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Uromodulin, also known as Tamm–Horsfall protein, is the most abundant protein in urine. It has recently been reported that uromodulin exists in a small amount in blood and that its concentration correlates with the estimated glomerular filtration rate (eGFR). First, we generated anti-human uromodulin mouse monoclonal antibodies (mAb(s)) and established a specific enzyme-linked immunosorbent assay (ELISA) for uromodulin. We then performed an observational clinical study to determine if there was a correlation between serum uromodulin concentration and estimates of kidney function and whether the serum uromodulin value could be a biomarker in clinical nephrology. The clinical study included 308 patients with and without chronic kidney disease and healthy volunteers. Serum concentrations of creatinine, cystatin C, and uromodulin were measured and correlations were sought between the eGFR calculated from the creatinine and cystatin C levels and the serum uromodulin concentration. There was a good correlation between the serum uromodulin concentration and the eGFR value calculated from the creatinine (r = 0.76) and cystatin C (r = 0.79) levels. The mean serum uromodulin level in the group with an eGFR > 90 mL/min/1.73 m2 calculated using cystatin C was significantly higher than that in the group with an eGFR of 80–89 mL/min/1.73 m2. The serum uromodulin measurement could be a useful biomarker for identification of patients with early deterioration of kidney function.

Bucillamine is a disease-modifying antirheumatic drug that is structurally similar to D-penicillamine. The major renal side effect of bucillamine and D-penicillamine is proteinuria caused by membranous nephropathy (MN). In addition to MN, combined crescent formation has been occasionally reported in D-penicillamine-induced MN, while crescent formation has been rarely reported in bucillamine-treated cases. Here, we describe a 76-year-old female who presented with nephrotic syndrome and rapidly progressive glomerulonephritis. She was receiving bucillamine as initial treatment for recently diagnosed rheumatoid arthritis, and renal biopsy showed MN with crescent formation. To the best of our knowledge, this is the first report of bucillamine-induced MN with crescent formation in the English literature.

A 43-year-old male experienced renal infarction (RI) following left upper lobectomy for lung cancer. The patient complained of acute-onset severe left flank pain on the 14th postoperative day. A contrast-enhanced computed tomography (CT) of the abdomen revealed RI by a large wedge-shaped defect in the left kidney. A chest CT scan located the thrombus in the stump (a blind-ended vessel) of the left superior pulmonary vein. Therefore, thromboembolic RI caused by pulmonary vein thrombosis was suspected. Anticoagulation therapy was initiated with heparin and warfarin to treat RI and to prevent further embolic episodes. Two months later, pulmonary vein thrombosis had resolved without the appearance of additional peripheral infarction. This case emphasizes the need to consider thrombus in the stump of the pulmonary vein as a cause of RI.

Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed "double positive" disease. Interestingly, the majority of "double positive" ANCA is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast, proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been reported, and as far as we know, none of the cases showed intrarenal arteritis. Herein, we report a case of PR3-ANCA-positive "double positive" anti-GBM disease presenting with pulmonary-renal syndrome and hemolytic uremic syndrome. The kidney biopsy showed crescentic glomerulonephritis, intrarenal arteritis, and thrombotic microangiopathy. This case newly describes PR3-ANCA-associated intrarenal arteritis in "double positive" anti-GBM disease.

Background Immunoglobulin heavy-and-light-chain amyloidosis (AHL amyloidosis) is a newly established disease entity where both the immunoglobulin heavy-chain and light-chain compose amyloid fibrils. The immunoglobulins responsible for the amyloid fibrils are generally identified by immunostaining and/or laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS). However, both techniques do not biochemically differentiate immunoglobulins that formed amyloid fibrils from non-responsible immunoglobulins. Case presentation We herein report a case of 67-year-old female patient with renal amyloidosis due to lymphoplasmacytic lymphoma secreting monoclonal immunoglobulin M (IgM)-kappa. Renal immunostaining monotypically positive for IgM-kappa and LMD-LC-MS/MS identification of mu heavy-chain and kappa light-chain were consistent with the diagnosis of AHL amyloidosis. In order to confirm that both the immunoglobulin heavy-chain and light-chain were forming amyloid fibrils, we performed LC-MS/MS of renal amyloid fibrils isolated by the traditional amyloid purification method. The additional LC-MS/MS identified kappa light-chain only without any heavy-chain component. These results were suggestive that amyloid fibrils were composed by kappa light-chain only and that the mu heavy-chain identified by immunostaining and LMD-LC-MS/MS was derived from the non-specific co-deposition of monoclonal IgM-kappa. Conclusion The case was AL amyloidosis with non-amyloid forming monoclonal immunoglobulin deposition. While immunostaining and LMD-LC-MS/MS are irreplaceable techniques to classify amyloidosis, confident exclusion of the present condition should be required to diagnose AHL amyloidosis.

AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.