The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition--A Randomized Control Trial.

BACKGROUND: Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied. METHODS: We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV. RESULT: After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001). CONCLUSION: Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00966615.

Public lacks knowledge on chronic kidney disease: telephone survey.

OBJECTIVES: To examine knowledge of chronic kidney disease in the general public. DESIGN: Cross-sectional telephone survey. SETTING: Hong Kong. PARTICIPANTS: Community-dwelling adults who spoke Chinese in Hong Kong. RESULTS: The response rate was 47.3% (516/1091) out of all subjects who were eligible to participate. The final survey population included 516 adults (55.6% female), of whom over 80% had received a secondary level of education or higher. Close to 20% of the participants self-reported a diagnosis of hypertension. Few (17.8%) realised the asymptomatic nature of chronic kidney disease. Less than half of these individuals identified hypertension (43.8%) or diabetes (44.0%) as risk factors of kidney disease. Awareness of high dietary sodium as a risk factor for chronic kidney disease was high (79.5%). CONCLUSIONS: The public in Hong Kong is poorly informed about chronic kidney disease, with major knowledge gaps regarding the influence of hypertension on kidney disease. We are concerned about the public's unawareness of hypertension being a risk factor for kidney disease. Future health education should target areas of knowledge deficits.

Expression of ACE and ACE2 in patients with hypertensive nephrosclerosis.

BACKGROUND: The interplay between intrarenal angiotensin-converting enzyme (ACE) and type 2 ACE (ACE2) might play important roles in the pathogenesis of hypertensive nephrosclerosis (HTN), but human data are limited. METHODS: Renal biopsy specimens of 41 patients with HTN and 10 transplant donors as controls (CTL) were studied. The glomerular and tubulointerstitial mRNA expression of ACE and ACE2 was measured by laser microdissection and real-time quantitative polymerase chain reaction. The corresponding protein level was determined by immunohistochemistry. RESULTS: Neither the glomerular nor tubulointerstitial mRNA expression of ACE or ACE2 correlated with the corresponding protein level by immunohistochemistry. The tubulointerstitial levels of ACE and ACE2 were significantly lower in HTN than CTL, while the glomerular ACE and ACE2 levels were similar between the groups. The tubulointersitial ACE and ACE2 levels significantly correlated with the estimated glomerular filtration rate (GFR) and inversely with the degree of histological damage. The glomerular ACE and ACE2 levels significantly correlated with the rate of GFR decline. The ratio of glomerular ACE and ACE2 level correlated with the estimated GFR and the degree of glomerulosclerosis. CONCLUSION: Our results suggest that intrarenal ACE and ACE2 may play an important role in the pathogenesis and progression of HTN. Studies based on the mRNA expression of ACE and ACE2 should be cautiously interpreted.

Intrarenal expression of microRNAs in patients with IgA nephropathy.

MicroRNAs (miRNAs) are noncoding, single-stranded RNA molecules that have important roles in a number of physiological and pathological processes. Previous studies have proved that miRNAs targeting ZEB1 and ZEB2 may repress epithelial-to-mesenchymal transition. In this work, we studied the intrarenal expression of miR-200 family, miR-205 and miR-192 in patients with immunoglobulin A (IgA) nephropathy. We studied 43 patients with biopsy-proven IgA nephropathy (IgA group). The intrarenal expression of miRNAs was quantified and compared with that of 15 patients with noninflammatory glomerulosclerosis (GS group) and 20 patients with nephrectomy for kidney cancer as controls (CTL group). The level of intrarenal miR-200c was downregulated, whereas the levels of intrarenal miR-141, miR-205 and miR-192 were upregulated in IgA but not GS group. Proteinuria significantly correlated with the intrarenal expression of miR-200c (r=-0.324, P=0.011) and glomerular filtration rate (GFR) significantly correlated with the intrarenal expression of miR-205 (r=-0.280, P=0.030). The degree of tubulointerstitial scarring correlated with miR-205 expression (r=0.389, P=0.021), whereas glomerulosclerosis correlated with miR-192 expression (r=-0.311, P=0.045). The rate of GFR decline significantly correlated with the intrarenal expression of miR-192 (r=0.373, P=0.015). The intrarenal expression of E-cadherin significantly correlated with the intrarenal expression of miR-200c (r=0.392, P=0.002). The results show that intrarenal expression of miR-200c, miR-141, miR-205 and miR-192 was diversely regulated and correlated with disease severity and progression in patients with IgA nephropathy. These miRNA species may be important in the pathogenesis and progression of IgA nephropathy.

Urinary FOXP3 mRNA in patients with lupus nephritis--relation with disease activity and treatment response.

OBJECTIVE: Regulatory T lymphocytes (Tregs) probably play an important role in the pathogenesis of SLE. METHODS: We quantified messenger RNA (mRNA) expression of FOXP3, a critical regulator for the development and function of Tregs, in the urinary sediment of 25 subjects with active lupus nephritis (LN), 17 with inactive lupus and 7 healthy subjects. RESULTS: We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 +/- 45.8 vs 0.8 +/- 1.0 vs 0.6 +/- 0.8 copy; P < 0.001). In the active group, urinary FOXP3 mRNA expression level was higher in patients with proliferative LN than non-proliferative nephritis (34.6 +/- 56.3 vs 2.7 +/- 2.1 copy; P = 0.019). Urinary FOXP3 mRNA level significantly correlated with SLEDAI (r = 0.668; P < 0.001) and proteinuria (r = 0.414; P = 0.006). In the active group, urinary FOXP3 mRNA level also significantly correlated with histological activity index (r = 0.541; P = 0.009) and marginally with intra-renal FOXP3 mRNA level (r = 0.360; P = 0.08). Urinary FOXP3 mRNA in patients with no response to therapy was higher than those with partial response or complete response (57.6 +/- 69.8 vs 2.4 +/- 1.9 copies; P = 0.02). CONCLUSION: We concluded that urinary FOXP3 mRNA is markedly up-regulated in patients with active LN, and the level of expression is closely correlated with the clinical and histological disease activity. A high urinary FOXP3 mRNA in LN predicts a poor therapeutic response. Measurement of FOXP3 mRNA in urine sediment may be a non-invasive biomarker for assessing the severity and risk stratification in LN.

A story half untold: adiposity, adipokines and outcomes in dialysis population.

In contrast to the associations of high body mass index (BMI) with increased mortality in the general population, high BMI is associated with better survival in dialysis patients. Nonetheless, high BMI/adiposity in chronic kidney disease (CKD)/dialysis patients is associated with insulin resistance, inflammation, dyslipidemia, atherosclerosis and coronary calcification as described in the general population. These apparently perplexing associations might be explained if (1) adiposity has dual competing effects on survival; a protective nutritional effect and a deleterious metabolic effect resulting in insulin resistance, dyslipidemia, hypertension and inflammation and (2) the level of kidney function modifies the relative importance of these effects. In this paradigm, the deleterious metabolic effects of obesity outweigh its protective nutritional effects in the non-CKD population, the deleterious metabolic effects of obesity are neutralized by its protective nutritional effects in the moderate CKD population and the deleterious metabolic effects of obesity are outweighed by its protective nutritional effects in stage V CKD on dialysis. In other words, the over-all effects of obesity on survival vary according to the level of kidney function and there is an interaction of body size and presence or absence of CKD on survival even though the metabolic effects of adiposity are not modified by the level of kidney function. Therefore, we propose that despite an association of adiposity with better survival, there is no reverse epidemiology of the associations traditional and nontraditional cardiovascular risk factors and disease with adiposity in dialysis patients.

Associations of body size with metabolic syndrome and mortality in moderate chronic kidney disease.

BACKGROUND AND OBJECTIVES: Obesity is associated with metabolic syndrome and poor outcomes in those with normal kidney function but better survival in dialysis patients. We examined whether chronic kidney disease (CKD) modifies the association of obesity with metabolic syndrome and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Analyses of 15,355 participants in limited access, public use Atherosclerosis Risk in Communities Study database. RESULTS: The prevalence of metabolic syndrome in (BMI) groups < 20, 20 to 24.9, 25 to 29.9, 30 to 34.9, and > or = 35 kg/m2 were 1, 6, 17, 28, and 35% and 9, 15, 32, 46, and 58% in participants without (n = 14,894) and with CKD (n = 461), respectively. Using BMI 20 to 24.9 kg/m2 as the reference, there was a U-shaped association of BMI with mortality in a parametric survival model of death. An interaction term of BMI and CKD added to the model was significant. In participants with (BMI) > or = 25 kg/m2, each 1-kg/m2 increase in BMI was associated with increased hazard of death only in those without CKD. Adjustment for components of metabolic syndrome, markers of inflammation, and cardiovascular conditions abolished these associations in participants without CKD but became protective in participants with CKD. CONCLUSIONS: The prevalence of obesity parallels metabolic syndrome in populations with and without CKD. However, the presence of CKD modifies the associations of obesity with mortality.

Cellular and morphological changes during neointimal hyperplasia development in a porcine arteriovenous graft model.

BACKGROUND: Implantation of a haemodialysis arteriovenous graft is often followed by the development of neointimal hyperplasia (NH) at the venous anastomosis. The nature of the proliferating cells in these lesions is not well understood. A better understanding of the cells contributing to NH is important to the development of preventive strategies. METHODS: Carotid-jugular PTFE grafts were placed in 21 pigs and characterized at various time points following implantation. Venous anastomotic tissues were harvested at 1, 7, 14, 21, 28 or 49 post-operative days for histology and immunohistochemistry. RESULTS: Van Gieson staining of the tissues showed that NH was apparent as early as day 7 and progressed over time. Even by day 1, there were cells expressing the proliferation marker Ki-67 in the venous adventitia, but not the media, at the anastomosis. Double immunohistochemical staining showed that these cells were positive for alpha-smooth muscle actin (alpha-SMA), but negative for smooth muscle myosin heavy chain (SM MHC), suggesting that the proliferating cells were myofibroblasts rather than smooth muscle cells. By day 7, proliferating cells were abundant in the adventitia and began to appear in the media, surrounded by extracellular matrix visualized using Trichrome staining. By day 49, alpha-SMA-positive, SM MHC-negative cells were predominant in the NH, and Ki-67 staining had largely vanished. CONCLUSIONS: These results are consistent with the hypothesis that adventitial fibroblasts are transformed into myofibroblasts and begin to proliferate within hours after graft placement. Migration of these cells towards the vessel lumen with subsequent proliferation appears to be a major contributor to NH formation. The pivotal role of the adventitial fibroblasts in the pathogenesis of NH provides a compelling rationale for therapies that target the transformation, proliferation and migration of these cells to prevent arteriovenous graft stenosis.