Risk factors and implications associated with ultrasound-diagnosed nephrocalcinosis in cats with chronic kidney disease.

BACKGROUND: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. OBJECTIVES: Identify risk factors associated with ultrasound-diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. ANIMALS: Thirty-six euthyroid client-owned cats with CKD. METHODS: Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound-diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. RESULTS: Ultrasound-diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log-transformed fibroblast growth factor-23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P < .001) and decreasing body weight (.02 ± .01 kg/month; P < .001) over time. CONCLUSIONS AND CLINICAL IMPORTANCE: Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats.

International Renal Interest Society best practice consensus guidelines for the diagnosis and management of acute kidney injury in cats and dogs.

Acute kidney injury (AKI) is defined as an injury to the renal parenchyma, with or without a decrease in kidney function, as reflected by accumulation of uremic toxins or altered urine production (i.e., increased or decreased). AKI might result from any of several factors, including ischemia, inflammation, nephrotoxins, and infectious diseases. AKI can be community- or hospital-acquired. The latter was not previously considered a common cause for AKI in animals; however, recent evidence suggests that the prevalence of hospital-acquired AKI is increasing in veterinary medicine. This is likely due to a combination of increased recognition and awareness of AKI, as well as increased treatment intensity (e.g., ventilation and prolonged hospitalization) in some veterinary patients and increased management of geriatric veterinary patients with multiple comorbidities. Advancements in the management of AKI, including the increased availability of renal replacement therapies, have been made; however, the overall mortality of animals with AKI remains high. Despite the high prevalence of AKI and the high mortality rate, the body of evidence regarding the diagnosis and the management of AKI in veterinary medicine is very limited. Consequently, the International Renal Interest Society (IRIS) constructed a working group to provide guidelines for animals with AKI. Recommendations are based on the available literature and the clinical experience of the members of the working group and reflect consensus of opinion. Fifty statements were generated and were voted on in all aspects of AKI and explanatory text can be found either before or after each statement.

Detection of nephrocalcinosis using ultrasonography, micro-computed tomography, and histopathology in cats.

BACKGROUND: Identification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain. OBJECTIVES: To compare ultrasonography, micro-computed tomography (µCT) and histopathology for identification of nephrocalcinosis. ANIMALS: Twelve kidneys from 7 euthyroid client-owned cats with CKD. METHODS: Descriptive study. Renal ultrasonography was performed ante-mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using µCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume-to-kidney tissue ratio (macro-VN:KT) and sagittal nephrocalcinosis area-to-kidney tissue ratio (macro-AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin-fixed, and paraffin-embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK-micro-AN:KT and AR-micro-AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation. RESULTS: Nephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro-VN:KT was 0.001%, 0.001%, and 0.019%, and the macro-AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK-micro-AN:KT was 0.21%, 2.85%, and 4.56%, and AR-micro-AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro-nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro-AN:KT) and microscopic (VK-micro-AN:KT) nephrocalcinosis (rs = 0.76; P = .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Ultrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time.

Ionized hypercalcemia in cats with azotemic chronic kidney disease (2012-2018).

BACKGROUND: Hypercalcemia is associated with chronic kidney disease (CKD) in cats, but studies assessing the physiologically relevant ionized calcium fraction are lacking. OBJECTIVES: To describe the prevalence and incidence rate of ionized hypercalcemia, and to explore predictor variables to identify cats at risk of ionized hypercalcemia in a cohort of cats diagnosed with azotemic CKD. ANIMALS: One hundred sixty-four client-owned cats with azotemic CKD. METHODS: Variables independently associated with ionized hypercalcemia at diagnosis of azotemic CKD were explored by binary logistic regression. Cats that were normocalcemic at diagnosis of azotemic CKD were followed over a 12-month period or until ionized hypercalcemia occurred and baseline predictor variables for ionized hypercalcemia explored using Cox proportional hazards and receiver operating characteristic curve analysis. RESULTS: Ionized hypercalcemia (median, 1.41 mmol/L; range, 1.38-1.68) was observed in 33/164 (20%) cats at diagnosis of azotemic CKD and was associated with male sex, higher plasma total calcium and potassium concentrations, and lower plasma parathyroid hormone concentrations. Twenty-five of 96 initially normocalcemic (26%) cats followed for minimum 90 days developed ionized hypercalcemia (median, 1.46 mmol/L; range, 1.38-1.80) at a median of 140 days after diagnosis of azotemic CKD (incidence rate, 0.48 per feline patient-year). Only body condition score was independently associated with incident ionized hypercalcemia. CONCLUSIONS AND CLINICAL IMPORTANCE: The occurrence of ionized hypercalcemia is high in cats with CKD. Continued monitoring of blood ionized calcium concentrations is advised.

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats.

BACKGROUND: Nephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored. OBJECTIVES: Identify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all-cause mortality. ANIMALS: Fifty-one euthyroid client-owned cats with International Renal Interest Society (IRIS) stages 2-3 azotemic CKD. METHODS: Retrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner-reported time-averaged phosphate-restricted diet (PRD) intake, where PRD comprised ≥50%, 10-50%, or none of food intake. RESULTS: Nephrocalcinosis was rated as mild-to-severe in 78.4% and absent-to-minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%-50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent-to-minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1-year period, and had shorter median survival times than cats with mild-to-severe nephrocalcinosis. CONCLUSION AND CLINICAL IMPORTANCE: Higher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.

Feline comorbidities: The intermingled relationship between chronic kidney disease and hypertension.

PRACTICAL RELEVANCE: Chronic kidney disease (CKD) is a highly prevalent disorder of senior cats. CKD is frequently diagnosed in association with hypertension, and the two conditions have an intermingled cause-and-effect relationship. Hypertensive target organ damage (TOD) to the eye, brain, heart and kidney significantly impacts the welfare of cats suffering from this comorbidity. Hypertension also drives proteinuria, which is an independent risk factor for progression and mortality in cats with CKD. Blood pressure monitoring and institution of effective antihypertensive treatment, where indicated, is therefore crucial in effective management of the feline CKD patient. Current guidelines recommend a target systolic blood pressure of <160 mmHg to minimise risk of TOD. Both amlodipine besylate and telmisartan are effective antihypertensive agents for use in these patients. CLINICAL CHALLENGES: Clinical signs of hypertension may not be apparent to owners of affected cats until severe hypertensive TOD is present. Despite this, blood pressure monitoring in cats with CKD is still infrequently performed, and hypertension likely remains underdiagnosed in this population. EVIDENCE BASE: This review is based upon evaluation of the currently available published literature, including relevant consensus statements. There is a large body of evidence supporting the association between hypertension and CKD in cats. However, significant aspects, such as the mechanisms behind this association, and effect of hypertension and antihypertensive treatment on mortality and progression of CKD, remain unclear. Further research is therefore required in order to improve understanding of these conditions.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 1: Physiology of calcium handling.

Mineral derangements are a common consequence of chronic kidney disease (CKD). Despite the well-established role of phosphorus in the pathophysiology of CKD, the implications of calcium disturbances associated with CKD remain equivocal. Calcium plays an essential role in numerous physiological functions in the body and is a fundamental structural component of bone. An understanding of calcium metabolism is required to understand the potential adverse clinical implications and outcomes secondary to the (mal)adaptation of calcium-regulating hormones in CKD. The first part of this two-part review covers the physiology of calcium homeostasis (kidneys, intestines and bones) and details the intimate relationships between calcium-regulating hormones (parathyroid hormone, calcitriol, fibroblast growth factor 23, α-Klotho and calcitonin) and the role of the calcium-sensing receptor.

A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 2: Pathophysiology of calcium disorder and extraosseous calcification.

Derangements in mineral metabolism are one of the main entities in chronic kidney disease-mineral and bone disorder (CKD-MBD). This is the second of a two-part review of the physiology and pathophysiology of calcium homeostasis in feline CKD-MBD. While dysregulation in calcium homeostasis is known to contribute to the development of vascular calcification in CKD, evidence characterising the relationship between serum calcium concentration and nephrocalcinosis and nephrolithiasis is limited. Recently, fibroblast growth factor 23 (FGF23) and α-Klotho have gained increased research interest and been shown to be important biomarkers for the prediction of CKD progression in human patients. However, conflicting evidence exists on their role in calcium homeostasis and vascular and soft tissue calcification. This review details the pathophysiology of calcium disorders associated with CKD-MBD and its implications on vascular and soft tissue mineralisation in human and feline patients. Further prospective studies investigating the clinical consequences of calcium disturbances in cats with CKD are warranted and this may provide additional insight into the pathophysiology of feline CKD-MBD.

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.

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

BACKGROUND: Dietary 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. OBJECTIVES: To 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. ANIMALS: Seventy-one geriatric (≥9 years) euthyroid client-owned cats with International Renal Interest Society (IRIS) stage 2 to 3 azotemic CKD. METHODS: Retrospective 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. RESULTS: Lower 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 (ß = .069 ± .029 mg/dL; P = .02), symmetric dimethylarginine (ß = .64 ± .29 µg/dL; P = .03), phosphate (ß = .129 ± .062 mg/dL; P = .04), and ln[FGF23] (ß = .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 IMPORTANCE: Lower 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.

The association of bacteriuria with survival and disease progression in cats with azotemic chronic kidney disease.

BACKGROUND: Cats with chronic kidney disease (CKD) have an increased prevalence of positive urine cultures (PUC). Limited information is available regarding the prognosis of cats with CKD and concurrent PUC. OBJECTIVE: To determine the association of PUC with survival time and disease progression in cats with CKD. ANIMALS: Medical records of 509 cats diagnosed with azotemic CKD between 1997 and 2018. METHODS: Cats were classified as having "no-PUC" or "PUC." The PUC cats were further classified as having 1 or multiple PUC, and also were classified based on the presence or absence of clinical signs of urinary tract infection (UTI). Progression of CKD was defined as a plasma creatinine concentration increase of ≥25% within 365 days of CKD diagnosis; PUC also must have occurred within this time frame. Survival time and frequency of CKD progression were compared between groups. RESULTS: No significant difference in survival time was found between cats with no-PUC and cats with any number of PUC (P = .91), or between cats with no-PUC, 1 PUC or multiple PUC (P = .37). Also, no significant difference was found in the frequency of CKD progression between PUC and no-PUC cats (P = .5), or among no-PUC, 1 PUC and multiple PUC cats (P = .22). When assessing cats with clinical signs of lower UTI, no significant difference was found in the frequency of CKD progression between cats with true UTI, subclinical bacteriuria or no-PUC (P = .8). CONCLUSIONS AND CLINICAL IMPORTANCE: When treated with antibiotics, PUC in cats with CKD do not affect disease progression or survival time.

Fibroblast growth factor 23 and symmetric dimethylarginine concentrations in geriatric cats.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that is increased in azotemic cats with chronic kidney disease (CKD) and predictive of the onset of azotemia in older cats. The introduction of symmetric dimethylarginine (SDMA) as a biomarker of glomerular filtration rate has led to the identification of cats in which SDMA is increased, but plasma creatinine concentrations remains within reference range. There is currently little understanding of the metabolic changes present in such cats. OBJECTIVES: To examine the relationship between plasma FGF23 and SDMA concentrations in non-azotemic geriatric cats. ANIMALS: Records of a cross section of client-owned cats (n = 143) without azotemic CKD. METHODS: Clinicopathological information was obtained from cats (≥ 9 years) from records of 2 first opinion practices. The relationship between plasma SDMA and FGF23 concentrations was examined using Spearman's correlation and variables compared using the Mann-Whitney U test. RESULTS: Cats with increased SDMA concentrations had significantly higher plasma FGF23 (P < .001) and creatinine (P < .001) concentrations compared to cats with SDMA concentrations within reference range. A weak positive relationship was demonstrated between plasma FGF23 and SDMA concentrations (r = .35, P < .001) and between plasma FGF23 and creatinine (r = .23, P = .005) concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: More cats with increased SDMA concentrations had higher FGF23 concentrations than those with SDMA concentrations within the reference range, suggesting the presence of an alteration in phosphate homeostasis. Further studies are warranted to identify influencing factors and to explore the utility of FGF23 concentration to inform management of cats with early stage CKD.

Development and validation of a multivariate predictive model to estimate serum ionized calcium concentration from serum biochemical profile results in cats.

BACKGROUND: Measurement of serum ionized calcium is not always available in practice. Total calcium (tCa) might not be reliable for determination of calcium status in cats. OBJECTIVES: To predict serum ionized calcium concentration from signalment, biochemistry profile and T4, and compare predicted ionized calcium (piCa) to tCa. ANIMALS: A total of 1701 cats from two hospitals. METHODS: Cross-sectional study. Cats with serum ionized calcium, biochemistry profile and T4 available were screened over 6 years and included in the training set (569 cats) to create a multivariate adaptive regression splines model to calculate piCa. Diagnostic performances of tCa and piCa and its prediction interval (PI) were compared in 652 cats from the same institution (test set) and 480 cats from a different hospital (external set). RESULTS: The final model included tCa, chloride, albumin, cholesterol, creatinine, BUN, body condition score, GGT, age, and potassium. For hypercalcemia, piCa was highly specific (test set: 99.8%; confidence interval [CI]: 99.5-100; external set: 97%; CI: 95.3-98.7) but poorly sensitive (test set: 30.4%; CI: 18.3-42.4; external set: 42.5%; CI: 31.7-53.3). For hypocalcemia, piCa was also highly specific (test set: 81.6%; CI: 78-85; external set: 99.6%; CI: 99-100) but poorly sensitive (test set: 57.6%; CI: 50.6-64.6; external set: 0%). These diagnostic performances were comparable to those of tCa. The upper and lower limits of piCa PI had high sensitivity for detecting ionized hypercalcemia and hypocalcemia, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Predicted ionized calcium is useful to confirm suspected hypercalcemia in cats and screen for hypercalcemia and hypocalcemia.

Primary hemostatic function in dogs with acute kidney injury.

BACKGROUND: Bleeding tendencies can occur with uremia. OBJECTIVES: To characterize primary hemostatic function in dogs with acute kidney injury (AKI). ANIMALS: Ten dogs with International Renal Interest Society AKI grade III or above and 10 healthy controls. METHODS: Prospective study comparing PCV, platelet count, platelet aggregometry (Multiplate), and von Willebrand factor antigen to collagen binding activity ratio (vWF:Ag:vWF:CBA) in 2 groups of dogs (AKI group versus controls). Buccal mucosal bleeding time was measured in the AKI group only. Data are presented as median [25th, 75th percentile] unless otherwise stated. Significance was set at P < .05. RESULTS: Mean PCV was significantly lower in the AKI (34.7%; ±SD, 8.8) than in the control (46.1%; ±SD, 3.6; P < .001) group. Platelet count was significantly higher in the AKI (350.5 × 103 /µL [301, 516]) than in the control (241 × 103 /µL [227, 251]; P = .01) group. Collagen-activated platelet aggregometry measured as area under the curve was significantly lower in the AKI (36.9 ± 17.7) than in the control (54.9 ± 11.2; P = .05) group. vWF:Ag:vWF:CBA was significantly higher in the AKI (2.2 [1.9, 2.6]) than in the control (1.1 [1.1, 1.2]; P = .01) group. There was a strong correlation between vWF:Ag:vWF:CBA and creatinine (r = 0.859; P < .001), but no other variables. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with AKI had decreased collagen-activated platelet aggregation and appear to have a type II von Willebrand disease-like phenotype as indicated by the high vWF:Ag:vWF:CBA.

Cutaneous and Renal Glomerular Vasculopathy: What Do We Know so Far?

Cutaneous renal glomerular vasculopathy (CRGV), colloquially named "Alabama rot," is an emerging condition in the United Kingdom, previously reported from the United States and Germany. The cause of CRGV is not yet determined; no definitive link to an infectious agent has been made. Dogs diagnosed with CRGV initially develop cutaneous lesions, and a proportion of these dogs go on to manifest acute kidney injury, which may result in oligoanuric acute renal failure. Antemortem diagnosis is challenging given the lack of a specific diagnostic test, and confirmation of CRGV is therefore currently dependent on identification of thrombotic microangiopathy on renal histopathology.

ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats.

An update to the 2007 American College of Veterinary Internal Medicine (ACVIM) consensus statement on the identification, evaluation, and management of systemic hypertension in dogs and cats was presented at the 2017 ACVIM Forum in National Harbor, MD. The updated consensus statement is presented here. The consensus statement aims to provide guidance on appropriate diagnosis and treatment of hypertension in dogs and cats.

Description of the Use of Plasma Exchange in Dogs With Cutaneous and Renal Glomerular Vasculopathy.

Cutaneous and renal glomerular vasculopathy (CRGV) is a rare disease affecting dogs, with a recent apparent increase in prevalence since 2012 in the UK. This disease is characterized by a vasculopathy affecting small vessels of the kidney and skin, leading to thrombotic microangiopathy. The underlying etiology remains unknown although clinicopathological and histological findings resemble features of certain forms of thrombotic microangiopathy in people, for which plasma exchange (PEX) is considered an important component of therapy. The objective of the present study is to describe the use of PEX as adjunctive treatment in dogs diagnosed with CRGV. A retrospective review of dogs diagnosed with CRGV between 2014 and 2016 treated with PEX was performed. Clinical records were reviewed and data relating to signalment, diagnostic tests and management strategies were summarized. Information and complications relating to PEX were recorded. Six dogs were diagnosed with CRGV (n = 2 ante-mortem, n = 4 post-mortem) and underwent PEX as part of their therapy. All dogs had cutaneous lesions and were azotemic with oliguria or anuria. All dogs underwent at least one PEX cycle; one dog had a single cycle PEX, three dogs two cycles PEX, and two dogs had one cycle PEX and one cycle of prolonged intermittent renal replacement treatment. Complications seen during PEX therapy included hypothermia (n = 4), tachycardia (n = 2), hypotension (n = 2), and hypocalcemia (n = 6). Two dogs survived to discharge, the remaining four dogs were euthanized. The positive outcome in two dogs treated with PEX despite the reported high mortality rate once acute kidney injury with oliguria/anuria occurs does not confirm success of this treatment. However, survival in two dogs that were initially oligoanuric highlights that further consideration and evaluation of PEX for this patient group is warranted for this specific disease. Additional studies are urgently needed to identify the underlying etiology of CRGV before more targeted therapies can be developed. Based on our findings, further evaluation of the role of PEX in this specific disease are warranted.

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease.

BACKGROUND: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. OBJECTIVES: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. ANIMALS: Records of 174 client-owned cats with IRIS stage 2-4 CKD. METHODS: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999-2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. RESULTS: Plasma tMg (reference interval, 1.73-2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, -0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35-5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54-5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04-154; P = .009) lost significance in multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation.

ISFM Consensus Guidelines on the Diagnosis and Management of Hypertension in Cats.

Practical relevance: Feline hypertension is a common disease in older cats that is frequently diagnosed in association with other diseases such as chronic kidney disease and hyperthyroidism (so-called secondary hypertension), although some cases of apparent primary hypertension are also reported. The clinical consequences of hypertension can be severe, related to 'target organ damage' (eye, heart and vasculature, brain and kidneys), and early diagnosis followed by appropriate therapeutic management should help reduce the morbidity associated with this condition. Clinical challenges: Despite being a common disease, routine blood pressure (BP) monitoring is generally performed infrequently, probably leading to underdiagnosis of feline hypertension in clinical practice. There is a need to: (i) ensure BP is measured as accurately as possible with a reproducible technique; (ii) identify and monitor patients at risk of developing hypertension; (iii) establish appropriate criteria for therapeutic intervention; and (iv) establish appropriate therapeutic targets. Based on current data, amlodipine besylate is the treatment of choice to manage feline hypertension and is effective in the majority of cats, but the dose needed to successfully manage hypertension varies between individuals. Some cats require long-term adjuvant therapy and, occasionally, additional therapy is necessary for emergency management of hypertensive crises. Evidence base: These Guidelines from the International Society of Feline Medicine (ISFM) are based on a comprehensive review of the currently available literature, and are aimed at providing practical recommendations to address the challenges of feline hypertension for veterinarians. There are many areas where more data is required which, in the future, will serve to confirm or modify some of the recommendations in these Guidelines.

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats.

In cats with chronic kidney disease (CKD), the most common histopathologic finding is tubulointerstitial inflammation and fibrosis. However, these changes reflect a nonspecific response of the kidney to any inciting injury. The risk of developing CKD is likely to reflect the composite effects of genetic predisposition, aging, and environmental and individual factors that affect renal function over the course of a cat's life. However, there is still little information available to determine exactly which individual risk factors predispose a cat to develop CKD. Although many cats diagnosed with CKD have stable disease for years, some cats show overtly progressive disease.