• Diabetic kidney disease is the most common cause of chronic renal failure, but be aware of red flags for alternative causes of renal dysfunction

• Consider investigation +/- referral for all patients with atypical features

• The first sign of diabetic kidney disease is typically albuminuria , but some patients present with an initial reduction in eGFR.

• Major factors that reduce the progression of diabetic kidney disease are:

• Effective treatment of hypertension including the maximum tolerated dose of a single renin-angiotensin-aldosterone system inhibitor (e.g.  ACE inhibitors (ACEi) OR angiotensin receptor blockers (ARB)) with a target blood pressure < 130/80 mmHg
• Effective glycaemic control
• SGLT2 inhibitors (benefits independent of glycaemic control)
  • NB: GLP1RAs slow the progression of albuminuria and decline in eGFR in diabetic kidney disease but are yet to be shown to prevent dialysis or renal death

• Diabetic kidney disease is diagnosed in a suitable patient with albuminuria (UCR > 3 mg/mmol) AND/OR eGFR < 60 mL/min. The four key areas of management are:

1. Renin/angiotensin/aldosterone (RAA) blockade +  manage hypertension aggressively aiming for target blood pressure < 130/80 mmHg
   • Start ACEi or ARB regardless of blood pressure if no concerns over hypotension and no contraindications (do not use in combination without specialist opinion and do not use either if on Entresto)
     • In women of childbearing age ensure effective contraception + not pregnant before starting
     • Repeat eGFR and potassium 2 - 4 weeks after starting
       • If > 30% reduction in eGFR reduce or stop the ACEi/ARB and consider renal artery stenosis
       • If potassium > 6 mmol/L reduce or stop the ACEi/ARB and consider seeking dietitian and/or renal advice
   • Maximise dose of ACEi/ARB before the addition of another agent (repeat eGFR + potassium 2-4 weeks after any dose increase)
   • If blood pressure not to target add a calcium channel blocker or thiazide diuretic (chlorthalidone is the preferred thiazide as it is long-acting)
   • In those with refractory hypertension consider adding spironolactone or eplenerone (beware increased risk of hyperkalaemia), OR an alpha blocker OR a beta-blocker
   • Consider advising patients with diabetic kidney disease to purchase a home blood pressure monitor (not funded) given the importance of BP control

2. Optimise glycaemic control

• Lifestyle management and metformin are still first-line management - remember to adjust metformin doses to renal function (see below)
• All patients with diabetic kidney disease should be on an SGLT2 inhibitor and/or GLP1RA unless contraindicated and regardless of glycaemic control or other glucose lowering therapies
  • NB: A SGLT2 inhibitor is typically preferable in diabetic kidney disease as as above GLP1RA are yet to be shown to prevent dialysis or renal death. However, GLP1RA are a useful alternative if a SGLT2 inhibitor is contraindicated or not tolerated. In particular, GLP1RAs can be used when the eGFR is between 15-30 mL/min. Dual SGLT2 inhibitor/GLP1 receptor agonist therapy provides likely additional cardiovascular protection, but it is not currently known whether it provides additional renal protection

3. Optimise cardiovascular risk

• Lifestyle management
• Strongly consider statin therapy regardless of 'calculated CVD risk' or LDL cholesterol levels given CKD  significantly increases CVD
• Smoking cessation

4. Monitor and review regularly

• Monitor serum eGFR, potassium, HbA1c, blood pressure and urinary ACR at least 3 monthly
• Adjust medications to achieve target blood pressure and HbA1c while minimising adverse effects
• Continue to optimise cardiovascular risk
• Review medication regimen if declining eGFR:
  • Metformin doses need to be reduced once eGFR < 45 mL/min + stopped when eGFR < 15 mL/min
  • As CKD progresses, doses of insulin and sulfonylureas may need to be reduced as insulin is renally cleared + gluconeogenesis will be reduced
• Consider referring to Renal team as per local DHB policy. Red flags for referral include:
  • eGFR < 30 mL/min
  • Decline in eGFR by > 15 mL/min/year
  • Decline in eGFR by > 30% with ACEi or ARB
  • Significant proteinuria out of proportion with glycaemic control
  • Possible alternative causes of renal dysfunction (see above)