Cushing’s syndrome, glucocorticoids and the kidney

Glucocorticoids (GCs) affect renal development and function in fetal and mature kidneys both indirectly, by influencing the cardiovascular system, and directly, by their effects on glomerular and tubular function. Excess GCs due to endogenous GC overproduction in Cushing’s syndrome or exogenous GC administration plays a pivotal role in hypertension and causes increased cardiac output, total peripheral resistance and renal blood flow. Glucocorticoids increase renal vascular resistance (RVR) in some species and experimental settings and decrease RVR in others. Short term administration of adrenocorticotrophic hormone or GCs causes an increased glomerular filtration rate (GFR) in humans, rats, sheep and dogs. Interestingly, chronic exposure may cause a decreased GFR in combination with a higher cardiovascular risk in human patients with Cushing’s syndrome. Glomerular dysfunction leads to proteinuria and albuminuria in canine and human Cushing’s patients, and some cases also show histological evidence of glomerulosclerosis. Tubular dysfunction is reflected by an impaired urinary concentrating ability and disturbed electrolyte handling, which can potentially result in increased sodium reabsorption, hypercalciuria and urolithiasis. Conversely, chronic kidney disease can also alter GC metabolism. More research needs to be performed to further evaluate the renal consequences of Cushing’s syndrome because of its implications for therapeutic aspects as well as the general well-being of the patient. Because there is a high incidence of Cushing’s syndrome in canines, which is similar to the syndrome in humans, dogs are an interesting animal model to investigate the link between hypercortisolism and renal function.