Survival and mortality analysis in two nephrology centers: A prospective observational study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) requiring dialysis therapy is increasing globally. Survival and mortality data of these patients in Germany are fragmentary since the nationwide registry was terminated in 2006. OBJECTIVE: The objective of this study was to analyze the survival, causes of death, and co-morbidities of dialysis patients in a German population cohort as well as to assess the factors influencing mortality in these patients. MATERIALS AND METHODS: We included adult, prevalent chronic dialysis patients from the German population who underwent hemodialysis and peritoneal dialysis at our centers between 2014 and 2018. We compared the characteristics of living and deceased patients and assessed survival. Patients with and without diabetes mellitus were also examined, and their co-morbidities were analyzed. RESULTS: Of the 425 patients included in our study (m/f: 235/190), 182 died within the observation period. Mean survival of patients with coronary artery disease (CAD) (n = 217), peripheral artery disease (PAD) (n = 128), and cardiorenal syndrome (CRS) (n = 99) was significantly reduced compared to patients without the disease (CAD: 4.2 vs. 6.4 years; PAD: 4.3 vs. 6.5 years; CRS: 3.7 vs. 7.3 years, p < 0.001, respectively). Patients with diabetes mellitus (n = 110) showed no reduced survival compared to patients without the disease (n = 315) (4.8 vs. 4.9 years, p = 0.421). Diastolic blood pressure (DBP) and C-reactive protein (CRP) levels were associated with dialysis time in linear regression analysis (DBP: R = 0.029, p < 0,001; CRP: R = 0.085, p < 0.001). CONCLUSION: Our results provide novel data regarding German CKD patients requiring dialysis and factors influencing mortality, which could serve as a useful reference for further studies.

Phospholipase A2 receptor autoantibodies and clinical outcome in patients with primary membranous nephropathy.

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an uncertain clinical outcome. The characterization of the phospholipase A2 receptor (PLA2R) as the major target antigen in primary MN and the detection of circulating autoantibodies in these patients is a major advance in understanding this disease. To test whether PLA2R antibody levels reflect disease activity or clinical outcome, we performed a prospective multicenter study of 133 adult patients with primary MN and detectable serum PLA2R antibodies who had not received immunosuppressive therapy. Patients were followed ≤24 months. PLA2R antibody levels associated with clinical disease activity (proteinuria) in patients with immunosuppressive therapy (n=101) or supportive care (n=32). Within 3 months, immunosuppressive therapy led to a sustained 81% reduction in PLA2R antibody levels paralleled by a 39% reduction in proteinuria. Patients who experienced remission of proteinuria after 12 months had significantly lower PLA2R antibody levels at the time of study inclusion compared with patients with no remission. Patients with high PLA2R antibody levels achieved remission of proteinuria significantly later than patients with low PLA2R antibody levels. PLA2R antibody levels fell over time in patients with spontaneous remission but remained elevated in patients who did not show a reduction in proteinuria. Multivariable Cox regression analysis confirmed PLA2R antibody level as an independent risk factor for not achieving remission of proteinuria. We conclude that a decrease in PLA2R antibody level is associated with a decrease of proteinuria in patients with primary MN.

Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy.

The M-type phospholipase A2 receptor (PLA2R) is the major target antigen in idiopathic membranous nephropathy with detectable autoantibodies in the serum of up to 70% of patients. In retrospective studies, the PLA2R-autoantibody titer in the serum was sometimes negative indicating their measurement alone may be inconclusive. In order to better differentiate between primary and secondary membranous nephropathy, we conducted a prospective study that included 88 patients with a histologic diagnosis of membranous nephropathy. Immunohistochemical analysis for PLA2R was faintly positive in kidneys from normal individuals and patients with various other glomerular injuries. In 61 of the 88 patients, PLA2R expression was strongly positive in glomeruli, and in 60 of these patients PLA2R autoantibodies were also detected in the serum. The 27 patients negative for serum PLA2R autoantibodies were faintly positive for PLA2R staining in glomeruli and in 15 of these patients a secondary cause was found. The remaining 12 patients have a yet undetected secondary cause of membranous nephropathy or have different glomerular antigens other than PLA2R. Thus, increased staining for PLA2R in glomeruli of renal biopsies tightly correlates with the presence of PLA2R autoantibodies in the serum and this may help discriminate between primary and secondary membranous nephropathy.