Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats

BACKGROUND: Hypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored. AIMS: To determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations. METHODS: Fifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response. RESULTS: Cats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response

Renal fibrosis in feline chronic kidney disease: known mediators and mechanisms of injury

Chronic kidney disease (CKD) is a common medical condition of ageing cats. In most cases the underlying aetiology is unknown, but the most frequently reported pathological diagnosis is renal tubulointerstitial fibrosis. Renal fibrosis, characterised by extensive accumulation of extra-cellular matrix within the interstitium, is thought to be the final common pathway for all kidney diseases and is the pathological lesion best correlated with function in both humans and cats. As a convergent pathway, renal fibrosis provides an ideal target for the treatment of CKD and knowledge of the underlying fibrotic process is essential for the future development of novel therapies. There are many mediators and mechanisms of renal fibrosis reported in the literature, of which only a few have been investigated in the cat. This article reviews the process of renal fibrosis and discusses the most commonly cited mediators and mechanisms of progressive renal injury, with particular focus on the potential significance to feline CKD

Survival and complications in cats treated with subcutaneous ureteral bypass.

To report the complications and factors affecting outcome for cats following placement of a subcutaneous ureteral bypass (SUB™). In this retrospective study, complications, the presence of a urinary tract infection and survival time were recorded following subctutaneous ureteral bypass placement. Factors affecting survival time were assessed using a Kaplan Meier curve and log rank test. Ninety-five cats had 130 subcutaneous ureteral bypasses placed. Ten cats did not survive to discharge. Forty cats died or were euthanised after discharge (42%); the median survival time of these cats was 530 days (range 7 to 1915). Minor complications occurred in 18 cats (19%) and major complications occurred in 46 cats (48%), the majority of which were after hospital discharge. Twenty-seven cats were diagnosed with a urinary tract infection (UTI) post-operatively. A significant association between long-term survival and creatinine at presentation was identified. The median survival time for cats presenting with creatinine concentration ≥440 μmol/L (International Renal Interest Society stage acute kidney injury (AKI) 4 and 5) was 530 days (95% CI 273-787 days), compared to a median survival time of 949 days (95% CI 655-1243 days; Log Rank P=0.024) for those cats presenting with creatinine <440 μmol/L (International Renal Interest Society stage AKI 1-3). In this population of cats, subcutaneous ureteral bypass placement was associated with an approximately 10% in-hospital mortality and a high complication rate. Most complications were manageable, resulting in an overall median survival time of over 2 years. [Abstract copyright: © 2020 British Small Animal Veterinary Association.

The association of bacteriuria with survival and disease progression in cats with azotemic chronic kidney disease

Background Cats with chronic kidney disease (CKD) have an increased prevalence of positive urine cultures (PUC). Limited information is available regarding the prognosis of cats with CKD and concurrent PUC. Objective To determine the association of PUC with survival time and disease progression in cats with CKD. Animals Medical records of 509 cats diagnosed with azotemic CKD between 1997 and 2018. Methods Cats were classified as having “no‐PUC” or “PUC.” The PUC cats were further classified as having 1 or multiple PUC, and also were classified based on the presence or absence of clinical signs of urinary tract infection (UTI). Progression of CKD was defined as a plasma creatinine concentration increase of ≥25% within 365 days of CKD diagnosis; PUC also must have occurred within this time frame. Survival time and frequency of CKD progression were compared between groups. Results No significant difference in survival time was found between cats with no‐PUC and cats with any number of PUC (P = .91), or between cats with no‐PUC, 1 PUC or multiple PUC (P = .37). Also, no significant difference was found in the frequency of CKD progression between PUC and no‐PUC cats (P = .5), or among no‐PUC, 1 PUC and multiple PUC cats (P = .22). When assessing cats with clinical signs of lower UTI, no significant difference was found in the frequency of CKD progression between cats with true UTI, subclinical bacteriuria or no‐PUC (P = .8). Conclusions and Clinical Importance When treated with antibiotics, PUC in cats with CKD do not affect disease progression or survival time

First genome-wide association study investigating blood pressure and renal traits in domestic cats

Hypertension (HTN) and chronic kidney disease (CKD) are common in ageing cats. In humans, blood pressure (BP) and renal function are complex heritable traits. We performed the first feline genome-wide association study (GWAS) of quantitative traits systolic BP and creatinine and binary outcomes HTN and CKD, testing 1022 domestic cats with a discovery, replication and meta-analysis design. No variants reached experimental significance level in the discovery stage for any phenotype. Follow up of the top 9 variants for creatinine and 5 for systolic BP, one SNP reached experimental-wide significance for association with creatinine in the combined meta-analysis (chrD1.10258177; P = 1.34 × 10(–6)). Exploratory genetic risk score (GRS) analyses were performed. Within the discovery sample, GRS of top SNPs from the BP and creatinine GWAS show strong association with HTN and CKD but did not validate in independent replication samples. A GRS including SNPs corresponding to human CKD genes was not significant in an independent subset of cats. Gene-set enrichment and pathway-based analysis (GSEA) was performed for both quantitative phenotypes, with 30 enriched pathways with creatinine. Our results support the utility of GWASs and GSEA for genetic discovery of complex traits in cats, with the caveat of our findings requiring validation

Associations between single nucleotide polymorphisms in the calcium sensing receptor and chronic kidney disease-mineral and bone disorder in cats

Feline chronic kidney disease (CKD) is associated with high variability in severity of CKD-mineral and bone disorder (CKD-MBD). The calcium sensing receptor (CaSR) regulates circulating parathyroid hormone (PTH) and calcium concentrations. Single nucleotide polymorphisms (SNPs) in the CaSR are associated with severity of secondary renal hyperparathyroidism and total calcium concentrations in human patients receiving haemodialysis. The objective of this study was to explore associations between polymorphisms in the feline CaSR (fCaSR) and biochemical changes observed in CKD-MBD. Client owned cats (≥ 9 years) were retrospectively included. SNP discovery was performed in 20 cats with azotaemic CKD and normal or dysregulated calcium concentrations. Non-pedigree cats (n = 192) (125 with azotaemic CKD and 66 healthy), Persians (n = 40) and Burmese (n = 25) were genotyped for all identified SNPs using KASP. Biochemical parameters from the date of CKD diagnosis or from first visit to the clinic (healthy cats) were used. Associations between genotype and ionized calcium, total calcium, phosphate, PTH and FGF-23 were performed for non-pedigree cats using logistic regression. Sequence alignment against the fCaSR sequence revealed eight novel exonic SNPs. KASP genotyping had high accuracy (99.6%) and a low failure rate (A was associated with logPTH concentration (adjusted for plasma creatinine concentration), with a recessive model having the best fit (G/G vs A/A-G/A, P = 0.031). Genetic variation in the fCaSR is unlikely to explain the majority of the variability in presence and severity of CKD-MBD in cats

Perceptions of Social Mobility: Development of a New Psychosocial Indicator Associated with Adolescent Risk Behaviors

Social class gradients have been explored in adults and children, but not extensively during adolescence. The first objective of this study was to examine the association between adolescent risk behaviors and a new indicator of adolescent relative social position, adolescent “perceived social mobility.” Second, it investigated potential underlying demographic, socioeconomic, and psychosocial determinants of this indicator. Data were taken from the 2004 urban adolescent module of Oportunidades, a cross-sectional study of Mexican adolescents living in poverty. Perceived social mobility was calculated for each subject by taking the difference between their rankings on two 10-rung ladder scales that measured (1) projected future social status and (2) current subjective social status within Mexican society. Adolescents with higher perceived social mobility were significantly less likely to report alcohol consumption, drinking with repercussions, compensated sex, police detainment, physical fighting, consumption of junk food or soda, or watching ≥4 h of television during the last viewing. They were significantly more likely to report exercising during the past week and using a condom during last sexual intercourse. These associations remained significant with the inclusion of covariates, including parental education and household expenditures. Multiple logistic regression analyses show higher perceived social mobility to be associated with staying in school longer and having higher perceived control. The present study provides evidence for the usefulness of perceived social mobility as an indicator for understanding the social gradient in health during adolescence. This research suggests the possibility of implementing policies and interventions that provide adolescents with real reasons to be hopeful about their trajectories

Weak localization effect on thermomagnetic phenomena

The quantum transport equation (QTE) is extended to study weak localization (WL) effects on galvanomagnetic and thermomagnetic phenomena. QTE has many advantages over the linear response method (LRM): (i) particle-hole asymmetry which is necessary for the Hall effect is taken into account by the nonequilibrium distribution function, while LRM requires expansion near the Fermi surface, (ii) when calculating response to the temperature gradient, the problem of WL correction to the heat current operator is avoided, (iii) magnetic field is directly introduced to QTE, while the LRM deals with the vector potential and and special attention should be paid to maintain gauge invariance, e.g. when calculating the Nernst effect the heat current operator should be modified to include the external magnetic field. We reproduce in a very compact form known results for the conductivity, the Hall and the thermoelectric effects and then we study our main problem, WL correction to the Nernst coefficient (transverse thermopower).Comment: 20 pages 2 figure