The circulating renin-angiotensin-aldosterone system is down-regulated in dogs with glomerular diseases compared to other chronic kidney diseases with low-grade proteinuria.

Glomerular diseases (GD) lead to a variety of disorders of the vascular and the total body water volumes. Various pathomechanisms, including vascular underfill and overfill, have been suggested to explain these disturbances. Accordingly, the circulating renin-angiotensin-aldosterone system (cRAAS) is expected to be activated as either a cause or a result of these fluid disorders. The aim of this study was to characterize the activity of the cRAAS in dogs with GD and to evaluate its relationship with the vascular volume status. In a prospective study, we evaluated the plasma renin activity and the serum aldosterone concentration in 15 dogs with GD. Their fluid volume status was estimated with clinical variables reflecting volemia and hydration, echocardiographic volume assessment, N-terminal pro B-type natriuretic peptide, blood urea nitrogen:creatinine ratio, and the urinary fractional excretion of sodium. Ten dogs with chronic kidney disease (CKD) with matching degree of azotemia were recruited as controls. The activity of the cRAAS was low in 10 dogs, normal in 3 dogs, high in 1 dog and equivocal (high renin-low aldosterone) in 1 dog with GD. These dogs had a lower cRAAS activity than dogs with CKD (p = 0.01). The clinical evaluation showed 8 hypovolemic and 7 non-hypovolemic dogs; 3 dehydrated, 9 euhydrated and 3 overhydrated dogs. The cRAAS activity was not different between hypovolemic and non-hypovolemic dogs. The down-regulated cRAAS without obvious association with the clinical volume status of these dogs with GD, suggests different mechanisms of fluid volume dysregulation in dogs with GD than previously assumed. This finding however should be confirmed in a focused larger scale study, as it may influence the use of cRAAS blockers as part of the standard therapy of GD in dogs.

Retrospective evaluation of the influence of azotemia on plasma lactate concentrations in hypotensive dogs and cats (2008-2018): 337 cases.

OBJECTIVE: To evaluate the relationship between azotemia and plasma lactate concentration in hypotensive dogs and cats presented to an emergency department. DESIGN: Retrospective case-control study. SETTING: University veterinary teaching hospital. ANIMALS: The electronic medical record database was searched for dogs and cats presented to the emergency department that had severe azotemia (creatinine ≥ 443.1 µmol/L [5 mg/dL]), hypotension (systolic blood pressure ≤ 90 mm Hg), and a plasma lactate measurement within 2 h of each another. Non-azotemic, normotensive dogs and cats; non-azotemic, hypotensive dogs and cats; and azotemic, normotensive dogs and cats that presented to the emergency department were used as control populations. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Severely azotemic, hypotensive dogs (n = 10) and cats (n = 63) had a lower plasma lactate than non-azotemic, hypotensive dogs and cats (P = 0.031 and P < 0.001, respectively). Median plasma lactate concentrations in hypotensive dogs (1.75 mmol/L) and cats (1.90 mmol/L) with severe azotemia were within reference intervals. CONCLUSIONS: Hypotensive dogs and cats with severe azotemia have decreased plasma lactate concentrations as compared to hypotensive, non-azotemic dogs and cats. The median plasma lactate in azotemic, hypotensive dogs and cats was within reference intervals. This may be due to either decreased cellular production of lactate or increased excretion of lactate. Further research is needed to determine which of these mechanisms is responsible and the clinical significance of plasma lactate concentrations in azotemic, hypotensive dogs and cats.

Uremia Preventing Osmotic Demyelination Syndrome Despite Rapid Hyponatremia Correction.

Hyponatremia is the most common electrolyte abnormality encountered both in the inpatient and outpatient clinical settings in the United States. Rapid correction leads to a deranged cerebral osmotic gradient causing osmotic demyelination syndrome. Coexisting azotemia is considered to be protective against osmotic demyelination syndrome owing to its counteractive effect on osmolarity change that occurs with rapid hyponatremia correction. In this article, we report the case of a 37-year-old male who presented with altered mentation, acute azotemia, and severe electrolyte derangements, with serum blood urea nitrogen 160 mg/dL, creatinine 8.4 mg/dL, sodium 107 mEq/L, potassium 6.1 mEq/L, bicarbonate 7 mEq/L, and anion gap of 33. Given refractory hyperkalemia with electrocardiogram changes, emergent dialysis was performed. Despite our efforts to avoid rapid correction, serum sodium was corrected to 124 mEq/L and blood urea nitrogen decreased to 87 mg/dL at the end of the 5-hour dialysis session. Fortunately, hospital course and 4-week post-discharge clinic follow-ups were uncomplicated with no neurological sequela confirmed by neurological examination and magnetic resonance imaging.

Serum concentration of homocysteine in spontaneous feline chronic kidney disease.

Serum homocysteine (Hcy) increases in people and dogs with chronic kidney disease (CKD). Hyperhomocysteinemia (HHcy) has also been associated with CKD-related hypertension and proteinuria. The aims of this study were to: (1) validate an enzymatic method for quantification of Hcy in feline serum; (2) evaluate whether HHcy was associated with the presence and severity of CKD, proteinuria or hypertension; and (3) determine whether HHcy could predict disease progression. The intra- and inter-assay coefficients of variation (CVs) and the recovery rates of linearity under dilution and spiking recovery tests of the enzymatic method were 3.1-6.7%, 11.6-12.5%, 96.9±5.4% and 96.9±5.4%, respectively. Healthy cats at risk of CKD (n=17) and cats with CKD (n=19) were sampled over a 6-month period (63 samples in total). Cats with CKD had significantly higher Hcy concentrations (P=0.005) than cats at risk. The concentration of Hcy was higher (P=0.002) in moderate-severe CKD than in mild CKD and correlated moderately with serum creatinine (P<0.0001; r=0.51). The concentration of Hcy increased with the magnitude of proteinuria and correlated weakly with urinary protein to creatinine ratio (P=0.045; r=0.26). HHcy was not associated with hypertension. At the time of enrollment, Hcy concentration was significantly higher (P=0.046) in cats that developed CKD compared to cats that remained stable. The enzymatic method for Hcy measurement in feline serum was precise and accurate. HHcy was relatively common in cats with advanced CKD and seemed to predict disease progression, but further studies are warranted.

Changes in thyroid and renal function after bilateral thyroidectomy in cats.

BACKGROUND: Iatrogenic hypothyroidism might worsen the prognosis of cats with azotemic CKD after thyroidectomy. Varying thyroxine concentrations influence utility of creatinine in assessing renal function. Symmetric dimethylarginine (SDMA) has limited studies in cats with changing thyroid status. OBJECTIVES: Thyroid status is stable 6 months post-thyroidectomy. Symmetric dimethylarginine and creatinine are linearly associated without influence from total thyroxine concentration (tT4). ANIMALS: Electronic records of 2 first opinion practices were searched using the term "thyroidectomy" to include 81 client-owned cats that had undergone bilateral thyroidectomy. METHODS: Retrospective cross-sectional study assessing thyroid hormone concentrations of 68 cats within 6 months of surgery. A longitudinal study of thyroid status in 23 cats with >18 months follow-up post-thyroidectomy. A generalized estimating equation assessed the associations of bodyweight, tT4 and creatinine concentrations on SDMA concentration. RESULTS: Sixty-eight cats had follow-up within 6 months. Fifteen cats (22%) had persistent, or recurrent, hyperthyroidism and 33 cats (49%) were hypothyroid. Twenty-three of the euthyroid/hypothyroid cats had long-term follow-up (595-1955 days); 4 cats (17%) remained hypothyroid, 19 cats (83%) were euthyroid (often transiently), and 9 of 23 cats (44%) developed recurrent hyperthyroidism. Symmetric dimethylarginine and creatinine were linearly associated, but hyperthyroid cats had higher SDMA concentrations, relative to creatinine (P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Cats have changes in thyroid function for years after bilateral thyroidectomy, with a high incidence of recurrent hyperthyroidism. Both SDMA and creatinine are affected by thyroxine concentrations, and the effect is greater in hyperthyroid cats.

Assessment and prediction of acute kidney injury in patients with decompensated cirrhosis with serum cystatin C and urine N-acetyl-ß-D-glucosaminidase.

BACKGROUND AND AIM: For appropriate management of acute kidney injury (AKI) in cirrhotic patients, accurate differentiation of the types of AKI, prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN) is very important. Urine N-acetyl-ß-D-glucosaminidase (NAG) has been proposed as a good tubular injury marker in many studies, but its efficacy in cirrhosis is unclear. This study was performed to evaluate the usefulness of urine NAG in patients with decompensated cirrhosis. METHODS: In 114 hospitalized patients with decompensated cirrhosis, we assessed serum creatinine, cystatin C, and urine NAG levels as markers for AKI differentiation and development and patient mortality. RESULTS: Thirty patients diagnosed with AKI at baseline had significantly higher serum creatinine and cystatin C levels, urine NAG levels, and Child-Pugh scores than those without AKI. Only urine NAG levels were significantly higher in patients with ATN than those with PRA or HRS (116.1 ± 46.8 U/g vs 39.4 ± 20.2 or 54.0 ± 19.2 U/g urinary creatinine, all P < 0.05). During a median follow up of 6.1 months, AKI developed in 17 of 84 patients: PRA in nine, HRS in six, and ATN in three. Higher serum cystatin C and urine NAG levels were independent predictors of AKI development in patients with decompensated cirrhosis. Survival was significantly associated with low serum cystatin C and urine NAG levels. CONCLUSION: Serum cystatin C and urine NAG levels are useful to differentiate types of AKI and are strong predictors for AKI development and mortality in patients with decompensated cirrhosis.

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.

Acute glomerulonephritis secondary to Streptococcus anginosus.

Streptococcus anginosus is a clinically important pathogen that is emerging globally but remains poorly investigated. Here, we report the first case of acute glomerulonephritis resulting from infection with S. anginosus Glomerulonephritis is typically caused by S. pyogenes and reports secondary to other strains including S. zooepidemicus and S. constellatus exist. Infection with S. anginosus in this patient was associated with acute nephritis (haematuria, oedema and hypertension), nephrotic syndrome and progressive azotemia. There was activation of the complement system. The presence of low C1q and elevated anti-C1q binding complexes points to a potential pathogenic role. Testing for streptococcal antigens was strongly positive. Emerging nephritogenic strains of S. anginosus present a significant health concern for both developed and developing countries.

Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism.

BACKGROUND: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. OBJECTIVES: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. ANIMALS: Two hundred and sixty-two hyperthyroid cats and 206 aged-matched, clinically normal cats. METHODS: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4 , and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131 I) and classified 131 I-treated cats as azotemic or nonazotemic based on persistent, post-treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. RESULTS: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4-8 months (median, 6 months) after 131 I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. CONCLUSIONS AND CLINICAL IMPORTANCE: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false-positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

BACKGROUND: The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. METHODS: This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. RESULTS: The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. CONCLUSIONS: Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis.

EDL peptide produced a nephroprotective effect on experimental models gentamycin-induced nephropathy and ischemia/reperfusion kidney injury in rats. The nephroprotective effect of EDL peptide manifested in prevention of oliguria and retention azotemia, a decrease in proteinuria and sodium excretion, prevention of critical decrease in activities of antioxidant enzymes, suppression of LPO, and normalization of energy supply to kidneys cells. Our findings confirm the prospects of further studies of the nephroprotective properties of peptide EDL in various pathologies of the kidneys.

Cardiac Troponin I and Amino-Terminal Pro B-Type Natriuretic Peptide in Dogs With Stable Chronic Kidney Disease.

BACKGROUND: Increased concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in dogs with azotemia have been documented. Knowledge of mechanisms behind increased concentrations of cardiac biomarkers in dogs with azotemia is warranted for correct interpretation of test results. OBJECTIVES: The aim of the article was to investigate possible associations between plasma concentrations of cTnI and NT-proBNP, respectively, and patient characteristics, glomerular filtration rate (GFR), a plasma volume factor (PVF) derived from scintigraphic examination (PVf), systolic blood pressure (SBP), selected hematologic and biochemical variables, and echocardiographic measurements in dogs with stable chronic kidney disease (CKD) and in healthy dogs. ANIMALS: Fifty student-, staff-, and client-owned dogs were included. Twenty-three of the dogs were healthy and 27 were diagnosed with CKD. METHODS: In this cross-sectional observational study, dogs with a previous diagnosis of CKD and healthy control dogs were included. At inclusion, all dogs were characterized by physical examination, repeated blood pressure measurements, complete urinalysis, hematology and biochemistry panel, echocardiography, abdominal ultrasound examination of the entire urinary tract, and scintigraphic examination for measurement of GFR. RESULTS: Plasma volume factor and PCV were independently associated with NT-proBNP (Radj2 = 0.42; P < .0001). Age, body weight (BW), and SBP were independently associated with cTnI (Radj2 = 0.50; P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Neither NT-proBNP nor cTnI concentrations were independently associated with measured GFR. Thus, findings were not suggestive of passive accumulation of either marker, suggesting that increased circulating concentrations of cTnI and NT-proBNP can be interpreted similarly in dogs with stable CKD as in dogs without CKD.

The effect of urea on refractometric total protein measurement in dogs and cats with azotemia.

BACKGROUND: While protein is the predominant solute measured in plasma or serum by a refractometer, nonprotein substances also contribute to the angle of refraction. There is debate in the current literature regarding which nonprotein substances cause factitiously high refractometric total protein measurements, as compared to the biuret assay. OBJECTIVES: The purpose of the study was to determine if the blood of azotemic animals, specifically with increased blood urea concentration, will have significantly higher refractometric total protein concentrations compared to the total protein concentrations measured by biuret assay. METHODS: A prospective case series was conducted by collecting data from azotemic (n = 26) and nonazotemic (n = 34) dogs and cats. In addition, an in vitro study was performed where urea was added to an enhanced electrolyte solution at increasing concentrations, and total protein was assessed by both the refractometer and spectrophotometer. Statistical analysis was performed to determine the effect of urea. RESULTS: The refractometric total protein measurement showed a positive bias when compared to the biuret protein measurement in both groups, but the bias was higher in the azotemic group vs the nonazotemic group. The mean difference in total protein measurements of the nonazotemic group (0.59 g/dL) was significantly less (P < .01) than the mean difference of the azotemic group (0.95 g/dL). The in vitro experiment revealed a positive bias with a proportional error. CONCLUSIONS: This study demonstrated that increasing concentrations of urea significantly increased the total protein concentration measured by the refractometer as compared to the biuret assay, both in vivo and in vitro.

Excess fluid volume: sociodemographic and clinical analysis in haemodialysis patients.

OBJECTIVE:: To analyse the defining characteristics and related factors in the nursing diagnosis Excess fluid volume and its relationship to sociodemographic and clinical variables in haemodialysis patients. METHOD:: Cross-sectional study, conducted using a form and physical examination, with a sample of 100 patients, between December 2012 and April 2013 at a university hospital and a dialysis clinic. RESULTS:: It was found 10 significant statistical associations between the defining characteristics/ related factors of Excess fluid volume and the sociodemographic and clinical variables. CONCLUSION:: The defining characteristics and related factors of Excess fluid volume could be influenced by sociodemographic and clinical variables in haemodialysis clientele.