Cornell, Lynn D.

Abstract Background Microhematuria is common in immunoglobulin A nephropathy (IgAN). However, current prognostication is based on proteinuria and mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, tubulointerstitial fibrosis and crescent (MEST-C) scores. Methods In this retrospective study, we evaluated whether MEST-C score components are associated with the presence of microhematuria at biopsy and whether the degree of microhematuria during follow-up is associated with change in estimated glomerular filtration rate (eGFR), after adjusting for clinical and histological parameters. We identified 125 patients with biopsy-proven IgAN and MEST-C scoring who were not on immunosuppressive therapy at biopsy. Microhematuria was defined as ≥3 red blood cells (RBCs)/high-power field (hpf). Results Of the 125 patients, 97 had microhematuria at baseline and were more likely to have M1, E1 and C ≥ 1 lesions (P < 0.05 for all) compared with patients without microhematuria. Of the 125 patients, 72 had follow-up data available. An increase in the degree of microhematuria was significantly associated with an eGFR decline of −0.81 mL/min/1.73 m2 [95% confidence interval (CI) −1.44 to −0.19, P = 0.01], after adjusting for follow-up time, proteinuria and T score. Severe microhematuria (≥21 RBCs/hpf) was associated with an even larger decline in eGFR (−3.99 mL/min/1.73 m2; 95% CI −6.9411 to −1.0552, P = 0.008), after similar adjustments. Conclusion Degree of microhematuria during follow-up is an independent predictor of eGFR decline after adjusting for clinical and histological parameters. Therefore, monitoring the degree of microhematuria as well as proteinuria is important when evaluating patients with IgAN. Additional studies using improvement in microhematuria as a primary surrogate outcome are needed.

Abstract Abstract 3992 Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications. Table 1. Demographics and hematologic characteristics AH/AHL AL p value No. of patients 17 202 Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 Age, median (range) 63 (50–77) 62 (36–86) 0.73 Additional organ involvement 8 (47%) 126 (62%) 0.3 Cardiac involvement 3 (18%) 100 (50%) 0.01* % of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82 ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53 Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73 Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* IQR, interquartile range. Table 2. Renal characteristics at kidney biopsy AH/AHL AL p value No. of patients 17 202 24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 % albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* IQR, interquartile range. Disclosures: No relevant conflicts of interest to declare.

Kidney disease is common in patients with multiple myeloma. Patients often present with acute kidney failure most commonly the result of light chain cast nephropathy. Presentation can also be in the form of nephrotic syndrome associated with immunoglobulin light chain amyloidosis or monoclonal immunoglobulin deposition disease and tubulopathy as in acquired light chain Fanconi syndrome. We present a case of a 56-year-old male with multiple myeloma who presented with chronic kidney disease and uric acid stones. Chemical analysis of the nephrolithiasis showed it to be entirely composed of uric acid. Fractional excretion of uric acid was elevated at 35.9%. Kidney biopsy was consistent with light chain proximal tubulopathy. Bone marrow biopsy showed 30% kappa light chain–restricted plasma cells. Genetic sequencing identified the light chain to be from the Vk1-33 subgroup. The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, with improvement of his kidney function. This case illustrates a rare presentation of multiple myeloma.

AbstractThe aim of this study was to investigate correlations between early subclinical findings (10‐ and 90‐day histology and gene expression data) and late outcomes (transplant glomerulopathy and graft loss) in positive crossmatch kidney transplants (+XMKTx). We compared 34 +XMKTx (19 receiving eculizumab and 15 receiving standard of care without eculizumab) to 13 −XMKTx (between August 2001 and August 2011). At 10 days, light microscopy identified subclinical inflammation in only 18% of +XMKTx, while intragraft gene expression identified inflammation in 79% (gene sets for activated macrophages, dendritic cells, NK cells or T cells). Inflammation persisted at 90 days and was associated with the development of transplant glomerulopathy by 2 years and graft loss. In contrast, endothelial cell (EC) changes present at 90 days by either electron microscopy or gene expression were not associated with transplant glomerulopathy or graft loss in this cohort. Eculizumab treatment did not appear to alter inflammation or EC changes. Therefore, intragraft inflammation might be an appropriate surrogate marker of progression and also a target of therapy to prevent chronic antibody‐mediated rejection.

AbstractMicrosporidia are opportunistic pathogens that usually cause a limited disease in the gastrointestinal tract. Occasionally, they can cause disseminated disease. In solid organ transplant recipients, disseminated disease has been reported only rarely. We describe a 68‐year‐old woman who presented with fever, cough, and acute kidney injury 6 months after kidney transplantation. Dissemination was confirmed by identification of microsporidial spores in urine and bronchoalveolar lavage fluid. Polymerase chain reaction analysis identified the species as Encephalitozoon cuniculi.