Diabetic nephropathy Flashcards
Define microvascular complications and give examples
Complications of smaller vessels
e.g:
Retinopathy
Nephropathy
Neuropathy
What is the relationship b/t glucose levels and microvascular complications?
- Extent of hyperglycaemia (as judged by HbA1c) is strongly associated with the risk of developing microvascular complications
What is the relationship b/t systolic bp and microvascular complication?
- Clear relationship between rising systolic BP (hypertension) and risk of MI and microvascular complications in people with T1DM and T2DM
- Therefore, prevention of complications requires reduction in HbA1c and BP control
(not just management of sugars- need to check BP, cholesterol, etc)
Describe the mechanism of damage behind microvascular complications of diabetes?
- Hyperglycaemia and hyperlipidemia can result in:
- Hypoxia
- Increased formation of mitochondrial superoxide free radicals in the endothelium (oxidative stress)
- Generation of glycated plasma proteins to form advanced glycation end products (AGEs): the more sugar= more AGEs you have - All 3 of these lead to activation of inflammatory pathways (pro- inflammatory cytokines)
- Damaged endothelium results in:
‘Leaky’ capillaries
Ischaemia
(= Nephropathy, Retinopathy, Neuropathy)
What is diabetic nephropathy?
“kidney damage caused by diabetes”
- Usually a clinical diagnosis in a patient with long-standing diabetes (>10 years) with albuminuria and/or reduced estimated glomerular filtration rate (eGFR)
- Most common cause of CKD
What are the presenting symptoms/ signs of diabetic nephropathy?
- Hypertension
- Oedema → in advancing diabetic nephropathy
- Polyuria
- Lethargy
What investigations are used to diagnose/ monitor diabetic nephropathy?
- First Line: Urinalysis → increased albumin: creatinine ratio (ACR) = microalbuminuria
- ACR (urine albumin:creatinine ratio) ->2.5 = microalbuminuria
- All patients should be screened annually using urinary ACR - Gold Standard: Renal Biopsy → shows kimmelstiel-wilson nodules (also mesangial expansion and GBM thickening)
- Serum Creatinine & estimated GFR → GFR raised in early disease but reduced in late disease
How is diabetic nephropathy managed?
- Antihypertensive Treatment → ACE inhibitors or ARBs are first line (renoprotective effect). Add CCB or Thiazide Diuretic as 2nd line.
- Tight Glycaemic Control
- Control Dyslipidaemia → Statins (atorvastatin)
- Dietary Modification → reduce protein and salt intake
- Smoking Cessation
Describe the mechanism of damage in diabetic nephropathy
- Hyperglycemia and hypertension leads to glomerular hypertension (pressure builds up in the glomerulus)
- Proteins are, therefore, forced/ leak out = proteinuria
- Causes damage to the glomerulus (decreased function)
- Leads to Glomerular and intersitial fibrosis and glomerular filtration rate decline
= RENAL FAILURE
What is the reltionship b/t nephropathy and the Renin- Angiotensin System?
System is more activated in patients with nephropathy
(treatment targets the RAS system)
How/ what parts of the RAS system are targeted in the treatment of nephropathy?
RAS system:
1. Liver releases Angiotensinogen
2. Kidney releases renin which converts the Angiotensinogen into Angiotensin I
3. ACE coverts Angiotensin I into Angiotensin II
4. Angiotensin II causes vasoconstriction and binds to Angiotensin receptors to promote the release of aldosterone (increasing salt/ water retention to increase bp/ hypertension)
Targets:
a. ACE inhibitors [ACEi] (antihypertensives which block ACE)
b. Angiotensin receptor blockers [ARBs] (antihypertensives which block the receptors)
DO NOT GIVE BOTH TOGETHER: EITHER OR
Blocking RAS with an ACE inhibitor (‘-pril) or angiotensin 2 receptor blocker (ARB, ‘-sartan’) reduces blood pressure & progression of diabetic nephropathy
All diabetes patients with microalbuminuria/proteinuria should have an ACEi/ARB even if normotensive (give max dose tolerated by bp)
No benefit to having both ACEi/ARB simultaneously
