Diabetic kidney disease Flashcards
How is diabetic kidney disease defined?
- Albuminuria - uACR ≥ 3.4mg/mmol
- Progressive reduction in eGFR
- In a long duration of diabetes
- > 10 years in T1DM
- May be present at diagnosis in T2DM
- Typically associated with retinopathy
How common is diabetic kidney disease?
In T1DM, 20-30% of patients will have albuminuria
In T2DM, 40% will have chronic kidney disease
What are some factors that increase risk of diabetic kidney disease?
- Glomerular hyperfiltration
- Smoking
- Obesity
- Physical inactivity
- Dyslipidaemia
- Proteinuria
- High dietary content of fat and proteins
- Race (African-Americans 3x more likely; Hispanic/Latino 1.3x more likely)
Describe the pathophysiology of diabetic kidney disease
- High glucose and increased glomerular pressure causes renal hypertrophy and hyper filtration
- This causes thickening of the GBM, fusion of foot processes, mesangial expansion, glomerulosclerosis and tubulointerstitial fibrosis
- Afferent arteriole vasodilation also increases filtration pressure
- Arterioles undergo hyalinosis
What are the 4 stages of diabetic kidney disease?
- Renal hypertrophy leads to hyperfiltration, with and an elevated eGFR occur early
- Dipstick tests positive, with over proteinuria
- As the levels of proteinuria rise, the eGFR can fall
- eGFR < 10, ESRD
How is diabetic kidney disease diagnosed?
Blood testing - Glucose, HbA1C, RFT
Urinalysis - Glucose, albuminuria
What are the 4 tiers of management in diabetic kidney disease?
- Lifestyle and self-management
- First-line drug therapy
- Additional drugs for heart and kidney protection
- Additional risk factor control
What are some lifestyle management options used in diabetic kidney disease?
- Diet changes - Low sugar
- Exercise
- Smoking cessation
- Weight loss
What are some drugs used as first-line drug therapy for diabetic kidney disease?
- Metformin
- SGLT2 inhibitor
- RAS blockade
- Statin
What are some drugs used as additional heart and kidney protective drugs in diabetic kidney disease?
- GLP-1
- Antiplatelet therapy
- ns-MRA
What are some additional risk factors controls for diabetic kidney disease?
- Lipid management
- Glycaemic control
- Blood pressure control
What are the 4 drug pillars of DKD management (4 main drugs that improve renal outcomes the most)
- RAS blockade
- SGLT2 inhibitors
- Ns-MRA
- GLP-1
What is RAS blockade?
This is the pharmacological blockade of the RAS system using Angiotensin-Converting Enzyme (ACE) and Angiotensin Receptor Blockers (ARB)
This allows for blood pressure control to help to slow renal hyperfiltration and hypertrophy
Target BP in albuminuria in DKD?
≤ 130/80
Target BP if no albuminuria in DKD?
≤ 140/90
What is an important thing to monitor in ACEi or ARB use?
Potassium levels
How do ACEis work in DKD?
ACEis decrease arterial BP and dilate the glomerular efferent arterioles, decreasing glomerular injury
They also decrease hyperfiltration by increasing the permeability selectivity of the filtering membrane, therefore decreasing microalbuminuria and therefore decreasing mesangial cell growth
How do SGLT2 inhibitors work in DKD?
SGLT2 inhibitors inhibit the SGLT2 Na+/Glucose co-transporter
This increases Na+ and Glucose secretion in the tubular fluid
This increases Na+ delivery to the macula densa
This activates the tubuloglomerular feedback mechanism, causing afferent arteriolar vasoconstriction
This decreases intra-glomerular pressure and therefore reduces CKD progression and albuminuria
It also allows for increased glucose excretion, therefore decreasing blood glucose concentration
What is a possible risk of SGLT2i in DKD?
There is a risk, however, of euglycaemic ketoacidosis
This is because a reduce in glucose causes a decrease in insulin
This causes an increase in lipolysis, increasing levels of free fatty acids, which undergo ß-oxidation to form ketones
What is an Ns-MRA?
Non-steroidal mineralocorticoid receptor antagonist
What is an example of an Ns-MRA used in DKD?
Finerenone
How do Ns-MRAs work in DKD?
It targets fibrosis and inflammation by blocking overactivation of the mineralocorticoid receptor in the kidneys and heart
This blocks action of aldosterone which aims to increase Na+ reabsorption and therefore water reabsorption and increases blood pressure
Blocking this decreases blood pressure and therefore decreases GFR, which has cardioprotective effects as well as a lower risk of CKD progression
What are some other diabetes-related urinary tract disorders?
- UTIs
- Contrast induced AKI
- Neurogenic bladder
- Renovascular disease
How does diabetes affect UTI risk?
diabetes have twice the incidence of UTI compared to those without diabetes. There is also a higher incidence of pyelonephritis and renal abscess formation in those with diabetes.
