From the Guidelines
The diagnosis of IgG4-related kidney disease requires a comprehensive approach combining clinical, laboratory, and imaging findings, with the definitive diagnosis relying on kidney biopsy showing dense lymphoplasmacytic infiltration with IgG4-positive plasma cells (>10 per high-power field or IgG4/IgG-positive plasma cell ratio >40%), storiform fibrosis, and often tubular basement membrane immune complex deposits, as supported by the most recent study 1.
Clinical Evaluation
Patients typically present with mild symptoms including fatigue, weight loss, or may be asymptomatic with incidental findings of kidney dysfunction. A thorough history, physical examination, and laboratory analysis of blood and urine are essential in the initial evaluation. The clinical context, including personal and family history, social and environmental factors, medications, and physical examination, should be evaluated to determine the causes of kidney disease 1.
Laboratory Tests
The diagnostic criteria include elevated serum IgG4 levels (>135 mg/dL), which is a hallmark laboratory finding, though not all patients exhibit this elevation. Urinalysis may show mild proteinuria and microscopic hematuria, while blood tests often reveal elevated creatinine, reduced estimated glomerular filtration rate, and sometimes hypocomplementemia.
Imaging Studies
Imaging studies are crucial, with contrast-enhanced CT typically showing multiple low-density lesions, diffuse kidney enlargement, or a solitary mass. MRI findings include hypointense lesions on T2-weighted images.
Kidney Biopsy
The definitive diagnosis requires kidney biopsy, which is essential for confirming the diagnosis and determining the extent of kidney involvement. The biopsy should be evaluated for dense lymphoplasmacytic infiltration with IgG4-positive plasma cells, storiform fibrosis, and tubular basement membrane immune complex deposits.
Differential Diagnosis
Alternative diagnoses like malignancy, infection, and other autoimmune conditions must be excluded. A comprehensive approach, including clinical, laboratory, and imaging findings, is necessary to diagnose IgG4-related kidney disease accurately.
Recent Guidelines
Recent guidelines, such as the 2021 KDIGO clinical practice guideline for the management of glomerular diseases, emphasize the importance of kidney biopsy in diagnosing and managing IgG4-related kidney disease 1. The guideline recommends a patient-centered discussion on the utility of a kidney biopsy for definitive diagnosis, especially in patients with suspected IgAN and higher levels of proteinuria or diminished or worsening eGFR.
From the Research
Diagnostic Criteria for IgG4-Related Kidney Disease
The diagnostic criteria for IgG4-related kidney disease (IgG4-RKD) include a combination of clinical evaluation, laboratory tests, and imaging studies. The following are some of the key diagnostic criteria:
- Clinical presentation: IgG4-RKD can present with a variety of symptoms, including acute or chronic kidney injury, proteinuria or nephrotic syndrome, mass lesion(s), and obstruction 2, 3, 4, 5.
- Laboratory tests:
- Imaging studies: Radiographic findings, including masses, can be present in some patients with IgG4-RKD 3, 4, 5.
- Renal biopsy: A renal biopsy is often necessary to confirm the diagnosis of IgG4-RKD. The biopsy typically shows plasma cell-rich interstitial nephritis with increased IgG4-positive plasma cells and fibrosis 2, 3, 4, 5.
Proposed Diagnostic Criteria
A proposed diagnostic criteria for IgG4-RKD, known as the 2020 version, includes the following:
- Serum IgG4 values and/or immunohistological staining for IgG4 in renal biopsy samples 6.
- Clinical findings highly suggestive of IgG4-RD, such as bilateral lacrimal, submandibular or parotid swelling, imaging findings compatible with type 1 autoimmune pancreatitis or retroperitoneal fibrosis 6.
- The presence of extra-renal organ involvement, such as biopsy-proven extra-renal lesions or clinical findings highly suggestive of IgG4-RD 6.
Diagnostic Challenges
The diagnosis of IgG4-RKD can be challenging due to its variable clinical presentation and the need for a renal biopsy to confirm the diagnosis. Additionally, the disease can mimic other conditions, such as ANCA-associated disease or other types of autoimmune or plasma cell-rich interstitial nephritis 2, 3, 4, 5. Therefore, a thorough clinical evaluation, laboratory tests, and imaging studies are necessary to establish an accurate diagnosis. The revised diagnostic criteria, such as the 2020 version, may improve the sensitivity and specificity of the diagnosis 6.