Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy.

BACKGROUND: Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. METHODS: A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. RESULTS: These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. CONCLUSIONS: Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.

Nephrotoxic Effects of Chemotherapeutic Agents.

Nephrotoxicity can be a severe complication of oncology treatment. The most common presentations of chemotherapy-related renal disorders include acute kidney injury, electrolyte abnormalities, acid base disturbances, hemolytic anemia, and hypertension. Oncology nurses should be aware of the potential renal complications of oncology therapeutics and advocate for appropriate monitoring and treatment of patients. This article reviews the most common chemotherapeutic agents that may cause nephrotoxicity.

Utility of Biomarkers in Cardiac Amyloidosis.

Cardiac amyloidosis is a growing field, with advancements in diagnosis and management. Cardiac biomarkers are used to predict survival and to develop severity staging systems. Cardiac biomarkers are also used in clinical practice to stratify patients for treatment and to evaluate response to therapies. The current review summarizes the major clinical utility of current biomarkers in patients with cardiac amyloidosis and provides insights about future areas of investigation.

Cardiovascular Risk Assessment and Management in Prerenal Transplantation Candidates.

Cardiovascular (CV) assessment in prerenal transplant patients varies by center. Current guidelines recommend stress testing for candidates if ≥ 3 CV risk factors exist. We evaluated the CV assessment and management in 685 patients referred for kidney transplant over a 7-year period. All patients had CV risk factors, and the most common cause of end-stage renal disease was diabetes. Thirty-three percent (n = 229) underwent coronary angiography. The sensitivity of stress testing to detect obstructive coronary artery disease (CAD) was poor (0.26). Patients who had no CAD, nonobstructive CAD, or CAD with intervention had significantly higher event-free survival compared with patients with obstructive CAD without intervention. There were no adverse clinical events (death, myocardial infarction, stroke, revascularization, and graft failure) within 30 days post-transplant in patients who had preoperative angiography (n = 77). Of the transplanted patients who did not have an angiogram (n = 289), there were 8 clinical events (6 myocardial infarctions) in the first 30 days. In conclusion, our results indicate that stress testing and usual risk factors were poor predictors of obstructive CAD and that revascularization may prove beneficial in these patients.