How to manage a non-hypertensive diabetic patient with hyperglycemia, dyslipidemia, impaired renal function (eGFR 68), hematuria, proteinuria, and elevated uACR, who refuses insulin therapy?

Management of Diabetic Patient with Hyperglycemia, Dyslipidemia, and Diabetic Kidney Disease Who Refuses Insulin

Add an SGLT2 inhibitor immediately to the current regimen, as this patient has severely elevated albuminuria (uACR 18.71 mg/mmol = ~167 mg/g) with eGFR 68 mL/min/1.73 m², meeting criteria for diabetic kidney disease requiring urgent renoprotective therapy beyond glycemic control alone. 1, 2

Immediate Medication Optimization

First Priority: Add SGLT2 Inhibitor

• Start empagliflozin, canagliflozin, or dapagliflozin immediately for patients with type 2 diabetes, eGFR ≥30 mL/min/1.73 m², and albuminuria, as SGLT2 inhibitors provide substantial renoprotective and cardiovascular benefits independent of glucose lowering 1, 2
• The CREDENCE trial demonstrated that SGLT2 inhibitors reduce risk of kidney failure and cardiovascular events specifically in patients with albuminuria >300 mg/g (this patient's uACR converts to approximately 167 mg/g, still indicating significant kidney disease) 2
• SGLT2 inhibitors are recommended as first-line therapy alongside metformin for diabetic kidney disease with eGFR ≥30 mL/min/1.73 m² 1

Second Priority: Ensure ACE Inhibitor or ARB Therapy

• This patient requires ACE inhibitor or ARB therapy given the severely elevated albuminuria (uACR >30 mg/g), even though blood pressure is currently normal 1, 3
• For albuminuria >300 mg/g (Grade A evidence) or 30-299 mg/g (Grade C evidence), ACE inhibitor or ARB is strongly recommended regardless of blood pressure status 1, 3
• Target a ≥30% reduction in urinary albumin within 3-6 months of initiating therapy, as this predicts slower CKD progression 4

Third Priority: Optimize Current Glycemic Therapy

• Continue metformin as it is safe and appropriate at eGFR 68 mL/min/1.73 m² and should be continued until eGFR falls below 30 mL/min/1.73 m² 1, 4, 5
• If the patient is not already on metformin, initiate it immediately as first-line therapy 1
• Add a long-acting GLP-1 receptor agonist (such as dulaglutide, semaglutide, or liraglutide) if glycemic targets are not achieved with metformin and SGLT2 inhibitor, as GLP-1 RAs reduce cardiovascular events and may prevent macroalbuminuria 1

Addressing Insulin Refusal

Non-Insulin Intensive Glycemic Management

• With blood glucose of 345 mg/dL (19.2 mmol/L), this patient requires aggressive glucose lowering, but triple therapy with metformin + SGLT2 inhibitor + GLP-1 RA can achieve substantial glucose reduction without insulin 1
• Target HbA1c <7.0% for most patients, though individualized targets between 6.5-8.0% may be appropriate based on hypoglycemia risk and comorbidities 1
• Monitor for genital mycotic infections and volume depletion as common SGLT2 inhibitor side effects, and counsel patient to temporarily hold SGLT2 inhibitor during acute illness with vomiting/diarrhea 1, 2

Patient Education Strategy

• Explain that the combination of metformin, SGLT2 inhibitor, and GLP-1 RA provides complementary mechanisms: metformin reduces hepatic glucose production, SGLT2 inhibitors increase urinary glucose excretion, and GLP-1 RAs enhance insulin secretion and reduce appetite 1, 2
• Emphasize that SGLT2 inhibitors and GLP-1 RAs protect the kidneys and heart independent of glucose lowering, making them essential even if glucose control improves 1, 2

Monitoring Strategy

Renal Function Surveillance

• Monitor eGFR and uACR every 3-6 months given the presence of Stage 3a CKD (eGFR 68 mL/min/1.73 m²) and moderately-to-severely elevated albuminuria 1
• Expect a transient eGFR reduction of up to 25-30% within 7-14 days after initiating SGLT2 inhibitor or ACE inhibitor/ARB—this is hemodynamic and acceptable, not a reason to discontinue therapy 1, 2
• Monitor serum creatinine and potassium within 7-14 days after starting ACE inhibitor/ARB, then at least annually 2

Glycemic Monitoring

• Check HbA1c every 3 months until glycemic targets are achieved, then every 6 months 1
• Consider continuous glucose monitoring or frequent self-monitoring of blood glucose to assess time-in-range (target >70% of readings between 70-180 mg/dL) 1

Investigation of Hematuria

Urgent Evaluation Required

• Hematuria in the presence of proteinuria and diabetes requires investigation to exclude non-diabetic kidney disease, particularly given the relatively preserved eGFR for the degree of albuminuria 6
• Obtain urinalysis with microscopy to assess for dysmorphic red blood cells (suggesting glomerular origin) versus isomorphic red blood cells (suggesting urological cause) 6
• Consider nephrology referral for possible renal biopsy if hematuria persists, especially if accompanied by: short diabetes duration, absence of diabetic retinopathy, rapid progression of kidney disease, or active urinary sediment 3, 6

Red Flags for Non-Diabetic Kidney Disease

• Hematuria with proteinuria does not always indicate diabetic nephropathy—26% of patients with hematuria and proteinuria found on routine examination had renal insufficiency at biopsy, with IgA nephropathy being most common 6
• Renal biopsy is important because pathologic changes do not always coincide with clinical manifestations 6

Lipid Management

Current Lipid Profile Assessment

• Total cholesterol 5.5 mmol/L (213 mg/dL) and triglycerides 2.73 mmol/L (242 mg/dL) indicate dyslipidemia requiring treatment 1
• Calculate LDL-C and non-HDL-C to determine cardiovascular risk and treatment targets 1

Statin Therapy Initiation

• Start moderate-to-high intensity statin therapy for patients with diabetes and CKD, targeting LDL-C <100 mg/dL (or <70 mg/dL if high cardiovascular risk, or <55 mg/dL if very high risk) 1
• Consider adding ezetimibe if LDL-C targets are not achieved with statin monotherapy 1
• Address elevated triglycerides with lifestyle modification (reduce refined carbohydrates, increase physical activity) and consider fibrate therapy if triglycerides remain >200 mg/dL despite statin therapy 1

Lifestyle Modifications

Dietary Interventions

• Limit sodium intake to <2 g/day (<5 g sodium chloride/day) to reduce blood pressure and slow kidney function decline 1
• Maintain protein intake at 0.8 g/kg/day based on ideal body weight—reducing protein below this level does not alter glycemic measures or slow GFR decline 1
• Emphasize Mediterranean-style diet with emphasis on vegetables, whole grains, lean proteins, and healthy fats 1

Physical Activity

• Recommend moderate-intensity physical activity for cumulative duration of at least 150 minutes per week, as physical activity offers cardiometabolic, renal, and cognitive benefits 1
• Counsel patient to avoid sedentary behavior and incorporate movement throughout the day 1

Nephrology Referral Criteria

Current Status: Monitoring Phase

• Nephrology referral is not immediately required at eGFR 68 mL/min/1.73 m² unless specific complications arise 4
• However, strongly consider referral now given the presence of unexplained hematuria with proteinuria, which may indicate non-diabetic kidney disease requiring biopsy 3, 6

Future Referral Triggers

• Refer to nephrology when eGFR falls below 45 mL/min/1.73 m² for coordinated care to slow progression 1
• Mandatory referral when eGFR drops below 30 mL/min/1.73 m² to prepare for kidney replacement therapy 1, 4
• Refer earlier if: rapid eGFR decline (>5 mL/min/1.73 m² per year), difficult-to-control hypertension or hyperkalemia, uncertainty about CKD etiology, or refractory hyperkalemia develops 1, 4

Common Pitfalls to Avoid

Medication Errors

• Never combine ACE inhibitor with ARB or direct renin inhibitor—this increases adverse effects without added benefit 2
• Do not discontinue ACE inhibitor/ARB for transient creatinine elevation up to 30% after initiation—this is expected hemodynamic effect 1, 2
• Avoid initiating metformin if eGFR falls below 30 mL/min/1.73 m², and discontinue if eGFR <30 mL/min/1.73 m² develops 5

Monitoring Failures

• Do not rely solely on serum creatinine, as it underestimates renal dysfunction until significant kidney damage has occurred 3
• Serial eGFR determinations are infrequent in clinical practice (only 7.8% of diabetic patients receive them), but are essential given that 30.9% of patients have eGFR decline ≥12 mL/min/1.73 m² over 3 years 7
• Failure to monitor renal function is independently associated with adverse cardiovascular and renal events (OR 1.35) 8

Clinical Assessment Errors

• Do not assume all albuminuria in diabetes is diabetic nephropathy, especially with hematuria, short diabetes duration, or absence of retinopathy 3
• Nephrotic range proteinuria (>3.5 g/day) is a strong risk factor for rapid renal function decline even in pre-dialysis patients with severely impaired renal function (3.89-fold increased risk) 9