Symmetric dimethylarginine correlates with the urea, creatinine, potassium, and clinical scores in feline urethral obstructions.

BACKGROUND: A urethral obstruction (UO) is an emergency commonly observed in male cats, which can result in significant clinical and laboratory alterations, leading to complications and death. OBJECTIVES: This study aimed to correlate symmetric dimethylarginine (SDMA) with the urea, creatinine, potassium, and bicarbonate levels in cats with UO. In addition, the correlation between clinical score and time of obstruction was evaluated. METHODS: Thirty male cats were selected and allocated into a control group (CG, n = 13) and an obstruction group (OG, n = 17). The laboratory analyses were conducted before treatment (M0) and at different times after treatment (12 h [M12], 24 h [M24], and 48 h [M48]). Correlations were established between SDMA and creatinine, urea, bicarbonate, potassium, time of obstruction, and the clinical score. RESULTS: A strong correlation (r > 0.6) was observed between SDMA and creatinine, urea, and potassium in the OG. Furthermore, there was substantial agreement (kappa value) between SDMA and creatinine at M24. A higher clinical score was associated with a longer time of obstruction. In the OG, at M48, the SDMA and creatinine levels were 50% and 41.2% higher, respectively. CONCLUSIONS: A correlation was observed between SDMA and creatinine in obstructed cats, and significant agreement between these values was observed 24 h after the unblocking treatment. A correlation among SDMA, urea, and potassium was observed. Approximately 9% more cats continued to have elevated SDMA levels after 48 h of treatment compared to creatinine. This suggests a slightly lower sensitivity of the latter biomarker but does not exclude the possibility of congruent and normalized values after a longer evaluation period.

2024 ISFM and AAFP consensus guidelines on the long-term use of NSAIDs in cats.

PRACTICAL RELEVANCE: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and are effective for the management of pain in cats. These Guidelines will support veterinarians in decision-making around prescribing NSAIDs in situations of chronic pain, to minimise adverse effects and optimise pain management. Information is provided on mechanism of action, indications for use, screening prior to prescription, use in the presence of comorbidities, monitoring of efficacy, and avoidance and management of adverse effects. CLINICAL CHALLENGES: The cat's unique metabolism should be considered when prescribing any medications, including NSAIDs. Chronic pain may be challenging to detect in this species and comorbidities, particularly chronic kidney disease, are common in senior cats. Management of chronic pain may be complicated by prescription of other drugs with the potential for interactions with NSAIDs. EVIDENCE BASE: These Guidelines have been created by a panel of experts brought together by the International Society of Feline Medicine (ISFM) and American Association of Feline Practitioners (AAFP). Information is based on the available literature, expert opinion and the panel members' experience.

Fibroblast growth factor-23 and Alpha-Klotho concentrations in dogs with canine Leishmaniasis.

This study aimed to assess the concentrations of Fibroblast Growth Factor-23 (FGF-23) and α-Klotho in healthy dogs and dogs at different stages of Canine Leishmaniasis (CanL), and investigate the changes of these parameters in relation to renal function and calcium­phosphorus metabolism. A total of 74 dogs (22 healthy and 52 with CanL) of varying ages, sexes, and medium-sized breeds were included. Dogs with CanL were categorized into different stages (Stage I-IV) based on Leishvet recommendations. In addition to routine hematological parameters, plasma FGF-23, serum α-Klotho, urea, creatinine, phosphorus, calcium, parathormone, vitamin D concentrations, and urine protein/creatinine ratio were measured. Data from healthy dogs were compared to dogs with CanL overall and by stage. Dogs with CanL exhibited higher concentrations of FGF-23 (p < 0.05), α-Klotho, and parathormone (p < 0.001), as well as lower concentrations of vitamin D and calcium (p < 0.001). FGF-23 concentration was particularly elevated in Stage IV compared to other stages. However, no significant differences in α-Klotho levels were observed among the stages. FGF-23 levels showed a weak positive correlation with urea and creatinine concentrations and a moderate positive correlation with urine protein/creatinine ratio. This study demonstrated increased levels of FGF-23 and α-Klotho in dogs with CanL for the first time. The increase in FGF-23 levels was more prominent in advanced stages of the disease and correlated with higher urea and creatinine concentrations. These findings may serve as a basis for future diagnostic and therapeutic investigations, contributing to the understanding of the pathophysiology of kidney disease in CanL.

Ionized hypercalcemia can resolve with nutritional modification in cats with idiopathic hypercalcemia or chronic kidney disease.

CASE SERIES SUMMARY: Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than 1.4:1 or both, based on diet history, were included in this case series. Ionized hypercalcemia was documented at least twice in all cats before enrollment. Cats were referred for evaluation of ionized hypercalcemia (n = 5) or were incidentally found to have ionized hypercalcemia (n = 5). After medical workups, cats were diagnosed with either idiopathic hypercalcemia (IHC; n = 7) or chronic kidney disease (n = 3). Cats receiving medications to treat IHC (eg, alendronate, corticosteroids) were excluded. Nutritional recommendations were made to transition the cats to diets with less thn 200 mg calcium per 100 kcal and a Ca:P ratio less than 1.4:1. Ionized calcium (iCa) concentrations were rechecked in all cats, with a median recheck time of 9 weeks (range 3-20). Of the 10 cats, nine (90%) had a decrease in iCa. Of the 10 cats, six (60%) became normocalcemic after the diet change, three (30%) had a partial response and one (10%) did not respond. Of the four cats that did not achieve normocalcemia with a change in diet, two (50%) received chia seeds (1-2 g per day), and at the next recheck, both cats' iCa concentrations had normalized. Three cats had a long-term follow-up. Ionized normocalcemia was maintained for at least two consecutive follow-up visits over a median follow-up period of 33 weeks (range 12-34). RELEVANCE AND NOVEL INFORMATION: Dietary calcium concentrations and the dietary Ca:P ratio appear to be important variables in considering nutritional approaches for hypercalcemic cats.

Correlation between urine anion gap and urine ammonia-creatinine ratio in healthy cats and cats with kidney disease.

BACKGROUND: Ammonium excretion decreases as kidney function decreases in several species, including cats, and may have predictive or prognostic value in patients with chronic kidney disease (CKD). Urine ammonia measurement is not readily available in clinical practice, and urine anion gap (UAG) has been proposed as a surrogate test. OBJECTIVES: Evaluate the correlation between urine ammonia-to-creatinine ratio (UACR) and UAG in healthy cats and those with CKD and determine if a significant difference exists between UAG of healthy cats and cats with CKD. ANIMALS: Urine samples collected from healthy client-owned cats (n = 59) and those with stable CKD (n = 17). METHODS: Urine electrolyte concentrations were measured using a commercial chemistry analyzer and UAG was calculated as ([sodium] + [potassium]) - [chloride]. Urine ammonia and creatinine concentrations had been measured previously using commercially available enzymatic assays and used to calculate UACR. Spearman's rank correlation coefficient between UAG and UACR was calculated for both groups. The UAG values of healthy cats and cats with CKD were assessed using the Mann-Whitney test (P < .05). RESULTS: The UAG was inversely correlated with UACR in healthy cats (P < .002, r0 = -0.40) but not in cats with CKD (P = .55; r0 = -0.15). A significant difference was found between UAG in healthy cats and those with CKD (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The UAG calculation cannot be used as a substitute for UACR in cats. The clinical relevance of UAG differences between healthy cats and those with CKD remains unknown.

A comprehensive analysis of albuminuria in canine chronic kidney disease.

BACKGROUND: Albuminuria, an important marker of decreased kidney function in chronic kidney disease (CKD), is not routinely used for CKD detection or proteinuria appearance. Its relationships with biochemical parameters and blood pressure in dogs are poorly understood. OBJECTIVES: This study aimed to evaluate the relationship of albuminuria with various CKD markers, its correlation with the urinary protein to creatinine ratio (UPC), and hypertension in dogs with early stages of CKD. It also sought to determine the usability of the urinary albumin to creatinine ratio (UAC) for CKD screening. METHODS: The study reviewed records of 102 dogs, categorising them into four groups based on disease status. UAC and UPC ratio, biochemistry and haematology variables, age, and systolic blood pressure were determined. RESULTS: The Pearson's correlation coefficient between log-transformed values of UPC and UAC was r = 0.902 (95% CI: 0.87 to 0.93). Median UAC ratio values were 2.1 mg/g for the Healthy control group (n = 17), 54.2 mg/g for early stages CKD (n = 42), 5.8 mg/g for Acute sick control (n = 30), and 104 mg/g for Chronic sick control (n = 13). Thresholding UAC ratio as an indicator for impaired kidney function with the threshold of 10 mg/g (established based on the receiver operating characteristic curve) had a sensitivity 81.8%, specificity of 89.4%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 80.1%. The correlation of UAC with biochemistry and haematology variables was statistically significant; for SDMA (µg/L), it was r = 0.566 and for other variables, it was weak to moderate. UAC was markedly elevated in cases of severe hypertension. CONCLUSIONS: UAC ratio was significantly different among dogs with impaired and not impaired kidney function. The correlation strength for the UAC and UPC ratios was high. UAC ratio may be a promising marker for proteinuria analysis in dogs with CKD or other kidney function alterations.

Untargeted metabolomic profiling of serum from client-owned cats with early and late-stage chronic kidney disease.

Evaluation of the metabolome could discover novel biomarkers of disease. To date, characterization of the serum metabolome of client-owned cats with chronic kidney disease (CKD), which shares numerous pathophysiological similarities to human CKD, has not been reported. CKD is a leading cause of feline morbidity and mortality, which can be lessened with early detection and appropriate treatment. Consequently, there is an urgent need for early-CKD biomarkers. The goal of this cross-sectional, prospective study was to characterize the global, non-targeted serum metabolome of cats with early versus late-stage CKD compared to healthy cats. Analysis revealed distinct separation of the serum metabolome between healthy cats, early-stage and late-stage CKD. Differentially abundant lipid and amino acid metabolites were the primary contributors to these differences and included metabolites central to the metabolism of fatty acids, essential amino acids and uremic toxins. Correlation of multiple lipid and amino acid metabolites with clinical metadata important to CKD monitoring and patient treatment (e.g. creatinine, muscle condition score) further illustrates the relevance of exploring these metabolite classes further for their capacity to serve as biomarkers of early CKD detection in both feline and human populations.

Occurrence of cardiovascular events in 168 cats with acute urinary tract obstruction.

Background: Cardiovascular dysfunction associated with acute kidney injury has been recently described in veterinary medicine, but limited information is available for cats with urinary tract obstruction (UTO). Objective: This retrospective study aimed to describe the type, frequency, timeline, and risk factors for cardiovascular events (CVEs) in cats treated for acute UTO. Animals and procedures: Medical records of cats admitted to the intensive care unit for either upper (ureteral: UUTO) or lower (urethral: LUTO) UTO from 2016 to 2021 were reviewed. Cardiovascular events were defined as development of arrhythmia, heart murmur or gallop sound, clinical signs consistent with fluid overload (CRFO), or decreased tissue perfusion (DTP). Results: One hundred and sixty-eight cats with UTO were recruited (56 with UUTO and 112 with LUTO). Cardiovascular events were reported in 61.9% of cases, including arrhythmia (33.6%), gallop rhythm (28.1%), heart murmur (15.3%), CRFO (14.4%), and DTP (8.6%). Potassium concentration, preexisting chronic kidney disease, and renal pelvic dilation at abdominal ultrasonography were associated with CVE occurrence in multivariate analysis. Conclusions: This study highlighted frequent CVEs in cats treated for UTO, with a potential strong impact on outcome. Therefore, cardiovascular parameters of cats with preexisting chronic kidney disease or those admitted with hyperkalemia or renal pelvic dilation should be closely monitored.

Survenue d'anomalies cardio-vasculaires chez 168 chats présentés pour obstruction du tractus urinaire. Contexte: Si des anomalies cardiovasculaires secondaires à une insuffisance rénale aigue ont été décrites récemment en médecine vétérinaire, ces données restent limitées concernant les obstructions du tractus urinaire (OTU) chez le chat. Objectif: Décrire le type, la fréquence, le délai d'apparition et les facteurs de risques d'anomalies cardio-vasculaires (ACV) chez des chats hospitalisés pour OTU aigue. Animaux et protocoles: Les dossiers médicaux des chats admis en unité de soins intensifs pour obstruction du tractus urinaire haut ( urétérales-OTUH) et bas (urétrales-OTUB) entre 2016 et 2021 ont été consultés. Les ACV retenus étaient des arythmies cardiaques, le développement de souffles cardiaques et de bruits de galop, les signes relatifs à une surcharge en fluide (SRSF) et de diminution de la perfusion tissulaire (SDPT). Résultats: Cent soixante-huit chats avec des OTU ont été recrutés (56 OTUH, 112 OTUB). Des ACV ont été observés dans 61,9 % des cas, incluant des arythmies (33,6 %), l'apparition de bruits de galop (28,1 %) et de souffles cardiaques (15,3 %), des SRSF (14,4 %) et des SDPT (8,6 %). La concentration plasmatique en potassium, la présence d'une MRC sous-jacente et d'une dilatation pyélique à l'échographie abdominale ont été associées à la présence d'ACV par l'analyse multivariée. Conclusions: Cette étude montre que les ACV surviennent fréquemment chez les chats présentés pour OTU, et suggère un impact sur la survie de ces animaux. Les animaux avec un historique de MRC, ceux présentés avec une hyperkaliémie et/ou avec une dilatation pyélique à l'échographie abdominale devraient être surveillés avec plus de précautions que les autres.(Traduit per les auteurs).

Serum symmetric dimethylarginine in older dogs: Reference interval and comparison of a gold standard method with the ELISA.

BACKGROUND: Serum symmetric dimethylarginine (SDMA) is used to screen for renal dysfunction in dogs. The gold standard technique for measuring SDMA, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is not widely available. Age-specific reference intervals for SDMA in older dogs are lacking. OBJECTIVES: Prospective study in older dogs to validate a commercially available LC-MS/MS method for SDMA, compare SDMA concentrations with concentrations measured using ELISA and obtain a reference interval (RI) for older dogs using both methods. ANIMALS: Client-owned older dogs undergoing health screening. METHODS: The LC-MS/MS method was analytically validated (limit of detection, precision, and linearity). Serum was sent cooled overnight for ELISA or was frozen at -80°C until batch analysis using LC-MS/MS. Results of LC-MS/MS and ELISA were compared and RIs for older dogs were calculated according to international guidelines. RESULTS: The LC-MS/MS method showed good linearity (r2 = .99) and precision (coefficient of variation <10%), with a laboratory RI between 8.0 and 14.0 µg/dL. Paired measurements were available from 118 different dogs. Median SDMA concentration were 9.4 (range, 5.0-21.2) using LC-MS/MS and 12.0 (range, 5.0-22.0) µg/dL using ELISA. Both methods significantly differed with a mean difference of 2.2 µg/dL. The RI for older dogs for LC-MS/MS was 4.4-15.0 µg/dL, and for ELISA was 6.4-17.4 µg/dL. CONCLUSIONS AND CLINICAL IMPORTANCE: The ELISA provided significantly higher SDMA concentrations compared to the validated LC-MS/MS method, indicating the need for device- or assay-specific RI. The obtained age-specific RI for SDMA is considerably higher in older dogs compared to the general laboratory RI.

Use of molidustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, in chronic kidney disease-associated anemia in cats.

BACKGROUND: Erythropoietic effects of molidustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, were previously demonstrated in healthy cats. OBJECTIVE: To evaluate the safety and erythropoietic effects of daily PO administration of molidustat in anemic cats with chronic kidney disease (CKD). ANIMALS: Twenty-one client-owned CKD cats (4-17 years old) with anemia. METHODS: Multicenter field study; randomized, masked, and placebo-controlled. Cats were treated PO once daily for 28 days with suspensions of control product (CP; n = 6) or 5 mg/kg of molidustat (n = 15). Hematocrit (HCT) was evaluated at weekly intervals. Individual cat treatment success was defined as a ≥4% point increase in HCT compared to baseline. RESULTS: Control group mean HCT remained low throughout the study (20.1%-23.4%). Mean HCT of molidustat-treated cats increased weekly, and a significant increase compared to baseline (23.6%) was first observed on Day 21 (27.3%; P < .001; 95% confidence interval [CI], 1.69-5.67). Compared to CP group, mean HCT was significantly higher on Day 21 (27.3% vs 20.1%; P < .001; 95% CI, 2.91-10.75) but not significantly higher on Day 28 (27.8% vs 23.4%; P = .06; 95% CI, -0.23 to 9.88). The number of individual treatment successes on Day 28 was higher among remaining molidustat-treated cats (7/14) compared to remaining control cats (1/5), but there was no significant difference between groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Daily PO molidustat administration may stimulate a clinically relevant erythropoietic response in anemic cats with CKD. This HIF-PH inhibitor may be an alternative for managing anemia in cats compared to recombinant EPO treatment.

MicroRNA-126 in dogs with immune complex-mediated glomerulonephritis.

BACKGROUND: Most proteinuric dogs with naturally occurring chronic kidney disease have amyloidosis (AMYL), glomerulosclerosis (GS), or immune complex-mediated glomerulonephritis (ICGN), each with different treatment and prognosis. A noninvasive and disease-specific biomarker is lacking. HYPOTHESIS: We hypothesized that the expression pattern of biofluid microRNA (miRNAs and miRs) would correlate with disease progression and categorization. ANIMALS: Archived serum and urine samples from 18 dogs with glomerular disease and 6 clinically healthy dogs; archived urine samples from 49 dogs with glomerular disease and 13 clinically healthy dogs. METHODS: Retrospective study. Archived biofluid samples from adult dogs with biopsy-confirmed glomerular disease submitted to the International Veterinary Renal Pathology Service between 2008 and 2016 were selected. Serum and urinary miRNAs were isolated and profiled using RNA sequencing. Urinary miR-126, miR-21, miR-182, and miR-486 were quantified using quantitative reverse transcription PCR. RESULTS: When comparing more advanced disease with earlier disease, no serum miRNAs were differentially expressed, but urinary miR-21 and miR-182 were 1.63 (95% CI: .86-3.1) and 1.45 (95% CI: .82-2.6) times higher in azotemic dogs, respectively (adjusted P < .05) and weakly correlated with tubulointerstitial fibrosis (miR-21: r = .32, P = .03; miR-182: r = .28, P = .05). Expression of urinary miR-126 was 10.5 (95% CI: 4.1-26.7), 28.9 (95% CI: 10.5-79.8), and 126.2 (95% CI: 44.7-356.3) times higher in dogs with ICGN compared with dogs with GS, AMYL, and healthy controls, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The miR-126 could help identify dogs that might benefit from immunosuppressive therapy in the absence of a biopsy. MiR-21 and miR-182 are potential markers of disease severity and fibrosis.

Decreased circulating transforming growth factor-beta (TGF-ß) and kidney TGF-ß immunoreactivity predict renal disease in cats with naturally occurring chronic kidney disease.

OBJECTIVES: The aim of the present study was to compare the circulating transforming growth factor-beta (TGF-ß) of clinically normal age-matched and naturally occurring chronic kidney disease (CKD) cats and to determine the correlation between the TGF-ß expression and histopathological changes in cats with CKD. METHODS: A total of 11 clinically normal age-matched and 27 cats with naturally occurring CKD were included in this study. Circulating TGF-ß was quantified by immunoassays. Kaplan-Meier analysis was used to calculate the association between survival time and the concentration of circulating TGF-ß. A general linear model was used to compare the circulating TGF-ß between groups. Immunohistochemical analyses revealed TGF-ß expression in renal tissues from cats with CKD that died during the study (n = 7) and in available archived renal tissue specimens taken at necropsy from cats that had previous CKD with renal lesions (n = 10). Correlations of the TGF-ß expression and clinical parameters (n = 7) and histopathological changes (n = 17) were analysed using Spearman's rank correlation. RESULTS: The median survival time of cats with a lower concentration of circulating TGF-ß was shorter than that of cats with a higher concentration. The area under the curve of circulating TGF-ß for predicting CKD was 0.781, indicating good differentiation. The study indicated a significant difference in circulating TGF-ß concentrations between clinically normal cats and those with CKD and demonstrated that TGF-ß expression is correlated with tubular atrophy. CONCLUSIONS AND RELEVANCE: The study findings suggest that decreased serum TGF-ß and tubular atrophy with TGF-ß immunoreactivity may be significant in cats with CKD.

Clinical management of feline chronic kidney disease in Portugal: a questionnaire-based study.

OBJECTIVES: The aim of the study was to characterise the clinical management of feline chronic kidney disease (CKD) by veterinary practitioners in Portugal. METHODS: A questionnaire-based study was designed to be completed by all veterinarians who had diagnosed and treated at least one case of feline CKD in the previous year. RESULTS: A total of 409 veterinary practitioners responded to the questionnaire, with approximately half of them diagnosing 2-5 cases of feline CKD per month (n = 219, 53.5%). Although a high proportion of these reported using the guidelines published by the International Renal Interest Society (n = 379, 92.7%), only 19.1% (n = 78) systematically performed systolic blood pressure (SBP) measurements in all of their patients. A renal diet was advised by almost all respondents (n = 406, 99.3%), but 36.9% (n = 150) of them considered that it represented less than 75% of the daily food intake for most of their patients. This dietary intervention was often prescribed regardless of stage (n = 298, 73.4%) and without a proper gradual diet transition. Appetite stimulants were frequently prescribed (n = 366, 89.5%), as well as a calcium channel blocker (n = 171, 41.8%) and an angiotensin-converting enzyme inhibitor (n = 245, 59.9%) to control systemic hypertension and proteinuria, respectively. Prescription of a phosphate binder was also common (n = 311, 76.0%). Regarding monitoring, 70.9% (n = 290) recommended that stable patients be reassessed every 2-3 months or more frequently, but only 35.7% (n = 146) were able to comply with this periodicity due to owners' constraints. CONCLUSIONS AND RELEVANCE: The findings showed that although most survey respondents are aware of international guidelines for the clinical management of cats with CKD, the SBP measurement still needs to be more systematic to allow proper substaging and detection of systemic hypertension. The monitoring frequency was lower than recommended. Furthermore, the introduction of a renal therapeutic diet should be refined to improve its acceptance rate.

Determination of age-specific reference intervals for selected serum and urinary biomarkers in elderly cats.

OBJECTIVES: Annual health screening is recommended in elderly cats to allow the early detection of conditions such as chronic kidney disease (CKD) and hyperthyroidism. Nevertheless, age-specific reference intervals (RIs) for renal and thyroid parameters in this population are lacking. The aim of this study was to determine age-specific RIs for selected serum and urine biomarkers related to CKD and hyperthyroidism, namely serum creatinine (sCr), symmetric dimethylarginine (SDMA), phosphate (P), total calcium (tCa), total thyroxine (TT4), urinary protein:creatinine ratio (UPC) and urine specific gravity (USG). These RIs were established for elderly cats (aged ⩾7 years) in general, as well as for mature adult cats (aged 7-10 years) and senior cats (aged >10 years) separately. METHODS: A prospective study was conducted on client-owned cats aged ⩾7 years and considered healthy by their owners. The cats were screened to rule out metabolic and systemic diseases by means of a thorough history, complete physical examination, blood examination and urinalysis. The data from 206 healthy elderly cats (134 mature adult and 72 senior cats) were included. Age-appropriate RIs were determined following the guidelines of the American Society of Veterinary Clinical Pathology and compared with existing laboratory RIs. RESULTS: Clinically relevant differences between the age-specific RI and the laboratory RI were found for several variables. Compared with the laboratory RI, the upper limit of the RI for cats aged ⩾7 years was lower for sCr, TT4 and P, and higher for SDMA. The lower limit of the age-appropriate RI was lower for USG. The new RI was almost identical to the existing laboratory RI for tCa and UPC. CONCLUSIONS AND RELEVANCE: Using age-specific RIs for renal and thyroid biomarkers in mature adult and senior cats has important clinical consequences for the interpretation of health screening results in elderly cats. This confirms the need to adapt laboratory RIs to the specific animal population for which the RI will be used.

Diagnostic assessment of two-dimensional shear wave elastography in relation to dimethyl arginine levels in dogs with chronic kidney disease.

BACKGROUND: In veterinary medicine, previous studies regarding the diagnostic performance of shear wave elastography (SWE) in chronic kidney disease (CKD) are not consistent with each other. Moreover, there has been no study evaluating the relationship between symmetric dimethyl arginine (SDMA) concentration and renal shear wave velocity (SWV) using two-dimensional SWE (2D SWE) in dogs with CKD. OBJECTIVES: This study aimed to evaluate the diagnostic capability of 2D SWE in dogs with CKD and to assess the relationship between renal SWV and SDMA concentration. METHODS: Dogs with healthy kidneys and dogs with CKD underwent 2D SWE and SDMA assay. Renal stiffness was estimated as renal SWV in m/s. RESULTS: SDMA concentration had a weak positive correlation with the left (r = 0.338, p = 0.022) and right renal SWV (r = 0.337, p = 0.044). Renal SWV was not significantly different between healthy kidney and CKD groups in the left (p = 0.085) and right (p = 0.171) kidneys. CONCLUSIONS: 2D SWE may could not distinguish between dogs with healthy kidney and dogs with early stage of CKD, but it would be useful for assessing the serial change of renal function in dogs.

Differentiation of stable kidney function versus progressive dysfunction in dogs.

BACKGROUND: Circulating creatinine and symmetric dimethylarginine (SDMA) are biomarkers of kidney function that have been used variously to define stable vs progressive chronic kidney disease (CKD). Slope monitoring of inverse biomarker values (creatinine-1 or SDMA-1 ) has shown promise, but quantitative criteria to distinguish stable vs progressive CKD using this approach are lacking. OBJECTIVE: Assessment of creatinine-1 and SDMA-1 slope cutoffs to distinguish stable vs progressive CKD. ANIMALS: One hundred ten clinically healthy university staff-owned dogs and 29 male colony dogs with progressive X-linked hereditary nephropathy (XLHN). METHODS: Retrospective analysis combining 2 prospective observational studies, 1 tracking kidney function biomarkers in healthy dogs (HDs) to a maximum of 3 years, and 1 tracking kidney function biomarkers in male colony dogs with progressive XLHN to a maximum of 1 year. The minimum slope of creatinine-1 or SDMA-1 as measured using the IDEXX SDMA test from HD was assigned as the slope cutoff for stable kidney function. RESULTS: The stable vs progressive slope cutoff was -0.0119 week × dL/mg for creatinine-1 and -0.0007 week × dL/µg for SDMA-1 . CONCLUSIONS AND CLINICAL IMPORTANCE: In the studied CKD population, progressive dysfunction can be distinguished from stable kidney function by using the slope of creatinine-1 or SDMA-1 . These criteria may serve to characterize CKD in other cohorts of dogs and to establish guidelines for degrees of progression rate in dogs with naturally occurring CKD.

Feline Morbillivirus: Clinical Relevance of a Widespread Endemic Viral Infection of Cats.

Feline morbillivirus (FeMV) was first isolated in 2012 from stray cats in Hong Kong. It has been found in association with tubulointerstitial nephritis (TIN), the most common cause of feline chronic kidney disease (CKD). However, viral host spectrum and virus tropism go beyond the domestic cat and kidney tissues. The viral genetic diversity of FeMV is extensive, but it is not known if this is clinically relevant. Urine and kidney tissues have been widely tested in attempts to confirm associations between FeMV infection and renal disease, but samples from both healthy and sick cats can test positive and some cross-sectional studies have not found associations between FeMV infection and CKD. There is also evidence for acute kidney injury following infection with FeMV. The results of prevalence studies differ greatly depending on the population tested and methodologies used for detection, but worldwide distribution of FeMV has been shown. Experimental studies have confirmed previous field observations that higher viral loads are present in the urine compared to other tissues, and renal TIN lesions associated with FeMV antigen have been demonstrated, alongside virus lymphotropism and viraemia-associated lymphopenia. Longitudinal field studies have revealed persistent viral shedding in urine, although infection can be cleared spontaneously.

Gastric pH and serum gastrin concentration in age-matched healthy dogs and dogs with chronic kidney disease.

BACKGROUND: Gastric hyperacidity and hypergastrinemia are purported to cause gastric ulceration in dogs with chronic kidney disease (CKD); however, no published studies have evaluated gastric pH with serum gastrin concentrations in dogs with CKD. HYPOTHESIS: To compare mean intragastric pH, mean percent pH distribution, and serum gastrin concentrations in dogs with CKD to age-matched, healthy dogs. We hypothesized there would be no difference in mean gastric pH or serum gastrin between groups. ANIMALS: Thirteen dogs with CKD; 10 aged-matched healthy dogs. METHODS: Prospective, case-control study. Serum chemistry, complete blood count, urinalysis, and serum gastrin concentrations were evaluated in all dogs before radiographic-assisted gastric placement of a pH capsule. Forty-eight-hour continuous gastric pH monitoring was performed in all dogs. Serum gastrin concentration, mean pH, and mean percentage time that gastric pH was strongly acidic (pH <1 and pH <2) were compared between groups using a repeated measures mixed-model ANOVA. RESULTS: No significant differences were observed between groups for any pH measurements, including mean ± SD gastric pH (CKD, 2.37 ± 0.87; healthy, 2.39 ± 0.99; P > .05). Serum gastrin concentrations were not significantly different between groups (median [range]: CKD, 10.5 ng/dL [<10-17.1]; healthy, 10.9 ng/dL [<10-15]; P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Our client-owned dogs with CKD did not have lower gastric pH or higher serum gastrin concentrations compared to healthy dogs. Our results suggest that prophylactic gastric acid suppression in dogs with CKD is not warranted unless other clinical indications for use are present.

Immunohistochemical analysis of renal oxidative damage in senior and geriatric cats with chronic kidney disease.

Oxidative stress is a well-known cause of chronic kidney disease (CKD). In this study, renal oxidative damage in azotaemic and non-azotaemic aged cats with naturally occurring CKD was investigated using immunohistochemistry for 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) as markers of oxidative tissue damage. Kidneys were obtained from aged (>10 years old) azotaemic (n = 13) and non-azotaemic (n = 7) cats. Immunoreactivity for 8-OHdG was found in the nuclei of glomeruli, proximal and distal tubules, loops of Henle and collecting ducts, whereas 4-HNE-positive signals were detected in the cytoplasm of distal nephrons in azotaemic and non-azotaemic cats. Quantitative analysis did not identify any significant differences between the azotaemic and non-azotaemic groups for any of the parameters examined. These results indicate that renal oxidative damage occurs in the kidneys of aged cats with CKD, regardless of whether they are azotaemic or non-azotaemic, emphasizing the importance of oxidative stress during early-stage CKD in senior and geriatric cats.

Adeno-associated virus-vectored erythropoietin gene therapy for anemia in cats with chronic kidney disease.

BACKGROUND: A treatment of chronic kidney disease (CKD)-associated anemia in cats is needed. SB-001 is an adeno-associated virus-vectored (AAV)-based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. HYPOTHESIS/OBJECTIVE: We hypothesized that SB-001 injection would lead to a sustained increase in PCV in cats with CKD-associated anemia. ANIMALS: Twenty-three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD-associated anemia were enrolled at 4 veterinary clinics. METHODS: In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB-001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. RESULTS: A response to SB-001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P < .003) increase in PCV from Day 0 to Day 28 (mean increase 6 ± 6 percentage points [pp]; n = 21), Day 42 (8 ± 9 pp; n = 21), Day 56 (10 ± 11 pp; n = 17), and Day 70 (13 ± 14 pp, n = 14). Twelve cats were hypertensive at baseline, 4 of which developed encephalopathy during the study. An additional 6 cats became hypertensive during the study. CONCLUSIONS AND CLINICAL IMPORTANCE: Results of this study suggest that SB-001 therapy represents a suitable single injection treatment that can address nonregenerative anemia in cats with CKD. It was generally well tolerated; however, hypertension and encephalopathy developed in some cats as previously described in association with erythropoiesis-stimulating agent therapy.