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Antihypertensive Drugs: Thiazide-Class Diuretics01:15

Antihypertensive Drugs: Thiazide-Class Diuretics

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Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...
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The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
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Glucose Transporters01:27

Glucose Transporters

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Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
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Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

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In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
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Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
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Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

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Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
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Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
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SGLT2 inhibitors and nephrolithiasis risk: a meta-analysis.

Mehmet Kanbay1, Crischentian Brinza2,3, Sidar Copur4

  • 1Department of Medicine, Division of Nephrology, Koç University School of Medicine, Istanbul, Turkey.

Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association
|August 8, 2024
PubMed
Summary

Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of nephrolithiasis, or kidney stones. This meta-analysis shows SGLT2 inhibitor therapy is associated with a lower incidence of kidney stones compared to placebo or active treatments.

Keywords:
calcium oxalateglucosurianephrolithiasisosmotic diuresissodium–glucose co-transporter 2 inhibitors

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Area of Science:

  • Nephrology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a class of anti-diabetic medications.
  • These drugs demonstrate beneficial effects on cardiovascular and renal outcomes, metabolic parameters, and body weight.
  • Emerging research explores their impact on nephrolithiasis (kidney stone) development, a condition affecting 10% of the population and posing risks for kidney injury.

Purpose of the Study:

  • To systematically review and meta-analyze the association between SGLT2 inhibitor therapy and the risk of nephrolithiasis.
  • To compare the incidence of kidney stones in patients treated with SGLT2 inhibitors versus control groups (placebo or active therapies).

Main Methods:

  • A comprehensive literature search was conducted across multiple databases (PubMed, Ovid MEDLINE, Web of Science, Scopus, Cochrane Library).
  • Systematic review and meta-analysis guidelines (PRISMA) were followed.
  • Data from six clinical trials, encompassing 11,635,698 patients with nephrolithiasis, were included in the analysis.

Main Results:

  • Nephrolithiasis occurred in 1.27% of patients in the SGLT2 inhibitor group versus 1.56% in the control arm.
  • SGLT2 inhibitor therapy was associated with a significantly lower risk of nephrolithiasis compared to placebo (OR 0.61, P < .00001).
  • A reduced risk was also observed compared to active therapies like GLP-1 and DPP-4 inhibitors (OR 0.66, P = .02).

Conclusions:

  • SGLT2 inhibitor therapy is associated with a reduced risk of nephrolithiasis.
  • Potential mechanisms include osmotic diuresis, reduced lithogenic substance concentration, anti-inflammatory/anti-fibrotic effects, and increased urine pH.
  • Further large-scale randomized clinical trials are warranted to confirm these findings and elucidate mechanisms.