Effect of Thyroxine Supplementation on Glomerular Filtration Rate in Hypothyroid Dogs

Background: Glomerular filtration rate (GFR) is decreased in humans with hypothyroidism, but information about kidney function in dogs with hypothyroidism is lacking.
Hypothesis: Hypothyroidism influences GFR in dogs. The objective of this study was to assess GFR in hypothyroid dogs before implementation of thyroxine supplementation and after re-establishing euthyroidism.
Animals: Fourteen hypothyroid dogs without abnormalities on renal ultrasound examination or urinalysis.
Methods: Blood pressure and GFR (measured by exogenous creatinine clearance) were measured before treatment (T0, n = 14) and at 1 month (T1, n = 14) and at 6 months (T6, n = 11) after beginning levothyroxine supplementation therapy (20 μg/kg/d, PO). The response to therapy was monitored at T1 by measuring serum total thyroxine and thyroid stimulating hormone concentrations. If needed, levothyroxine dosage was adjusted and reassessed after 1 month. Statistical analysis was performed using a general linear model. Results are expressed as mean ± standard deviation.
Results: At T0, the average age of dogs in the study group was 6.3 ± 1.4 years. Their average body weight decreased from 35 ± 18 kg at T0 to 27 ± 14 kg at T6 ( P < .05). All dogs remained normotensive throughout the study. GFR increased significantly with levothyroxine supplementation; the corresponding results were 1.6 ± 0.4 mL/min/kg at T0, 2.1 ± 0.4 at T1, and 2.0 ± 0.4 at T6 ( P < .01).
Conclusion: GFR was <2 mL/min/kg in untreated hypothyroid dogs. Re-establishment of a euthyroid state increased GFR significantly.     

A Single‐Blood‐Sample Method Using Inulin for Estimating Feline Glomerular Filtration Rate

Background

Application of a multisample method using inulin to estimate glomerular filtration rate (GFR) in cats is cumbersome.

Objectives

To establish a simplified procedure to estimate GFR in cats, a single‐blood‐sample method using inulin was compared with a conventional 3‐sample method.

Animals

Nine cats including 6 clinically healthy cats and 3 cats with spontaneous chronic kidney disease.

Methods

Retrospective study. Inulin was administered as an intravenous bolus at 50 mg/kg to cats, and blood was collected at 60, 90, and 120 minutes later for the 3‐sample method. Serum inulin concentrations were colorimetrically determined by an autoanalyzer method. The GFR in the single‐blood‐sample method was calculated from the dose injected, serum concentration, sampling time, and estimated volume of distribution on the basis of the data of the 3‐sample method.

Results

An excellent correlation was observed (r = 0.99, P = .0001) between GFR values estimated by the single‐blood‐sample and 3‐sample methods.

Conclusions and Clinical Importance

The single‐blood‐sample method using inulin provides a practicable and ethical alternative for estimating glomerular filtration rate in cats.     

Plasma von Willebrand Factor Antigen Concentration and Buccal Mucosal Bleeding Time in Dogs With Experimental Hypothyroidism

This study was undertaken to investigate the effects of hypothyroidism on buccal mucosal bleeding time and von Willebrand factor antigen (vWf:Ag) concentrations. Hypothyroidism was induced in 8 adult dogs by administration of iodine 131. Four healthy dogs acted as controls. Measurement of plasma vWf:Ag and serum thyroxine and triiodothy-ronine concentrations, and buccal mucosal bleeding time were made before induction of hypothyroidism, for 23 weeks after ¹³¹I administration, and during 5 weeks of levothyroxine supplementation. No significant changes in buccal mucosal bleeding times were noted during the study. After an insignificant increase in vWfAg concentration in hypothyroid dogs, levothyroxine treatment was associated with a significant decrease in vWf:Ag concentration in hypothyroid dogs when compared with controls. Results of this study suggest that hypothyroidism does not induce acquired von Willebrand's disease or significant defects in primary hemo-stasis. J Vet Intern Med 1996;10:60–64. Copyright © 1996 by the American College of Veterinary Internal Medicine .     

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.     

Glomerular Filtration Rate and Renal Volume in Dogs with Congenital Portosystemic Vascular Anomalies before and after Surgical Ligation

Glomerular filtration rate (GFR) and renal volume were evaluated in dogs with confirmed portosystemic vascular anomalies (PSVA) before and after surgical ligation of their PSVA. Pre- and postligation CBC, serum biochemistry, urinalysis, abdominal ultrasonography with measurement of renal volume, and per rectal scintigraphy were performed to document resolution of abnormalities consistent with portosystemic shunting. GFR was estimated by plasma 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance before (n = 21) and after (n = 12) surgical correction of PSVA. Preligation 99mTc-DTPA GFR was increased (median, 5.64 mL/minute/kg; range, 3.53-8.49 mL/minute/kg; reference range, 2.83-4.47 mL/minute/kg) in 81% (17/21) of dogs. Postligation 99mTc-DTPA GFR decreased in all 12 evaluated dogs (median change = -42%; P < .001). Preligation renal volume was above the reference range for the left and right kidneys in 71% (10/14) and 69% (11/16) of dogs evaluated, respectively. Right renal volume decreased significantly (n = 5; median change, -45%; P = .03) after surgical ligation of PSVA. These findings document increased GFR and renal volume in dogs with PSVA, which may explain in part the low blood urea nitrogen and serum creatinine concentrations encountered in these dogs. Knowledge of changes in GFR associated with PSVA ligation may prove helpful in the anesthetic, drug, and dietary management of affected dogs.     

Glomerular filtration rate in dogs with leishmaniasis and chronic kidney disease

BACKGROUND: Glomerular filtration rate (GFR) measurement is an indicator of kidney function. However, its usefulness in dogs at early stages of spontaneous chronic kidney disease (CKD) of glomerular origin, where routine laboratory techniques are not sufficiently sensitive, remains unproved. HYPOTHESIS: That GFR is reduced in proteinuric nonazotemic or mildly azotemic dogs with CKD secondary to leishmaniasis. ANIMALS: Twenty-six dogs with CKD secondary to leishmaniasis and 10 healthy dogs (control group). METHODS: CBC, serum biochemistry, and urinalysis (microalbuminuria and urine protein/creatinine ratio [UPC]) were performed in all dogs. GFR was calculated by measuring exogenous creatinine clearance. Based on degree of proteinuria and serum creatinine concentration (SCr), dogs were classified as group A (control; n = 10): UPC < 0.2, SCr < 1.4 mg/dL; group B (n = 8): UPC, 0.2-0.5, SCr < 1.4 mg/dL; group C (n = 10): UPC > 0.5, SCr < 1.4 mg/dL; group D (n = 5): SCr, 1.4-2 mg/dL; group E (n = 3): SCr > 2 mg/dL. Results: GFR (mL/kg/min) was 3.9 +/- 0.29, 4.4 +/- 0.74, 4.5 +/- 1.44, 2.8 +/- 0.97, and 1.5 +/- 0.43 for groups A, B, C, D, and E, respectively. Eleven dogs (1 from group B, 3 from group C, 4 from group D, and all 3 dogs from group E) had an abnormally low GFR. Four dogs from group B and 5 dogs from group C had a GFR above the upper reference range (>4.5 mL/min/kg). CONCLUSION AND CLINICAL RELEVANCE: Some proteinuric nonazotemic or mildly azotemic dogs with leishmaniasis have low GFR, but glomerular hyperfiltration occurs in other dogs.     

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.     

Serum Lipoprotein Changes in Dogs with Renal Disease

Background

People with renal disease develop a dyslipidemia that contributes to progression of renal injury and development of cardiovascular disease. Lipoproteins in dogs with renal disease have not been investigated.

Hypothesis

Dogs with chronic kidney disease (CKD) have dyslipidemia characterized by increased lower density lipoproteins and decreased high‐density lipoproteins (HDLs). The degree of dyslipidemia is positively correlated with severity of disease, as reflected by serum creatinine concentration.

Animals

Prospective study of client‐owned dogs presented to the Cornell University Hospital for Animals: 29 dogs with confirmed CKD, 5 dogs with nephrotic syndrome (NS), and 12 healthy control dogs presented for routine vaccinations, dental cleaning, or owned by students.

Methods

Lipoprotein electrophoresis was used to quantify relative proportions of the 3 main classes of lipoproteins in canine serum: low‐density lipoproteins (LDL), very low‐density lipoproteins (VLDL), and HDL. Serum cholesterol and creatinine concentrations; urinalysis and urine protein‐to‐creatinine ratio were measured by standard methods.

Results

Dyslipidemia was consistently found in dogs with CKD and NS and was characterized by a decrease in HDL and variable increases in LDL and VLDL. Dogs with NS had a proportionately greater increase in the VLDL fraction, as compared with dogs with CKD.

Conclusion and Clinical Importance

Dyslipidemia similar to that documented in people with renal disease occurs in dogs with CKD, despite serum cholesterol concentrations often being within the reference interval. The contribution of altered lipoproteins to the pathogenesis of renal disease in dogs warrants additional study.     

Plasma Renin Activity and Aldosterone Concentrations in Hypertensive Cats with and without Azotemia and in Response to Treatment with Amlodipine Besylate

Background

Role of renin‐angiotensin aldosterone system (RAAS) in feline systemic hypertension is poorly understood.

Objectives

Examine plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in normotensive and hypertensive cats with variable renal function and in response to antihypertensive therapy.

Animals

One hundred and ninety‐six cats >9 years from first opinion practice.

Methods

PRA, PAC, and aldosterone‐to‐renin ratio (ARR) were evaluated in cats recruited prospectively and grouped according to systolic blood pressure (SBP) and renal function (nonazotemic normotensive [Non‐Azo‐NT], nonazotemic hypertensive [Non‐Azo‐HT], azotemic normotensive [Azo‐NT], azotemic hypertensive [Azo‐HT]). Changes in PRA and PAC were evaluated with antihypertensive therapy (amlodipine besylate).

Results

Plasma renin activity (ng/mL/h; P = .0013), PAC (pg/mL; P < .001), and ARR (P = 0.0062) differed significantly among groups. PRA (ng/mL/h) was significantly lower in hypertensive (Non‐Azo‐HT; n = 25, median 0.22 [25th percentile 0.09, 75th percentile 0.39], Azo‐HT; n = 44, 0.33 [0.15, 0.48]) compared with Non‐Azo‐NT cats (n = 57, 0.52 [0.28, 1.02]). Azo‐HT cats had significantly higher PAC (n = 22, 149.8 [103.1, 228.7]) than normotensive cats (Non‐Azo‐NT; n = 26, 45.4 [19.6, 65.0], Azo‐NT; n = 18, 84.1 [38.6, 137.8]). ARR was significantly higher in Azo‐HT (n = 20, 503.8 [298.8, 1511]) than Azo‐NT cats (n = 16, 97.8 [77.0, 496.4]). Significant increase in PRA was documented with antihypertensive therapy (pretreatment [n = 20] 0.32 [0.15–0.46], posttreatment 0.54 [0.28, 1.51]), but PAC did not change.

Conclusions and Clinical Importance

Hypertensive cats demonstrate significantly increased PAC with decreased PRA. PRA significantly increases with antihypertensive therapy. Additional work is required to determine the role of plasma aldosterone concentration in the pathogenesis of hypertension and whether this relates to autonomous production or activation of RAAS without demonstrable increase in PRA.