnent destroyed eryrocye, crys ttc) homogeneous (en cytoplasm docs aot conti gules orate pric), In pas wih the epreicsdrme cr phages ny be engorged with iid drops, appearing sx oal at Bodie Nacrphages ave bee undinthe rn of patent wih live GN, In our experience, macrophages are eqn seen a the re of ide trasplant eps th BK vrs nection ae Ine dcasion): Hower urinary macophges snot yet on fred dag any pei condon. Renal Tubular Epithelial Cells “The rena tubular epithelia clls (RTECS) derive from the exfoliation of the tubular epithelium. In the urine, RTECS can difer in size (iameter ~9 to 25 pm) and shape, fom roundish to ectangular oF columnat, with a central or peripheral large nucleus (Fig. 4-1, F). IRTECS are not found in the normal individual but can be found in all patients with conditions associated with acute tubular damage, such at ATN," acute interstitial nephritis, and acute celular rejee tion of a renal allograf. In smaller numbers, RTECS can aso be found in glomerular diseases In ATN, these cell are frequently ‘damaged and necrotic and may be present in casts (so-called epithe> lial east), Transitional Epithelial Cells ‘The transitional epithelial clls derive from the exfoliation of the troepithelium, which lines the urinary tract from calyees to the bladder in women and othe proximal urethra in men. This multiay- ered epithelium has small cells in the deep layers and larger cells in the superficial ayers. When present in large numbers (.,21/bigh power field (hp), cell ofthe deep epithelial ayers (diameter ~10 9 8 um; Fig 4-1, P suggest severe damage of uroepthelium, as caused by neoplasia, stone, abstruction, or longstanding bladder catheters or ureteral stents Transitional cells of the superficial layers (iam eter =17 t0 43 um: Fig. 4-1, G) are a common finding being assoc ‘ted with rill damage of wroepthelim, as may occur in esti Squamous Epithelial Cells ‘The squamous epithelial cells (diameter 17 wo 118 jm: Fig, 1. H) derive from the urethra or from the external genitalia. In small numbers, squamous cells ae a normal finding, bu in large numbers, they indicate urine contamination from genital secretions Lipids Lipids are found inthe urine a drops, which are spherical transl cent yellowish particles of diferent size that can be isolated or in “smore s mainy of iegularties ca izes ond shapes. Neutrophis. Note thei typical lobulated nucle renal tubular epthelal cel &, Two cols rom dee? PE, sie, and ratio of rules to eytopasm between FSCORY,ctiginal magnification x80) ing an internal lamellar structure, and bodies: and cholesterol crystals (see Crystals) All these particles irregular or truncated b tain mainly cholesterol esters and free cholesterol and under). thas recently h Polarized light have the appearance of Maltese crosses with sym- diagnostic importance = ‘metric arms (Fi » These lipids are typical of glomerular diseases associated with ‘marked proteinuria, usually but not invariably in the nephrotic Casts range Casts are cylindrical structures that f In Fabry disease, urine sediment contains fatty particles even in renal tubules and collecting dee the absence of proteinuria (see Chapter 48). These particles differ Horsallplycoprottn, alee Saad n in the lumen of distal i is made of Tamm ndulin, which is secreted by — Figure $2 Fay panicles. 4, ogi cast Normal individual renal eae aingranlar ——_Nowmal individu ena ease Wary Renal date with function impairment Fay Proteinuria: nephrtsystrome | ermtvoorte (lomeruiar hematuria; polerative! | ecotcing GN eal tubular ‘cate tubular necrosis sete inertia | spmetat cot nephritis proiteratve GN, nephrotic Soca Syndrome ‘itll ant) 2 for enthrayt cast: hemoglobinuria emoglbin s “used by mtravaicla heros yegletin hobdomyoyi esbin Jaundice caused by increased direct bilrdbin acral fungal Bacterial or fungal infection in the hier Centaining Normal individu; eral stone disease [mines ‘According to components present in the cast Table 42 Types of casts and their main clinical essodatons the ces of the thick ascending limb of Henle loop. Trapping of Particles within the cast matrix results in cats with diferent appe {nces, each of which may have specific clinical significance (Table 42), Because casts form in the renal tubules, whatever particle is Contained ina cast derives from the kidneys. Specific casts include the following {nd eolsted Grove) ound bpd crplts hsymmetec ars Fly he worcated Wales cross. (Ongnl magntcation 400 paca contrast mictecopyB, Same 18 Hyaline casts are colorless with a ow refractive index (Fig 4-3 A). They are easily scen with phase contrast microscopy but can be overlooked when bright-eld microscopy i used. Hyalin casts itis concentrated and on of Taam Horsfll ‘may accur in normal urine especially wh acid (both conditions favoring previ Poein). In patients with renal disease, hyaline casts are usualy associated with other types of casts Hyalne granular casts contain variable amounts of granules within the hyaline mate (Fig 43, 8) and are the most common mixed casts (described later): Hyaline-granlar casts are rare in non i paients with renal di normal individuals but ae c eases such as GN” and acute inertial nephritis 18 Granular casts can be finely granular (Fig 43, C ranula, Both types are typical of renal disease, Recent studies hhave demonstrate hat granular casts together with RTECS™ or with epithelial casts” ae a sensitive marker of ATN. t= Waxy casts derive their name from their appearance, which is similar to that of melted wax (Fig. 4-3, D). They are typally found in patients with renal disease associated with renal impaie ment, whether acute, rapidly progressive or chronic: 1m Fatty costs contain varable amounts of lipid droplets, isolated, in clumps, or packed, or even oval ft bois or cholesterol crystal Fatty casts ate typical of ‘marked proteinuria or the nephrotic syndrome 18 Exythrocte casts may contain a few erythrocytes (Fig. 43, Bor so many that the mari ofthe east cannot be identified. Eryth lomerular bleeding of paints with nerular diseases associated with ‘pte cast are usually considered a marker of ‘even though a recent report found them in 28 acute intestiial nephritis have a brownish hue and usually a coarsely ramular appearance, which derives (rom the degradation of erythrocytes entrapped within the cast matrs (Fig. 4-3, F. There fore, hemoglobin casts have the stme clinical significance as erythrocyte casts Hemoglobin casts may also derive from hemoglobinuria as may occur in intravascular hemolysis from any cause. In these patients, hemoglobin casts have a smooth ——____—_ 18 Leukocyte casts contain variable amounts of polymorphonuclear leukocytes (Fig. 4-3, G). They can be found in patients vith acute pyelonephritis and acute interstitial nephritis, but are rare in GN? ‘© Renal tubular epithelial cell casts (so-called epithelia casts) contain variable numbers of RTECS, which can be identified by their prominent nucleus (Fig 4-3, H). Epithelial casts indicate damage ‘ofthe renal tubular epithelium and can therefore be found in the urine of patients with ATTN.” acute interstitial nephritis, and even glomerular disease.” '# Myoglobin casts ar pigmented cylinders, with the myoglobin p viding their color. They may be similar to hemoglobin casts (Fi 43, From which myoglobin cass can be distinguished by the

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