Can Myeloma Patients Have Completely Normal Kidney Structure?
No, myeloma patients with active disease and significant free light chain production cannot maintain completely normal kidney structure, as the pathophysiology of myeloma inherently causes tubular and interstitial damage even before clinical renal impairment becomes apparent.
Structural Changes Occur Early in Disease Course
- Tubular injury begins at the microscopic level once monoclonal free light chains exceed normal production, even when serum creatinine remains normal 1.
- The proximal tubular endocytic process becomes overloaded when light chains are overproduced, triggering cell stress responses including activation of p38 MAPK and NF-κB pathways that produce inflammatory cytokines 2.
- Light chains are filtered through the glomerulus and endocytosed by proximal tubule cells via megalin/cubilin receptors; when overwhelmed, this leads to tubular cell injury and death 2.
Spectrum of Structural Damage
Proximal Tubular Changes
- Direct tubular toxicity occurs from light chain-induced hydrogen peroxide production and activation of inflammatory pathways (NF-κB, ASK1, JAK-STAT), promoting apoptosis and tubulointerstitial fibrosis 1.
- Functional impairment can manifest as Fanconi syndrome (glucosuria, aminoaciduria, hypophosphatemia) due to failure of proximal tubular reabsorptive capacity, indicating structural damage even without elevated creatinine 1, 2.
Distal Tubular and Interstitial Pathology
- Cast nephropathy develops when excess free light chains interact with Tamm-Horsfall protein in the loop of Henle, forming obstructive casts that cause tubular rupture 1, 3, 4.
- Tubular casts result in tubular atrophy proximal to the obstruction and progressive interstitial inflammation and fibrosis 1.
- These structural changes persist even after treatment initiation and can progress to end-stage renal disease 5.
Clinical Implications
When Structural Damage Becomes Apparent
- Acute kidney injury risk increases significantly when serum free light chain concentrations exceed 80-200 mg/dL, though structural damage begins at lower levels 1, 3.
- At diagnosis, 25-50% of myeloma patients have some degree of renal impairment (eGFR <60 mL/min/1.73 m²), indicating pre-existing structural damage 1.
- Even patients without clinical renal impairment at diagnosis have microscopic tubular changes when light chain production is elevated 2.
Rare Exception
- The only scenario where kidney structure might remain truly normal is in very early, smoldering myeloma with minimal free light chain production that has not yet exceeded the kidney's clearance capacity 2.
- However, once myeloma meets diagnostic criteria (particularly as a myeloma-defining event), some degree of structural change is virtually inevitable if free light chains are elevated 1.
Critical Pitfall to Avoid
- Do not assume normal kidney structure based solely on normal serum creatinine or eGFR, as functional impairment and structural damage can be present before these markers become abnormal 1, 2.
- Early tubular dysfunction may manifest only as proteinuria or subtle tubular defects (Fanconi syndrome) while creatinine remains normal 1, 2.