Complement activation and cryoglobulinemia are common in monoclonal gammopathy of renal significance: Data from a case series.

INTRODUCTION: Monoclonal gammopathy of renal significance (MGRS) denotes kidney diseases caused by monoclonal immunoglobulins in patients who do not have an overt hematological malignancy. Treatment is primarily directed against the underlying clone. Complement activation and cryoglobulinemia are known factors that can contribute to tissue damage, however, the full extent of their involvement is not clear. MATERIALS AND METHODS: This was a retrospective study including all patients with MGRS referred for consultation to our hospital over a 3-year period. RESULTS: We identified 17 patients, of which 12 had proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Treatment with anti-clonal or immunosuppressive therapy was successful in 60% of patients with PGNMID, and treatment success was more common in patients with λ chain (100%) compared to κ chain deposits (20%). Serum markers of complement involvement were identified in 41% of all patients (88% of tested samples), most commonly high serum C5b-9 values or anti-factor H autoantibodies (both 24%). Patients with complement involvement did not respond well to treatment, which was unsuccessful in all treated patients with anti-factor H autoantibodies and 75% of patients with high serum C5b-9 values. Cryoglobulinemia was identified in 29% of all patients (71% tested samples) and was monoclonal in 40% of positive cases and mixed in 60%. None of the patients with cryoglobulinemia had organized deposits, however, there was a trend toward more common intramembranous deposits. In patients with monoclonal cryoglobulinemia both anti-clonal and immunosuppressive treatment were unsuccessful. All patients with mixed cryoglobulinemia were treated successfully with immunosuppressive therapy. CONCLUSION: Treatment of patients with PGNMID was successful in most cases. Complement involvement as well as monoclonal and mixed cryoglobulinemia were relatively common in our cohort, with the first two generally associated with unsuccessful treatment and the latter with successful treatment.

Tubular urinary indexes reliably distinguish between primary tubulointerstitial and primary glomerular diseases in patients referred for kidney biopsy.

AIMS: Kidney biopsy remains the gold standard for accurately diagnosing renal diseases. Urinalysis and assessment of renal function are the cornerstones for assessment of patients prior to biopsy. There is significant overlap in the results of routine urine parameters (proteinuria, erythrocyturia, leukocyturia) among different kidney diseases, which hinders the possibility of adequately estimating disease etiology prior to the biopsy. The aim of our study was to assess whether diverse markers of glomerular and tubular proteinuria - urinary albumin, IgG, α-1-microglobulin (α-1-m) and N-acetyl-ß-D-glucosaminidase (NAG) - are capable of distinguishing between patients with primary tubulointerstitial (TID) and primary glomerular disease (GLOM). METHODS: Our study is a retrospective, single-center, consecutive case series of patients referred for kidney biopsy. We analyzed routine urinalysis results performed on a second morning urine sample immediately prior to the biopsy. RESULTS: Patients with TID had significantly higher values of α-1-m and NAG, with lower values of albumin and IgG in the urine compared to patients with GLOM. Three tubular urinary indexes had high sensitivity and specificity for distinguishing TID from GLOM: NAG/albumin, α-1-m/proteinuria, and α-1-m/albumin, with the highest values in the latter index (96.6% and 98.2%, respectively, cut-off point ≥ 0.33). CONCLUSIONS: Prior to kidney biopsy, tubular urinary indexes may present a valuable tool in distinguishing patients with TID from patients with GLOM.
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Treatment of Antibody-Mediated Rejection After Kidney Transplantation - 10 Years' Experience With Apheresis at a Single Center.

Antibody-mediated rejection (AMR) is a major cause of kidney graft failure. We aimed to analyze treatment and outcome of AMR in a national cohort of 75 biopsy-proven acute (43 patients, 57%) or chronic active (32 patients, 43%) AMR episodes between 2000 and 2015. The mean patients' age was 46 ± 16 years, the majority was treated with plasma exchange, 4% received immunoadsorption and 7% received both. The majority received pulse methylprednisolone and low-dose CMV hyperimmune globulin, 20% received bortezomib and 13% rituximab. Concomitant infection was treated in 40% of patients. The immediate treatment outcome was successful in 91%, the 1- and 3-year graft survival rates were 71% and 57%, while 3-year patient survival was 97%. Chronic active AMR was associated with worse graft survival than acute AMR (log rank P = 0.06). To conclude, intensive treatment with apheresis and additional immunosuppression was effective in reversing AMR, but long-term graft survival remains markedly decreased, especially in chronic active AMR.

Goodpasture's syndrome with concomitant immune complex mixed membranous and proliferative glomerulonephritis.

Classical Goodpasture's (GP) syndrome is a monophasic illness characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis with linear IgG deposition along the glomerular and distal tubular basement membrane and estructive necrotizing diffuse extracapillary crescentic glomerulonephritis. The majority of patients have circulating anti-glomerular basement membrane (GBM) antibodies, detectable with standard anti-GBM ELISA. Concurrence of GP syndrome with proliferative glomerulonephritis has only rarely been described. In this report, for the first time we describe in a 21-year-old woman GP syndrome with 50% crescentic sclerosing glomerulonephritis with linear immunofluorescence characteristic of anti-GBM pathogenesis, combined with mixed membranous and membranoproliferative glomerulonephritis with granular immunofluorescence and subepithelial, mesangial and subendothelial deposits characterizing immune complex pathogenesis. The clinical picture was also unusual for GP syndrome, manifesting a recurrent but non-progressive course, nephrotic syndrome, normal renal function and low values of anti-GBM antibodies, identified only by novel more sensitive techniques.