How does fever cause proteinuria?

How Fever Causes Proteinuria

Direct Mechanism

Fever causes proteinuria through temperature-induced alterations in glomerular permeability, leading to increased passage of proteins (particularly albumin) across the glomerular filtration barrier, combined with impaired tubular reabsorption of filtered proteins. 1, 2, 3

Pathophysiological Mechanisms

Glomerular Component

• Elevated body temperature (≥38.4-38.5°C) directly alters glomerular capillary permeability, allowing increased passage of plasma proteins, particularly albumin 2, 4, 3
• This produces a glomerular pattern of proteinuria with selectivity ranging from poorly to highly selective depending on the degree of barrier disruption 4, 3
• The mechanism involves temperature-related transient glomerular alterations affecting the charge and size selectivity of the filtration barrier 2
• Urinary B7-1 (CD80) expression increases during fever, indicating podocyte involvement in the glomerular barrier dysfunction, with significantly higher levels in bacterial versus viral infections 1

Tubular Component

• Fever causes a tubular type of proteinuria characterized by increased excretion of low-molecular-weight proteins like β2-microglobulin and lysozyme 1, 3
• This results from impaired proximal tubular reabsorption capacity for filtered proteins during febrile states 3
• The tubular proteinuria occurs universally in febrile patients and disappears rapidly (within 12 hours) once fever subsides 2, 3

Uromodulin Paradox

• Unlike other proteins, uromodulin (Tamm-Horsfall protein) decreases during fever (10.5 ± 1 vs. 26.7 ± 2.2 arbitrary units in controls), demonstrating that febrile proteinuria is not a generalized increase in all urinary proteins 1

Clinical Characteristics

Magnitude and Threshold

• Proteinuria occurs only when body temperature exceeds 38.4-38.5°C 4, 3
• Mild proteinuria (<0.5-1 g/24h in adults, <0.65 g/24h using sensitive methods) can be explained by altered glomerular function from temperature alone 2
• Approximately 5.6% of febrile children develop detectable proteinuria during acute illness 4
• In experimental hyperthermia (40-41°C for 1-2 hours), 50% of healthy volunteers developed proteinuria 2

Reversibility

• Tubular proteinuria resolves rapidly (within 12 hours) after fever subsides in all cases 2, 3
• Glomerular proteinuria may persist longer, with only 50% resolving quickly after defervescence 3
• All alterations in healthy individuals reverse to normal within 12 hours of temperature normalization 2

Important Clinical Caveats

When Fever Alone Does NOT Explain Proteinuria

• Proteinuria exceeding 0.5-1 g/24h in adults suggests underlying glomerular or tubulo-interstitial disease rather than fever alone, possibly caused by immunologic or toxic products from the infectious process 2
• Proteinuria with slow regression after fever resolution indicates parainfectious nephropathy rather than functional disorder 2
• Pre-existing mild glomerulopathy (even if subclinical) predisposes to pathological proteinuria during fever in all affected individuals 2

Diagnostic Pitfalls

• Dipstick screening shows high false-positive rates (~70%), requiring confirmation with quantitative methods like sulfosalicylic acid or protein-to-creatinine ratio 4
• The specific etiology of fever (bacterial vs. viral) does not appear to influence whether proteinuria occurs, though B7-1 levels are higher in bacterial infections 1, 4
• Fever is a recognized physiological cause of transient proteinuria that must be considered before attributing proteinuria to chronic kidney disease 5

Clinical Significance

• Fever-induced proteinuria represents a benign, transient phenomenon when mild and rapidly reversible 5, 6
• However, marked or persistent proteinuria during febrile illness likely signals parainfectious nephropathy requiring further evaluation 2
• Repeat testing after fever resolution is essential to distinguish transient febrile proteinuria from underlying kidney disease 5, 6