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Objectives: Evaluation of haem dipstick pad, urine protein, urine pH and urine protein:creatinine ratio results as a marker of bacteriuria in dogs and cats with inactive urine sediment., Materials and Methods: Cats and dogs with contemporaneous urine dipstick, microscopic sediment analysis and microbiological culture and sensitivity results over a four-year period (2016 to 2020) were retrospectively identified. Dogs and cats with active urine sediments (at least five erythrocytes and/or five leukocytes per high-power field) and/or spermaturia were excluded. Association between urine pH, haem dipstick result, protein dipstick result and urine protein:creatinine ratio with bacteriuria were evaluated using binary logistic regression analysis. Likelihood ratios for bacteriuria were calculated at different diagnostic thresholds., Results: A total of 668 and 169 dog and cat urine samples were included. Of these, 166 dogs (25%) had a positive urine culture, whilst only 29 cats (17%) had a positive urine culture. In dogs and cats, any positive haem dipstick result was significantly associated with bacteriuria, although only a ≥4+ haem positive result in dogs was associated with a small increase in the likelihood of a positive urine culture, and positive likelihood ratios did not support the use of haem dipstick results as a screening test for bacteriuria in cats. pH, urine protein:creatinine ratio and protein dipstick results were not associated with bacteriuria., Clinical Significance: Our findings provide proof of concept that haem dipstick pad results in dogs with inactive sediment and without spermaturia might be useful as a screening test for bacteriuria, although further studies are required to confirm these findings., (© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Objectives: To validate a methodology for isolating feline urinary extracellular vesicles and characterise the urinary extracellular vesicle population and proteome in cats with normal renal function and cats with normotensive or hypertensive chronic kidney disease., Methods: Feline urinary extracellular vesicles were isolated using three different methods (precipitation alone, precipitation followed by size exclusion chromatography and ultrafiltration followed by size exclusion chromatography, which were compared via transmission electron microscopy and nanoparticle tracking analysis. Cats with normal renal function (n=9), normotensive chronic kidney disease (n=10) and hypertensive chronic kidney disease (n=9) were identified and urinary extracellular vesicles isolated from patient urine samples via ultrafiltration followed by size exclusion chromatography. Extracellular vesicle size and concentration were determined using nanoparticle tracking analysis, and subsequently underwent proteomic analysis using liquid chromatography with tandem mass spectrometry to identify differences in protein expression between categories., Results: Urinary extracellular vesicle preparations contained particles of the expected size and morphology, and those obtained by ultrafiltration + size exclusion chromatography had a significantly higher purity (highest particle: protein ratio). The urinary extracellular vesicle proteomes contained extracellular vesicle markers and proteins originating from all nephron segments. Urinary extracellular vesicle concentration and size were unaffected by renal disease or hypertension. There were no differentially expressed proteins detected when comparing urinary extracellular vesicles derived from cats in the healthy category with the combined chronic kidney disease category, but five differentially expressed proteins were identified between the normotensive chronic kidney disease and hypertensive chronic kidney disease categories., Clinical Significance: Feline urinary extracellular vesicles can be successfully isolated from stored urine samples. Differentially expressed urinary extracellular vesicle proteins were discovered in cats with hypertensive chronic kidney disease, and warrant further investigation into their utility as biomarkers or therapeutic targets., (© 2022 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Background: Hypercalcemia is commonly associated with chronic kidney disease (CKD) in cats., Objectives: To explore the calcitonin response to naturally occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the relationship of plasma calcitonin with ionized calcium, alkaline phosphatase (ALP), and urinary calcium excretion., Animals: Thirty-three client-owned cats with azotemic CKD and ionized hypercalcemia from first opinion practice., Methods: Cohort study. Calcitonin was measured with an immunoradiometric assay in heparinized plasma. Simple correlations were assessed with Kendall's rank correlation, and the within-subject correlations of calcitonin with ionized calcium and other clinicopathological variables were calculated with a bivariate linear mixed effects model., Results: Calcitonin concentrations above the lower limit of detection (>1.2 pg/mL; range, 1.7-87.2 pg/mL) were observed in 11 of 33 hypercalcemic cats (responders). Blood ionized calcium concentration did not differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found for calcitonin and ionized calcium to correlate between cats (τ b  = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within-subject correlation coefficient [r within ], 0.83; 95% confidence interval [CI], 0.63-0.92). Calcitonin correlated negatively over time with plasma ALP (r within , -0.55; 95% CI, -0.79 to -0.16)., Conclusions and Clinical Importance: Calcitonin does not appear to have an important role in calcium metabolism in cats with CKD., (Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Currently, no test can accurately predict the development of azotemia after treatment of hyperthyroidism. Serum cystatin C concentrations (sCysC) might be less influenced by changes in body muscle mass and so better indicate the presence of concurrent chronic kidney disease (CKD) in hyperthyroidism., Hypotheses: sCysC will be higher in hyperthyroid cats that develop azotemia compared with hyperthyroid cats that remain nonazotemic after treatment; sCysC will be higher in nonhyperthyroid cats with azotemic CKD than healthy older cats and, sCysC will decrease after treatment of hyperthyroidism., Animals: Ninety-one cats treated in first opinion practice., Methods: Case-control study. sCysC were compared between hyperthyroid cats which developed azotemia within 4 months of successful treatment of hyperthyroidism (pre-azotemic group) and hyperthyroid cats which remained nonazotemic after treatment (nonazotemic group), and between nonhyperthyroid cats with azotemic CKD and healthy older cats. sCysC were also compared between hyperthyroid cats before treatment and at time of establishment of euthyroidism. Data are presented as median [25th, 75th percentile]., Results: Baseline sCysC were not different between the pre-azotemic and nonazotemic groups (1.9 [1.4, 2.3] mg/L versus 1.5 [1.1, 2.2] mg/L, respectively; P = .22). sCysC in nonhyperthyroid cats with azotemic CKD and healthy older cats were not significantly different (1.5 [1.0, 1.9] mg/L versus 1.2 [0.8, 1.4] mg/L, respectively; P = .16). sCysC did not change significantly after treatment of hyperthyroidism (pretreatment 1.8 [1.2, 2.3] mg/L, after treatment 1.6 [1.1, 2.4] mg/L; P = .82)., Conclusions and Clinical Importance: sCysC do not appear to be a reliable marker of renal function in hyperthyroid cats., (Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objectives: Evaluation of urine albumin:creatinine ratio, urine cystatin C:creatinine ratio, urine protein:creatinine ratio and urine specific gravity as screening tests for azotaemic chronic kidney disease in cats., Methods: A group of cats over eight years old were defined as either (i) healthy non-azotaemic (n=40) if they had serum creatinine concentration <153 µmol/L and no history of apparent disease or (2) having azotaemic chronic kidney disease (n=12) if they had serum creatinine concentration >153 µmol/L with urine specific gravity <1·035. Urine albumin:creatinine ratio, urine cystatin C:creatinine ratio, urine protein:creatinine ratio and urine specific gravity were compared between the two groups., Results: Urine cystatin C:creatinine ratio was significantly lower in cats with azotaemic chronic kidney disease than that in healthy cats [3·7 (1·4, 4·3)×10(-6) versus 13·9 (6·3, 24·7)×10(-6) ; P=0·011]. Urine specific gravity was also significantly lower in the azotaemic chronic kidney disease group than that in the healthy group [1·022 (1·017, 1·028) versus 1·043 (1·034, >1·050); P<0·001]. Urine albumin:creatinine ratio and urine protein:creatinine ratio were not significantly different between the groups (P=0·075 and P=0·965, respectively)., Clinical Significance: Urine cystatin C:creatinine ratio and urine specific gravity were significantly lower in cats with azotaemic chronic kidney disease than that in healthy cats; however, neither biomarker was an adequate sole screening test for azotaemic chronic kidney disease., (© 2015 British Small Animal Veterinary Association.)

Many hyperthyroid cats develop azotaemic chronic kidney disease (aCKD) following treatment, which has led to the hypothesis that hyperthyroidism might be detrimental to renal function. Renin-angiotensin-aldosterone system (RAAS) activation occurs in hyperthyroidism, which could cause peri-tubular hypoxia, tubular damage and the development of aCKD. Urinary vascular endothelial growth factor:creatinine ratio (VEGFCR) is postulated to be a marker of tubular hypoxia. VEGFCR was correlated with plasma renin activity (PRA) and compared between hyperthyroid cats that did and did not develop aCKD following treatment (pre-azotaemic and non-azotaemic groups respectively). PRA was positively correlated with VEGFCR (rs = 0.382; P = 0.028); however, pre-azotaemic hyperthyroid cats had significantly lower VEGFCR than non-azotaemic cats at baseline (median 122.3 fg/g versus 167.0 fg/g; P < 0.001). RAAS activation in hyperthyroidism is associated with increased VEGFCR; however, increased VEGFCR was not correlated with the development of aCKD. Therefore, tubular hypoxia may not be a mechanism for renal damage in hyperthyroid cats., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate possible pathophysiological mechanisms (reduced plasma calcitriol concentrations and/or presence of concurrent or masked chronic kidney disease) for hypocalcaemiain hyperthyroid cats., Methods: Prospective cohort study. Routine plasma biochemical parameters, plasma parathyroid hormone and calcitriol concentrations, ionized calcium concentrations, and venous pH, were measured at diagnosis and following treatment of hyperthyroidism. Linear regression analysis was used to determine predictors of ionized calcium concentration., Results: Hyperthyroid cats (n=45) had lower ionized calcium concentrations than healthy geriatric cats (n=52), however, ionized calcium concentrations were higher in hyperthyroid cats with concurrent or masked chronic kidney disease than non-azotaemic hyperthyroid cats. Plasma calcitriol concentrations were higher in hyperthyroid cats than control cats. Plasma total thyroxine concentration and venous pH were independent predictors of ionized calcium concentration. Plasma total thyroxine concentration was also a predictor of ionized calcium concentration after adjustment for plasma parathyroid hormone and calcitriol concentrations., Clinical Significance: Hypocalcaemia in hyperthyroid cats is not associated with the presence of concurrent or masked chronic kidney disease or reduced plasma calcitriol concentrations. Increased thyroid hormone concentrations might influence ionized calcium concentrations through a mechanism, yet to be determined, that is independent of control by parathyroid hormone and calcitriol., (© 2013 British Small Animal Veterinary Association.)

Background: Hypertension is present in some hyperthyroid cats at diagnosis or can develop after treatment for hyperthyroidism. Activation of the renin-angiotensin-aldosterone system (RAAS) could be involved in the pathogenesis of hypertension., Hypothesis: Hyperthyroid cats that develop hypertension before or after treatment for hyperthyroidism will have greater RAAS activation than normotensive cats., Animals: Ninety-nine hyperthyroid cats., Methods: Retrospective case-control study. Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in untreated hyperthyroid hypertensive cats (HT-Pre group), initially normotensive hyperthyroid cats that develop hypertension after treatment (HT-Post group), and hyperthyroid cats that are normotensive (NT group). Data are presented as median [25th, 75th percentile]., Results: Baseline PRA was not significantly different among the 3 groups (HT-Pre group 1.50 [0.05, 2.37] ng/mL/h, HT-Post group 0.66 [0.17, 2.31] ng/mL/h, NT group 1.11 [0.57, 2.18] ng/mL/h; P = .44). PRA decreased significantly after treatment in the NT group (1.09 [0.53, 2.47] versus 0.22 [0.05, 0.76] ng/mL/h; P < .001) and the HT-Post group (0.71 [0.17, 2.33] versus 0.28 [0.07, 0.57] ng/mL/h; P = .006). Baseline PAC was not significantly different among the 3 groups (HT-Pre group 72.2 [40.0, 145.6] pg/mL, HT-Post group 69.7 [43.3, 142.6] pg/mL, NT group 109.0 [68.2, 184.6] pg/mL; P = .10). PAC decreased significantly after treatment in the NT group (114.4 [56.6, 204.1] versus 59.5 [32.4, 98.2] pg/mL; P < .001) but did not change significantly in the HT-Post group (61.2 [44.9, 124.0] versus 58.4 [42.0, 97.7] pg/mL; P = .59)., Conclusions and Clinical Importance: RAAS activation occurs in hyperthyroid cats, but is not associated with the development of hypertension. PAC is not influenced by changes in PRA in hyperthyroid cats that develop hypertension after treatment, perhaps indicating RAAS dysfunction in these cats., (Copyright © 2013 by the American College of Veterinary Internal Medicine.)

Objectives: To evaluate calcium and phosphate homeostasis in hyperthyroid cats and determine if plasma parathyroid hormone and fibroblast growth factor-23 are associated with the presence of -azotaemic chronic kidney disease and/or have prognostic significance., Methods: Retrospective cohort study. Logistic regression analysis and Cox regression analysis were performed to identify if parathyroid hormone and fibroblast growth factor-23 were predictors of development of azotaemia following treatment and survival time, respectively., Results: Two hundred and seven hyperthyroid cats were included. Elevated plasma parathyroid hormone concentrations, hyperphosphataemia, decreased plasma fibroblast growth factor-23 concentrations and hypocalcaemia were documented; however, all parameters returned to reference intervals following treatment of hyperthyroid cats without azotaemic chronic kidney disease. After adjustment for plasma creatinine concentration, baseline plasma parathyroid hormone and fibroblast growth factor-23 concentrations were not predictors of the development of azotaemia following treatment. Baseline plasma fibroblast growth factor-23 concentrations were associated with all-cause mortality; however, this association was not maintained after adjustment for packed cell volume., Clinical Significance: Changes in plasma parathyroid hormone and fibroblast growth factor-23 concentrations which occur in hyperthyroid cats are not mediators of progression of chronic kidney disease; however, fibroblast growth factor-23 would appear to have some prognostic significance in hyperthyroidism., (© 2012 British Small Animal Veterinary Association.)

Background: Iatrogenic hypothyroidism can occur after treatment of hyperthyroidism, and is correlated with a reduced glomerular filtration rate in humans and dogs., Hypothesis: Cats with iatrogenic hypothyroidism after treatment for hyperthyroidism will have a greater incidence of azotemia than euthyroid cats., Animals: Eighty client owned cats with hyperthyroidism., Methods: Two retrospective studies. (1) Longitudinal study of 12 hyperthyroid cats treated with radioiodine (documented as euthyroid after treatment), to assess changes in plasma thyroid stimulating hormone (TSH) concentration over a 6-month follow-up period, (2) Cross-sectional study of 75 hyperthyroid cats (documented as euthyroid) 6 months after commencement of treatment for hyperthyroidism to identify the relationship between thyroid status and the development of azotemia. Kaplan-Meier survival analysis was performed to identify relationships between thyroid and renal status and survival., Results: Plasma TSH concentrations were not suppressed in 7 of 8 cats with hypothyroidism 3 months after radioiodine treatment. The proportion of cats with azotemia was significantly (P= .028) greater in the hypothyroid (16 of 28) than the euthyroid group (14 of 47). Twenty-eight of 41 cats (68%) with plasma TT4 concentration below the laboratory reference range had an increased plasma TSH concentration. Hypothyroid cats that developed azotemia within the follow-up period had significantly (P= .018) shorter survival times (median survival time 456 days, range 231-1589 days) than those that remained nonazotemic (median survival time 905 days, range 316-1869 days)., Conclusions and Clinical Importance: Iatrogenic hypothyroidism appears to contribute to the development of azotemia after treatment of hyperthyroidism, and reduced survival time in azotemic cats., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

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.