• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• Q. Which are two important pathogenic mechanisms causing kidney disease in patients with diabetes ?

  • Glomerular hypertrophy
  • intraglomerular hypertension

• Q. What produces glomerular hyperfiltration?

  • It is mainly due to afferent arteriole vasodilatation
  • SGLT2 is increased in people with diabetes because of hyperglycemia  hence there is increase sodium reabsorption
  • This causes afferent vasodilatation
  • This further leads to Glomerular hyperfiltration
  • Glomerular hyperfiltration produces intraglomerular hypertension which leads to diabetic kidney disease
  • AGE, IGF1, sorbitol, ANP etc have similar role on afferent arterial vasodilatation.

• Q. Why does RAAS inhibitor protect the kidney?

  • ACEI / ARB cause vasodilatation of afferent and efferent arteriole, but efferent arterial vasodilatation is more than Afferent arterial vasodilatation
  • Hence this reduce the glomerular filtration pressure and hence protects the kidney

• Q. Summarize the mechanism of renal damage in Diabetic nephropathy and how SGLT2 and ACEI protect the kidney? #Conceptual-Learning ^[1]

  • Step 1- Tubuloglomerular feedback
    • Reduced GFR → reduced flow rate in kidney → increase Na reabsorption → reduced Na reaching the Macula densa → macula densa signals release of renin → RAAS → angiotensin II → efferent vasoconstriction → increase of GFR
      • Angiotensin II produces both afferent and efferent Vasocontriction but efferent > afferent – hence the net increase of GFR
    • Vice versa occurs, if there is an increase of GFR
  • Step 2 – Hypefilteration in diabetics
    • People with diabetes have Glomerular hyperfiltration
    • This is because IGF1, AGE, sorbitol  afferent vasodilatation which increase GFR
    • Hence intact Tubuloglomerular feedback is required for normalizing GFR
  • Step 3 Role of glycosuria
    • In Diabetes there is an increase of glucose in urine hence SGLT2 is activated → to increase Sodium and glucose reabsorption → remember, more Na is reabsorbed →, so less Sodium to Macula densa → , so more Renin release !!
    • Already the GFR is high due to hyperfiltration and this adds fuel to the fire
    • So there is a loss of Tubuloglomerular feedback in diabetics
  • Step 4 – Fuel to the fire
    • Hypertension and loss of nephrons further increase pressure on the remaining nephron and increase GFR
    • Hence producing Intraglomerular hypertension and glomerular hypertrophy
  • Step 4 – Now for ACEI relief
    • ACEI provides noticeable relief by blocking the RAAS pathway preventing the increase of GFR caused by the renin system
  • Step 5- SGLT2i
    • SGLT2i inhibits sodium and glucose reabsorption and hence  keep the tubuloglomerular feedback intact!
    • Hence it is renoprotective

Multimedia

Talk on # How SGLT2 inhibitors protect the kidney in patients with Diabetes mellitus? by Dr. Om J Lakhani (Date: April 9, 2021)