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Pruebas de función renal
Dr. Cristhian Mauricio Bueno LaraEspecialista en Medicina Interna – Universidad Autónoma de Bucaramanga
Fellow en Nefrología – Universidad del Valle
Filtrado glomerularMarcadores exógenos
Richard J. Johnson, John Feehally, Jurgen Floege. Comprehensive clinical nephrology. Fifth edition 2015
Filtrado glomerularCreatinina
Richard J. Johnson, John Feehally, Jurgen Floege. Comprehensive clinical nephrology. Fifth edition 2015
Depuración creatinina: (140 – Edad) x (Peso en Kg) / 72 x Creatinina sérica en
mg/dL x (0.86 si se es mujer)
Filtrado glomerularCreatinina
From 249 pairs of measured creatinineclearances in males, creatinine excretion(mg/kg) was found to decrease linearly withage. The linear regression of creatinineexcretion against age led to development of aformula which can be used to successfullypredict creatinine clearance from age, weight,and serum creatinine. [The SCI
® indicates that
this paper has been cited in more than 700publications, making it the most-cited articlepublished in this journal.]
Creatinine Clearance Prediction
D.W. CockcroftDivision of Respiratory Medicine
Royal University HospitalSaskatoon, Saskatchewan S7N 0X0
Canada
It is with amusement, that after almost 20years as an academic �asthmatologist,� thathouse officers recognize my name as that at-tached to the widely used �Cockcroft-Gault� for-mula for predicting creatinine clearance.
In 1972-1973, in order to do a third year ofgeneral medicine residency at the Royal VictoriaHospital (Montreal), two of my colleagues and Icame up with an original idea; we each chose amedical subspecialty and rotated the three ofourselves through them. Thus, as a trainee inter-ested in chest-allergy, I came to do a solitarythree-month rotation as a subspecialty nephrol-ogy resident working with M.H. Gault at theQueen Mary Veterans� Hospital in Montreal. Myfirst attempt at the customary small research
project, a case report, proved unsuccessful. Mysecond research project was to verify the accu-racy of a nomogram which predicted creatinineclearance based on serum creatinine, age, andweight.
1 The investigation expanded to include a
review of 505 pairs of measured endogenouscreatinine clearance values in males. Of the 505,249 pairs were reproducible and arbitrarily as-sumed to be �accurate.� The 498 (249 x 2) datapoints were condensed by a �statistical trick� to 7data points on a graph in which the mean creat-inine excretion (mg/kg) for each decade wasplotted against age. A striking negative linearcorrelation was seen. Following completion ofclinical rounds on a cold Saturday morning inMontreal in February 1973, Gault and I werereviewing the graph and the linear regression ofcreatinine excretion vs. age, when I had the sud-den revelation that this regression could beturned into a formula to predict creatinine clear-ance:
-(140 age)(wt kg)C =cr
72 × S (mg/100mL)cr
This formula yields results which are in rea-sonably good agreement with measurementsobtained from 24-hour urine collections. It thusallows a quick and easy assessment of creatinineclearance as long as serum creatinine (thus renalfunction) is in a steady state. The performance ofthis formula and its �SI unit� equivalent re accu-racy, advantages, and limitations has been re-cently reviewed.
2 The many references to this
paper, often, as in some major textbooks, withoutexplicit citation, appear to relate primarily to itsvalue in drug kinetic studies.
3
1. Siersbaek-Nielsen K, Hansen J M, Kampmann J & Kristenson M. Rapid evaluation of creatinine clearance. Lancet 1:1133-4, 1971.
(Cited 245 times.)
2. Gault M H, Longerich L L, Harnett J D & Wesolowski C. Predicting glomerular function from adjusted serum creatinine. Nephron
62:249-56, 1992.
3. Oates J A & Wilkinson G R. Principles of drug therapy. (Wilson J D, Braunwald E, Isselbacher K J, Petersdorf R G, Martin J B, Fauci
A S & Root R K. eds.) Harrison's principles of internal medicine. New York: McGraw Hill, 1991. p. 361-73.
Received October 29, 1992
8 CURRENT CONTENTS® ©1992 by ISI®
Cockcroft D W & Gault M H. Prediction of creatinine clearance from serum creatinine. Nephron 16:31-41,
1976. [Departments of Medicine, Queen Mary Veterans� Hospital, Montreal, Quebec, and Memorial
University; St. John�s, Newfoundland, Canada]
This Week�s Citation Classic® CC/NUMBER 48
NOVEMBER 30, 1992Cockcroft and Gault
1976
Comparador:
Depuración de
creatinina
Filtrado glomerularCreatinina
MDRD
2006
Comparador:
Iotalamato
Filtrado glomerularCreatinina
MDRD
2006
Depuración creatinina: 175 x ( Creatinina sérica x 0.0011312)-1.154 x (Edad en
años)-0.203 x (0.742 si es mujer) x (1.212 si es raza negra)
Filtrado glomerularCreatinina
Richard J. Johnson, John Feehally, Jurgen Floege. Comprehensive clinical nephrology. Fifth edition 2015
MDRD
No valida en menores de 18 años, mayores de 70 años y mujeres
embarazadas.
Filtrado glomerularCreatinina
CKD EPI
2009
Comparador:
Iotalamato
Filtrado glomerularCreatinina
CKD EPI
2009
Mujer afroamericana
Si CrS ≤ 0.7: 166 x (Creatinina sérica/ 0.7)-0.329 x 0.993Edad de paciente
Si CrS > 0.7: 166 x (Creatinina sérica/ 0.7)-1.209 x 0.993Edad de paciente
Hombre afroamericano
Si CrS ≤ 0.7: 163 x (Creatinina sérica/ 0.9)-0.411 x 0.993Edad de paciente
Si CrS > 0.7: 163 x (Creatinina sérica/ 0.7)-1.209 x 0.993Edad de paciente
Mujer otras razas
Si CrS ≤ 0.7: 144 x (Creatinina sérica/ 0.7)-0.329 x 0.993Edad de paciente
Si CrS > 0.7: 144 x (Creatinina sérica/ 0.7)-1.209 x 0.993Edad de paciente
Hombre otras razas
Si CrS ≤ 0.7: 141 x (Creatinina sérica/ 0.7)-0.411 x 0.993Edad de paciente
Si CrS > 0.7: 141 x (Creatinina sérica/ 0.7)-1.209 x 0.993Edad de paciente
Filtrado glomerularCreatinina
Filtrado glomerularCreatinina
Pierre Delanaye and Christophe Mariat. The applicability of eGFR equations to different populations. Nat. Rev.
Nephrol. 9, 513–522 (2013)
514 | SEPTEMBER 2013 | VOLUME 9 www.nature.com/ nrneph
results, although this issue has been largely resolved
with the implementation of calibration standardization
for serum creatinine. Most manufacturers have now
developed serum creatinine kit assays that use a stand-
ardized calibration against serum creatinine measured
by mass spectrometry, namely the isotope dilution mass
spectrometry (IDMS)-traceable creatinine assays.26 Use
of IDMS-traceable assays has limited the bias observed
between the assays (and thus the laboratories) for both
the Jaffe and enzymatic methods. However, even if a
given Jaffe assay is IDMS-traceable, its precision would
still be lower than that of an enzymatic method.
Owing to the limitations of serum creatinine as a bio-
marker for GFR, it is better to use serum creatinine as
part of GFR-estimating equations that permit a certain
degree of correction (for example, by use of the covari-
ate ‘age’ to account for muscle mass or use of a corrected
coefficient to account for IDMS traceability). The value
of serum creatinine concentration per se does not mean
the same in terms of GFR if gender, age and ethnicity
are not considered.19,27 Moreover, since the relation-
ship between serum creatinine and GFR is not linear
but exponential, an increase of serum creatinine from
53 mol/l to 106 mol/l will be equivalent, in terms of
percentage of decreased GFR, to a serum creatinine
increase from 177 mol/l to 354 mol/l. This exponential
relationship is fundamental and may be missed if serum
creatinine alone is considered.3,6,28
Key points
Even when developed through rigorous process, creatinine-based equations for
estimating glomerular filtration rate (GFR) are not systematically applicable to
every clinical situation
Examples of clinical situations in which the applicability of the commonly
used equations has been questioned include particular ethnic groups, kidney
transplant recipients and the elderly
The applicability of the MDRD study equation and of the CKD-EPI equation has
been more extensively documented than the applicability of the Cockcroft–Gault
equation
Although cystatin C—as a GFR marker—outperforms creatinine in many
situations where equations are usually less accurate, cystatin-C-based GFR
estimating equations have not yet been definitively validated
The use of reference methods of GFR measurement in situations in which
equations are known to be suboptimal should be considered
The int roduct ion of equat ions The first creatinine-based equation for estimating GFR
was probably the one proposed by Effersoe in 1957.29
Several other equations were proposed thereafter but
the two most popular equations until 2009 were the
Cockcroft–Gault equation proposed by Cockcroft and
Gault in 197630 and the Modification of Diet in Renal
Disease (MDRD) study equation proposed by Levey et al.
in 1999.28
Cockcroft–Gault equation
The Cockcroft–Gault equation was developed from a
limited cohort of 249 hospitalized patients (Table 1).30
One of the main advantages of this equation was its math-
ematical simplicity, which made it useful at the bedside
of the patient. Today, this advantage is obviously less rel-
evant as computers and smartphones can easily calculate
the results of more elaborate mathematical equations.31
The Cockcroft–Gault equation had several weaknesses, as
follows: it estimates 24 h creatinine clearance, not GFR; the
development dataset included only Caucasian individuals
and only 4% of these were women; serum creatinine was
measured by an accurate but not a standardized method;
and the covariate ‘weight’ that is integrated in the equa-
tion is a potential source of imprecision in individuals
with abnormal body mass index (BMI).30,32 Several authors
correct the Cockcroft–Gault result by body surface area
(BSA),14,28 although this adjustment was not recommended
by Cockcroft and Gault. Such a correction is questionable,
notably because weight is a key variable in both BSA and
in the Cockcroft–Gault formulae.31 Moreover—and this
point does not apply just for the Cockcroft–Gault equa-
tion—BSA indexation per se might be misleading in
individuals with extreme BMI, such as anorexic or obese
patients.31,33 The Cockcroft–Gault equation has been very
popular and is still used in some settings, especially for
drug-dosing recommendations.34–36
MDRD equation
In 1999, Levey et al. proposed a new creatinine-based
equation, the MDRD equation (Table 1). This equation
was intended to estimate ‘true’ GFR measured by the
urinary clearance of iothalamate and indexed by BSA.28
The indexing by BSA probably explains why ‘weight’ was
Table 1 | Comparison of methodologies used for the development of the three most used creatinine-based GFR equations
Feature Cockcroft–Gault equation MDRD equation CKD-EPI creatinine equation
Year of publication 1976 1999 2009
Sample size 249 1,628 5,504
Reference method Creatinine clearance Iothalamate Iothalamate
Mean GFR ± SD 73 ± 37 ml/ min 40 ± 21 ml/ min/ 1.73 m2 68 ± 40 ml/ min/ 1.73 m2
Percentage women 4 40 43
Percentage Caucasians 100 88 63
Mean age ± SD (years) NA 51 ± 13 47 ± 15
Mean BMI ± SD (kg/ m2) NA 27 ± 4 28 ± 6
Abbreviations: BMI, body mass index; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; NA, not available; SD, standard deviation.
REVIEWS
© 2013 Macmillan Publishers Limited. All rights reserved
Filtrado glomerularCreatinina
2010
Fórmulas Exactitud Subestimación Sobrestimación
Cockroft Gault 63 % 8% 29%
MDRD 65% 20% 15%
CKD EPI 69% 8% 23%
Filtrado glomerularCreatinina
Wieneke Marleen Michels. Performance of the Cockcroft-Gault, MDRD, and New CKD- EPI Formulas in Relation to
GFR, Age, and Body Size. Clin J Am Soc Nephrol 5: 1003–1009, 2010
Filtrado glomerularCreatinina
Genero: Masculino
Raza: Negra
Edad: 84 años
Peso: 46 kg
Creatinina: 1.2 mg/dl
Cockcroft Gault: 29.8
ml/min/1.73 m2
Grado 4
CKD EPI: 64 ml/min/1.73 m2
Grado 2
Filtrado glomerularCreatinina
2004
Filtrado glomerularCreatinina
Filtrado glomerularCreatinina
2012
Comparador:
Iohexol
BIS 1:
TFG: 3736 x Creatinina-0.87 x Edad-0.95 x (0.82 si es mujer)
BIS 2:
TFG: 767 x Cistatina-0.61 x Edad-0.57x Creatinina-0.40 x (0.87
si es mujer)
Filtrado glomerularCreatinina
2012
Filtrado glomerularCistatina C
2008
Filtrado glomerularCistatina C
2008
Filtrado glomerularCistatina C
2008
Filtrado glomerularCistatina C
2008
Filtrado glomerularOtros marcadores
2015
Richard J. Johnson, John Feehally, Jurgen Floege. Comprehensive clinical nephrology. Fifth edition 2015
Filtrado glomerularUrea
Patrick T. Murray. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from
the 10th Acute Dialysis Quality Initiative consensus conference. Kidney International (2014) 85, 513–521
Marcadores Injuria Aguda
• Molécula de 140 kDa
• Medición en orina por ensayo colorimétrico.
Jennifer R. Charlton, Didier Portilla and Mark D. Okusa. A basic science view of acute kidney injury biomarkers.
Nephrol Dial Transplant (2014) 29: 1301–1311
Marcadores Injuria Aguda
N-Acetil – β – D- Glucosaminidasa
Original Article
M easurement of tubular enzymuria facilitates early detection of acuterenal impairment in the intensive care unit
Justin Westhuyzen1, Zoltan H. Endre2, Graham Reece3, David M. Reith4, David Saltissi2 andThomas J. Morgan3
1Conjoint Renal Laboratory, Queensland Health Pathology Service, 3Intensive Care Unit and 2Department of Renal
M edicine, Royal Brisbane Hospital, Brisbane, Australia and 4Dunedin School of M edicine, University of Otago, Dunedin,
New Zealand
Abstract
Background. Early detection of acute tubular necrosis(ATN) could permit implementation of salvage thera-piesand improvepatient outcomesin acuterenal failure(ARF). The utility of single and combined measure-ments of urinary tubular enzymes in predicting ARFin critically ill patients has not been evaluated usingthereceiver-operatingcharacteristic (ROC) plot method.M ethods. In this prospective pilot study, 26 consecu-tive critically ill adult patients admitted to theintensive-care unit were studied. Urine samples werecollected twicedaily for up to 7 days. ARF wasdefinedas an increase in plasma creatinine of P 50% andP 0.15 mmolul. ROC plot analysis was applied to thetubular marker data to derive optimum cut-offs forARF.Results. Four of the 26 study subjects (15.4%) devel-oped ARF. Indexed to urinary creatinine concen-tration, c glutamyl transpeptidase (cGT), alkalinephosphatase (AP), N-acetyl-glucosaminidase (NAG),and a- and p-glutathione S-transferase (a- and p-GST)but not lactate dehydrogenase (LDH) were higher inthe ARF group on admission (P- 0.05). cGT, anda- and p-GST remained elevated at 24 h. The onset ofARF based on changes in plasma creatinine variedfrom 12 h to 4 days (median 36 h). ROC plot analysisshowed that cGT, p-GST, a-GST, AP and NAG hadexcellent discriminating power for ARF (AUC 0.950,0.929, 0.893, 0.863 and 0.845, respectively). The dis-criminating strength of creatinine clearance, whilelower, was still significant (AUC 0.796). Positive andnegative predictive values for ARF on admission were67u100% for cGT, 67u90% for AP, 60u95% for a-GST,and 67u100% for p-GST indices. Positive and negativepredictive values for ARF for creatinine clearance
O 23 mlumin were 50 and 91%, respectively. Creatinineclearances tended to be lower in ARF than in non-ARF patients on admission (Ps 0.06) and were signi-ficantly lower (Ps 0.008) after 12 h. Plasma urea andfractional sodium excretion were unhelpful.Conclusions. Tubular enzymuria on admission to theICU is useful in predicting ARF. The cheapness andwide availability of automated assays for cGT and APsuggests that estimation of these enzymes in randomurinesamplesmay beparticularly useful for identifyingpatients at high risk of ARF.
Keywords: acute renal failure; acute tubular necrosis;alkaline phosphatase; creatinine clearance; creatinine;c-glutamyl transpeptidase; intensive care; tubularmarkers
Introduction
Acute renal failure (ARF) is common in intensive careunits (ICU), with a 10–30% incidence that is 5-foldhigher than among medical ward patients [1–4]. Themortality rate for hospitalized patients who developARF is some five times higher than without ARF [5].Despite the introduction of continuous renal replace-ment therapy and biocompatible membranes, themortality associated with this diagnostic category hasimproved little over the last 15 years [1,3,4]. Significantimprovements in the outcome of these patients seemcontingent upon either prevention or the early detec-tion of renal impairment. The routinely availableclinical parameters of kidney disease—plasma creati-nine and urea—do not in practice provide either asensitive or specific indication of renal function, andreveal ARF well after the injury inducing ARF hasoccurred. Clearly, more specific and sensitive markersare desirable for the early detection of an initiallyoccult pathophysiological process.
Correspondence and offprint requests to: Z. Endre, AssociateProfessor, Department of M edicine, Clinical Sciences Building,Royal Brisbane Hospital, Herston 4029, Queensland, Australia.Email: [email protected]
Nephrol Dial Transplant (2003) 18: 543–551
# 2003 European Renal Association–European Dialysis and Transplant Association
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Original Article
Measurement of tubular enzymuria facilitates early detection of acuterenal impairment in the intensive care unit
Justin Westhuyzen1, Zoltan H. Endre2, Graham Reece3, David M. Reith4, David Saltissi2 andThomas J. Morgan3
1Conjoint Renal Laboratory, Queensland Health Pathology Service, 3Intensive Care Unit and 2Department of Renal
Medicine, Royal Brisbane Hospital, Brisbane, Australia and 4Dunedin School of Medicine, University of Otago, Dunedin,
New Zealand
Abstract
Background. Early detection of acute tubular necrosis(ATN) could permit implementation of salvage thera-piesand improvepatient outcomesin acuterenal failure(ARF). The utility of single and combined measure-ments of urinary tubular enzymes in predicting ARFin critically ill patients has not been evaluated usingthereceiver-operatingcharacteristic(ROC) plot method.Methods. In this prospective pilot study, 26 consecu-tive critically ill adult patients admitted to theintensive-care unit were studied. Urine samples werecollected twicedaily for up to 7 days. ARF wasdefinedas an increase in plasma creatinine of P 50% andP 0.15 mmolul. ROC plot analysis was applied to thetubular marker data to derive optimum cut-offs forARF.Results. Four of the 26 study subjects (15.4%) devel-oped ARF. Indexed to urinary creatinine concen-tration, c glutamyl transpeptidase (cGT), alkalinephosphatase (AP), N-acetyl-glucosaminidase (NAG),and a- and p-glutathioneS-transferase (a- and p-GST)but not lactate dehydrogenase (LDH) were higher inthe ARF group on admission (P- 0.05). cGT, anda- and p-GST remained elevated at 24 h. The onset ofARF based on changes in plasma creatinine variedfrom 12 h to 4 days (median 36 h). ROC plot analysisshowed that cGT, p-GST, a-GST, AP and NAG hadexcellent discriminating power for ARF (AUC 0.950,0.929, 0.893, 0.863 and 0.845, respectively). The dis-criminating strength of creatinine clearance, whilelower, was still significant (AUC 0.796). Positive andnegative predictive values for ARF on admission were67u100% for cGT, 67u90% for AP, 60u95% for a-GST,and 67u100% for p-GST indices. Positive and negativepredictive values for ARF for creatinine clearance
O 23 mlumin were50 and 91%, respectively. Creatinineclearances tended to be lower in ARF than in non-ARF patients on admission (Ps 0.06) and were signi-ficantly lower (Ps 0.008) after 12 h. Plasma urea andfractional sodium excretion were unhelpful.Conclusions. Tubular enzymuria on admission to theICU is useful in predicting ARF. The cheapness andwide availability of automated assays for cGT and APsuggests that estimation of these enzymes in randomurinesamplesmay beparticularly useful for identifyingpatients at high risk of ARF.
Keywords: acute renal failure; acute tubular necrosis;alkaline phosphatase; creatinine clearance; creatinine;c-glutamyl transpeptidase; intensive care; tubularmarkers
Introduction
Acute renal failure (ARF) is common in intensive careunits (ICU), with a 10–30% incidence that is 5-foldhigher than among medical ward patients [1–4]. Themortality rate for hospitalized patients who developARF is some five times higher than without ARF [5].Despite the introduction of continuous renal replace-ment therapy and biocompatible membranes, themortality associated with this diagnostic category hasimproved littleover thelast 15 years [1,3,4]. Significantimprovements in the outcome of these patients seemcontingent upon either prevention or the early detec-tion of renal impairment. The routinely availableclinical parameters of kidney disease—plasma creati-nine and urea—do not in practice provide either asensitive or specific indication of renal function, andreveal ARF well after the injury inducing ARF hasoccurred. Clearly, more specific and sensitive markersare desirable for the early detection of an initiallyoccult pathophysiological process.
Correspondence and offprint requests to: Z. Endre, AssociateProfessor, Department of Medicine, Clinical Sciences Building,Royal Brisbane Hospital, Herston 4029, Queensland, Australia.Email: [email protected]
Nephrol Dial Transplant (2003) 18: 543–551
# 2003 European Renal Association–European Dialysis and Transplant Association
by
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26Pacientes
Jennifer R. Charlton, Didier Portilla and Mark D. Okusa. A basic science view of acute kidney injury biomarkers.
Nephrol Dial Transplant (2014) 29: 1301–1311
Marcadores Injuria Aguda
Interleucina 18
• Células mononucleares,
macrófagos y células
túbulos proximales.
Marcadores Injuria Aguda
Interleucina 18
2002
• Familia de las proteínas ligadas a ácidos grasos (FABP)
• Expresada en el intestino, páncreas, riñón, pulmones y estómago.
Jennifer R. Charlton, Didier Portilla and Mark D. Okusa. A basic science view of acute kidney injury biomarkers.
Nephrol Dial Transplant (2014) 29: 1301–1311
Marcadores Injuria Aguda
Proteína asociada a ácidos grasos
hepáticos
Marcadores Injuria Aguda
Proteína asociada a ácidos grasos
hepáticos
2007
Jennifer R. Charlton, Didier Portilla and Mark D. Okusa. A basic science view of acute kidney injury biomarkers.
Nephrol Dial Transplant (2014) 29: 1301–1311
Marcadores Injuria Aguda
Molécula de injuria renal 1 (KIM-1)
Marcadores Injuria Aguda
Molécula de injuria renal 1 (KIM-1)
2012
Jennifer R. Charlton, Didier Portilla and Mark D. Okusa. A basic science view of acute kidney injury biomarkers.
Nephrol Dial Transplant (2014) 29: 1301–1311
Marcadores Injuria Aguda
Lipocalina asociada a la gelatinasa
del neutrófilo
Marcadores Injuria Aguda
2009
76%Sensibilidad
85.1%Sensibilidad
GRACIAS