Sylvie Daminet

Interactions between thyroid and kidney function in pathological conditions of these organ systems: A review

Thyroidal status affects kidney function already in the embryonic stage. Thyroid hormones influence general tissue growth as well as tubular functions, electrolyte handling and neural input. Hyper- and hypo-functioning of the thyroid influences mature kidney function indirectly by affecting the cardiovascular system and the renal blood flow, and directly by affecting glomerular filtration, electrolyte pumps, the secretory and absorptive capacity of the tubuli, and the structure of the kidney. Hyperthyroidism accelerates several physiologic processes, a fact which is reflected in the decreased systemic vascular resistance, increased cardiac output (CO), increased renal blood flow (RBF), hypertrophic and hyperplastic tubuli, and increased glomerular filtration rate (GFR). Renal failure can progress due to glomerulosclerosis, proteinuria and oxidative stress. Hypothyroidism has a more negative influence on kidney function. Peripheral vascular resistance is increased with intrarenal vasoconstriction, and CO is decreased, causing decreased RBF. The influence on the different tubular functions is modest, although the transport capacity is below normal. The GFR is decreased up to 40% in hypothyroid humans. Despite the negative influences on glomerular and tubular kidney function, a hypothyroid state has been described as beneficial in kidney disease. Kidney disease is associated with decreased thyroid hormone concentrations caused by central effects and by changes in peripheral hormone metabolism and thyroid hormone binding proteins. Geriatric cats form an animal model of disease because both hyperthyroidism and chronic kidney disease (CKD) have high prevalence among them, and the link between thyroid and kidney affects the evaluation of clinical wellbeing and the possible treatment options.

Routine Health Screening: Findings in apparently healthy middle-aged and old cats

Study rationale: Veterinary practitioners often perform geriatric health screening in cats. Unfortunately, scientific information regarding clinical and laboratory abnormalities and normal blood pressure values in elderly cats is scarce. This prospective study evaluated routine health screening tests in apparently healthy middle-aged and old cats. Protocol: One hundred cats of 6 years and older underwent blood pressure measurement, physical examination, blood and urine analysis, indirect fundoscopy and bilateral Schirmer tear tests. Findings: Mean systolic blood pressure (SBP) was 133.6 ± 21.5 mmHg. Increased SBP (>160 mmHg) was observed in eight cats, submandibular lymphadenopathy in 32, gingivitis in 72, heart murmur in 11, thyroid goitre in 20, increased creatinine in 29, hyperglycaemia in 25, increased total thyroxine in three, feline immunodeficiency virus positivity in 14, crystalluria in 41, borderline proteinuria in 25 and overt proteinuria in two. Mean tear production was very similar for both eyes and none of the cats had ocular lesions secondary to hypertension. Clinical significance: Old cats (>10 years) had significantly higher SBP, heart rate, murmur frequency, thrombocyte count, urine protein:creatinine ratio and serum urea and bilirubin concentrations, and significantly lower body condition score, haematocrit, albumin and total calcium concentrations than middle-aged cats (6–10 years). The common occurrence of physical examination and laboratory abnormalities in apparently healthy old cats underlines the need for regular health checks and the development of age-dependent laboratory reference intervals.

Urinary Markers in Healthy Young and Aged Dogs and Dogs with Chronic Kidney Disease

BACKGROUND Blood urea nitrogen and serum creatinine concentrations only detect a decrease of > 75% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage. HYPOTHESIS Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N-acetyl-beta-D-glucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs. ANIMALS Ten dogs with CKD, 10 healthy young dogs (age 1-3 years), and 10 healthy older dogs (age > 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis. METHODS Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs. RESULTS uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers. CONCLUSION The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia.

Risk Factors and Clinical Presentation of Cats with Feline Idiopathic Cystitis

Feline idiopathic cystitis (FIC) is the most common cause of feline lower urinary tract disease (FLUTD). This retrospective, case-controlled study evaluated possible risk factors associated with FIC and compared different clinical presentations in 64 cats with FIC. Several risk factors known to be involved in FLUTD were identified as playing a role in FIC. Of the stressful situations considered, most did not occur with increased frequency in cats with FIC compared to controls, except for a house move. The presence of pyuria, haematuria and an increased urine protein:creatinine ratio were significantly higher in obstructed males compared with non-obstructed males. An obstruction was significantly more likely in cats with struvite crystalluria compared with cats without struvite crystalluria. These findings suggest that urethral plugs might be an important cause or contributing factor of obstruction in FIC. Episodes of FIC seem to occur mainly in susceptible cats in combination with a deficient environment.

Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine ☆

Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia.

Dogs as carriers of the emerging pathogen Arcobacter.

Dogs and cats living in a household have previously been identified as a risk factor for human infection with Campylobacter and Helicobacter. In this study, carried out between July 2006 to September 2007, feces and oral swabs from 267 dogs and 61 cats were examined for the presence of the emerging pathogen Arcobacter. Isolates, obtained by an Arcobacter selective isolation procedure, were identified with an Arcobacter species-specific multiplex-PCR and characterized by modified enterobacterial repetitive intergenic concensus PCR. No arcobacters were isolated from cats. Five dogs excreted arcobacters in the feces and two other dogs carried arcobacters in the mouth. In the follow-up, one dog excreted the same Arcobacter butzleri strain for at least 1 week. Six dogs carried each an unique A. cryaerophilus strain although three of them lived in the same family. Therefore, beside the consumption of food and water, contact with dogs is another potential source of Arcobacter infection.

Validation of immunoassays for the candidate renal markers C-reactive protein, immunoglobulin G, thromboxane B2 and retinol binding protein in canine urine

The study of early markers for glomerular and tubular dysfunction in dogs with renal diseases holds promise to gain new insights in the pathogenesis of canine nephropathies. However, the validation of such markers in canine urine is largely lacking. Therefore, immunoassays for the quantification of a set of four urinary markers, C-reactive protein (CRP), immunoglobulin G (IgG), thromboxane B(2) (TXB(2)) and retinol binding protein (RBP), were validated by determining their sensitivity, reproducibility, precision and accuracy in a large patient group. The results show that the immunoassays are appropriate for analysis of urinary CRP, IgG, TXB(2) and RBP in dogs. Furthermore, the significant differences in urinary concentrations of the selected glomerular and tubular markers between healthy (H) dogs and dogs with several types of nephropathies (R) support their future application in both clinical settings and research models.

Oligofructose and inulin modulate glucose and amino acid metabolism through propionate production in normal-weight and obese cats

The effect of dietary oligofructose and inulin supplementation on glucose metabolism in obese and non-obese cats was assessed. Two diets were tested in a crossover design; a control diet high in protein (46 % on DM basis), moderate in fat (15 %), low in carbohydrates (27 %), but no soluble fibres added; and a prebiotic diet, with 2.5 % of a mixture of oligofructose and inulin added to the control diet. Eight non-obese and eight obese cats were allotted to each of two diets in random order at intervals of 4 weeks. At the end of each testing period, intravenous glucose tolerance tests were performed. Area under the glucose curve (AUCgluc) was increased (P = 0.022) and the second insulin peak was delayed (P = 0.009) in obese compared to non-obese cats. Diets did not affect fasting plasma glucose concentrations, blood glucose response at each glucose time-point after glucose administration, AUCgluc, fasting serum insulin concentrations, area under the insulin curve, and height and appearance time of insulin response. Yet, analysis of acylcarnitines revealed higher propionylcarnitine concentrations (P = 0.03) when fed the prebiotic diet, suggesting colonic fermentation and propionate absorption. Prebiotic supplementation reduced methylmalonylcarnitine (P = 0.072) and aspartate aminotransferase concentrations (P = 0.025), both indicating reduced gluconeogenesis from amino acids. This trial evidenced impaired glucose tolerance and altered insulin response to glucose administration in obese compared to non-obese cats, regardless of dietary intervention; yet modulation of glucose metabolism by enhancing gluconeogenesis from propionate and inhibition of amino acid catabolism can be suggested.

Evaluation of Kidney Injury in Dogs with Pyometra Based on Proteinuria, Renal Histomorphology, and Urinary Biomarkers

BACKGROUND Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. OBJECTIVES To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. ANIMALS Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. METHODS Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive protein, urinary thromboxane B(2)) and tubular function (urinary retinol-binding protein, urinary N-acetyl-β-d-glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. RESULTS UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05-8.69) compared with healthy bitches (0.08, 0.02-0.16) (P < .01). Twenty-two of 47 dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. CONCLUSION Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra-associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis in dogs.

Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in hyperthyroid cats before and after treatment with radioiodine

BACKGROUND Glomerular filtration rate (GFR) can be measured by clearance methods of different markers showing discrepancies and different reproducibility in healthy cats. Studies comparing different methods of GFR measurement in hyperthyroid cats have not yet been performed. HYPOTHESIS Plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT), and endo-iohexol (PenICT) could lead to differences in GFR measurement and the need to use the same clearance method when comparing GFR before and after radioiodine treatment in hyperthyroid cats. ANIMALS Fifteen client-owned hyperthyroid cats. METHODS GFR was measured 1 day before and 1, 4, 12, and 24 weeks after treatment. Intravenous injection of iohexol was followed immediately by IV injection of creatinine. Plasma creatinine was measured by an enzymatic method. Plasma endo- and exo-iohexol were measured by high-performance liquid chromatography coupled to ultraviolet detection. RESULTS Globally, the 3 GFR methods resulted in significantly different (P < .001) GFR results. GFR results among the different methods were the same (P= .999) at all time points. All 3 techniques indicated decreasing GFR after (131)I treatment. For each GFR technique, a significant decrease in GFR was observed between time point 0 and all other time points. This decrease stabilized 4 weeks after treatment, with very little decline afterward. CONCLUSION AND CLINICAL IMPORTANCE It is mandatory to use the same GFR technique in follow-up studies. GFR testing at 4 weeks posttreatment could allow assessment of the final renal functional loss after treatment in hyperthyroid cats.