Renal · Year 2 · from Renal
Case 3: Fanconi Syndrome from Multiple Myeloma
Patient Presentation
A 67-year-old male presents with bone pain, fatigue, and recurrent fractures. He is found to have anemia and hypercalcemia on routine labs.
History of Present Illness
- Progressive lower back pain for 6 months
- Fatigue and weakness
- 15-pound unintentional weight loss
- Increased thirst and urination
- Two pathologic rib fractures from minimal trauma
Physical Examination
- Blood pressure: 128/78 mmHg
- Pallor
- Point tenderness over lumbar spine and ribs
- No hepatosplenomegaly
- No lymphadenopathy
Workup
Laboratory Studies:
- Hemoglobin: 9.2 g/dL
- Creatinine: 2.1 mg/dL
- Calcium: 11.8 mg/dL (elevated)
- Albumin: 3.2 g/dL
- Total protein: 10.5 g/dL (elevated - protein gap)
- Glucose (serum): 95 mg/dL (normal)
- Uric acid: 2.1 mg/dL (low)
- Phosphorus: 2.2 mg/dL (low)
- Bicarbonate: 18 mEq/L (low)
Urinalysis:
- Glucose: 2+ (despite normal serum glucose)
- Protein: 2+
- pH: 5.8
Additional Studies:
- SPEP: M-spike present (IgG kappa)
- 24-hour urine: Glucosuria, aminoaciduria, phosphaturia
- Skeletal survey: Lytic lesions in spine, ribs, skull
Diagnosis
Multiple Myeloma with Light Chain-Induced Fanconi Syndrome
Discussion
This case illustrates proximal tubule dysfunction:
- Fanconi Syndrome: The lecture describes generalized proximal tubule dysfunction affecting multiple transport systems. Light chain deposition in proximal tubule cells impairs:
- Glucose reabsorption via SGLT2 (glucosuria at normal serum glucose)
- Amino acid reabsorption (aminoaciduria)
- Phosphate reabsorption (phosphaturia, hypophosphatemia)
- Uric acid reabsorption (hypouricemia)
- Bicarbonate reabsorption via NHE3 (Type 2 proximal RTA)
- Proximal Tubule Functions: The PCT normally reabsorbs 65-70% of filtered sodium, water, glucose, amino acids, phosphate, and bicarbonate. Global dysfunction causes loss of all these substances.
Treatment
- Hematology consultation for myeloma treatment
- Chemotherapy with bortezomib-based regimen
- Phosphate supplementation for hypophosphatemia
- Bicarbonate supplementation for metabolic acidosis
- Bisphosphonates (with caution given renal function)
- Hydration to prevent cast nephropathy
Clinical Pearl
Fanconi syndrome causes glucosuria despite normal blood glucose - the proximal tubule simply cannot reabsorb the filtered glucose. This distinguishes it from diabetic glucosuria where glucose appears because of hyperglycemia exceeding the normal transport maximum.
Image Reference
For visual reference of tubular transport concepts, see:
- Wikimedia Commons: Proximal convoluted tubule - Histology showing brush border
- Radiopaedia: Renal tubular acidosis - Clinical information
- StatPearls: Nephron Histology - Tubular segment identification
Learning Points
- Glucose Transport Maximum: The renal threshold for glucose is ~180-200 mg/dL. Above this, SGLT2 and SGLT1 are saturated and glucosuria occurs.
- SGLT2 vs SGLT1: SGLT2 handles 90% of glucose reabsorption with low affinity/high capacity; SGLT1 handles 10% with high affinity as a "safety net."
- NCC and Calcium: Thiazide diuretics and Gitelman syndrome (both affecting NCC) cause hypocalciuria, useful for treating hypercalciuric nephrolithiasis.
- Fanconi Syndrome Components: Look for the combination of glucosuria with normal glucose, aminoaciduria, phosphaturia, uricosuria, and type 2 RTA.
- Na+/K+-ATPase: This basolateral pump establishes the sodium gradient that drives all secondary active transport in the nephron.