Iron Status of Cats with Chronic Kidney Disease

Background

Iron deficiency is a proposed mechanism for the anemia that occurs in cats with chronic kidney disease (CKD). Minimal research investigating the iron status of these cats has been performed.

Objective

To compare indicators of iron status in cats with CKD versus healthy cats and cats with nonrenal illness (NRI). To compare indicators of iron status in anemic versus nonanemic cats with CKD.

Animals

Thiry‐nine client or employee owned healthy cats, 40 cats with CKD and 34 cats with NRI included.

Methods

Exclusion criteria included prior iron or erythropoiesis stimulating agent administration, blood transfusion, or concurrent CKD and NRI. Complete blood counts, serum chemistries, serum iron concentrations, total iron binding capacity (TIBC), and ferritin concentrations were measured and percent transferrin saturation (TSAT) calculated on all cats. Data were analyzed using nonparametric statistical testing.

Results

No statistically significant differences were detected among groups for iron concentration (P = .50), ferritin concentration (P = .47), or TSAT (P = .19). TIBC was significantly lower in CKD (median 262 μg/dL; IQR 233–302; range 165–488) versus healthy cats (median 316 μg/dL; IQR 272–345, range 196–464); (P = .0030). When comparing anemic (hemoglobin <9.5 g/dL) versus nonanemic cats with CKD, TSAT was significantly lower (P = .033) in anemic (median 20.2%; IQR 17.8–34.5; range 17.6–35.9) compared to nonanemic (median 29.0%; IQR 25.5–44.1; range 11.5–94.4). No statistically significant differences found for ferritin concentration (P = .94), iron concentration (P = .21) or TIBC (P = .97).

Conclusions and Clinical Importance

These results indicate that an iron deficient state exists in anemic cats with CKD and is more likely functional rather than absolute.     

Quantitative Contrast‐enhanced Ultrasonographic Assessment of Naturally Occurring Pancreatitis in Dogs

Background

Quantitative contrast‐enhanced ultrasonography (CEUS) can detect pancreatic perfusion changes in experimentally induced canine pancreatitis. However, its usefulness in detecting perfusion changes in naturally occurring pancreatitis is unclear.

Hypothesis/Objectives

To determine the feasibility of using CEUS to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis.

Animals

Twenty‐three client‐owned dogs with pancreatitis, 12 healthy control dogs.

Methods

Dogs diagnosed with pancreatitis were prospectively included. CEUS of the pancreas and duodenum were performed. Time‐intensity curves were created from regions of interest in the pancreas and duodenum. Five perfusion parameters were obtained for statistical analyses: time to initial up‐slope, peak time (Tp), time to wash‐out (TTW), peak intensity (PI), and area under the curve (AUC).

Results

For the pancreas, Tp of the pancreatitis group was prolonged when compared to controls (62 ± 11 seconds versus 39 ± 13 seconds; P < .001). TTW also was prolonged but not significantly (268 ± 69 seconds versus 228 ± 47 seconds; P = .47). PI and AUC were increased when compared to controls (95 ± 15 versus 78 ± 13 MPV; P = .009 and 14,900 ± 3,400 versus 11,000 ± 2,800 MPV*s; P = .013, respectively). For the duodenum, PI and AUC were significantly increased in the pancreatitis group when compared to controls.

Conclusions and Clinical Importance

Contrast‐enhanced ultrasonography can detect pancreatic perfusion changes in naturally occurring canine pancreatitis characterized by delayed peak with prolonged hyperechoic enhancement of the pancreas on CEUS. Additionally, duodenal perfusion changes secondary to pancreatitis were observed.     

Computed Tomographic Angiography of the Pancreas in Cats with Chronic Diabetes Mellitus Compared to Normal Cats

Background

Diabetes mellitus (DM) is a common endocrinopathy in cats. No known diagnostic test or patient characteristic at the time of diagnosis can predict likely disease course, unlike in people in whom computed tomographic angiography (CTA) is used. No published data exist regarding the CTA appearance of the pancreas in cats with DM, and thus, it is unknown what if any CTA variables should be further assessed for associations with pancreatic endocrine function.

Hypothesis/Objectives

A significant difference in pancreatic attenuation, volume, and size will be identified between normal cats and those with chronic DM on CTA.

Animals

Ten healthy control cats and 15 cats with naturally occurring DM present for >12 months.

Methods

Prospective cross‐sectional study comparing pancreatic attenuation, enhancement pattern, size, volume, pancreatic volume‐to‐body weight ratio (V:BW), pancreatic arterial: portal phase ratio (A:P), time‐to‐arterial enhancement, and time‐to‐peak portal enhancement on CTA between sedated healthy control cats and those with chronic DM.

Results

The pancreas in cats with chronic DM was significantly larger, had higher volume, higher V:BW, and shorter time‐to‐peak portal enhancement on CTA when compared to normal cats.

Conclusions and Clinical Importance

Peak portal enhancement time, pancreatic size, pancreatic volume, and V:BW can be used to differentiate normal sedated cats from those with chronic DM by CTA. These variables warrant further investigation to identify possible associations with endocrine function.     

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Background

Fibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat.

Objectives

To investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months.

Animals

214 azotemic, client‐owned cats (≥9 years).

Methods

Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression.

Results

In the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression.

Conclusions and Clinical Importance

Plasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD.     

Changes in Systolic Blood Pressure over Time in Healthy Cats and Cats with Chronic Kidney Disease

Background

Hypertension is a common problem in older cats, most often associated with chronic kidney disease (CKD). Cross‐sectional studies have suggested that blood pressure in cats increases with age.

Hypothesis/Objectives

To determine whether blood pressure in cats increases with age and whether this occurs independently of the presence of CKD. To investigate risk factors for developing hypertension.

Animals/Subjects

Two hundred and sixty‐five cats with CKD and 133 healthy cats ≥9 years were retrospectively identified.

Methods

Four groups were created according to status at initial evaluation (CKD or healthy) and blood pressure at the last included visit (normotensive [NT] or developed hypertension [DH]): Healthy‐NT, Healthy‐DH, CKD‐NT and CKD‐DH. Systolic blood pressure (SBP) over time slopes were compared with 0 and between groups. Risk factors for the development of hypertension were investigated, and associations of biochemical and clinical variables with SBP were examined.

Results

Cats that were hypertensive at CKD diagnosis (n = 105) were not included in further analyses. Twenty‐seven cats with CKD and 9 healthy cats developed hypertension ≥3 months after diagnosis of CKD or their first visit. Systolic blood pressure significantly increased with age in all cats (P < .001). Healthy cats were at less risk than cats with CKD to become hypertensive (hazard ratio 0.2, P < .001), with creatinine being an independent risk factor for the development of hypertension.

Conclusions and Clinical Importance

The high prevalence of hypertension in azotemic cats in this study shows the importance of monitoring of SBP in elderly cats, and in particular in cats with CKD.     

Precision Medicine in Cats: Novel Niemann‐Pick Type C1 Diagnosed by Whole‐Genome Sequencing

State‐of‐the‐art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state‐of‐the‐art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole‐genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 25× genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann‐Pick type C1 on cat chromosome D3.47456793 caused by an adenine‐to‐cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population.     

Assessment of Vascular Perfusion Kinetics Using Contrast‐enhanced Ultrasound for the Diagnosis of Prostatic Disease in Dogs

Vascular perfusion was assessed in 10 dogs without prostatic abnormalities and 26 dogs with prostatic disease using contrast‐enhanced ultrasound. The time to reach peak contrast intensity (TTP) and peak perfusion intensity (PPI) were measured, and histological biopsies were collected from each dog. Biopsies confirmed normal prostate (n = 10), benign prostatic hyperplasia (n = 11), mixed benign pathology (n = 9), prostatitis (n = 1), prostatic malignancy [adenocarcinoma (n = 4); leiomyosarcoma (n = 1)]. In normal dogs, mean PPI was 16.8% ± 5.8 SD, and mean TTP was 33.6 ± 6.4 s. Benign conditions overall were not statistically different from normal dogs (p > 0.05); for benign prostatic hyperplasia, mean PPI was 16.9 ± 3.8%, and mean TTP was 26.2 ± 5.8 s; for mixed benign pathology mean PPI was 14.8 ± 7.8%, and mean TTP was 31.9 ± 9.7 s; for prostatitis, PPI was 14.2%, and TTP was 25.9 s. The malignant conditions overall had perfusion values that differed from the normal dogs (p < 0.05), although evaluation of the data for individual malignancies did not demonstrate a consistent trend; for adenocarcinomas, the PPI was numerically higher with a mean of 23.7 ± 1.9%, and the mean TTP was 26.9 ± 4.8 s, whilst for the dog with leiomyosarcoma values were numerically lower with a PPI of 14.1% and TTP of 41.3 s. Contrast‐enhanced ultrasound appears to offer some ability to document differences in perfusion that may differentiate between malignant and benign lesions, although studies with larger numbers of animals are required to confirm this contention.