A recent AJKD Core Curriculum by Hogan et al reviews the pathogenesis, diagnosis, and treatment of dysproteinemic kidney diseases. Test your knowledge on this topic with the quiz below.
For a PDF version of the questions & answers, please click here.
1. A 73-year-old female with a past medical history of IDDM T2, hypertension, and hyperlipidemia presented to the hospital with 1 month of neck and shoulder pain with associated paresthesia and weakness in the fingertips. The pain radiates down both arms. There is no history of recent fall or trauma. Current medications include: lantus 20 units QD, lisinopril 20 mg QD, and atorvastatin 40mg QD. She was also taking ibuprofen 600 mg 3-4 times daily for 3 weeks for the pain with no significant relief. Initial laboratory tests show a serum creatinine 1.48 mg/dL, calcium 14.1 mg/dL, and elevated protein gap of 6.2. The remainder of her chemistry panel is normal. In the ED, CT of the cervical spine disclosed a pathologic C7 fracture. In this setting of renal insufficiency, hypercalcemia, elevated protein gap and pathologic fracture, which combination of screening tests for plasma cell dyscrasias is most sensitive?
UPEP, SPEP, and Serum IFE
UPEP, SPEP, and Serum FLC Assay
SPEP, Serum IFE, and Serum FLC assay
Correct! SPEP is inexpensive and widely available, with an 88% sensitivity for detecting a monoclonal gammopathy in patients with multiple myeloma. UPEP can increase the detection rate when added to SPEP but has a low sensitivity by itself. Adding serum IFE to SPEP increases sensitivity to 94%, and also identifies the type of monoclonal protein. However, it is not quantitative like the serum FLC, which not only increases the sensitivity to nearly 100% but also quantifies the amount of light chain production. See Table 1.
UPEP, SPEP, and Serum IFE
2. The following screening tests were done. Serum IFE revealed a monoclonal IgG kappa protein, and serum FLC assay measured the kappa at 16.8, lambda at 1.56, and a kappa/lambda ratio of 10.77. Multiple IV boluses of normal saline were given and the serum calcium normalized. However, the serum Cr continued to worsen despite the improvement in calcium, and progressed to 2.5 mg/dL. The patient underwent anterior cervical corpectomy of C7 with arthrodesis fusion with structural allograft from iliac crest for C6-T1. Specimens were sent to pathology from the bone fragment which revealed plasmacytoma. If a kidney biopsy was to be performed in this patient what would be the most common expected finding?
Nodular mesangial sclerosis and tubular basement membrane thickening
Hypereosinophilic PAS negative fractured casts within the tubules
Correct! The most common cause for decreased GFR in patients with multiple myeloma is light chain cast nephropathy. Cast nephropathy is the result of monoclonal FLCs binding and precipitating with the Tamm-Horsfall protein in the distal nephron. Typically, patients do not have nephrotic syndrome, as the disease primarily affects the tubules. The remaining choices suggest diseases like amyloid or light chain deposition disease, which tend to cause more glomerular damage and subsequent proteinuria, which this patient does not have. See Panels A-B from Figure 1
Endocapillary and membranoproliferative glomerulonephritis with granular staining for IgG heavy chain
Noncongophillic, polychromatophillc, PAS-positive intracapillary deposits
3. Type I cryoglobulinemia is diagnosed by the presence of monoclonal immunoglobulins that precipitate at colder temperatures. The primary disease that is associated with type 1 cryoglobulins are plasma cell dyscrasias such as multiple myeloma, Waldenstroms macroglobulinemia, and lymophoplasmacytic lymphoma. As these proteins precipitate, they can damage surrounding tissues in the skin, nervous system, and kidney. Where does precipitation primarily occur in cryoglobulinemic kidney disease?
Correct! Cryoglobulins are mostly found in the glomerular capillaries, which show on microscopy as intracapillary “cryoplugs”. The patients often also exhibit an endocapillary MPGN pattern of injury.
4. Which of the following is associated with improved mortality benefit in patients with AL amyloidosis?
Absence of clonal plasma cells on bone marrow biopsy
Reduction of serum FLC to normal
Correct! A complete hematologic response to AL amyloid is reduction of the serum FLC to normal, along with negative SPEP, UPEP, serum and urine IFE. A partial response is defined by a decrease in FLC by > 50%.
Amyloid deposits within the tubules and vasculature
< 5% plasma cells on bone marrow biopsy
5. Which of the following findings on electron microscopy best describes the pattern of light chain deposition disease?
Random nonbranching fibrils
Parallel, hollow microtubules
Punctate, powdery electron dense deposits
Correct! This is the characteristic finding of light chain deposition disease. On light microscopy, patients will have nodular mesangial sclerosis, and on IF there is linear staining that restricts to the monoclonal protein (typically kappa, in 80% of patients with light chain deposition disease). The presence of random nonbranching fibrils suggests amyloidosis, and parallel, hollow microtubules that are larger in diameter are diagnostic of immunotactoid glomerulopathy. See Figure 2
Dense intramembranous “sausage-shaped” deposits
6. Which of the following dysproteinemic kidney diseases is associated with low-grade proteinuria, metabolic acidosis, hypokalemia, hypophosphatemia, hypouricemia, and normoglycemic glycosuria?
Light chain proximal tubulopathy
Correct! LCPT is rare, accounting for just 5% of kidney biopsies in patients with monoclonal gammopathy.The abnormal light chain clone is reabsorbed in the proximal tubule via the megalin/cublin receptor by clathrin-mediated endocytosis. Once internalized, the light chain can cause damage to the lysosomes, resulting in generalized proximal tubule dysfunction (Fanconi syndrome). These patients manifest with hypokalemia, hypophosphatemia, hypouricemia, normoglycemic glycosuria, and aminoaciduria. Patients without all of these features may have partial Fanconi syndrome.
Light chain deposition disease
Light chain cast nephropathy
Light chain amyloidosis
– Post prepared by Angela Pauline Calimag @CalimagPauline (PGY-1, Internal Medicine, UIC/Advocate Christ Medical Center), AJKDBlog Guest Contributor, and Quiz prepared by Edgar Lerma, AJKDBlog Contributor. Follow him @edgarvlermamd.
To view this Core Curriculum (FREE), please visit AJKD.org.
Title: Dysproteinemia and the Kidney: Core Curriculum 2019
Authors: Jonathan J. Hogan, Mariam Priya Alexander, and Nelson Leung