Reedmorrison5288

IgG (mainly IgG3) is the most commonly involved isotype in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Here we describe the first series of PGNMID with deposition of monoclonal immunoglobulin light chain only (PGNMID-light chain). This multicenter cohort of 17 patients presented with nephritic or nephrotic syndrome with underlying hematologic conditions of monoclonal gammopathy of renal significance (71%) or multiple myeloma (29%). Monoclonal immunoglobulin was identified by serum and urine immunofixation in 65% and 73%, respectively, with abnormal serum free light chain in 83%, and a detectable bone marrow plasma cell clone in 88% of patients. Renal biopsy showed a membranoproliferative pattern in most patients. By immunofluorescence, deposits were restricted to glomeruli and composed of restricted light chain (kappa in 71%) and C3, with granular appearance and subendothelial, mesangial and subepithelial distribution by electron microscopy. Proteomic analysis in four cases of kappa PGNMID-light chain revealed spectra for kappa constant and variable domains, without evidence of Ig heavy chains; spectra for proteins of the alternative pathway of complement and terminal complex were detected in three. The classical pathway was not detected in three cases. After median follow up of 70 months, the renal response was dependent on a hematologic response and occurred in six of ten patients treated with plasma cell-directed chemotherapy but none of five patients receiving other therapies. Thus, PGNMID-light chain differs from PGNMID-IgG by higher frequency of a detectable pathogenic plasma cell clone. Hence, proper recognition is crucial as anti-myeloma agents may improve renal prognosis. Activation of an alternative pathway of complement by monoclonal immunoglobulin light chain likely plays a role in its pathogenesis. With the increasing availability of linked electronic health records, long-running cohorts, and high-throughput technologies, the potential for epidemiology research to improve the care of patients with kidney disease is greater than ever before. In this review, we highlight the application of epidemiology techniques to identify, evaluate, and address chronic kidney disease. We discuss studies that inform guidelines, identify health disparities, evaluate the genetic basis of disease, and relate data on omics, such as proteomics, metabolomics, and genetics, to outcomes. We describe how observational data have been used to facilitate the conduct of randomized controlled trials through enhanced identification of high-risk individuals and the evaluation of surrogate kidney disease outcomes as well as to address clinical questions where randomized controlled trials are impractical or infeasible. Finally, we discuss consumer engagement in research, including that of patients, policymakers, payers, and health care system, and the role of kidney disease epidemiology research in implementation science and as a key source of data and methodology for precision medicine. Under physiological states, the nervous system and the kidneys communicate with each other to maintain normal body homeostasis. However, pathological states disrupt this interaction as seen in hypertension, and kidney damage can cause impaired renorenal reflex and sodium handling. In acute kidney injury (AKI) and chronic kidney disease (CKD), damaged kidneys can have a detrimental effect on the central nervous system. CKD is an independent risk factor for cerebrovascular disease and cognitive impairment, and many factors, including retention of uremic toxins and phosphate, have been proposed as CKD-specific factors responsible for structural and functional cerebral changes in patients with CKD. However, more studies are needed to determine the precise pathogenesis. Epidemiological studies have shown that AKI is associated with a subsequent risk for developing stroke and dementia. Deucravacitinib However, recent animal studies have shown that the renal nerve contributes to kidney inflammation and fibrosis, whereas activation of the cholinergic anti-inflammatory pathway, which involves the vagus nerve, the splenic nerve, and immune cells in the spleen, has a significant renoprotective effect. Therefore, elucidating mechanisms of communication between the nervous system and the kidney enables us not only to develop new strategies to ameliorate neurological conditions associated with kidney disease but also to design safe and effective clinical interventions for kidney disease, using the neural and neuroimmune control of kidney injury and disease. Membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) is a recently described pattern of glomerulonephritis with a unique histopathology. The pattern is characterized by subepithelial and/or mesangial immune deposits that are "masked", to immunoglobulin staining by routine immunofluorescence but strongly stain for IgG and kappa light chain after protease digestion. Patients with this pattern of glomerulonephritis are most commonly young females presenting with proteinuria and a vague history of autoimmune disease such as low titer antinuclear antibodies. Here we compared the mass spectrometry profile of laser capture microdissected glomeruli from nine MGMID renal biopsies with eight biopsies showing other patterns of membranous glomerulopathy. The protein most significantly increased in MGMID was serum amyloid P. Immunostaining showed serum amyloid P colocalized with IgG in the glomeruli of MGMID but not with PLA2R-associated membranous glomerulopathy. Serum amyloid P was positive in the glomeruli of all 32 MGMID biopsies but negative in biopsies of other types of membranous glomerulopathies such as those associated with PLA2R and THSD7A. There were four biopsies with glomerular serum amyloid P staining among the 173 biopsies that did not fulfill criteria for MGMID or amyloidosis. All four of these biopsies with positive serum amyloid P staining had a membranous pattern of glomerulopathy with IgG kappa deposits that only differed from MGMID by the lack of "masking". Thus, positive staining within glomerular deposits for serum amyloid P identifies a unique form of glomerulonephritis likely sharing a common pathophysiologic mechanism of disease.