Applied Evidence

Exercise-induced proteinuria?

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Urinalysis reveals an excessive level of protein, but your patient is a runner. How concerned should you be?


 

References

PRACTICE RECOMMENDATIONS

Rely on a spot urine microalbumin-to-creatinine or protein-to-creatinine ratio to accurately assess proteinuria. B

Repeat testing if routine urinalysis detects proteinuriaespecially if the patient reports having exercised in the previous 24 hours. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series

CASE As part of a routine physical examination, urinalysis reveals that a patient new to your practice is excreting an excessive level of protein. The patient is physically fit and shared during the history taking that he is an avid runner. The physical examination and other laboratory values were unremarkable. How concerned should you be about the finding of proteinuria?

Exercise-induced proteinuria is generally benign and a function of the intensity—rather than the duration—of exercise.1 It occurs most often among athletes participating in such sports as running, swimming, rowing, football, or boxing.2 It’s also transient—lasting 24 to 48 hours.1 Recognizing exercise-induced proteinuria is fairly straightforward—once you know what to look for.

But first, a word about the processes at work.

Diverse processes that work alone—or together

The normal range of protein excretion in healthy individuals is 150 to 200 mg of protein per day, of which albumin constitutes 10 to 20 mg.3 Individuals with proteinuria persistently higher than this level need further evaluation.

Diverse processes leading to proteinuria—working alone or concomitantly—occur at the level of the nephron.3

Glomerular proteinuria results from increased filtration of macromolecules such as albumin across the glomerular capillary barrier. This type of proteinuria can occur with different glomerulopathies, upright posture, or exercise.4

Researchers have not identified the mechanisms leading to postexercise proteinuria, but there are several theories. (For more on this, see “Why does exercise increase protein excretion?”.)

Tubular proteinuria is due to a deranged tubular apparatus with an intact glomerulus. This results in the escape of β2-microglobulin and immunoglobulin light chains from proximal tubular reabsorption. It is often missed on dipstick testing, which detects only albumin. This type of proteinuria is usually seen in tubulointerstitial diseases or in patients with idiopathic nephrotic syndrome.5

Overflow proteinuria occurs when small molecular light chains escape the glomerular filtration barrier and overwhelm the tubular reabsorptive capacity. This type of proteinuria can be seen in multiple myeloma, and is detectable by protein-to-creatinine ratio or urine protein electrophoresis.

Why does exercise increase protein excretion?

The root cause of exercise-induced proteinuria is unclear, but the renin-angiotensin system (RAS) and prostaglandins are thought to play a major role. The plasma concentration of angiotensin II increases during exercise, leading to filtration of protein through the glomerular membrane.30 And angiotensin-converting enzyme (ACE) inhibitors have been shown to significantly diminish exercise-induced proteinuria, thus supporting this theory.31,32

Also, strenuous exercise increases sympathetic nervous system activity as well as blood levels of catecholamines, thereby increasing permeability of the glomerular capillary membrane.33 Furthermore, lactate increases with strenuous exercise and causes conformational changes in serum proteins that, when coupled with glomerular barrier changes, can lead to increased permeability and protein excretion.

The surest means of detecting proteinuria
Albumin excretion >300 mg/d is called macroalbuminuria, overt proteinuria, or dipstick-positive proteinuria. Albumin persistently excreted in the urine between 30 and 300 mg/d is referred to as microalbuminuria.

Because microalbuminuria is not detectable by a standard urine dipstick test, some providers routinely screen for protein with the microalbumin-to-creatinine ratio. A first-voided morning urine specimen is recommended, but random urine samples are an acceptable alternative.6 The microalbumin-to-creatinine ratio is recommended as a screen for early diabetic nephropathy and other kidney diseases. And a positive test result may also suggest increased risk of cardiovascular disease.6 Microalbuminuria is defined as persistent albumin excretion between 30 and 300 mg/d.7

When exercise is a factor, here’s what to look for

As noted earlier, exercise-induced proteinuria is a function of the intensity of the exercise. Moderate and strenuous (vigorous) exercise are the 2 types of exercise that come into play when discussing proteinuria. Differentiating them is not precise, but is often defined by maximal oxygen consumption (vigorous=60% of VO2max; moderate <60% VO2max); metabolic equivalents (vigorous=6 METS; moderate <6 METS); walking/running speeds (various); and heart rate reserve (vigorous=60% HRR; moderate <60% HRR).8

Moderate exercise produces glomerular proteinuria, with an increase in macromolecular (albumin) filtration across the glomerular barrier. Strenuous exercise increases glomerular filtration of low-molecular-weight proteins (β2-microglobulin), which overwhelm the reabsorbing capacity of the tubular apparatus, causing temporary dysfunction and tubular proteinuria.9 Thus, the pathophysiology is mixed, with a major contribution from glomerular proteinuria.10

Strenuous exercise can cause protein excretion to exceed 1.5 mg/min.11 However, it seldom rises beyond 1 to 2 g/d,4 and this increase usually reverts to normal physiologic levels within 24 to 48 hours after exercise.12

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