Background: Encapsulating peritoneal sclerosis (EPS) is a rare and devastating fibrotic complication in patients treated with peritoneal dialysis. Transforming growth factor-β₁ (TGF-β₁) has been reported to be a pivotal factor in the induction of EPS. Ribozymes are RNA molecules that enzymatically cleave the target mRNAs and are expected to be utilized as a novel nucleic acid-based therapy. We examined the effects of the chimeric DNA-RNA hammerhead ribozyme targeting TGF-β₁ mRNA on a peritoneal sclerosis rat model to develop a possible gene therapy for EPS.
Methods: To create an animal model of peritoneal sclerosis, rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline (CHX) for 14 days. On day 4, the chimeric ribozyme or mismatch ribozyme was intraperitoneally injected. On day 15, samples of peritoneum were obtained from the rats, and expression of TGF-β₁ mRNA and fibronectin mRNA in peritoneal tissues were evaluated by quantitative real-time PCR analysis.
Results: Injections of CHX significantly increased the submesothelial thickness, and increased the expression of TGF-β₁ and fibronectin mRNA in the rat peritoneum. Treatment with the chimeric ribozyme significantly reduced the CHX-induced peritoneal thickness, and expression of TGF-β₁ and fibronectin mRNA in peritoneal tissues.
Conclusions: These results indicate that the chimeric DNA-RNA hammerhead ribozyme targeting TGF-β₁ mRNA has the potential for use as a gene therapy agent for EPS.

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The association between pulse wave velocity (PWV) and chronic kidney disease mineral and bone disorder (CKD-MBD) was investigated in CKD 1-5 patients without dialysis.
Pulse pressure (PP), PWV, serum Cr, non-HDL-cholesterol, Alb, Ca, Pi, calcitriol, intact-PTH and BAP were measured in sixty patients not receiving a phosphate binder or vitamin D. Using the relationship between age and baPWV in healthy subjects, we determined ΔbaPWV (measured baPWV-calculated baPWV) as an index for the effect of CKD-related factors.
ΔbaPWV was significantly higher in diabetic patients (p<0.00001). Simple regression analysis revealed that ΔbaPWV was positively correlated with PP (p<0.05) and Log (intact-PTH) (p<0.01), but negatively correlated with Log (estimated GFR) and Log (calcitriol) (p<0.01). Multiple regression analysis revealed that ΔbaPWV was significantly associated with PP and calcitriol, or PP and intact-PTH.
These results suggest a relationship between PWV and CKD-MBD.

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A 71-year-old man was admitted to our hospital because of fever and rapidly progressive renal insufficiency over a month. He had depression and Alzheimer's disease as complications. On admission, his serum creatinine was 5.4mg/dL, and the serum CRP and MPO-ANCA were 18.2mg/dL and 285EU, respectively. A computed tomographic chest scan showed pericardiac effusion and fibrosis in both lower lung fields. Although microscopic polyangiitis (MPA) was inferred from a positive MPO-ANCA, renal biopsy could not be carried out. The initial therapy was started with pulse methylprednisolone therapy, followed by oral administration of prednisolone at the dose of 1mg/kg (60mg/day). As a result, his fever and inflammatory findings disappeared, and renal insufficiency was ameliorated with a smooth recovery and the pericardial effusion was markedly diminished. However, on the 18th hospital day, chest radiography revealed a nodular shadow in the right lung. Fungus infection was suspected because his serum beta-D-glucan level was extremely high (above 999pg/mL). Mikafungin, therefore, was started at a dose of 75mg/day and then, the dose was increased up to 300mg/day. Nevertheless, he finally died of respiratory failure on the 26th hospital day.
The autopsy findings revealed a cavity of 4.0×3.0×3.0 centimeters in size in the upper lobe of the right lung. There was a great number of fungal threads with a septal wall branched in a Y-shaped figure around the cavity, thus indicating pulmonary aspergilloma. Intranuclear inclusion bodies staining positive for cytomegalovirus were observed in all the lung fields, suggestive of a cytomegalovirus infection.
In the kidney, a cellular crescent formation was noted in the majority of glomeruli showing crescentic glomeluronephritis, compatible with MPA.

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