Renal Fanconi syndrome as a cause of chronic kidney disease in patients with monoclonal gammopathy of undetermined significance: partially reversed renal function by high-dose dexamethasone with bortezomib

Renal Fanconi syndrome (FS) is a rare complication of plasma cell dyscrasias, including monoclonal gammopathy of undetermined signifi cance (MGUS) and multiple myeloma. It is characterized by the impairment of renal proximal tubular function leading to normoglycemic glycosuria, aminoaciduria, hypophosphatemia, hypouricemia and proximal renal tubular acidosis [1,2]. Th is can also cause metabolic changes, osteomalacia and renal dysfunction from chronic kidney disease (CKD) to end-stage renal failure (ESRD). Although renal FS with MGUS is an indolent disease and its treatment is still controversial, a considerable number of patients develop ESRD. Here, we describe two patients with serum free light chain (FLC) κ -positive MGUS who developed CKD due to renal FS. Treatment with high-dose dexamethasone and bortezomib resulted in partial improvement of renal function in both of the patients. A 76-year-old man was referred to our hospital due to progressive renal failure over the previous 1-year period. Th e results of physical examination were unremarkable. Laboratory examinations showed a white blood cell count of 11 400/mm 3 with normal diff erentials, hemoglobin 12.4 g/dL and platelet count of 233  10 3 /mm 3 . A urine dipstick test indicated positivity for protein (1  ) and glucose (4 ) and hyperaminoaciduria was detected in 17 of a total of 39 measured amino acids. Th e urine β 2 -microglobulin ( β 2 M) level was 21.0 mg/L (normal range: 0.016 – 0.518 mg/L). Th e serum creatinine level was 3.8 mg/dL (normal range: 0.6 – 1.2 mg/dL), uric acid level was 3.7 mg/dL (normal range: 3.5 – 6.9 mg/dL) and phosphate level was 1.5 mg/dL (normal range: 2.7 – 5.0 mg/dL). Arterial blood gas analysis revealed metabolic acidosis with normal anion gap (base excess:  6.5 mEq/L; HCO 3 : 17.1 mEq/L). Th e level of serum pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP) was elevated to 10.6 ng/mL (normal range: 0 – 4.5 ng/mL). Serum immunoglobulin A (IgA) was elevated to 998 mg/dL (normal range: 62 – 370 mg/dL), and the other classes of immunoglobulin were within the respective normal limits. Immunoelectrophoresis detected IgA κ paraprotein in serum and FLC κ in urine. Serum FLC κ was 284 mg/L (normal range: 2.4 – 18.9 mg/L) and FLC λ was 13.9 mg/L (normal range: 4.4 – 26.2 mg/L). A bone marrow aspirate (BMA) showed 8.2% plasma cells with eosinophilic inclusions (Figure 1). A bone marrow biopsy indicated that approximately 5% of infi ltrating plasma cells were positive for CD138 on immunohistochemistry and negative on Congo red staining. No cytogenetic abnormalities were found. Th ese fi ndings were consistent with a diagnosis of IgA κ MGUS with renal FS. After obtaining written informed consent from the patient and approval from the Institutional Review Board (IRB) of Kameda General Hospital, treatment with high-dose dexamethasone (40 mg/day for 4 days in the fi rst week and 20 mg/day for 2 days in the following 3 weeks) was administered. Serum FLC κ decreased to 2.91 mg/L and urine Bence Jones protein dropped below the limit of detection. His serum creatinine also decreased to 1.9 mg/dL, but metabolic abnormalities remained unchanged. However, serum FLC κ and creatinine levels increased again 2 months later. Treatment with bortezomib (1.3 mg/m 2 ) and low-dose dexamethasone (20 mg), given at 2-week intervals, was instituted as maintenance therapy. Eighteen months after the initial diagnosis, his serum FLC remained within normal limits and serum creatinine was stable at around 2.0 mg/dL. A 54-year-old man was admitted to our hospital for evaluation of worsening renal function and Bence Jones proteinuria. Th e results of physical examination were unremarkable. Laboratory data showed a white blood cell count of 5500/mm 3 with normal diff erentials, hemoglobin level of 15.7 g/dL and platelet count of 323  10 3 /mm 3 . Urine was positive for protein (1 ) and glucose (2 ). Hyperaminoaciduria was also detected in 23 of the total 39 amino acids measured. Th e urine β 2 M level was 62.9 mg/L. Th e serum creatinine level was 1.6 mg/dL, uric acid level was 2.4 mg/dL and phosphate level was 2.2 mg/dL. Serum FLC κ was elevated to 991 mg/L and the FLC λ level was 14.9 mg/L. Th e serum 1CTP level was elevated to 6.9 ng/mL. Serum and urine immunoelectrophoresis detected Bence Jones L eu k L ym ph om a D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y D al ho us ie U ni ve rs ity o n 10 /0 5/ 13