Dialysate vascular endothelial growth factor is an independent determinant of serum albumin levels and predicts future withdrawal from peritoneal dialysis in uremic patients.

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium-derived factor (PEDF) has anti-vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty-seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤ 3.31 g/dL) and low hemoglobin (≤ 11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.

Effects of switching from calcium carbonate to lanthanum carbonate on bone mineral metabolism in hemodialysis patients.

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis (HD) patients. This study was performed to examine the effects of switching from calcium carbonate (CC) to lanthanum carbonate (LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks. Patients underwent determinants of blood chemistries such as serum calcium (Ca), phosphorus, parathyroid hormone (PTH) and vitamin D status, and interleukin-6 (IL-6) mRNA levels in whole blood cells were evaluated by real-time PCR just before and after the treatment with LC. Corrected Ca [corrected] levels were significantly reduced, but serum phosphorus levels (P levels) were unchanged after LC treatment. Switching to LC increased whole-PTH, osteocalcin, 1,25(OH)(2) D(3) levels and 1,25(OH)(2) D(3)/25(OH)D(3) ratio. 1,25(OH)(2) D(3)/25(OH)D(3) ratio was negatively correlated with HD duration. Furthermore, whole blood cell IL-6 mRNA levels were significantly reduced by LC treatment. We provided that the switching from CC to LC improved Ca overload and ameliorated vitamin D and inflammatory status in HD patients. These observations suggest that LC may play a protective role for the progression of atherosclerosis and vascular calcification in these patients.

[Clinical evaluation of tonsillectomy with modified high-dose intravenous methylprednisolone therapy in patients with IgA nephropathy].

Immunoglobulin A nephropathy (IgAN) is now recognized as the most common form of primary glomerulonephritis worldwide and is the major cause of end-stage renal disease. As reported, the renal survival rate is 61% at 20 years and the renal prognosis of this disease is relatively poor on long-term observation, hence various protocols have been attempted to control this disease. At Iizuka Hospital, a prospective study of tonsillectomy with methylprednisolone pulse therapy was performed for the treatment of patients with IgA nephropathy from August 2002. We reviewed the clinical efficacy of our protocol. From August 2002 to July 2006, 31 patients whose IgA nephropathy was demonstrated by percutaneous renal biopsy were administered our regimen. In our study, 12 patients had an observation period of more than 24 months. Our protocol consisted of tonsillectomy with one course of methylprednisolone pulse therapy. Methylprednisolone at the daily dose of 1,000 mg for 3 consecutive days followed by oral steroid at the daily dose of 20 mg, was gradually tapered, and discontinued one year later. All of the patients were administered angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with favorable control of hypertension. The mean observation period for the 12 patients with IgA nephropathy was 37.4 months. The mean age at renal biopsy was 34.8 +/- 12.2 years. The male-female ratio was 3:9. At the renal biopsy in our hospital, mean creatinine value was 0.95 +/- 0.38 mg/dL, mean creatinine clearance was 92.1 +/- 34.9 mL/min, and the mean urinary protein and urinary creatinine ratio was 3.52 +/- 4.36. After 24 months, mean creatinine value was 1.03 +/- 0.59 mg/dL, mean creatinine clearance was 91.2 +/- 42.3 mL/min, and the mean urinary protein and urinary creatinine ratio was 0.83 +/- 0.98. Urinary protein and urine occult blood became negative in 66.7% of patients, and the urinary remission rate was 58.3%. On our protocol, mean length of the hospital stay was 11.4 +/- 4.7 days. Our prospective study showed that tonsillectomy with one course of methylprednisolone pulse therapy in IgA nephropathy appears to be beneficial for urinary remission and contributes to a short hospital stay.