We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients.
We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2±0.1×106 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), interleukin-6(IL-6), IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-β), smooth muscle actin (𝛼-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24.
Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-β, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study.
Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies.

[This corrects the article DOI: 10.3389/fphys.2022.885802.].

Long-term peritoneal dialysis as currently performed, causes structural and functional alterations of the peritoneal dialysis membrane. This decay is brought about by the continuous exposure to commercially available glucose-based dialysis solutions. This review summarizes our knowledge on the peritoneum in the initial phase of PD, during the first 2 years and the alterations in function and morphology in long-term PD patients. The pseudohypoxia hypothesis is discussed and how this glucose-induced condition can be used to explain all peritoneal alterations in long-term PD patients. Special attention is paid to the upregulation of hypoxia inducing factor-1 and the subsequent stimulation of the genes coding for glucose transporter-1 (GLUT-1) and the growth factors transforming growth factor-β (TGFβ), vascular endothelial growth factor (VEGF), plasminogen growth factor activator inhibitor-1 (PAI-1) and connective tissue growth factor (CTGF). It is argued that increased pseudohypoxia-induced expression of GLUT-1 in interstitial fibroblasts is the key factor in a vicious circle that augments ultrafiltration failure. The practical use of the protein transcripts of the upregulated growth factors in peritoneal dialysis effluent is considered. The available and developing options for prevention and treatment are examined. It is concluded that low glucose degradation products/neutral pH, bicarbonate buffered solutions with a combination of various osmotic agents all in low concentration, are currently the best achievable options, while other accompanying measures like the use of RAAS inhibitors and tamoxifen may be valuable. Emerging developments include the addition of alanyl glutamine to the dialysis solution and perhaps the use of nicotinamide mononucleotide, available as nutritional supplement.

暂无摘要。

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long-term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP-7 levels markedly increased in the patients with PD, and the elevated MMP-7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP-7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP-7 activated mitogen-activated protein kinases (MAPKs)-extracellular signal-regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin-1 (AQP-1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP-7-mediating AQP-1 up-regulation and cellular homeostasis. In summary, all the findings indicate that MMP-7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP-7 might be a non-invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.

BACKGROUND: The number of patients on peritoneal dialysis (PD) in our hospital has increased during the past 5 years, but the number discontinuing PD has also increased. The purpose of this study was to identify the risk factors for PD discontinuation by analyzing the association between technical survival period (defined as the duration of PD) and various clinical factors.
METHODS: We retrospectively investigated 87 patients who were started on PD at our hospital and attended regularly from April 2015 to March 2020, and we analyzed the association between technical survival period and various clinical factors. We also looked for associations between technical survival period and hospitalizations for heart failure, peritonitis, and exit-site infections among patients undergoing PD.
RESULTS: The patients using renin-angiotensin-aldosterone system inhibitors (RASi) (P = 0.0218), those with left ventricular ejection fraction (LVEF) > 50% (P = 0.0194) when they started PD, and those with estimated glomerular filtration rate (eGFR) ≥ 6 (mL/ min/1.73m2) (P = 0.0013) at the initiation of PD showed significantly longer technical survival period, and those who were hospitalized for heart failure had significantly shorter period (P = 0.0008).
CONCLUSIONS: Treatment of RASi, LVEF > 50% and eGFR ≥ 6 mL/ min/1.73m2 when the initiation of PD and better volume control to prevent ultrafiltration failure and heart failure may improve technical survival period in patients undergoing PD.

Peritoneal dialysis (PD) is an important renal replacement therapy for patients with end-stage renal diseases, which is limited by peritoneal neoangiogenesis leading to ultrafiltration failure (UFF). Vascular endothelial growth factor (VEGF) and its receptors are key angiogenic factors involved in almost every step of peritoneal neoangiogenesis. Impaired mesothelial cells are the major sources of VEGF in the peritoneum. The expression of VEGF will be up-regulated in specific pathological conditions in PD patients, such as with non-biocompatible peritoneal dialysate, uremia and inflammation, and so on. Other working cells (i.e. vascular endothelial cells, macrophages and adipocytes) can also stimulate the secretion of VEGF. Meanwhile, hypoxia and activation of complement system further aggravate peritoneal injury and contribute to neoangiogenesis. There are several signalling pathways participating in VEGF-mediated peritoneal neoangiogenesis including tumour growth factor-β, Wnt/β-catenin, Notch and interleukin-6/signal transducer and activator of transcription 3. Moreover, VEGF is highly expressed in dialysate effluent of long-term PD patients and is associated with peritoneal transport function, which supports its role in the alteration of peritoneal structure and function. In this review, we systematically summarize the angiogenic effect of VEGF and evaluate it as a potential target for the prevention of peritoneal neoangiogenesis and UFF. Preservation of the peritoneal membrane using targeted therapy of VEGF-mediated peritoneal neoangiogenesis may increase the longevity of the PD modality for those who require life-long dialysis.

暂无摘要。

Continuous exposure to peritoneal dialysis (PD) fluid results in peritoneal fibrosis and ultimately causes ultrafiltration failure. Noncoding RNAs, including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have been reported to participate in ultrafiltration failure in PD. Therefore, our study aimed to investigate the mechanism of lncRNA 6030408B16RIK in association with miR-326-3p in ultrafiltration failure in PD. Peritoneal tissues were collected from uremic patients with or without PD. A uremic rat model with PD was first established by 5/6 nephrectomy. The relationship between lncRNA 6030408B16RIK, miR-326-3p and WISP2 was identified using luciferase reporter, RNA pull-down and RIP assays. After ectopic expression and depletion treatments in cells, expression of α-SMA, phosphorylated β-catenin, FSP1, E-cadherin and Vimentin was evaluated by RT-qPCR and Western blot analyses, and Collagen III and CD31 expression by immunohistochemistry. Ultrafiltration volume and glucose transport capacity were assessed by the peritoneal equilibration test. Expression of lncRNA 6030408B16RIK and WISP2 was up-regulated and miR-326-3p expression was poor in peritoneal tissues of uremic PD patients and model rats. LncRNA 6030408B16RIK competitively bound to miR-326-3p and then elevated WISP2 expression. Silencing of lncRNA 6030408B16RIK and WISP2 or overexpression of miR-326-3p was shown to decrease the expression of α-SMA, phosphorylated β-catenin, FSP1, Vimentin, Collagen III and CD31, while reducing glucose transport capacity and increasing E-cadherin expression and ultrafiltration volume in uremic PD rats. In summary, lncRNA 6030408B16RIK silencing exerts an anti-fibrotic effect on uremic PD rats with ultrafiltration failure by inactivating the WISP2-dependent Wnt/β-catenin pathway via miR-326-3p.

BACKGROUND: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPVSBIA) during the peritoneal dwell.
METHODS: IPVSBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPVSBIA calibration and calculation of instantaneous ultrafiltration volume (UFVSBIA) possible. UFVSBIA was defined as IPVSBIA - 2 L.
RESULTS: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPVSBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFVdrain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFVSBIA (0.55 ± 0.17 L). Peak UFVSBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFVSBIA by 0.49 ± 0.28 L (95% CI: 0.27-0.7) and UFVdrain by 0.52 ± 0.31 L (95% CI: 0.29-0.76), respectively.
CONCLUSIONS: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPVSBIA and identify the time to peak UFVSBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions.