Dietary magnesium supplementation in cats with chronic kidney disease: A prospective double-blind randomized controlled trial.

BACKGROUND: Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored. OBJECTIVES: Evaluate effects of a magnesium-enriched phosphate-restricted diet (PRD) on CKD-mineral bone disorder (CKD-MBD) variables. ANIMALS: Sixty euthyroid client-owned cats with azotemic CKD, with 27 and 33 allocated to magnesium-enriched PRD or control PRD, respectively. METHODS: Prospective double-blind, parallel-group randomized trial. Cats with CKD, stabilized on a PRD, without hypermagnesemia (tMg >2.43 mg/dL) or hypercalcemia (plasma ionized calcium concentration, (iCa) >6 mg/dL), were recruited. Both intention-to-treat and per-protocol (eating ≥50% of study diet) analyses were performed; effects of dietary magnesium supplementation on clinicopathological variables were evaluated using linear mixed effects models. RESULTS: In the per-protocol analysis, tMg increased in cats consuming a magnesium-enriched PRD (ß, 0.25 ± .07 mg/dL/month; P < .001). Five magnesium supplemented cats had tMg >2.92 mg/dL, but none experienced adverse effects. Rate of change in iCa differed between groups (P = .01), with decreasing and increasing trends observed in cats fed magnesium-enriched PRD and control PRD, respectively. Four control cats developed ionized hypercalcemia versus none in the magnesium supplemented group. Log-transformed plasma fibroblast growth factor-23 concentration (FGF23) increased significantly in controls (ß, 0.14 ± .05 pg/mL/month; P = .01), but remained stable in the magnesium supplemented group (ß, 0.05±.06 pg/mL/month; P =.37). CONCLUSIONS AND CLINICAL IMPORTANCE: Magnesium-enriched PRD is a novel therapeutic strategy for managing feline CKD-MBD in cats, further stabilizing plasma FGF23 and preventing hypercalcemia.

Corrigendum: Rapid typing of Klebsiella pneumoniae and Pseudomonas aeruginosa by Fourier-transform Infrared spectroscopy informs infection control in veterinary settings.

[This corrects the article DOI: 10.3389/fmicb.2024.1334268.].

Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

BACKGROUND: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. OBJECTIVES: Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. ANIMALS: Thirty-six euthyroid client-owned cats with CKD. METHODS: Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. RESULTS: Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time. CONCLUSIONS AND CLINICAL IMPORTANCE: Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats.

International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

Detection of nephrocalcinosis using ultrasonography, micro-computed tomography, and histopathology in cats.

BACKGROUND: Identification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain. OBJECTIVES: To compare ultrasonography, micro-computed tomography (µCT) and histopathology for identification of nephrocalcinosis. ANIMALS: Twelve kidneys from 7 euthyroid client-owned cats with CKD. METHODS: Descriptive study. Renal ultrasonography was performed ante-mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using µCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume-to-kidney tissue ratio (macro-VN:KT) and sagittal nephrocalcinosis area-to-kidney tissue ratio (macro-AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin-fixed, and paraffin-embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK-micro-AN:KT and AR-micro-AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation. RESULTS: Nephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro-VN:KT was 0.001%, 0.001%, and 0.019%, and the macro-AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK-micro-AN:KT was 0.21%, 2.85%, and 4.56%, and AR-micro-AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro-nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro-AN:KT) and microscopic (VK-micro-AN:KT) nephrocalcinosis (rs = 0.76; P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time.

Rapid typing of Klebsiella pneumoniae and Pseudomonas aeruginosa by Fourier-transform Infrared spectroscopy informs infection control in veterinary settings.

Introduction: The emergence of multi-drug resistant (MDR) pathogens linked to healthcare-associated infections (HCAIs) is an increasing concern in modern veterinary practice. Thus, rapid bacterial typing for real-time tracking of MDR hospital dissemination is still much needed to inform best infection control practices in a clinically relevant timeframe. To this end, the IR Biotyper using Fourier-Transform InfraRed (FTIR) spectroscopy has the potential to provide fast cluster analysis of potentially related organisms with substantial cost and turnaround time benefits. Materials and methods: A collection of MDR bacterial isolates (n = 199, comprising 92 Klebsiella pneumoniae and 107 Pseudomonas aeruginosa) obtained from companion animal (i.e., dogs, cats and horses) clinical investigations, faecal and environmental screening from four veterinary facilities between 2012 and 2019 was analysed retrospectively by FTIR spectroscopy. Its performance was compared against MLST extracted from whole genomes of a subset of clustering isolates (proportionally to cluster size) for investigation of potential nosocomial transmission between patients and the surrounding hospital environments. Results: Concordance between the FTIR and MLST types was overall high for K. pneumoniae (Adjusted Rand Index [ARI] of 0.958) and poor for P. aeruginosa (ARI of 0.313). FTIR K. pneumoniae clusters (n = 7) accurately segregated into their respective veterinary facility with evidence of intra-hospital spread of K. pneumoniae between patients and environmental surfaces. Notably, K. pneumoniae ST147 intensely circulated at one Small Animal Hospital ICU. Conversely, Pseudomonas aeruginosa FTIR clusters (n = 18) commonly contained isolates of diversified hospital source and heterogeneous genetic background (as also genetically related isolates spread across different clusters); nonetheless, dissemination of some clones, such as P. aeruginosa ST2644 in the equine hospital, was apparent. Importantly, FTIR clustering of clinical, colonisation and/or environmental isolates sharing genomically similar backgrounds was seen for both MDR organisms, highlighting likely cross-contamination events that led to clonal dissemination within settings. Conclusion: FTIR spectroscopy has high discriminatory power for hospital epidemiological surveillance of veterinary K. pneumoniae and could provide sufficient information to support early detection of clonal dissemination, facilitating implementation of appropriate infection control measures. Further work and careful optimisation need to be carried out to improve its performance for typing of P. aeruginosa veterinary isolates.

Prospective evaluation of novel biomarkers of acute kidney injury in dogs following cardiac surgery under cardiopulmonary bypass.

OBJECTIVE: To assess the occurrence of acute kidney injury (AKI) in dogs undergoing cardiac surgery under cardiopulmonary bypass (CPB) and explore associations between traditional and novel serum and urinary biomarkers. DESIGN: Prospective cohort study conducted between July 2018 and April 2019. SETTING: University teaching hospital. ANIMALS: Nineteen dogs undergoing cardiac surgery under CPB with preoperative serum creatinine <140 µmol/L (<1.6 mg/dl). INTERVENTIONS: Blood and urine samples were obtained at 4 time points: preoperatively following general anesthesia induction, immediately postoperatively, and 2 and 4 days postoperatively (T1 , T2 , T3 , and T4 ). AKI was defined as an increase in serum creatinine ≥26.4 µmol/L (≥0.3 mg/dl) above baseline within 48 hours. Serum creatinine, C-reactive protein (CRP), symmetric dimethylarginine (SDMA), inosine, beta-aminoisobutyric acid (BAIB), urinary clusterin (uClus), and urinary cystatin B (uCysB) were measured. Data were log-transformed (log10 ) when appropriate and assessed using linear mixed-effects models. MEASUREMENTS AND MAIN RESULTS: AKI occurred in 3 of 19 dogs (15.8%, 95% confidence interval: 0.047-0.384). Inosine increased at T2 (adjusted mean ± standard error: 53 ± 5.6) in all dogs, and then gradually decreased. Log10 uCysB increased at T2 (2.3 ± 0.1) in all dogs and remained high. Log10 CRP and log10 uClus increased significantly at T3 (1.9 ± 0.1 and 3.6 ± 0.1, respectively) in all dogs and remained increased. There was a significant positive association between serum creatinine and SDMA (P < 0.001, estimate ± standard error: 0.06 ± 0.00), between log10 CRP and log10 uClus (P < 0.001, 0.35 ± 0.08), between SDMA and creatinine as well as between SDMA and BAIB (P < 0.001, 11.1 ± 0.83 and P < 0.001, 1.06 ± 0.22, respectively) for all dogs at all time points. CONCLUSIONS: Inosine and uCysB concentrations changed in all dogs immediately following a surgery under CPB and may indicate tubular injury. Further studies are required to ascertain the usefulness of those biomarkers in early detection of AKI.

Ionized hypercalcemia in cats with azotemic chronic kidney disease (2012-2018).

BACKGROUND: Hypercalcemia is associated with chronic kidney disease (CKD) in cats, but studies assessing the physiologically relevant ionized calcium fraction are lacking. OBJECTIVES: To describe the prevalence and incidence rate of ionized hypercalcemia, and to explore predictor variables to identify cats at risk of ionized hypercalcemia in a cohort of cats diagnosed with azotemic CKD. ANIMALS: One hundred sixty-four client-owned cats with azotemic CKD. METHODS: Variables independently associated with ionized hypercalcemia at diagnosis of azotemic CKD were explored by binary logistic regression. Cats that were normocalcemic at diagnosis of azotemic CKD were followed over a 12-month period or until ionized hypercalcemia occurred and baseline predictor variables for ionized hypercalcemia explored using Cox proportional hazards and receiver operating characteristic curve analysis. RESULTS: Ionized hypercalcemia (median, 1.41 mmol/L; range, 1.38-1.68) was observed in 33/164 (20%) cats at diagnosis of azotemic CKD and was associated with male sex, higher plasma total calcium and potassium concentrations, and lower plasma parathyroid hormone concentrations. Twenty-five of 96 initially normocalcemic (26%) cats followed for minimum 90 days developed ionized hypercalcemia (median, 1.46 mmol/L; range, 1.38-1.80) at a median of 140 days after diagnosis of azotemic CKD (incidence rate, 0.48 per feline patient-year). Only body condition score was independently associated with incident ionized hypercalcemia. CONCLUSIONS AND CLINICAL IMPORTANCE: The occurrence of ionized hypercalcemia is high in cats with CKD. Continued monitoring of blood ionized calcium concentrations is advised.

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats.

BACKGROUND: Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored. OBJECTIVES: Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all-cause mortality. ANIMALS: Fifty-one euthyroid client-owned cats with International Renal Interest Society (IRIS) stages 2-3 azotemic CKD. METHODS: Retrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner-reported time-averaged phosphate-restricted diet (PRD) intake, where PRD comprised ≥50%, 10-50%, or none of food intake. RESULTS: Nephrocalcinosis was rated as mild-to-severe in 78.4% and absent-to-minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%-50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent-to-minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1-year period, and had shorter median survival times than cats with mild-to-severe nephrocalcinosis. CONCLUSION AND CLINICAL IMPORTANCE: Higher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.

Feline comorbidities: The intermingled relationship between chronic kidney disease and hypertension.

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is a highly prevalent disorder of senior cats. CKD is frequently diagnosed in association with hypertension, and the two conditions have an intermingled cause-and-effect relationship. Hypertensive target organ damage (TOD) to the eye, brain, heart and kidney significantly impacts the welfare of cats suffering from this comorbidity. Hypertension also drives proteinuria, which is an independent risk factor for progression and mortality in cats with CKD. Blood pressure monitoring and institution of effective antihypertensive treatment, where indicated, is therefore crucial in effective management of the feline CKD patient. Current guidelines recommend a target systolic blood pressure of <160 mmHg to minimise risk of TOD. Both amlodipine besylate and telmisartan are effective antihypertensive agents for use in these patients. CLINICAL CHALLENGES: Clinical signs of hypertension may not be apparent to owners of affected cats until severe hypertensive TOD is present. Despite this, blood pressure monitoring in cats with CKD is still infrequently performed, and hypertension likely remains underdiagnosed in this population. EVIDENCE BASE: This review is based upon evaluation of the currently available published literature, including relevant consensus statements. There is a large body of evidence supporting the association between hypertension and CKD in cats. However, significant aspects, such as the mechanisms behind this association, and effect of hypertension and antihypertensive treatment on mortality and progression of CKD, remain unclear. Further research is therefore required in order to improve understanding of these conditions.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 1: Physiology of calcium handling.

Mineral derangements are a common consequence of chronic kidney disease (CKD). Despite the well-established role of phosphorus in the pathophysiology of CKD, the implications of calcium disturbances associated with CKD remain equivocal. Calcium plays an essential role in numerous physiological functions in the body and is a fundamental structural component of bone. An understanding of calcium metabolism is required to understand the potential adverse clinical implications and outcomes secondary to the (mal)adaptation of calcium-regulating hormones in CKD. The first part of this two-part review covers the physiology of calcium homeostasis (kidneys, intestines and bones) and details the intimate relationships between calcium-regulating hormones (parathyroid hormone, calcitriol, fibroblast growth factor 23, α-Klotho and calcitonin) and the role of the calcium-sensing receptor.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 2: Pathophysiology of calcium disorder and extraosseous calcification.

Derangements in mineral metabolism are one of the main entities in chronic kidney disease-mineral and bone disorder (CKD-MBD). This is the second of a two-part review of the physiology and pathophysiology of calcium homeostasis in feline CKD-MBD. While dysregulation in calcium homeostasis is known to contribute to the development of vascular calcification in CKD, evidence characterising the relationship between serum calcium concentration and nephrocalcinosis and nephrolithiasis is limited. Recently, fibroblast growth factor 23 (FGF23) and α-Klotho have gained increased research interest and been shown to be important biomarkers for the prediction of CKD progression in human patients. However, conflicting evidence exists on their role in calcium homeostasis and vascular and soft tissue calcification. This review details the pathophysiology of calcium disorders associated with CKD-MBD and its implications on vascular and soft tissue mineralisation in human and feline patients. Further prospective studies investigating the clinical consequences of calcium disturbances in cats with CKD are warranted and this may provide additional insight into the pathophysiology of feline CKD-MBD.

The effect of attenuating dietary phosphate restriction on blood ionized calcium concentrations in cats with chronic kidney disease and ionized hypercalcemia.

BACKGROUND: Hypercalcemia is commonly observed in cats with azotemic chronic kidney disease (CKD). Dietary phosphate restriction is considered standard of care but may contribute to the development of hypercalcemia. The optimal dietary management strategy for these cats is unclear. OBJECTIVES: To describe the effect of feeding a moderately phosphate-restricted diet (MP; 1.5 g/Mcal phosphorus; Ca : P ratio, 1.3) to cats with concurrent azotemic CKD and ionized hypercalcemia. ANIMALS: Client-owned cats with ionized hypercalcemia (ionized calcium [iCa] concentration >1.4 mmol/L) at diagnosis of CKD (n = 11; baseline hypercalcemics) or after CKD diagnosis while eating a phosphate-restricted clinical renal diet (0.8 g/Mcal phosphorus; Ca : P ratio, 1.9; n = 10; RD hypercalcemics). METHODS: Changes in variables over time, after starting MP at visit 1, were assessed using linear mixed model analysis within each group of cats. Data are reporte as median [25th, 75th percentiles]. RESULTS: At visit 1, iCa was 1.47 [1.42, 1.55] mmol/L for baseline hypercalcemics and 1.53 [1.5, 1.67] mmol/L for RD hypercalcemics. Blood iCa decreased (P < .001) when RD hypercalcemics were fed MP, with iCa <1.4 mmol/L in 8/10 cats after 2.2 [1.8, 3.7] months. Plasma phosphate concentrations did not change. In contrast, the baseline hypercalcemic group overall showed no change in iCa but a decrease in plasma phosphate concentration during 8.8 [5.5, 10.6] months on the MP diet, although 4/11 individual cats achieved iCa <1.4 mmol/L by 3.4 [1.0, 6.2] months. CONCLUSIONS AND CLINICAL IMPORTANCE: Attenuation of dietary phosphate restriction could result in normalization of iCa in cats that develop hypercalcemia while eating a clinical renal diet.

Risk factors associated with disturbances of calcium homeostasis after initiation of a phosphate-restricted diet in cats with chronic kidney disease.

BACKGROUND: Dietary phosphate restriction improves survival in cats with chronic kidney disease (CKD). However, feeding a phosphate-restricted diet may disrupt calcium homeostasis leading to hypercalcemia in some cats. OBJECTIVES: To identify risk factors associated with increasing plasma total calcium (tCa) concentration after transition to a phosphate-restricted diet and to explore its role in CKD-mineral and bone disorder (CKD-MBD) in cats. ANIMALS: Seventy-one geriatric (≥9 years) euthyroid client-owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD. METHODS: Retrospective cross-sectional cohort study. Changes in plasma tCa concentration in the first 200 days of diet transition were assessed using linear regression. Binary logistic regressions were performed to identify risk factors for increasing calcium concentration. Changes in clinicopathological variables associated with CKD-MBD over time were explored using linear mixed model and generalized linear mixed model analyses. RESULTS: Lower baseline plasma potassium (odds ratio [OR] = 1.19 per 0.1 mmol/L decrease; P = .003) and phosphate (OR = 1.15 per 0.1 mmol/L decrease; P = .01) concentrations remained independent risk factors for increasing plasma tCa concentration. Plasma creatinine (ß = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (ß = .64 ± .29 µg/dL; P = .03), phosphate (ß = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (ß = .103 ± .035 pg/mL; P = .004) concentrations had significantly increased rates of change in cats with increasing plasma tCa concentration over time. CONCLUSION AND CLINICAL IMPORTANCE: Lower plasma potassium or phosphate concentrations or both at the time of transition of cats with CKD to a phosphate-restricted diet are independently associated with increased risk of an increase in plasma tCa concentration. Increasing plasma tCa concentration is associated with progression of CKD.

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.

Hypertension, retinopathy, and acute kidney injury in dogs: A prospective study.

BACKGROUND: Systemic hypertension (SH) is a potential complication of acute kidney injury (AKI) in dogs. OBJECTIVE: To describe the prevalence of SH and hypertensive retinopathy in dogs with AKI, to investigate the relationship between SH and severity of AKI and to assess possible factors associated with SH. ANIMALS: Fifty-two dogs with AKI. METHODS: Prospective observational study of dogs presenting to a tertiary referral center that fulfilled the International Renal Interest Society (IRIS) guidelines for the diagnosis of AKI. Systolic blood pressure measurement, urine protein/creatinine ratio (UPCR), urine output, presence of hypertensive retinopathy and fluid overload (FO), survival to discharge and duration of hospitalization were subsequently assessed. The prevalence of SH was calculated and the relationship between SH and recorded factors was examined by nonparametric statistics. RESULTS: The prevalence of SH (≥160 mm Hg) on admission or during hospitalization was 75% (39/52) and in 56% (22/39) of cases this was severe (≥180 mm Hg). Sixteen percent (7/43) of dogs had evidence of hypertensive retinopathy and 77% (24/31) dogs had UPCR >0.5. Forty-two percent (22/52) dogs had FO on admission or during hospitalization. There was no association between SH and IRIS AKI grade, oligo/anuria, survival to discharge, duration of hospitalization or proteinuria. Dogs with FO on presentation were more likely to be hypertensive at admission compared to dogs without FO (P = .02). Dogs that did not survive to discharge were more likely to have FO (P = .007). CONCLUSIONS AND CLINICAL IMPORTANCE: Systemic hypertension is common in dogs with AKI. Systemic hypertension might be associated with FO, which itself is associated with nonsurvival. Monitoring for SH and FO is therefore warranted in dogs with AKI.

Dysautonomia in 53 cats and dogs: retrospective review of clinical data and outcome.

BACKGROUND: Dysautonomia is a disease characterised by degeneration of autonomic neurons. METHODS: The aim of this study was to perform a retrospective multicentre review of clinical data relating to cats and dogs diagnosed with dysautonomia and to evaluate their outcome. RESULTS: Cats (n=34) and dogs (n=19) with clinical signs consistent with dysautonomia were considered for this retrospective study. Reported clinical findings included oesophageal and gastrointestinal dysmotility and distension, urinary retention, reduced or absent tear production, third eyelid protrusion and inappropriate mydriasis. Treatment was supportive and included gastrointestinal prokinetics, feeding tube placement (oesophageal and percutaneous endoscopic gastrostomy tubes) and medications to treat urinary retention. The survival to discharge was 29 per cent in cats and 47 per cent in dogs. The overall survival in cats was 21 per cent and that in dogs was 32 per cent. Survival of greater than 2 years was seen in six cats and in three dogs. CONCLUSION: This paper illustrates that some animals are able to survive this disease and can have a good long-term prognosis, which is an infrequently reported finding for this disease.

Clinical utility of estimation of glomerular filtration rate in dogs.

BACKGROUND: Glomerular filtration rate (GFR) estimation is the gold standard for assessment of renal function, although the clinical utility of this test is unclear. OBJECTIVES: To describe the clinical utility of GFR estimation in dogs. ANIMALS: Medical records of 132 dogs that had serum iohexol clearance measured between 2012 and 2017. METHODS: Iohexol clearance and clinical records were reviewed and submitting practices contacted to obtain outcome data. Dogs were classified into 4 groups based on the reason for performing GFR estimation: A1 (screening for pre-azotemic chronic kidney disease [CKD], n = 105), A2 (confirmation of azotemic CKD, n = 3), B (screening for pre-azotemic acute kidney injury, n = 19), and C (miscellaneous causes, n = 5). Descriptive review of the clinical utility of GFR estimation is provided. RESULTS: For dogs in Group A1, renal disease was diagnosed in 9/9 dogs with a GFR ≥40% decreased below the mean GFR of their body weight category, in 5/6 dogs with a ≥30% but <40% reduction in GFR and in 7/9 dogs with a ≥20% but <30% reduction in GFR. CONCLUSIONS AND CLINICAL IMPORTANCE: Glomerular filtration rate estimation is useful for the diagnosis of CKD before the onset of azotemia.

Relationship between serum iohexol clearance, serum SDMA concentration, and serum creatinine concentration in non-azotemic dogs.

BACKGROUND: Serum creatinine and symmetric dimethylarginine (SDMA) are used as surrogate markers of glomerular filtration rate (GFR) in clinical practice. Data pertaining to the correlations between GFR, SDMA, and serum creatinine in client-owned dogs are limited. OBJECTIVES: To describe the relationship between GFR, SDMA, and serum creatinine in a population of client-owned dogs, and to compare clinical utility of SDMA to GFR estimation for detecting pre-azotemic chronic kidney disease. ANIMALS: Medical records of 119 dogs that had GFR estimation performed via serum iohexol clearance between 2012 and 2017. METHODS: Prospective study using archived samples. GFR, SDMA, and serum creatinine results were reviewed and submitting practices contacted for outcome data. All dogs included in the study population were non-azotemic. Correlations between GFR, SDMA, and serum creatinine were determined by regression analysis. Sensitivity, specificity, and positive and negative likelihood ratios of different cutoffs for SDMA and serum creatinine for detecting decreased GFR were calculated, using a 95% confidence interval. RESULTS: Serum creatinine and SDMA were moderately correlated with GFR (R2 = 0.52 and 0.27, respectively, P < .0001) and with each other (R2 = 0.33, P < .0001). SDMA >14 µg/dL was sensitive (90%) but nonspecific (50%) for detecting a ≥40% decrease in GFR. Optimal SDMA concentration cutoff for detecting a ≥40% GFR decrease was >18 µg/dL (sensitivity 90%, specificity 83%). CONCLUSIONS AND CLINICAL IMPORTANCE: In non-azotemic dogs being screened for decreased renal function, using a cutoff of >18 µg/dL rather than >14 µg/dL increases the specificity of SDMA, without compromising sensitivity.

Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats. OBJECTIVES: To examine the relationship between plasma FGF23 and SDMA concentrations in non-azotemic geriatric cats. ANIMALS: Records of a cross section of client-owned cats (n = 143) without azotemic CKD. METHODS: Clinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and FGF23 concentrations was examined using Spearman's correlation and variables compared using the Mann-Whitney U test. RESULTS: Cats with increased SDMA concentrations had significantly higher plasma FGF23 (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma FGF23 and SDMA concentrations (r = .35, P < .001) and between plasma FGF23 and creatinine (r = .23, P = .005) concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: More cats with increased SDMA concentrations had higher FGF23 concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of FGF23 concentration to inform management of cats with early stage CKD.