Proteinuria in dogs and cats

Proteinuria is defined as the presence of protein in the urine. Normally, circulating serum proteins are blocked by the glomerulus due to size and/or charge. Any small proteins that pass through a healthy glomerulus are reabsorbed by the renal tubules or broken down by renal tubular epithelial cells. Persistent proteinuria, in the absence of lower urinary tract disease or reproductive tract disease, is usually an indication of renal damage or dysfunction. Less commonly persistent proteinuria can be caused by increased circulating levels of low molecular weight proteins. This article reviews mechanisms of proteinuria in dogs and cats and discusses the importance of screening for and ultimately treating proteinuria.     

Measurement, interpretation, and implications of proteinuria and albuminuria.

Proteinuria is a common disorder in dogs and cats that can indicate the presence of chronic kidney disease (CKD) before the onset of azotemia or the presence of more severe CKD after the onset of azotemia. Although a direct pathogenetic link between glomerular disease, proteinuria, and progressive renal damage has not been established, attenuation of proteinuria has been associated with decreased renal functional decline in several studies. There is a need to continue to increase our understanding of the effects of proteinuria on the glomerulus, the tubule, and the interstitium in dogs and cats.     

Assessment and management of proteinuria in dogs and cats: 2004 ACVIM Forum Consensus Statement (small animal)

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.     

Associations between proteinuria, systemic hypertension and glomerular filtration rate in dogs with renal and non-renal diseases

Proteinuria and systemic hypertension are well recognised risk factors in chronic renal failure (CRF). They are consequences of renal disease but also lead to a further loss of functional kidney tissue. The objectives of this study were to investigate the associations between proteinuria, systemic hypertension and glomerular filtration rate (GFR) in dogs with naturally occurring renal and non-renal diseases, and to determine whether proteinuria and hypertension were associated with shorter survival times in dogs with CRF. Measurements of exogenous creatinine plasma clearance (ECPC), urine protein:creatinine ratio (UPC), and Doppler sonographic measurements of systolic blood pressure (SBP) were made in 60 dogs with various diseases. There was a weak but significant inverse correlation between UPC and ECPC, a significant inverse correlation between SBP and ECPC and a weak but significant positive correlation between UPC and SBP. Some of the dogs with CRF were proteinuric and almost all were hypertensive. Neoplasia was commonly associated with proteinuria in the dogs with a normal ECPC. CRF was the most common cause leading to hypertension. In the dogs with CRF, hypertension and marked proteinuria were associated with significantly shorter survival times.     

Physiologic and pathophysiologic fundamentals of proteinuria--a review

The term proteinuria is taken to mean abnormally high protein excretion in the urine. Proteinuria is the consequence of glomerular filtration of plasma proteins, their subsequent reabsorption by the proximal tubular cells and secretion of protein by the tubular cells and distal urinary tract. In physiological conditions, the structural integry of the glomerular filtration barrier prevents the abnormal passage of albumin (molecular mass 66 kDa) and high-molecular-weight proteins (> 66 kDa), whereas the passage of low-molecular-weight proteins (< 66 kDa) is almost completely unrestricted. Proteins that arrive the tubular lumen are reabsorbed by endocytosis after binding to the megalin-cubilin complex. An increased load of proteins in the tubular lumen leads to the saturation of the reabsorptive mechanism and higher urinary protein excretion. Proteinuria can originate from prerenal, renal and postrenal causes. Elevated tubular protein concentrations have been recognized to be toxic to tubular cells and associated with the progression of chronic renal disease. Therefore, the quantitative and qualitative evaluation of proteinuria is important for the diagnosis of renal disease.     

Survival and the Development of Azotemia after Treatment of Hyperthyroid Cats

Background: Hyperthyroidism complicates the diagnosis of chronic kidney disease (CKD) as it increases glomerular filtration rate. No practical and reliable means for identifying those cats that will develop azotemia after treatment for hyperthyroidism has been identified. Hyperthyroidism is associated with proteinuria. Proteinuria has been correlated with decreased survival of cats with CKD and with progression of CKD. Hypothesis: Proteinuria and other clinical parameters measured at diagnosis of hyperthyroidism will be associated with the development of azotemia and survival time. Animals: Three hundred client owned hyperthyroid cats treated in first opinion practice. Methods: Retrospective, cohort study relating clinical parameters in hyperthyroid cats at diagnosis to the development of azotemia within 240 days of diagnosis and survival time (all cause mortality). Multivariable logistic regression analysis was used to identify factors that were predictive of the development of azotemia. Multivariable Cox regression analysis was used to identify factors associated with survival. Results: Three hundred cats were eligible for survival analysis and 216 cats for analysis of factors associated with the development of azotemia. The median survival time was 417 days, and 15.3% (41/268) cats developed azotemia within 240 days of diagnosis of hyperthyroidism. Plasma concentrations of urea and creatinine were positively correlated with the development of azotemia. Plasma globulin concentration was negatively correlated with the development of azotemia. Age, urine protein : creatinine ratio, and the presence of hypertension were significantly correlated with decreased survival time. Urine specific gravity and PCV were significantly correlated with increased survival time. Conclusions and Clinical Importance: The proteinuria associated with hyperthyroidism is not a mediator of progression of CKD; however, it does correlate with all cause mortality.     

The prevalence of albuminuria in dogs and cats in an ICU or recovering from anesthesia

Objective – To evaluate the prevalence of albuminuria in dogs and cats admitted to the ICU or recovering from an anesthetic event. Design – Prospective clinical study over a 10‐week period in 2003. Setting – Veterinary teaching hospital. Animals – One hundred and five dogs and 22 cats. Interventions – Urine was collected from dogs and cats admitted to the ICU or recovering from an anesthetic event. When possible, a second urine sample was collected approximately 48 hours later from those animals that had albuminuria during the initial screening. Measurements and Main Results – All dog samples and most cat samples were screened for albumin using a commercial point‐of‐care immunoassay. Aliquots of samples that tested positive were stored at –20°C until subsequent albumin quantification via antigen capture ELISA. Albuminuria was detected in 63 of 105 (60.0%) dogs and in 14 of 22 (63.6%) cats; the prevalence was higher in animals admitted to ICU than in those recovering from anesthesia. In subsequent samples from 26 dogs, urine albumin decreased in 20 (76.9%) when compared with the first sample; urine albumin was undetectable in 5 (19.2%). In subsequent samples from 6 cats, 4 (66.7%) had decreases in urine albumin when compared with the first sample; 1 (16.7%) was negative for urine albumin. Eleven of 12 dogs (91.7%) and 3 of 4 cats (75%) that died within 3 days of admission to the ICU had abnormal urine albumin; whereas 52 of 93 (55.9%) and 11 of 18 (61.1%) dogs and cats, respectively, who survived more than 3 days had abnormal urine albumin. Dogs with albuminuria were at increased risk of death. Conclusions – The prevalence of albuminuria in animals admitted to the ICU or recovering from anesthesia is higher than reported previously and transient in some patients. The presence of albuminuria may be a negative prognostic indicator in this population.     

Use of urine albumin/creatinine ratio for estimation of proteinuria in cats and dogs

The clinical utility of the urine albumin/creatinine ratio (UAC) using a simplified analyzer for estimation of proteinuria was studied in cats and dogs. Measurement results for diluted feline and canine albumin standard solutions showed linearity. Although conversion formulas (y=1.28x+1.04 and y=1.67x+10.47 for cats and dogs, respectively) were necessary, urine albumin concentrations could be determined in both animals. In cats and dogs with proteinuria, the UAC changed parallel with the urine protein/ creatinine ratio (UPC), and the Log UAC and Log UPC were significantly correlated (r=0.803 (p<0.01) in cats, r=0.801 (p<0.01) in dogs). The UAC using an UAC analyzer could be used clinically as one of the basic in-hospital laboratory tests for estimation of proteinuria in cats and dogs.     

Screening for proteinuria in cats using a conventional dipstick test after removal of cauxin from urine with a Lens culinaris agglutinin lectin tip

Proteinuria is an important indicator of urinary tract disease and urine dipsticks are simple and sensitive tools to screen for this marker. However, the use of dipsticks to screen for proteinuria may not be appropriate in cats, since cauxin, a 70 kDa glycoprotein, is secreted by the kidneys in clinically normal animals of this species. To circumvent this problem, a Lens culinaris agglutinin (LCA) lectin tip was developed to remove cauxin from feline urine, followed by conventional urine dipstick testing for proteinuria. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) with Coomassie brilliant blue R-250 staining indicated that >90% cauxin in the urine of 13 clinically normal cats was trapped by the LCA lectin tip, so that the dipstick protein ‘score’ changed from ‘positive’ (?30 mg/dL) for untreated urine to ‘negative’ (?10 mg/dL) for lectin tip-treated urine. In contrast, SDS–PAGE indicated that lectin tip-treated samples from 20 animals with renal disease contained high concentrations of albumin and low-molecular weight proteins; dipstick testing of lectin tip-treated urine resulted in a consistently positive protein score. The accuracy of the dipstick method for detecting cats with abnormal proteinuria is enhanced if dipsticks are used with urine samples that have first been passed through the LCA lectin tip.     

Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria

BACKGROUND: Tubulointerstitial kidney disease is a common cause of illness and death in pet cats and is typically not associated with overt proteinuria. HYPOTHESIS: Proteinuria would be independently related to survival in cats with renal failure, with or without hypertension. ANIMALS: The study included 136 client-owned cats; 28 apparently normal, 14 hypertensive but not azotemic, 66 azotemic but not hypertensive, and 28 both hypertensive and azotemic. METHODS: Cox's proportional hazards model was used to determine the influence of initial plasma creatinine concentration, proteinuria (urine protein-to-creatinine ratio or albumin-to-creatinine ratio), age, and systemic hypertension on the risk of death or euthanasia during the follow-up period. Multivariable linear regression was used to determine the relation between severity of proteinuria and predictive variables, including age, plasma creatinine concentration, systolic blood pressure, sex, and urine specific gravity. RESULTS: Plasma creatinine concentration and proteinuria were very highly related to survival. The hazard ratio (95% confidence intervals) for death or euthanasia was 2.9 (1.4-6.3) and 4.0 (2.0-8.0) for urine protein-to-creatinine ratio 0.2-0.4 and >0.4, respectively, compared with the baseline group with a urine protein-to-creatinine ratio of <0.2 and were 2.4 (1.2-4.8) and 4.9 (2.3-10.2) for an albumin-to-creatinine ratio of 30-82 mg/g and <82 mg/g, respectively, compared with a baseline group with albumin-to-creatinine ratio of <30 mg/g. Treated hypertensive cats did not have reduced survival, although systolic blood pressure, together with plasma creatinine concentration was positively related to the magnitude of proteinuria. CONCLUSIONS AND CLINICAL IMPORTANCE: Despite the relatively low concentrations of proteinuria typical of chronic renal disease in cats, this measurement is of prognostic significance.     

Effects of urinary tract inflammation and sample blood contamination on urine albumin and total protein concentrations in canine urine samples

BACKGROUND: Urinary tract inflammation and hemorrhage are believed to be common causes of proteinuria in dogs based on results of studies that measured total urine protein concentration. A method to quantify urine albumin (UAlb) concentration in dogs recently has become available; however, the effect of inflammation on albuminuria is unknown. OBJECTIVES: The goals of this study were to determine the effects of urinary tract inflammation, as indicated by pyuria and sample blood contamination, on UAlb concentration and on urine protein:creatinine (UPC) ratio in dogs. METHODS: Urine samples were obtained from dogs with pyuria that were presented to a veterinary teaching hospital or were part of a laboratory colony. To mimic the effects of hematuria, canine whole blood was added to a microscopically normal canine urine sample that had baseline albumin and total protein concentrations below the limits of detection. UAlb concentration was measured using a canine albumin-specific competitive ELISA. UPC ratio was determined using routine methods. RESULTS: Of 70 samples with pyuria, 67% had negligible UAlb concentrations and 81% had normal UPC ratios. UAlb concentration but not UPC ratio was significantly higher (P < 0.05) in samples with concurrent hematuria or bacteriuria. When whole blood was added to normal urine, UAlb concentration did not exceed 1 mg/dL until the sample became visibly pink; the UPC did not exceed 0.4 at any dilution. CONCLUSIONS: Many dogs with pyuria do not have albuminuria or proteinuria; however, albuminuria may be more likely in dogs with pyuria and concurrent hematuria or bacteriuria. Hematuria may not cause an increase in UAlb concentration until it becomes macroscopic and even then may not increase the UPC ratio.     

Samoyed hereditary glomerulopathy: serial, clinical and laboratory (urine, serum biochemistry and hematology) studies.

Human hereditary nephritis refers to familial glomerular diseases which may progress to renal failure. Samoyed hereditary glomerulopathy has been shown previously to be a model for hereditary nephritis. Clinical and laboratory studies were performed to follow progression to renal failure in 44 dogs in a family with Samoyed hereditary glomerulopathy. Affected males appeared healthy for their first three months but then became progressively wasted. Proteinuria was detected between two to three months of age; after five months, urine protein electrophoresis showed pre-albumin, albumin and alpha and beta globulin peaks. From three months onward, a reduced glomerular filtration rate was detected. Serum albumin decreased while amylase, urea, creatinine and phosphate increased from four to five months of age. Death from renal failure occurred by 15 months. Carrier females also became thinner and developed proteinuria between two and three months of age, but neither renal failure nor death ensured. Hence, SHG progressed rapidly in affected males but not in carrier females.     

Evaluation of Predictors of the Development of Azotemia in Cats

Background: Chronic kidney disease (CKD) is a common condition in geriatric cats. Diagnosis is based on the development of persistent azotemia with inadequate urine concentrating ability. Biomarkers are sought for early identification.
Hypothesis: Clinical variables, urine concentrating ability, proteinuria, and N -acetyl-β- d -glucosaminidase (NAG) index will be predictive of cats at risk of developing azotemia within 12 months.
Animals: Client-owned nonazotemic geriatric (≥9 years) cats.
Methods: Prospective longitudinal cohort study monitoring a population of healthy nonazotemic geriatric cats every 6 months until development of azotemia, death, or the study end point (September 30, 2007). Multivariable logistic regression analysis was used to assess baseline clinical, biochemical, and urinalysis variables, urine protein to creatinine ratio (UP/C), urine albumin to creatinine (UA/C) ratio, and urinary NAG index as predictors of development of azotemia.
Results: One hundred and eighteen cats were recruited with a median age of 13 years. Ninety-five cats (80.5%) had been followed or reached the study end point by 12 months of which 30.5% (29/95) developed azotemia. Age, systolic blood pressure, plasma creatinine concentration, urine specific gravity, UP/C, UA/C, and NAG index were significantly associated with development of azotemia in the univariable analysis ( P ≤ .05). However, in the multivariable analysis, only plasma creatinine concentration with either UP/C (Model 1) or UA/C (Model 2) remained significant.
Conclusions and Clinical Importance: This study demonstrates a high incidence of azotemia in a population of previously healthy geriatric cats. Proteinuria at presentation was significantly associated with development of azotemia although causal association cannot be inferred. Evaluation of NAG index offered no additional benefit.     

Diet modulates proteinuria in heterozygous female dogs with X-linked hereditary nephropathy

Young adult heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) have glomerular proteinuria but are otherwise healthy. Because data regarding dietary influences on the magnitude of proteinuria in dogs with spontaneous glomerular disease are not available, 12 such dogs were studied in a double crossover experiment intended to determine effects of altering dietary protein intake for up to 6 weeks. Dogs were blocked by urine protein : creatinine ratio (UPC) and randomly assigned to receive 2 diets: high protein (34.6% dry matter [DM], HP) or low protein (14.1% DM, LP) fed in HP-LP-HP or LP-HP-LP sequence. Food intake was measured daily, body weight (BW) was measured twice weekly, and UPC, plasma creatinine, blood urea nitrogen, phosphorus, albumin, and protein concentrations were measured at 2-week intervals. Nutrient digestibility was measured during the third treatment period. Diet had a significant effect (P < .0001) on all measured variables except plasma phosphorus (P > .5), but unintended differences in digestibility of protein and energy (P < or = .01) prevented assignment of the diet effect exclusively to protein. Proteinuria was greater (UPC 4.7 +/- 2.2 versus 1.8 +/- 1.1, P < .0001) when the HP diet was fed, but the LP diet did not maintain starting BW or plasma albumin concentration within the normal reference range. Diet greatly affects the magnitude of proteinuria in XLHN carrier females. Dietary protein restriction can reduce proteinuria in dogs with glomerular disease, but BW and blood protein concentrations may not be maintained if the restriction is too severe.     

Proteomic analysis of urine from male dogs during early stages of tubulointerstitial injury in a canine model of progressive glomerular disease

Background: Sensitive and specific noninvasive biomarkers for tubulointerstitial injury are lacking, and proteomic techniques provide a powerful tool for biomarker discovery. Objective: The aim of this study was to identify novel urinary biomarkers of early tubulointerstitial injury in canine progressive renal disease using both 2‐dimensional differential in‐gel electrophoresis (2‐D DIGE), which identifies individual proteins, and surface‐enhanced laser desorption ionization time‐of‐flight mass spectrometry (SELDI‐TOF), which generates protein peak profiles. Methods: Urine was collected from 6 male dogs with X‐linked hereditary nephropathy (XLHN) at 2 time points (TP): 1) the onset of overt proteinuria (urine protein:creatinine ratio>2) and 2) the onset of azotemia (creatinine ≥1.2 mg/dL); corresponding renal biopsies were analyzed from 3 of the dogs. Urine samples from the 6 dogs were subjected to analysis by 2‐D DIGE and SELDI‐TOF. Urinary retinol‐binding protein (RBP) was evaluated in 25 male dogs with XLHN and normal control dogs by Western blot analysis. Results: Clinical data and histologic evaluation revealed reduced renal function and increased tubulointerstitial fibrosis at TP 2. A number of urine proteins and protein peaks were differentially present at the 2 time points, with several known biomarkers of renal disease identified in addition to several promising new biomarkers. RBP was first detected in urine approximately 2 months before onset of azotemia (TP 2), but after onset of overt proteinuria, and amounts increased with progression of disease. Conclusions: Proteomic techniques were successfully used to identify urinary biomarkers of renal disease in dogs with XLHN. Urinary RBP is a promising biomarker for early detection of tubulointerstitial damage and progression to end‐stage renal disease.     

Early diagnosis of renal disease and renal failure.

The main goal of early diagnosis of renal disease and renal failure in dogs and cats is to enable timely application of therapeutic interventions that may slow or halt disease progression. Strategies for early diagnosis of renal disease use urine tests that detect proteinuria that is a manifestation of altered glomerular permselectivity or impaired urine-concentrating ability as well blood tests to evaluate plasma creatinine concentration. Animals with progressive renal disease should be carefully investigated and treated appropriately.Animals with mild, possibly nonprogressive, renal disease should be monitored adequately to detect any worsening trends,which should lead to further investigation and treatment even if the increments of change are small.     

Comparison of urinary protein concentration and protein/creatinine ratio vs routine microscopy in urinalysis of dogs: 500 cases (1987-1988)

The clinical problems and results of urinalyses of 500 dogs were reviewed and summarized to compare the sensitivities for detection of abnormalities indicative of urinary system disease among qualitative (sulfosalicylic acid [SSA]), quantitative (Coomassie brilliant blue [CBB]), and indexed (urinary protein/creatinine ratio [U(P/C)]) determinations of urinary protein loss vs microscopic examination of urine sediment. False-negative rates for the detection of microscopically abnormal urine specimens were 5.4% for SSA greater than or equal to 1+, 8.5% for CBB greater than or equal to 1.0 mg/ml, 9.7% for U(P/C) greater than or equal to 1.0, and 7.7% for CBB + U(P/C). A discriminatory U(P/C) value of 2.0 would have excluded dogs with clinically relevant proteinuria in the lower ranges. Proteinuria was not detected in 4.4% (22/500) of the specimens in which important numbers of leukocytes or bacteria were observed. False-negative rates for combined interpretation of quantitative protein concentration and U(P/C) were not significantly different (P greater than 0.10) from SSA alone. Degrees of azotemia were higher (high serum creatinine concentration, P greater than 0.10 and high serum urea nitrogen concentration, P less than 0.05) and prevalence of chronically diseased dogs was greater (P less than 0.005) in dog categories with higher U(P/C) values. More quantitative determinations of urinary protein loss as a screening test offer potential labor-saving and diagnostic advantages in the identification of urinary disease over more qualitative routine screening methods.     

Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers

Background: Proteinuria is a feature of pyometra‐associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. Objectives: To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Animals: Forty‐seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Methods: Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C‐reactive protein, urinary thromboxane B₂) and tubular function (urinary retinol‐binding protein, urinary N‐acetyl‐β‐d ‐glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. Results: UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05–8.69) compared with healthy bitches (0.08, 0.02–0.16) (P < .01). Twenty‐two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Conclusion: Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra‐associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.     

Protein profiling of urine from dogs with renal disease using ProteinChip analysis.

Measurement of total urinary proteins in individuals that tested positive by urinary dipstick is a typical method for assessing the presence of potentially serious renal disorders. In the absence of such overt proteinuria, however, measurement of specific urinary proteins may be useful in the diagnosis of nephropathies and may provide greater insight into the pathogenesis. The urine of 28 dogs (16 with renal disease and 12 healthy) was evaluated to determine whether specific low-molecular-weight proteins or the pattern of protein excretion could also be used as a marker of tubular dysfunction in dogs. Specific proteins were assessed by immunological methods, whereas protein profiles were determined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (MS). In particular, changes in the excretion of retinol-binding protein (RBP) and Tamm-Horsfall protein (THP) appear to be of clinical relevance in the diagnosis of canine kidney diseases. The pattern of urinary protein and peptides revealed specific changes in abundance in dogs with renal disease at molecular masses (kD) of 11.58, 12.41, 12.60, 14.58, 20.95 (RBP), 27.85, and 65.69 (albumin). In conclusion, comparable proteins as in humans might be used as urinary markers for proximal (RBP) and distal (THP) tubular dysfunction in dogs. Surface-enhanced laser desorption/ionization time-of-flight MS is a promising tool for the study of kidney physiology and pathophysiology and might aid in the discovery of new biomarkers of renal disease.     

Comparison of signalment, clinicopathologic findings, histologic diagnosis, and prognosis in dogs with glomerular disease with or without nephrotic syndrome

Background: Nephrotic syndrome (NS) develops most commonly in people with glomerular diseases associated with marked albuminuria. Hypernatremia, hypertension, and progressive renal failure are more prevalent in nephrotic than nonnephrotic human patients. Hypothesis/Objectives: Dogs with NS have higher serum cholesterol, triglyceride, and sodium concentrations, higher urine protein:creatinine ratios (UPC) and systolic blood pressure, and lower serum albumin concentrations than dogs with nonnephrotic glomerular disease (NNGD). NS is associated with membranous glomerulopathy and amyloidosis. Affected dogs are more likely to be azotemic and have shorter survival times. Animals: Two hundred and thirty‐four pet dogs (78 NS dogs, 156 NNGD dogs). Methods: Multicenter retrospective case‐control study comparing time‐matched NS and NNGD dogs. NS was defined as the concurrent presence of hypoalbuminemia, hypercholesterolemia, proteinuria, and extravascular fluid accumulation. Signalment, clinicopathologic variables, histopathologic diagnoses, and survival time were compared between groups. Results: Age, serum albumin, chloride, calcium, phosphate, creatinine, and cholesterol concentrations, and UPC differed significantly between NS and NNGD dogs. Both groups were equally likely to be azotemic at time of diagnosis, and NS was not associated with histologic diagnosis. Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (< or ≥1.5 mg/dL), survival of NS versus NNGD dogs was only significantly different in nonazotemic dogs (51 versus 605 days, respectively). Conclusions and Clinical Importance: Presence of NS is associated with poorer prognosis in dogs with nonazotemic glomerular disease. Preventing development of NS is warranted; however, specific interventions were not evaluated in this study.