Neutrophil Gelatinase–Associated Lipocalin in Dogs with Naturally Occurring Renal Diseases

Background

Neutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail.

Hypothesis/Objectives

The goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease.

Animals

Client‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined.

Methods

Serum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively.

Results

Serum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time.

Conclusion

sNGAL is a useful prognostic marker when evaluating dogs with CKD.     

Pharmacokineatic Aspects of Measurement of Glomerular Filtration Rate in the Dog: A Review

Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmnacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.     

Perinephric pseudocysts in the cat: a retrospective study and review of the literature

Perinephric pseudocysts (PNPs) are fluid-filled fibrous sacs that surround the kidney and are not lined by an epithelium. In cats, PNPs are idiopathic, but they usually occur in association with chronic renal failure (CRF). Thirteen cats with PNPs were examined. PNPs occurred in mixed breed cats of either sex with a median age of 16 years. The PNP was palpable on physical examination and usually was interpreted as renomegaly. Clinicopathologic findings reflected CRF, and urinary tract infection was common. Rarely, a primary renal disease was diagnosed concurrent with PNPs and CRF. Diagnosis of PNPs was made by ultrasound examination and fine-needle aspiration, and treatment was by surgical removal of the PNP or ultrasound-guided drainage. Compared to previous reports of PNPs, this series of cats tended to be older and no sex predilection was found, but other findings were similar to those in the literature. Cats with PNPs may have a favorable prognosis if CRF is not severe and no other concurrent diseases are present.     

Escherichia coli pyometra induces transient glomerular and tubular dysfunction in dogs

Background: Pyometra in dogs has been associated with renal injury. Hypothesis: Examine pyometra‐related nephropathy by evaluating novel renal biomarkers. Animals: Twenty‐five dogs with Escherichia coli pyometra. Fourteen clinically healthy bitches of comparable age. Methods: Prospective study. Urinary biomarkers determined by immunoassays (uIgG, uCRP, uAlb, uRBP, uTXB₂) or colorimetric test (uNAG) with results normalized to urine creatinine concentration. Nonparametric Mann‐Whitney U‐test and Wilcoxon's signed‐rank test used to compare healthy dogs and dogs with pyometra, and dogs with pyometra at initial and follow‐up examination. Results: Urinary biomarkers (median, range) significantly increased in dogs with pyometra (uIgG/Cr: 169.7 mg/g, 4.8–1052.9; uCRP/Cr: 0.260 mg/g, 0.006–3.030; uAlb/Cr: 89.5 mg/g, 8.8–832.7; uRBP/Cr: 1.66 mg/g, 0.05–21.44; uNAG/Cr: 5.8 U/g, 1.6–27.7; uTXB₂/Cr: 15.3 μg/g, 3.2–139.6) compared with healthy bitches (uIgG/Cr: 3.4 mg/g, 0.6–8.9; uCRP/Cr: below detection limit; uAlb/Cr: 17.5 mg/g, 1.3–166.3; uRBP/Cr: 0.13 mg/g, 0.02–0.44; uNAG/Cr: 2.4 U/g, 1.4–7.4; uTXB₂/Cr: 2.4 μg/g, 1.2–4.7) (P < .001). Six months after ovariohysterectomy, urinary biomarkers in pyometra group (uIgG/Cr: 4.7 mg/g, 1.5–99.8; uCRP/Cr: below detection limit; uAlb/Cr: 13.9 mg/g, 2.1–471.2; uRBP/Cr: 0.05 mg/g, 0.02–0.32; uNAG/Cr: 1.6 U/g, 0.9–3.3; uTXB₂/Cr: 3.3 μg/g, 1.0–6.9) were significantly lower than before surgery (P < .01), and not significantly different to those of healthy dogs (P > .05). Conclusion and Clinical Importance: Pyometra‐related renal dysfunction affects the nephron both at glomerular and proximal tubular level and is a transient process in most dogs with E. coli pyometra.     

山羊异体肾移植试验小结

本文叙述11头山羊同种异体肾移植的方法;观察受肾羊术前与术后的体温、呼吸、心跳和肾脏大小的变化;测定受肾羊的血常规、淋巴细胞转化率、玫瑰花瓣形成率和血清蛋白的变化;对其中两头羊的移植肾分别在100、160天进行X线造影观察其状态;对另两只移植肾在术后第7、14、21、28天进行手术取移植肾的皮质1mm~3进行电镜观察移植肾超微结构的变化。     

Effects of renal impairment on the disposition of orally administered enalapril, benazepril, and their active metabolites

The pharmacokinetics of benazepril, enalapril, and their active metabolites (benazeprilat and enalaprilat) were compared after a single administration of each product by the oral route at the recommended dosage (0.5 mg/kg for both drugs) in the dog before and after moderate experimental renal impairment. Ten dogs were randomly assigned to 2 groups of 5 animals in a 2-period crossover design for angiotensin-converting enzyme inhibitor administration. Renal failure was surgically induced by right nephrectomy and electrocoagulation of the remaining kidney. Renal mass reduction induced a significant decrease (P < .001) in glomerular filtration rate (GFR) (1.7 +/- 0.3 versus 3.3 +/- 0.7 mL/kg/minute). No significant differences before and after surgery were observed for enalapril and benazepril kinetics. The area under the curve (AUC) for enalaprilat increased after surgery from 23.6 +/- 14.7 to 42.4 +/- 20.9 micrograms.minute/mL (P < .01). Mean peak plasma concentration (Cmax) was increased in the impaired dogs (59.1 +/- 23.3 versus 43.9 +/- 32.9 ng/mL), but this variation was not significant (P > .05). Renal failure had no significant effect on AUC for benazeprilat (13.8 +/- 9.8 versus 14.9 +/- 5.0 micrograms.minute/mL) (P > .05), but Cmax decreased significantly (from 55.0 +/- 26.4 to 31.9 +/- 17.7 ng/mL) (P < .05). Multiple regression analysis showed that both GFR and AUC for enalapril were highly significant variables that explained the variation in AUC for enalaprilat (R2 = .86, P < .001) but not for benazeprilat (R2 = .12, P > .05). The results of this study indicate that exposure to enalaprilat, but not to benazeprilat, is increased in dogs with subclinical renal impairment.     

Effect of spironolactone on diuresis and urine sodium and potassium excretion in healthy dogs

ObjectivesTo document the diuretic effect of different oral doses of spironolactone (SP) in healthy dogs.BackgroundSP is currently mentioned as a diuretic agent in the dog. However, the recommended doses were empirically defined and their corresponding diuretic effect has never been documented in dogs.Animals, materials and methodsEight adult Beagle dogs were used for two separate 2 * 2 cross-over designs. In the first cross-over, 4 dogs received SP orally for 8 days at 1 and 2 mg/kg per day. In the second cross-over the 4 other dogs received SP similarly, but at 4 and 8 mg/kg per day. Dogs were weighed on the first and last day of each period. Plasma SP and canrenone (the main active metabolite of SP) were assayed by high performance liquid chromatography (HPLC). Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium and potassium were measured during the SP treatment.ResultsTwo hours after SP administration, SP was metabolized into canrenone. A significant 14 and 22% decrease in urine potassium excretion was observed at 1 and 2 mg/kg, respectively, but not at the two other dose levels. Daily water consumption, urine weight, urine specific gravity, and urine excretion of sodium were not significantly altered by the SP treatment regardless of dose.ConclusionsRepeated oral administration of SP at 1, 2, 4 or 8 mg/kg for 8 days had no effect on water and sodium diuresis in healthy dogs.     

Progressive Juvenile Glomerulonephropathy in 16 Related French Mastiff (Bordeaux) Dogs

Background: Familial juvenile glomerulonephropathy (JGN) is reported in several breeds of dogs. The mode of inheritance and spectrum of pathological lesions vary among breeds. A progressive JGN was detected in a pedigree of French Mastiff (FM) dogs. Objectives: To describe clinical, laboratory, and histopathologic findings in related FM dogs suffering from progressive JGN and to determine the mode of inheritance of this condition. Animals: Sixteen affected and 35 healthy related FM dogs Methods: FM dogs <24 months of age and diagnosed with chronic kidney disease with evidence of proteinuria entered the study. Clinical, laboratory, histopathologic findings, and pedigree data were recorded. Results: Clinical signs were typical of progressive glomerulopathy with resultant renal failure. Increased blood urea nitrogen, creatinine and total cholesterol concentrations, and proteinuria were found in all patients. Affected dogs had abnormal kidney structure on abdominal ultrasound examination. Histopathologic examination revealed extensive cystic glomerular atrophy, glomerular hypercellularity, and capillary wall thickening without immune complex deposition when tested with immunohistochemistry or immunofluorescence. Electron microscopy did not disclose specific primary glomerular lesions. Mean age at death was 20 months and mean length of survival after diagnosis was 6 months. Both males and females from healthy parents were affected. An autosomal recessive mode of transmission is suspected, but a more complex mode of inheritance cannot be excluded. Conclusions and Clinical Importance: Progressive familial JGN occurs in FM dogs. Characterization of the pathogenesis and mode of inheritance of this disease warrants additional study.     

Relationship between Serum Symmetric Dimethylarginine Concentration and Glomerular Filtration Rate in Cats

Background

Direct measurement of glomerular filtration rate (GFR) is the preferred method to assess renal function in cats, but it is not widely used in the diagnosis of chronic kidney disease (CKD). In cats with CKD, symmetric dimethylarginine (SDMA) has been shown to increase and to correlate with plasma creatinine concentrations.

Hypothesis

In cats, reduced GFR corresponds with increased serum SDMA concentration.

Animals

The study group consisted of ten client‐owned cats whose GFR had been measured previously. Cats ranged in age from 11.1 to 16.9 years; both azotemic and nonazotemic animals were included.

Methods

Glomerular filtration rate was determined for each cat by plasma iohexol clearance using the three sample slope‐intercept method, and serum SDMA concentration was measured by liquid chromatography‐mass spectrometry.

Results

A linear relationship was observed between GFR and the reciprocal of serum SDMA concentration (R ² = 0.82, P < .001). A similar relationship was found between GFR and the reciprocal of plasma creatinine concentration (R ² = 0.81, P < .001).

Conclusions and Clinical Importance

Increased serum SDMA concentrations were observed in cats with reduced renal function as determined by direct measurement of GFR. This finding indicates that SDMA could have clinical applications in the diagnosis of CKD in cats.