Protective effect of Cyclo(His-Pro) on peritoneal fibrosis through regulation of HDAC3 expression.

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.

Comparison of the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in CKD patients: an rs-fMRI study.

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease. METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups. RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen. CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

Peritoneal Dialysis Catheter Complications after Insertion by Surgeons, Radiologists, or Nephrologists.

SIGNIFICANCE STATEMENT: The Advancing American Kidney Health Initiative aims to increase rates of utilization of peritoneal dialysis (PD) in the United States. One of the first steps to PD is successful catheter placement, which can be performed by surgeons, interventional radiologists, or nephrologists. We examined the association between operator subspecialty and risk of needing a follow-up procedure in the first 90 days after initial PD catheter implantation. Overall, we found that 15.5% of catheters required revision, removal, or a second catheter placement within 90 days. The odds of requiring a follow-up procedure was 36% higher for interventional radiologists and 86% higher for interventional nephrologists compared with general surgeons. Further research is needed to understand how to optimize the function of catheters across different operator types. BACKGROUND: The US government has implemented incentives to increase the use of PD. Successful placement of PD catheters is an important step to increasing PD utilization rates. Our objective was to compare initial outcomes after PD catheter placement by different types of operators. METHODS: We included PD-naïve patients insured by Medicare who had a PD catheter inserted between 2010 and 2019. We examined the association between specialty of the operator (general surgeon, vascular surgeon, interventional radiologist, or interventional nephrologist) and odds of needing a follow-up procedure, which we defined as catheter removal, replacement, or revision within 90 days of the initial procedure. Mixed logistic regression models clustered by operator were used to examine the association between operator type and outcomes. RESULTS: We included 46,973 patients treated by 5205 operators (71.1% general surgeons, 17.2% vascular surgeons, 9.7% interventional radiologists, 2.0% interventional nephrologists). 15.5% of patients required a follow-up procedure within 90 days of the initial insertion, of whom 2.9% had a second PD catheter implanted, 6.6% underwent PD catheter removal, and 5.9% had a PD catheter revision within 90 days of the initial insertion. In models adjusted for patient and operator characteristics, the odds of requiring a follow-up procedure within 90 days were highest for interventional nephrologists (HR, 1.86; 95% confidence interval [CI], 1.56 to 2.22) and interventional radiologists (odds ratio, 1.36; 95% CI, 1.17 to 1.58) followed by vascular surgeons (odds ratio, 1.06; 95% CI, 0.97 to 1.14) compared with general surgeons. CONCLUSIONS: The probability of needing a follow-up procedure after initial PD catheter placement varied by operator specialty and was higher for interventionalists and lowest for general surgeons.

Inhibition of STAT3 by S3I-201 suppress peritoneal fibroblast phenotype conversion and alleviate peritoneal fibrosis.

Peritoneal fibrosis is a common pathological response to long-term peritoneal dialysis (PD) and a major cause for PD discontinuation. Understanding the cellular and molecular mechanisms underlying the induction and progression of peritoneal fibrosis is of great interest. In our study, in vitro study revealed that signal transducer and activator of transcription 3 (STAT3) is a key factor in fibroblast activation and extracellular matrix (ECM) synthesis. Furthermore, STAT3 induced by IL-6 trans-signalling pathway mediate the fibroblasts of the peritoneal stroma contributed to peritoneal fibrosis. Inhibition of STAT3 exerts an antifibrotic effect by attenuating fibroblast activation and ECM production with an in vitro co-culture model. Moreover, STAT3 plays an important role in the peritoneal fibrosis in an animal model of peritoneal fibrosis developed in mice. Blocking STAT3 can reduce the peritoneal morphological changes induced by chlorhexidine gluconate. In conclusion, our findings suggested STAT3 signalling played an important role in peritoneal fibrosis. Therefore, blocking STAT3 might become a potential treatment strategy in peritoneal fibrosis.

Empagliflozin attenuates epithelial-to-mesenchymal transition through senescence in peritoneal dialysis.

Epithelial-to-mesenchymal transition (EMT) is considered as one of the senescence processes; reportedly, antisenescence therapies effectively reduce EMT. Some models have shown antisenescence effects with the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor. Therefore, our study investigated the antisenescence effects of empagliflozin as an SGLT2 inhibitor in a peritoneal fibrosis model and their impact on EMT inhibition. For in vitro study, human peritoneal mesothelial cells (HPMCs) were isolated and grown in a 96-well plate. The cell media were exchanged with serum-free M199 medium with d-glucose, with or without empagliflozin. All animal experiments were carried out in male mice. Mice were randomly classified into three treatment groups based on peritoneal dialysis (PD) or empagliflozin. We evaluated changes in senescence and EMT markers in HPMCs and PD model. HPMCs treated with glucose transformed from cobblestone to spindle shape, resulting in EMT. Empagliflozin attenuated these morphological changes. Reactive oxygen species production, DNA damage, senescence, and EMT markers were increased by glucose treatment; however, cotreatment with glucose and empagliflozin attenuated these changes. For the mice with PD, an increase in thickness, collagen deposition, staining for senescence, or EMT markers of the parietal peritoneum was observed, which, however, was attenuated by cotreatment with empagliflozin. p53, p21, and p16 increased in mice with PD compared with those in the control group; however, these changes were decreased by empagliflozin. In conclusion, empagliflozin effectively attenuated glucose-induced EMT in HPMCs through a decrease in senescence. Cotreatment with empagliflozin improved peritoneal thickness and fibrosis in PD.NEW & NOTEWORTHY Epithelial-to-mesenchymal transition (EMT) is considered one of the senescence processes. Antisenescence therapies may effectively reduce EMT in peritoneal dialysis models. Human peritoneal mesothelial cells treated with glucose show an increase in senescence and EMT markers; however, empagliflozin attenuates these changes. Mice undergoing peritoneal dialysis exhibit increased senescence and EMT markers, which are decreased by empagliflozin. These findings suggest that empagliflozin may emerge as a novel strategy for prevention or treatment of peritoneal fibrosis.

Development of PD in lower-income countries: a rational solution for the management of AKI and ESKD.

It is estimated that >50% of patients with end-stage kidney disease (ESKD) in low-resource countries are unable to access dialysis. When hemodialysis is available, it often has high out-of-pocket expenditure and is seldom delivered to the standard recommended by international guidelines. Hemodialysis is a high-cost intervention with significant negative effects on environmental sustainability, especially in resource-poor countries (the ones most likely to be affected by resultant climate change). This review discusses the rationale for peritoneal dialysis (PD) as a more resource and environmentally efficient treatment with the potential to improve dialysis access, especially to vulnerable populations, including women and children, in lower-resource countries. Successful initiatives such as the Saving Young Lives program have demonstrated the benefit of PD for acute kidney injury. This can then serve as a foundation for later development of PD services for end-stage kidney disease programs in these countries. Expansion of PD programs in resource-poor countries has proven to be challenging for various reasons. It is hoped that if some of these issues can be addressed, PD will be able to permit an expansion of end-stage kidney disease care in these countries.

AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

BACKGROUND: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. METHODS: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. RESULTS: The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. CONCLUSIONS: A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).

2-Deoxy-glucose ameliorates the peritoneal mesothelial and endothelial barrier function perturbation occurring due to Peritoneal Dialysis fluids exposure.

Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal transition (MMT). We investigated whether administration of 2-DG with several PDF affects the permeability of mesothelial and endothelial barrier of the PM. The antifibrotic effect of 2-DG was confirmed by the gel contraction assay with embedded mesothelial (MeT-5A) or endothelial (EA.hy926) cells cultured in Dianeal® 2.5 % (CPDF), BicaVera® 2.3 % (BPDF), Balance® 2.3 % (LPDF) with/without 2-DG addition (0.2 mM), and qPCR for αSMA, CDH2 genes. Moreover, 2-DG effect was tested on the permeability of monolayers of mesothelial and endothelial cells by monitoring the transmembrane resistance (RTM), FITC-dextran (10, 70 kDa) diffusion and mRNA expression levels of CLDN-1 to -5, ZO1, SGLT1, and SGLT2 genes. Contractility of MeT-5A cells in CPDF/2-DG was decreased, accompanied by αSMA (0.17 ± 0.03) and CDH2 (2.92 ± 0.29) gene expression fold changes. Changes in αSMA, CDH2 were found in EA.hy926 cells, though αSMA also decreased under LPDF/2-DG incubation (0.42 ± 0.02). Overall, 2-DG mitigated the PDF-induced alterations in mesothelial and endothelial barrier function as shown by RTM, dextran transport and expression levels of the CLDN-1 to -5, ZO1, and SGLT2. Thus, supplementation of PDF with 2-DG not only reduces MMT but also improves functional permeability characteristics of the PM mesothelial and endothelial barrier.

Peritoneal dialysis promotes microbial-driven biosynthesis pathways of sesquiterpenes and triterpenes compounds in end-stage renal disease patients.

The concept of the gut-kidney axis is gaining significant attention due to the close relationship between gut microbiota and kidney disease. Peritoneal dialysis is recognized as a crucial renal replacement therapy for end-stage renal disease (ESRD). The alterations in gut microbiota and related mechanisms after receiving this dialysis method are not fully understood. This study conducted shotgun metagenomic sequencing on fecal samples from 11 end-stage renal disease patients who did not receive dialysis (ESRD_N) and 7 patients who received peritoneal dialysis (ESRD_P). After quality control and correlation analysis of the data, our study is aimed at exploring the impact of peritoneal dialysis on the gut microbiota and health of ESRD patients. Our research findings indicate that the complexity and aggregation characteristics of gut microbiota interactions increase in ESRD_P. In addition, the gut microbiota drives the biosynthesis pathways of sesquiterpenes and triterpenes in ESRD_P patients, which may contribute to blood purification and improve circulation. Therefore, our research will lay the foundation for the prevention and treatment of ESRD.

Outcomes of Integrated Home Dialysis Care: Results From the Canadian Organ Replacement Register.

RATIONALE & OBJECTIVE: The integrated home dialysis model proposes the initiation of kidney replacement therapy (KRT) with peritoneal dialysis (PD) and a timely transition to home hemodialysis (HHD) after PD ends. We compared the outcomes of patients transitioning from PD to HHD with those initiating KRT with HHD. STUDY DESIGN: Observational analysis of the Canadian Organ Replacement Register (CORR). SETTINGS & PARTICIPANTS: All patients who initiated PD or HHD within the first 90 days of KRT between 2005 and 2018. EXPOSURE: Patients transitioning from PD to HHD (PD+HHD group) versus patients initiating KRT with HHD (HHD group). OUTCOME: (1) A composite of all-cause mortality and modality transfer (to in-center hemodialysis or PD for 90 days) and (2) all hospitalizations (considered as recurrent events). ANALYTICAL APPROACH: A propensity score analysis for which PD+HHD patients were matched 1:1 to (1) incident HHD patients ("incident-match" analysis) or (2) HHD patients with a KRT vintage at least equivalent to the vintage of PD+HHD patients at the transition time ("vintage-matched" analysis). Cause-specific hazards models (composite outcome) and shared frailty models (hospitalization) were used to compare groups. RESULTS: Among 63,327 individuals in the CORR, 163 PD+HHD patients (median of 1.9 years in PD) and 711 HHD patients were identified. In the incident-match analysis, compared to the HHD patients, the PD+HHD group had a similar risk of the composite outcome (HR, 0.88 [95% CI, 0.58-1.32]) and hospitalizations (HR, 1.04 [95% CI, 0.76-1.41]). In the vintage-match analysis, PD+HHD patients had a lower hazard for the composite outcome (HR, 0.61 [95% CI, 0.40-0.94]) but a similar hospitalization risk (HR, 0.85 [95% CI, 0.59-1.24]). LIMITATIONS: Risk of survivor bias in the PD+HHD cohort and residual confounding. CONCLUSIONS: Controlling for KRT vintage, the patients transitioning from PD to HHD had better clinical outcomes than the incident HHD patients. These data support the use of integrated home dialysis for patients initiating home-based KRT. PLAIN-LANGUAGE SUMMARY: The integrated home dialysis model proposes the initiation of dialysis with peritoneal dialysis (PD) and subsequent transition to home hemodialysis (HHD) once PD is no longer feasible. It allows patients to benefit from initial lifestyle advantages of PD and to continue home-based treatments after its termination. However, some patients may prefer to initiate dialysis with HHD from the outset. In this study, we compared the long-term clinical outcomes of both approaches using a large Canadian dialysis register. We found that both options led to a similar risk of hospitalization. In contrast, the PD-to-HHD model led to improved survival when controlling for the duration of kidney failure.

Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association of clinical factors, including prior treatment with HD, with PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc (DCI) outpatient facility between January 1, 2010, and September 30, 2019. EXPOSURE: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOME: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5,224 patients who initiated PD at a DCI facility, 3,174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1,108 transitioned beyond 90 days ("PD-late"); 1,472 (28%) subsequently transferred from PD to HD. The PD-early and PD-late patients had a higher risk of transfer to HD as compared with PD-first patients (in the first 9 months: adjusted hazard ratio [AHR], 1.51 [95% CI, 1.17-1.96] and 2.41 [95% CI, 1.94-3.00], respectively; and after 9 months: AHR, 1.16 [95% CI, 0.99-1.35] and AHR, 1.43 [95% CI, 1.24-1.65], respectively). More peritonitis episodes, fewer home visits, lower serum albumin levels, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is an important kidney replacement modality with several potential advantages compared with in-center hemodialysis (HD). However, a substantial number of patients transfer to in-center HD early on, without having experienced the quality-of-life and other benefits that come with sustained maintenance of PD. Using retrospective data from a midsize national dialysis provider, we found that initiating dialysis with PD is associated with longer maintenance of PD, compared with initiating dialysis with HD and a later switch to PD. However, many of those who initiate PD-late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower small protein removal are other risk factors for PD-to-HD transfer that may be amenable to intervention.

Recent Advances in Kidney Replacement Therapy in Infants: A Review.

Kidney replacement therapy (KRT) is used to treat children and adults with acute kidney injury (AKI), fluid overload, kidney failure, inborn errors of metabolism, and severe electrolyte abnormalities. Peritoneal dialysis and extracorporeal hemodialysis/filtration can be performed for different durations (intermittent, prolonged intermittent, and continuous) through either adaptation of adult devices or use of infant-specific devices. Each of these modalities have advantages and disadvantages, and often multiple modalities are used depending on the scenario and patient-specific needs. Traditionally, these therapies have been challenging to deliver in infants due the lack of infant-specific devices, small patient size, required extracorporeal volumes, and the risk of hemodynamic stability during the initiation of KRT. In this review, we discuss challenges, recent advancements, and optimal approaches to provide KRT in hospitalized infants, including a discussion of peritoneal dialysis and extracorporeal therapies. We discuss each specific KRT modality, review newer infant-specific devices, and highlight the benefits and limitations of each modality. We also discuss the ethical implications for the care of infants who need KRT and areas for future research.

Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

Impact of Parathyroidectomy Versus Oral Cinacalcet on Bone Mineral Density in Patients on Peritoneal Dialysis With Advanced Secondary Hyperparathyroidism: The PROCEED Pilot Randomized Trial.

RATIONALE & OBJECTIVE: Parathyroidectomy and calcimimetics have been used to reduce fracture risk in patients with kidney failure and advanced secondary hyperparathyroidism (SHPT), but direct comparisons of these treatment approaches have not been implemented. This pilot study compared their effects on bone mineral density (BMD) in this patient population. STUDY DESIGN: A prospective pilot open-label randomized trial. SETTING & PARTICIPANTS: 65 patients receiving maintenance peritoneal dialysis with advanced SHPT recruited from 2 university-affiliated hospitals in Hong Kong. INTERVENTIONS: Total parathyroidectomy with forearm autografting versus oral cinacalcet treatment for 12 months. OUTCOME: Prespecified secondary end points including changes in BMD z and T scores of femoral neck, lumbar spine, and distal radius 12 months after treatment initiation and also categorized as osteopenia or osteoporosis according to the World Health Organization. RESULTS: Both total parathyroidectomy and cinacalcet significantly improved BMD of the lumbar spine and femoral neck over 12 months, but the total parathyroidectomy group had a greater increase than the cinacalcet-treated group (P<0.001). The proportion of study participants classified as having osteopenia/osteoporosis by femoral neck T-score fell from 78.2% to 51.7% in the total parathyroidectomy group (P<0.001) and from 65.7% to 52.0% in cinacalcet-treated group after 12 months (P=0.7). The proportion of participants with a T-score at the lumbar spine classified as osteopenia/osteoporosis fell from 53.1% to 31.0% in the total parathyroidectomy group (P=0.01) and from 59.4% to 53.8% with cinacalcet (P=0.3). No significant change was observed in BMD T or z score of the distal radius over 12 months with either intervention. LIMITATIONS: Bone histology was not assessed, and the study duration was 12 months. CONCLUSIONS: A large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Total parathyroidectomy increased the BMD of the lumbar spine and femoral neck and reduced osteopenia/osteoporosis more than oral cinacalcet. FUNDING: Grants from academic (The University of Hong Kong Research) and not-for-profit (Hong Kong Society of Nephrology) entities. REGISTRATION: Registered at Clinicaltrials.gov with study number NCT01447368. PLAIN-LANGUAGE SUMMARY: It is not known whether oral cinacalcet and surgical parathyroidectomy differ in their effects on bone parameters in patients with advanced secondary hyperparathyroidism (SHPT) receiving peritoneal dialysis. This pilot randomized trial evaluated the effect of medical versus surgical therapy on bone mineral densities (BMD) as prespecified secondary study end points. The findings showed that a large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Parathyroidectomy increased the BMD of the lumbar spine and femoral neck more than cinacalcet over 12 months. Parathyroidectomy reduced the proportion of patients with osteopenia/osteoporosis at the lumbar spine and femoral neck more than cinacalcet after 12 months. Neither intervention led to an increase in the BMD of the distal radius over 12 months.

The prevalence of HIV resistance mutations and their influence on the shedding of HIV-1 into peritoneal dialysis effluent.

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end-stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV-1 into peritoneal dialysis (PD) effluents. This cross-sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD, collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV-1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartile range [IQR], 38.0-47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5-11) years. Among participants with detectable HIV-1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV-1 (p = 0.001) with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels (ρ = 0.649, p < 0.001), T-cell CD4 count (ρ = -0370, p < 0.004), serum creatinine (ρ = -0.396, p < 0.002), and white blood cell count (ρ = -0.294, p < 0.023) levels were significant factors correlated with the detection of HIV-1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001) were also significantly correlated with detection of HIV-1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T-cell CD4 count were correlated with HIV-1 shedding into PD effluents.

High Osmol Gap Hyponatremia Caused by Icodextrin: A Case Series Report.

Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.

Effect of End-Stage Renal Disease Prospective Payment System on Utilization of Peritoneal Dialysis in Patients with Kidney Allograft Failure.

INTRODUCTION: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown. METHODS: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience. RESULTS: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience. CONCLUSION: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure.

Trends, Outcomes, and Economic Implications of Peritoneal Dialysis-Associated Peritonitis Hospitalizations: A National Cohort Study.

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.

Autonomic Nervous System Dysfunction in Peritoneal Dialysis Patients: An Underrecognized Cardiovascular Risk Factor?

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.

Availability and Quality of Dialysis Care in Rural versus Urban US Counties.

INTRODUCTION: Rural areas face significant disparities in dialysis care compared to urban areas due to limited access to dialysis facilities, longer travel distances, and a shortage of healthcare professionals. The objective of this study was to conduct a national examination of rural-urban differences in quality of dialysis care offered across counties in the USA. METHODS: Data were gathered from Medicare-certified dialysis facilities in 2020 from the Centers for Medicare and Medicaid Services website. To identify high-need counties, county-level estimated crude prevalence of diabetes in adults was obtained from the 2022 CDC PLACES data portal. Our analysis reviewed 3,141 counties in the USA. The primary outcome measured was whether the county had a dialysis facility. Among those counties that had a dialysis facility, additional outcomes were the average star rating, whether peritoneal dialysis was offered, and whether home dialysis was offered. RESULTS: The type of services offered by dialysis facilities varied significantly, with peritoneal dialysis being the most commonly offered service (50.8%), followed by home hemodialysis (28.5%) and late-shift services (16.0%). These service availabilities are more prevalent in urban facilities than in rural facilities. The Centers for Medicare and Medicaid Services Five Star Quality ratings were quite different between urban and rural facilities, with 40.4% of rural facilities having a ranking of five, compared to 27.1% in urban. CONCLUSION: The majority of rural counties lack a single dialysis facility. Counties with high rates of chronic kidney disease, diabetes, and blood pressure, deemed high need, were less likely to have a highly rated dialysis facility. The findings can be used to further inform targeted efforts to increase diabetes educational programming and design appropriate interventions to those residing in rural communities and high-need counties who may need it the most.