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Renal Failure: Dose Adjustments01:11

Renal Failure: Dose Adjustments

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In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
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Antihypertensive Drugs: Potassium-Sparing Diuretics01:28

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Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
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The renal tubule is divided into three parts: the proximal convoluted tubule (PCT), the Loop of Henle (LOH), and the distal convoluted tubule (DCT).
Proximal Convoluted Tubule (PCT):
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The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
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Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
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Adrenal gland disorders manifest when the production of adrenal hormones deviates from the norm, resulting in either excessive or insufficient concentrations.
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Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines.

Thomas Uslar1, Andrew J Newman2, Alejandra Tapia-Castillo1

  • 1Department of Endocrinology, CETREN-UC, Red Salud UC-CHRISTUS, Pontificia Universidad Católica de Chile, Santiago 8330077, Chile.

The Journal of Clinical Endocrinology and Metabolism
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Chronic kidney disease (CKD) involves reduced 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) activity, impacting cortisol and mineralocorticoid receptor (MR) activation even in normal kidney function. This decline contributes to hypertension and cardiovascular disease in CKD.

Keywords:
11β-hydroxysteroid dehydrogenase type 2chronic kidney diseasecortisolcortisonemineralocorticoid receptor activation

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Area of Science:

  • Endocrinology
  • Nephrology
  • Cardiovascular Medicine

Background:

  • Chronic kidney disease (CKD) may involve 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency.
  • This insufficiency could lead to increased cortisol-mediated mineralocorticoid receptor (MR) activation.

Purpose of the Study:

  • To investigate if 11βHSD2 insufficiency occurs across a spectrum of kidney function, including normal ranges.
  • To assess the relationship between kidney function, 11βHSD2 activity, and MR activation.

Main Methods:

  • Recruited adult participants (n=601) across a range of estimated glomerular filtration rates (eGFR).
  • Measured serum cortisol-to-cortisone (F/E) ratios as a biomarker for 11βHSD2 activity.
  • Assessed 11βHSD2 activity using F/E and androgen ratios under various physiological conditions in a validation cohort.

Main Results:

  • Lower eGFR correlated with higher F/E ratios, indicating reduced 11βHSD2 activity.
  • This association persisted in individuals with normal eGFR and after specific physiological challenges.
  • Higher F/E ratios and lower eGFR were linked to increased renal MR activity, indicated by potassium excretion.

Conclusions:

  • A continuous decline in 11βHSD2 activity was observed with decreasing eGFR, present even in individuals with normal kidney function.
  • Cortisol-mediated MR activation is implicated in the development of hypertension and cardiovascular disease in CKD.