Blood pressure (BP) and volume control are critical components of dialysis care and have substantial impacts on patient symptoms, quality of life, and cardiovascular complications. Yet, developing consensus best practices for BP and volume control have been challenging, given the absence of objective measures of extracellular volume status and the lack of high-quality evidence for many therapeutic interventions. In February of 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference titled Blood Pressure and Volume Management in Dialysis to assess the current state of knowledge related to BP and volume management and identify opportunities to improve clinical and patient-reported outcomes among individuals receiving maintenance dialysis. Four major topics were addressed: BP measurement, BP targets, and pharmacologic management of suboptimal BP; dialysis prescriptions as they relate to BP and volume; extracellular volume assessment and management with a focus on technology-based solutions; and volume-related patient symptoms and experiences. The overarching theme resulting from presentations and discussions was that managing BP and volume in dialysis involves weighing multiple clinical factors and risk considerations as well as patient lifestyle and preferences, all within a narrow therapeutic window for avoiding acute or chronic volume-related complications. Striking this challenging balance requires individualizing the dialysis prescription by incorporating comorbid health conditions, treatment hemodynamic patterns, clinical judgment, and patient preferences into decision-making, all within local resource constraints.

In 2017, Kidney Disease: Improving Global Outcomes (KDIGO) published a Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Since then, new lines of evidence have been published related to evaluating disordered mineral metabolism and bone quality and turnover, identifying and inhibiting vascular calcification, targeting vitamin D levels, and regulating parathyroid hormone. For an in-depth consideration of the new insights, in October 2023, KDIGO held a Controversies Conference on CKD-MBD: Progress and Knowledge Gaps Toward Personalizing Care. Participants concluded that the recommendations in the 2017 CKD-MBD guideline remained largely consistent with the available evidence. However, the framework of the 2017 Guideline, with 3 major sections-biochemical abnormalities in mineral metabolism; bone disease; and vascular calcification-may no longer best reflect currently available evidence related to diagnosis and treatment. Instead, future guideline efforts could consider mineral homeostasis and deranged endocrine systems in adults within a context of 2 clinical syndromes: CKD-associated osteoporosis, encompassing increased fracture risk in patients with CKD; and CKD-associated cardiovascular disease, including vascular calcification and structural abnormalities, such as valvular calcification and left ventricular hypertrophy. Participants emphasized that the complexity of bone and cardiovascular manifestations of CKD-MBD necessitates personalized approaches to management.

Summary: Background and objectives: Sudden death is common in hemodialysis patients, but whether modifiable practices affect the risk of sudden death remains unclear. Design, setting, participants, & measurements: This study analyzed 37,765 participants in 12 countries in the Dialysis Outcomes and Practice Patterns Study to explore the association of the following practices with sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time [TT] <210 minutes, Kt/V 5.7% of postdialysis weight, low dialysate potassium [K_D <3]), and prescription of Q wave/T wave interval–prolonging drugs. Cox regression was used to estimate effects on mortality, adjusting for potential confounders. An instrumental variable approach was used to further control for unmeasured patient-level confounding. Results: There were 9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient-years; median follow-up, 1.59 years). Associations with sudden death included hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and 1.10 for low Kt/V. Compared with K_D ≥3 mEq/L, the sudden death rate was higher for K_D ≤1.5 and K_D=2–2.5 mEq/L. The instrumental variable approach yielded generally consistent findings. The sudden death rate was elevated for patients taking amiodarone, but not other Q wave/T wave interval–prolonging drugs. Conclusions: This study identified modifiable dialysis practices associated with higher risk of sudden death, including short TT, large ultrafiltration volume, and low K_D. Because K_D <3 mEq/L is common and easy to change, K_D tailoring may prevent some sudden deaths. This hypothesis merits testing in clinical trials.

Uncontrolled complement activation can cause or contribute to glomerular injury in multiple kidney diseases. While complement activation plays a causal role in atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G), over the past decade a rapidly accumulating body of evidence has shown a role for complement activation in multiple other kidney diseases, including diabetic nephropathy and several glomerulonephritides. The number of available complement inhibitor therapies has also increased during the same period. In 2022 KDIGO convened a Controversies Conference, The Role of Complement in Kidney Disease, to address the expanding role of complement dysregulation in the pathophysiology, diagnosis, and management of various glomerular diseases, diabetic nephropathy, and other forms of HUS. Conference participants reviewed the evidence for complement playing a primary causal or secondary role in progression for several disease states and considered how evidence of complement involvement might inform management. Participating patients with various complement-mediated diseases and caregivers described concerns related to life planning, implications surrounding genetic testing, and the need for inclusive implementation of effective novel therapies into clinical practice. The value of biomarkers in monitoring disease course and the role of the glomerular microenvironment in complement response were examined, and key gaps in knowledge and research priorities were identified.

Significance Statement: Membranous nephropathy (MN) results from antibodies targeting an antigen in the glomerular basement membrane (GBM). The target antigens identified so far include PLA2R, THSD7A, NELL1, SEMA3B, and EXT1/EXT2. Using laser microdissection and mass spectrometry analysis, the authors identified a novel protein, protocadherin 7 (PCDH7), that is present in the GBM of a subset of patients with MN who are negative for all of the known antigens associated with MN. PCDH7 shows granular GBM staining and colocalizes with Ig in the GBM. Furthermore, antibodies to PCDH7 were detected in both the serum and kidney biopsy tissue from individuals with PCDH7-associated MN but not from controls. These findings suggest that PCDH7-associated MN defines a distinct type of MN. Background: Membranous nephropathy (MN) results from deposition of antigen-antibody complexes along the glomerular basement membrane (GBM). PLA2R, THSD7A, NELL1, and SEMA3B account for 80%–90% of target antigens in MN. Methods: We performed laser microdissection and mass spectrometry (MS/MS) in kidney biopsies from 135 individuals with PLA2R-negative MN, and used immunohistochemistry/immunofluorescence and confocal microscopy to confirm the MS/MS finding, detect additional cases, and localize the novel protein. We also performed MS/MS and immunohistochemistry on 116 controls and used immunofluorescence microscopy to screen biopsy samples from two validation cohorts. Western blot and elution studies were performed to detect antibodies in serum and biopsy tissue. Results: MS/MS studies detected a unique protein, protocadherin 7 (PCDH7), in glomeruli of ten (5.7%) PLA2R-negative MN cases, which also were negative for PLA2R, THSD7A, EXT1/EXT2, NELL1, and SEMA3B. Spectral counts ranged from six to 24 (average 13.2 [SD 6.6]). MS/MS did not detect PCDH7 in controls (which included 28 PLA2R-positive cases). In all ten PCDH7-positive cases, immunohistochemistry showed bright granular staining along the GBM, which was absent in the remaining cases of PLA2R-negative MN and control cases. Four of 69 (5.8%) cases in the validation cohorts (all of which were negative for PLA2R, THSD7A, EXT1, NELL1, and SEMA3B) were PCDH7-positive MN. Kidney biopsy showed minimal complement deposition in 12 of the 14 PCDH7-associated cases. Confocal microscopy showed colocalization of PCDH7 and IgG along the GBM. Western blot analysis using sera from six patients showed antibodies to nonreduced PCDH7. Elution of IgG from frozen tissue of PCDH7-associated MN showed reactivity against PCDH7. Conclusions: MN associated with the protocadherin PCDH7 appears to be a distinct, previously unidentified type of MN.