American Journal of Nephrology最新文献

Introduction: Nephroprotection in pediatric chronic kidney disease (CKD) has a major positive impact, both on residual renal function and on quality of life, by delaying the need for renal replacement therapy. To this day, nephroprotective drugs used in children are mainly limited to angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers; interestingly, as suggested by trials conducted in adults with CKD, sodium-glucose cotransporter 2 inhibitors (SGLT2i) might also be beneficial to pediatric patients. However, there are no validated data to this date documenting the effect of SGLT2i in pediatric patients with CKD.

Methods: We present a retrospective single-center study reporting the use of dapagliflozin in pediatric patients with CKD, aiming to evaluate dapagliflozin safety profile as well as its potential for renal protection. Our study describes 7 patients with a mean age of 13.3 years (+/- 7.029) presenting with identified glomerulopathy, leading to CKD and already treated by ACE inhibitors. Patients received a daily dose of dapagliflozin of 5 or 10 mg.

Results: Over a period of 15 months, all patients reported the medication as easy to use. After an initial dip, estimated glomerular filtration rate decline slope stabilized in all patients. Urinary albumin-over-creatinine ratio had a strong tendency to decrease after 6 months of treatment (p = 0.0684). Systolic blood pressure also had a tendency to decrease after 6 months of treatment (p = 0.1). No significant side effect was reported by the patients.

Conclusion: The promising results presented in this study support the use of SGLT2i in pediatric patients with CKD, although larger, randomized controlled trials in pediatric patients are necessary to better characterize their effectiveness in this particular population.

Introduction: We previously completed a trial of renal pelvic denervation for treating hypertension that reduced blood pressure by the 2-month primary endpoint. However, information on the durability of effectiveness is a critical requirement for device therapy and we now report data up to 12 months.

Methods: This was an open-label, single-arm feasibility study in patients with increased blood pressure despite taking an average of 2.7 medications. The key endpoint reported here was ambulatory blood pressure at 12 months following renal pelvic denervation.

Results: In the 17 patients (mean age: 56) studied, there was a reduction from the baseline of 148 + 8.7 mm Hg in the primary endpoint of mean daytime systolic blood pressure at 12 months of 19.1 (26.7, 11.6) mm Hg, p < 0.001, as compared with the 2-month result of 19.4 (24.9, 14.0) mm Hg. The 24-h systolic blood pressure fell by 19.3 (26.7, 11.9), p < 0.001, and nighttime systolic fell by 18.7 (27.5, 9.8), p < 0.001, mm Hg at 12 months. Diastolic pressures also fell significantly from baseline at 12 months. As well, automated office systolic blood pressure was reduced from the baseline of 156.5 ± 12.3 by 24.8 (33.2, 16.8) mm Hg, p < 0.001, at 12 months as compared with 22.4 (31.5, 13.3) at 2 months. All blood pressure changes at 12 months were not different from those at 2 months, thus confirming the durability of the procedure. There were no serious procedural, clinical, or laboratory adverse events related to the intervention. Serum creatinine fell from 1.03 ± 0.22 to 0.82 ± 0.16 mg/dL, and estimated glomerular filtration rate rose from 79.6 ± 17.8 to 96.3 ± 16.4 mL/min/1.73 m2 by 12 months, again sustaining effects seen at 2 months.

Conclusion: These findings provide evidence that the significant blood pressure-lowering effects of renal pelvic denervation are durable and safe for at least 1 year and provide the basis for a pivotal randomized blinded trial to further define the safety and effectiveness of this procedure.

Background: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent.

Objectives: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients.

Methods: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis.

Results: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders.

Conclusions: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.

Introduction: The chemokine receptor CCR4 is expressed by diverse CD4+ T cell subsets including regulatory T cells (Tregs) but its functional importance for leukocyte recruitment and the relevance of its two corresponding chemokines CCL17 and CCL22 have not been studied in immune-mediated crescentic glomerulonephritis (cGN).

Methods: Utilizing the single-cell RNA sequencing (scRNAseq) data in analyzing leukocytes isolated from both human and murine nephritic kidneys, we identified CCL17 as a potential therapeutic target in immune-mediated renal disease. Using a mouse model of murine cGN, we then delineated the effects of targeting CCL17 by neutralizing antibodies and in Ccl17 gene-deficient mice.

Results: Unsupervised scRNAseq analyses identified the CCL17-CCR4 axis as a mechanism potentially involved in renal T-cell migration. Analyses of functional kidney impairment and histopathological kidney damage revealed an attenuation of crescentic GN in anti-CCL17 antibody-treated mice which was corroborated using in Ccl17 gene-deficient mice. Immunohistochemical analyses revealed that these changes were accompanied by an affected renal Treg recruitment in both experimental approaches.

Conclusion: The chemokine receptor CCR4 and its corresponding chemokine CCL17 are expressed in human and murine cGN and targeting the CCR4-CCL17 axis by neutralizing antibodies as well as Ccl17 gene deficiency led to increased renal Treg recruitment and reduced histological and functional kidney damage in murine cGN.

Introduction: The aim of this study was to explore the renoprotective effects of Klotho on podocyte injury mediated by complement activation and autoantibodies in idiopathic membranous nephropathy (IMN).

Methods: Rat passive Heymann nephritis (PHN) was induced as an IMN model. Urine protein levels, serum biochemistry, kidney histology, and podocyte marker levels were assessed. In vitro, sublytic podocyte injury was induced by C5b-9. The expression of Klotho, transient receptor potential channel 6 (TRPC6), and cathepsin L (CatL); its substrate synaptopodin; and the intracellular Ca2+ concentration were detected via immunofluorescence. RhoA/ROCK pathway activity was measured by an activity quantitative detection kit, and the protein expression of phosphorylated-LIMK1 (p-LIMK1) and p-cofilin in podocytes was detected via Western blotting. Klotho knockdown and overexpression were performed to evaluate its role in regulating the TRPC6/CatL pathway.

Results: PHN rats exhibited proteinuria, podocyte foot process effacement, decreased Klotho and Synaptopodin levels, and increased TRPC6 and CatL expression. The RhoA/ROCK pathway was activated by the increased phosphorylation of LIMK1 and cofilin. Similar changes were observed in C5b-9-injured podocytes. Klotho knockdown exacerbated podocyte injury, while Klotho overexpression partially ameliorated podocyte injury.

Conclusion: Klotho may protect against podocyte injury in IMN patients by inhibiting the TRPC6/CatL pathway. Klotho is a potential target for reducing proteinuria in IMN patients.

Introduction: Peritoneal dialysis-associated peritonitis (PDAP) is a serious complication of peritoneal dialysis, associated with significant morbidity, modality transition, and mortality. Here, we provide an update on the national burden of this significant complication, highlighting trends in demographics, treatment practices, and in-hospital outcomes of PDAP from 2016 to 2020.

Methods: Utilizing a national all-payer dataset of hospitalizations in the USA, we conducted a retrospective cohort study of adult hospitalizations with a primary diagnosis of PDAP from 2016 to 2020. We analyzed demographic, clinical, and hospital-level data, focusing on in-hospital mortality, PD catheter removal, length of stay, and healthcare expenses. Multivariable logistic regression adjusted for demographic and clinical covariates was employed to identify risk factors associated with adverse outcomes.

Results: There was a stable burden of annual PDAP admissions from 2016 to 2020. Healthcare expenditures associated with PDAP were high, totaling over USD 75,000 per admission. Additionally, our data suggest geographic inconsistencies in treatment patterns, with treatment at western and teaching hospitals associated with increased rates of catheter removal relative to northeastern and non-teaching centers and a mean cost of nearly USD 55,000 more in Western states compared to Midwest states. 23.2% of episodes resulted in the removal of the PD catheter. Risk factors associated with adverse outcomes included older age, higher Charlson comorbidity index scores, peripheral vascular disease, and the need for vasopressors.

Conclusion: PDAP is a major cause of mortality among PD patients, and there is a vital need for future studies to examine the impact of hospital location and teaching status on PDAP outcomes, which can inform treatment practices and resource allocation.

Introduction: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs.

Methods: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278).

Results: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563).

Conclusion: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.