IRIS Stage Research Articles

Fecal bile acid dysmetabolism and reduced ursodeoxycholic acid correlate with novel microbial signatures in feline chronic kidney disease.

Microbial-derived secondary bile acids (SBAs) are reabsorbed and sensed via host receptors modulating cellular inflammation and fibrosis. Feline chronic kidney disease (CKD) occurs with progressive renal inflammation and fibrosis, mirroring the disease pathophysiology of human CKD patients. Prospective cross-sectional study compared healthy cats (n = 6) with CKD (IRIS Stage 2 n = 17, Stage 3 or 4 n = 11). Single timepoint fecal samples from all cats underwent targeted bile acid metabolomics. 16S rRNA gene amplicon sequencing using DADA2 with SILVA taxonomy characterized the fecal microbiota. CKD cats had significantly reduced fecal concentrations (median 12.8 ng/mg, Mann-Whitney p = 0.0127) of the SBA ursodeoxycholic acid (UDCA) compared to healthy cats (median 39.4 ng/mg). Bile acid dysmetabolism characterized by <50% SBAs was present in 8/28 CKD and 0/6 healthy cats. Beta diversity significantly differed between cats with <50% SBAs and > 50% SBAs (PERMANOVA p < 0.0001). Twenty-six amplicon sequence variants (ASVs) with >97% nucleotide identity to Peptacetobacter hiranonis were identified. P. hiranonis combined relative abundance was significantly reduced (median 2.1%) in CKD cats with <50% SBAs compared to CKD cats with >50% SBAs (median 13.9%, adjusted p = 0.0002) and healthy cats with >50% SBAs (median 15.5%, adjusted p = 0.0112). P. hiranonis combined relative abundance was significantly positively correlated with the SBAs deoxycholic acid (Spearman r = 0.5218, adjusted p = 0.0407) and lithocholic acid (Spearman r = 0.5615, adjusted p = 0.0156). Three Oscillospirales ASVs and a Roseburia ASV were also identified as significantly correlated with fecal SBAs. The gut-kidney axis mediated through microbial-derived SBAs appears relevant to the spontaneous animal CKD model of domestic cats. This includes reduced fecal concentrations of the microbial-derived SBA UDCA, known to regulate inflammation and fibrosis and be reno-protective. Microbes correlated with fecal SBAs include bai operon containing P. hiranonis, as well as members of Oscillospirales, which also harbor a functional bai operon. Ultimately, CKD cats represent a translational opportunity to study the role of SBAs in the gut-kidney axis, including the potential to identify novel microbial-directed therapeutics to mitigate CKD pathogenesis in veterinary patients and humans alike.

The Effect of Renaltec on Serum Uremic Toxins in Cats with Experimentally Induced Chronic Kidney Disease.

Serum uremic toxins markedly increase in cats with chronic kidney disease (CKD) and have deleterious consequences. Renaltec is an oral adsorbent that binds uremic toxin precursors in the gut. In this prospective cohort study utilizing 13 purpose-bred cats with remnant kidney model-induced CKD (12 IRIS Stage 2, 1 IRIS Stage 3) eating a standardized renal diet, we aimed to assess the effect of Renaltec administration on serum indoxyl sulfate (IDS) and p-cresol sulfate (pCS) concentrations. Cats were sequentially treated with standard of care for 56 days, 500 mg Renaltec orally once daily for 56 days, and then three months later, 500 mg Renaltec orally twice daily for 56 days. Serum IDS and pCS concentrations were measured 28 and 56 days after the administration of Renaltec. Blood pressure and kidney function were measured before and 56 days after the administration of Renaltec. Significant decreases in serum IDS and pCS concentrations were observed for both once- and twice-daily dosing, particularly during the first 28 days of administration. More cats with BID dosing had clinically significant reductions in serum IDS and pCS concentrations than with SID dosing. Renaltec can reduce the serum concentrations of deleterious gut-derived uremic toxins in cats with CKD.

Treatment of Canine Leishmaniasis with Meglumine Antimoniate: A Clinical Study of Tolerability and Efficacy.

Antimoniate therapy, in association with allopurinol, is one of the first-line treatments of canine leishmaniasis (CanL). This study evaluates the potential adverse effects associated with aNm in the treatment of CanL through both a retrospective analysis and a long-term prospective study also aimed to investigate its efficacy. The retrospective study reviewed records of 87 dogs with CanL with at least one follow-up available during or at the end of therapy with aNm (Glucantime®) at a dose of 50 mg/kg administered subcutaneously twice a day in association with allopurinol. In total, 29.8% of dogs showed adverse effects during treatment as local reactions at the injection site (n = 6), severe systemic reaction to pain (originating from the inoculation site) with depression and anorexia (n = 4), systemic disease due to renal function worsening (n = 4), acute pancreatitis (n = 1), diarrhea (n = 5), vomiting (n = 3) and severe idiosyncratic skin reactions (n = 3). Of these dogs, 13 (14.9%) required treatment suspension. The prospective study included 16 dogs, selected among the LeishVet stages II and III CKD IRIS stage 1 (International Renal Interest Society staging of canine Chronic Kidney Disease) and treated with the same aNm plus allopurinol protocol as in the retrospective study and observed for 360 days; 2 dogs were excluded for severe reactions at the injection site. Mild and transient adverse events were reported in the other 4 dogs. The criteria used to evaluate the efficacy of treatment with aNm were as follows: a reduction in the clinical score and improvement and/or normalization of laboratory parameters, negativization of PCR on the bone marrow samples and disease-free interval time. The proportion of reduction in the clinical score reached 91.9% at D180. No animals showed clinical laboratory relapse during the whole study duration and interestingly, the PCR results showed complete negativity between D0 and D60 in 78.5% of animals. Veterinarians must be vigilant regarding the potentially serious adverse effects associated with aNm and promptly stop drug administration if unexpected clinical manifestations occur. On the other hand, they should not discard its use for CanL treatment since it is confirmed that aNm in association with allopurinol is highly effective in controlling CanL.

Supplementation of vitamin E as an addition to a commercial renal diet does not prolong survival of cats with chronic kidney disease

BackgroundThe aim of this double-blind, placebo-controlled study was to investigate the effect of vitamin E supplementation as an addition to a commercial renal diet on survival time of cats with different stages of chronic kidney disease (CKD). In addition, we were interested whether vitamin E supplementation affects selected oxidative stress and clinical parameters. Thirty-four cats with CKD and 38 healthy cats were included in the study. Cats with CKD were classified according to the IRIS Guidelines; seven in IRIS stage 1, 15 in IRIS stage 2, five in IRIS stage 3 and seven in IRIS stage 4. Cats with CKD were treated according to IRIS Guidelines. Cats with CKD were randomly assigned to receive vitamin E (100 IU/cat/day) or placebo (mineral oil) for 24 weeks in addition to standard therapy. Plasma malondialdehyde (MDA) and protein carbonyl (PC) concentrations, DNA damage of peripheral lymphocytes and plasma vitamin E concentrations were measured at baseline and four, eight, 16 and 24 weeks thereafter. Routine laboratory analyses and assessment of clinical signs were performed at each visit.ResultsVitamin E supplementation had no effect on the survival time and did not reduce the severity of clinical signs. Before vitamin E supplementation, no significant differences in vitamin E, MDA and PC concentrations were found between healthy and CKD cats. However, plasma MDA concentration was statistically significantly higher (p = 0.043) in cats with early CKD (IRIS stages 1 and 2) than in cats with advanced CKD (IRIS stages 3 and 4). Additionally, DNA damage was statistically significantly higher in healthy cats (p ≤ 0.001) than in CKD cats. Plasma vitamin E concentrations increased statistically significantly in the vitamin E group compared to the placebo group four (p = 0.013) and eight (p = 0.017) weeks after the start of vitamin E supplementation. During the study and after 24 weeks of vitamin E supplementation, plasma MDA and PC concentrations and DNA damage remained similar to pre-supplementation levels in both the placebo and vitamin E groups.ConclusionsVitamin E supplementation as an addition to standard therapy does not prolong survival in feline CKD.

Hemogram-Derived Inflammatory Markers in Cats with Chronic Kidney Disease.

Chronic kidney disease (CKD) is characterized by chronic inflammation, which mediates the progressive replacement of functional nephrons by fibrotic tissue. Hemogram-derived inflammatory markers are known to serve as markers of pathological conditions; however, their diagnostic value in feline CKD is still unknown. The aim of this retrospective study was to investigate selected hemogram-derived inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammatory index (SII)) in cats at different clinical stages of CKD. Eighty-eight client-owned cats with CKD and thirty-two healthy control cats were included. Cats with CKD were divided into two groups: early CKD (IRIS stage 1 and 2; 62 cats) and progressed CKD (IRIS stage 3 and 4; 26 cats). The values of inflammatory markers were compared between the two CKD groups and the control group. All investigated hemogram-derived inflammatory markers were significantly (p < 0.05) greater in cats with advanced CKD than in those in the other two groups. Additionally, we demonstrated a statistically significant weak to moderate correlation between serum urea, creatinine, selected hematologic and urinary parameters, and the investigated inflammatory markers in cats with CKD. Chronic inflammation can be easily and inexpensively assessed with hemogram-derived markers.

Effect of Oligo-Fucoidan, Fucoxanthin, and L-Carnitine on Chronic Kidney Disease in Dogs: A Retrospective Study.

Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD. A total of 50 patients (OFL, n = 28; control, n = 22) were included in the analysis. A significant difference was identified in serum blood urea nitrogen and creatinine concentrations between the control and OFL groups at 6 months. No significant difference in electrolytes was found between the groups. A significant difference was identified in serum creatinine concentration between the control and OFL groups in azotemic (CKD IRIS stage 2-4) at 6 months. The OFL compounds showed a reno-protective effect, consistent with previous animal studies. The OFL combination can potentially delay the progression of canine CKD and be used as an adjuvant therapy.

Assessment of the effect of gabapentin on blood pressure in cats with and without chronic kidney disease.

The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD). A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location. After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; P = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; P = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; P = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups). Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.

Inflammatory Status and Chronic Kidney Disease in Cats: Old and New Inflammatory Markers—A Pilot Prospective Study

This prospective study aimed to evaluate inflammatory status in cats affected by chronic kidney disease (CKD) at IRIS stages 2–4, using serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) as inflammatory markers. Thirty-two cats with CKD and ten clinically healthy cats (i.e., control group) were enrolled. The recording of signalment data, complete physical examinations, and abdominal ultrasonography were performed for each animal. Additionally, ESR levels, complete blood count, clinical chemistry (including SAA determination), serum protein electrophoresis, and complete urinalysis were executed. This study’s results showed that mean ESR and SAA concentrations in cats with CKD were statistically higher compared to those of the control group (p = 0.0005 and p = 0.007, respectively). The SAA concentration was significantly increased at IRIS stages 2, 3, and 4 compared to the control group. Meanwhile, the ESR was significantly higher in cats at IRIS stages 3 and 4 (p = 0.0003 and p = 0.0007, respectively), but not at IRIS stage 2, compared to the control group. These results provide evidence that feline CKD is associated with a systemic inflammatory status. Moreover, the rise in ESR appears to be more linked to advanced stages of the disease and could, therefore, correlate with the uremic condition.

Juvenile primary acquired hypothyroidism in a dog with suspected renal dysplasia

AbstractA 1‐year 3‐month‐old, female, neutered crossbreed dog presented for investigation of polyuria, polydipsia and azotaemia. Subsequent biochemistry, endocrine testing and abdominal ultrasound identified hypercholesterolaemia, thyroglobulin autoantibody‐positive hypothyroidism, and IRIS stage II non‐hypertensive, non‐proteinuric suspected renal dysplasia, with a concurrent Escherichia coli urinary tract infection. The patient responded well clinically to levothyroxine treatment, with improvement in hypercholesterolaemia, azotaemia and demeanour at home. At follow‐up biochemistry assessment, hyperphosphataemia and hypercalcaemia (total and ionised) were documented, presumed to be driven by renal insufficiency and renal secondary hyperparathyroidism, although this aetiology was not definitively proven. Normalisation of these values was noted following renal diet implementation and addition of phosphate binders. This case highlights acquired primary hypothyroidism with evidence of thyroiditis in a juvenile dog with suspected congenital renal dysplasia.

#4810 DIAGNOSTIC AND THERAPEUTIC IMPACTS OF AIM ON END-STAGE KIDNEY DISEASE

Abstract Background and Aims End-stage kidney disease (ESKD) is life-threating, and indispensably requires dialysis which however imposes huge burdens on patients’ QOL and medical expense. No therapies to prevent CKD progression to the end-stage have reached clinic to date. Patients undergoing dialysis exhibit a high mortality mainly due to cardiovascular diseases (CVDs), but no biomarkers are available to predict the patients’ death and the incidence of cardiovascular disease (CVD), the major cause of death, before initiation of dialysis. AIM is a macrophage-derived circulating protein present in blood at relatively high levels (∼5 μg/mL). We initially identified AIM as a supporter of macrophage survival, and it is now known as a facilitator of repair in many diseases. In healthy state, AIM associates with IgM pentamer through disulfide-bond formation and charge-based interaction with IgM-Fc, using the solitary cysteine residue and the positively charged-amino acid cluster present at the carboxyl-terminus. During various diseases including acute kidney injury, hepatocellular carcinoma and peritonitis, AIM dissociates from IgM and binds to the body-derived types of inflammatory elements using the identical sites necessary for binding to IgM, thereby promoting their phagocytic removal by phagocytes. Method In 561 CKD patients of all stages and 310 dialysis patients, we analyzed the serum AIM and the serum solute profiles, and thereby assessed their efficacy in predicting survival and CVD risk after dialysis induction. Additionally, a therapeutic efficacy of recombinant AIM (rAIM) in preventing CKD progression to end-stage was addressed in house cats, that are highly susceptible to CKD and show a similar disease course to humans. Results AIM dissociated from IgM pentamer along CKD progression. Dialytic patients showing low levels of AIM dissociation before initiation of dialysis harbored less serum detrimental solutes, exhibited lower risk of CVD and had better survival than those with high grades of AIM dissociation, suggesting that the IgM-free AIM represents the state of serum toxic solutes, and predicts patients’ prognosis before initiation of dialysis. In addition, treatment of pre-uremic (late IRIS stage 3) cats, 50% of which died of severe uremia within 196 days after diagnosis, with recombinant AIM prevented aggravation of renal function and inflammation, as well as serum toxic solute profile, thereby improving the cats’ survival dramatically. Importantly, the same serum toxin/inflammatory solutes regulatable by rAIM in cats influenced dialysis patients’ prognosis. Conclusion There results promise the effects of AIM treatment in humans, reducing the need for dialysis. Our findings could be a platform for new CKD therapies and predictive diagnoses to improve the prognosis of patients with ESKD.

Pyothorax caused by Nocardia sp. in a cat Case report

Nocardiosis is an infection caused by ubiquitous opportunistic bacteria and is rare in felines. In retrospective studies of the infection in the species, pyothorax was found in only about 5% of the cases described, with the most frequent forms being cutaneous and subcutaneous. This report describes Nocardia spp. as an etiologic agent of pyothorax in a feline leukemia virus (FeLV)-positive female cat. A 10-year-old female mixed-breed cat, positive for FeLV, with chronic kidney disease IRIS stage 2, was examined with a severe dyspneic onset, suspected of pleural effusion. It also had skin lesions in the interscapular region. The patient underwent thoracentesis, and a dense, creamy, fetid, and flocculated liquid was collected. Radiography was performed after draining the pleural fluid, which showed images suggestive of atelectasis of the left lung lobes and pneumonia. The collected material was sent for analysis, which found that it was a septic exudate. In addition, it was referred for bacterial culture in a special medium due to suspicion of nocardiosis. Long-term treatment with amoxicillin + clavulanic acid resolved the clinical case.

Management of hyperkalemia in critically ill renal patients undergoing peritoneal dialysis

Hyperkalemia is defined as a plasma or serum potassium concentration above the established reference range and is frequently encountered in various pathologies. The potassium gradient between the intra- and extracellular compartments plays a key role in action potential generation by excitable cells. Serum potassium concentration in patients diagnosed with chronic kidney disease is usually balanced, but hyperkalemia may develop in patients with acute kidney injury in stage III and IV. According to recent studies, hyperkalemia is a serious complication in patients diagnosed with chronic kidney disease in IRIS stage II, III and IV. The occurrence and severity of hyperkalemia may also be aggravated by the inadequate administration of potassium in enteral or parenteral fluids, metabolic acidosis, and the use of angiotensin-converting enzyme inhibitors. Excess potassium is continuously excreted by the kidneys, and its concentrations in urine are higher than those in serum. Compromised excretion will predictably lead to both hyperkalemia and azotemia. The extent of these changes is variable and depends on the underlying etiology. Hyperkalemia can be treated by antagonizing its effects on cell membranes with calcium gluconate, or by introducing extracellular potassium into cells with sodium bicarbonate or glucose. Also, the removal of potassium from the body can be done through dialysis.

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 &lt; 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.

Characterization of preoperative cardiovascular status and association with outcome following feline renal allograft transplantation: 166 cases.

To retrospectively evaluate preoperative historical, biochemical, and cardiovascular screening data for predictors of survival to discharge and long-term survival in feline renal allograft recipients from 1 institution. 166 cats that underwent renal transplantation at the University of Pennsylvania between 1998 and 2018. Medical records were reviewed for preoperative historical information, biochemical data, and cardiac assessment including auscultation findings, pre- and postoperative systolic blood pressure measurements, thoracic radiographic evaluation, and echocardiographic measurements. The need for hemodialysis, the number of surgical procedures, native kidney biopsy diagnosis and survival time was also recorded. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% CI. Univariable and multivariable analysis were performed to determine variables that were independently associated with survival to discharge and long-term survival. The patient population primarily consisted of adult male DSH cats (70%) diagnosed with IRIS stage 4 CKD (66.3%). Abnormalities identified on preoperative cardiac assessment, including hypertension, the presence of a murmur, echocardiographic changes, and radiographic signs of congestive heart failure, were not associated with survival to discharge or long-term survival. Age was the only single significant variable associated with survival, and the risk of death increased by 11% (95% CI, 6% to 17%) for every 1 year in patient age. The presence of cardiac abnormalities identified during the screening process of cats presenting for transplantation should not immediately exclude a potential candidate for the procedure. Owners considering transplantation should be educated on the impact of age on survival following surgery.

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

BackgroundChronic 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.ObjectivesTo 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.AnimalsSix client‐owned adult dogs with IRIS Stage 2 and 3 CKD.MethodsProspective study. Serum 25‐hydroxyvitamin D (25[OH]D), 1,25‐dihydroxyvitamin D (1,25[OH]2D), 24,25‐dihydroxyvitamin D (24,25[OH]2D), 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.ResultsAll 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)2D (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)2D (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 ImportanceShort‐term calcifediol supplementation in this small group of CKD dogs appeared to decrease ACE activity.

Essential and Non-Essential Amino Acids in Dogs at Different Stages of Chronic Kidney Disease.

Simple SummaryHuman patients affected by chronic kidney disease reported alterations of serum amino acid pattern, as a consequence of several metabolic complications of the renal disease. Our study aimed to evaluate possible differences in serum pattern of essential and non-essential amino acids between dogs with chronic kidney disease and clinically healthy subjects. Canine chronic kidney disease resulted in an association with a significant serum deficiency of the majority of both essential and non-essential amino acids. The amino-acidic disorder was particularly evident when protein-energy wasting syndrome was present, suggesting a potential key role of pathological conditions, such as inflammation, insulin resistance, and increased protein breakdown.Abnormalities of serum amino acid profile, mostly characterized by a reduction in essential amino acids (EAAs) and an increase in non-essential amino acids (NEAAs), have been documented in human chronic kidney diseases (CKD). Amino acid disorders have been associated with CKD complications, such as metabolic acidosis and malnutrition. The aim of the present study was to evaluate EAAs and NEAAs in dogs affected by CKD at different IRIS stages, with particular reference to calcium–phosphate abnormalities, metabolic acidosis, and protein-energy wasting syndrome (PEW). Serum EAAs (L-histidine, L-isoleucine, L-leucine, L-lysine, methionine, L-phenylalanine, L-threonine, tryptophan, L-valine, and L-arginine) and serum NEAAs (L-alanine, L-aspartic acid, L-cysteine, L-glutamic acid, glycine, proline, L-serine, and L-tyrosine) were analyzed with HPLC in a group of dogs with CKD (n = 62), and in a group of healthy dogs (n = 25). CKD dogs showed significantly lower serum levels of histidine (p < 0.000), isoleucine (p < 0.000), tryptophan (p < 0.000), alanine (p = 0.013), cysteine (p < 0.000), and serine (p = 0.002), and significantly higher levels of proline (p < 0.000), leucine (p = 0.001), lysine (p < 0.000), valine (p < 0.000), arginine (p = 0.002), glutamic acid (p = 0.002), and glycine (p = 0.010) compared to healthy dogs. Dogs with abnormal calcium x phosphate values showed significantly higher levels of cysteine (p = 0.003), and lower levels of tryptophan (p = 0.025) compared to CKD dogs with normal CaxP. Dogs with metabolic acidosis showed significantly higher levels of phenylalanine (p = 0.035) and leucine (p = 0.034) compared to CKD dogs without metabolic acidosis. Dogs with PEW showed significantly lower levels for most of amino acids. In PEW dogs, the median distribution of both EAAs (p = 0.000) and NEAAs (p = 0.001) was significantly lower. The serum pattern of both EAAs and NEAAs was significantly different in CKD dogs compared to healthy dogs, although no association with the progression of the IRIS stage was found.

Serum and Fecal Amino Acid Profiles in Cats with Chronic Kidney Disease.

The purpose of the study was to quantify serum and fecal amino acids (AA) in cats with chronic kidney disease (CKD) and compare to healthy cats. Thirty-five cats with International Renal Interest Society Stage 1–4 CKD and 16 healthy mature adult and senior client-owned cats were included in this prospective cross-sectional study. Sera were analyzed for 25 AA concentrations using an ion exchange chromatography AA analyzer with post column ninhydrin derivatization. Voided fecal samples were analyzed for 22 AA concentrations using liquid chromatography with tandem mass spectrometry. CKD cats had lower serum concentrations of phenylalanine (mean difference ± standard error of the mean: 12.7 ± 4.3 µM; p = 0.03), threonine (29.6 ± 9.2 µM; p = 0.03), tryptophan (18.4 ± 5.4 µM; p = 0.005), serine (29.8 ± 12.6 µM; p = 0.03), and tyrosine (11.6 ± 3.8 µM; p = 0.01) and higher serum concentrations of aspartic acid (4.7 ± 2.0 µM; p = 0.01), β-alanine (3.4 ± 1.2 µM; p = 0.01), citrulline (5.7 ± 1.6 µM; p = 0.01), and taurine (109.9 ± 29.6 µM; p = 0.01) when compared to healthy cats. Fecal AA concentrations did not differ between healthy cats and CKD cats. 3-Methylhistidine-to-creatinine did not differ between healthy cats with and without muscle loss. Cats with CKD IRIS Stages 1–4 have a deranged serum amino acid profile compared to healthy cats.

Effect of domperidone (leisguard\xae) on antibody titers, inflammatory markers and creatinine in dogs with leishmaniosis and chronic kidney disease

BackgroundImmunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).MethodsDogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.ResultsOf the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563).ConclusionsThis study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.Graphical abstract

Clinical and Nutritional Follow-up of Cats with Chronic Kidney Disease Fed with a Renal Prescription Diet

Background: The use of prescription diets for cats with chronic kidney disease (CKD) is one of the main management approach of this disease in cats, and is considered a renoprotective strategy that may promote increased survival and/or improve quality of life, according to the stage of CKD. Besides that, nutritional assessment is important to monitor the maintenance of quality of life of the patients and their response to disease, especially those with chronic conditions. The aim of this study was to follow the clinical and nutritional status of cats with chronic kidney disease (CKD) IRIS stages II, III and IV fed with a renal prescription diet, followed for 12 months. Materials, Methods &amp; Results: Patients were fed exclusively with a dry renal prescription diet and medications for the management of CKD were prescribed when needed. Exclusion criteria were cats that already received a renal prescription diet or medications for the treatment of CKD. Cats were evaluated every 2 months, considering body weight (BW), body condition score (BCS), muscle mass score (MMS), clinical and laboratory parameters. In all assessments, a complete blood count and biochemistry were performed by conventional methods with the patient fasted for 12 h. In addition, urinalysis, urinary protein:creatinine ratio (UPC) and urine culture were performed from a urine sample collected by cystocentesis. The quantitative variables were tested for their stability on consecutive assessments using the non-parametric Friedman test, and did not present significant variation during follow-up, except for systolic blood pressure (SBP). Eight cats with a diagnosis of CKD were included in the study and 6 of them remained in the same CKD stage during follow-up. On cat died due to an unrelated CKD cause. Regarding nutritional assessment, 5 of 7 cats maintained BW during the 12 months. Of these, 4 also maintained MMS and BCS. Three of 7 cats presented a decrease in MMS, 2 of which presented also a decreased BW and one maintained BW.Discussion: IRIS staging results combined with Friedman’s analysis demonstrated that the diet and the clinical management were effective in the non-progression of CKD in this study. As renal injury is not expected to be reversed in CKD, the maintenance of cats in the same IRIS stages and the minimum variation of the parameters is considered a positive result in this study. Hypertensive cats started on antihypertensive therapy during the study, achieving adequate control of SBP in most cases, what can justify the variation of this clinical parameter over the 12 months. Hyperphosphatemia was a frequent alteration, included stage II cats, and presented a positive response to nutritional and medical therapy. Despite CKD staging progression was not observed in most cats using serum creatinine as a single parameter, some cats presented BW and MMS reduction, which may have influenced this result. Weight loss and muscle wasting may have occurred by several reasons, including periods of hyporexia, presence of concomitant diseases, aging process or reduced protein content on renal prescription diets. This study enhances the importance of the association of clinical and nutritional management in the maintenance of cats with CKD. We suggest that other studies are done during longer periods of time and with a larger sample to support the results found. We also suggest new studies to evaluate the protein requirements for cats with CKD.

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

BackgroundChronic 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.ObjectiveTo provide an extended‐release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD‐MBD.AnimalsTen dogs with International Renal Interest Society stages 2 and 3 CKD.MethodsIn 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]2D), 24,25‐dihydroxyvitamin D (24,25[OH]2D), 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.ResultsAll 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)2D (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)2D (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 ImportanceCalcifediol 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.