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ACVIM Consensus Statement

J Vet Intern Med 2005;19:377–385

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians
with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of
the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking the panel
provides interpretive recommendations based on their collective expertise. The Consensus Statement is intended
to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment.
Topics of statements and panel members to draft the statements are selected by the Board of Regents with
input from the general membership. A draft is prepared and input from Diplomates is solicited at the Forum
and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by
the Board of Regents of the ACVIM before publication.

Assessment and Management of Proteinuria in Dogs and Cats:
2004 ACVIM Forum Consensus Statement (Small Animal)
George E. Lees, Scott A. Brown, Jonathan Elliott, Gregory F. Grauer, and Shelly L. Vaden

Emerging data indicate that more attention should be given to the detection, evaluation, monitoring, and treatment of dogs and
cats with proteinuria. The purposes of this consensus statement are to describe an appropriate approach for accomplishing these
tasks and to provide specific recommendations for assessing and managing dogs and cats with proteinuria based on data that are
currently available. Because proteinuria and albuminuria have numerous possible causes, they must be assessed appropriately to
determine their implications for the patient. This assessment involves localization of the origin of the proteinuria as well as
determination of its persistence and magnitude. Because persistent renal proteinuria usually indicates presence of chronic kidney
disease, which sometimes is a progressive disorder, its detection identifies dogs and cats that have increased risk for adverse health
outcomes. Thus, urine testing that will detect proteinuria should be a component of the clinical evaluations of dogs and cats under
all circumstances that prompt their veterinarians to also perform comprehensive hematologic and serum biochemical evaluations.
At a minimum, this testing should consist of a complete urinalysis that includes a satisfactorily accurate semiquantitative test for
protein, and positive reactions should be properly followed with further testing. The appropriate response to persistent renal
proteinuria depends on the magnitude of proteinuria and the status of the patient. The recommended response generally involves
continued monitoring, further investigation, and therapeutic intervention, which should be implemented as an escalating series of
inclusive, stepwise responses.
Key words: Albuminuria; Canine; Chronic kidney disease; Feline.

R esults of recent studies suggest that in dogs and cats,
as in humans, persistent proteinuria is associated with
greater frequency of renal morbidity, renal mortality, and
proteinuria is associated with an increased risk of mortality
due to all causes even in cats with renal function that is
otherwise good (ie, adequate urine-concentrating ability,
mortality of all causes.1,a,b Moreover, risk of developing nonazotemic) when their proteinuria is 1st discovered.b
these adverse outcomes increases as the magnitude of pro- Although data from studies of dogs and cats are sparse,
teinuria increases.1 Existing data supporting these state- results of recent studies also suggest that when markedly
ments are derived mainly from studies of dogs and cats with proteinuric dogs and cats are treated with angiotensin-con-
chronic renal failure (CRF) (ie, animals with chronic kidney verting-enzyme inhibitors having renoprotective effects (ie,
disease [CKD] that already is causing azotemia).1,a How- effects that decrease or delay adverse outcomes), a reduc-
ever, examination of some recent data also indicates that tion in the magnitude of proteinuria is also observed during
treatment.2,3 This same phenomenon is now well docu-
From the Department of Small Animal Clinical Sciences, College of mented in humans with many different types of renal dis-
Veterinary Medicine, Texas A&M University, College Station, TX ease.4–7
(Lees); the Department of Physiology and Pharmacology, College of
Observation that greater proteinuria is associated with
Veterinary Medicine, University of Georgia, Athens, GA (Brown); the
Department of Veterinary Basic Sciences, Royal Veterinary College,
more rapid renal disease progression and that interventions
London, England, UK (Elliott); the Department of Clinical Sciences, that reduce proteinuria also are renoprotective has fueled
College of Veterinary Medicine, Kansas State University, Manhattan, speculation and much investigation about the possible role
KS (Grauer); and the Department of Clinical Sciences, College of of proteinuria as a direct cause of further glomerular or
Veterinary Medicine, North Carolina State University, Raleigh, NC tubulointerstitial injury in subjects with progressive ne-
(Vaden). Presented in part at the 22nd Annual Veterinary Medical phropathies (reviewed by Remuzzi and Bertani,8 Keane,9
Forum, American College of Veterinary Internal Medicine, Minneap- and Zoja et al10). At the mechanistic level, the precise role
olis, MN, June 9–13, 2004. of proteinuria in renal disease progression currently is un-
Reprint requests: George E. Lees, DVM, MS, Department of Small
certain, especially in dogs and cats. Moreover, even if pro-
Animal Clinical Sciences, College of Veterinary Medicine, Texas A&M
University, 4474 TAMU, College Station, TX 77843-4474; e-mail:
teinuria is harmful, such questions as ‘‘how much protein-
glees@cvm.tamu.edu. uria?,’’ ‘‘of what kind?,’’ ‘‘for how long?,’’ and ‘‘to pro-
Copyright q 2005 by the American College of Veterinary Internal duce what changes?’’ cannot be answered with the data that
Medicine are presently available from studies of dogs or cats. Nev-
0891-6640/05/1903-0015/$3.00/0 ertheless, regardless of proteinuria’s role as a mediator of

Prerenal (Definition: due to abnormal plasma content of proteins that traverse glomerular capillary walls having normal permselectivity prop- erties). hemoglobin or myoglobin. Pathological (Definition: proteinuria that is attributable to structural or functional lesions within the kidneys. we have a strong con- sensus that veterinarians should give more attention to the Proteinuria has numerous possible causes. urine obtained by cystocentesis. pertension) or impaired tubular handling of filtered proteins (possibly marking the presence of tubulointerstitial dys. Normal proteins that are not normally present free in the plasma. Categories of Causes of Proteinuria function) or both. Renal (Definition: due to abnormal renal handling of normal plasma proteins). it promptly resolves when the condition that is generating it resolves. none of the methods illary walls (possibly marking the presence of immune entirely replaces the others. but sediment for evidence of inflammation or hemorrhage. ureter. uria that we recommend. look for dysproteinemia that might ex- Definition of Proteinuria plain the proteinuria). eg. and urethra [including into the urethra from the prostate gland in males]). These plasma proteins traffic into the urine from glomerular capillaries. we recommend for use in dogs and cats is slightly adapted Our goals herein are to describe a comprehensive cog. fever. Several different methods to detect proteinuria increased risk of adverse outcomes and for response to ren. If proteinuria is not prerenal and not extraurinary. or intraglomerular hy. Glomerular (Definition: due to lesions altering the permselectivity properties of the glomerular capillary wall). then Urine obtained from healthy dogs or cats with healthy it is ‘‘urinary. albumin).378 Lees et al Table 1. urinary bladder. Postrenal (Definition: due to entry of protein into the urine after it enters the renal pelvis). Step 2. and treatment of dogs cation scheme for categories of causes of proteinuria that and cats with proteinuria. monitoring. proteinuria generally is taken to mean detection of an abnormal (ie. To exclude ‘‘extra-urinary postrenal. The hall- marks of this type of proteinuria are that it is mild and transient. but we believe the cognitive framework will ommended diagnostic process for localization of proteinuria serve to guide development and implementation of future in dogs and cats as outlined in Table 1 is explained as recommendations. as well as of the effects of interventional thera- Step 1. For these reasons.11 More- nitive framework with which to approach this task. To exclude ‘‘prerenal. evaluation. immunoglobulin light chains (Bence-Jones proteins). from the one published by DiBartola et al (Table 1). Each of these meth- because of altered vascular permeability of glomerular cap. vascular inflammation. de- marker of clinically important events in the kidney arises termination of urine protein to creatinine ratio (UPC). eg. ods has its place in veterinary practice. acute interstitial nephritis] causing exudation of proteins into the urinary space). as a diagnostic term. Urinary (Definition: due to entry of proteins derived from hemorrhagic or exudative processes affecting the walls of the urine excretory pathway. we believe that it is important to assiduously follow provide veterinarians with specific recommendations for as. The value of proteinuria as a quantitative tests performed by conventional urinalysis. They consist mainly of low molecular weight proteins. The rationale underlying the rec- mendations. plementary fashion. as listed in the table. regardless of their magnitude or duration). follows. that is. We recognize that on. Extraurinary (Definition: due to entry of proteins derived from secretions or from hemorrhagic and/or exudative processes affecting the genital tract and/or external genitalia during voiding or in the process of collecting urine for analysis). Tubular (Definition: due to lesions that impair the tubular recovery of plasma proteins that ordinarily traverse glomerular capillary walls having normal permselectivity properties). renal pelvis. and because it can occur and subsequently vary in magnitude assay of urine albumin concentration. but may also include small amounts of moderate molecular weight proteins (eg. and so on). the definitions of the categories. localization of the likely source of the proteinuria in dogs and cats—its causes. strenu- ous exercise. can be used to evaluate dogs and cats. These include semi- oprotective interventions. sensus statement will invigorate the ongoing quest for When evidence of an excessive amount of protein is de- greater understanding of the clinical pathophysiology of tected by urinalysis.’’ and the next step is to evaluate the urine kidneys typically contains a small amount of protein. Abnormal proteins. cation scheme is that it provides a specific correlate for each going and future research will generate new information step in the diagnostic approach for localization of protein- that may necessitate modification of the specific recom. To rule in ‘‘urinary postrenal. and they can be used in a com- complexes. and proteinuria involves these sequential steps: diagnosis. renal injury. eg. and to over. These proteins traffic into the urine from peritubular capillaries. The key distinction here is that the proteinuria is not attributable to presence of renal lesions. Functional (Definition: proteinuria that is due to altered renal physiology during or in response to certain transient phenomena. Categories of causes of proteinuria based on the site or mechanism of the underlying abnormality. sessing and managing dogs and cats with proteinuria based The most important reason why we prefer this classifi- on data that are currently available. consequences. proteinuria is an important marker both for in the urine. Interstitial (Definition: due to inflammatory lesions or disease processes [ie. The classifi- detection.’’ evaluate plasma protein Defining and Classifying Proteinuria concentration (ie.’’ evaluate pies. Our sincere hope also is that this con.’’ find evidence of . excessive) amount of protein Step 3.

fever. the final steps in the localization process buminuria expressed either as urine albumin to creat- are: inine ratios or as concentrations (mg/dL) in urine sam- Step 5.’’ find ● Localization—the process of determining the likely evidence of inflammation associated with clinical signs site or mechanism that is causing the proteinuria. The of active nephritis (eg. before death due to other causes). To rule in ‘‘pathologic. Moreover. includes the history. ‘‘pathologic tubular renal’’ proteinuria (i. of proteinuria in dogs and cats. parent adverse consequences for their health despite the fact sistent renal proteinuria that can be detected (ie. In addition. can be categorized as follows: . tios to assess proteinuria and quantitative assays (eg. to be tran- sient. glomerular renal’’ experience an increase in tality attributable to CKD that progresses at a sufficiently the magnitude of proteinuria that is sufficient to rule out rapid rate to cause clinical illness during their lifetimes. in step 7) that renal lesions persist for the remainder of their lives. UPC $ 2. this conclusion (ie. that can be quite long but nonetheless are subsequently fol- ment. tender kidneys.’’ which is low-grade (ie. to obtain reliable indices of the magnitude of urine ● ‘‘pathologic. a larger (but not yet well- Definition of Persistent Renal Proteinuria defined) number of seemingly healthy dogs and cats have CKD that is either nonprogressive or so slowly progressive The term persistent renal proteinuria is subsequently that it never generates recognizable morbidity or mortality used herein to refer to the types of proteinuria identified in (ie. A substan- that is currently available unless or until animals with tial number of dogs and cats experience morbidity or mor- ‘‘pathologic. To rule in ‘‘functional renal’’ if the proteinuria Implications of Persistent Renal Proteinuria is mild and proves. glomerular renal’’ (albeit low-grade) or ‘‘pathologic tubular renal’’ if the protein. ● Persistence—determining whether or not proteinuria but typically persistent. However. micro. nephrotic if therapy is indicated. but also typically is persistent. persistent microalbu. normal electrolyte excretion. renal fail. information needed to make this assessment always ure). for monitoring trends. ● ‘‘pathologic. manifestations of renal failure but can be manifested as hy- pertension alone. urine sediment evidence of inflammation or hemorrhage as well as results of blood tests that are sufficient (in the remaining possibilities are: the context of the other known findings) to exclude ● ‘‘functional renal. Canine and Feline Proteinuria Consensus Statement 379 inflammation or hemorrhage with or without clinical Assessment of proteinuria involves investigation of 3 key signs of excretory pathway disease (eg. some steps 5 and 7 above.. which actually is an uncommon cause magnitude. including a If the proteinuria is ‘‘urinary’’ and not associated with sediment examination) and sometimes a urine culture. To rule in ‘‘pathologic. These 2 types of proteinuria cannot be reliably CKD in dogs and cats that is identified in this way has a distinguished from one another by conventional testing wide range of possibilities in its clinical course. sporadically) or steadily once it becomes Detection and Assessment of Persistent evident. Persistent renal proteinuria. In some cases. with follow-up evaluation. ab. Step 6. interstitial renal. Persistent re. enzyme-linked immunosorbent assay [ELISA]) for al- Consequently. but tubular proteinuria often occurs in the ● Magnitude—use of appropriate quantitative methods absence of such findings. 2 or more weeks apart. Additionally. persists over time requires repeated testing on 3 or uria is accompanied by normoglycemic glucosuria. it must be assessed with CKD identified by finding persistent renal proteinuria appropriately to determine its implications for the patient. pollakiuria) but elements: without apparent clinical signs of nephritis. animals have stable. the range of day-to-day variation that may be observed malities and help to identify the tubular origin of the in animals with generally stable proteinuria. the results of a complete urinalysis (ie.010) to assess microalbuminuria. Such methods include UPC ra- range).0. mild.e. animals Proteinuria not only must be detected. or both that demonstrate comparison of serial values requires appreciation of the presence of multiple tubular reabsorptive abnor. proteinuria. or ‘‘light’’) and transient. the entire spectrum of persistent. as defined above. with follow-up evaluation. indicates uria is mild but proves. of low dysproteinemia. physical examination findings. subclinical CKD for extended periods of time principal focus of the remainder of this consensus state. more occasions. Said differently. animals with CKD includes those animals that have seem- el has been asked to make recommendations and is the ingly stable. UPC $ 2. such protein. General Implications Step 7. with the methods that are currently available. to be the existence of CKD. including response to treatment albuminuria alone) to very substantial (ie. to specific magnitude of proteinuria is sufficiently high to support gravity 1. glomerular renal. Renal Proteinuria Based on the apparent clinical course of disease.’’ which also is low-grade.’’ which can be of any protein loss is crucial for clinical decision-making and magnitude ranging from very low-grade (eg. Step 4. tubular renal. glomerular renal’’ if the ples diluted in a standardized fashion (eg. Illness caused by such progressive CKD usually is due to as in step 5). Another important (but also not yet well defined) group of nal proteinuria is the type of proteinuria for which this pan. subclinical CKD that generates no ap- minuria is the mildest form (ie. To rule in ‘‘pathologic.0 in dogs and cats). lowed by further renal disease progression that may occur intermittently (ie. lowest magnitude) of per.

extended periods ($6 months) without apparent dis. there trends. magnitude of animals that are progressing during the monitoring period proteinuria may diminish as the nephropathy approaches its from those that are not progressing. animals actually may have stable (ie. followed by: sive CKD. In this setting of uncer.380 Lees et al 1. small amounts of albumin may appear in the urine. transient microalbu- time. 3. and should prompt further in- evident. inflammatory. For the purposes of this consensus statement. extended periods (ie. whenever there is a disruption in en- decisions are formulated based on incorrect assumptions dothelial architecture to the point that the vessels leak. Microalbumin- ther: uria usually is attributable to altered glomerular permselec- a. this lesser magnitude of porarily versus indefinitely stable. only transiently if the animal survives and recovers from tection of progressively worsening trends. currently is no practical way to reliably determine the por- 2. essentially unchang. mals that actually have or will eventually develop progres- ease progression. subclinical CKD. Therefore. serial evaluations having demonstrated worsening cause or contribute to microalbuminuria. time is crucial. finding persistent renal proteinuria can alert the animal’s ing) renal lesions for extended periods that end because of veterinarian and owner to the existence of a previously un- reactivation of old or superimposition of new processes of suspected threat to the animal’s health. On the other hand. Progressive increases in the mag- nitude of microalbuminuria are likely to be indicative of When the progressive nature of an animal’s CKD is not active. subclinical CKD should detect worsening proteinuria that may be observed do not necessarily mean trends in a timely manner if and when they occur. monitoring is the key to minimizing such errors. the strength Persistent microalbuminuria is the mildest detectable of evidence that is available to support specific statements . nephrons through which protein loss can occur. defined tion of microalbuminuria. subclinical CKD can be proposed. actually be experiencing ongoing renal damage (ie. that is due to tubular as by: opposed to glomerular dysfunction. Thus. Timely discovery of renal injury. defined by ei. ongoing renal injury. if proteinuria should permit eventual differentiation of animals with tem. form of abnormal renal handling of protein. Re. endothelial injury throughout the circulation. subclinical CKD. should prompt further action. a. ifested by animals that actually have indefinitely stable. $6 months) without apparent Because microalbuminuria is the mildest detectable form disease progression. such as a rising its illness. subclinical CKD. That is. including magnitude of proteinuria. in animals with end stage because there are fewer and fewer remaining currently stable. monitoring will not fore. tial benefit of screening apparently healthy animals for pro- trating ability and well-preserved excretory function). tell the future. if any. or traverses the normal glomerular filtration barrier also can b. those with apparently progressive CKD. there currently is no way to In animals with serious. minuria from each other. renal lesions that are progressing) that merely is hidden from detection during cause persistent renal proteinuria are incited by mechanisms this period. De. especially when a treatable underlying infectious. finding that the condition has already reached an ad. albeit tainty. either failing to give treat. Moreover. monitoring the animal’s renal disease status over vestigation. minuria or mild proteinuria may occur as an indication of ment that might be helpful or giving treatment that is un. tivity. about which scenario is present. such nels’’ to aid in the detection of such disorders. or even tory structural and functional changes in the relatively un. and thus that the renal disease has improved. subclinical CKD. lesions In many dogs (and probably cats). those with indefinitely stable. including in necessary and could be harmful) will occur if therapeutic the kidneys. defined subclinical CKD as well as the form of persistent renal by: proteinuria that is most likely to be 1st manifested by ani- a. but impaired tubular handling of the albumin that vanced stage. adequate monitoring of animals as renal failure progresses. really is a mediator renal injury. causing microalbuminuria alone or nal proteinuria or microalbuminuria is an important poten- mild proteinuria in animals with adequate urine-concen. gardless of such possibilities. the kidneys can serve as ‘‘senti- damaged portions of the kidneys. by diseases that are not primary renal. Strength of Evidence Levels verity. intermittently (ie. systems (ie. those with temporarily stable. That is. it is both the form b. Such animals may had been at earlier stages of the disease. monitoring is the key to eventually dif- b. especially if ongoing that are initiated by disease processes located in other organ damage is being contemporaneously offset by compensa. Again. However. sporadically) or steadily worsening of persistent renal proteinuria that is most likely to be man- trends. This scenario also is plausible. ferentiating these 2 categories of animals with microalbu- ease or failure. Such monitoring is only able to distinguish In animals with CKD causing renal failure. proteinuria might actually be as damaging (or more dam- At least 2 possible scenarios for animals with temporarily aging) to the remaining nephrons as more severe proteinuria stable. followed by: of abnormal renal handling of protein. and treatment errors (ie. magnitude of proteinuria. urinary.c That is. reductions in the magnitude of with stable. or neoplas- the durations of periods of apparent stability are protracted tic condition because of a clinical investigation that is or when the functional consequences of the renal lesions prompted by detecting previously unsuspected persistent re- are especially mild (eg. but demonstration of stable or improving indices of disease se. This scenario is plausible. life-threatening illnesses (eg. Indeed. reliably tell these 2 scenarios apart at any one moment in dogs and cats in intensive care units). teinuria. death or euthanasia for reasons unrelated to renal dis. disorders). is an indication for nothing more than continued monitoring.

logic and serum biochemical evaluations (ie. Specific Implications in Cats should be a component of routine clinical evaluations of apparently healthy dogs and cats in any circumstances that In cats. and evidence categorized as Level 3 above) of reduced survival in cats being associated with is the weakest (ie. including dog and cat urine specimens. of persistent renal proteinuria is either UPC $0. should be a component of the clinical evaluations of dogs comes increases as the magnitude of proteinuria increases and cats with any serious illnesses that also prompt their (Level 1). the risk of all-cause mortality false-positive dipstick colorimetric test reactions commonly progressively increases as UPC at initial diagnosis increases occur in highly concentrated or highly alkaline (pH $7.16 (Level 2). even within the conventional reference range.a.5 or mi. Nevertheless. morbidity and mortality.0) sometimes are observed in of a complete urinalysis that includes conventional semi- cats with progressive renal failure near end stage. by SSA alone. the risk of all-cause mortality also in the face of a positive dipstick result (see microalbumin- increases as UPC or albuminuria at initial evaluation in- uria section below). high frequency of false-positive results). vals while such disorders are being managed for extended buted to a postrenal cause. as a prerenal or postrenal cause. with positive reactions the UPC value. croalbuminuria found repeatedly in 3 or more specimens or by SSA performed in an attempt to verify a positive obtained 2 or more weeks apart that cannot be attributed to dipstick reaction) are sufficient to exclude the exis- . UPC chemistry tests are performed as part of routine health eval- values $1.0 occur uncommonly. confirmed by SSA) In cats. Evidence categorized as Level 1 is the strongest as . having a UPC value $1. periods. Urine testing that will detect proteinuria.30. studies comparing the implications of albumin. In addition.2. sored (ie. least convincing).b ● Strong positive reactions ($11. proteinuria was associated with reduced survival of some kind. Canine and Feline Proteinuria Consensus Statement 381 regarding the implications of proteinuria in dogs or cats. magnitudes of proteinuria that are within the currently ac- cepted reference range for healthy animals have generated Specific Implications in Dogs new uncertainties about cutoff values for proteinuria that should be used to define the health status of cats. microalbuminuria is evidence of persistent renal known to often become complicated by proteinuric renal proteinuria when it is found repeatedly in 3 or more spec. Because In cats with renal failure. In one study. the better the prognosis. if it is present. animals with chronic illnesses that are In dogs. disease should be tested for proteinuria at #6-month inter- imens obtained 2 or more weeks apart and cannot be attri. UPC values $0. for the presence of glomerular disease.0 usually is due to glomerular renal disease (Level 3). cutoffs needed to differentiate cats with good outcomes ● Weak positive reactions (trace. risk of adverse out. However. and data sufficient for the prehensive hematologic and serum biochemical evaluations formulation of general statements about the implications of (ie.13 or a SSA turbidometric test alone. are an indication to proceed with determination of uria (measured with a species-specific immunoassay) and UPC ratio either immediately or at least after repeated proteinuria (measured by conventional UPC ratios) have testing in 2–4 weeks verifies persistence of the posi- thus far shown little difference between the 2.0 (but usually still . if it is present. the examination of well as specific recommendations for therapeutic interven.0. but the UPC tive reactions. All positive reactions. point-of-care teste or a quantitative ELISA 2).6. has been categorized in 3 levels as described in the range for UPC in noncastrated male cats should be as high Appendix.0 at When and How to Test for Proteinuria initial evaluation is associated with increased risk of uremic Urine testing that will detect proteinuria. confirmed by SSA) are from cats with adverse outcomes are much lower than the an indication at least for repeated testing in 2–4 weeks UPC cutoffs that currently are widely used in cats.5 are evidence of persistent re.0 in cats should prompt a high index of suspicion uations of apparently healthy dogs and cats). renal diseases that cause proteinuria with UPC also prompt their attending veterinarians to perform com- values $1.1 attending veterinarians to perform comprehensive hemato- In dogs.43 at initial evaluation was associated test. regardless of the creases. but UPC values At a minimum. Alternatively. persistent renal proteinuria with UPC values $2. quantitative evaluations of protein concentration. In dogs. Reliance on dipstick tests alone is not rec- of nonazotemic cats. Nonetheless. That is. In urine specific gravity. were alive at the end of the study or were lost to follow-up) was 0. urine tests for proteinuria should consist $1. the recent observations (as cited (ie.b assay could be used to confirm the presence of albuminuria In nonazotemic cats. ● Negative reactions (by dipstick alone. should prompt a follow-up evaluation one study.12 In dogs with renal failure. urinalyses nal proteinuria when they are found repeatedly in 3 or more should be done when CBCs and serum chemistry tests are specimens obtained 2 or more weeks apart and cannot be performed to evaluate dogs and cats with undiagnosed ill- attributed to a prerenal or postrenal cause. hav- confirmed by a sulfasalicylic acid (SSA) turbidometric ing a UPC value $0. whereas the median UPC for cats that were cen- tions (ie.d satisfactory test methods are UPC values within the reference range. most convincing). some data suggests that the upper limit of the reference tions.5) across the full spectrum of possible UPC values. Additionally. urinalyses should be done when CBCs or serum bio- proteinuria in such cats are not available. the lower either a dipstick colorimetric test. the current conventional definition mination of UPC ratio if the positive reactions persist. a with an increased risk of mortality due to all causes (Level species-specific. nesses). with deter- In cats (as in dogs).b to check for persistence of the proteinuria. The median UPC for cats that died ommended because of the low specificity of positive reac- was 0.

determinations of UPC ratios should be per- formed to guide clinical decision-making and to monitor trends. For animals in which proteinuria is documented or sus- pected.382 Lees et al tence of all forms of proteinuria except microalbumin- uria (see below). is recommended under the following circum. as well as investigation (espe- cially invasive tests) without sufficient evidence. this approach might be from breeds or families that are genetically predis. that are known to often become complicated by pro- teinuric nephropathies. Specific Recommendations (Fig 2) Persistent renal proteinuria always should prompt action. ● Intervene (highest level)—refers to prescribing dietary ● When results of conventional evaluations for protein- changes. and once again. or both in an uria are negative in dogs and cats with serious ill- attempt to beneficially modify the course of disease or nesses. inflammatory. which Dogs that have a ‘‘high-positive’’ reaction for urine al- might arise from monitoring. portantly. one should uria are negative in apparently healthy dogs that are only monitor (ie. if it is be done) in order to discover an underlying systemic present. individuals circumstances. However. depending on the situation. should be sequential and inclusive. as well as monitor (ie. one should investigate mality is desired by the veterinarian or animal owner. disease or to define the animal’s renal disease more stances: exactly. Implementation of this escalating response approach ● When results of conventional evaluations for protein. to justify the risk to the bumin when using the species-specific. proach precludes intervention without appropriate inves- sible. pending on the situation. the following series of escalating steps that depend on the subclinical CKD because they are nonetheless at risk magnitude of proteinuria and patient status (Fig 1): to have (or to develop) progressive CKD that then may ● Monitor (lowest level)—refers to repeating 1 or more require therapeutic intervention (ie. Im- posed to such disorders) are being prospectively mon. immediate or sequential. Urine testing that will detect microalbuminuria. and finding such a ‘‘high-positive’’ reaction is an indication to proceed with UPC determinations. and use stances that are the least compelling. nosable. treatable infectious. That is. use of pharmacologic agents. correct implementation of this escalating ap- itored to detect onset of the disease as early as pos. one should intervene ● When dogs or cats that are known to be at risk for as well as investigate and monitor in the most compelling developing a glomerular renal disease (eg. Such a step- ● When conventional evaluations for proteinuria pro. that would not tests that have been done previously in order to detect otherwise be indicated) or to evaluate response to ther- changes with passing time. including response to treatment when therapeutic interventions are indicated. more compelling circumstances. de- duce equivocal or conflicting results. inclusive stepwise as much as 90% (ie. those that would not otherwise the animal’s renal disease.5. and especially in those with chronic illnesses improve the animal’s health. The categories of possible actions are: General Principles ● Prospective monitoring—meant to promptly detect Appropriate responses to persistent renal proteinuria are worsening trends in animals that appear to have stable. that is commercially available frequently also have a UPC $0. tigation and monitoring. The variation of UPC ratios observed in cats with values within the reference Fig 1. changes that ● Diagnostic investigation—meant to detect any diag- should prompt further action) in a timely manner. the variation in UPC values observed in dogs with stable proteinuria sug- gests that serial UPC ratios probably need to differ by as much as 40%. high level of confidence that a cat’s magnitude of pro- teinuria has increased. Further. The main purpose of mon. point-of-care teste animal and the cost to the owner. . in other of the most sensitive test that might detect an abnor. However. by-step approach might be immediate or sequential. but not intervene). apy. Schematic representation of the recommended paradigm for range suggests that serial UPC ratios need to differ by responding to proteinuria with a series of escalating. especially in the lower ranges of abnor- mality. not investigate or intervene) in circum- $6 years old and cats that are $8 years old. to conclude with a high level of confidence that the prevailing magnitude of proteinuria actually has changed (increased or decreased). or neo- ● Investigate (higher level)—refers to performing new plastic disease that might be the underlying cause of or additional tests (ie. itoring is to detect worrisome trends (ie. nearly double) to conclude with a responses. Recommended Responses to Persistent but appropriate actions depend on the prevailing magnitude Renal Proteinuria of proteinuria and the clinical status of the patient.

In- deed. controlled clinical trial.0. Additionally. Canine and Feline Proteinuria Consensus Statement 383 omega-3 fatty acid supplementation). inflammatory or neoplastic condition is already apparent (ie.0. to slow the rate of renal disease progression) and The recommendation to treat azotemic dogs with persis- using reduction of the magnitude of proteinuria as one tent renal proteinuria and UPC values $0. ● Nonazotemic dogs or cats with persistent renal pro- teinuria and UPC values $2.5 is based mainly index of therapeutic response.0 is should prompt specific escalating responses to proteinuria depending supported only by expert opinion (Level 3). In a study of dogs with the remnant kid- with reduced quantity but high-quality protein with ney model of CRF that also had mild proteinuria.0. The treatment strategies on the results of experimental studies.2 However. Diagnostic investigation that is focused on finding a po- tentially treatable underlying disease and adequate contin- ued monitoring are recommended for: ● Nonazotemic dogs and cats with rising magnitudes of persistent microalbuminuria. placebo-controlled trial of enalapril therapy for dogs with glomerulonephritis reported by Grauer et al (Level 1). pro- spective monitoring should be combined with appro- priate treatment for the underlying condition. Prospective monitoring sufficient to accomplish timely detection of any worsening trends is recommended for: ● Nonazotemic dogs and cats with persistent microal- buminuria. MA. Recommended cutoffs for the magnitude of proteinuria that mendation to initiate treatment if UPC values are $2.4.0 is based mainly on the results of a randomized. and (C) in azotemic cats. microalbuminuria. ● Cats with CKD causing azotemia and UPC values $0. and the recom- Fig 2. low-dose aspirin therapy. ● Nonazotemic dogs and cats with persistent renal pro- teinuria and UPC values $1. After appropriate investigation and specific treatment of any underlying disease that is identified. on patient status (A) in nonazotemic dogs and cats. all dogs en- tered into that trial had UPC values $3. only 1 recommendation is even partially supported by results of a randomized. urine all of the dogs in that trial were fed a renal diet and given protein to creatinine ratio.5. enalapril . to administer an angiotensin-converting-enzyme inhibitor drug or both.5. (B) in azotemic dogs. ● Nonazotemic dogs and cats with persistent renal pro- teinuria and UPC values $0. Therefore. when possible. (ie. previously diagnosed or now clinically evident) in dogs or cats in this category. Note: When an under- lying infectious. The recommendation to treat nonazotemic dogs with per- sistent renal proteinuria and UPC values $2. albeit in the target to be considered are to feed an appropriate diet (one species (Level 2). UPC. Strength of Evidence Levels for Recommended Interventions Recommendations for responding to proteinuria are pro- vided herein despite the fact that few data with which to address these important clinical questions are available. therapeutic inter- vention accompanied by adequate monitoring is recom- mended for: ● Dogs with CKD causing azotemia and UPC values $0. whether or not the benefits of enalapril therapy that were observed in that trial were in any way dependent on either of these concomitant ● Therapeutic intervention—meant to be renoprotective treatments is uncertain.

et al.117:209–225. are provided as expert opinion (Level 3).64: b Walker D. Effect of the angiotensin- larly. Brown CA. Elliott J. J Lab Clin Med 2000.329:1456–1462. J Am Vet Med Assoc 1985. Indeed.349:1857– with renal disease may need to pay greater attention to pro- 1863. non-azotaemic cats. et al. Greco DS. Markwell P. Infectious Diseases Society of America. Treating feline renal failure: An evidence-based ap- This work was supported by the American College of proach.354:359–364. J Lab Clin Med 1998. in studies of dogs with the rem- nant kidney model of CRF. et al. cific circumstances of individual cases. Gherardi G. Harris TL. Providing The Collaborative Study Group. J Comp Pathol 1997. Although veterinarians caring for animals aliano di Studi Epidemiologici in Nefrologia).18:417–418 (abstract). Treatment of X-linked able data are available regarding a renoprotective reduction hereditary nephritis in Samoyed dogs with angiotensin converting en- of proteinuria (ie. Jensen WA. Fort Collins. N Engl J Med 1998. Vet Clin Pathol 1991. Rohde RD.20:95–97. Moore LE. Bertani T. LaForce FM. proteinuria might 10. Working Group on Steroid Use. Center SA. Vaden SL. Brown SA.384 Lees et al therapy reduced proteinuria and modulated progressive re. Jacob F. References nal injury. TX. they also should not lose sight of the proven im. Although this is not intended to be an all- 11. Dallas. N Engl J Med 1993. 17. as well as combating 12. Alberti D.35(Suppl 1):S97–S105. non-diabetic nephropathy. et al. renal insufficiency. 3. Crossley KB. Antimicrobial Agents Committee. Cellular responses to protein well be relatively unimportant compared with one or more overload: Key event in renal disease progression. Jensen WA. dogs and cats with renal disease or renal failure. Baumal R. Chesney PJ. Zoja C.D.16 sus placebo as a treatment for canine idiopathic glomerulonephritis. J Am Vet Med Assoc and slowed renal disease progression. Curr Opin Nephrol Hypertens 2004. Am J Kidney Dis 2000. McGowan J. Getzy DM. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.135:275–286. Jacobs G. but athies. Evaluation of the ef- excretion in cats with renal failure and/or hypertension. Brown SA. et al. Osborne CA. J Am Anim Hosp Assoc attention include feeding an appropriate diet. DiBartola SP. 13. Smith AR. Brown L. Renoprotective prop- This consensus statement is focused on detection and erties of ACE-inhibition in non-diabetic nephropathies with non-ne- treatment of animals with persistent renal proteinuria. Ruggenenti P. Currently. 2004. 334:939–945. Grodecki KM. Remuzzi G. Lancet 1997. Effects of dietary ventional urine protein test strip method and a qualitative ELISA for polyunsaturated fatty acid supplementation in early renal insufficiency the detection of canine and feline albuminuria. metabolic acidosis. 8. Polzin DJ. zyme (ACE) inhibitor. The effect of portance of attending to other problems that often arise in angiotensin-converting-enzyme inhibition on diabetic nephropathy. Am J Vet Res 2003. 15. Final Caveats 5. Benigni A.16:537–546. J Vet Intern Med in dogs. The GISEN Group (Gruppo It- appropriately. . et al. Randomised placebo-controlled trial of effect of ramipril on de- in dogs and cats that are important to evaluate and treat cline in glomerular filtration rate and risk of terminal renal failure in proteinuric. which is but one of many possible manifestations of CKD 6. Grauer GF. Polzin DJ. Keane WF.131:447– Intern Med 2004. Hunsicker LG.187:820–824. other problems. Brown SA. 24-Hour urine pro- anemia. no data are available regarding renoprotective reduc. and inadequate appetite.14 Additionally. whereas supplemen- 2005. some of the other issues that often deserve cluding 24-hour protein excretion in the dog. 16. et al. Elliott J.17:405 (abstract). Remuzzi G. Moore FM. 7. Evaluation of the asso- omega-3 polyunsaturated fatty acids reduced proteinuria ciation between initial proteinuria and morbidity rate or death in dogs with naturally occurring chronic renal failure. et al. May 29–June 1. J Vet ids in dogs with renal insufficiency. phrotic proteinuria. Brum SL. CO lines for the use of systemic glucocorticosteroids in the management of selected infections. Bain RP. details about the proper management of these other prob.R. Lancet 1999. Simi. converting-enzyme inhibitor benazepril on the progression of chronic tion of microalbuminuria in either dogs or cats. 4.18:417 (abstract). J Vet Intern fects of inhibition of angiotensin converting enzyme with enalapril in Med 2003. et al. Lewis EJ. Finco DR. J All other recommendations in this consensus statement Vet Intern Med 2000. Chew DJ.18:418–419 (abstract). Janin G.13:31–37. Brown CA. creased proteinuria and improved outcome) in cats.15. N Engl J Med 1996. J Vet Intern Med 2004. The prevalence of of chronic administration of dietary omega-3 polyunsaturated fatty ac- microalbuminuria in dogs and cats in an intensive care unit. d Grauer GF. Brown CA. Maschio G. tein/creatinine ratio in dogs with protein-losing nephropathies. Relation of survival time and urinary protein 14. 18. depending on the spe. 455. dogs with induced chronic renal insufficiency. teinuria. dietary supplementation with 1. Wilkinson E. Crowell WA.339:1448–1456. Pathophysiology of progressive nephrop- lems is beyond the scope of this consensus statement.165:1–13. Urine protein determination in dogs and cats: Comparison of dipstick and sulfasalicylic acid proce- Footnotes dures. Comparison of con. controlling 1980.14:526–533.226:393–400. hyperphosphatemia and hypertension. Smith CA. Beneficial effects c Turman CA. Effects of enalapril ver- proteinuria and enhanced progression. Predictors of survival in 321–327.-Screen Urine Test. J Infect Acknowledgment Dis 1992. gressive renal disease. Gains MJ. Proteinuria: Its clinical importance and role in pro- address than is proteinuria. no cit. a Syme HM. Syme HM. Quantitative urinalysis in- inclusive list. Guide- e E. they are individually and collectively no less important to 9. Heska. rum. administration of a treatment that de. American College of Veterinary Internal Medicine 20th Fo- Veterinary Internal Medicine. 2002. Crowell WA. Perna A. healthy. tation with omega-6 polyunsaturated fatty acids increased 2.

preferably from more than 1 center ● Multiple time series ● Dramatic results in uncontrolled experiments Level 3 Based on: ● Opinions of respected authorities on the basis of clinical experience ● Descriptive studies ● Studies in other species ● Pathophysiologic justification ● Reports of expert committees a Initially adapted from the work of McGowan et al17 by Polzin. Strength of evidence levels used to annotate statements regarding specific implications of proteinuria and specific recommendations for therapeutic interven- tions.18 .a Level 1 (best evidence) Based on data obtained from: ● At least 1 properly randomized controlled clinical trial Level 2 Based on data obtained from: ● At least 1 well-designed clinical trial without randomization ● Cohort or case-controlled analytic studies ● Studies using acceptable laboratory models or simulations in the target species. Canine and Feline Proteinuria Consensus Statement 385 Appendix.