Summary Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13. In general, severe deficiency of plasma ADAMTS13 activity (<10 IU/dL) with or without detectable inhibitory autoantibodies against ADAMTS13 supports the diagnosis of TTP if a patient presents with thrombocytopenia and microangiopathic hemolytic anemia (i.e. schistocytes, elevated serum lactate dehydrogenase, decreased hemoglobin and haptoglobin) without other known etiologies that cause thrombotic microangiopathy (TMA). Normal to moderately reduced plasma ADAMTS13 activity (>20 IU/dL) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. While plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS13 mutations, daily therapeutic plasma exchange remains the initial treatment of choice for acquired TTP with autoantibodies. Immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide, and splenectomy, etc. should be considered to eliminate autoantibodies for sustained remission. Other emerging therapeutic modalities, including recombinant ADAMTS13, adeno-associated virus (AAV) 8-mediated gene therapy, platelet-delivered ADAMTS13, and antagonists targeting the interaction between platelet glycoprotein 1b and VWF are under investigation. This review highlights the recent progress in our understanding of the pathogenesis, diagnosis, and current and potential novel therapies for hereditary and acquired TTP.

IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culminate in the development of primary IgA nephropathy. Whether secondary forms of the disease share common pathways triggered by underlying disorders or different mechanisms leading to similar pathologic findings remains to be determined. In this article we describe the most frequent etiologies for secondary IgA nephropathy and review the available literature for the pathophysiology.

Given the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence.

BackgroundIgA nephropathy (IgAN) is the leading primary GN worldwide. The disease is thought to result from glomerular deposition of circulating immune complexes of IgG bound to galactose-deficient IgA1 (Gd-IgA1). However, routine immunofluorescence microscopy fails to detect IgG in many kidney biopsies from patients with IgAN and the specificity of IgG in immunodeposits has not been tested.MethodsWe used remnant frozen kidney-biopsy specimens from 34 patients with IgAN; 14 were IgG-positive and 20 were IgG-negative by routine immunofluorescence microscopy. Six patients with primary membranous nephropathy (MN) and eight with lupus nephritis (LN) served as controls. IgG in the kidney tissue was extracted and its amount determined by ELISA. IgG molecular integrity was assessed by SDS-PAGE immunoblotting. Antigenic specificity of extracted IgG was determined by ELISA using phospholipase A2 receptor (PLA2R) or Gd-IgA1 as antigen. In addition, ten other IgAN cases, six IgG-positive and four IgG-negative by routine immunofluorescence, were used for colocalization studies by confocal microscopy.ResultsIgG extracted from MN but not IgAN immunodeposits reacted with PLA2R. Conversely, IgG extracted from IgAN but not MN or LN immunodeposits reacted with Gd-IgA1. Even IgAN kidney-biopsy specimens without IgG by routine immunofluorescence microscopy had IgG specific for Gd-IgA1. Confocal microscopy confirmed the presence of IgG in the IgAN biopsies with colocalization of glomerular IgA and IgG.ConclusionsThese results reveal for the first time that IgAN kidney biopsies, with or without IgG by routine immunofluorescence, contain Gd-IgA1–specific IgG autoantibodies. These findings support the importance of these autoantibodies in the pathogenesis of IgAN.