Glomerular diseases最新文献

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on HLA antigens.

Materials and methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from two North American and one European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. Prevalence of HLA antigens was compared to external healthy controls of European ancestry (n=15,740). Graft survival was assessed by Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses.

Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR=1.68, P=0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR=0.46, P<0.001) and HLA-DQ6 (32% vs. 45%, OR=0.59, P=0.003); however, the frequency of these HLA antigens were similar in recurrent versus non-recurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA-matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival.

Discussion/ conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLA antigens associated with IgAN in the native kidney and HLA-matching in recipients of deceased or living unrelated transplants are not.

Introduction: Minimal change disease in childhood can follow a frequently relapsing or steroid-dependent course in up to 40% of cases. Second-line immunosuppressive medications that are used to manage these patients are associated with significant adverse effects. There is a need for safer alternative treatments for difficult-to-treat nephrotic syndrome. Therefore, we conducted an open-label feasibility study to assess the safety and efficacy of a gluten-free diet as treatment for pediatric patients with difficult-to-treat nephrotic syndrome. As a second aim, we sought to determine if the plasma zonulin concentration can identify those who are more likely to respond to this intervention.

Methods: Seventeen patients were placed on a gluten-free diet for 6 months. A positive response was defined as a 50% reduction in the relapse rate compared to the preceding 6 months or the ability to discontinue 1 immunosuppressive drug.

Results: Five (29%) participants had a positive response to the dietary intervention. The gluten-free diet was well tolerated with no clinical or laboratory adverse events. Plasma zonulin concentration was elevated in patients who failed to benefit from the gluten-free diet.

Discussion/conclusion: A gluten-free diet may be a useful adjunctive intervention for patients with difficult-to-treat nephrotic syndrome that can be implemented prior to resorting to second-line immunosuppressive therapy. Development of the plasma zonulin level as a biomarker to predict efficacy would facilitate rational use of a gluten-free diet in the management of nephrotic syndrome.

Background: Primary IgA Nephropathy (IgA N) is a very common and often progressive glomerular disease. At present, the diagnosis of IgA N is totally dependent on kidney biopsy, but the prospect for a future diagnosis by means of a "liquid" biopsy is promising. A great deal is now understood regarding its diverse clinical and pathological features as well as its epidemiology, genetics, prognosis, and pathogenesis. Treatment approaches are now on increasingly solid evidence-based grounds, but many uncertainties continue to be devil the field. Better means of categorization of patients into a hierarchy of progression risk at the time of diagnosis will undoubtedly refine and personalize treatment decisions.

Summary: The panorama of treatment strategies is undergoing a rapid transformation, largely due to an increase in large randomized clinical trials testing available agents and novel therapeutic classes. It is anticipated that the combination of better prognostic tools and new strategies for treatment of IgA N will alter the landscape of therapeutic algorithms for patients with IgA N.

Key messages: This review seeks to describe some of the evolutionary changes in the approach to treatment of IgA N, to place them in the context of current management, and to identify knowledge gaps that need to be addressed.

Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent additional pathologies being even rarer. Tissue diagnosis requires a combination of crescentic histomorphology, immunofluorescence showing "paint brush stroke" pattern of linear IgG or rarely IgA, and serum anti-GBM antibodies subject to the disease course and treatment. The authors describe one such case with a dual pathology involving IgA nephropathy and atypical anti-GBM disease.

Case presentation: A 13-year-old girl presenting with features of rapidly progressive glomerulonephritis underwent a renal biopsy showing a mesangioproliferative histology with crescents and an immunofluorescence pattern indicating a dual pathology of IgA nephropathy and anti-GBM nephritis. Additional ancillary testing including staining for IgG subclasses and galactose-deficient IgA (KM55) helped to confirm the diagnosis. She responded to steroid pulses and plasma exchange therapy, was off dialysis after 8 weeks with a serum creatinine level of 1.5 mg/dL, and however remains proteinuric at last follow-up.

Conclusion: Concurrent anti-GBM nephritis and IgA nephropathy is a rare occurrence and possibly arises from a complex interaction between the anti-GBM antibodies and the basement membrane unmasking the antigens for IgA antibodies. Additional newer techniques like immunofluorescence for KM55 are helpful in establishing the dual pathology.

Background: Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. It is defined by mesangial IgA deposition, with consequent mesangial cell proliferation, inflammation, and tubulointerstitial fibrosis.

Summary: Approximately 30% of affected patients will progress to end-stage kidney disease within 20 years of diagnosis. Currently, there is no disease-specific treatment available and management recommendations are, in general, limited to optimization of lifestyle measures and use of renin-angiotensin-aldosterone system blockers. More recently, advances in the understanding of the pathogenesis of IgAN have informed the development of novel therapeutic strategies that are now being tested in clinical trials. These have focused on different areas that include modulating the production of poorly galactosylated IgA1, which is central to the development of IgAN, and inhibiting the downstream signaling pathways and complement activation that are triggered following mesangial IgA1 deposition. In this review, we will summarize important pathogenic mechanisms in IgAN and highlight important areas of interest where treatment strategies are being developed.

Key messages: IgAN is a common form of primary glomerulonephritis for which there is no current approved specific therapy. Recent advances in the understanding of its pathogenesis have led to the development of novel therapies, with the hope that new treatment options will be available soon to treat this condition.

Introduction: Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an infrequent immune complex-mediated condition characterized by nonpruritic urticarial lesions, low serum complement levels, and autoantibodies, associated with systemic manifestations like arthralgia/arthritis, angioedema, ocular inflammation with conjunctivitis, episcleritis, uveitis, renal, gastrointestinal, and pulmonary involvement. HUVS and systemic lupus erythematosus (SLE) overlap and the criteria for identifying HUVS as an entity distinct from SLE are lacking. Despite the diagnostic criteria established by Schwartz et al. [Curr Opin Rheumatol. 2014;26(5):502-9], differentiation from SLE is sometimes difficult as patients often also fulfill the classification criteria of the American College of Rheumatology (ACR). The prognosis of HUVS depends on the organ system involved. Lung disease results in significant morbidity and mortality and is made worse by smoking. Kidney involvement with glomerulonephritis may ultimately result in end-stage renal disease with the need for kidney transplant. Death may also occur due to acute laryngeal edema.

Case presentation: We pre-sent a case of a 40-year-old female who had a diagnosis of SLE, presented with severe odynophagia, was found to have an erythematous macular rash, and had acute kidney injury attributed to contrast-related injury and cardiorenal syndrome. After the resolution of the AKI, she continued to have hematuria and low-grade proteinuria that led to a kidney biopsy that aided in the diagnosis of HUVS.

Discussion/conclusion: Given the rarity of this disease and the difficulty in differentiating HUVS from other rheumatological diseases such as SLE, further accumulation of cases is necessary to understand the best diagnostic modality for this entity.

Introduction: Kidney biopsy findings in patients with human immunodeficiency virus (HIV) are diverse, and optimal therapy for the various immune complex diseases in the setting of HIV is unknown.

Case presentation: A man with well-controlled HIV developed nephrotic range proteinuria, and kidney biopsy revealed lupus-like glomerulonephritis with a predominantly membranous pattern of injury. He opted for conservative therapy and experienced spontaneous and sustained remission. Subsequent testing revealed neural epidermal growth factor-like 1 (NELL1)-positive glomerular immune deposits. NELL1-positive glomerular immune deposits were identified in a total of 2 of 5 tested HIV-associated membranous nephropathy (MN), which were morphologically dissimilar and one of which weakly co-expressed phospholipase A2 receptor (PLA2R).

Discussion: This case suggests potentially different outcomes in patients with immune complex diseases in the setting of HIV based on disease etiology and histopathology. HIV-associated MN is occasionally NELL1-positive.

Introduction: The term monoclonal gammopathy of renal significance (MGRS) has been described to include patients with renal manifestations associated with circulating monoclonal proteins with or without a clonal lymphoproliferation (B-cell or plasma cell) and not meeting diagnostic criteria for an overt hematological malignancy. A host of MGRS-associated lesions have been described that involve various renal compartments. Our study describes the histomorphological spectrum of MGRS cases at our center in the last 5 years and description as per the classification system of the International Kidney and Monoclonal Gammopathy Research Group (IKMG).

Material and methods: Retrospective analysis was carried out of all the renal biopsies with characteristic monoclonal immunoglobulin lesions for histopathological diagnosis between years 2015 and 2020 and reviewed by two independent pathologists.

Results: Most patients in the study belonged to the fifth decade, with a median age of 50 years (mean 50.14 ± 10.43) range (24-68 years) with a male preponderance. Most patients presented with proteinuria as the sole manifestation (66.6%). Many of the patients (48%) had an M spike by serum protein electrophoresis or urinary protein electrophoresis with an abnormal serum free light chain assay (60.8%). AL amyloidosis was the most common diagnosis observed on histopathological evaluation (68.7%), followed by light chain deposition disease (10.4%).

Conclusion: MGRS lesions are infrequently encountered in the practice of nephropathology and pose a diagnostic challenge due to the limitation of a congruent clinical or hematological picture. A thorough histological examination with immunofluorescence and electron microscopy often precipitates in the right diagnosis and prompts timely management.