International Renal Interest Society Stage Research Articles

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

BackgroundDietary 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.ObjectivesTo investigate responses in cats with early CKD to varying dietary protein, P, and calcium (Ca) : P ratio.AnimalsNineteen research colony cats with International Renal Interest Society stages 1‐2 CKD.MethodsIn 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.ResultsWhile 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 ImportanceCats 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.

Serum fibroblast growth factor-23 concentrations in young and mature adult cats with chronic kidney disease.

The aim of this study was to investigate serum fibroblast growth factor (FGF)-23 concentrations in young and mature adult cats with chronic kidney disease (CKD). The present study retrospectively investigated the serum samples and medical records of 1-8-year-old clinically healthy cats (control group, n = 7) and cats with CKD (n = 54). Cats with CKD were divided into four stages based on serum creatinine concentrations, according to the International Renal Interest Society (IRIS) CKD guidelines. Serum FGF-23 concentrations were compared between cats in the control group, IRIS stages 1, 2 and 3-4 CKD. Continuous variables were analysed using correlations and multiple linear regression. Serum FGF-23 concentrations were significantly higher in cats with IRIS stages 1, 2 and 3-4 CKD, compared with those in the control group (P = 0.02, P = 0.002 and P = 0.002, respectively). Additionally, serum FGF-23 concentrations in cats with IRIS stages 3-4 CKD had higher serum FGF-23 concentrations than those with IRIS stages 1 and 2 CKD (P = 0.04 and P = 0.02, respectively). In the multiple linear regression analysis, serum urea nitrogen concentration, serum phosphorus concentration and blood ionised calcium concentration were independent variables predicting serum FGF-23 concentration. Serum FGF-23 concentrations in younger cats with CKD increased in early-stage CKD and were associated with mineral metabolic markers, as also occurs in geriatric cats.

Cystatin C and Neutrophil Gelatinase-Associated Lipocalin as Early Biomarkers for Chronic Kidney Disease in Dogs

Early diagnosis of chronic kidney disease (CKD) could facilitate timely and appropriate monitoring and therapy. Traditional biomarkers have limitations. Thus, new biomarkers are needed. The objective of the present study was to compare renal biomarkers (including symmetric dimethylarginine [SDMA], cystatin C [CysC], and urine neutrophil gelatinase-associated lipocalin [NGAL]-creatinine ration [UNCR]) and creatinine (CREA) for early detection of CKD in dogs. Nine healthy dogs and 32 dogs with CKD were included in this study. All dogs underwent physical examination, blood analysis (included CREA and SDMA), urinalysis, and imaging examinations. CysC and NGAL levels were measured in serum and urine, respectively. SDMA, CysC, and UNCR were significantly elevated in dogs with CKD and IRIS stage Ι (P < .0001) than in controls. CysC demonstrated a strong correlation with CREA (r2 = 0.6556, P < .0001). CysC (sensitivity 93.55%, specificity 100%) had the highest sensitivity for detecting CKD, followed by UNCR (sensitivity 90%, specificity 100%), SDMA (sensitivity 84.37%, specificity 100%), and CREA (sensitivity 43.75%, specificity 100%). Additionally, CysC and UNCR (sensitivity 88.89%, specificity 100%) exhibited higher sensitivity and specificity than CREA (sensitivity 88.89%, specificity 66.67%) and SDMA (sensitivity 88.89%, specificity 88.89%) in dogs with CKD International Renal Interest Society (IRIS) stage Ι. CysC as a marker of glomerular filtration rate (GFR) and urinary NGAL as a marker of tubular damage could be used to detect CKD early in dogs better than CREA and SDMA.

Influence of preanalytical factors on feline proteinuria.

To date, little information is available about the effect of preanalytical factors on the urinary protein-to-creatinine (UPC) ratio in cats. We aimed to evaluate the effect of a commercially available cat litter, creatinine measurements at three different dilutions of urine, and different storage conditions on the UPC ratio in cats. Feline urine specimens were prospectively collected. Twenty-two whole-urine specimens were placed uncovered and in contact with cat litter for 1hour; 25 urine supernatants were diluted 1:10, 1:20, and 1:100 for creatinine measurements. The correlation, difference, agreement, and concordance in classifying specimens according to International Renal Interest Society staging were determined. Storage effects on UPC ratios were assessed in specimens stored for 6hours at +20℃ (n=20), 1week at +4℃ (n=20), and 3months at -20℃ (n=25). Specimens were also subjected to four freeze-thaw cycles (n=20). Results were compared, and clinical significance was assessed by comparing each UPC ratio to the inter-assay range of the baseline value. Exposure to cat litter did not affect UPC ratios. A positive proportional bias was found in the 1:100 dilution compared with the 1:20 dilution; however, concordance was high for all comparisons. At +20, +4℃, and after four repeated freeze-thaw cycles, UPC ratios were stable. Compared with baseline values, UPC ratios decreased (P<.01) after 8 and 12weeks at -20℃. However, all UPC ratios were within the inter-assay variability of the baseline value. Exposure to cat litter did not affect UPC ratios, but further studies are necessary to evaluate other potential variables. The effects of the dilutions and storage conditions were clinically acceptable, although the 1:20 and 1:100 dilutions were not perfectly comparable.

Erythrogram Patterns in Dogs with Chronic Kidney Disease.

Anemia is considered a common finding in dogs with chronic kidney disease (CKD), typically as normochromic, normocytic, and non-regenerative. Although anemia can occur at any CKD IRIS (International Renal Interest Society) stage, its severity is related with the loss of kidney function. The aim of the present study was to retrospectively evaluate quantitative and morphological abnormalities of the erythrogram in dogs at different CKD IRIS stages. A total of 482 CBCs from 3648 initially screened were included in the study. Anemia was present in 302/482 (63%) dogs, in the majority of which it was normochromic, normocytic, and non-regenerative (295/302; 98%). The number of reticulocytes was <60,000/μL in the majority of dogs (248/295; 84%), with a correlation between poor regeneration rate and progression of CKD (p = 0.0001). The frequency of anemia significantly differed (p = 0.0001) among the IRIS stages: 108/231 (47%) in IRIS 2, 77/109 (71%) in IRIS 3, and 117/142 (82%) in IRIS 4. Dogs at IRIS stages 3 and 4 were more likely to have moderate to severe anemia, compared to dogs at IRIS stage 2 (p = 0.0001). Anisocytosis was the most frequent morphological abnormality (291/482; 60%), whereas the presence of poikilocytosis showed an association with progression of IRIS stages (p = 0.009). Among different morphological abnormalities, the frequency of fragmented red blood cells and Howell–Jolly bodies showed a significant association with the progression of CKD. Anemia was a frequent finding in CKD dogs, mostly associated with none to poor regeneration rate. Similar to human medicine, advanced CKD stages are more frequently characterized by morphological alterations, such as fragmented red blood cells and Howell–Jolly bodies, which may suggest a more severe condition of reduced bone marrow activity and microangiopathy.

Incidence and treatment of feline renal lymphoma: 27 cases.

Lymphoma is the most common feline hematopoietic malignancy. Incidence of renal lymphoma has not been reported as a subset of a large population of feline lymphoma cases. Previous studies have reported renal lymphoma as both a singular entity as well as a component of multicentric disease. The clinical presentation, diagnostic evaluation, therapy and outcomes related to renal lymphoma have not been reported since Mooney et al in 1987. This retrospective study aimed to describe the incidence of renal lymphoma, clinical signs, treatment and survival. Using a database of cats diagnosed with lymphoma between January 2008 and October 2017, cats with renal lymphoma were selected for further analysis. Cases were retrospectively staged according to Mooney et al (1987) and Gabor et al (1998). Data collected included age, clinical signs, clinicopathologic data, diagnostic imaging findings, lymphoma diagnostic method(s), treatment protocol(s) and survival time. Analyses comparing median survival based on therapy administered, renal lymphoma vs multicentric lymphoma, central nervous system involvement, presence of azotemia, anemia and International Renal Interest Society (IRIS) stage at diagnosis were performed. From a population of 740 cats with lymphoma, 27 cats had renal lymphoma (incidence, 3.6%), and 14 of those cats had multicentric lymphoma. Fewer stage IV and V cases were identified in this data set compared with Mooney et al; however, not all cats were completely staged. Median survival (range) for cats receiving corticosteroids alone compared with those receiving an L-CHOP (L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisolone)-based protocol was 50 days (20-1027 days) in the corticosteroid group and 203 days (44-2364 days) for the L-CHOP group (P = 0.753) for cats that died secondary to lymphoma. Neither clinical stage nor other factors were predictive of survival. Prospective studies are required to determine the optimal chemotherapy protocol.

Retrospective evaluation of refeeding syndrome in cats: 11 cases (2013-2019).

The aim of this study was to describe the clinicopathological findings, management and outcome of cats with refeeding syndrome (RS) following prolonged starvation. Records from four referral hospitals were searched between May 2013 and November 2019 and retrospectively evaluated. Inclusion criteria were the presence of a risk factor for RS, such as severe weight loss or emaciation following a period of presumed starvation, hypophosphataemia or a delta phosphorous exceeding 30% reduction following refeeding, being treated on the basis of a clinical diagnosis of RS and one or more derangement of hypokalaemia, hypoglycaemia or hyperglycaemia. Eleven cats were identified, which had been missing for a median of 6 weeks (range 3-104 weeks). Mean ± SD percentage weight loss was 46% ± 7% (n = 8). Eight of 11 cats developed hypophosphataemia with a mean delta phosphorous of -47% ± 9%. All cats were documented to be hypokalaemic. During hospitalisation, 10/11 cats developed hyperglycaemia and 7/11 cats developed hypoglycaemia. Cardiovascular, gastrointestinal and neurological signs were common. Eight of 11 cats displayed new or progressive neurological deficits after refeeding, including mentation changes and cerebellar dysfunction. All cats became anaemic and seven cats required a blood transfusion. Eight cats survived to discharge after a mean of 14 ± 4 days of hospitalisation. Six cats developed acute kidney injury (AKI; International Renal Interest Society stage 1). The presence of AKI (P = 0.024) was associated with non-survival and maximum bilirubin concentration was significantly higher in non-survivors (P = 0.018). Cats with RS in this cohort had been missing, presumed starved, for more than 3 weeks. In addition to hypophosphataemia and hypokalaemia, altered glucose homeostasis and organ damage involving the liver and kidneys were common. Cats with RS appear to have a good prognosis, but prolonged intensive care is required.

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

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

Analytical and Clinical Validation of a New Immunoenzymatic Method for the Measurement of Canine Parathyroid Hormone

Simple SummaryIn dogs affected with chronic kidney disease (CKD), mineral disorders, including renal hyperparathyroidism (RHPT), are frequent. Secondary RHPT is the increase in serum parathyroid hormone (PTH), that can have a significant impact in the disease progression. Despite its clinical utility, the measurement of serum PTH is not routinely executed due to limited availability of validated methods. The aims of this study were: the analytical validation of a new method for PTH measurement in dogs and analysis of the preliminary association of the obtained results with the renal status. Twenty-seven samples obtained from dogs that were healthy or affected with CKD were analysed. PTH was measured using a commercially available human assay. The precision and accuracy of this method were assessed and the PTH stability at different temperatures was evaluated. Clinical validation was performed by comparing PTH values with clinicopathological parameters often altered during CKD, such as creatinine and phosphorus, and with the disease severity. The method showed an optimal precision and accuracy; the stability was compatible with the standard sample processing times. PTH was positively associated with creatinine and phosphorus. The investigated method was successfully validated in dogs, allowing its use for clinical purposes.Renal hyperparathyroidism (RHPT) is one of the main complications in dogs affected with Chronic Kidney Disease (CKD). The measurement of serum parathyroid hormone (PTH) could be of clinical utility for the disease’s treatment and follow-up; however, PTH is not routinely determined due to limited available methods, often not fully validated in dogs. The aims of this study were the analytical validation of an immunoenzymatic method for the measurement of PTH in canine serum and the analysis of preliminary association of the obtained results with renal function. Twenty-six samples obtained from dogs healthy or affected with CKD were analysed. PTH was measured using a two-site immunoenzymometric human assay (ST AIA-PACK® Intact PTH, Tosoh Bioscience). The analytical validation protocol evaluated the assay precision and accuracy. Also, the PTH’s storage stability at 20 °C, 4 °C and −20 °C was assessed. Clinical validation was performed by comparing PTH values with creatinine, phosphorus and International Renal Interest Society (IRIS) stage. The method showed optimal precision and accuracy, whereas stability was adequate up to 4 h at 20 °C, 24 h at 4 °C and 6 months at −20 °C. PTH was positively associated with creatinine, phosphorus and IRIS stage. The investigated method was thus successfully validated in dogs, allowing its use for clinical purpose.

Evaluation of Urinary Big Endothelin-1 in Feline Spontaneous CKD.

Simple SummaryChronic kidney disease is a common and progressive disease of elderly cats. It is a cause of pet suffering and owner expense. Biologic biomarkers for early diagnosis and for noninvasive evaluation of kidney damage are certainly useful in both research and clinical practice. In this study, we evaluated the biomarker big endotelin-1 in the urine of cats affected with chronic kidney disease. Big endothelin-1 is molecule linked to inflammation and pressure regulation, and it was not previously evaluated in nephropathic cats. We found that urinary big endothelin was increased in patients at late stage of the disease and in patients with proteinuria (a marker of kidney damage). Despite that, big endothelin 1 seemed not to be a useful biomarker for disease progression. According to results of this preliminary study, we suggest this biomarker for future research on feline kidney disease.The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1–4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3–4 (median: 21.9; range: 1.88–55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00–46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00–55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.

Evaluation of platelet function in cats with and without kidney disease: a pilot study.

The aims of this study were to determine if stable chronic kidney disease (CKD) cats and uremic crisis cats have altered platelet function, and to determine the prevalence of positive fecal occult blood in CKD cats. Platelet function in normal cats, clinically stable International Renal Interest Society (IRIS) stage 2-4 CKD cats and CKD cats experiencing a uremic crisis were evaluated using impedance aggregometry. Area under the curve (AUC) at 6 mins was calculated for saline, adenosine diphosphate (AUCADP) and arachidonic acid (AUCASPI). The AUC in addition to hematocrit, platelet count and mean platelet volume (MPV) were compared between groups using the Kruskal-Wallis test followed by Dunn's post-hoc analysis. Guaiac fecal occult blood tests were performed on fecal samples and results were compared between groups using a χ2 for trend test. AUCADP (P = 0.04) and AUCASPI (P = 0.05) were significantly higher in uremic crisis cats compared with normal cats at 6 mins. Hematocrit was significantly higher in normal cats when compared with IRIS stage 3 and 4 (P = 0.002) and uremic crisis (P = 0.0008) cats, with no difference among groups for platelet count or MPV. The proportion of cats with positive fecal occult blood samples was significantly different between groups (P = 0.0017); 50% uremic crisis cats, 33% IRIS stage 3 and 4 cats, and 10% IRIS stage 2 cats were positive, while no normal cats were positive. The proportion of cats with platelet clumping was significantly different between groups (P = 0.03). Platelet hyper-reactivity may be occurring in CKD cats experiencing a uremic crisis. The etiology of positive fecal occult blood samples in CKD cats is unclear and did not appear to be related to decreased platelet function as measured in this study and requires further investigation.

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

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. 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. 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). 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.

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.

Fibroblast growth factor-23 as an early marker of CKD-mineral bone disorder in dogs: preliminary investigation.

To examine the relationship between fibroblast growth factor-23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs. Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor-23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor-23. Serum fibroblast growth factor-23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor-23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor-23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor-23. This preliminary study suggests that canine fibroblast growth factor-23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.

How Ultrasound Can Be Useful for Staging Chronic Kidney Disease in Dogs: Ultrasound Findings in 855 Cases.

In patients affected by chronic kidney disease (CKD), some ultrasonographic (US) abnormalities have been shown to correlate better than others with the progression of the disease. The aim of the study was to evaluate the prevalence of the most frequent renal US abnormalities in dogs at different stages of CKD, and to investigate their association with CKD International Renal Interest Society (IRIS) stages. Medical records and ultrasonographical report of 855 dogs were retrospectively included. The most frequent renal ultrasonographic abnormalities were: increased cortical echogenicity, abnormal ratio of cortico-medullary junction (C/M) and pyelectasia. A statistically significant difference in the prevalence of irregular contour, abnormal cortico-medullary junction, abnormal C/M, increased cortical echogenicity, and pyelectasia was found for dogs at different IRIS stages. The number of dogs with more than one US abnormality increased significantly with the progression of IRIS stage. In conclusion, increased cortical echogenicity, abnormal C/M junction and pyelectasia were the most prevalent US abnormalities in our CKD population. Although none of the US abnormalities showed a significantly higher prevalence, the number of dogs presenting > 3 US abnormalities increased significantly from IRIS 2 to IRIS 4. Renal US is an excellent ancillary diagnostic test, which should be used together with renal functional parameters, to monitor the progression of CKD.

Survival and complications in cats treated with subcutaneous ureteral bypass.

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

Dietary management of the cat with early chronic kidney disease

Chronic kidney disease (CKD) is a highly prevalent disease and common cause of morbidity and mortality in older cats. Early diagnosis and management of CKD is thought to be able to slow disease progression and impact positively on quality of life and longevity. Dietary management with a therapeutic renal diet is regarded as the mainstay of treatment for feline CKD from International Renal Interest Society (IRIS) stage 2 onwards. However, since the advent of markers such as symmetric dimethylarginine that have enabled clinicians to detect non-azotaemic CKD (IRIS stage 1 and some early stage 2 patients) there has been growing debate about how to best manage these patients. There are a limited number of studies investigating this. Following the previous article, which explored diagnosis and staging of CKD, this part focuses on dietary management, including an overview of the evidence base for the therapeutic renal diets traditionally used from IRIS stage 2 and our current understanding and evidence to support potential dietary changes in cats with early (IRIS stage 1 or early stage 2) CKD. Discussion of how and when these should be made is also included.

Diagnostic utility of different models used to assess the acid-base balance in cats with chronic kidney disease.

Metabolic acidosis is diagnosed based on the concentration of bicarbonate ions and partial pressure of carbon dioxide in arterial blood, although acid-base balance (ABB) disorders may also be diagnosed based on the serum ion concentrations in order to determine the values of strong ion difference (SID), anion gap (AG), corrected anion gap (AGcorr) and chloride/sodium ratio (Cl-/Na+). The aim of this study was to assess and compare the classic model, the value of the AG, AGcorr, and Cl-/Na+ in the diagnosis of ABB disorders in cats with chronic kidney disease (CKD). The study group consisted of 80 cats with CKD, divided into four groups based on the guidelines of the International Renal Interest Society (IRIS). The control group (C) included 20 healthy cats. Metabolic acidosis - diagnosed based on the classic model (Hendersson-Hasselbalch equation) - was found in IRIS group IV. AG, AGcorr, SID calculated for IRIS groups II, III and IV were lower than in group C, while the value of AGdiff and Cl-/Na+ in those groups was higher than in group C. We can conclude that ABB analysis using the classic model enabled the detection of ABB disorders in cats in stage IV CKD. However, the analysis of the AG, AGcorr and Cl-/Na+ values enabled the diagnosis of acid-base balance disorders in cats with IRIS stage II, III and IV CKD.

Effects of low-dose meloxicam in cats with chronic kidney disease.

Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD). Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (β):creatinine ratio, urine clusterin, urine cystatin B and serum inosine. No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-β:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months (P = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects. No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.

Relationship between ultrasonographically determined renal dimensions and International Renal Interest Society stages in cats with chronic kidney disease.

BackgroundThe correlation between renal dimensions and renal function in cats with chronic kidney disease (CKD) is unclear.Hypothesis/ObjectivesTo investigate the relationship between renal dimensions and CKD severity in cats using ultrasound examination.AnimalsNineteen healthy cats and 30 cats with CKD.MethodsRenal ultrasound images obtained between 2012 and 2016 were reviewed. Severity of CKD was determined using the International Renal Interest Society CKD staging system. Renal length, cortical thickness, medullary thickness, and corticomedullary ratio were measured, and the relationship between these renal dimensions and serum creatinine concentrations as well as differences in dimensions between the control and disease groups was investigated. The sensitivity and specificity of the renal dimensions for differentiation of the CKD also were evaluated.ResultsThe disease group was subdivided into stage I to II (15 cats) and stage III to IV (15 cats) groups. Cortical thickness was significantly decreased in both disease groups and negatively correlated with disease severity. Compared with other renal dimensions, cortical thickness had a stronger linear correlation with the reciprocal of the serum creatinine concentration and superior diagnostic performance (Youden index: left kidney, 90.0% sensitivity and 94.7% specificity for a cutoff of 4.7 mm; right kidney, 83.3% sensitivity and 94.7% specificity for a cutoff of 4.5 mm).Conclusions and Clinical ImportanceDecreased renal cortical thickness is observed in cats with loss of renal function. Measurement of cortical thickness using ultrasonography could be a useful method to evaluate the progression of CKD in cats.