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Peritoneal ultrafiltration failure is a common reason for peritoneal dialysis (PD) withdrawal as well as mortality in PD patients. Based on the three-pore system, inter-cellular small pores and trans-cellular ultra-small pores (aquaporin-1) are mainly responsible for water transfer across the peritoneum. Both small and ultra-small pores-dependent water (free water) transport decline accompanied with time on PD, with more significant decrease in free water, resulting in peritoneal ultrafiltration failure. The reduction of free water transport is associated with fast peritoneal solute transfer, reduced crystalloid osmotic gradient due to increased interstitial glucose absorption, and declined osmotic conductance to glucose resulted from impaired aquaporin-1 function and peritoneal interstitial fibrosis. The decline of small pore-based water is mainly because of fast loss of crystalloid osmotic gradient, decrease of hydrostatic pressure mediated by peritoneal vasculopathy, as well as reduced absolute number of small pores. The current review discusses the advance on pathogenesis of acquired peritoneal ultrafiltration failure in long-term PD.
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Objective:To evaluate the influencing factors of carotid-femoral pulse wave velocity (CF-PWV) and its value to predict outcomes in peritoneal dialysis (PD) patients.Methods:Eligible patients undergoing PD in Renji Hospital of Shanghai Jiao Tong University between August 2016 and July 2018 were recruited and prospectively followed up until death, PD cessation, or to the end of the study. CF-PWV was measured by an arterial pulse wave velocity meter to assess arterial stiffness (July 31, 2020). Overhydration was measured by bioimpedance spectroscopy. The patients were divided into CF-PWV≤10 m/s group and CF-PWV>10 m/s group according to the measured value of CF-PWV. The influencing factors of elevated CF-PWV were analyzed by multivariate logistic regression. Survival curves were generated using the Kaplan-Meier method and multivariate Cox proportional hazards models were used to analyze the difference for all-cause mortality and cardiovascular disease (CVD) mortality between the two groups.Results:A total of 224 PD patients were enrolled, including 133 males (59.4%). The age was (55.2±13.4) years old, and median PD vintage was 22.3(6.5, 59.3) months. Among them, 47(21.0%) patients were comorbid with diabetes, and 37(16.5%) patients had CVD history. The median CF-PWV was 9.6(8.4, 11.4) m/s for the cohort, and 105(46.9%) participants had CF-PWV over 10 m/s. Compared with CF-PWV≤10 m/s group, CF-PWV>10 m/s group patients had older age, increased percentage of diabetes and CVD (all P<0.05). Multivariate logistic analysis showed that increased age ( OR=1.070, 95% CI 1.043-1.099, P<0.001), diabetes ( OR=3.693, 95% CI 1.646-8.287, P=0.002) and higher overhydration ( OR=1.238, 95% CI 1.034-1.483, P=0.020) were independent influencing factors for elevated CF-PWV in PD patients. After followed up for 37.4(25.6, 41.7) months, 24 patients died, including 19 cases of CVD-related deaths. Kaplan-Meier survival analysis showed that all-cause mortality and CVD mortality were significantly higher in the CF-PWV>10 m/s group than those in CF-PWV≤10 m/s group (Log-rank χ2=6.423, P=0.011; Log-rank χ2=6.243, P=0.012, respectively). Multivariate Cox proportional hazards models showed that increased age was an independent influencing factor for both all-cause mortality and CVD mortality ( HR=1.057, 95% CI 1.010-1.107, P=0.018; HR=1.062, 95% CI 1.009-1.118, P=0.022). Conclusions:Increased arterial stiffness is relatively common in PD patients. Higher CF-PWV in PD patients is associated with increased age, diabetes and higher overhydration, and it is probably a valuable predictor of outcome in PD patients.
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Objective To investigate the prevalence and risk factors of sarcopenia in peritoneal dialysis (PD) patients.Methods The patients who underwent regular peritoneal dialysis at Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between November 2016 and March 2018 were enrolled.Handgrip strength (HGS) was measured to assess muscle strength.Bioelectrical impedance spectroscopy (BIS) was applied to measure the lean tissue index (LTI).Reduced LTI plus decreased HGS was defined as sarcopenia.The prevalence of sarcopenia in PD patients was evaluated.According to the presence or absence of sarcopenia,they were divided into the sarcopenia group and the non-sarcopenia group,and the differences in clinical indicators between the two groups were compared.Multivariate logistic regression was used to explore the risk factors of sarcopenia in PD patients.Results A total of 207 patients were enrolled in the study with age of (55.3±13.7) years and a median PD duration of 22.9(7.3,60.9) months.Of them,122 patients (58.9％) were male,45 patients (21.7％) had diabetics and 32 patients (15.5％) suffered from cardiovascular diseases.There were 27 patients (13.0％) diagnosed with sarcopenia.These patients presented with longer PD duration,more prevalent diabetics,lower residual renal function (RRF) and serum pre-albumin,greater ratio of extracellular water to intracellular water (ECW/ICW) and high sensitive C-reactive protein in contrast with those in the non-sarcopenia group (all P ＜ 0.05).Multivariate logistic analysis showed that male (OR=3.94,95％ CI 1.35-11.50,P=0.O12),longer PD duration (OR=1.01,95％CI 1.00-1.02,P=0.029) and higher ECW/ICW (OR=1.09,95％CI 1.05-1.14,P ＜ 0.001) were independent risk factors of sarcopenia in PD patients.Conclusions Sarcopenia is common in PD patients.Male,longer PD duration and higher ECW/ICW were independent risk factors of sarcopenia in PD patients.
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Objective To investigate the incidence of left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients with different hydration statuses,and analyze the risk factors of LVH in PD patients.Methods PD patients in Renji Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled.Demographic data of patients were collected and biochemical parameters were measured.Hydration status index overhydration (OH) was measured by bioimpedance spectroscopy,and LVH was diagnosed by echocardiography.Logistic regression was used to analyze the risk factors of LVH.Results A total of 113 PD patients aged 58.98(48.89,65.33) years with median PD duration 46.20(18.08,72.75) months were enrolled in present study,among whom 60 patients (53.1％) had LVH.OH ＞ 1.1 L was detected in 80 patients (70.8％),among whom 34 patients (42.5％) had subclinical overhydration (SCOH).LVH was however diagnosed in 33(71.7％) clinical overhydrated (COH) patients and 17(50.0％) SCOH patients (n=34).In the normal hydrated (OH≤1.1 L) patients (n=33),LVH was detected in 10 patients (30.3％).Multivariate logistic regression showed that high OH (OR=1.730,95％CI 1.274-2.348,P ＜ 0.001) and low hemoglobin (OR=0.965,95％CI 0.940-0.991,P=0.008) were the independent risk factors of LVH.Conclusions LVH is common in PD patients,especially in overhydrated patients.High OH and low hemoglobin were the independent risk factors of LVH.
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Objective · To explore influencing factors associated with the hydration status in peritoneal dialysis (PD) patients.Methods · Eligible PD patients treated in Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine from September 2016 to January 2017 were enrolled.Demographic data of patients were collected and biochemical indexes were measured.Their peritoneal transport characteristics and dialysis adequacy were evaluated.Hydration status index overhydration (OH) value was measured with bioimpedance spectroscopy.Multivariate linear regression was used to analyze the independent factors associated with the OH.Results · A total of 147 PD patients with a median age of 58.52 years and a median PD duration of 43.03 months were enrolled.Of them,90 (61.2％) were male,21(14.3％) were accompanied by diabetes mellitus,and 107 (72.8％)were overhydrated (OH＞1.1L).Compared to those with normal hydration status (OH ≤ 1.1 L),the overhydrated patients had higher proportion of diabetes,BSA,Charlson comorbidity score,brain natriuretic peptide (BNP),4 h D/Pcr,and 24 h dialysate protein,and lower tKt/V,serum albumin than the normal hydrated patients (all P＜0.05).Multivariate linear regression showed that comorbid diabetes mellitus (P=0.000),higher 4h D/Pcr (P=0.000),and lower serum albumin level (P=0.001) were independent relevant factors for the increase of OH.Conclusion· Overhydration is common in PD patients.Comorbid diabetes mellitus,higher 4 h D/Pcr,and lower serum albumin are independent relevant factors for the hydration status in PD patients.
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Objective By simulating a high-glucose condition of peritoneal dialysis (PD)fluid,to explore the effect of high glucose on the expression of leptin and its relationship with peritoneal angiogenesis.Methods Adipocytes differentiated from 3T3-L1 were divided into high glucose group (139 mmol/l glucose) and high mannitol group.Leptin levels in supernatant collected at 0 h,12 h,24 h and 48 h were measured by ELISA.Endothelial cells (ECs) were respectively cultured with normal glouse,high glucose,high mannitol condition,supernatants of adipocyte induced by normal glouse,high glucose and high mannitol,high glucose supernatants+leptin antibody,and high mannitol supernatants + leptin antibody.Tubular structure formation and migration of ECs were detected.Results Adipocytes exposed to high glucose for 48 h produced more leptin as compared with control group,high mannitol group,12 h-high glucose group and 24 h-high glucose group (all P ＜ 0.05).Compared with ECs in normal group,ECs in high glucose had less tubular structure formation and increased migration (all P ＜ 0.01).Compared with those of ECs in high glucose,the tubular structure formation and the migration of ECs in adipocyte supernatants induced by high glucose had increased (all P ＜ 0.01),and these effects were reduced by leptin antibody (all P ＜ 0.01).Conclusion There is an up-regulation of leptin in adipocytes exposed to high glucose,which may be an alternative way to prevent peritoneal angiogenesis.
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Objective To explore the effect of soluble tyrosine kinase 2 fusion protein (sTie-2-Fc) on peritoneal angiogenesis, solute transport and ultrafi]tration capacity in uremic rats undergoing peritoneal dialysis (PD). Methods Thirty-two male Wistar rats were randomly divided into sham-operation group, uremic group, uremic PD group, and sTie-2-Fc group (all n=8).Uremic PD group and sTie-2-Fc group received intraperitoneal infusion of 3 ml/100 g of peritoneal dialysis fluid (PDF) containing 4.25% glucose twice daily for 4 weeks. Rats in sTie-2-Fc group were infused with PDF supplemented with 1 μg sTie-2-Fc. Before the rats were sacrificed, a peritoneal equilibration test (PET) was performed to evaluate the peritoneal solute transport and ultrafiltration capacity, and omenta was obtained for anti-CD31 immunohistochemical staining to determine the vessel density. Results Compared to their counterparts in sham-operation group,rats in uremic group had higher 2 h-dialysate to plasma creatinine concentration ratio (D/Pcr, 0.78±0.05 vs 0.70±0.09, P=0.028), lower 2 h to initial dialysate glucose concentration ratio (D/D0, 0.69±0.05 vs 0.76±0.07, P=0.033), decreased peritoneal ultrafiltration [UF, (2.29±0.50) ml vs (4.58±1.64) ml, P=0.005], and increased omental vessel density [(5.8±3.0)/HP vs (1.6±0.5)/HP, P＜0.01]. When compared to uremic group, rats in uremic PD group showed higher D/Pcr (0.89±0.05 vs 0.78±0.05, P=0.001), lower D/D0 (0.47±0.09 vs 0.69±0.05, P＜0.01), decreased UF [(0.40±0.59) ml vs (2.29±0.50) mi, P=0.005] and more omental vessels [(16.7±1.2)/HP vs (5.8±3.0)/HP, P＜0.01]. Improved peritoneal UF [(1.56±0.48) ml vs (0.40±0.59) mi, P=0.014] and decreased omental vessels [(9.2± 1.2)/HP vs (16.7 ± 1.2)/HP, P＜0.01] were observed in rats treated with sTie-2-Fc compared with those in uremic PD group, however, the differences of D/Pcr (0.87±0.06 vs 0.89±0.05, P=0.122) and D/D0 (0.60±0.11 vs 0.47±0.09, P=0.06) between these two groups did not reach statistical significance. Conclusion sTie-2-Fc preserves peritoneal ultrafiltration capacity and ameliorates peritoneal angiogenesis caused by uremia and exposure to bioincompatibal PDF.
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Objective To investigate the association between angiopoietin-2 (Angpt-2) and peritoneal angiogenesis in a uremic peritoneal dialysis (PD) rat model. Methods Uremic (subtotal nephrectomy) rats were established and divided into non-PD, 10 d-PD, 28 d-PD and 56 d-PD groups. Standard PD solution was applied in the study. Rats undergone sham operation without PD were used as control group. Vessel density of the peritoneum was detected and quantified with anti-CD31 immunohistochemical staining. Expressive levels of Angpt-2 and vascular endothelial growth factor (VEGF) were examined in the peritoneum by real-time PCR and Western blotting. Results The non-PD group was characterized by increased vessel density in the peritoneum compared with that of the control group [(5±3)/HP vs (1±1)/HP]. Progressive angiogenesis was found in 10 d-PD, 28 d-PD and 56 d-PD groups [(10±5)/HP, (17±5)/HP, (19±4)/HP]. Furthermore, expressive levels of Angpt-2 and VEGF increased significantly in the non-PD group compared with the control (P<0.01), and such expressions were significantly higher in the PD groups as compared to non-PD group (P<0.01), but no difference was found among the PD groups. Both VEGF and Angpt-2 levels were positively correlated with vessel density(r=0.7756, P<0.01; r=0.5223, P<0.05). Conclusions Uremia and PD promote peritoneal angiogenesis in rats. Increased expression level of Angpt-2 in peritoneum is positively correlated with peritoneal angiogenesis. Angpt-2 may be a new therapeutic target of peritoneal angiogenesis.