Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats ( n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.

We have previously reported that the diameter of the inferior vena cava (IVC) reflects the amount of body fluid in hemodialyzed (HD) patients. The present study was undertaken to depict the criteria of IVC diameters for determining dry weight (DW) in anuric HD patients. In healthy subjects, the maximal diameters during quiet expiration (IVCe) and the minimal diameters during quiet inspiration (IVCi) were 16.7 +/- 3.2 and 5.7 +/- 5.4 mm, respectively (mean +/- SD). The collapsibility index (CI, 1 - IVCi/IVCe), which inversely correlates with the central venous pressure, was 0.68 +/- 0.29. In anuric HD patients, the IVCe/CI values before and after HD were 14.9 +/- 3.2/0.68 +/- 0.24 and 8.2 +/- 2.3/0.94 +/- 0.09, respectively. IVCe decreased proportionally to the amount of ultrafiltration. In HD patients with hypervolemic pulmonary edema, the IVCe and CI values were 22.4 +/- 2.9 and 0.22 +/- 0.11, respectively. We proposed that IVCe/CI after HD is 8 +/- 3 mm/0.9 +/- 0.1 as the markers of DW in anuric HD patients and that an IVCe value > or = 22 mm together with a CI < or = 0.22 implies the warning level of body fluid retention.

The present study examined how arginine vasopressin (AVP) affects nitric oxide (NO) metabolism in cultured rat glomerular mesangial cells (GMC). GMC were incubated with test agents and nitrite, and intracellular cGMP content, inducible nitric oxide synthase (iNOS) mRNA, and iNOS protein were analyzed by the Griess method, enzyme immunoassay, and Northern and Western blotting, respectively. AVP inhibited lipopolysaccharide (LPS)- and interleukin-1β (IL-1β)-induced nitrite production in a dose- and time-dependent manner, with concomitant changes in cGMP content, iNOS mRNA, and iNOS protein. This inhibition by AVP was reversed by V1- but not by oxytocin-receptor antagonist. Inhibition by AVP was also reproduced on LPS and interferon-γ (IFN-γ). Protein kinase C (PKC) inhibitors reversed AVP inhibition, whereas PKC activator inhibited nitrite production. Although dexamethasone and pyrrolidinedithiocarbamate (PDTC), inhibitors of nuclear factor-κB, inhibited nitrite production, further inhibition by AVP was not observed. AVP did not show further inhibition of nitrite production with actinomycin D, an inhibitor of transcription, or cycloheximide, an inhibitor of protein synthesis. In conclusion, AVP inhibits LPS- and IL-1β-induced NO production through a V1 receptor. The inhibitory action of AVP involves both the activation of PKC and the transcription of iNOS mRNA in cultured rat GMC.

To examine the effect of hyperosmolality on Na(+)/H(+) exchanger (NHE) activity in mesangial cells (MCs), we used a pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein-AM, to measure intracellular pH (pH(i)) in a single MC from rat glomeruli. All the experiments were performed in CO(2)/HCO(-)(3)-free HEPES solutions. Exposure of MCs to hyperosmotic HEPES solutions (500 mosmol/kgH(2)O) treated with mannitol caused cell alkalinization. The hyperosmolality-induced cell alkalinization was inhibited by 100 microM ethylisopropylamiloride, a specific NHE inhibitor, and was dependent on extracellular Na(+). The hyperosmolality shifted the Na(+)-dependent acid extrusion rate vs. pH(i) by 0.15-0.3 pH units in the alkaline direction. Removal of extracellular Cl(-) by replacement with gluconate completely abolished the rate of cell alkalinization induced by hyperosmolality and inhibited the Na(+)-dependent acid extrusion rate, whereas, under isosmotic conditions, it caused no effect on Na(+)-dependent pH(i) recovery rate or Na(+)-dependent acid extrusion rate. The Cl(-)-dependent cell alkalinization rate under hyperosmotic conditions was partially inhibited by pretreatment with 5-nitro-2-(3-phenylpropylamino)benzoic acid, DIDS, and colchicine. We conclude: 1) in MCs, hyperosmolality activates NHE to cause cell alkalinization, 2) the acid extrusion rate via NHE is greater under hyperosmotic conditions than under isosmotic conditions at a wide range of pH(i), 3) the NHE activation under hyperosmotic conditions, but not under isosmotic conditions, requires extracellular Cl(-), and 4) the Cl(-)-dependent NHE activation under hyperosmotic conditions partly occurs via Cl(-) channel and microtubule-dependent processes.

We have previously reported that the maximal inferior vena cava (IVC) diameter during quiet expiration (IVCe) measured by ultrasonography correlates well with the amount of body fluid, especially the circulating blood volume(2) and proposed using the criteria of IVC diameter to determine dry weight (DW) in anuric hemodialyzed (HD) patients: standard IVCe of pre- and post-HD are 14.9 +/- 0.4 and 8.2 +/- 0.3 mm, respectively (1). However, the same post-HD IVC criterion should not be applied to nonoliguric HD patients because it could result in rapid deterioration of residual renal function due to forced dehydration. Although the biochemical DW marker plasma atrial natriuretic peptide (ANP) is useful to evaluate hypervolemia but not hypovolemia, both hyper- and hypovolemia can be detected by IVC measurement. In the present study, we investigated whether the IVC diameter serves as an optimal evaluation of DW in nonoliguric HD (NO-HD) patients, avoiding not only overhydration but also dehydration. The IVCe and plasma ANP levels were measured in 14 euvolemic patients with chronic renal failure at conservative period (CP-CRF) and 11 NO-HD patients, in whom the average daily urine volume was more than 500 ml/day. In NO-HD patients, DW was adjusted to attain the euvolemic state with normotensive blood pressure, lack of edema, and lack of temporal oliguria after HD. The ANP in CP-CRF patients was 109.3 +/- 15.3 pg/ml, and pre- and post-HD ANP levels in NO-HD patients were 145.3 +/- 23.5 and 97.5 +/- 13.5 pg/ml, respectively. IVCe in CP-CRF was 13.4 +/- 0.9 mm, and pre- and post-HD IVCe in NO-HD patients were 14.2 +/- 1.0 mm and 11.9 +/- 0.9 mm, respectively. Although the post-HD IVCe was greater (i.e., less hypovolemic) than that in anuric HD patients, and close to the IVCe in CP-CRF, pre-HD IVCe was comparable with that in anuric HD patients. In addition, the pre-HD ANP level was no higher than that in CP-CRF. Thus, in NO-HD patients, the post-IVCe of 11.9 +/- 0.9 mm would be a marker for an appropriate DW setting avoiding severe post-HD dehydration as well as excessive hypervolemia during the interdialytic period.