Microalbuminuria

  • Asymptomatic healthy persons with dipstick proteinuria on 2 consecutive occasions: 0.5–5%

Sustained proteinuria: Proteinuria >1–2 g/24 h is also commonly associated with glomerular disease. Patients often will not know they have proteinuria unless they become edematous or notice foamy urine on voiding.

Transient or Functional proteinuria: Proteinuria is nonsustained, generally <1 g/24 h. Fever, exercise, obesity, sleep apnea, emotional stress, orthostatic, seizures, and congestive heart failure can explain transient proteinuria. Proteinuria only seen with upright posture is called orthostatic proteinuria. Occasionally, isolated proteinuria sustained over multiple clinic visits is found in diabetic nephropathy, nil lesion, mesangioproliferative glomerulonephritis, and FSGS. Proteinuria in most adults with glomerular disease is nonselective, containing albumin and a mixture of other serum proteins, while in children with nil lesion from minimal change disease, the proteinuria is selective and largely composed of albumin.

  • Primary glomerular causes: FSGN, IgA nephropathy (Berger's dz), IgM nephropathy, MPGN, membranous nephropathy, minimal change dz.

  • Secondary glomerular causes: Alport's synd., amyloidosis, SLE, DM, NSAIDs, penicillamine, gold, ACEI, Fabry's dz, HIV, syphilis, hepatitis, post-streptococcal inf., lymphoma, solid tumors, sarcoidosis, SCD

  • Tubular causes: aminoaciduria, NSAIDs, Abx, Fanconi synd., heavy metal ingestion, HTN nephrosclerosis, interstitial nephritis.

  • Overflow causes: hemoglobinuria, multiple myeloma, myoglobinuria

  • Non-pathologic causes of proteinuria: CHF, fever, heat injury, emotional stress, heavy physical exertion, seizures, inflammatory process, most acute illnesses, pregnancy, standing upright, UTI, urologic H'ge.

Definition: Proteinuria is defined as excess protein >150 mg/L or greater over 24 hours (10 - 30 mg/dL) excreted in the urine.

    • Normal protein excretion

      • < 150 mg total protein/d and ~30 mg albumin/d

    • Microalbuminuria

      • 30–300 mg albumin/d or 30–350 protein/d

      • Also defined as 30–300 μg albumin/mg creatinine

      • It is not detectable by dipstick analysis.

    • Macroalbuminuria and moderate proteinuria

      • 300–3500 mg albumin/d or 300–3500 mg protein/g creatinine

      • Also defined as >300 μg albumin/mg creatinine but < 30 mg albumin/g creatinine

    • Nephrotic-range proteinuria

      • >3500 mg albumin/d or >3500 mg protein/g creatinine

Isolated proteinuria

  • Proteinuria in the presence of an otherwise normal urinary sediment, a radiologically normal urinary tract, and absence of known renal disease

Epidemiology:

Urine Assays for Albuminuria/Proteinuria

A UPCR (mg/mg) of <0.2 is normal, while a ratio of 3.5 or more is considered in nephrotic range.

A UACR (mg/g) of <30 is normal, >30 to 300 is microalbuminuria, and >300 is considered nephropathy; this test is more sensitive than the UPCR.

Dipstick: proteinuria

1+ = 30 mg/dL

2+ = 100 mg/dL

3+ = 300 mg/dL

4+ = 1000 mg/dL

Proteinuria is an independent risk factor for the progression of kidney disease and a marker of progressive atherosclerosis.

Microalbuminuria is an early, sensitive, and prognostic marker of diabetic and hypertensive nephropathy, an independent risk factor for CVD in patients with and without concurrent DM or HTN, a marker of endothelial dysfunction, and a risk factor of VTE.

Average urine protein excretion in adults in 80 mg/day.

Albumin, immunoglobulines, beta2-microglobuline, and Tamm-Horsfall mucoproteins

Factors causing false-positive results for proteinuria:

  • Concentrated urine

  • Dehydration

  • Dipstick immersed too long

  • Gross hematuria

  • Highly alkaline urine (pH >7.5)

  • Iodinated contrast agent

  • Presence of mucus, semen, WBCs

The 24-h urine collection is the gold standard, as protein excretion may vary with the circadian rhythm. To ensure adequacy of the specimen, also measure urine creatinine concentration. The total creatinine in the sample should be between 0.8 and 1.5 g; lower amounts suggest an inadequate sample.

Work up of persisten proteinuria:

Laboratory:

    • Electrolytes, CB with diff, lipid, albumin, protein, ESR, glucose.

    • ANA: SLE and other rheumatological d/o

    • C3, C4: Low levels suggest cyroglobulinemia, SLE, post-streptococcal or membranoproliferative GN

    • ANCA: vasculitis

    • ASO, anti-DNase B titers: Poststreptococcal GN

    • HIV, VDRL, hepatitis B and C serology: infectious glomerular proteinuria

    • Serum urate: tubulointerstitial disease

    • Urine and plasma protein electrophoresis: Monoclonal gamma peak in BJ proteinuria vs the broad heterogeneous peak in tubular proteinuria

Imaging:

  • CXR: SLE, sarcoidosis, vasculitis

  • Renal U/S: abnormal renal size, scarring, and possible obstruction; allows planning for Bx.

Urine microscopy:

  • Bacteria: UTI

  • Blood cells:

    • Dysmorphic RBCs and RBC casts: Glomerular disease

    • RBCs: UTI

    • WBCs and WBC casts: Interstitial disease, pyelonephritis, UTI

  • Fatty casts, free fat, or oval bodies: Nephrotic range proteinuria

  • Waxy, granular, or cellular casts: Advanced chronic renal disease.

Renal biopsy is usually not indicated in mild proteinuria <1 g/day with normal renal function and negative urine sediment. Nephrology referral is needed for all patients with proteinuria >2 g/day, microscopic urinary signs or renal disease, renal insufficiency. Renal bx should be considered in adults with persistent proteinuria. Nephrotic range proteinuria, except in the obvious diabetic and/or HTN need renal bx.