How Times Have Changed! A Cornucopia of Antigens for Membranous Nephropathy

The identification of the major target antigen phospholipase A2 receptor (PLA2R) in the majority of primary (idiopathic) cases of membranous nephropathy (MN) has been followed by the rapid identification of numerous minor antigens that appear to define phenotypically distinct forms of disease. This article serves to review all the known antigens that have been shown to localize to subepithelial deposits in MN, as well as the distinctive characteristics associated with each subtype of MN. We will also shed light on the novel proteomic approaches that have allowed identification of the most recent antigens. The paradigm of an antigen normally expressed on the podocyte cell surface leading toin-situimmune complex formation, complement activation, and subsequent podocyte injury will be discussed and challenged in light of the current repertoire of multiple MN antigens. Since disease phenotypes associated with each individual target antigens can often blur the distinction between primary and secondary disease, we encourage the use of antigen-based classification of membranous nephropathy.</jats:p

Gitelman syndrome patient managed with amiloride during pregnancy and lactation

Abstract Gitelman Syndrome (GS) is a rare autosomal-recessive tubular disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, hyperreninemic hyperaldosteronism, and normotension. Management of GS during pregnancy is particularly challenging due to pregnancy-associated renal physiological changes and due to controversial safety profiles regarding teratogenicity of medications commonly used for GS management in non-pregnant patients. We report a case of a 20-year-old female patient diagnosed of GS who was treated with amiloride during pregnancy and lactation due to persistent hypokalemia resistant to oral supplementation therapy. Use of amiloride facilitated control of hypokalemia and hypomagnesemia in the mother without causing any noticeable side effects in the newborn

Key role for EphB2 receptor in kidney fibrosis

Abstract Erythropoietin producing hepatocellular (Eph)–Eph receptor interacting (Ephrin) receptor–ligand signaling has been implicated in the development of tissue fibrosis, though it has not been well defined in the kidney. We detected substantial up-regulation of expression and phosphorylation of the EphB2 receptor tyrosine kinase in fibrotic kidney tissue obtained both from mice subjected to the unilateral renal ischemia–reperfusion (IR) model at 14 days and in patients suffering from chronic kidney disease (CKD). Knockout (KO) mice lacking EphB2 expression exhibited a normal renal structure and function, indicating no major role for this receptor in kidney development or action. Although IR injury is well-known to cause tissue damage, fibrosis, and renal dysfunction, we found that kidneys from EphB2KO mice showed much less renal tubular injury and retained a more preserved renal function. IR-injured kidneys from EphB2 KOs exhibited greatly reduced fibrosis and inflammation compared with injured wildtype (WT) littermates, and this correlated with a significant reduction in renal expression of profibrotic molecules, inflammatory cytokines, NADPH oxidases, and markers for cell proliferation, tubular epithelial-to-mesenchymal transition (EMT), myofibroblast activation, and apoptosis. A panel of 760 fibrosis-associated genes were further assessed, revealing that 506 genes in WT mouse kidney following IR injury changed their expression. However, 70.9% of those genes were back to or close to normal in expression when EphB2 was deleted. These data indicate that endogenous EphB2 expression and signaling are abnormally activated after kidney injury and subsequently contribute to the development of renal fibrosis via regulation of multiple profibrotic pathways.</jats:p