Clinical evaluation of sodium sulfanilate clearance for the diagnosis of renal disease in dogs

Sodium sulfanilate (ss) clearance time was measured in 13 clinically normal dogs and in 24 dogs with suspected renal disease. The results were compared with those from more routine tests of renal function to assess whether measurement of ss clearance provided additional information about the degree of renal dysfunction. It was concluded that ss clearance is a more sensitive measure of renal dysfunction than is serum creatinine or blood urea nitrogen. Sodium sulfanilate half-life was increased before the complete loss of ability to concentrate urine; however, urine concentrating ability was impaired in some dogs with normal ss clearance. In dogs with glomerular disease, proteinuria developed before increased ss clearances. However, ss clearance was a more reliable method of monitoring the degree of renal dysfunction than was protein concentration in single urine samples.     

Renal concentrating ability in dehydrated hyponatremic dogs

Eleven hyponatremic dogs were unable to concentrate their urine during periods of severe dehydration and azotemia. When normonatremia was reestablished in eight of the dogs, their renal concentrating ability returned. Six dogs, including the 3 dogs in which normonatremia was not reestablished, died or were euthanatized; renal lesions were not found during postmortem examination. Two dogs had hypoadrenocorticism, which has been documented as a cause of hyponatremia and impaired renal concentrating ability. Two dogs had gastrointestinal disease, which has been documented as a cause of hyponatremia, but not of impairment of renal concentrating ability. All dogs without hypoadrenocorticism had clinical and clinicopathologic indications of blood loss, which has not been documented as a cause of hyponatremia or impairment of renal concentrating ability. Hyponatremia (less than 120 mEq/L) was induced by chronic blood removal in a dog maintained on a low-sodium diet. During the period of hyponatremia, the dog became azotemic, hypotensive, and severely dehydrated; renal concentrating ability was impaired. We conclude that hyponatremia may be caused by hemorrhage, but irrespective of the cause, hyponatremia impairs renal concentrating ability.     

Gastroenteritis of basenji dogs

Intestinal digestive and absorptive function and the gross and histologic appearance of the gastrointestinal tract were evaluated in Basenji dogs with chronic diarrhea, asymptomatic Basenji dogs, and healthy control dogs. Gastric rugal hypertrophy, lymphocytic gastritis, and gastric mucosal atrophy occurred in asymptomatic and affected Basenji dogs. All affected dogs had moderate or severe intestinal lesions characterized by villous clubbing and fusion, increased tortuosity of intestinal crypts, and diffuse infiltration of mononuclear inflammatory cells. Intestinal lesions in asymptomatic Basenji dogs invariably were less severe than those in affected dogs, but the small intestinal lamina propria of asymptomatic Basenji dogs consistently contained greater numbers of mononuclear inflammatory cells than did that of control dogs. The proportion of cells containing each immunoglobulin isotype (IgG, IgM, IgA) was similar among affected Basenji dogs, asymptomatic Basenji dogs, and control dogs. As compared to healthy beagle controls, intestinal function was abnormal in both affected and asymptomatic Basenji dogs evaluated by combined N-benzoyl-L-tyrosyl-p-aminobenzoic acid and d-xylose test, but malabsorption and maldigestion were most pronounced in affected Basenji dogs.     

Effects of general anesthesia and surgery on renal function in healthy dogs

OBJECTIVES: To evaluate renal function in healthy dogs undergoing general anesthesia and ovariohysterectomy without concurrent IV administration of fluids. ANIMALS: 35 healthy client-owned dogs. PROCEDURE: Dogs were medicated with promazine hydrochloride (0.05 mg/kg of body weight, SC) approximately 45 minutes before induction of anesthesia with thiopental sodium (10 to 15 mg/kg, IV). Anesthesia was maintained with 2% halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students under the direct supervision of a veterinary surgeon. Renal function was assessed (serum urea and creatinine concentrations, fractional clearance of sodium, urine alkaline phosphatase [ALP] and gamma-glutamyltransferase [GGT] activities, urine specific gravity, and enumeration of renal tubular epithelial cells in urine sediment) prior to and 24 and 48 hours after surgery. RESULTS: Duration of general anesthesia ranged from 80 to 310 minutes. Urine specific gravity and ALP activity and serum urea and creatinine concentrations did not change over time. Fractional clearance of sodium decreased 24 and 48 hours after surgery, whereas urine GGT activity and the ratio of urine GGT activity to urine creatinine concentration increased 24 hours after surgery, compared with presurgery values. Renal tubular epithelial cells increased in number in urine sediment from 11 of 35 (31.4%) dogs and 5 of 35 (14.3%) dogs 24 and 48 hours after surgery, respectively. However, this increase was not clinically relevant. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fluids to healthy dogs undergoing general anesthesia and elective surgery may not be necessary for maintenance of renal homeostasis.     

Massive hematuria of nontraumatic renal origin in dogs

Massive hematuria of renal origin was diagnosed in 4 dogs. In all dogs, blood and blood clots were clearly visible in the urine. Serum urea nitrogen and urine concentrating ability were normal. All dogs were anemic, and results of coagulation and platelet function tests were within normal limits. Excretory urography indicated hydroureter and hydronephrosis in all dogs, with filling defects in the bladder attributable to large blood clots in 2 dogs. Cystotomy and catheterization of the ureters enabled identification of one kidney as the source of bleeding in 3 dogs. Unilateral nephrectomy and ureterectomy resolved their hematuria. The results of histologic examination were normal in 2 dogs. The 3rd dog had evidence of pyelitis. Cystoscopy of the 4th dog did not reveal hematuria from either ureter. The dog was not operated on and it continued to have intermittent hematuria.     

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.     

Acute response of urine pH following ammonium chloride administration to dogs

To test the acidifying ability of the distal portion of the nephrons in healthy dogs, 0.2 g of NH4Cl/kg of body weight was given PO. Samples for venous blood gas analysis and urine pH were taken hourly for 6 hours. Systemic acidemia developed, as evidenced by a statistically significant (P less than 0.05) decrease in blood pH 1 hour after NH4Cl administration. Four hours after administration, mean urine pH decreased to a low of 5.16 +/- 0.1 and was less than 5.5 3 hours after administration. Changes in urine pH 2 hours after administration were statistically significant (P less than 0.05). In human beings, NH4Cl loading is used to detect patients with distal renal tubular acidosis (defective hydrogen ion secretion by the distal nephrons) and normal acid/base values. Distal renal tubular acidosis is diagnosed if urine pH fails to decrease to less than 5.5 after NH4Cl administration. On the basis of the findings of this study, a similar value would be valid for dogs.     

Gastric Acid Secretion in Basenji Dogs With Immunoproliferative Enteropathy

Gastric acid secretion was studied in 13 Basenji dogs with immunoproliferative enteropathy. Considerable variation in the severity of gastritis and enteritis existed among dogs. Basenji dogs were categorized into two groups on the basis of postmortem gastric and intestinal histology (group I, gastritis and enteritis; group II, only enteritis). Pentagastrin-induced gastric acid secretory capacity was increased (P less than 0.002) in group II dogs as compared to healthy Beagle controls. Gastric acid secretory capacity of Basenji dogs with gastritis and enteritis (group I) was not different from that observed in control dogs. Basal serum gastrin concentrations and secretin-stimulated serum gastrin concentrations of either group of Basenji dogs did not differ from controls. On the basis of symptomatology, Basenji dogs with diarrhea had significantly increased basal and postsecretin stimulation gastrin concentrations (P = 0.01) when compared with asymptomatic Basenji or healthy control dogs. These findings support a potential role for altered gastric acid secretory capacity in the pathogenesis of immunoproliferative enteropathy of Basenji dogs. Results of the secretin stimulation studies support previous pathologic studies that failed to detect gastrin-secreting tumors. Incorporated into this investigation was a trial to determine whether the combination of oxymorphone and acepromazine could be used for acid secretory studies. Compared to pentobarbital, which has been frequently used for acid secretory studies in a research setting, the drug combination resulted in increased gastric fluid volumes, a comparative increase in acid secretion, and a rapid uneventful recovery. We conclude that the combination of oxymorphone and acepromazine provides an acceptable means of restraint in dogs undergoing acid secretory studies.     

Urinary tract manifestations of protothecosis in dogs

Records of 13 dogs with systemic infection with Prototheca sp. from 3 veterinary teaching hospitals were reviewed. Acute renal failure secondary to disseminated infection with Prototheca zopfii was diagnosed in 2 dogs. In 1 dog, acute renal failure developed during administration of immunosuppressive drugs for treatment of anterior uveitis. During diagnostic evaluation of this dog, Prototheca sp. organisms were noted in urine sediment and renal biopsy specimens. In the 2nd dog, acute renal failure was diagnosed after treatment for bacterial cystitis. After diagnosis of protothecosis, organisms were successfully isolated by aerobic urine culture. Both dogs with acute renal failure did not respond to conventional medical therapy. In total, Prototheca sp. was noted in urine sediment in 4 of 8 dogs and successfully cultured from urine in 5 of 7 dogs. Four of 5 dogs had organisms noted in the kidneys on histopathologic examination. In all dogs, the species identified was P zopfii. Sensitivity testing of 3 isolates revealed wide differences in in vitro drug resistance. Examination and culture of urine is recommended as a practical method for diagnosis of systemic infection with Prototheca sp.     

Lymphocyte transformation and humoral immune factors in Basenji dogs with immunoproliferative small intestinal disease

Serum protein concentrations and 4 immunologic factors were determined in 5 Basenji dogs with immunoproliferative small intestinal disease. There was no correlation between the total serum proteins, immunoglobulin G and immunoglobulin M concentrations, and physical health status of the animals. The severity of clinical signs correlated roughly with decrease in albumin and increase in globulin concentrations. The main changes were detected in beta- and fast gamma-globulins. The total hemolytic complement levels were decreased in the 2 most severely affected animals below the minimal laboratory values observed in healthy animals. Alteration in the intrinsic responsiveness of lymphocytes to various mitogens did not correlate with progression in severity of the disease. Correlation between the appearance of blastogenesis-suppressing substances in serum and the severity of the disease was only partial: Sera (at 20% concentration) from the 2 most severely affected dogs completely suppressed blastogenesis induced by all 3 mitogens. The sera of 3 other dogs either did not suppress or suppressed only concanavalin A-induced mitogenesis and to a lesser extent phytohemagglutinin-induced mitogenesis without correlations to the overall clinical status. The disturbances of immunologic mechanisms were detected after the appearance of clinical disease, were not considered the cause of immunoproliferative small intestinal disease, may represent a manifestation of the secondary infection, and may contribute to aggravation of the clinical course.     

Evaluation of a modified water-deprivation test for diagnosis of polyuric disorders in dogs.

A modified water-deprivation test was performed on 12 polyuric and 4 clinically normal dogs. Immediately after maximal urine osmolality had been achieved with water deprivation, antidiuretic hormone was injected to test further renal concentrating ability. The test provided accurate diagnosis of severe hypothalamic-neurohypophyseal diabetes insipidus in 3 dogs, partial diabetes insipidus in 2 dogs, and primary (psychogenic) polydipsia in 2 dogs. Five polyuric dogs with hyperadreno corticism had a response to the modified water-deprivation test similar to that of dogs with partial diabetes indipidus.     

Chronic renal failure in young dogs–possible renal dysplasia

The clinico-pathological findings are described in thirteen young dogs with advanced renal disease. All but three dogs were less than 2 years old. Some had signs of renal dysfunction since birth. Presenting signs were variable but anorexia, lethargy and weight loss were most frequent. All dogs had raised blood urea levels and most passed dilute urine; proteinuria and anaemia were variable findings. At necropsy all dogs had extra-renal lesions of renal failure and finely granular or lobulated, shrunken kidneys. The microscopical appearances of the kidneys were not those of amyloidosis, inflammatory or glomerular disease but were considered likely to be of developmental origin. The renal lesions were divided into three histologically distinct groups.

• 1 Predominantly cystic and connective tissue changes, characterized by striking dilatation of glomerular capsular spaces and cortical tubules.
• 2 Atypical connective tissue changes in which there were segmental bands of fibrous tissue containing primitive glomerular and tubular structures.
• 3 Predominantly glomerular and connective tissue changes, characterized by varying degrees of glomerulosclerosis and widespread calcification of glomeruli, tubules and blood vessels.

All groups had cortical and medullary interstitial fibrosis but minimal inflammatory cell infiltrates.     

Fanconi syndrome in a basenji

Renal tubular dysfunction resembling canine Fanconi syndrome in a Basenji dog is described. The signs and laboratory results were similar to other reports of this disease. Therapy to correct some of the clinical signs and serum chemistry abnormalities was attempted.     

Renal pathology and urinary protein excretion in a 14-month-old Bernese mountain dog with chronic renal failure

The renal pathology and urinary protein pattern of a 14-month-old female Bernese mountain dog with chronic renal failure was investigated. Sodium dodecyl sulphate-polyacrylamid gel electrophoresis and subsequent Western blot analysis of urine showed the presence of heavy and light chains of immunoglobulin, transferrin, albumin, vitamin D-binding protein, transthyretin and retinol-binding protein (RBP), but no excretion of Tamm-Horsfall protein (THP). Histopathological examinations of the kidneys revealed severe membranous glomerulonephritis accompanied by tubular dilatation, tubular atrophy and interstitial fibrosis. The renal expression of megalin, the main endocytic receptor for the re-uptake of proteins in proximal tubules, RBP and THP was reduced or completely absent, indicating severe tubular dysfunction. The identified urinary proteins may be of interest as additional markers for the diagnosis of juvenile nephropathy in Bernese mountain dogs.     

Urinary gamma-glutamyl transferase and the degree of renal dysfunction in 75 bitches with pyometra

In 75 bitches with pyometra single urine samples were examined for gamma-glutamyl transferase (gamma-GT), protein, glucose, specific gravity, bacteria, red blood cells and white blood cells. Serum samples were examined for urea, creatinine, inorganic phosphate and gamma-GT. Biochemical findings were compared with the degree of illness (clinical signs). Twenty one bitches had no signs of renal disease. Seventeen showed only glomerular damage indicated by proteinuria without signs of proximal tubular damage. Thirty seven bitches had increased urinary gamma-GT levels, indicating proximal tubular lesions, which were associated with proteinuria in 35 and renal failure in 16 of them, and worse clinical findings. In all bitches with pyometra serum levels of gamma-GT were comparable to values in control bitches. Glomerular dysfunction seemed to precede proximal tubular lesions, so that gamma-GT-uria in bitches with pyometra was not an early but rather a late indication of a more profound degree of renal dysfunction, that is, proximal tubular renal damage developed after glomerular dysfunction and preceding renal failure.     

电针疗法对AKI犬的肾功能、钙磷代谢、抗氧化能力以及NRF2信号通路的影响

急性肾损伤(acute kidney injury, AKI)目前已成为犬最主要的一种肾系疾病,尤其在老年犬中发病率逐年上升。近年来,针刺疗法在宠物临床已得到广泛的应用,并逐渐从治疗瘫痪等外科疾病向治疗宠物内科疾病的方向发展。本研究以腺嘌呤为造模药物建立急性肾损伤犬模型,采用电针疗法进行治疗。研究电针疗法对于犬的肾功能、钙磷代谢、抗氧化能力以及对于NRF2通路相关蛋白的影响,探究电针疗法对犬的急性肾损伤的治疗作用。选取24只3～4 kg健康比格犬,随机分为对照组、造模组、常规治疗组、电针干预组、电针治疗组和联合治疗组。第1～15天为造模期,第16～30天为治疗期。试验结束后检测尿比重、血清中尿素氮(BUN)、肌酐(CREA)、尿酸(UA)、钙(Ca²⁺)和磷(P³⁺)的变化;影像诊断X光检测肾变化情况;检测血清及肾组织的超氧化物歧化酶(SOD)和丙二醛(MDA);病理组织学观察各组试验犬肾组织病变的严重程度;采用qRT-PCR和Western blot方法检测各组试验犬肾组织中与抗氧化相关基因和蛋白的表达情况;用免疫组织化学的方法检测肾组织中...     

Kidney Injury Molecule-1 in the detection of early kidney injury in dogs with leptospirosis

Renal damage, a common feature in canine leptospirosis, ranges from a subclinical affection to kidney dysfunction and death. Chances of recovery can be improved by early intervention. However, traditional biomarkers (serum urea and creatinine) have limited relevance for precocity. Kidney Injury Molecule-1 (KIM-1) is a transmembrane protein upregulated in early stages of tubular injury. This study evaluated the use of urinary KIM-1 to detect early renal injury in naturally occurring canine leptospirosis. This exploratory research included 30 dogs divided into two groups: (1) dogs with leptospirosis (n = 25) and (2) healthy dogs (n = 5). Leptospira sp. infection was diagnosed through urine PCR and/or direct bacteriologic culture and/or serology (single MAT titters ≥800). Additionally, stage of infection was further characterized in acute and subacute phases based on the onset of clinical symptoms from 3 to 7 days. Urinary KIM-1 (uKIM-1) concentrations were measured in both groups with a commercial canine ELISA kit.uKIM-1 levels were statistically different (P < 0.01) between the studied groups, especially in non-azotemic dogs (P = 0.0042). The biomarker showed 88 % sensibility to diagnosis of kidney injury at> 1.49 ng/mL cut-off. Urine KIM-1 was negatively correlated with urine specific gravity (USG) but accompanied histopathological evidence of renal degeneration, necrosis and regeneration processes, extending information on kidney health. Measurement of KIM-1 in the urine of canine patients was able to detect naturally occurring acute and subacute leptospirosis accompanied by tubular injury in early non-azotemic infections.     

Surface ultrastructure of pyruvate kinase-deficient erythrocytes in the Basenji dog.

The scanning electron microscope was used to study the surface morphologic features of erythrocytes from a Basenji dog with hereditary hemolytic anemia due to a pyruvate kinase-deficient erythrocytes (RBC). Cells from this dog were compared with RBC from normal dogs and from dogs with regenerative anemias unrelated to pyruvate kinase deficiency. Demonstration of spherical RBC with uniform spicules on their surface (spheroechinocytes) may provide a morphologic explanation for the shortened erythrocytic life-span previously reported in congenital hemolytic anemia of Basenji dogs. Spherical, spiculated RBC were not found in blood from normal dogs or from anemic dogs with reticulocytoses. The surface of reticulocytes from all dogs with regenerative anemia was roughened, with pronounced folding of the cell membrane.     

Urine sampling for real-time polymerase chain reaction based diagnosis of canine leishmaniasis.

A real-time polymerase chain reaction (PCR) assay was used for quantifying Leishmania infantum DNA in urine samples from naturally infected dogs. Forty-one infected dogs were divided into 3 groups: 22 dogs showing only cutaneous signs (group 1), 12 dogs showing hematuria (group 2), and 7 dogs affected by severe nephropathy (group 3). Groups 2 and 3 dogs showed altered laboratory parameters related to an impairment of renal function. The real-time PCR analysis showed higher levels of Leishmania DNA in the lymph node aspirates from all groups of infected dogs versus those measured in their blood or urine. Interestingly, urine samples from dogs belonging to groups 2 and 3 contained a higher Leishmania DNA load than that detected in their blood. This finding suggests that a real-time PCR analysis of urine from infected dogs could be a useful and noninvasive tool for monitoring the severity of leishmaniasis.     

Renal involvement in dogs with babesiosis

Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium), fractional clearance of sodium (FcNa) and potassium (FcK), urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n = 10) and 3 groups of babesiosis cases were studied: mild uncomplicated (n = 10), severe uncomplicated (n = 11), and complicated (n = 9). All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serum electrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant damage or acute renal failure.