Laboratory tests - proteinuria

Normal urinary protein

Normal urinary protein <150 mg/day; albumin <30 mg/day
- ~40% Tamm-Horsfall (uromodulin), ~40% albumin, remainder low-molecular-weight

Type	Mechanism	Protein	Typical amount
Glomerular	Loss of size/charge barrier - podocyte or GBM injury	Albumin	Any, up to nephrotic
Tubular	Failure to reabsorb filtered LMW protein	beta2-microglobulin, retinol-binding protein, alpha1-microglobulin	Usually <1-2 g/day
Overflow	Excess filtered load overwhelms reabsorption	Free light chains, myoglobin, haemoglobin, lysozyme	Variable
Post-renal	Inflammation/secretion distal to glomerulus	IgA, mucus	Small

Nephrotic range = >3.5 g/day (ACR >300 mg/mmol, PCR >350 mg/mmol)
- Nephrotic RANGE is a number; nephrotic SYNDROME adds hypoalbuminaemia, oedema and hyperlipidaemia

Albuminuria present in ~6-8% of Australian adults
Albuminuria is an independent predictor of cardiovascular death and kidney failure at every level of eGFR
Prevalence far higher in diabetes (~30-40% lifetime), hypertension, and Aboriginal and Torres Strait Islander communities

Glomerular filtration barrier: fenestrated endothelium -> GBM -> podocyte slit diaphragm (nephrin, podocin)
- Size barrier (~70 kDa) + negative charge barrier (heparan sulphate)
- Albumin 69 kDa and anionic -> normally almost entirely excluded
Podocyte injury -> foot process effacement -> albuminuria (minimal change, FSGS, diabetes)
GBM/immune-complex injury -> albuminuria + haematuria + casts (GN)
Proteinuria is itself nephrotoxic
- Filtered protein -> proximal tubular uptake -> NF-kB activation, complement, cytokines -> tubulointerstitial fibrosis
- -> the reason lowering proteinuria is a therapeutic target, not just a marker

Orthostatic proteinuria - only in <30 y; absent in the first morning void; benign
Exercise, fever, heart failure, seizure, acute illness - repeat before investigating

Test	Detects	Caveats
Dipstick	Albumin only, threshold ~150-300 mg/L	Misses light chains and tubular protein entirely. False +ve: alkaline urine, concentrated urine, chlorhexidine, haematuria. False -ve: dilute urine
Spot ACR (first-morning preferred)	Albumin	The standard for screening and staging
Spot PCR	Total protein	Use when non-albumin protein expected (myeloma, tubular disease)
24 h collection	Total protein	Superseded except in pregnancy/discordance; collection errors common
Serum + urine EPG, serum free light chains	Monoclonal protein	*Mandatory if PCR >> ACR*, or unexplained CKD >50 y

*Dipstick-negative but PCR high = light chains until proven otherwise*
ACR and PCR are both creatinine-normalised - falsely high in the sarcopenic, falsely low in the muscular

Confirm on a repeat first-morning sample (>=2 of 3 over 3 months)
Urine microscopy - dysmorphic RBCs, red cell casts = glomerulonephritis, urgent
Bloods: UEC, albumin, glucose/HbA1c, lipids, EPG/FLC, ANA, ANCA, anti-GBM, complement, hepatitis B/C, HIV
Renal ultrasound
Biopsy if: nephrotic syndrome without a clear cause, proteinuria with glomerular haematuria, unexplained declining eGFR, or suspected systemic disease

By risk band

A1 (ACR <3) - address CV risk factors; no specific therapy
A2-A3, or any diabetic kidney disease
- 1. RAS blockade - ACEi or ARB titrated to the maximum tolerated dose
  - *Never combine ACEi + ARB* - inc hyperkalaemia, AKI, no outcome benefit
  - Accept a creatinine rise up to ~30% and stable K+
- 2. SGLT2 inhibitor - dapagliflozin or empagliflozin, irrespective of diabetes if ACR >=~22.6 mg/mmol (or eGFR 20-45)
- 3. Finerenone - non-steroidal MRA, added for residual albuminuria in type 2 diabetes with CKD
- 4. BP target <120/80 (standardised measurement); GLP-1 RA for additional cardiorenal and weight benefit in T2DM
Nephrotic syndrome - add loop diuretic + salt restriction (<2 g Na/day), statin, and assess VTE risk (anticoagulate if albumin <20-25 g/L, especially membranous)
Disease-specific immunosuppression only after a histological or serological diagnosis

ACR + eGFR at least annually; 6-monthly or more if A3 or falling eGFR
Target: >=30% reduction in albuminuria - a validated surrogate for slowed progression

Diabetes, hypertension, obesity - the dominant causes
Glomerulonephritis of any type; lupus nephritis
Multiple myeloma / AL amyloid (overflow and glomerular)
Pre-eclampsia
Reflux nephropathy, chronic tubulointerstitial disease (tubular pattern)
Drugs - NSAIDs, gold, penicillamine, lithium, pamidronate, interferon, VEGF inhibitors, checkpoint inhibitors
Obstructive sleep apnoea, heart failure, sickle cell disease
Fabry disease, Alport syndrome

Degree of proteinuria is the strongest modifiable predictor of progression to ESKD in almost every glomerular disease
Albuminuria predicts cardiovascular death independently of eGFR - the risk gradient begins well below the "abnormal" threshold
Reduction in albuminuria with treatment predicts renal survival
Complications of sustained heavy proteinuria:
- VTE (renal vein thrombosis - highest in membranous nephropathy)
- Infection (urinary loss of IgG and complement) - encapsulated organisms
- Hyperlipidaemia, protein malnutrition, vitamin D and thyroxine-binding globulin loss
- Refractory oedema, AKI from over-diuresis

10 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.