The glucose degradation product methylglyoxal induces immature angiogenesis in patients undergoing peritoneal dialysis.

The accumulation of glucose degradation products (GDPs) can lead to tissue damage in patients with diabetes and those undergoing long-term peritoneal dialysis (PD). Angiogenesis is occasionally observed in the peritoneal membrane of patients undergoing PD, where it is associated with failure of ultrafiltration. To investigate the mechanism underlying the influence of angiogenesis on fluid absorption, we evaluated the effects of accumulation of the glucose degradation product methylglyoxal (MGO) on angiogenesis in vitro, and analyzed the association with angiogenesis in the peritoneal membrane. To this end, we measured the levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF)-BB in cultured endothelial and smooth muscle cells after administration of MGO. The expression of PDGF-BB mRNA and protein decreased significantly after exposure to MGO, while the expression of VEGF mRNA increased (both P < 0.01). The expression of PDGF-Rß mRNA in cultured smooth muscle cells did not change after administration of MGO, although the expression of VEGF mRNA increased (P < 0.01). We also evaluated the associations between the number of capillary vessels, peritoneal function, and the degree of MGO deposition using peritoneum samples collected from patients undergoing PD. The number of immature capillary vessels was significantly associated with peritoneal dysfunction and the degree of MGO accumulation (both P < 0.01). In conclusion, MGO enhances the production of VEGF and suppresses the production of PDGF-BB, potentially leading to disturbance of angiogenesis in the peritoneal membrane. Accumulation of MGO in the peritoneum may cause immature angiogenesis and peritoneal dysfunction.

Advanced glycation end products are associated with immature angiogenesis and peritoneal dysfunction in patients on peritoneal dialysis.

BACKGROUND: Deposition of advanced glycation end products (AGEs) is frequently found in the peritoneum of patients on peritoneal dialysis (PD). Angiogenesis is also observed in the peritoneum. However, the clinical significance of AGEs and angiogenesis in the peritoneum is not fully understood. We evaluated the maturation of capillary vessels and investigated whether AGEs are associated with angiogenesis and peritoneal function in the peritoneal membrane. METHODS: Peritoneum obtained when PD catheters were removed from 61 patients with PD was analyzed. The peritoneum was immunohistochemically stained with anti-CD34 (for endothelial cells), anti-alpha smooth muscle actin (αSMA) (for pericytes), and anti-AGE antibodies. We defined CD34-positive and αSMA-negative vessels as immature capillary vessels in peritoneal membranes using serial sections. We evaluated the associations between vessel density, peritoneal function (dialysate-to-plasma ratio for creatinine (D/P creatinine)), and the degree of AGE deposition. RESULTS: AGE accumulation in the interstitium was positively associated with the duration of PD (p < 0.01). AGE accumulation in the interstitium and vascular wall was positively correlated with the use of acidic solution (p < 0.05) and the maximum value of D/P creatinine (p < 0.05). AGE accumulation in the vascular wall was significantly associated with immature capillary density (CD34+/αSMA-) in the peritoneum (p < 0.01). Vessel density was not significantly correlated with the last measurement of D/P creatinine (p = 0.126, r = 0.202), However, immature capillary density was positively correlated with the last measurement of D/P creatinine (p < 0.05, r = 0.278). CONCLUSIONS: AGE accumulation is significantly associated with immature angiogenesis and peritoneal dysfunction in patients undergoing PD.

Brain atrophy in peritoneal dialysis and CKD stages 3-5: a cross-sectional and longitudinal study.

BACKGROUND: Brain atrophy has been reported in patients with end-stage renal disease receiving hemodialysis, although its mechanism is unknown. However, little is known regarding brain atrophy in patients receiving peritoneal dialysis (PD). Therefore, we examined brain volume and its annual change over 2 years in PD patients compared with patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). STUDY DESIGN: Cross-sectional and longitudinal cohort. SETTING & PARTICIPANTS: 62 PD patients and 69 patients with NDD-CKD with no history of cerebrovascular disease who underwent brain magnetic resonance imaging (MRI) were recruited in a cross-sectional study. Among them, 34 PD patients and 61 patients with NDD-CKD, who underwent a second brain MRI after 2 years, were recruited in a longitudinal study. PREDICTOR: PD therapy versus NDD-CKD. OUTCOMES & MEASUREMENTS: T1-weighted magnetic resonance images were analyzed. Total gray matter volume (GMV), total white matter volume (WMV), and cerebrospinal fluid space volume were segmented, and each volume was quantified using statistical parametric mapping software. Normalized GMV and WMV values were calculated by division of GMV and WMV by intracranial volume to adjust for variations in head size. We compared normalized GMV and normalized WMV between PD patients and patients with NDD-CKD in the cross-sectional study and the annual change in normalized GMV in the longitudinal study. RESULTS: In the cross-sectional study, normalized GMV, which was correlated inversely with age, was lower in PD patients than in patients with NDD-CKD. However, normalized WMV, which was not correlated with age, was comparable between the groups. Annual change in normalized GMV was significantly higher in PD patients than in patients with NDD-CKD. These differences remained significant even after adjustment for potential confounding factors. LIMITATIONS: A short observation period and high dropout rate in the longitudinal study. CONCLUSIONS: Decline in normalized GMV is faster in PD patients than in patients with NDD-CKD.

Diabetes influences peritoneal morphology in uremic patients at the initiation of peritoneal dialysis.

BACKGROUND: The peritoneum begins to undergo morphologic changes before the start of peritoneal dialysis (PD), particularly in diabetic patients. The present study was conducted to investigate the effects of diabetes on the peritoneum. METHODS: This study involved 17 patients who began receiving PD and had diabetes as an underlying disease (DM group), and 30 patients without diabetes who served as a control group (nonDM group). At the start of PD, the parietal peritoneum was sampled to assess submesothelial connective tissue thickness, number of capillaries and postcapillary venules, and indications of vasculopathy (grades 0 - 3). RESULTS: Submesothelial connective tissue thickness was significantly greater in the DM group than in the nonDM group (p < 0.01). The number of capillaries was significantly greater in the DM group (p < 0.01). Based on multivariate linear regression analysis, diabetes was identified as a significant independent variable of both submesothelial connective tissue thickness and number of capillaries (p < 0.01). CONCLUSIONS: In diabetic patients, morphologic changes of the peritoneum are marked at the start of PD.

Pseudorenal failure due to intraperitoneal bladder rupture after blunt trauma: usefulness of examining ascitic fluid sediment.

A 42-year-old man noted decreased urine output and visited our emergency department. He said that 3 days previously, he had gotten drunk and fallen down a set of stairs. Blood tests and abdominal contrast-enhanced computed tomography revealed no abnormalities. A serum creatinine level of 5.89 mg/dL led to a diagnosis of acute renal failure and his hospitalization. After admission, his ascitic fluid level gradually increased, suggesting urine leakage into the peritoneal cavity. Microscopic examination of his ascitic fluid sediment revealed the presence of hyaline casts enclosing renal tubular epithelial cells. Cystography demonstrated contrast medium leakage into the peritoneal cavity, which led to a diagnosis of bladder rupture. Examination of ascitic fluid sediment is simple and very useful for diagnosing bladder rupture.

The improvement of renal survival with steroid pulse therapy in IgA nephropathy.

BACKGROUND: The benefits of steroid therapy in immunoglobulin A nephropathy (IgAN) have not been established. METHODS: The effect of steroids on kidney survival was retrospectively investigated in 702 patients with IgAN by multivariate analyses. RESULTS: There were 295 men and 407 women. The median follow-up period was 62 months. One hundred and ninety-four patients were treated with oral steroids (oral steroid group). Thirty-four patients were treated with methylprednisolone (mPSL) pulse therapy (pulse steroid group) followed by oral prednisolone (PSL). In 474 patients, no steroid was used (no steroid group). The urinary protein-creatinine ratio and histological grade were significantly different among treatment groups and were highest in the pulse steroid group followed by the oral steroid group and lowest in the no steroid patients. Serum creatinine was significantly higher in the pulse steroid group than in other two groups. Eighty-five patients developed end-stage renal failure (ESRF) requiring dialysis. [corrected] In multivariate analysis, steroid pulse therapy significantly decreased the risk of ESRF while oral steroid treatment did not improve renal survival in this cohort. CONCLUSION: We found that pulse steroid therapy improved kidney survivals in IgAN. Since the clinical findings and histological grade were the most severe in patients treated with mPSL pulse therapy, such therapy may prevent progression of IgAN.

Dialysis-related hypotension as a cause of progressive frontal lobe atrophy in chronic hemodialysis patients: a 3-year prospective study.

BACKGROUND/AIM: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. METHODS: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age +/- SD 53 +/- 10 (range 28-77) years; mean HD duration +/- SD 11 +/- 6 (range 1-22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. RESULTS: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 +/- 2.2%) and was not different in 1998 (13.1 +/- 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 +/- 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 +/- 4.2% (range 55.8-71.3%) and decreased significantly to 59.7 +/- 4.7% (range 50.2-70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). CONCLUSION: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.

Controlled, prospective trial of steroid treatment in IgA nephropathy: a limitation of low-dose prednisolone therapy.

BACKGROUND: No accepted therapy has been established for progressive immunoglobulin A (IgA) nephropathy. METHODS: A prospective, randomized, controlled trial of low-dose prednisolone therapy was performed in patients with IgA nephropathy with moderate histological characteristics. Forty-three patients in the steroid group and 47 patients in the control group were included in the study. The initial dose of prednisolone was 20 mg/d, gradually tapered to 5 mg/d during 2 years. RESULTS: Baseline urine protein-creatinine ratio (UP-UCR) was significantly greater in the steroid group than in controls. Follow-up duration was 65 +/- 25 months in the steroid group and 64 +/- 23 months in controls. Changes in UP-UCR from baseline, ie, UP-UCR at last follow-up minus UP-UCR at baseline, were significantly lower in the steroid group than in controls (steroid group, -0.84 +/- 1.78; controls, 0.26 +/- 1.65; P = 0.0034). Kidney survival was similar in both groups. Patients were divided into two subgroups according to clinical course. There were 28 improved patients and 15 unimproved patients in the steroid group and 27 improved patients and 20 unimproved patients in the control group. In the steroid group, UP-UCR was significantly greater in the unimproved than improved subgroup (3.1 +/- 2.6 versus 1.8 +/- 1.5). CONCLUSION: These data suggest that our protocol had an antiproteinuric effect, but could not improve kidney survival. Because the effect of steroid therapy to prevent the progression of IgA nephropathy is believed to be linked closely to reduction in urinary protein, an insufficient dose of prednisolone in our protocol may be the reason for the discrepancy between the effect on proteinuria and kidney survival.