Proteinuria

Note that this guidance excludes pregnancy and nephrotic level proteinuria (>3.5g/d, protein/creatinine ratio >300mg/mmol). Both of these require investigation in their own right. Nephrotic level proteinuria usually requires renal biopsy to establish the cause, unless this is immediately evident.

 

Why is proteinuria important?

Checking for proteinuria is important in:

  • diagnosing CKD (some patients can have proteinuria as the only sign of CKD – i.e. with normal GFR and kidney imaging)
  • risk-stratification to guide management (e.g. patients with proteinuria may benefit from ACE/ARB to delay CKD progression)
  • risk-stratification to guide prognostication (e.g. patients with proteinuria are at greater risk of cardiovascular disease and CKD progression)
  • monitoring CKD progression / response to treatment

 

How to check for proteinuria

Dipstick urinalysis can be used to screen for proteinuria, but the result will be affected by urinary concentration.  (Patients with proteinuria but dilute urine may have a false-negative dip result; patients with no proteinuria but a concentrated urine may have a false-positive.)

For more accurate quantification, send a spot urine sample in a universal container.  (Ideally send an early morning urine, but a random sample will be accurate enough in most patients.)  Request either an albumin:creatinine ratio (uACR) or protein:creatinine ratio (uPCR).  Results are expressed as a ratio to urine creatinine concentration in order to correct for urinary dilution.  In patients with diabetes, uACR is preferred because it is a more sensitive measure of kidney damage and finding even low-levels of albuminuria may change management (e.g. supporting the use of ACEi/ARBs).

 

How to interpret the result

In the UK, uACR and uPCR results are expressed as mg / mmol.  (Take care to note the units as elsewhere they may be different.)  Many physicians – particularly those who trained when 24 hr urine collections were used more widely – prefer to think in terms of protein excretion rate (PER), measured in grams / day.  As a rough rule of thumb, uPCR 100 = uACR 70 = 1 g protein excretion per day.

Very approximately:

uACR (mg/mmol) uPCR (mg/mmol) uPER (g/day) clinical relevance 
< 3 < 15 < 0.15 normal
> 3 > 15 > 0.15 slightly abnormal *(dipstick may be negative); consider ACEi/ARB and SGLT2i in diabetes
> 30 > 50 > 0.5 dipstick-positive; abnormal but low risk of progressive CKD *; consider ACEi/ARB  and SGLT2i in all
> 70 > 100 > 1.0 higher-risk of progressive CKD *
> 220 > 350 > 3.5 nephrotic-range

* These are rough guides; the clinical context is important when interpreting proteinuria.  Concurrent haematuria and proteinuria suggests intrinsic renal disease, even at low levels of proteinuria.

Establishing that the result is a true positive

Persistent proteinuria is abnormal and implies intrinsic renal disease.  Check separate samples including an early morning sample to establish that the finding is consistent.

Transient low-level proteinuria may be detected in:

  • acute febrile illness
  • urine infection
  • exercise-induced proteinuria
  • ‘orthostatic proteinuria’ – absent in early morning sample (though this requires monitoring, and may require further investigation if levels of protein are high)
Work-up

Assess history, blood pressure, renal function, seek evidence of diabetes mellitus (random blood glucose and glycosylated Hb).

The presence of the following increase the likelihood of significant renal disease, and indicate that further nephrological investigations are appropriate:

  • proteinuria greater than PCR >100mg/mmol or ACR >70 has been labelled as a referral threshold, but risk is graded, with greater risk of progressive renal disease in younger
  • haematuria also present (this halves official referral threshold to PCR 50, ACR 30)
  • impaired renal function (if it is deteriorating, investigation is urgent)
  • hypertension (less suggestive with increasing age)
  • history suggestive of systemic disorder (eg new onset of arthralgia, malaise, acute phase response)
  • family history of renal disease

 

What could be causing the proteinuria?

Almost any renal disease, or any type of renal injury, can cause proteinuria. Glomerular diseases are always responsible for heavy proteinuria (nephrotic syndrome), and lesser proteinuria may therefore be an early sign of these. However it may also be seen in people with tubulointerstitial renal disease, and in those with vascular renal injury from atherosclerosis or possibly longstanding hypertertension.

 

What is the significance of proteinuria?

In the absence of features predisposing to renal disease, the risk of serious pathology is related to the level of proteinuria. Low levels or intermittent proteinuria can be managed by regular (6-12 monthly) monitoring of urine testing, blood pressure, and serum creatinine.

 

How should it be managed?

Because of the association of proteinuria with progression of renal injury, rigorous attention to blood pressure control is strongly recommended if renal function is impaired (see information on blood pressure in renal disease).

 

When should patients be referred for further investigation?

The new development or worsening of any of the risk factors for intrinsic renal disease indicates that nephrological assessment is appropriate.

 

SUMMARY of regular monitoring for low-risk patients with < 1g protein/d (uPCR=100, uACR=70)

Every 6 months, extending to 12-24 months if all is unchanged, check:

  • blood pressure
  • quantitate proteinuria (PCR or ACR)
  • serum creatinine
Further information

Patient information on proteinuria is available from EdRenINFO, our web pages containing information about kidney diseases for patients, doctors and all medical staff. Patient info on nephrotic syndrome is also available.

Proteinuria from the EdRenHANDBOOK covers use of spot urine sample values to substitute for some 24 hour collections. Handbook information is aimed primarily at hospital doctors and concerns immediate management of renal problems.

UK CKD eGuide