Can an uncontrolled Diabetes Mellitus type 2 (DM2) patient have proteinuria without microalbuminuria?

Proteinuria Without Microalbuminuria in Uncontrolled Type 2 Diabetes

Yes, an uncontrolled Type 2 diabetes patient can have proteinuria without microalbuminuria, as approximately 30% of patients with type 2 diabetes and chronic kidney disease show proteinuria without the typical diabetic nephropathy pattern that begins with microalbuminuria. 1

Understanding Albuminuria and Proteinuria in Type 2 Diabetes

• Microalbuminuria is defined as urinary albumin excretion of 30-299 mg/24h, 30-299 mg/g creatinine on a random spot urine sample, or 20-199 μg/min on a timed collection 2, 3
• Clinical albuminuria (macroalbuminuria) is defined as urinary albumin excretion ≥300 mg/24h, ≥300 mg/g creatinine, or ≥200 μg/min 2
• In type 1 diabetes, kidney disease typically follows a predictable progression from microalbuminuria to macroalbuminuria to declining GFR 2
• In type 2 diabetes, the kidney disease pattern is more heterogeneous and less predictable 2

Pathophysiology of Kidney Disease in Type 2 Diabetes

• About 40% of type 2 diabetes patients with microalbuminuria show typical diabetic nephropathy changes on biopsy 2
• Approximately 30% have normal or near-normal biopsy results despite having albuminuria 2
• Another 30% have increased severity of tubulointerstitial, vascular, and/or glomerulosclerotic lesions unrelated to classic diabetic glomerulopathy 2
• Research has shown that about 30% of adults with type 2 diabetes and chronic renal insufficiency (GFR <60 mL/min/1.73m²) have neither retinopathy nor albuminuria 1

Clinical Implications

• The kidney structural-functional relationships established in type 1 diabetes are less precise in type 2 diabetes 2
• A substantial number of patients with type 2 diabetes and proteinuria have little or no diabetic glomerulopathy lesions 2
• GFR may decrease in patients with type 2 diabetes even when albumin excretion is still in the microalbuminuric range 4
• Renal insufficiency can develop in type 2 diabetes through pathways that don't involve the classic progression from microalbuminuria to macroalbuminuria 1

Screening Recommendations

• All patients with type 2 diabetes should have both urinary albumin excretion and estimated glomerular filtration rate (eGFR) assessed 2
• Standard dipstick tests detect albuminuria above 300 mg/g creatinine but are not sensitive enough for microalbuminuria 2, 3
• Specific assays are needed to detect microalbuminuria because standard hospital laboratory assays for urinary protein are not sufficiently sensitive 2
• Due to variability in urinary albumin excretion, diagnosis of abnormal albumin excretion requires confirmation with 2 of 3 specimens collected within a 3-6 month period 2, 3

Common Pitfalls and Caveats

• Several factors can cause transient elevations in urinary albumin excretion, including exercise within 24 hours, infection, fever, congestive heart failure, marked hyperglycemia, marked hypertension, pyuria, and hematuria 2, 3
• First morning void samples are preferred to minimize effects of orthostatic proteinuria, which is common in adolescents and usually considered benign 2, 3
• Non-diabetic causes of proteinuria should be considered, especially in patients with type 2 diabetes who have proteinuria without retinopathy 2
• Failure to adjust for creatinine can lead to errors from variations in urine concentration 3

Clinical Approach

• For uncontrolled type 2 diabetes patients with proteinuria but no microalbuminuria, consider:
  • Non-diabetic kidney disease that may require specific therapy 2
  • Tubulointerstitial or vascular kidney disease rather than classic diabetic nephropathy 2, 1
  • The need for nephrology referral for further evaluation, including possible kidney biopsy 2
• The absence of retinopathy in a patient with proteinuria suggests non-diabetic kidney disease 2
• Aggressive control of blood pressure, glycemia, and other cardiovascular risk factors is essential regardless of the pattern of kidney disease 2, 4

Understanding that proteinuria without microalbuminuria can occur in type 2 diabetes is important for proper diagnosis and management of kidney disease in these patients.