The role of anticomplement therapy in the management of the kidney allograft.

As the number of patients living with kidney failure grows, the need also grows for kidney transplantation, the gold standard kidney replacement therapy that provides a survival advantage. This may result in an increased rate of transplantation from HLA-mismatched donors that increases the rate of antibody-mediated rejection (AMR), which already is the leading cause of allograft failure. Plasmapheresis, intravenous immunoglobulin therapy, anti-CD20 therapies (i.e., rituximab), bortezomib and splenectomy have been used over the years to treat AMR as well as to prevent AMR in high-risk sensitized kidney transplant recipients. Eculizumab and ravulizumab are monoclonal antibodies targeting the C5 protein of the complement pathway and part of the expanding field of anticomplement therapies, which is not limited to kidney transplant recipients, and also includes complement-mediated microangiopathic hemolytic anemia, paroxysmal nocturnal hemoglobinuria, and ANCA-vasculitis. In this narrative review, we summarize the current knowledge concerning the pathophysiological background and use of anti-C5 strategies (eculizumab and ravulizumab) and C1-esterase inhibitor in AMR, either to prevent AMR in high-risk desensitized patients or to treat AMR as first-line or rescue therapy and also to treat de novo thrombotic microangiopathy in kidney transplant recipients.

A novel risk factor for malignancy: Albuminuria.

Cancer is the second leading cause of death among the adult population following cardiovascular diseases. Prevention and earlier diagnosis are among the cornerstones in the management of malignancies. Albuminuria is a diagnostic criterion for chronic kidney disease and has been associated with multiple conditions including cardiovascular diseases and systemic inflammation while the association between albuminuria and malignancy has been inadequately addressed. Large-scale observational studies with long follow-up periods demonstrate a statistically significant association between albuminuria and overall malignancy incidence, especially urothelial malignancy incidence. However, the underlying pathophysiology linking these two entities is not a straightforward causal relationship but most likely a multidirectional relationship including a causal link. In this narrative review, we evaluate the clinical studies investigating the association between albuminuria and malignancy along with potential underlying mechanisms linking them. We also summarize data on the impact of treatment modalities prescribed for albuminuria and/or proteinuria on the prevention or prognosis of malignancies.