Pruebas de función renal - 2015

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


Depuración creatinina: (140 – Edad) x (Peso en Kg) / 72 x Creatinina sérica en

mg/dL x (0.86 si se es mujer)


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


MDRD

2006

Comparador:

Iotalamato


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)



MDRD

No valida en menores de 18 años, mayores de 70 años y mujeres

embarazadas.


CKD EPI

2009

Comparador:

Iotalamato


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



Mujer otras razas



Hombre otras razas





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


2010

Fórmulas Exactitud Subestimación Sobrestimación

Cockroft Gault 63 % 8% 29%

MDRD 65% 20% 15%

CKD EPI 69% 8% 23%


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


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


2004


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)


2012

Filtrado glomerularCistatina C

2008

Filtrado glomerularOtros marcadores

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


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]


# 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]


# 2003 European Renal Association–European Dialysis and Transplant Association

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100%Sensibilidad

81%Especificidad

26Pacientes




Interleucina 18

• Células mononucleares,

macrófagos y células

túbulos proximales.


Interleucina 18

2002

• Familia de las proteínas ligadas a ácidos grasos (FABP)

• Expresada en el intestino, páncreas, riñón, pulmones y estómago.




Proteína asociada a ácidos grasos

hepáticos


Proteína asociada a ácidos grasos

hepáticos

2007




Molécula de injuria renal 1 (KIM-1)


Molécula de injuria renal 1 (KIM-1)

2012




Lipocalina asociada a la gelatinasa

del neutrófilo


2009

76%Sensibilidad

85.1%Sensibilidad

GRACIAS

Pruebas de función renal - 2015

Health & Medicine

Transcript of Pruebas de función renal - 2015