Pathological characteristics of light chain crystalline podocytopathy.

Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 patients (68% male, median age 56 years). Most (80%) patients presented with proteinuria and chronic kidney disease, with nephrotic syndrome in 28%. Crystalline keratopathy and Fanconi syndrome were present in 22% and 10%, respectively. The hematologic condition was monoclonal gammopathy of renal significance (MGRS) in 55% and multiple myeloma in 45%. The serum monoclonal immunoglobulin was IgG κappa in 86%. Histologically, 60% exhibited focal segmental glomerulosclerosis (FSGS), often collapsing. Ultrastructurally, podocyte LC crystals were numerous with variable effacement of foot processes. Crystals were also present in proximal tubular cells as light chain proximal tubulopathy (LCPT) in 80% and in interstitial histiocytes in 36%. Significantly, frozen-section immunofluorescence failed to reveal the LC composition of crystals in 88%, requiring paraffin-immunofluorescence or immunohistochemistry, with identification of kappa LC in 87%. The LC variable region gene segment, determined by mass spectrometry of glomeruli or bone marrow plasma cell sequencing, was IGKV1-33 in four and IGKV3-20 in one. Among 21 patients who received anti-plasma cell-directed chemotherapy, 50% achieved a kidney response, which depended on a deep hematologic response. After a median follow-up of 36 months, 26% progressed to kidney failure and 17% died. The mean kidney failure-free survival was 57.6 months and was worse in those with FSGS. In sum, LCCP is rare, mostly associates with IgG κappa MGRS, and frequently has concurrent LCPT, although Fanconi syndrome is uncommon. Paraffin-immunofluorescence and electron microscopy are essential to prevent misdiagnosis as primary FSGS since kidney survival depends on early diagnosis and subsequent clone-directed therapy.

Pseudohyperphosphatemia in a hyperphosphatemic hemodialysis patient.

Hyperphosphatemia is a predictable consequence of end-stage renal disease. Pseudohyperphosphatemia is a spurious elevation of serum phosphate in samples containing a substance that interferes with the laboratory assay for phosphate. The most common cause is a paraprotein in disorders such as Waldenström's macroglobulinemia and multiple myeloma. We report here a case of pseudohyperphosphatemia in a hyperphosphatemic patient with end-stage renal disease on long-term hemodialysis caused by a saline solution containing phosphorus used to dilute the patient's serum sample in the clinical chemistry laboratory. Investigations showed that the phosphorus most likely was introduced at the time of saline manufacture. Pseudohyperphosphatemia resulting from the manufacture and distribution of saline-containing phosphorus could be a cause of abnormally high serum phosphate measurements in hyperphosphatemic dialysis patients whose serum samples must be diluted in the laboratory. Such spuriously elevated results can lead to inappropriate changes in medications and subject patients to additional hemodialysis treatments.