A 46-year-old Caucasian man who was enjoying a dynamic life was referred to our hospital for a clinical pattern dominated by kidney failure, hypercalcemia, and lower back pain.
In 10 months before, he was hospitalized in his home country for fatigue, general malaise, and lower back pain; for these symptoms, he took NSAIDs for at least three weeks before admission. His past clinical history was negative. At that time, the laboratory routine showed severe kidney failure (sCr: 6 mg/dL, BUN: 41 mg/dL), low-grade proteinuria (urine protein to creatinine ratio (UPCR): 0.17), normoglycemic glycosuria, and microscopic hematuria. Eosinophilia (1.921/mm3), mild anemia (Hb: 11.9 g/dL), and hypercalcemia (2,6 mmol/L) were concomitant. A kidney biopsy was performed, and a diagnosis of drug-induced acute interstitial nephritis secondary to NSAID therapy was made. Coherently, he was treated with a regimen of prednisone 0.5 mg/kg/day for four months and then gradually tapered. After discharge, the serum creatinine came down, stabilizing around 2.5 mg/dl. However, soon after corticosteroids were interrupted, fatigue, general malaise, and low back pain came back associated with significant weight loss.
The nadir of his clinical discomfort occurred while on vacation in Sardinia. He was admitted to our Division for general malaise, fatigue, and deteriorated general conditions. At that time, he was not on any medication except vitamin D supplementation. Compared with the last control three months before, kidney function deteriorated from a serum creatinine of 3.2 mg/dl to 6.6 mg/dL; urinalysis showed normoglycemic glycosuria, low-grade microscopic hematuria, and elevated proteinuria (UPCR: 7.53). Other laboratory investigations revealed mild anemia (Hb: 11 g/dL), moderate to severe hypercalcemia (total calcium: 13.8 g/dL), and relevant eosinophilia (3.515/mm3). We performed an extensive immunological and microbiological panel that resulted in an unremarkable result. Serum electrophoresis showed significant hypogammaglobulinemia (0.6 g/dl), while IgG (552 mg/dl) and IgM (24 mg/dl) were significantly reduced. The patient underwent a kidney biopsy.
Kidney Biopsy: we counted 18 glomeruli, of which two were globally sclerosed. Glomeruli had a normal morphology. The interstitium was occupied by intense lymphomonocytic infiltration with rare eosinophils and neutrophils with sporadic signs of direct aggression against tubular structures. Proximal tubules were extensively involved compared with distal portions and showed diffuse simplification (Figs. 1 and 2). In the vital segments, proximal tubular cells (PTC) were filled with eosinophilic, fuchsine-positive, silver–negative droplets and occasional cuboid cytoplasmatic crystals. Tubuli were focally occupied by granular casts composed of mixed cellular debris and proteinaceous crystalloids. Diffuse interstitial fibrosis and tubular atrophy were concomitant, affecting approximately 50% of the sample. Fractured casts and birefringent material were not observed. The vessels did not show pathological features. Pronase-based immunofluorescence microscopy showed brightly κ-positive PTC cytoplasm. These findings were confirmed by immunohistochemistry (IHC) using kappa light chain antisera. Electron microscopy substantially confirmed the previous findings. It showed numerous rhomboidal and needle-shaped crystalline inclusions within lysosomes or in the cytoplasm of PTCs, while the glomeruli were unremarkable. Congo-red and thioflavin T were negative. Definitively, a diagnosis of acute on chronic interstitial nephritis with κ-light chain proximal tubulopathy with intracellular crystals was made.
The clinical presentation and laboratory findings exhibited strong indications of "CRAB" (hypercalcemia, kidney failure, anemia, bone lesions). Despite the absence of an M-spike on serum protein electrophoresis, which posed a notable confounding factor during the first admission, the monoclonal κ-light chain was detected through serum and urine immunofixation. It was further quantitated using free light chain (FLC κ-serum 6.915 mg/L; FLC λ-serum 7,6 mg/L, FLC κ/λ 909), and elevated levels of kappa and lambda light chains were observed in urinary tests (κ-urine 233 mg/L; λ-urine 9,67 mg/L). A radiographic assessment of the skeletal segments revealed the presence of extensive osteolytic lesions. Bone marrow biopsy confirmed the presence of monoclonal κ-restricted plasma cells (70%), leading to a conclusive diagnosis of multiple myeloma.
We initiated a trial of daily plasmapheresis for a total of 15 sessions, along with a treatment plan including bortezomib, dexamethasone, and thalidomide. Unexpectedly, in four months after the first admission, while achieving a very good partial response and stabilization of kidney function (sCr 2.6 mg/dl), the fourth cycle was discontinued due to a Listeria monocytogenes infection. The patient developed acute liver and kidney failure that required replacement therapy. Sadly, the patient's condition continued to deteriorate until he passed away.