Diabetic kidney disease

Question 1

How is diabetic kidney disease defined?

Answer 1

• 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

Question 2

How common is diabetic kidney disease?

Answer 2

In T1DM, 20-30% of patients will have albuminuria

In T2DM, 40% will have chronic kidney disease

Question 3

What are some factors that increase risk of diabetic kidney disease?

Answer 3

• 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)

Question 4

Describe the pathophysiology of diabetic kidney disease

Answer 4

• 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

Question 5

What are the 4 stages of diabetic kidney disease?

Answer 5

1. Renal hypertrophy leads to hyperfiltration, with and an elevated eGFR occur early
2. Dipstick tests positive, with over proteinuria
3. As the levels of proteinuria rise, the eGFR can fall
4. eGFR < 10, ESRD

Question 6

How is diabetic kidney disease diagnosed?

Answer 6

Blood testing - Glucose, HbA1C, RFT
Urinalysis - Glucose, albuminuria

Question 7

What are the 4 tiers of management in diabetic kidney disease?

Answer 7

1. Lifestyle and self-management
2. First-line drug therapy
3. Additional drugs for heart and kidney protection
4. Additional risk factor control

Question 8

What are some lifestyle management options used in diabetic kidney disease?

Answer 8

• Diet changes - Low sugar
• Exercise
• Smoking cessation
• Weight loss

Question 9

What are some drugs used as first-line drug therapy for diabetic kidney disease?

Answer 9

• Metformin
• SGLT2 inhibitor
• RAS blockade
• Statin

Question 10

What are some drugs used as additional heart and kidney protective drugs in diabetic kidney disease?

Answer 10

• GLP-1
• Antiplatelet therapy
• ns-MRA

Question 11

What are some additional risk factors controls for diabetic kidney disease?

Answer 11

• Lipid management
• Glycaemic control
• Blood pressure control

Question 12

What are the 4 drug pillars of DKD management (4 main drugs that improve renal outcomes the most)

Answer 12

• RAS blockade
• SGLT2 inhibitors
• Ns-MRA
• GLP-1

Question 13

What is RAS blockade?

Answer 13

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

Question 14

Target BP in albuminuria in DKD?

Answer 14

≤ 130/80

Question 15

Target BP if no albuminuria in DKD?

Answer 15

≤ 140/90

Question 16

What is an important thing to monitor in ACEi or ARB use?

Answer 16

Potassium levels

Question 17

How do ACEis work in DKD?

Answer 17

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

Question 18

How do SGLT2 inhibitors work in DKD?

Answer 18

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

Question 19

What is a possible risk of SGLT2i in DKD?

Answer 19

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

Question 20

What is an Ns-MRA?

Answer 20

Non-steroidal mineralocorticoid receptor antagonist

Question 21

What is an example of an Ns-MRA used in DKD?

Answer 21

Finerenone

Question 22

How do Ns-MRAs work in DKD?

Answer 22

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

Question 23

What are some other diabetes-related urinary tract disorders?

Answer 23

• UTIs
• Contrast induced AKI
• Neurogenic bladder
• Renovascular disease

Question 24

How does diabetes affect UTI risk?

Answer 24

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.