Proteinuric Dogs Research Articles

Thromboelastometry used for evaluation of blood coagulability in dogs with kidney diseases

Kidney diseases as protein-losing nephropathies are predisposing conditions for thrombosis/thromboembolism in dogs due to increased blood coagulability. The aim of this study was to use thromboelastometry for investigation of changes in haemostasis in dogs affected by renal proteinuria alone or concomitant with azotemia. The study was done at 55 client-owned, healthy (n = 34), proteinuric (n = 14), and proteinuric/azotemic (n = 7) dogs. Blood coagulation was assessed by means of standard coagulation profile and thromboelastometry (in-TEM, ex-TEM, and fib-TEM). In proteinuric dogs only the maximum clot firmness and maximum clot elasticity significantly increased (P< 0.05), whereas in the proteinuric/azotemic dogs the thromboelastometric profiles showed a pronounced increase of blood coagulability, as indicated by significant changes (P< 0.05) of the variables clotting time, clot formation time, α angle, maximum clot firmness and maximum clot elasticity. After correction for group affiliation, the linear regression analysis showed a non significant association between changes in proteinuria and thromboelastometric profiles. In conclusion, thromboelastometric changes indicating hypercoagulabilty were more consistently found in the dogs with proteinuria/azotemia, than in those with proteinuria alone, suggesting that the former dogs can be considered at higher thrombotic risk. This is the first study where thromboelastometry has been applied to the investigation of haemostatic changes in dogs with kidney diseases.

Serum cardiac troponin I concentrations in dogs with leishmaniasis: correlation with age and clinicopathologic abnormalities

There is anecdotal evidence of myocardial injury in dogs with leishmaniasis due to generalized vasculitis and myocarditis. The aims of this study were to evaluate serum concentration of cardiac troponin I (cTnI) as an indicator of myocardial injury in dogs with leishmaniasis and to assess the relationship between cTnI concentration and age, serum antibody titer, and a variety of blood analytes. In this retrospective study, serum cTnI concentration was measured in dogs with leishmaniasis and in age-matched healthy dogs. Diagnosis was based on clinical signs and moderate-to-high seropositivity for Leishmania as measured by ELISA. Correlations between cTnI concentration and ELISA seropositivity, PCV, concentrations of serum creatinine, total protein, albumin, and globulin, albumin:globulin ratio (A/G), and urine protein:creatinine ratio (UPC) were investigated. The Mann-Whitney test was used to compare analytes between dogs with normal and increased (> 0.06 μg/L) cTnI concentration and to compare cTnI concentrations between dogs with and without anemia, azotemia, and proteinuria. In dogs with leishmaniasis (n = 40), median cTnI concentration was higher than in control dogs (n = 11) (P = .011). Sixteen dogs (40%) with leishmaniasis had increased cTnI concentration; cTnI was moderately to weakly correlated with decreased albumin concentration, decreased A/G, increased UPC, decreased PCV, positive Leishmania titer, and increased age. Dogs with leishmaniasis had significantly higher total protein and globulin concentrations and lower PCV, albumin concentration, and A/G than control dogs. Hematologic and biochemical analytes did not differ significantly between dogs with cTnI concentration within the reference interval and those with increased concentrations. Concentration of cTnI was higher in proteinuric dogs compared with nonproteinuric dogs (P = .017). A proportion of dogs with leishmaniasis have increased serum cTnI concentration, indicative of some degree of cardiac injury. Additional studies are needed to investigate the relationship between leishmaniasis and possible myocardial injury.

Evaluation of Kidney Injury in Dogs with Pyometra Based on Proteinuria, Renal Histomorphology, and Urinary Biomarkers

Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. 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. Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. 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 B(2)) 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. 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. 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.

C-reactive protein concentrations in serum of dogs with naturally occurring renal disease

The current study was undertaken to investigate the relation between serum C-reactive protein (CRP) concentrations and parameters of renal function in dogs with naturally occurring renal disease. Dogs were assigned to groups according to plasma creatinine concentration, urinary protein-to-creatinine ratio (UP/UC), and exogenous plasma creatinine clearance (P-Cl(Cr)) rates. Group A (healthy control dogs; n = 8): non-azotemic (plasma creatinine <125 µmol/l) and nonproteinuric (UP/UC <0.2), with P-Cl(Cr) rates >90 ml/min/m(2); group B (n = 11): non-azotemic, nonproteinuric dogs with reduced P-Cl(Cr) rates (50-89 ml/min/m(2)); group C (n = 7): azotemic, borderline proteinuric dogs (P-Cl(Cr) rates: 22-67 ml/min/m(2)); and group D (n = 6): uremic, proteinuric dogs (not tested for P-Cl(Cr)). The serum CRP concentrations were measured via commercial enzyme-linked immunosorbent assay. The CRP concentrations in the clinically healthy dogs (group A) ranged from 2.09 mg/l to 8.60 mg/l (median: 3.21 mg/l). In comparison with dogs of group A, median CRP concentrations were significantly (P < 0.01) elevated in dogs of group B (17.6 mg/l, range: 17.0-19.2 mg/l), group C (24.8 mg/l, range: 18.0-32.5 mg/l), and group D (59.7 mg/l, range: 17.7-123 mg/l). Serum CRP was significantly related to P-Cl(Cr) (r = -0.83; P < 0.001), plasma creatinine (r = 0.81; P < 0.001), UP/UC (r = 0.70; P < 0.001), and leukocytes (r = 0.49; P < 0.01). The significant relations between serum CRP concentrations and biochemical parameters of kidney function in plasma and urine suggest that a stimulation of the acute phase response is implicated in the pathogenesis of canine renal disease.

Day-to-Day Variation of the Urine Protein : Creatinine Ratio in Female Dogs with Stable Glomerular Proteinuria Caused by X-Linked Hereditary Nephropathy

Interpretation of serial urine protein:creatinine (UPC) values is confounded by a lack of data regarding random biologic variation of UPC values in dogs with stable glomerular proteinuria. That there is minimal day-to-day variability in the UPC of dogs with unchanging proteinuria and the number of measurements needed to reliably estimate UPC varies with the magnitude of proteinuria. Forty-eight heterozygous (carrier) female dogs with X-linked hereditary nephropathy (XLHN) causing stable proteinuria. Urine samples were obtained daily by cystocentesis for 3 consecutive days on 183 occasions (549 samples). The UPC was measured for each sample with a single dry-film chemistry auto-analyzer. Data were analyzed retrospectively by a power of the mean model because the variance of UPC values within the 3-day evaluation periods increased as the magnitude of proteinuria increased. To demonstrate a significant difference (P < .05) between serial values in these proteinuric dogs, the UPC must change by at least 35% at high UPC values (near 12) and 80% at low UPC values (near 0.5). One measurement is adequate to reliably estimate the UPC when UPC <4, but 2-5 determinations are necessary at higher UPC values. These guidelines for interpretation of serial UPC values in female dogs with XLHN may also be helpful for interpretation of UPC values in dogs with other glomerulopathies.

ACVIM Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment, and Prevention

The purpose of this report is to offer a consensus opinion of ACVIM diplomates on the diagnosis, treatment, and prevention ofBorrelia burgdorferiinfections in dogs (canine Lyme disease). Clinical syndromes known to commonly be associated with canine Lyme disease include polyarthritis and glomerulopathy. Serological test results can be used to document exposure toB. burgdorferibut not prove illness. Although serum enzyme‐linked immunosorbent assay/indirect fluorescent antibody assay titers can stay positive for months to years after treatment, quantitative C6 peptide antibody paired tests need more study. Serological screening of healthy dogs is controversial because it can lead to overdiagnosis or overtreatment of normal dogs, most of which never develop Lyme disease. However, serological screening can provide seroprevalence and sentinel data and stimulate owner education about tick infections and control. Although it is unknown whether treatment of seropositive healthy dogs is beneficial, the consensus is that seropositive dogs should be evaluated for proteinuria and other coinfections and tick control prescribed. Tick control can include a product that repels or protects against tick attachment, thereby helping to prevent transmission of coinfections as well asBorreliaspp. Seropositive dogs with clinical abnormalities thought to arise from Lyme disease generally are treated with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer treatment as well as medications and diets for protein‐losing nephropathy. The ACVIM diplomates believe the use of Lyme vaccines still is controversial and most do not administer them. It is the consensus opinion that additional research is needed to study predictors of illness, “Lyme nephropathy,” and coinfections in Lyme endemic areas.

ACVIM Small Animal Consensus Statement on Lyme Disease in Dogs: Diagnosis, Treatment, and Prevention

The purpose of this report is to offer a consensus opinion of ACVIM diplomates on the diagnosis, treatment, and prevention of Borrelia burgdorferi infections in dogs (canine Lyme disease). Clinical syndromes known to commonly be associated with canine Lyme disease include polyarthritis and glomerulopathy. Serological test results can be used to document exposure to B. burgdorferi but not prove illness. Although serum enzyme-linked immunosorbent assay/indirect fluorescent antibody assay titers can stay positive for months to years after treatment, quantitative C6 peptide antibody paired tests need more study. Serological screening of healthy dogs is controversial because it can lead to overdiagnosis or overtreatment of normal dogs, most of which never develop Lyme disease. However, serological screening can provide seroprevalence and sentinel data and stimulate owner education about tick infections and control. Although it is unknown whether treatment of seropositive healthy dogs is beneficial, the consensus is that seropositive dogs should be evaluated for proteinuria and other coinfections and tick control prescribed. Tick control can include a product that repels or protects against tick attachment, thereby helping to prevent transmission of coinfections as well as Borrelia spp. Seropositive dogs with clinical abnormalities thought to arise from Lyme disease generally are treated with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer treatment as well as medications and diets for protein-losing nephropathy. The ACVIM diplomates believe the use of Lyme vaccines still is controversial and most do not administer them. It is the consensus opinion that additional research is needed to study predictors of illness, "Lyme nephropathy," and coinfections in Lyme endemic areas.

A model of autosomal recessive Alport syndrome in English cocker spaniel dogs

Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal models of Alport syndrome. An autosomal recessive form of progressive hereditary nephritis (HN) was studied in 10 affected, 3 obligate carrier, and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, pathological, and ultrastructural features of the disease were characterized. Expression of basement membrane (BM) proteins was examined with an immunohistochemical technique using monospecific antibodies. Affected dogs had proteinuria and juvenile-onset chronic renal failure. Glomerular basement membrane (GBM) thickening and multilamellation typical of HN were observed in all renal specimens obtained from proteinuric dogs, and severity of GBM ultrastructural abnormalities varied with the clinical stage of disease. Expression of alpha3(IV) and alpha4(IV) chains was totally absent in the kidney of affected dogs. Expression of alpha5(IV) and a6(IV) chains was normal in Bowman's capsule, collecting tubular BM and epidermal BM of affected dogs. The alpha5(IV) chain was not expressed in distal tubular BM of affected dogs. Expression of alpha5(IV) chains was markedly reduced but not absent, and expression of alpha6(IV) chains was present in GBM of affected dogs. Expression of alpha1-alpha2(IV) chains in GBM of affected dogs was increased. Features of obligate carriers were similar to those of unaffected dogs. We conclude that HN in ECS dogs is a naturally occurring animal model of autosomal recessive Alport syndrome. However, it differs from human disease in the persistence of alpha5(IV) chains in GBM and in the appearance of a6(IV) chains in GBM.

Composition of protein in urine from dogs with pyoderma

The protein fractions in urine from proteinuric dogs with and without pyoderma were estimated. Fifteen dogs with pyoderma (five with superficial and 10 with deep pyoderma) were compared with 10...

Sodium dodecyl sulfate polyacrylamide gel electrophoresis of canine urinary proteins for the analysis and differentiation of tubular and glomerular diseases.

A preliminary investigation was performed to evaluate the use of a new, noninvasive technique for the localization of canine renal lesions by electrophoresis of urinary proteins. Urine specimens from six clinically healthy, nonproteinuric dogs and 12 dogs with persistent proteinuria were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). Urine electrophoretic patterns of proteinuric dogs were classified as glomerular (n = 4), tubular (n = 2), or mixed (glomerular and tubular) (n = 6), based on the number and molecular weight of the silver-stained protein bands. Renal tissues from biopsies or necropsies were obtained from eight of the dogs with proteinuric disease. Interpretation of seven of eight electrophoretograms agreed with the histologic interpretation of renal lesions. We concluded SDS PAGE is a potentially valuable technique for detection and localization of renal lesions in dogs with proteinuric disease.

Proteinuria in the dog: a pathomorphological study of 51 proteinuric dogs

Renal cortical biopsies of 51 dogs with spontaneous proteinuria were examined by histology, electron microscopy and immunofluorescence. Glomerular lesions were classified in four groups: mesangioproliferative, membranoproliferative and membranous glomerulonephritis and amyloidosis. The glomerular and the tubulointerstitial lesions were graded, using a semiquantitative system. The results were used for the calculation of correlation coefficients between several parameters. A positive correlation was found between the severity of glomerular and tubulointerstitial lesions. Fibrin detection by immunofluorescence and histochemical methods appeared not to be correlated. The presence of electron dense deposits correlated only with the fluorescence for IgG and C3. Fluorescence for IgA and IgM was frequently observed in cases with or without dense deposits.

Membranous nephropathy in the dog.

Membranous nephropathy, a disease syndrome characterized by severe proteinuria and often accompanied by the nephrotic syndrome, was identified in 29% of a population of 46 proteinuric dogs. Renal lesions were characterized by the presence of subepithelial immunoglobulin deposits distributed diffusely along the glomerular capillary wall. Advanced stages were associated with progressive thickening of capillary basement membranes and incorporation of the immune deposits. These changes were followed by either glomerulosclerosis or recovery. Characteristic morphologic stages were correlated with clinical pathologic findings which showed that the level of proteinuria, hypoalbuminemia, and consequent nephrotic syndrome was most severe in the initial stages of membranous nephropathy while the level of azotemia increased in the more advanced stages of the syndrome.

Proteinuria in the dog: a clinicopathological study in 51 proteinuric dogs

In 51 dogs with predominantly massive urinary protein loss, the daily loss was quantified and glomerular and tubulointerstitial lesions from renal biopsies were characterised and graded using histology, immune fluorescence and electron microscopy. The highest median daily urinary protein loss occurred in dogs with membranous glomerulonephritis (median 380 mg kg-1 d-1) and renal amyloidosis (median 257 mg kg-1 d-1). Although in nine febrile dogs the urinary protein loss was transient, both glomerular and tubular lesions were diagnosed in five and seven of these dogs, respectively. The pattern of urinary proteins was determined using sodium dodecyl-sulphate polyacrylamide gel electrophoresis. The albumin fractional clearance (FC) was raised in 46 dogs, whereas the FCS of the low molecular weight (MW) protein fraction (MW less than 66,000) and high molecular weight protein fraction (MW more than 66,000) were raised in 42 and 28 dogs, respectively. Both the high molecular weight protein FC and albumin FC significantly correlated to the grade of glomerular lesions, whereas the low molecular weight protein FC only moderately significantly correlated to the grade of tubular lesions. The selectivity index, calculated as (formula; see text) did not differentiate between the various forms of glomerulopathies. The urinary lysozyme concentration was significantly correlated to the grade of tubular lesions. It is concluded that although quantitative and qualitative measurements of urinary proteins can provide additional clinical information, they do not have a reliable predictive value and histopathological examination of renal tissue is still necessary for the final diagnosis.

Assessment of renal blood flow in dogs: analysis of I-hippuran blood clearance in healthy dogs and in dogs with proteinuria

In 30 clinically healthy dogs (weights 7.5 to 57 kg) and in 41 proteinuric dogs the 131I-hippuran blood disappearance curve after single injection was determined (0 to 90 minutes), described by a bi-exponential function and analysed according to a two compartment model. The dependence of the blood clearance (C), representing an effective renal blood flow, on the bodyweight (W) (kg) could be described with both a linear function (C = 61 + 13.2 W ml min-1) and a power function (C = 30.56 W0.79 ml min-1) in the healthy dogs. The results of the regression between blood clearance and bodyweight were reproducible (r = 0.92, n = 10 residual error 12 per cent, P less than 0.01).

Glomerular lesions associated with proteinuria in clinically healthy dogs.

Spontaneous proteinuria in otherwise clinically normal adult Beagles 4-6 years old was studied for 2 years. Eighteen dogs, representing a population of 218 Beagles, were placed into three groups: group I, nonproteinuric; group II, intermittently proteinuric; group III, persistently proteinuric. The groups were alike on the basis of laboratory tests, except urinary protein loss. Proteinuria was persistent in most affected dogs but not progressive during the 2 years. The loss of proteins with high molecular weight, including alpha-, beta-, and gamma-globulins, suggested the proteinuria was of glomerular origin. There were glomerular lesions but no other significant change in the kidneys and urogenital system. Lesions were generalized and characterized by prominent, local or diffuse mesangial proliferation and by thickening, wrinkling, and splitting of the glomerular basement membrane. The subendothelial space was often widened and contained electron-dense deposits. Similar electron-dense deposits, as well as lipid and mineral, were in the mesangium. Alterations in visceral epithelial cells and endothelium were prominent. Periglomerular sclerosis was present but tended not to correlate with the severity of mesangial change in any given renal corpuscle. The severity of both mesangial and periglomerular changes increased with increasing proteinuria. Immunofluoescence studies demonstrated granular discontinuous localization of IgG and betaIC-globulins in the glomerular capillaries and mesangium. Similar localization was seen but to a lesser extent in nonproteinuric dogs. The glomerular lesions seen in these clinically healthy, proteinuric dogs are similar to those described in various canind diseases associated with terminal renal failure.