Asymptomatic hematuria and/or proteinuria refers to a group of glomerular diseases characterized by glomerular-origin hematuria and/or mild to moderate proteinuria without edema, hypertension, or renal dysfunction. These conditions are typically identified through laboratory testing. In the absence of renal biopsy to obtain pathological findings, this term is used to describe such conditions.
Pathology
This group of diseases can result from various pathological types of primary glomerular diseases, though the pathological changes are often mild. Examples include:
- Minimal change glomerulonephritis (characterized by segmental mesangial cell and matrix proliferation in the glomeruli),
- Mild mesangial proliferative glomerulonephritis,
- Focal segmental glomerulonephritis (a focal glomerular disease with segmental endothelial and mesangial cell proliferation in the affected glomeruli).
Clinical Manifestations
Most patients are asymptomatic, with the condition often discovered during routine health examinations due to microscopic hematuria or proteinuria. There is no edema, hypertension, or renal dysfunction. Some patients may experience transient hematuria following high fever or intense physical activity, which resolves within a short period. Recurrent isolated hematuria, especially when closely associated with upper respiratory tract infections, raises suspicion for IgA nephropathy. Persistent isolated hematuria in patients with a family history should prompt consideration of thin basement membrane nephropathy.
Laboratory Findings
Urinalysis
Microscopic hematuria and/or proteinuria may be present. Proteinuria is typically >0.5 g/24h but usually <2.0 g/24h, predominantly consisting of albumin.
Urinary red blood cell morphology
Phase-contrast microscopy or red blood cell volume distribution curve analysis can confirm the glomerular origin of hematuria.
Immunological tests
Tests such as antinuclear antibodies, anti-double-stranded DNA antibodies, immunoglobulin levels, and complement levels are usually normal. Some patients with IgA nephropathy may exhibit elevated serum IgA levels.
Renal function and imaging
Renal function tests and imaging studies (e.g., ultrasound, intravenous pyelography, CT, or MRI) generally show no abnormalities.
Renal biopsy is not always necessary for patients with isolated hematuria, as the prognosis is often favorable, and 5–15% of cases remain undiagnosed even after biopsy. Patients with hematuria accompanied by proteinuria typically have a slightly more severe condition and prognosis than those with isolated hematuria. When clinical differentiation between IgA nephropathy and other renal diseases is not possible, renal biopsy is recommended for disease evaluation and treatment guidance. If hematuria, proteinuria, and/or renal dysfunction worsen during follow-up, renal biopsy should be performed promptly to establish a definitive diagnosis.
Diagnosis and Differential Diagnosis
Asymptomatic hematuria and/or proteinuria lacks specific clinical symptoms and can be easily overlooked, emphasizing the importance of clinical follow-up. Additionally, the possibility of other causes must be excluded.
Urinary red blood cell morphology
Phase-contrast microscopy or red blood cell volume distribution curve analysis can help differentiate the source of hematuria. Glomerular-origin red blood cells are predominantly deformed, often appearing as "budding-like" structures.
Non-glomerular hematuria
For non-glomerular hematuria, conditions such as nutcracker syndrome (left renal vein compression syndrome) and surgical causes of hematuria (e.g., urinary tract stones, tumors, or inflammation) should be considered.
Imaging studies
Ultrasonography or CT of the urinary system can assist in differential diagnosis.
If hematuria is confirmed to be glomerular in origin and there is no edema, hypertension, or renal dysfunction, this condition should be considered. It is important to carefully exclude other possible glomerular diseases before diagnosing this condition. These include systemic diseases (e.g., ANCA-associated vasculitis, lupus nephritis, Henoch-Schönlein purpura nephritis), Alport syndrome, thin basement membrane disease, and atypical cases of the recovery phase of acute nephritis. Differentiation can be made based on clinical presentation, family history, and laboratory findings, with renal biopsy being necessary for definitive diagnosis in some cases.
For patients with isolated asymptomatic proteinuria, urine protein quantification, urine protein component analysis, and urine protein electrophoresis are needed to determine the nature of the proteinuria. If necessary, tests for Bence-Jones protein and serum protein immunoelectrophoresis should be performed. Particular attention should be given to cases where qualitative urine protein tests suggest low protein levels, but 24-hour urine protein quantification reveals significant proteinuria, as this may indicate the presence of monoclonal gammopathy.
Before making a diagnosis, pseudoproteinuria (e.g., caused by significant hematuria from tumors), overflow proteinuria, functional proteinuria (occurring only during intense exercise, fever, or cold exposure), and orthostatic proteinuria (seen in adolescents, caused by lumbar lordosis in the upright position, with proteinuria disappearing when supine) must be excluded. Nutcracker syndrome (left renal vein compression) and other secondary glomerular diseases (e.g., diabetic nephropathy, renal amyloidosis, multiple myeloma) should also be ruled out. Renal biopsy may be required for definitive diagnosis in some cases.
Compared to isolated asymptomatic hematuria or proteinuria, the presence of hematuria combined with proteinuria (≥0.5 g/d) significantly increases the likelihood of chronic glomerulonephritis. This group of glomerular diseases carries a higher risk of progression and is an indication for renal biopsy to confirm the pathological type. Once pathological findings are obtained through biopsy, the diagnosis should be replaced by the specific pathological diagnosis.
Treatment
For patients with proteinuria <1.0 g/d, predominantly albumin, and without hematuria, the condition is referred to as isolated proteinuria, which generally has a good prognosis and rarely leads to renal dysfunction. However, recent studies have shown that in a small subset of patients with proteinuria ranging from 0.5–1.0 g/d, renal biopsy may reveal significant pathological changes, which warrants attention.
The management of this condition focuses on monitoring disease progression and avoiding exposure to nephrotoxic factors. The principles of diagnosis and treatment include:
- Regular monitoring and follow-up (every 3–6 months), including surveillance of urinalysis, renal function, and blood pressure. Female patients require closer monitoring before and during pregnancy.
- Protecting renal function and avoiding factors that may cause renal damage (refer to Section 1 of this chapter).
For patients with proteinuria (especially >1.0 g/d), treatment with ACE inhibitors (ACEI) or angiotensin receptor blockers (ARB) is recommended, with blood pressure monitoring during therapy.
For patients with recurrent chronic tonsillitis, particularly those with hematuria and proteinuria closely associated with tonsillar inflammation, tonsillectomy may be considered after the acute phase subsides.
If hypertension or renal dysfunction develops during follow-up, treatment should follow the guidelines for chronic glomerulonephritis.
Prognosis
Asymptomatic hematuria and/or proteinuria may persist for a long time, with a generally favorable prognosis, though the condition may fluctuate over time. Most patients maintain stable renal function over the long term, some recover spontaneously, while a subset of patients may experience increased proteinuria, hypertension, and renal dysfunction.