Nonproteinuric Dogs Research Articles

Association of proteinuria at time of diagnosis with survival times in dogs with lymphoma.

Lymphoma has been implicated as a possible cause of proteinuria in dogs. However, information about the potential importance of proteinuria in dogs with lymphoma is limited. To determine if the presence of proteinuria at diagnosis was associated with median survival times in dogs with lymphoma and if lymphoma stage (I-V) or type (B vs T) were associated with the presence of proteinuria. Eighty-six client-owned dogs with a new diagnosis of lymphoma between 2008 and 2020. This was a retrospective cross-sectional study with dogs divided into proteinuric or nonproteinuric groups based on dipstick urine protein (protein ≥30 mg/dL classified as proteinuric) or a ratio of dipstick protein to urine specific gravity (ratio ≥1.5 classified as proteinuric). Dogs were excluded for: (1) treatment within 2 months with glucocorticoid, anti-neoplastic, or anti-proteinuric therapies, (2) diagnosed hypercortisolism or renal lymphoma, (3) active urine sediment, or (4) urine pH >8. Survival analysis utilized a Kaplan-Meier estimator and log-rank testing. There was a significant difference in median survival between proteinuric and nonproteinuric dogs classified by urine dipstick (245 days [91, 399] vs 335 days [214, 456]; P = .03) or UP : USG (237 days [158, 306] vs 304 days [173, 434]; P = .03). No difference in prevalence of proteinuria was identified between stages (I-V) or types (B and T). Proteinuria appears to be negatively associated with survival time in dogs newly diagnosed with lymphoma.

Serum Symmetric Dimethylarginine as an Early Marker of Excretory Dysfunction in Canine Leishmaniosis (L. infantum) Induced Nephropathy.

The aims of the study were to determine whether symmetric dimethylarginine (SDMA) was increased in dogs with leishmaniosis and to assess its relationship with creatinine concentration and urinary protein : creatinine ratio (UPC) to determine its utility as a marker of early excretory dysfunction. Fifty-three dogs with leishmaniosis classified according to the LeishVet clinical staging (stage I, n = 5, stage II, n = 30; stage III, n = 12; stage IV, n = 6) were selected and compared with 41 clinically healthy dogs. Thirty-nine dogs with leishmaniosis were also followed up for six months. SDMA concentrations on the day of diagnosis were significantly higher in dogs with leishmaniosis with respect to control dogs and in dogs from LeishVet stage IV when compared with the other stages. Increased UPC (>0.5), SDMA (>19 μg/dL), and creatinine concentrations (≥1.4 mg/dL) were found in 47.1%, 15.1%, and 9.4% of dogs with leishmaniosis, respectively. SDMA concentration was increased in 24% of proteinuric dogs, in 7% of nonproteinuric dogs, and in four of five dogs with increased creatinine. SDMA concentration ≥ 25 μg/dL was associated with clinical chronic kidney disease (CKD) after six months. Our results did not demonstrate advantages in using SDMA concentration as an early marker of CKD when compared to creatinine and UPC in canine leishmaniosis.

Effects of storage conditions on results for quantitative and qualitative evaluation of proteins in canine urine.

OBJECTIVE To investigate effects of storage conditions on the canine urine protein-to-creatinine ratio (UPC) and on SDS-agarose gel electrophoresis (AGE) of urinary proteins. SAMPLE Urine specimens from 20 proteinuric (UPC > 0.5) and 20 nonproteinuric (UPC ≤ 0.2) dogs. PROCEDURES UPC and SDS-AGE were performed on urine specimens stored at room temperature (20°C) and 4°C for up to 5 days and at -20° and -80°C for up to 360 days; some specimens were subjected to 3 freeze-thaw cycles. Results were compared with those obtained for fresh urine specimens. RESULTS UPC was not affected by storage at room temperature or by freezing. A decrease in UPC was observed for specimens from nonproteinuric dogs after 5 days at 4°C (10%) and from both groups after 90 days at -20° and -80°C (≤ 20% and ≤ 15%, respectively). The SDS-AGE profiles revealed no visual changes regardless of duration of storage for specimens stored at room temperature, 4°C, and -80°C, except for 1 profile after 360 days at -80°C. Repeated freeze-thaw cycles did not affect SDS-AGE profiles. Appearance or strengthening of high-molecular-weight bands that could alter interpretation was evident in SDS-AGE profiles after storage at -20°C for ≥ 15 days (31/40 dogs). CONCLUSIONS AND CLINICAL RELEVANCE Storage of urine at -20° or -80°C for up to 1 year influenced the UPC without affecting clinical interpretation. Storage of urine specimens at -20°C impaired visual analysis of SDS-AGE. When SDS-AGE cannot be performed on fresh or recently refrigerated urine specimens, storage at -80°C is recommended.

Proteinuria reduction after treatment with miltefosine and allopurinol in dogs naturally infected with leishmaniasis.

Aim:The aim of this study was to evaluate changes in proteinuria in dogs naturally infected with visceral leishmaniasis, following treatment with miltefosine (MLF) and allopurinol.Materials and Methods:Medical records of 40 dogs with leishmaniasis, treated with 2 mg/kg MLF every 24 h PO and 10 mg/kg allopurinol every 12 h for 28 days were reviewed. 20 dogs were included in the study, and clinical staging was performed following guidelines of the Canine leishmaniasis (CanL) Working Group, and dogs were categorized for proteinuria according to the International Renal Interest Society (IRIS) staging system. Clinical score, indirect fluorescent antibody test titer, serum total protein, gamma globulin (IgG), serum creatinine and urea concentration, and urine protein creatinine ratio (UP/C) were recorded at the time of diagnosis before the start of therapy (D0) and at the end of 28 days of therapy (D28).Results:Following the CanL Working Group staging, all 20 dogs were classified as the clinical Stage C (Clinical disease) before and after the cycle of treatment. Before the cycle of therapy, dogs were categorized according to the IRIS staging system, as: 9/20 non-proteinuric (NP), 7/20 borderline proteinuric (BP), and 4/20 proteinuric (P). After treatment, 12/20 dogs were NP, 7/20 were BP, and 1/20 was P. There was a significant change in UP/C values before and after one cycle of treatment with MLF. In detail, after 28 days of therapy, 2 of 9 NP dogs became BP, 3 of the 7 BP dogs became NP, and 2 of the 4 P dogs became NP.Conclusion:This study showed a significant decrease in UP/C values occurred after one cycle of treatment with MLF and allopurinol in dogs naturally affected with CanL. This suggests that MLF does not increase proteinuria, and the use of MLF could be considered for the management of dogs with leishmaniasis, particularly in those with impaired renal function at the time of diagnosis.

Serum ferritin and paraoxonase-1 in canine leishmaniosis

Ferritin and paraoxonase-1 (PON-1) were measured in dogs experimentally infected by Leishmania infantum (during experimental infection and following treatment) and also in naturally-infected dogs which presented different degrees of proteinuria. Experimentally-infected dogs were monitored for 7 months post-infection, then treated for 3 months with allopurinol, and their response to therapy was followed for 11 additional months. Naturally-infected dogs were staged based on the urine protein/creatinine (UPC) ratio into three groups as follows: group 1 (non-proteinuric; UPC ratio: <0.2), group 2 (borderline proteinuric; UPC ratio: 0.2-0.5) and group 3 (proteinuric; UPC ratio>0.5). An increase in serum ferritin values and a decrease in PON-1 activity were observed 2 months after infection. Both analytes returned to preinfection values following treatment. Significantly higher concentrations of ferritin were observed in dogs classified as either borderline or proteinuric when compared with non-proteinuric dogs whereas serum PON-1 activity was decreased only in proteinuric dogs.

Big-endothelin 1 (big ET-1) and homocysteine in the serum of dogs with chronic kidney disease

This study was aimed at determining the serum concentration of homocysteine (Hcy) and big endothelin-1 (big ET-1, the precursor of endothelin) in dogs with chronic kidney disease (CKD) with and without hypertension, proteinuria and inflammation, in order to explore their role as biomarkers of hypertension associated with CKD. Hcy and big ET-1 were measured using an enzyme-linked immunosorbent assay and an enzymatic cyclic reaction, respectively, in dogs with CKD staged, as proposed by the International Renal Interest Society (IRIS), using serum creatinine, urinary protein to creatinine (UPC) ratio and systolic blood pressure, and classified as affected or not by inflammation based on the serum concentration of C-reactive protein (CRP).Serum Hcy was significantly higher in dogs of IRIS stages II, III and IV compared with controls and in proteinuric compared with non-proteinuric dogs. No differences relating to the degree of hypertension or to the CRP concentration were found. Serum big ET-1 significantly increased in dogs of IRIS stage IV compared with controls, in proteinuric compared with non-proteinuric dogs, in dogs with severe hypertension compared with those without hypertension, and in dogs with increased CRP compared to those with normal CRP concentrations. Hcy only correlated with serum creatinine but big ET-1 significantly correlated with serum creatinine, UPC ratio, systolic blood pressure, and increased CRP. In conclusion, both Hcy and big ET-1 increase in dogs with CKD. Although further research is needed, big ET-1, but not Hcy, may also be considered as a biomarker of hypertension.

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.

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.

Evaluation of a urine dipstick test for confirmation or exclusion of proteinuria in dogs

To evaluate a urine dipstick test as a possible replacement for urine protein-to-creatinine (UPC) ratio for identifying proteinuria in dogs. 507 urine samples from adult dogs. Urine dipstick, UPC ratio, specific gravity (USG), and sediment testing were performed on 507 samples. With UPC ratio as the reference criterion, diagnostic accuracy of the urine dipstick test was calculated for the entire data set and for urine samples grouped by USG (< or = 1.012 or > 1.012; < 1.030 or > or = 1.030). A UPC ratio < 0.2 was used to indicate absence of proteinuria. The sensitivity of the urine dipstick test for detection of proteinuria was > 90% when 0 mg of protein/dL (a 0+ result) was used to indicate a negative test result, and the specificity ranged from 40% to 60%, depending on the USG. Sensitivity decreased to a range of 56% to 81% when 30 mg of protein/dL (a 1+ result) was used as the cutoff, depending on the USG, but the specificity increased to > 90%. The likelihood of correctly identifying nonproteinuric dogs was low when the USG was < or = 1.012, particularly when samples with a 1+ result were considered negative. For dogs with a dipstick-test result of 1+ and USG < or = 1.012, proteinuria should be assessed by use of the UPC ratio; dogs with a USG value > 1.012 are likely nonproteinuric. When used together, the urine dipstick test and USG measurement were reliable as a rapid alternative to UPC ratio determination in dogs in this study.

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.

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.