Zanzhe Yu

Determinants of Peritoneal Membrane Function Over Time

Changes to peritoneal membrane function over time result in the development of ultrafiltration failure in a proportion of PD patients and pose a risk for the rarer condition of encapsulating peritoneal sclerosis. These changes are characterized by an increase in the transport rate for small solutes owing to increased vascularity and/or peritoneal blood flow and in more severe cases a reduction in the osmotic conductance of the membrane that likely reflects progressive fibrosis. Both of these processes are preceded by exposure of the membrane to glucose when using conventional dialysis solutions, although this usually is necessitated and likely exacerbated by loss of residual renal function and recurrent peritonitis. Mediators of membrane injury and thus potential biomarkers include inflammatory cytokines, notably local interleukin-6 production, which also appears to determine solute transport characteristics at the start of peritoneal dialysis, local production of vascular endothelial growth factor, and transforming growth factor β-associated epithelial to mesenchymal transition of the mesothelium leading to membrane fibrosis. Low glucose degradation product solutions may ameliorate the mesothelial injury associated with high glucose exposure, but evidence that they prevent or delay changes in membrane function over time is lacking. In the meantime, avoidance of excessive glucose exposure, preservation of residual renal function, and prevention of peritonitis remain the most logical treatment strategies for this problem.

Circulating levels of asymmetric dimethylarginine are an independent risk factor for left ventricular hypertrophy and predict cardiovascular events in pre-dialysis patients with chronic kidney disease.

BACKGROUND Several studies have related the circulating level of asymmetric dimethylarginine (ADMA) to cardiac remodeling and cardiovascular (CV) events in end-stage renal disease (ESRD) patients. Studies investigating this relationship in patients with pre-dialysis chronic kidney disease (CKD) are lacking. METHODS We enrolled 76 CKD patients (age, 46.7+/-14.3 years, 39 females) and 15 controls (age, 40.1+/-18.5 years, 6 females). Clinical parameters, blood biochemistry and echocardiographic findings were recorded, and plasma ADMA concentrations measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Patients were prospectively followed up for a median of 15 (range, 6-24) months. RESULTS Plasma ADMA was significantly elevated in CKD patients compared with controls (41.56+/-12.76 microg/mL vs 17.12+/-7.09 microg/mL, P<0.001), and correlated with the left ventricular mass index (LVMI) (r=0.597, P<0.001). During follow-up, 25 patients experienced new CV events and their plasma ADMA level was significantly elevated (48.27+/-13.70 vs 34.91+/-6.38 in CV event-free patients, P<0.001). Cox regression analysis further confirmed that ADMA was an independent risk factor for CVD (HR=1.175, 95%CI[1.070-1.290], P=0.001). CONCLUSION Similar to findings in ESRD patients, elevated circulating levels of ADMA may increase the risk of LVH and CV events in pre-dialysis CKD patients.

Adiponectin Is Related to Carotid Artery Plaque and a Predictor of Cardiovascular Outcome in a Cohort of Non-Diabetic Peritoneal Dialysis Patients

Aims: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. Methods: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for cardiovascular events. Results: The serum adiponectin concentration was elevated and inversely related to C-reactive protein and interleukin-6 in the patients. The adiponectin level of patients with carotid plaques was significantly lower than in those without plaques (p < 0.01). Kaplan-Meier analysis showed that the cumulative survival without new cardiovascular events was better in patients with higher adiponectin levels than in those with lower adiponectin levels. Conclusion: Serum adiponectin levels are inversely related with markers of systemic inflammation and signs of atherosclerosis which may explain why hyperadiponectinemia in this study was associated with better cardiovascular outcome.

Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients

BACKGROUND Inflammation, hypoalbuminaemia and peritoneal protein clearance are important predictors of survival in patients treated with peritoneal dialysis (PD). We hypothesized that the common link is abnormal endothelial barrier function. To test this, we explored associations between hypoalbuminaemia, systemic albumin leak and soluble markers of systemic inflammation and endothelial injury. METHODS This was a cross-sectional study of 41 prevalent PD patients. Endothelial barrier function was measured as transcapillary escape rate of (125)I albumin [transcapillary escape rate of albumin (TER(alb))]. Seventeen plasma biomarkers including pro-inflammatory cytokines, endothelial biomarkers and metalloproteinases were measured. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) were used to explore the hypothesis. RESULTS The mean TER(alb) was 13.7 ± 8.9 (%/h), higher than in non-uraemic subjects 8.22 ± 5.8 (%/h). Three patient clusters were defined from HCA according to their biomarker patterns. Cluster 1 was characterized by inflammation, hypoalbuminaemia, overhydration and intermediate TER(alb). Cluster 2 was non-inflamed, preserved muscle mass and more normal TER(alb). Cluster 3 had highest TER(alb), platelet activation, preserved plasma albumin and intermediate high-sensitivity C-reactive protein levels. Two principal components (PCs) were identified from the biomarker matrix, PC1, indicating platelet activation and PC2, pro-inflammatory. TER(alb) was positively related to PC1 but not PC2. Diabetes and ischaemic heart disease were associated with PC1 and PC2, respectively. CONCLUSIONS This exploratory analysis indicates that endothelial barrier function is decreased in PD patients and is associated with diabetic status and markers of platelet activation more than inflammation. In contrast, hypoalbuminaemia is associated more with inflammation and atherosclerotic disease indicating a more complex relationship between systemic endothelial barrier function, inflammation and hypoalbuminaemia which requires further validation.

Sodium Thiosulfate: An Emerging Treatment for Calciphylaxis in Dialysis Patients

Calciphylaxis is a rare but life-threatening complication seen in dialysis patients. We report a case with calciphylaxis and severe secondary hyperparathyroidism. Sodium thiosulfate (STS) was used for treatment in this case. The painful skin ulcers improved significantly soon after treatment, with a slight reduction in the calcium-phosphorus product. Total parathyroidectomy was carried out 6 months after the STS therapy, which successfully solved hyperparathyroidism and the high calcium-phosphorus profiles. Until now, no recurrence of calciphylaxis has been observed during the more than 7 years of follow-up. STS, as a chelating agent for calcium and iron, is an emerging treatment option for calciphylaxis; however, the mechanisms of STS in treating calciphylaxis are not clear. Our case demonstrates that STS treatment did not work through normalizing calcium-phosphorus profiles, although to optimize hyperparathyroidism and to control calcium and phosphorus levels is clearly part of the general treatment of calciphylaxis. The literature on STS treatment for calciphylaxis in dialysis patients was also reviewed.

Longitudinal Study of Small Solute Transport and Peritoneal Protein Clearance in Peritoneal Dialysis Patients

BACKGROUND AND OBJECTIVES Peritoneal protein clearance (Pcl) is determined by both effective (small pores) membrane area and relative capillary leakiness (large pores). It is not known how these two components change with duration of peritoneal dialysis (PD) in the context of progressive membrane injury and differential attrition of patients with higher Pcl, which has been associated with increased mortality risk in several studies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients treated continuously from 2000 to 2011 for a minimum of 4 years were selected from the longitudinal prospective Stoke PD Study. Pcl, membrane area (peritoneal solute transport rate [PSTR]), dialysis prescription, and residual renal function were measured every 6 months, along with comorbidity and peritonitis events. Multilevel multivariate analysis was used to determine associations with Pcl over time, taking into account within-subject correlations. RESULTS From 280 incident patients, 335 datasets were analyzed from 49 patients receiving treatment for 4 years. Pcl correlated with PSTR at baseline (R=0.61; P<0.01), but over time there was progressive uncoupling of this relationship (year 4, R=0.28; P=0.05) with increasing PSTR (0.66-0.74; P<0.01) and stable Pcl (78.4-81.9 ml/d; P=0.7). Multivariate analysis found that age, PSTR, daily ultrafiltration, and sodium removal were significant predictors of Pcl when adjusted for sex, comorbidity, glucose exposure, and residual renal function. Peritonitis was associated with increased PSTR but a similar pattern of uncoupling. CONCLUSION There is a progressive dissociation of the small- and large-pore pathways with time on PD, which would be in keeping with a switch from local inflammation early on to progressive fibrosis, combined with increased vascular surface area. Measuring longitudinal changes in Pcl may complement membrane function tests used to monitor progressive injury.

Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis

Objectives An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis. Methods Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6–0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded. Results The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group. Conclusions Restriction of dietary protein intake to 0.6–0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.

Brain natriuretic peptide is related to carotid plaques and predicts atherosclerosis in pre-dialysis patients with chronic kidney disease

BACKGROUND Although brain natriuretic peptide (BNP) concentration has been associated with atherosclerosis and ischemic cardiovascular diseases (CVD) in the general population, less is known about this relationship in pre-dialysis chronic kidney disease (CKD) patients. METHODS We prospectively analyzed 227 pre-dialysis patients with CKD [median estimated glomerular filtration rate (eGFR): 28.82 (11.65-48.20) ml/min/1.73 m(2)]. At enrollment, BNP concentrations, biochemical and echocardiographic parameters were measured, and carotid artery ultrasound was performed. Patients were prospectively followed for a mean 31.8 months (range 0.5-57.0 months). Ischemic CV events and patient outcomes were recorded. RESULTS Median BNP concentration at enrollment was significantly higher in the CKD patients than in a control group [53.9 (16.2-181.0) pg/ml vs. 9.4 (7.0-15.3) pg/ml, P<0.01]. BNP concentration was positively related with the carotid intima-media thickness of the common carotid artery (CCA-IMT) and left ventricular mass index (LVMI) and was significantly higher in patients with than without carotid plaques (P<0.01). Logistic regression analysis confirmed that lgBNP concentration was independently correlated with carotid plaques. Thirty-two patients experienced ischemic cardiovascular (ICV) events during follow-up. Kaplan-Meier analysis showed that cumulative survival without new ICV events was better in patients with lower than with higher BNP concentrations (P<0.01). Cox regression analysis showed that BNP was an independent risk factor for ICV events (HR=3.167, 95%CI=1.398-7.171, P<0.01). CONCLUSIONS Similar to findings in the general population, elevated BNP level is related to atherosclerosis and an increased risk of ICV events in pre-dialytic CKD patients.

High-Sensitivity C-Reactive Protein: An Independent Risk Factor for Left Ventricular Hypertrophy in Patients with Lupus Nephritis

Objective. To determine the prevalence of left ventricular hypertrophy (LVH) and its associated risk factors in lupus nephritis (LN) patients. Methods. 287 LN patients (age: 38.54 ± 13.31, 262 female) were recruited. Echocardiography and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Their relationship was evaluated by univariate correlation analysis and multivariate regression analysis. Results. The prevalence of LVH in this cohort was 21.25% (n = 61). Serum hs-CRP level was significantly elevated in patients with LVH compared to those without (8.03 (3.22–30.95) versus 3.93 (1.48–9.48) mg/L, P < .01), and correlated with left ventricular mass index (LVMI) (r = 0.314, P = .001). Multivariate regression analysis further confirmed that hs-CRP was an independent risk factor (β = 0.338, P = .002) for LVH in patients with LN. Conclusions. Our findings demonstrated that serum hs-CRP level is independently correlated with LVMI and suggested that measurement of hs-CRP may provide important clinical information to investigate LVH in LN patients.

Urgent-Start Peritoneal Dialysis and Hemodialysis in ESRD Patients: Complications and Outcomes

Background Several studies have suggested that urgent-start peritoneal dialysis (PD) is a feasible alternative to hemodialysis (HD) in patients with end-stage renal disease (ESRD), but the impact of the dialysis modality on outcome, especially on short-term complications, in urgent-start dialysis has not been directly evaluated. The aim of the current study was to compare the complications and outcomes of PD and HD in urgent-start dialysis ESRD patients. Methods In this retrospective study, ESRD patients who initiated dialysis urgently without a pre-established functional vascular access or PD catheter at a single center from January 2013 to December 2014 were included. Patients were grouped according to their dialysis modality (PD and HD). Each patient was followed for at least 30 days after catheter insertion (until January 2016). Dialysis-related complications and patient survival were compared between the two groups. Results Our study enrolled 178 patients (56.2% male), of whom 96 and 82 patients were in the PD and HD groups, respectively. Compared with HD patients, PD patients had more cardiovascular disease, less heart failure, higher levels of serum potassium, hemoglobin, serum albumin, serum pre-albumin, and lower levels of brain natriuretic peptide. There were no significant differences in gender, age, use of steroids, early referral to a nephrologist, prevalence of primary renal diseases, prevalence of co-morbidities, and other laboratory characteristics between the groups. The incidence of dialysis-related complications during the first 30 days was significantly higher in HD than PD patients. HD patients had a significantly higher probability of bacteremia compared to PD patients. HD was an independent predictor of short-term (30-day) dialysis-related complications. There was no significant difference between PD and HD patients with respect to patient survival rate. Conclusion In an experienced center, PD is a safe and feasible dialysis alternative to HD for ESRD patients with an urgent need for dialysis.