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.

Betaine and Soluble Fiber Improve Body Composition and Plasma Metabolites in Cats with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in cats and cachexia (loss of lean body mass) is a concern. A nutrition-based intervention was investigated in cats with CKD for its effects on body composition, the plasma metabolome, and possible implications on health. METHODS: After a 4-week prefeed period with the control food, cats with CKD (N = 24) were randomized to one of six groups to consume a control food; a food supplemented with 0.5% betaine, 0.39% oat beta-glucan, and 0.27% short-chain fructooligosaccharides (scFOS, test food 1); and a food supplemented with 0.5% betaine, 0.59% oat beta-glucan, and 0.41% scFOS (test food 2) in a William's Latin Square design, each for 10 weeks. Body composition was assessed via dual-energy X-ray absorptiometry measurements, and the plasma metabolome was characterized. RESULTS: Despite no significant differences in daily intake among the three foods, significant increases in total body mass, lean body mass, and lean plus bone mineral composition were observed when cats with CKD consumed test food 1 compared with the control food; numerical increases were seen with test food 2 versus the control food. Plasma metabolomics indicated increased one-carbon metabolism following consumption of test food 1 and/or 2, with significant increases in sarcosine and numerical increases in methionine. Lower levels of plasma trans-4-hydroxyproline and N-methylproline following consumption of test foods 1 and 2 indicates reduced collagen breakdown and perhaps reduced fibrosis. Several acylcarnitines and branched-chain fatty acids associated with CKD were also reduced when cats ate test food 1 or 2 versus the control food. Higher plasma levels of sphingomyelins with consumption of test food 1 or 2 may reflect less severe CKD. CONCLUSIONS: Consumption of foods with supplemental betaine and fibers by cats with CKD led to improvements in body composition and changes in the plasma metabolome that correspond to better kidney health.

Body Composition of Healthy Cats and Cats with Chronic Kidney Disease Fed on a Dry Diet Low in Phosphorus with Maintenance Protein.

The aim was to evaluate the effect of feeding a low-phosphorus and maintenance protein diet in healthy cats and cats with chronic kidney disease (CKD) with IRIS stages 1 (CKD-1) and 2 (CKD-2). Cats were initially fed a senior diet (30 days) followed by the renal diet (60 days). Body composition, body weight (BW), muscle mass score (MMS), and body condition score (BCS) were assessed before (T30) and after renal diet intake (T60). General mixed linear models were used to assess the effects of fixed groups and moments (T30 × T60), as well as their interaction, in addition to the random effects of animals within each group. Unlike healthy cats and cats with CKD-1, cats with CKD-2 had a loss of BW, lower BCS (p < 0.005), and lower MMS (p = 0.0008) after 60 days of consuming the renal diet. The fat mass and lean body mass (LBM), determined by the deuterium isotopes method, did not change in all cats between T0 and T60. In healthy cats and cats with CKD-1, the renal diet resulted in maintenance of BW, BCS and MMS; but cats with CKD-2 presented lower BCS and did not reduce phosphatemia after consumption.

C-reactive protein concentrations are higher in dogs with stage IV chronic kidney disease treated with intermittent hemodialysis.

In chronic kidney disease dogs, the inflammatory process increases C-reactive protein concentrations. This study aimed to determine C-reactive protein serum concentrations in stage IV chronic kidney disease dogs treated with intermittent hemodialysis. A prospective cohort study was conducted with 23 dogs allocated into three groups: control group (CG, n = 7), intermittent hemodialysis group (IHG, n = 8) and clinical treatment group (CTG, n = 8), both comprised of stage IV chronic kidney disease dogs. One blood sample from CG (initial evaluation) and two samples from IHG and CTG (first- and last-moment) were obtained to determine C-reactive protein concentration, total leukocytes, platelets, erythrocytes, total plasma protein, serum albumin, urea, creatinine, and phosphorus. C-reactive protein was higher in IHG compared to CG in the first- and last-moments (p <0.001) and compared to CTG in the first-moment (p = 0.0406). C-reactive protein presented moderate positive correlation with leukocytes (r = 0.5479; p = 0.01), and moderate negative correlation with albumin (r = - 0.5974; p = 0.006) and red blood cells (r = - 0.5878, p = 0.01). A high correlation coefficient was observed in the tests' evaluation (CI = 0.59-0.78; r = 0.70; P<0.0001). In conclusion, both assays used in this study to measure C-reactive protein have provided safe and reliable quantification of the results. Additionally, despite IHG dogs presented an active inflammatory profile, intermittent hemodialysis has proven to be beneficial, leading to a clinical improvement in life quality of patients, and thus being recommended for stage IV CKD dogs when performed by trained professionals.

Effect of calcifediol supplementation on renin-angiotensin-aldosterone system mediators in dogs with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) leads to low serum concentrations of vitamin D metabolites. Thus, hypovitaminosis D associated with CKD might contribute to disease progression via increased concentration of renin angiotensin aldosterone system (RAAS) mediators. OBJECTIVES: To evaluate whether supplementation with calcifediol affects equilibrium concentrations of selected mediators of the RAAS. We hypothesized that vitamin D supplementation will decrease concentration of circulating RAAS mediators in dogs with CKD. ANIMALS: Six client-owned adult dogs with IRIS Stage 2 and 3 CKD. METHODS: Prospective study. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), RAAS mediators (angiotensin I/II/III/IV/1-5/1-7, and aldosterone), and surrogate angiotensin converting enzyme (ACE) activity (calculated by the ratio of angiotensin II to angiotensin I) were evaluated at baseline, after 3 months of calcifediol supplementation, and 2 months after discontinuing administration of supplement. RESULTS: All serum vitamin D metabolite concentrations increased significantly by month 3 (P < .001): 25(OH)D (median 250 ng/mL; range, 204-310), compared to baseline (median 43.2 ng/mL; range, 33.8-58.3 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 57.3-88.1 pg/mL) compared to baseline (median 35.2 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 68.4 ng/mL; range, 22.1-142.0 ng/mL) compared to baseline (median 14.4 ng/mL; range, 9.0-21.3 ng/mL). Calculated ACE activity was significantly lower at month 3 (median 0.5; range, 0.4-1.0) compared to baseline (median 0.7; range, 0.6-1.3; P = .01). There were no significant differences in any of the evaluated RAAS variables at any other time-point. CONCLUSIONS AND CLINICAL IMPORTANCE: Short-term calcifediol supplementation in this small group of CKD dogs appeared to decrease ACE activity.

Feeding cats with chronic kidney disease food supplemented with betaine and prebiotics increases total body mass and reduces uremic toxins.

Cats with chronic kidney disease (CKD) have a decreased ability to maintain body weight. As CKD advances, loss of body weight contributes to morbidity and mortality. The goal of this study was to evaluate the combined effects of feeding betaine and prebiotics on body weight of both CKD and healthy cats. The pre-trial food (control food) was a complete and balanced dry food designed to aid in the management of CKD. Test food was the control food supplemented with betaine (0.500%) and prebiotics: long-chain oat beta-glucan (0.586%) and 0.407% short chain fructooligosaccharides (scFOS). The CKD cats (n = 7) were fed pre-trial food for 28 days and then randomly assigned to control food or test food. Each food was fed for 8 weeks in a cross-over study design. In a second study, healthy cats received control food or test food for 8 weeks (n = 8 each group). Blood, urine, and fecal samples were collected to evaluate concentrations of relevant kidney function biomarkers and metabolites at the end of each feeding period for CKD cats, and blood samples were collected monthly to evaluate concentrations of plasma metabolites for healthy cats. Body weight and composition were measured using dual-energy X-ray absorptiometry (DEXA) scan at baseline and after each feeding period. Total body mass was significantly higher in CKD cats after consuming test food compared with control food (P = 0.004), with no significant difference in food intake while consuming test or control food (P = 0.34). Test food did not affect total body mass or composition of healthy cats. Indole compounds produced by bacterial metabolism were decreased in urine and increased in feces of CKD cats fed test food, and plasma concentrations were negatively correlated with the level of kidney function, indicating a potential benefit of consuming test food. In healthy cats, consuming test food resulted in significantly decreased concentrations of plasma P-cresol sulfate (P = 0.004) and increased concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA; both P < 0.05), despite the fact that both control and test foods had similar concentrations of these long-chain fatty acids, 0.03% and 0.02%, respectively. These results suggest that the addition of betaine and prebiotics to the control food formula may have increased total body mass in CKD cats by enhancing one-carbon metabolism and by modulating the gut microbiome.

Blood concentration of symmetric dimethylarginine correlates with kidney damage as assessed with a proposed histologic grading system for chronic kidney disease in tigers (Panthera tigris).

OBJECTIVE: To determine the utility of blood symmetric dimethylarginine (SDMA) concentration measurement as a diagnostic tool for chronic kidney disease (CKD) in tigers (Panthera tigris) by comparing results for SDMA with those for traditional renal biomarkers and investigating correlations between these biomarkers and histopathologic kidney changes in tigers with CKD. SAMPLE: Blood, urine, and kidney samples from 35 tigers with CKD from 2 sanctuaries. PROCEDURES: Blood (serum or plasma) and urine samples were collected antemortem. Necropsy, including gross and histologic assessment, was performed for tigers that died or were euthanized for quality-of-life reasons. Results for CKD biomarkers in blood (BUN, creatinine, phosphorus, and SDMA concentrations) and urine (protein concentration, urine protein-to-creatinine ratio, and urine specific gravity) were evaluated for correlation with histologic kidney damage scored with an objective grading scale defined by percentage of inflammation, fibrosis, and tubular atrophy. RESULTS: Symmetric dimethylarginine had the strongest significant correlation (ρ = 0.667) with histologic kidney damage score, followed by urine specific gravity (ρ = -0.639), blood creatinine concentration (ρ = 0.624), and BUN (ρ = 0.588). No significant correlation with kidney score was identified for blood phosphorus concentration, urine protein concentration, or the urine protein-to-creatinine ratio. CLINICAL RELEVANCE: We recommend SDMA be prioritized as a renal biomarker in tigers, with SDMA results considered in addition to those of other traditional renal biomarkers when assessing kidney function in tigers. Additionally, the grading scale we developed could be replicated across patients and pathologists for more consistent postmortem assessment of CKD in tigers.

Clinical progression of cats with early-stage chronic kidney disease fed diets with varying protein and phosphorus contents and calcium to phosphorus ratios.

BACKGROUND: Dietary protein and phosphorus (P) restriction is the mainstay for nutritional management of chronic kidney disease (CKD). However, adequate restriction levels for cats with early CKD remain unclear. OBJECTIVES: To investigate responses in cats with early CKD to varying dietary protein, P, and calcium (Ca) : P ratio. ANIMALS: Nineteen research colony cats with International Renal Interest Society stages 1-2 CKD. METHODS: In an opportunistic longitudinal case study, cats were fed a low protein (59 g/Mcal), low P (0.84 g/Mcal) dry diet (LP-LP; Ca : P = 1.9) for 18 months and later transitioned onto a moderate protein (76-98 g/Mcal), moderate P (1.4-1.6 g/Mcal) dry-wet diet regimen (MP-MP; Ca : P = 1.4-1.6) for 22 months. Fold-changes in serum creatinine, total Ca (tCa) and P (primary outcomes) and fibroblast growth factor 23 (FGF23) were assessed by linear-mixed models. RESULTS: While feeding LP-LP, mean serum creatinine decreased (0.87-fold, 95% confidence interval [CI] 0.81, 0.93, P < .001) to within reference range after 6 months, while increases in total Ca (tCa; 1.16-fold, 95% CI 1.11, 1.22, P < .001) and FGF23 (2.72-fold, 95% CI 1.72, 4.31, P < .001), but not in P (1.03-fold, 95% CI 0.945, 1.124, P = .94), were observed after 17 months. On MP-MP, mean creatinine, tCa and P remained within reference ranges and did not significantly change (P = .11, P = .98, and P = 1, respectively), while FGF23 significantly decreased (0.58-fold, 95% CI 0.36, 0.95, P = .02) after 22 months. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with early CKD developed hypercalcemia after long-term feeding of a highly P-restricted diet. Increasing dietary P and reducing Ca : P ratio maintained renal markers, while improving Ca-P balance. Cats with early CKD could benefit from moderately protein- and P-restricted diets.

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.

Plasma and urinary F2-isoprostane markers of oxidative stress are increased in cats with early (stage 1) chronic kidney disease.

OBJECTIVES: Oxidative stress contributes to chronic kidney disease (CKD) progression in humans and rodent models; F2-isoprostanes (F2-IsoPs) are established biomarkers of oxidative stress. Our primary aim was to evaluate plasma F2-IsoPs in cats with International Renal Interest Society stage 1 and 2 CKD, compared with healthy cats, and to determine whether plasma and urinary F2-IsoPs are equivalent biomarkers. The secondary aim was to assess whether consumption of a renal diet enriched in omega-3 fatty acids led to improvements in plasma and urinary F2-IsoPs. METHODS: Plasma and urinary F2-IsoPs were measured in 24 cats with stage 1 or 2 CKD, and 12 unaffected controls aged ⩾6 years. Twelve CKD cats were re-evaluated after feeding a commercial renal diet for at least 4 weeks. RESULTS: Median plasma F2-IsoPs were significantly higher in stage 1 CKD (96.2 pg/ml), early stage 2 CKD (83.2 pg/ml) and late stage 2 CKD (80.8 pg/ml) compared with healthy cats (22.8 pg/ml; P = 0.03-0.002). Median urinary F2-IsoPs were significantly higher in cats with stage 1 CKD (231.2 pg/mg) compared with healthy cats (152.5 pg/mg) or cats with late stage 2 CKD (124.8 pg/mg; P = 0.01). Plasma F2-IsoPs remained increased, while urinary F2-IsoPs fell with transition from stage 1 to stage 2 CKD. Feeding a commercial renal diet led to significant decreases in plasma F2-IsoPs in the small group of cats with stage 1 CKD (25-75% decrease) compared with cats with stage 2 CKD (20% decrease to 53% increase; P = 0.01). CONCLUSIONS AND RELEVANCE: Oxidative stress is prominent in cats with stage 1 CKD. Plasma and urinary F2-IsoPs are not interchangeable biomarkers in cats with stage 2 CKD. Placebo-controlled studies are indicated to evaluate dietary or pharmacologic doses of omega-3 fatty acids on redox stress and progression of renal dysfunction in cats with stage 1 CKD.

Effects of calcifediol supplementation on markers of chronic kidney disease-mineral and bone disorder in dogs with chronic kidney disease.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) in dogs is associated with hypovitaminosis D, increased parathyroid hormone (PTH), and increased fibroblast growth factor-23 (FGF-23) concentrations. Best practice for vitamin D metabolite supplementation in CKD-MBD remains unknown. OBJECTIVE: To provide an extended-release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD-MBD. ANIMALS: Ten dogs with International Renal Interest Society stages 2 and 3 CKD. METHODS: In a prospective study, dogs received a calcifediol supplement for 84 days. Serum 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2 D), 24,25-dihydroxyvitamin D (24,25[OH]2 D), creatinine, calcium, phosphorus, PTH, plasma FGF-23 concentrations, and urine profiles were measured monthly during supplementation. Urine calcium to creatinine (UCa/Cr) ratios and fractional excretion of calcium, phosphorus, and sodium were determined. RESULTS: All serum vitamin D metabolite concentrations increased significantly by day 84 (P < .001): [25(OH)D (median 249.9 ng/mL; range, 149.7-469.9 ng/mL) compared to baseline (median 50.2 ng/mL; range, 31.3-66.0 ng/mL); 1,25(OH)2 D (median 66.1 pg/mL; range, 56.9-88.1 pg/mL) compared to baseline (median 37.3 pg/mL; range, 29.3-56.7 pg/mL); 24,25(OH)2 D (median 81.4 ng/mL; range, 22.1-151.7 ng/mL) compared to baseline (median 15.4 ng/mL; range, 6.9-40.6 ng/mL)]. There were no significant differences in calcium, phosphorus, PTH concentrations, UCa/Cr or fractional excretion of calcium. No dog developed ionized hypercalcemia. Plasma FGF-23 concentrations increased by day 84 (median 1219 pg/mL; range, 229-8824 pg/mL) compared to baseline (median 798 pg/mL; range, 103-4.145 pg/mL) (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Calcifediol supplementation for 84 days was well-tolerated in dogs with IRIS stages 2 and 3 CKD. It remains to be determined how long-term supplementation would affect CKD progression and QOL.

Expression analysis of protease-activated receptor-2 in cats.

Chronic kidney disease (CKD) is a common disease in geriatric cats. Despite its high prevalence, the pathogenesis of feline CKD is poorly understood. Recently, there has been increasing evidence for the role of protease-activated receptor-2 (PAR-2) in the progression of CKD in humans and rodents. However, the role of PAR-2 in feline CKD has not been evaluated. In this study, we determined nucleotide sequence of feline PAR-2 from the kidney, evaluated PAR-2 mRNA and protein expression in normal feline tissues, and analyzed functional expression in the feline kidney epithelial cell line Crandell-Rees Feline Kidney (CRFK). The open reading frame of feline PAR-2 comprised 1,194 bp and encoded 397 amino acids, showing 90%, 90%, and 85% identities to human, dog, and mouse PAR-2, respectively. In healthy cats, expression levels of the PAR-2 mRNA and protein were relatively higher in the gastrointestinal tract and kidney, and was lowest in the heart. The feline PAR-2 protein expression was confirmed, and stimulation of trypsin and PAR-2 agonists induced a prompt increase in the intracellular calcium ion concentration in CRFK cells. The present study will provide fundamental information for investigation of the involvement of PAR-2 in the pathogenesis of CKD in cats.

Nutritional and laboratory parameters affect the survival of dogs with chronic kidney disease.

Chronic kidney disease is a common disease in dogs, and factors such as serum concentrations of creatinine, albumin, and phosphorus at the moment of diagnosis may influence the survival of these patients. The present retrospective study aimed to evaluate the relationship between survival in dogs with chronic kidney disease and laboratory parameters (creatinine, phosphorus, albumin, and hematocrit) and nutritional parameters (body condition score, muscle mass score, type of food, appetite and feeding method). A total of 116 dogs with chronic kidney disease stages 2 to 4 were included, and survival was calculated considering the time between diagnosis and death. Survival curves were configurated by Kaplan-Meier analysis and a comparison between survival curves was performed by the log-rank test. Factors related to survival were disease stage (p<0.0001), serum phosphorus concentration (p = 0.0005), hematocrit (0.0001), body condition score (p = 0.0391), muscle mass score (p = 0.0002), type of food (p = 0.0009), feeding method (p<0.0001) and appetite (p = 0.0007). Based on data obtained in this study, it is possible to conclude that early diagnosis, as well as nutritional evaluation and renal diet intake, are determinant strategies to increase survival in dogs with chronic kidney disease.

Investigation on urinary and serum alpha klotho in dogs with chronic kidney disease.

BACKGROUND: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. The kidney is known to be the main source of soluble alpha-klotho and the principal regulator of its concentration. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD. RESULTS: Serum and urinary alpha klotho concentrations were measured by a commercially available canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal-Wallis test. Spearman's correlation coefficient was used to evaluate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations. The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD was significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and serum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure. CONCLUSIONS: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho is associated with CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Although serum klotho concentration was negatively correlated with sSDMA levels, it was not apparently related to IRIS CKD stage or other parameters known to be associated with CKD.

Acute on chronic kidney disease in cats: Etiology, clinical and clinicopathologic findings, prognostic markers, and outcome.

BACKGROUND: Chronic kidney disease (CKD) and acute decompensation of CKD (ACKD) are common in cats. OBJECTIVES: To characterize the etiology, clinical and clinicopathologic findings, and the short- and long-term prognosis of feline ACKD. ANIMALS: One hundred cats with ACKD. METHODS: Retrospective study, search of medical records for cats with ACKD. RESULTS: Common clinical signs included anorexia (85%), lethargy (60%), weight loss (39%), and vomiting (27%). Suspected etiologies included ureteral obstruction (11%), renal ischemia (9%), pyelonephritis (8%), others (6%), or unknown (66%). Hospitalization duration was longer in survivors versus nonsurvivors (median = 7 days, range = 2-26 versus median = 3 days, range = 2-20, respectively, P < .001). The survival rate to discharge was 58%. Age, serum creatinine, urea, and phosphorous concentrations were higher and venous blood pH was lower in nonsurvivors. However, only serum phosphorus remained associated with the short-term outcome in the multivariable model (P = .02; 95% confidence interval = 1.03-1.39). Survivors had a median survival time of 66 days after discharge. Serum creatinine concentrations at presentation as well as at discharge were associated with long-term survival (P < .002 for both). CONCLUSIONS: The short-term prognosis of ACKD is comparable to acute kidney injury, while the long-term prognosis is guarded.

The Multicomponent, Multitarget Therapy SUC in Cats with Chronic Kidney Disease: A Multicenter, Prospective, Observational, Nonrandomized Cohort Study.

BACKGROUND: We compared the natural multicomponent, multitarget therapy SUC (Solidago compositum ad us. vet., Ubichinon compositum and Coenzyme compositum, Heel GmbH, Baden-Baden, Germany) to the well-known angiotensin-converting enzyme inhibitor benazepril in a prospective, observational, nonrandomized, two-arm cohort study of cats with chronic kidney disease (CKD). The objective was to assess the tolerability and the effectiveness of SUC in cats with CKD. MATERIAL AND METHODS: One hundred thirty-six cats were screened for CKD, and 70 cats were eligible for the study. Thirty-three cats were assigned to the SUC treatment, and 35 cats received benazepril. All cats were diagnosed with CKD. The follow-up period was 168 days. Response was assessed as an improved or stable serum creatinine from baseline to the end of the study. Additionally, a clinical summary score, as measure of quality of life, was evaluated. RESULTS: Serum creatinine remained close to baseline in both study groups with slightly improved values in the SUC group. The clinical summary score improved significantly in the SUC group on days 3, 7, 28, 56 and 112, but not on day 168. CONCLUSIONS: Within the limitations of the study, the results carry implications for the usefulness of SUC as an interesting new treatment option for feline CKD. The results indicate that SUC might be more effective if given at least twice weekly.

Retrospective study of the efficacy of oral potassium supplementation in cats with kidney disease.

OBJECTIVES: The aim of this study was to assess the effect of three oral potassium supplements (potassium gluconate tablets [PGT], potassium gluconate granules [PGG] and potassium citrate granules [PCG]) on hypokalemia and serum bicarbonate in cats with chronic kidney disease (CKD). METHODS: Medical records (2006-2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within 1-6 weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference interval, and an increase to >4 mEq/l. RESULTS: Thirty-seven cats met inclusion criteria (16 PGT, 11 PGG, 10 PCG). Dosing ranged from 0.21 to 1.6 mEq/kg/day for PGT, from 0.25 to 1.48 mEq/kg/day for PGG and from 0.04 to 1.34 mEq/kg/day for PCG. After supplementation, 36/37 cats had an increase in potassium, 34/37 increased to within the reference interval and 24/37 had an increase in potassium to >4 mEq/l. There was a statistically significant difference in serum potassium post-supplementation for all three treatments: PGT (P = 0.0001), PGG (P = 0.001) and PCG (P = 0.002). There was a positive correlation between PGT dose and change in potassium concentration (P = 0.04), but there was no significant correlation for PGG or PCG. In cats that had data available, serum bicarbonate increased >2 mEq/l in 1/6 PGT, 1/6 PGG and 3/4 PCG cats. CONCLUSIONS AND RELEVANCE: All three potassium supplements were effective in treating hypokalemia secondary to CKD in the majority of cats despite variable dosing. Data were limited to assess the alkalinizing effect and prospective studies are needed.

A plasma calcium-phosphorus product can be used to predict the lifespan of dogs with chronic kidney disease.

A serum calcium-phosphorus (sCaPP) product was assessed for prediction of survival in dogs affected with chronic kidney disease (CKD). Dogs (N = 150) were retrospectively studied and followed up to determine their lifespan using 25 healthy dogs as controls. Blood and urine analyses were performed and blood pressure was measured. The dogs were divided into groups according to sCaPP (higher or lower than 70 mg2/dL2) and International Renal Interest Society (IRIS) stage (IRIS 1-4). Shorter survival was observed with sCaPP > 70 mg2/dL2 compared to dogs with sCaPP < 70 mg2/dL2 [45.48 days (range: 5.8 to 149 days) versus 505.40 days (range: 113.31 to 539.52 days), mean (95% confidence interval); P ≤ 0.001 respectively]. Similarly, dogs with advanced IRIS stages showed higher levels of sCaPP [mean (95% confidence interval) in mg2/dL2; IRIS 1: 42.83 (range: 29.58 to 62.10); IRIS 2: 63.18 (range: 46.34 to 90.09); IRIS 3: 95.57 (range: 88.34 to 127.19); IRIS 4: 130.38 (range: 125.16 to 153.52)], accompanied by lower survival rates. Therefore, sCaPP could represent a valuable tool in the prognosis of canine CKD.

Un produit plasmatique calcium-phosphore peut être utilisé pour prédire la durée de vie de chiens avec une maladie rénale chronique. Un produit sérique calcium-phosphore (sCaPP) fut évalué pour prédire la survie de chiens souffrant de maladie rénale chronique (CKD). Des chiens (N = 150) furent étudiés rétrospectivement et suivis pour déterminer leur survie en utilisant 25 chiens en santé comme témoins. Des analyses urinaires et sanguines furent effectuées et la pression sanguine fut mesurée. Les chiens furent divisés en groupes en fonction de leur sCaPP (plus élevé ou plus faible que 70 mg2/dL2) et de leurs stages selon l'International Renal Interest Society (IRIS) (IRIS 1­4). Un temps de survie plus court fut observé avec une sCaPP > 70 mg2/dL2 comparativement aux chiens avec une sCaPP < 70 mg2/dL2 [45,48 jours (varie de 5,8 à 149 jours) versus 505,40 jours (varie de 113,31 à 539,52 jours), moyenne (intervalle de confiance 95 %); P ≤ 0,001 respectivement]. De manière similaire, les chiens avec un stages IRIS avancé avaient des niveaux de sCaPP plus élevés [moyenne (intervalle de confiance 95 %) en mg2/dL2; IRIS 1 : 42,83 (varie de 29,58 à 62,10); IRIS 2 : 63,18 (varie de 46,34 à 90,09); IRIS 3 : 95,57 (varie de 88,34 à 127,19); IRIS 4 : 130,38 (varie de 125,16 à 153,52], accompagnés de taux de survie plus bas. Ainsi, la valeur de sCaPP pourrait représenter un outil utile dans le pronostic des maladies rénales chroniques chez le chien.(Traduit par Dr Serge Messier).

A nutraceutical diet based on Lespedeza spp., Vaccinium macrocarpon and Taraxacum officinale improves spontaneous feline chronic kidney disease.

Chronic kidney disease is characterized by structural and/or functional impairment of one or both kidneys persisting for more than 3 months. In cats, chronic kidney disease can frequently occur in animals aged over 9 years with an incidence of approximately 10%. Thirty-four client-owned, neutered cats, suffering from stage II-III chronic kidney disease and diagnosed according to the International Renal Interest Society guidelines were randomly assigned to receive either a control diet (n = 17) or a nutraceutical diet (ND; n = 17) for 90 days. Both diets were commercialized for management of CKD symptoms. The diets were identical except that the ND contained tablets that consisted of 60-80% hydrolysed proteins, 20-40% minerals and active substances, that are, Lespedeza spp. 0.0588%, Vaccinium macrocarpom 0.0371%, and Taraxacum officinale 0.0231%. No adverse effects were reported during this study. Both diets resulted in an improvement in CKD symptoms. After a 90-day evaluation, creatinine, blood urea nitrogen, total proteins, and aspartate aminotransferase significantly decreased in cats that received the ND. A significant decrease was also observed in urine turbidity score, color score, and total proteins in cats that received the ND. We have found that a ND based on Lespedeza spp., Vaccinium macrocarpon, and Taraxacum officinale improves key indicators of renal failure in cats affected by chronic kidney disease.

A long term feed supplementation based on phosphate binders in Feline Chronic Kidney Disease.

Chronic kidney disease (CKD) is a very common disorder in elderly cats. A proper renal diet represents the most efficient therapeutic intervention to improve survival and life quality in feline patients with 3 and 4 International Renal Interest Society (IRIS) stages. Twenty cats were selected in this study. Ten were administered the dietary supplementation for 360 days and the other ten, whose owners did not give consent for any supplemental therapies apart from the renal diet, were selected from a clinical database and used as control group. The present study is a long term study (360 days) aiming to evaluate the efficacy and palatability of a dietary supplementation containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in cats diagnosed with 3 and 4 IRIS stages of CKD. The owners were asked to fill in questionnaires to get information on the cat's appetite, the palatability of the given supplement, the presence of vomit and/or diarrhoea, general health and vitality. Hematochemical, biochemical and urinary analyses were performed on day 0, 30, 60, 90, 120, 150,180 and 360. GraphPad Prism® software was used to perform statistical analysis. Our study shows that the given dietary supplement reduced serum phosphorus and increased serum bicarbonate values in cats with CKD. In turn, this supplement could be used as a support therapy in cats with advanced CKD improving their clinical conditions without any adverse reaction. Finally, it is important to underline that all the animals completed the study and the owners reported a good palatability of the feed supplement.