American Journal of Nephrology最新文献

Introduction: Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high.

Methods: The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc).

Results: In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups.

Conclusion: Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.

Introduction: Recurrent IgA deposition is common after kidney transplantation. However, it is difficult to define whether IgA deposition is innocuous or contributes to organ damage. Next, although complement is known to be involved in the pathogenesis of IgA nephropathy (IgAN), its involvement has not been studied systematically in kidney transplant recipients (KTR).

Methods: KTR with biopsy-proven native IgAN who underwent kidney biopsy after transplantation between 1995 and 2020 were included. Recurrent IgA deposition was defined as IgA deposit in the glomerulus. Staining of complement factors C4d, C3d, and C5b-9 were quantitatively evaluated using ImageScope.

Results: Sixty-seven KTR (85% male, 46±13 years old, 12 [6-24] months after transplantation, 58% with indication biopsy) were included in the analyses. Of them, 25 (37%) had recurrent IgA deposition. There were no clinical differences between KTR with and without recurrent IgA deposition. C3d and C5b-9 were always present in biopsies with IgA deposition, while C4d was present in 48% of the biopsies. During a median follow-up of 9.6 [4.8-14] years, 18 (27%) KTR developed death-censored graft failure. Recurrent IgA deposition was not associated with graft failure. Of the evaluated complement factors, only C4d staining was associated with graft failure in KTR with recurrent IgA deposition (Hazard ratio = 2.55, 95% confidence interval = 1.07-6.03, p = 0.034).

Conclusions: Recurrent IgA deposition was not associated with graft failure in itself. C4d, when present, is strongly associated with graft loss in KTR with recurrent IgA deposition, suggesting a pathogenic role for the lectin pathway in recurrent IgAN.

Introduction: The relationship between fat mass and osteoporosis, sarcopenia, and osteosarcopenia is complex. While higher fat mass generally has a negative impact on bone and muscle health in the general population, the impact in peritoneal dialysis (PD) patients is less well understood.

Methods: In this study of 359 PD patients, sarcopenia was identified using appendicular skeletal muscle per square meter (ASM/m2), with cut-off values of <7.0 kg/m2 for men and <5.5 kg/m2 for women. Fat tissue index (FTI) and lean tissue index (LTI) were determined using body composition monitoring, with the lowest tertile classified as low FTI and low LTI. Bone mineral density was measured, with a T-score below -2.5 indicating osteoporosis.

Results: The prevalence of osteoporosis, sarcopenia, and osteosarcopenia was 25%, 32%, and 15%, respectively. Notably, 60% of osteoporotic patients had sarcopenia, and about 45% of sarcopenic patients had osteoporosis. Patients with osteoporosis were older and had significantly lower LTI (15.3 vs. 12.7 kg/m2, p < 0.001) and ASM (7.3 vs. 5.8 kg/m2, p < 0.001). Osteoporotic patients also had lower FTI, but this was more pronounced in men than in women. Patients with both sarcopenia and osteoporosis had the lowest LTI and FTI compared to those with only one or neither condition. Low FTI was a significant determinant for osteoporosis (OR, 2.34; 95% CI, 1.43-3.85; p = 0.001), sarcopenia (OR, 2.91; 95% CI, 1.82-4.64; p < 0.001), and osteosarcopenia (OR, 2.34; 95% CI, 1.30-4.24; p = 0.005) in univariate analysis, and these associations remained significant after adjustment for age and body mass index.

Conclusion: Osteoporosis and sarcopenia are common and interrelated in PD patients. Low fat mass, but not normal/high fat mass, was significantly associated with these conditions, suggesting the importance of maintaining adequate fat mass in PD patients.

Background: Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms.

Summary: Mass spectrometry analysis of tissue samples in the USA shows immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvements are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the USA have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement.

Key messages: This review focuses on AL, AA, and ATTR amyloidosis due to their common systemic presentations. Recent US-based clinicopathologic studies challenge conventional beliefs that toxicity is primarily driven by amyloid deposition and highlight the role of the complement pathway. Diagnostic methods, particularly mass spectrometry, are crucial for accurate typing. Treatment strategies vary depending on the underlying type, with AL amyloidosis primarily targeting plasma cell clones, AA amyloidosis addressing underlying inflammation with systemic therapies, and ATTR amyloidosis focusing on ATTR stabilization or gene silencing.

Background: Cancer, hypertension, and kidney disease are closely interrelated. Knowledge of the potential hypertensive and nephrotoxic effects of antineoplastic medications is critical to minimizing interruptions in cancer treatment.

Summary: Antineoplastic medications can cause hypertension, proteinuria, and kidney injury, often mediated by common mechanisms. Notably, inhibitors of the vascular endothelial growth factor pathway have the strongest association with both hypertension and proteinuria, typically acute in onset and often reversible after drug discontinuation. The abrupt rise in blood pressure can cause clinically significant hypertensive syndromes and contribute to overall morbidity. Significant proteinuria can herald kidney failure. Close monitoring of blood pressure and renal function during antineoplastic therapy and appropriate hypertension treatment are important. This article reviews available literature and proposes a step-by-step approach to manage cancer patients with concurrent hypertension and kidney disease.

Key messages: For antineoplastic medications with known hypertensive effect, blood pressure should be checked at baseline and serially during cancer treatment. Hypertensive crisis with end-organ damage, significant proteinuria, microscopic hematuria, or unexplained acute kidney injury necessitates drug cessation until further evaluation and resolution. In patients with chronic kidney disease and cancer therapy-related hypertension, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker is the preferred antihypertensive choice. Finally, multidisciplinary collaboration in these patients will yield the best results.

Background: In patients with end-stage kidney disease (ESKD) receiving peritoneal dialysis (PD), cardiovascular events represent the predominant cause of morbidity and mortality, with cardiac arrhythmias and sudden death being the leading causes of death in this population. Autonomic nervous system (ANS) dysfunction is listed among the non-traditional risk factors accounting for the observed high cardiovascular burden, with a plethora of complex and not yet fully understood pathophysiologic mechanisms being involved.

Summary: In recent years, preliminary studies have investigated and confirmed the presence of ANS dysfunction in PD patients, while relevant results from cohort studies have linked ANS dysfunction with adverse clinical outcomes in these patients. In light of these findings, ANS dysfunction has been recently receiving wider consideration as an independent cardiovascular risk factor in PD patients. The aim of this review was to describe the mechanisms involved in the pathogenesis of ANS dysfunction in ESKD and particularly PD patients and to summarize the existing studies evaluating ANS dysfunction in PD patients.

Key messages: ANS dysfunction in PD patients is related to multiple complex mechanisms that impair the balance between SNS/PNS, and this disruption represents a crucial intermediator of cardiovascular morbidity and mortality in this population.

Background: Chronic kidney disease (CKD) presents a persistent global health challenge, characterized by complex pathophysiology and diverse progression patterns. Metabolomics has emerged as a valuable tool in unraveling the intricate molecular mechanisms driving CKD progression.

Summary: This comprehensive review provides a summary of recent progress in the field of metabolomics in kidney disease with a focus on spatial metabolomics to shed important insights to enhancing our understanding of CKD progression, emphasizing its transformative potential in early disease detection, refined risk assessment, and the development of targeted interventions to improve patient outcomes.

Key message: Through an extensive analysis of metabolic pathways and small-molecule fluctuations, bulk and spatial metabolomics offers unique insights spanning the entire spectrum of CKD, from early stages to advanced disease states. Recent advances in metabolomics technology have enabled spatial identification of biomarkers to provide breakthrough discoveries in predicting CKD trajectory and enabling personalized risk assessment. Furthermore, metabolomics can help decipher the complex molecular intricacies associated with kidney diseases for exciting novel therapeutic approaches. A recent example is the identification of adenine as a key marker of kidney fibrosis for diabetic kidney disease using both untargeted and targeted bulk and spatial metabolomics. The metabolomics studies were critical to identify a new biomarker for kidney failure and to guide new therapeutics for diabetic kidney disease. Similar approaches are being pursued for acute kidney injury and other kidney diseases to enhance precision medicine decision-making.

Introduction: Hyporesponsiveness to erythropoiesis stimulating agents (ESAs) is important problem in dialysis patients. While proton pump inhibitors (PPIs) may inhibit iron absorption, few studies have examined associations between PPIs and ESA-resistant anemia in hemodialysis patients. This study examined the associations between PPIs and ESA-resistant anemia in hemodialysis patients.

Methods: The present study was a cross-sectional study using repeated 4-month observations, up to eight observations/patient, from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS). The primary outcome was erythropoietin resistance index (ERI). ESA dose, hemoglobin, proportion of erythropoietin-resistant anemia, transferrin saturation (TSAT), and ferritin were also examined. Linear or risk-difference regression models were used with generalized estimating equations to account for repeated measurements.

Results: Of 1,644 patients, 867 patients had PPI prescriptions (52.7%). Patients prescribed PPI had higher ERI, higher ESA dose, and lower TSAT levels. Multivariable analysis for 12,048 four-month observations showed significantly greater ERI in PPI users (adjusted difference 0.95 IU/week/kg/[g/dL] [95% CI: 0.40-1.50]). Significant differences were also found in ESA dose (336 IU/week [95% CI: 70-602]) and the prevalence of erythropoietin-resistant anemia (3.9% [2.0-5.8%]) even after adjusted for TSAT and ferritin. Among possible mediators between the association of PPIs and anemia, TSAT was significantly different between PPI users and non-users (adjusted difference, -0.82% [95% CI: -1.56 to -0.07]).

Conclusions: This study showed the associations between PPI and ERI, ESA dose, and TSAT in hemodialysis patients; physicians should consider anemia's associations with PPIs in hemodialysis patients.

Introduction: Diabetes mellitus is a common cause of kidney failure and is often complicated by autonomic neuropathy, which may have implications for blood pressure (BP) homeostasis during hemodialysis (HD).

Methods: In this post hoc analysis of the Frequent Hemodialysis Network (FHN) Daily Trial, we used random effects Poisson and linear regression models to estimate the association of diabetes (vs. not) with intra-dialytic hypotension (IDH) and peri-dialytic BP parameters, respectively. We tested for differential associations according to the randomized treatment (6/week vs. 3/week HD) and pre-HD systolic BP.

Results: Of the 244 patients with intra-dialytic BP data, 100 (41%) had diabetes at baseline. The mean age was 51 ± 14 years; overall, 39% were female. In adjusted models, diabetes (vs. not) was associated with a 93% higher risk of developing IDH (IRR: 1.93; 95% CI: 1.26, 2.95). There was no evidence that the randomized treatment assignment modified the association between diabetes and IDH (pinteraction = 0.32), but more potent associations were noted among those with higher pre-HD systolic BP (pinteraction < 0.001). Diabetes (vs. not) was associated with a lower adjusted nadir intra-HD BP (-4.2; 95% CI: -8.3, -0.2 mm Hg) but not with the pre- or post-HD systolic BP.

Conclusions: Among participants of the FHN Daily Trial, patients with diabetes had a higher risk of IDH and lower nadir intra-HD systolic BP than patients without diabetes, even when undergoing HD up to 6 times per week.