Ingrid van Hoek

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.

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT4) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 μg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT4 measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT4 concentration, T/S uptake ratio before and 6 h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 μg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Within- and between-examiner agreement for two thyroid palpation techniques in healthy and hyperthyroid cats

Thyroid gland palpation is an important aid for diagnosing feline hyperthyroidism in an early stage to prevent development of deleterious complications. Our objectives were to assess within- and between-examiner agreement for two thyroid gland palpation techniques in cats and to correlate palpation results with ultrasonographic thyroid measurements. Nine client-owned hyperthyroid (12.6±2.4 years) and 10 healthy control cats (7.4±5.4 years) entered this prospective study. Both thyroid glands of all cats were palpated twice by three blindfolded clinicians with the classic palpation technique [technique 1 (T1)] and the technique described by Norsworthy GD, Adams VJ, McElhaney MR, Milios JA [(2002a) Relationship between semi-quantitative thyroid palpation and total thyroxine concentration in cats with and without hyperthyroidism. Journal of Feline Medicine and Surgery 4, 139–143] [technique 2 (T2)]. A semi-quantitative score from 1 to 6 was assigned to the gland size. After clipping of the ventral cervical region, another palpation session followed by ultrasonography of the thyroid glands was performed. Average weighted κ-values within- and between-examiners were 0.864 and 0.644 for T1 and 0.732 and 0.532 for T2. T1 did lead to significantly smaller within- (P=0.007) and between-examiner (P=0.048) differences than T2. Significant correlation coefficients (P<0.001) between the palpation scores of both techniques and ultrasonographic thyroid lobe length (T1: 0.43; T2: 0.38) were observed. No significant difference before and after clipping was found (T1: P=0.503; T2: P=0.607). The first time that all cats were palpated by either technique, significant score differences between control and hyperthyroid cats were observed both for T1 (P=0.002) and T2 (P=0.003). Both feline thyroid gland palpation techniques have good within- and between-examiner agreements. Based on this study, the classic palpation technique is preferred.

Thyroid stimulation with recombinant human thyrotropin in healthy cats, cats with non-thyroidal illness and in cats with low serum thyroxin and azotaemia after treatment of hyperthyroidism

This study investigated the recombinant human thyrotropin (rhTSH) stimulation test in healthy cats (group 1), cats with non-thyroidal illness (group 2) and cats with low serum total T4 (TT4) and azotaemia after 131I treatment (group 3). Serum TT4 responses and thyroidal pertechnetate uptake after administration of 25 μg rhTSH IV were assessed. Baseline serum TT4 was significantly lower in group 3 compared with group 1, but not between other group pairs. Serum TT4 increased significantly in groups 1 and 2 but not in group 3 after rhTSH administration. Post-rhTSH serum TT4 concentrations differed significantly between groups 1 and 3 and groups 2 and 3, but not between groups 1 and 2. Thyroid/salivary gland uptake ratio (T/S uptake ratio) differed only significantly between groups 1 and 3. Stimulation with rhTSH is valuable to differentiate euthyroidism from iatrogenic hypothyroidism in cats.

A diet with a struvite relative supersaturation less than 1 is effective in dissolving struvite stones in vivo.

Magnesium ammonium phosphate (struvite) is one of the most common minerals found in feline uroliths. Previous studies have shown the efficacy of acidifying calculolytic diets (inducing urine pH < 6.5), in dissolving struvite stones in cats. Recent work in our laboratory found that wet and dry test diets induce a struvite urinary relative supersaturation (RSS) < 1 and that the urine of healthy cats fed the dry test diet dissolved feline struvite stones in vitro. The objective of the present study was to demonstrate the efficacy of those test diets on naturally occurring struvite urocystoliths in cats. A total of twenty-one cats were used, of which seventeen completed the study. Of the seventeen cats, eight were fed the wet test diet and nine the dry test diet. Uroliths dissolved in a median of 18 (10-55) d. In the remaining four cats, uroliths failed to dissolve and were removed surgically. Quantitative analysis showed that these uroliths contained either calcium oxalate or calcium phosphate. The present study demonstrates that diets that induce a struvite RSS < 1 result in struvite stone dissolution in vivo.

Comparison of plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol over a range of glomerular filtration rates expected in cats

The study investigated plasma clearance of exogenous creatinine (PECCT), exo-iohexol (PexICT) and endo-iohexol (PenICT) in six healthy cats, four cats with chronic kidney disease (CKD) and six hyperthyroid (HT) cats to assess potential differences in glomerular filtration rate (GFR) measurement over a wide range of GFR values. The PECCT, PexICT and PenICT were performed in a combined protocol. There was a significant difference between PexICT and PenICT and PECCT in healthy cats. Differences between clearance techniques are suggested to be correlated to range in GFRs and should be taken into account when GFR is measured.

Simplified methods for estimating glomerular filtration rate in cats and for detection of cats with low or borderline glomerular filtration rate

Objectives Diagnosis of early feline chronic kidney disease (CKD) is challenging. Glomerular filtration rate (GFR) is the best overall indicator of kidney function, but multisample plasma clearance methods to determine GFR are labour intensive, time consuming and stressful for feline patients. This study aimed to develop simplified methods to detect decreased GFR in cats. Methods Data from a nine-sample combined plasma exogenous creatinine–iohexol clearance test of 73 cats were used. Limited sampling strategies were developed by comparing all sampling time combinations with the complete nine sampling times set and selecting the best sampling time combinations based on maximum relative error. By regression analysis, the ability of routine blood (serum creatinine, serum urea) and urine (urine specific gravity, urinary protein:creatinine ratio) variables to predict GFR or identify cats with low or borderline GFR was examined. Cut-off clearance marker concentrations to predict low or borderline GFR was determined at three time points after marker injection. All procedures were analysed for three clearance markers (exo-iohexol, creatinine, endo-iohexol). Results For reliable estimation of GFR, at least three blood samples for clinical purposes and five blood samples for research purposes are required. Regression formulae based on routine variables did not reliably predict GFR, but accurately identified cats with low (sensitivity 96.5–98.2%; specificity 60–91.3%) or borderline (sensitivity 91.1–96%; specificity 76.5–81.8%) GFR. Clearance marker concentrations exceeding given marker cut-off concentrations also identified cats with low or borderline GFR with high sensitivities and specificities. Conclusions and relevance These simplified methods will facilitate the detection of early kidney dysfunction in cats. Early diagnosis allows timely therapeutic intervention, and future studies must reveal whether this improves the long-term outcome of cats with CKD.

A critical review of food-associated factors proposed in the etiology of feline hyperthyroidism:

Since the first description of feline hyperthyroidism (HT) in 1979, several studies have been undertaken to define the etiology of the disease. Epidemiologic studies, after investigating non-food- and food-associated factors, suggest a multifactorial etiology. However, in the absence of prospective cohort studies that can confirm a cause-and-effect relationship between HT and associated risk factors, no causative factor for HT has been identified to date. Feline HT resembles toxic nodular goiter in humans, with autonomously functioning upregulated iodide uptake systems. Contribution of the diet to HT development remains controversial. The purpose of this paper is to review critically the reported food-associated risk factors for HT.

Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat

Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111 MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24 h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT4) and for the thyroid to salivary gland ratio with sodium pertechnetate γ-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT4 and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.

Determination of optimal sampling times for a two blood sample clearance method using 51Cr-EDTA in cats

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma 51chromium ethylene diamine tetra-acetic acid (51Cr-EDTA) clearance were investigated. After intravenous administration of 51Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7±2.5 ml/min/kg (mean±standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r2≥0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r2 for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies.