What is the best management approach for a 52-year-old male with poorly controlled diabetes (HbA1c of 12.7%), hematuria, and an elevated UACR of 18.71 mg/mmol, despite normal serum creatinine, to reduce cardiovascular and renal risk?

Management of Poorly Controlled Diabetes with Diabetic Kidney Disease and Hematuria

Immediate Glycemic Management

This 52-year-old male with severely uncontrolled diabetes (HbA1c 12.7%) and moderately elevated albuminuria (UACR 18.71 mg/mmol) requires immediate initiation of combination glucose-lowering therapy with an SGLT2 inhibitor plus a GLP-1 receptor agonist, alongside maximally-dosed ACE inhibitor or ARB therapy, to reduce cardiovascular and renal mortality risk. 1

Glucose-Lowering Strategy

• Start combination therapy immediately given the HbA1c is >2% above goal, as recommended for patients requiring aggressive glycemic control 1
• Add an SGLT2 inhibitor (canagliflozin, empagliflozin, or dapagliflozin) as first-line therapy for patients with diabetes and albuminuria >3 mg/mmol (equivalent to >30 mg/g), which provides proven cardiovascular and renal protection independent of glucose lowering 2, 3, 4
• Combine with a GLP-1 receptor agonist with proven cardiovascular outcomes trial (CVOT) benefits, as the combination of SGLT2i and GLP-1 RA is encouraged to improve outcomes 1
• Target HbA1c reduction of 2-3% over 3-6 months to reach individualized goal, typically <7% for this age group without significant comorbidities 1

SGLT2 Inhibitor Dosing

• Canagliflozin 100 mg once daily before the first meal, with potential increase to 300 mg if eGFR remains ≥60 mL/min/1.73 m² and additional glycemic control is needed 3
• Empagliflozin 10 mg once daily, with potential increase to 25 mg for additional glycemic control 4
• Monitor for genital mycotic infections and volume depletion, particularly in the first weeks of therapy 3, 4

Renal Protection Strategy

Blood Pressure and RAAS Blockade

• Initiate or maximize ACE inhibitor or ARB therapy to the highest tolerated dose, as this is strongly recommended for UACR ≥30 mg/g (≥3 mg/mmol) to slow CKD progression and reduce cardiovascular events 1, 5
• Target blood pressure <130/80 mmHg to reduce cardiovascular mortality and slow CKD progression 1
• Monitor serum creatinine/eGFR and potassium within 7-14 days after ACE inhibitor/ARB initiation or dose adjustment, then at least annually 1, 2, 5
• Accept up to 30% increase in serum creatinine after ACE inhibitor/ARB initiation without discontinuing therapy, as this is expected and acceptable 2

Additional Antihypertensive Therapy

• Add a dihydropyridine calcium channel blocker as second-line agent if blood pressure remains >130/80 mmHg 1
• Add a thiazide-like diuretic (chlorthalidone or indapamide preferred) as third-line agent 1
• Consider mineralocorticoid receptor antagonist (finerenone) if blood pressure targets are not met on three classes including a diuretic, as this reduces cardiovascular death and end-stage kidney disease in patients with diabetic kidney disease and albuminuria 1, 5

Hematuria Evaluation

Urgent Assessment Required

• Refer to nephrology immediately for evaluation of hematuria in the setting of diabetic kidney disease, as this may indicate non-diabetic kidney disease requiring kidney biopsy 1
• Rule out urinary tract infection with urine culture, as urosepsis and pyelonephritis are more common in patients with diabetes and SGLT2 inhibitors increase this risk 3
• Exclude urologic malignancy with cystoscopy and upper tract imaging if infection is ruled out, particularly given the patient's age and sex 1
• Do not attribute hematuria solely to diabetic nephropathy, as isolated hematuria is uncommon in diabetic kidney disease and warrants investigation for alternative etiologies 1

Monitoring During Workup

• Hold SGLT2 inhibitor temporarily if urinary tract infection is confirmed until infection resolves 3
• Continue ACE inhibitor/ARB therapy during hematuria workup unless acute kidney injury develops 1, 5

Cardiovascular Risk Reduction

Lipid Management

• Initiate high-intensity statin therapy immediately if not already prescribed, as this patient has diabetes with additional cardiovascular risk factors (albuminuria, poorly controlled glucose) 1
• Target LDL cholesterol reduction of ≥50% from baseline 1
• Monitor lipid panel 4-12 weeks after statin initiation to assess response 1

Antiplatelet Therapy

• Consider aspirin 75-162 mg daily for primary prevention given the elevated cardiovascular risk from diabetes, albuminuria, and likely hypertension 1

Monitoring Protocol

Short-Term (First 3 Months)

• Check HbA1c every 4-6 weeks until glycemic targets are approached 1
• Monitor serum creatinine, eGFR, and potassium at 1-2 weeks after each medication adjustment, then monthly for 3 months 1, 2, 5
• Repeat UACR in 3 months to assess treatment response, as two of three elevated samples over 6 months are needed to confirm persistent albuminuria 5, 6
• Monitor blood pressure weekly at home with transmitted data until target <130/80 mmHg is achieved 1

Long-Term (After 3 Months)

• Check HbA1c every 3 months until stable at goal, then every 6 months 1
• Monitor UACR annually to assess progression of kidney disease 1, 5
• Check serum creatinine, eGFR, and potassium at least annually or more frequently if abnormalities develop 1, 5
• Annual lipid panel to monitor statin efficacy 1

Lifestyle Modifications

• Restrict dietary sodium to <2,300 mg/day to manage blood pressure and reduce cardiovascular risk 1
• Maintain protein intake at 0.8 g/kg/day (recommended daily allowance) to slow CKD progression 1, 5
• Target ≥5-10% weight reduction through caloric restriction and physical activity if overweight 1
• Smoking cessation if applicable, as smoking accelerates albuminuria progression 1

Critical Pitfalls to Avoid

• Never combine ACE inhibitor with ARB, as this increases adverse events (hyperkalemia, acute kidney injury) without additional benefit 1
• Do not discontinue SGLT2 inhibitor due to modest increases in serum creatinine (<30% increase), as renal benefits persist despite initial eGFR decline 2
• Do not delay nephrology referral for hematuria evaluation, as this may represent rapidly progressive glomerulonephritis or malignancy requiring urgent intervention 1
• Avoid attributing all symptoms to diabetes, particularly the hematuria which requires thorough urologic and nephrologic evaluation 1
• Do not use SGLT2 inhibitors if eGFR falls below 30 mL/min/1.73 m² for glycemic control, though they may be continued for heart failure or CKD indications at lower eGFR 3, 4