Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

OBJECTIVES: The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). METHODS: A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. RESULTS: After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). CONCLUSIONS AND RELEVANCE: Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.

Measurement of Ghrelin as a Marker of Appetite Dysregulation in Cats with and without Chronic Kidney Disease.

Appetite abnormalities and weight loss are important comorbidities in the treatment of chronic kidney disease (CKD) in cats. Ghrelin, a key hormone involved in the regulation of appetite and metabolism, is a potential marker of appetite dysregulation in cats with CKD. The aim of this study was to compare the plasma concentrations of acylated, desacyl, and total ghrelin in normal cats and cats with CKD. Storage methodology was investigated prior to evaluating ghrelin concentrations in normal and CKD cats to facilitate clinical sample collection. Twelve normal cats and twelve cats with CKD were enrolled. Plasma acylated and total ghrelin concentrations were measured using radioimmunoassay. Desacyl ghrelin was calculated (total ghrelin minus acylated ghrelin). Cats with CKD had significantly increased total ghrelin and calculated desacyl ghrelin concentrations in comparison to normal cats (p < 0.0001 and p = 0.0001). There was no significant difference in active ghrelin concentrations between groups. Both total ghrelin and calculated desacyl ghrelin were significantly correlated with serum creatinine concentrations (p < 0.0001, r = 0.70 and p < 0.0001, r = 0.73). Elevated plasma desacyl ghrelin concentrations in cats with CKD provides evidence for dysregulation of appetite in feline CKD.

Measuring 25-hydroxyvitamin D in cats: comparison of a whole-blood lateral flow assay, 2 dried-blood-spot tests, and serum LC-MS/MS.

Measuring 25-hydroxyvitamin D (25D) can be a challenge in veterinary medicine because of laboratory accessibility and required sample volume. We compared 2 dried-blood-spot (DBS) tests and a lateral flow assay (LFA) to the gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS). We hypothesized that there would be good agreement among the tests, within a clinically significant limit of agreement of ± 25 nmol/L. We collected blood from 6 healthy purpose-bred 2-y-old cats at 6 times over 6 wk, and measured 25D concentrations with all 4 tests. Agreement of the 3 candidate tests and LC-MS/MS was evaluated via Bland-Altman analysis, Passing-Bablok regression, and Lin correlation coefficients. Bland-Altman analysis demonstrated that the mean bias was >± 25 nmol/L for all 3 candidate tests in comparison to serum LC-MS/MS concentrations. The 95% CIs for the mean bias did not include zero, further supporting the presence of significant bias among methods. Additionally, all 3 tests had poor agreement with serum LC-MS/MS concentrations when analyzed by Lin correlation coefficient analysis, and bias between methods was further characterized by Passing-Bablok analysis. Based on these results, none of these 3 tests is recommended as an alternative to LC-MS/MS testing for 25D measurement in cats.

Assessment of peritubular capillary rarefaction in kidneys of cats with chronic kidney disease.

BACKGROUND: Hypoxia is a key driver of fibrosis and is associated with capillary rarefaction in humans. OBJECTIVES: Characterize capillary rarefaction in cats with chronic kidney disease (CKD). ANIMALS: Archival kidney tissue from 58 cats with CKD, 20 unaffected cats. METHODS: Cross-sectional study of paraffin-embedded kidney tissue utilizing CD31 immunohistochemistry to highlight vascular structures. Consecutive high-power fields from the cortex (10) and corticomedullary junction (5) were digitally photographed. An observer counted and colored the capillary area. Image analysis was used to determine the capillary number, average capillary size, and average percent capillary area in the cortex and corticomedullary junction. Histologic scoring was performed by a pathologist masked to clinical data. RESULTS: Percent capillary area (cortex) was significantly lower in CKD (median 3.2, range, 0.8-5.6) compared to unaffected cats (4.4, 1.8-7.0; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.36, P = .0013), glomerulosclerosis (r = -0.39, P = <.001), inflammation (r = -.30, P = .009), and fibrosis (r = -.30, P = .007). Capillary size (cortex) was significantly lower in CKD cats (2591 pixels, 1184-7289) compared to unaffected cats (4523 pixels, 1801-7618; P = <.001) and was negatively correlated with serum creatinine concentrations (r = -.40, P = <.001), glomerulosclerosis (r = -.44, P < .001), inflammation (r = -.42, P = <.001), and fibrosis (r = -.38, P = <.001). CONCLUSIONS AND CLINICAL IMPORTANCE: Capillary rarefaction (decrease in capillary size and percent capillary area) is present in kidneys of cats with CKD and is positively correlated with renal dysfunction and histopathologic lesions.

Serum concentrations of gabapentin in cats with chronic kidney disease.

OBJECTIVES: The purpose of this study was to assess serum concentrations of gabapentin in cats with chronic kidney disease (CKD) vs clinically healthy cats. METHODS: Five healthy cats were enrolled in a pharmacokinetic study. A single 20 mg/kg dose of gabapentin was administered orally and blood was obtained at 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24 and 36 h via a jugular catheter. Serum gabapentin concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Non-compartmental pharmacokinetic analysis was performed. The same five healthy cats plus 25 cats with stable International Renal Interest Society stage 2 (n = 14) and 3 (n = 11) CKD were enrolled in a limited sampling study. Cats in both groups received a single 10 mg/kg dose of gabapentin, and serum gabapentin concentrations and compliance scores were obtained 3 and 8 h post-administration. RESULTS: Cats with CKD had significantly higher dose-normalized serum gabapentin concentrations than normal cats at 3 h (P = 0.0012 CKD vs normal 10 mg/kg; P = 0.008 CKD vs normal 20 mg/kg) and 8 h (P <0.0001 CKD vs normal 10 mg/kg; P <0.0001 CKD vs normal 20 mg/kg). Both 3 and 8 h dose-normalized serum gabapentin concentrations were significantly correlated with serum creatinine (3 h: P = 0.03, r = 0.39; 8 h: P = 0.001, r = 0.57) and symmetric dimethylarginine (3 h: P = 0.03, r = 0.41; 8 h: P = 0.007, r = 0.48). There was a significant correlation between 3 h serum gabapentin concentrations and compliance scores (P = 0.0002, r = 0.68). CONCLUSIONS AND RELEVANCE: Cats with CKD that received 10 mg/kg of gabapentin had significantly higher dose-normalized serum concentrations than normal cats that received 20 mg/kg, supporting the need to dose-reduce in this patient population.

Renal Senescence, Telomere Shortening and Nitrosative Stress in Feline Chronic Kidney Disease.

Kidney tissues from cats with naturally occurring chronic kidney disease (CKD) and adult and senior cats without CKD were assessed to determine whether telomere shortening and nitrosative stress are associated with senescence in feline CKD. The histopathologic assessment of percent global glomerulosclerosis, inflammatory infiltrate, and fibrosis was performed. Senescence and nitrosative stress were evaluated utilizing p16 and iNOS immunohistochemistry, respectively. Renal telomere length was evaluated using telomere fluorescent in situ hybridization combined with immunohistochemistry. CKD cats were found to have significantly increased p16 staining in both the renal cortex and corticomedullary junction compared to adult and senior cats. Senior cats had significantly increased p16 staining in the corticomedullary junction compared to adult cats. p16 staining in both the renal cortex and corticomedullary junction were found to be significantly correlated with percent global glomerulosclerosis, cortical inflammatory infiltrate, and fibrosis scores. p16 staining also correlated with age in non-CKD cats. Average telomere length was significantly decreased in CKD cats compared to adult and senior cats. CKD cats had significantly increased iNOS staining compared to adult cats. Our results demonstrate increased renal senescence, telomere shortening, and nitrosative stress in feline CKD, identifying these patients as potential candidates for senolytic therapy with translational potential.