NEW INSIGHTS INTO DECLINING KIDNEY FUNCTION IN HYPERTHYROID CATS AFTER TREATMENT WITH 131I Ingrid van Hoek Thesis submitted in fulfillment of the requirements for the degree of doctor (Ph.D.) in Veterinary Sciences, Faculty of Veterinary Medicine, Ghent University, 2008 Promotor: Prof. Dr. S. Daminet Department of Medicine and Clinical Biology of Small Animals Faculty of Veterinary Medicine Ghent University Salisburylaan 133, B-9820, Merelbeke, België This PhD was financed by the Bijzonder Onderzoeks Fonds of Ghent University. The study in § 2.3 was possible through the generous support from Royal Canin S.A., Aimargues, France. Printing and distribution of the thesis was enabled through the support from: Royal Canin S.A., Aimargues, France Janssen Animal Health, Beerse, Belgium Intervet/Schering-Plough Animal Health, Boxmeer, The Netherlands Idexx Laboratories, Hoofddorp, The Netherlands Vetoquinol S.A., Aartselaar, Belgium van Hoek, Ingrid New insights into declining kidney function in hyperthyroid cats after treatment with 131I. Ingrid van Hoek Universiteit Gent, Faculteit Diergeneeskunde Vakgroep Geneeskunde en Klinische Biologie van de Kleine Huisdieren ISBN: 9789058641571 Illustraties: Wiebe en Lisa, Bert van de Wijgert, 2008. “Far too noisy, my dear Mozart. Far too many notes.” Emperor Ferdinand of Austria commenting on "The Marriage of Figaro" 1786 CONTENTS LIST OF ABBREVIATIONS GENERAL INTRODUCTION .......................................................................................... 1 SCIENTIFIC AIMS ............................................................................................................ 7 CHAPTER 1: REVIEW OF THE LITERATURE ....................................................... 11 Adapted from 2 articles: I. van Hoek, K. Peremans, T. Waelbers, E. Vandermeulen, S. Daminet (2007). Non-surgical treatment of feline hyperthyroidism: options and considerations. Vlaams Diergeneeskundig Tijdschrift 76:69-80. and I. van Hoek, S. Daminet. Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review. General and Comparative Endocrinology. In press. 1.1 Thyroid physiology .............................................................................................................. 13 1.2 Feline hyperthyroidism ...................................................................................................... 16 1.3 Treatment of feline hyperthyroidism .............................................................................. 17 1.3.1 Anti-thyroid medication ........................................................................................... 18 1.3.2 Radioactive iodine (131I) ........................................................................................... 19 1.4 Direct and indirect effects of thyroid hormones on kidney function ...................... 20 1.4.1 Cardiac output ............................................................................................................ 21 1.4.2 Systemic vascular resistance .................................................................................... 22 1.4.3 Renal blood flow ........................................................................................................ 23 1.4.4 Renal tubules .............................................................................................................. 24 1.4.5 Glomerular filtration rate .......................................................................................... 25 1.4.6 Proteinuria ................................................................................................................... 28 1.5 Evaluation of kidney function in hyperthyroid cats .................................................... 29 1.5.1 Measurement of glomerular filtration rate .............................................................. 29 1.5.2 Retinol binding protein as an urinary marker ......................................................... 30 1.5.3 Hyperthyroidism and kidney failure ........................................................................ 31 1.5.4 Hyperthyroidism masking co-existing disease....................................................... 33 1.6 Diagnostic challenges with non-thyroidal illness .......................................................... 34 1.6.1 Concurrent hyperthyroidism and CKD ................................................................... 34 1.6.2 Post-treatment renal azotemia and low serum TT4 concentration ...................... 35 1.7 Conclusion ............................................................................................................................. 36 CONTENTS CHAPTER 2: EVALUATION OF GFR TECHNIQUES .............................................. 47 § 2.1 COMPARISON AND REPRODUCIBILITY OF GFR MEASUREMENTS IN YOUNG ADULT AND AGED HEALTHY CATS ............................................................... 51 Adapted from: I. van Hoek, E. Vandermeulen, L. Duchateau, H.P. Lefebvre, S. Croubels, K. Peremans, I. Polis, S. Daminet (2007). Comparison and reproducibility of plasma clearance of exogenous creatinine, exo- iohexol, endo-iohexol and 51Cr-EDTA in young adult and aged healthy cats. Journal of Veterinary Internal Medicine 21:950-958. § 2.2 EVALUATION OF GFR MEASUREMENTS IN HYPERTHYROID CATS BEFORE AND AFTER TREATMENT WITH RADIOIODINE ..................................... 73 Adapted from: I. van Hoek, H.P. Lefebvre, H.S. Kooistra, S. Croubels, D. Binst, K. Peremans, S. Daminet (2008). Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in hyperthyroid cats before and after treatment with radioiodine. Journal of Veterinary Internal Medicine 22:879-885. § 2.3 EVALUATION OF GFR MEASUREMENTS IN HEALTHY CATS, CATS WITH HYPERTHYROIDISM AND CATS WITH CHRONIC KIDNEY DISEASE 95 Adapted from: I. van Hoek, H.P. Lefebvre, D. Paepe, S. Croubels, V. Biourge, S. Daminet. Plasma clearance of exogenous creatinine, exo-iohexol, and endo-iohexol in healthy cats, cats with hyperthyroidism and cats with chronic kidney disease. Journal of Feline Medicine and Surgery. In review. CHAPTER 3: EVALUATION OF URINARY RETINOL BINDING PROTEIN AS AN EARLY MARKER OF RENAL DAMAGE IN CATS ........................................ 113 § 3.1 VALIDATION OF URINARY RETINOL BINDING PROTEIN IN CATS .... 117 Adapted from: I. van Hoek, S. Daminet, S. Notebaert, I. Janssens, E. Meyer (2008). Immunoassay of urinary retinol binding protein as a putative renal marker in cats. Journal of Immunological Methods 329:208-213. § 3.2 RETINOL BINDING PROTEIN IN SERUM AND URINE OF HYPERTHYROID CATS BEFORE AND AFTER TREATMENT WITH RADIOIODINE .......................................................................................................................... 131 Adapted from: I. van Hoek, E. Meyer, L. Duchateau, K. Peremans, S. Daminet. Retinol binding protein in serum and urine of hyperthyroid cats before and after treatment with radioiodine. Journal of Veterinary Internal Medicine. In review. CONTENTS CHAPTER 4: FOLLOW UP OF KIDNEY FUNCTION IN HYPERTHYROID CATS AFTER TREATMENT WITH RADIOIODINE ............................................. 149 Adapted from: I. van Hoek, H.P. Lefebvre, K. Peremans, E. Meyer, S. Croubels, E. Vandermeulen, H. Kooistra, J.H. Saunders, D. Binst, S. Daminet (2009). Short and long term follow up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine. Domestic Animal Endocrinology 36:45-56. CHAPTER 5: EVALUATION OF rhTSH STIMULATION IN CATS ..................... 181 § 5.1 SERUM THYROXINE AND THYROID SCINTIGRAPHY IN EUTHYROID CATS ............................................................................................................................................ 185 Adapted from: I. van Hoek, K. Peremans, E. Vandermeulen, L. Duchateau, K. Gommeren, S. Daminet. Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats. Journal of Feline Medicine and Surgery. In press. § 5.2 COMPARISON BETWEEN HEALTHY CATS, CATS WITH NON- THYROIDAL ILLNESS AND CATS SUSPECTED OF IATROGENIC HYPOTHYROIDISM WITH POST-TREATMENT RENAL AZOTEMIA .............. 201 Adapted from: I. van Hoek, E. Vandermeulen, K. Peremans, S. Daminet. Thyroid stimulation with recombinant human thyrotropin in cats with low serum thyroxin and renal azotemia after treatment of hyperthyroidism with 131I. Journal of Feline Medicine and Surgery. In review. GENERAL DISCUSSION ............................................................................................. 217 1. Evaluation of plasma clearance methods ............................................................. 219 2. Evaluation of urinary RBP as a marker of kidney function ................................ 221 3. Long term effects of 131I treatment on kidney function and possible prediction of post-treatment renal azotemia ......................................................................... 223 4. Evaluation of rhTSH stimulation test to measure thyroid function in cats with post-treatment renal azotemia suspected of iatrogenic hypothyroidism .............. 225 SUMMARY ..................................................................................................................... 229 SAMENVATTING ......................................................................................................... 235 DANKWOORD ..............................................................................................................