What are other differential diagnoses (DDs) to consider in a patient with renal issues?

Differential Diagnoses for Patients with Renal Issues

When evaluating patients with renal issues, a comprehensive differential diagnosis should include monoclonal immunoglobulin-associated disorders, viral-associated nephropathies, complement-mediated diseases, and various systemic conditions affecting the kidneys. 1

Monoclonal Immunoglobulin-Associated Renal Diseases

• Light-chain cast nephropathy: Characterized by tubular casts composed of monoclonal light chains, typically associated with multiple myeloma 1
• Light-chain deposition disease: Presents with nodular sclerosing glomerulopathy and is often associated with multiple myeloma 1
• AL amyloidosis: Features Congo red-positive deposits with apple-green birefringence under polarized light, affecting glomeruli, interstitium, and vessels 1
• Light-chain proximal tubulopathy: Requires paraffin immunofluorescence for detection when routine studies are negative 1
• Proliferative glomerulonephritis with monoclonal immunoglobulin deposits: Often presents with membranoproliferative pattern and may have negative serum/urine studies for monoclonal immunoglobulins 1
• C3 glomerulopathy associated with monoclonal immunoglobulins: The monoclonal protein activates the alternative pathway of complement 1

Viral-Associated Nephropathies

• HIV-associated nephropathy (HIVAN): Classic presentation is collapsing focal segmental glomerulosclerosis (FSGS), particularly in patients of African ancestry with APOL1 high-risk variants 1
• FSGS not otherwise specified: Distinct from collapsing FSGS seen in HIVAN 1
• HIV immune complex-related diseases: Including IgA nephropathy, lupus-like glomerulonephritis, membranous nephropathy, and membranoproliferative glomerulonephritis 1
• COVID-19-associated nephropathy (COVAN): Resembles HIVAN with collapsing FSGS, associated with APOL1 high-risk variants 1

Other Glomerular Diseases

• Membranoproliferative glomerulonephritis: Can be primary or secondary to infections, autoimmune diseases, or monoclonal gammopathies 1
• Membranous glomerulopathy: Primary or secondary to autoimmune diseases, infections, or malignancies 1
• Mesangial proliferative glomerulonephritis: Common histological finding in various glomerular diseases 1, 2
• Crescentic glomerulonephritis: Defined by crescents in at least 50% of glomeruli in immune complex-mediated diseases 1

Tubular and Interstitial Disorders

• Acute tubular injury: Can be associated with various nephrotoxins, ischemia, or as part of other renal diseases 1
• Interstitial nephritis: May be drug-induced, infection-related, or associated with systemic diseases 1, 2
• Medullary sponge kidney: Congenital malformation with cystic dilatation of collecting ducts, presenting with nephrolithiasis, urinary tract infections, and distal renal tubular acidosis 3
• Distal renal tubular acidosis: Can be primary or secondary to various conditions, often associated with medullary nephrocalcinosis 4
• Bartter syndrome: Characterized by hypokalemic metabolic alkalosis, normal to high urinary calcium excretion, and polyuria 1

Systemic Diseases with Renal Manifestations

• Diabetic nephropathy: Leading cause of end-stage renal disease, characterized by nodular glomerulosclerosis 1, 5
• Lupus nephritis: Various patterns including mesangial, focal, diffuse proliferative, and membranous forms 5, 2
• Rheumatoid arthritis-associated nephropathy: Includes secondary amyloidosis, drug-induced nephropathy, and mesangial glomerulonephritis 2
• Rosai-Dorfman-Destombes disease: Rare cause of renal involvement presenting as discrete masses or diffuse infiltration, with symptoms including hematuria, flank pain, and renal failure 1
• Liver disease-associated nephropathy: Common in advanced liver disease, with creatinine-based methods being inaccurate for GFR estimation 5

Diagnostic Approach

• Urinalysis with microscopic examination: Assess for pathological casts (RBC, WBC, granular, waxy, fatty) which can indicate specific renal pathologies 6
• Serum and urine protein studies: Evaluate for monoclonal proteins using immunofixation, even when routine studies are negative 1
• Kidney biopsy: Essential for definitive diagnosis, with standardized reporting including primary diagnosis, pattern of injury, and chronicity index 1
• Special stains: Congo red for amyloidosis, immunofluorescence for immune deposits, and mass spectrometry for amyloid typing when results are equivocal 1, 7

Clinical Pitfalls and Caveats

• Patients with monoclonal gammopathy may have renal diseases not directly related to monoclonal immunoglobulin deposition, requiring careful clinicopathologic correlation 1
• Renal vasculitides and tubulointerstitial nephropathies are more frequently identified by ultrasound than glomerular nephropathies, as glomeruli account for only 8% of renal parenchyma 8
• Microhematuria requires urologic evaluation in all patients aged 35 years and older, even with known renal disease 1
• Patients on anticoagulation therapy with hematuria require both urologic and nephrologic evaluation regardless of the type or level of anticoagulation 1
• Early or mild renal parenchymal diseases may present with normal ultrasound appearance and normal resistive indices, necessitating biopsy for definitive diagnosis 8