PDI
JANUARY 2015 – VOL. 35, NO. 1
SHORT REPORTS
DISCLOSURES
The authors have no financial conflicts of interest to declare. Nelson Kopyt* Anshul Kumar Vibha Agrawal Lehigh Valley Health Network Allentown, PA *email: [email protected] REFERENCES 1. Dalrymple B, Mattick JS. An analysis of the organization and evolution of type 4 fimbrial (MePhe) subunit proteins. J Mol Evol 1987; 25:261–9. 2. Bøvre K. Family VIII. Neisseriaceae Prevot. In N. R. Krieg, ed. Manual of Systematic Bacteriology, Baltimore: The Williams & Wilkins co.; 1984: 288–309. 3. Knapp JS. Historical perspectives and identification of Neisseria and related species. Clin Microbiol Rev 1988; 1:415–31. 4. Gonorrhea Laboratory Information Kingella denitrificans. Centers for Disease Control and Prevention. [http://www.cdc.gov/std/Gonorrhea/ lab/Kden.htm] 5. Henriksen SD, Bøvre K. Transfer of Moraxella kingae Henriksen and Bøvre to the genus Kingella gen. nov. in the family Neisseriaceae. Int J Syst Bacteriol 1976; 26:447–50.
6. Snell JJS, Lapage SP. Transfer of some saccharolytic Moraxella species to Kingella Henriksen and Bøvre 1976, with descriptions of Kingella indologenes sp. nov. and Kingella denitrficans sp. nov. Int J Syst Bacteriol 1976; 26:451–8. 7. Hollis DG, Wiggins GL, Weaver RE. An unclassified gram-negative rod isolated from the pharynx on Thayer-Martin medium (selective agar). Appl Microbiol 1972; 24:772–7. 8. Brown, AM, Rothburn MM, Roberts C, Nye FJ. Septicaemia with probable endocarditis caused by Kingella denitrificans. J Infect 1987; 15:225–8. 9. Khan JA, Sharp S, Mann KR, Brewer J. Kingella denitrificans prosthetic endocarditis. Am J Med Sci 1986; 291(3):187–9. 10. Goldman IS, Ellner PD, Francke EL, Garvey GJ, Neu HC, Squilla N. Infective endocarditis due to Kingella denitnficans. Ann Intern Med 1980; 93:152–3. 11. Swann RA, Holmes B. Infective endocarditis caused by Kingella denitrificans. J Clin Pathol 1984; 37:1384–7. 12. Kim YH, Panday V, Reilly C. Isolation of Kingella denitrificans from a corneal ulcer. Cornea 2011; 30(4):472–3. 13. Morrison VA, Wagner KF. Clinical manifestations of Kingella kingae infections: case report and review. Rev Infect Dis 1989; 11:776–82. 14. Lalan SP, Warady BA, Blowey D, Waites KB, Selvarangan R. Mycoplasma edwardii peritonitis in a patient on maintenance peritoneal dialysis. Clin Nephrol 2015; 83(1):45–8. 15. Hassan IJ, Hayek L. Endocarditis caused by Kingella denitificans. J Infect 1993; 27:291–5. 16. Claesson B, Falsen E, Kjellman B. Kingella kingae infections: a review and a presentation of data from 10 Swedish cases. Scand J of Infect Dis 1985; 17: 233–43. 17. Geraci J, Wilson W. Endocarditis due to gram-negative bacteria. Report of 56 cases. Mayo Clinical Proceedings 1982; 57:145–8. 18. Figueiredo AE, Poli de Figueiredo CE, d’Avila DO. Peritonitis prevention in CAPD: to mask or not? Perit Dial Int 2000; 20:354–8. doi: 10.3747/pdi.2013.00248
Successful Treatment of Encapsulating Peritoneal Sclerosis by Hemodialysis and Peritoneal Lavage Using Dialysate Containing Dissolved Hydrogen Encapsulating peritoneal sclerosis (EPS) is the most serious and life-threatening complication of peritoneal dialysis (PD) therapy, as mortality is extremely high once it occurs. According to recent reports (1–5), mortality rate of EPS is 14 – 84%. Extensive fibrosing of the peritoneum in patients with EPS leads to symptoms of malnutrition and small bowel obstruction (ileus). Encapsulation can progress so that the bowel eventually becomes completely cocooned. The outcomes of several medical approaches such as tamoxifen, steroids, and newer immunosuppressive agents to retard EPS progression (6) remain poor. Moreover, in some alive cases, surgical approach (enterolysis, peritonectomy) is inevitable to cure symptoms of ileus (6). Dissolved hydrogen (H2) has a unique biological antioxidative and anti-inflammatory capacity (7). Accumulating evidence suggests that H2 ameliorates organ damage in various models of ischemia and inflammation (8). Clinical applications of H2 to pro-inflammatory disorders have been investigated, particularly for use during hemodialysis (HD) therapy (9–15). In addition, we recently showed that peritoneal dialysate containing high H2 concentrations could reduce both peritoneal and systemic oxidative stress in the clinical setting (16). 107
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due to Kingella species, nothing has been mentioned about using intraperitoneal antibiotics with PD fluid. Although our patient attempted to maintain strict sterile precautions and took appropriate care of her PD catheter site, 1 possibility may be that she contaminated the PD set with her oral secretions while coughing. She did admit that maybe 1 – 2 times she failed to use a facemask. This is a hypothesis only, as there is no definitive evidence of causality in our case. There is also no evidence in our case of the organism traversing the gastrointestinal tract to gain entrance into the peritoneal cavity. The possibility of causation via blood borne entry from the oral cavity or aerosol contamination seems to be the most plausible. Figueiredo et al. (18) suggested that use of a face mask during CAPD bag exchange gives no extra protection against peritoneal contamination. More importantly, patients must be educated to perform the connect/disconnect operation carefully, and to strictly observe accidental contamination of the hands. But the description was limited to a single renal unit with a seemingly small number of patients. Also, the patients were healthy and not sick like our patient who was coughing intermittently. This stresses the importance of strict hand hygiene and using a mask, especially if sick, before doing PD exchanges. She will be continued on long-term antibiotics for 6 weeks, her PD catheter was removed, and she will undergo intermittent hemodialysis with a tunneled catheter. In retrospect, she may have had a better outcome with intraperitoneal antibiotics. After completing her 42 days of antibiotics and close follow-up with regard to the clinical response, she will be re-evaluated regarding timing for the placement of a new PD catheter.
JANUARY 2015 – VOL. 35, NO. 1 PDI
SHORT REPORTS
In the present case study, dialysate enriched with H2 for both hemodialysis (HD) therapy and peritoneal lavage caused symptoms and laboratory signs of EPS to decrease. CASE HISTORY
TABLE 1 Laboratory Data Upon Admission Blood findings White blood cells Red blood cells Hemoglobin Hematocrit Platelets Total protein Albumin Total billirubin Aspartate aminotransferase Alanine aminotransferase Lactate dehydrogenase Gamma-glutamyl transpeptidase Urea nitrogen Creatinine Uric acid Sodium Chloride Potassium Calcium Inorganic phosphorus C-reactive protein Culture
12,600/μL 371 × 104/μL 12.0 g/dL 34.0% 14.9 × 104/μL 5.2 g/dL 2.9 g/dL 0.26 mg/dL 15 IU/L 13 IU/L 286 IU/L 8 IU/L 89.6 mg/dL 15.69 mg/dL 7.6 mg/dL 121 mEq/L 87 mEq/L 5.2 mEq/L 8.2 mg/dL 4.3 mg/dL 23.62 mg/dL Negative
Effluent fluid (sediment) findings Red blood cells >100/HPF White blood cells >500/HPF Mesothelial cells (-) Bacteria (+) Culture Negative HPF = high-power field.
108
Figure 1 — Macroscopic findings at laparoscopic examination. (A) Both visceral and parietal peritonea are whitish and thickened. Intestine is encapsulated by thin membrane. (B) Specimen of parietal peritoneum obtained under laparoscopic monitoring. 254×366mm (72 × 72 DPI)
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A 63-year-old Japanese man with a 6-year history of continuous ambulatory peritoneal dialysis (CAPD) presented to our emergency room with constipation and nausea of 7 days’ duration. The patient had been diagnosed with diabetes mellitus at the age of 40, and had begun PD at the age of 57. Peritoneal permeability in the fast peritoneal equilibrium test remained at a high average. He had been prescribed with 2.27% glucose dialysate (2 L/bag, 2 bags/day) and 7.5% icodextrin dialysate (2 L/bag, 1 bag/day). He had no past history of infectious peritonitis nor hemoperitoneum. Defecation ability ceased 7 days before presenting at our emergency room with constipation and nausea. His blood pressure was 155/80 mmHg, pulse 70 beats/min and temperature 37.8°C. His abdomen was distended with slight diffuse tenderness. A glycerin enema failed to elicit bowel movement and he was admitted with suspected EPS. Table 1 shows the
laboratory findings. Inflammatory markers (white blood cells and C-reactive protein [CRP]) were elevated (12,600 /μL and 23.62 mg/dL, respectively). Effluent fluid was slightly cloudy with elevated numbers of white blood cells in the sediment. Infectious peritonitis was tentatively diagnosed based on these findings. The patient’s oral intake was stopped and total parenteral nutrition was started. Peritoneal therapy was discontinued and hemodialysis (HD) was started on hospital day 3. The patient had nausea that was not improved by intravenous ceftazidime and the effluent remained cloudy. Repetitive effluent fluid culture remained negative. The peritoneal catheter was laparoscopically removed and re-implanted on hospital day 10. A laparoscopic examination revealed that the intestine was encapsulated by a thin white membrane (Figure 1). Figure 2A shows the histological
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JANUARY 2015 – VOL. 35, NO. 1
SHORT REPORTS
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Figure 2 — Histological findings of parietal peritoneum before (A, B) and after (C, D) treatment with hydrogen-enriched dialysate. (A) Thin membrane covering peritoneum consists mainly of homogeneous or lamellar fibrinous material containing fibroblasts stained with hematoxylin and eosin (HE). Mononuclear cell infiltration is visible in some areas (arrowheads). (B) Fibrinous materials (red or blue with Masson trichrome stain) suggest fibrin or organized fibrin components. (C) Sub-mesothelial connective tissue (compact zone) has become obviously thinner after treatment with H2 (mean: 190 μm; HE stain). (D) Surface is covered by mesothelial monolayer and fibrinous materials are absent (Masson trichrome stain). 254×366mm (72 × 72 DPI)
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JANUARY 2015 – VOL. 35, NO. 1 PDI
DISCUSSION
This case study showed that delivering H2 via HD and peritoneal lavage, in addition to oral prednisolone therapy, ameliorated EPS. Thus, H2 might have potential as a novel medical treatment for EPS. We cannot point out the definitive trigger of EPS occurrence in this case. However, the possible contribution of bacterial translocation (profound bacterial peritonitis) might be considered. Several case reports have described medical treatment of EPS using mainly tamoxifen and/or corticosteroid (17–20). One case-control study found that prophylactic tamoxifen suppressed EPS occurrence (21), and a nationwide cohort study in Japan showed that corticosteroid therapy caused 38.5% of EPS to go into remission (22). However, harmful ef fects such as ischemic stroke and pulmonary embolism are associated with tamoxifen and opportunistic infection is associated with corticosteroid. In contrast, H2 has been tested particularly in the field of deepwater diving, and no toxicity was identified even at high concentrations (23). Thus, H2 has therapeutic potential for pathological states that are related to oxidative stress and inflammation (24). 110
Figure 3 — Course of serum C-reactive protein and effluent white and red blood cells. 254x366mm (72 × 72 DPI) CRP = C-reactive protein; WBC = white blood cells; RBC = red blood cells; HPF = high-power field.
Dissolved hydrogen had been regarded as chemically i nactive until the discovery of its antioxidant effects (5). Since then, accumulating reports have indicated that H2 could be a useful new therapeutic modality in many biomedical fields. Consuming H2-enriched water exhibits anti-oxidative capabilities without detrimental effects in experimental (25–29) and clinical settings, including type II diabetes mellitus (30), metabolic syndrome (31), myopathies (progressive muscular dystrophy and polymyositis/dermatomyositis) (32), and rheumatoid arthritis (33). In addition, we also reported the clinical feasibility of using H2-enriched water as the dialysate for HD (13–15) and PD (16). The findings of these previous reports and the present case study indicate that H2 delivered via HD and peritoneal lavage could be useful as a novel medical treatment for EPS. In addition,
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findings of a biopsy specimen from the parietal peritoneum (hemotoxilin-eosinstain). Visualization using Masson trichrome revealed a peritoneal surface that was up to 2,000 μm thick and mainly comprised red or blue homogeneous or lamellar fibrinous material containing scatted fibroblasts. Figure 2B shows fibrin or organized fibrin components. Mesothelium was not identified. These findings and the clinical course indicated a final diagnosis of EPS. Prednisolone (30 mg/day) combined with peritoneal lavage using peritoneal dialysate somewhat improved the nausea and decreased the serum CRP level. However, the nausea worsened and CRP became elevated when the prednisolone dose was reduced to 20 mg/day on hospital day 21. Considering the possible contribution of oxidative stress on the pathogenesis of EPS, HD using H2-enriched dialysate (12) was started on hospital day 31. This decreased the CRP value (Figure 3) and improved the nausea. Oral intake was started on hospital day 38 without the recurrence of nausea. Peritoneal lavage using H2-enriched peritoneal solution was started on hospital day 40 to minimize peritoneal damage as described (16). This strategy obviously diminished the cloudiness of the effluent fluid due to blood (Figure 3). The prednisolone dose was gradually tapered to 0 by hospital day 77 and the patient was discharged on hospital day 94. Two months later, the peritoneal catheter was laparoscopically removed and a peritoneal biopsy was obtained. Intestinal encapsulation was not evident. The mean thickness of the sub-mesothelial connective tissue (compact zone) was 190 μm, and it was covered by a monolayer of mesothelial cells (Figure 2C and D). The patient has remained free of signs of EPS including ileus until now (for 18 months after the catheter removal).
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regular use of H2-enriched peritoneal dialysate might be an interesting focus of clinical trials from the viewpoint of peritoneal preservation. CONCLUSION
The present case report shows the efficacy of delivering H2 via HD and peritoneal lavage in EPS treatment. This experience suggests that hydrogen has potential as a novel medical treatment for EPS, and thus further investigation regarding this treatment is warranted. DISCLOSURES
Hiroyuki Terawaki1* Hirofumi Nakano2 Wan-Jun Zhu3 Masaaki Nakayama3 Dialysis center1 Fukushima Medical University, Fukushima, Japan Department of Internal Medicine2 Kashima Hospital, Iwaki, Japan Department of Nephrology3 Fukushima Medical Hospital, Fukushima, Japan *email: [email protected] REFERENCES 1. Hong KD, Bae JH, Jang YJ, Jung HY, Cho JH, Choi JY, et al. Encapsulating peritoneal sclerosis: case series from a university center. Korean J Intern Med 2013; 28:587–93. 2. Vidal E, Edefonti A, Puteo F, Chimenz R, Gianoglio B, Lavoratti G, et al. Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis. Nephrol Dial Transplant 2013; 28:1603–9. 3. Habib SM, Korte MR, Betjes MG. Lower mortality and inflammation from post-transplantation encapsulating peritoneal sclerosis compared to the classical form. Am J Nephrol 2013; 37:223–30. 4. Shroff R, Stefanidis CJ, Askiti V, Edefonti A, Testa S, Ekim M, et al. Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group. Nephrol Dial Transplant 2013; 28:1908–14. 5. Latus J, Ulmer C, Fritz P, Rettenmaier B, Biegger D, Lang T, et al. Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis-experience of a referral centre in Germany. Nephrol Dial Transplant 2013; 28:1021–30. 6. Lo WK, Kawanishi H. Encapsulating peritoneal sclerosis – medical and surgical treatment. Perit Dial Int 2009; 29:S211–4. 7. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13:688–94. 8. Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17:2241–52. 9. Huang KC, Yang CC, Lee KT, Chien CT. Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced
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The authors have no financial conflicts of interest to declare.
water. Kidney Int 2003; 64:704–14. 10. Huang KC, Hsu SP, Yang CC, Ou-Yang P, Lee KT, Morisawa S, et al. Electrolysed-reduced water reduced hemodialysis-induced e rythrocyte impairment in end-stage renal disease patients. Kidney Int 2006; 70:391–8. 11. Huang KC, Hsu SP, Yang CC, Ou-Yang P, Lee KT, Morisawa S, et al. Electrolysed-reduced water dialysate improves T-cell damage in end-stage renal disease patients with chronic haemodialysis. Nephrol Dial Transplant 2010; 25:2730–7. 12. Nakayama M, Kabayama S, Terawaki H, Nakayama K, Kato K, Sato T, et al. Less-oxidative hemodialysis solution rendered by cathode-side application of electrolyzed water. Hemodial Int 2007; 11:322–7. 13. Nakayama M, Kabayama S, Nakano H, Zhu WJ, Terawaki H, Nakayama K, et al. Biological effects of electrolyzed water in hemodialysis. Nephron Clin Pract 2009; 112:c9–15. 14. Nakayama M, Nakano H, Hamada H, Itami N, Nakazawa R, Ito S. A novel bioactive haemodialysis system using dissolved dihydrogen (H2) produced by water electrolysis: a clinical trial. Nephrol Dial Transplant 2010; 25:3026–33. 15. Terawaki H, Zhu WJ, Matsuyama Y, Terada T, Takahashi Y, Sakurai K, et al. Effect of a hydrogen (H2)-enriched solution on the albumin redox of hemodialysis patients. Hemodial Int 2014;18:459–66. 16. Terawaki H, Hayashi Y, Zhu WJ, Matsuyama Y, Terada T, Kabayama S, et al. Transperitoneal administration of dissolved hydrogen for peritoneal dialysis patients. A novel approach to suppress oxidative stress in the peritoneal cavity. Med Gas Res 2013; 3:14. 17. Allaria PM, Giangrande A, Gandini E, Pisoni IB. Continuous ambulatory peritoneal dialysis and sclerosing encapsulating peritonitis: tamoxifen as a new therapeutic agent? J Nephrol 1999;12:395–7. 18. Evrenkaya TR, Atasoyu EM, Unver S, Basekim C, Baloglu H, Tulbek MY. Corticosteroid and tamoxifen therapy in sclerosing encapsulating peritonitis in a patient on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 2004;19:2423–4. 19. Summers AM, Clancy MJ, Syed F, Harwood N, Brenchley PE, Augustine T, et al. Single-center experience of encapsulating peritoneal sclerosis in patients on peritoneal dialysis for end-stage renal failure. Kidney Int 2005; 68:2381–8. 20. Bhandari S, Wilkinsos A, Sellars L. Sclerosing peritonitis: value of immunosuppression prior to surgery. Nephrol Dial Transplant 1994; 9:436–7. 21. del Peso G, Bajo MA, Gil F, Aguilera A, Ros S, Costero O, et al. Clinical experience with tamoxifen in peritoneal fibrosing syndromes. Adv Perit Dial 2003; 19:32–5. 22. Kawanishi H, Kawaguchi Y, Fukui H, Hara S, Imada A, Kubo H, et al. Encapsulating peritoneal sclerosis in Japan: a prospective, controlled, multicenter study. Am J Kidney Dis 2004; 44:729–37. 23. Fontanari P, Badier M, Guillot C, Tomei C, Burnet H, Gardette B, et al. Changes in maximal performance of inspiratory and skeletal muscles during and after the 7.1-MPa Hydra 10 record human dive. Eur J Appl Physiol 2000; 81:325–8. 24. Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17:2241–52. 25. Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S. Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 2008; 377:1195–8. 26. Sato Y, Kajiyama S, Amano A, Kondo Y, Sasaki T, Handa S, et al. Hydrogenrich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice. Biochem Biophys Res Commun 2008; 375:346–50. 27. Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol 2009; 64:753–61. 28. Cardinal JS, Zhan J, Wang Y, Sugimoto R, Tsung A, McCurry KR, et al. Oral hydrogen water prevents chronic allograft nephropathy in rats. Kidney Int 2010; 77:101–9.
SHORT REPORTS 29. Zhu WJ, Nakayama M, Mori T, Nakayama K, Katoh J, Murata Y, et al. Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats. Nephrol Dial Transplant 2011; 26:2112–8. 30. Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008; 28:137–43. 31. Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic
JANUARY 2015 – VOL. 35, NO. 1 PDI syndrome – an open label pilot study. J Clin Biochem Nutr 2010; 46:140–9. 32. Ito M, Ibi T, Sahashi K, Ichihara M, Ito M, Ohno K. Open-label trial and randomized, double-blind, placebo-controlled crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Med Gas Res 2011; 1:24. 33. Ishibashi T, Sato B, Rikitake M, Seo T, Kurokawa R, Hara Y, et al. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. Med Gas Res 2012; 2:27. doi: 10.3747/pdi.2013.00255
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DISCLOSURES
The authors have no financial conflicts of interest to declare. Nelson Kopyt* Anshul Kumar Vibha Agrawal Lehigh Valley Health Network Allentown, PA *email: [email protected] REFERENCES 1. Dalrymple B, Mattick JS. An analysis of the organization and evolution of type 4 fimbrial (MePhe) subunit proteins. J Mol Evol 1987; 25:261–9. 2. Bøvre K. Family VIII. Neisseriaceae Prevot. In N. R. Krieg, ed. Manual of Systematic Bacteriology, Baltimore: The Williams & Wilkins co.; 1984: 288–309. 3. Knapp JS. Historical perspectives and identification of Neisseria and related species. Clin Microbiol Rev 1988; 1:415–31. 4. Gonorrhea Laboratory Information Kingella denitrificans. Centers for Disease Control and Prevention. [http://www.cdc.gov/std/Gonorrhea/ lab/Kden.htm] 5. Henriksen SD, Bøvre K. Transfer of Moraxella kingae Henriksen and Bøvre to the genus Kingella gen. nov. in the family Neisseriaceae. Int J Syst Bacteriol 1976; 26:447–50.
6. Snell JJS, Lapage SP. Transfer of some saccharolytic Moraxella species to Kingella Henriksen and Bøvre 1976, with descriptions of Kingella indologenes sp. nov. and Kingella denitrficans sp. nov. Int J Syst Bacteriol 1976; 26:451–8. 7. Hollis DG, Wiggins GL, Weaver RE. An unclassified gram-negative rod isolated from the pharynx on Thayer-Martin medium (selective agar). Appl Microbiol 1972; 24:772–7. 8. Brown, AM, Rothburn MM, Roberts C, Nye FJ. Septicaemia with probable endocarditis caused by Kingella denitrificans. J Infect 1987; 15:225–8. 9. Khan JA, Sharp S, Mann KR, Brewer J. Kingella denitrificans prosthetic endocarditis. Am J Med Sci 1986; 291(3):187–9. 10. Goldman IS, Ellner PD, Francke EL, Garvey GJ, Neu HC, Squilla N. Infective endocarditis due to Kingella denitnficans. Ann Intern Med 1980; 93:152–3. 11. Swann RA, Holmes B. Infective endocarditis caused by Kingella denitrificans. J Clin Pathol 1984; 37:1384–7. 12. Kim YH, Panday V, Reilly C. Isolation of Kingella denitrificans from a corneal ulcer. Cornea 2011; 30(4):472–3. 13. Morrison VA, Wagner KF. Clinical manifestations of Kingella kingae infections: case report and review. Rev Infect Dis 1989; 11:776–82. 14. Lalan SP, Warady BA, Blowey D, Waites KB, Selvarangan R. Mycoplasma edwardii peritonitis in a patient on maintenance peritoneal dialysis. Clin Nephrol 2015; 83(1):45–8. 15. Hassan IJ, Hayek L. Endocarditis caused by Kingella denitificans. J Infect 1993; 27:291–5. 16. Claesson B, Falsen E, Kjellman B. Kingella kingae infections: a review and a presentation of data from 10 Swedish cases. Scand J of Infect Dis 1985; 17: 233–43. 17. Geraci J, Wilson W. Endocarditis due to gram-negative bacteria. Report of 56 cases. Mayo Clinical Proceedings 1982; 57:145–8. 18. Figueiredo AE, Poli de Figueiredo CE, d’Avila DO. Peritonitis prevention in CAPD: to mask or not? Perit Dial Int 2000; 20:354–8. doi: 10.3747/pdi.2013.00248
Successful Treatment of Encapsulating Peritoneal Sclerosis by Hemodialysis and Peritoneal Lavage Using Dialysate Containing Dissolved Hydrogen Encapsulating peritoneal sclerosis (EPS) is the most serious and life-threatening complication of peritoneal dialysis (PD) therapy, as mortality is extremely high once it occurs. According to recent reports (1–5), mortality rate of EPS is 14 – 84%. Extensive fibrosing of the peritoneum in patients with EPS leads to symptoms of malnutrition and small bowel obstruction (ileus). Encapsulation can progress so that the bowel eventually becomes completely cocooned. The outcomes of several medical approaches such as tamoxifen, steroids, and newer immunosuppressive agents to retard EPS progression (6) remain poor. Moreover, in some alive cases, surgical approach (enterolysis, peritonectomy) is inevitable to cure symptoms of ileus (6). Dissolved hydrogen (H2) has a unique biological antioxidative and anti-inflammatory capacity (7). Accumulating evidence suggests that H2 ameliorates organ damage in various models of ischemia and inflammation (8). Clinical applications of H2 to pro-inflammatory disorders have been investigated, particularly for use during hemodialysis (HD) therapy (9–15). In addition, we recently showed that peritoneal dialysate containing high H2 concentrations could reduce both peritoneal and systemic oxidative stress in the clinical setting (16). 107
Downloaded from http://www.pdiconnect.com/ at UNIVERSITY OF IOWA LIBRARIES on July 25, 2015
due to Kingella species, nothing has been mentioned about using intraperitoneal antibiotics with PD fluid. Although our patient attempted to maintain strict sterile precautions and took appropriate care of her PD catheter site, 1 possibility may be that she contaminated the PD set with her oral secretions while coughing. She did admit that maybe 1 – 2 times she failed to use a facemask. This is a hypothesis only, as there is no definitive evidence of causality in our case. There is also no evidence in our case of the organism traversing the gastrointestinal tract to gain entrance into the peritoneal cavity. The possibility of causation via blood borne entry from the oral cavity or aerosol contamination seems to be the most plausible. Figueiredo et al. (18) suggested that use of a face mask during CAPD bag exchange gives no extra protection against peritoneal contamination. More importantly, patients must be educated to perform the connect/disconnect operation carefully, and to strictly observe accidental contamination of the hands. But the description was limited to a single renal unit with a seemingly small number of patients. Also, the patients were healthy and not sick like our patient who was coughing intermittently. This stresses the importance of strict hand hygiene and using a mask, especially if sick, before doing PD exchanges. She will be continued on long-term antibiotics for 6 weeks, her PD catheter was removed, and she will undergo intermittent hemodialysis with a tunneled catheter. In retrospect, she may have had a better outcome with intraperitoneal antibiotics. After completing her 42 days of antibiotics and close follow-up with regard to the clinical response, she will be re-evaluated regarding timing for the placement of a new PD catheter.
JANUARY 2015 – VOL. 35, NO. 1 PDI
SHORT REPORTS
In the present case study, dialysate enriched with H2 for both hemodialysis (HD) therapy and peritoneal lavage caused symptoms and laboratory signs of EPS to decrease. CASE HISTORY
TABLE 1 Laboratory Data Upon Admission Blood findings White blood cells Red blood cells Hemoglobin Hematocrit Platelets Total protein Albumin Total billirubin Aspartate aminotransferase Alanine aminotransferase Lactate dehydrogenase Gamma-glutamyl transpeptidase Urea nitrogen Creatinine Uric acid Sodium Chloride Potassium Calcium Inorganic phosphorus C-reactive protein Culture
12,600/μL 371 × 104/μL 12.0 g/dL 34.0% 14.9 × 104/μL 5.2 g/dL 2.9 g/dL 0.26 mg/dL 15 IU/L 13 IU/L 286 IU/L 8 IU/L 89.6 mg/dL 15.69 mg/dL 7.6 mg/dL 121 mEq/L 87 mEq/L 5.2 mEq/L 8.2 mg/dL 4.3 mg/dL 23.62 mg/dL Negative
Effluent fluid (sediment) findings Red blood cells >100/HPF White blood cells >500/HPF Mesothelial cells (-) Bacteria (+) Culture Negative HPF = high-power field.
108
Figure 1 — Macroscopic findings at laparoscopic examination. (A) Both visceral and parietal peritonea are whitish and thickened. Intestine is encapsulated by thin membrane. (B) Specimen of parietal peritoneum obtained under laparoscopic monitoring. 254×366mm (72 × 72 DPI)
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A 63-year-old Japanese man with a 6-year history of continuous ambulatory peritoneal dialysis (CAPD) presented to our emergency room with constipation and nausea of 7 days’ duration. The patient had been diagnosed with diabetes mellitus at the age of 40, and had begun PD at the age of 57. Peritoneal permeability in the fast peritoneal equilibrium test remained at a high average. He had been prescribed with 2.27% glucose dialysate (2 L/bag, 2 bags/day) and 7.5% icodextrin dialysate (2 L/bag, 1 bag/day). He had no past history of infectious peritonitis nor hemoperitoneum. Defecation ability ceased 7 days before presenting at our emergency room with constipation and nausea. His blood pressure was 155/80 mmHg, pulse 70 beats/min and temperature 37.8°C. His abdomen was distended with slight diffuse tenderness. A glycerin enema failed to elicit bowel movement and he was admitted with suspected EPS. Table 1 shows the
laboratory findings. Inflammatory markers (white blood cells and C-reactive protein [CRP]) were elevated (12,600 /μL and 23.62 mg/dL, respectively). Effluent fluid was slightly cloudy with elevated numbers of white blood cells in the sediment. Infectious peritonitis was tentatively diagnosed based on these findings. The patient’s oral intake was stopped and total parenteral nutrition was started. Peritoneal therapy was discontinued and hemodialysis (HD) was started on hospital day 3. The patient had nausea that was not improved by intravenous ceftazidime and the effluent remained cloudy. Repetitive effluent fluid culture remained negative. The peritoneal catheter was laparoscopically removed and re-implanted on hospital day 10. A laparoscopic examination revealed that the intestine was encapsulated by a thin white membrane (Figure 1). Figure 2A shows the histological
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Figure 2 — Histological findings of parietal peritoneum before (A, B) and after (C, D) treatment with hydrogen-enriched dialysate. (A) Thin membrane covering peritoneum consists mainly of homogeneous or lamellar fibrinous material containing fibroblasts stained with hematoxylin and eosin (HE). Mononuclear cell infiltration is visible in some areas (arrowheads). (B) Fibrinous materials (red or blue with Masson trichrome stain) suggest fibrin or organized fibrin components. (C) Sub-mesothelial connective tissue (compact zone) has become obviously thinner after treatment with H2 (mean: 190 μm; HE stain). (D) Surface is covered by mesothelial monolayer and fibrinous materials are absent (Masson trichrome stain). 254×366mm (72 × 72 DPI)
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DISCUSSION
This case study showed that delivering H2 via HD and peritoneal lavage, in addition to oral prednisolone therapy, ameliorated EPS. Thus, H2 might have potential as a novel medical treatment for EPS. We cannot point out the definitive trigger of EPS occurrence in this case. However, the possible contribution of bacterial translocation (profound bacterial peritonitis) might be considered. Several case reports have described medical treatment of EPS using mainly tamoxifen and/or corticosteroid (17–20). One case-control study found that prophylactic tamoxifen suppressed EPS occurrence (21), and a nationwide cohort study in Japan showed that corticosteroid therapy caused 38.5% of EPS to go into remission (22). However, harmful ef fects such as ischemic stroke and pulmonary embolism are associated with tamoxifen and opportunistic infection is associated with corticosteroid. In contrast, H2 has been tested particularly in the field of deepwater diving, and no toxicity was identified even at high concentrations (23). Thus, H2 has therapeutic potential for pathological states that are related to oxidative stress and inflammation (24). 110
Figure 3 — Course of serum C-reactive protein and effluent white and red blood cells. 254x366mm (72 × 72 DPI) CRP = C-reactive protein; WBC = white blood cells; RBC = red blood cells; HPF = high-power field.
Dissolved hydrogen had been regarded as chemically i nactive until the discovery of its antioxidant effects (5). Since then, accumulating reports have indicated that H2 could be a useful new therapeutic modality in many biomedical fields. Consuming H2-enriched water exhibits anti-oxidative capabilities without detrimental effects in experimental (25–29) and clinical settings, including type II diabetes mellitus (30), metabolic syndrome (31), myopathies (progressive muscular dystrophy and polymyositis/dermatomyositis) (32), and rheumatoid arthritis (33). In addition, we also reported the clinical feasibility of using H2-enriched water as the dialysate for HD (13–15) and PD (16). The findings of these previous reports and the present case study indicate that H2 delivered via HD and peritoneal lavage could be useful as a novel medical treatment for EPS. In addition,
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findings of a biopsy specimen from the parietal peritoneum (hemotoxilin-eosinstain). Visualization using Masson trichrome revealed a peritoneal surface that was up to 2,000 μm thick and mainly comprised red or blue homogeneous or lamellar fibrinous material containing scatted fibroblasts. Figure 2B shows fibrin or organized fibrin components. Mesothelium was not identified. These findings and the clinical course indicated a final diagnosis of EPS. Prednisolone (30 mg/day) combined with peritoneal lavage using peritoneal dialysate somewhat improved the nausea and decreased the serum CRP level. However, the nausea worsened and CRP became elevated when the prednisolone dose was reduced to 20 mg/day on hospital day 21. Considering the possible contribution of oxidative stress on the pathogenesis of EPS, HD using H2-enriched dialysate (12) was started on hospital day 31. This decreased the CRP value (Figure 3) and improved the nausea. Oral intake was started on hospital day 38 without the recurrence of nausea. Peritoneal lavage using H2-enriched peritoneal solution was started on hospital day 40 to minimize peritoneal damage as described (16). This strategy obviously diminished the cloudiness of the effluent fluid due to blood (Figure 3). The prednisolone dose was gradually tapered to 0 by hospital day 77 and the patient was discharged on hospital day 94. Two months later, the peritoneal catheter was laparoscopically removed and a peritoneal biopsy was obtained. Intestinal encapsulation was not evident. The mean thickness of the sub-mesothelial connective tissue (compact zone) was 190 μm, and it was covered by a monolayer of mesothelial cells (Figure 2C and D). The patient has remained free of signs of EPS including ileus until now (for 18 months after the catheter removal).
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regular use of H2-enriched peritoneal dialysate might be an interesting focus of clinical trials from the viewpoint of peritoneal preservation. CONCLUSION
The present case report shows the efficacy of delivering H2 via HD and peritoneal lavage in EPS treatment. This experience suggests that hydrogen has potential as a novel medical treatment for EPS, and thus further investigation regarding this treatment is warranted. DISCLOSURES
Hiroyuki Terawaki1* Hirofumi Nakano2 Wan-Jun Zhu3 Masaaki Nakayama3 Dialysis center1 Fukushima Medical University, Fukushima, Japan Department of Internal Medicine2 Kashima Hospital, Iwaki, Japan Department of Nephrology3 Fukushima Medical Hospital, Fukushima, Japan *email: [email protected] REFERENCES 1. Hong KD, Bae JH, Jang YJ, Jung HY, Cho JH, Choi JY, et al. Encapsulating peritoneal sclerosis: case series from a university center. Korean J Intern Med 2013; 28:587–93. 2. Vidal E, Edefonti A, Puteo F, Chimenz R, Gianoglio B, Lavoratti G, et al. Encapsulating peritoneal sclerosis in paediatric peritoneal dialysis patients: the experience of the Italian Registry of Pediatric Chronic Dialysis. Nephrol Dial Transplant 2013; 28:1603–9. 3. Habib SM, Korte MR, Betjes MG. Lower mortality and inflammation from post-transplantation encapsulating peritoneal sclerosis compared to the classical form. Am J Nephrol 2013; 37:223–30. 4. Shroff R, Stefanidis CJ, Askiti V, Edefonti A, Testa S, Ekim M, et al. Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group. Nephrol Dial Transplant 2013; 28:1908–14. 5. Latus J, Ulmer C, Fritz P, Rettenmaier B, Biegger D, Lang T, et al. Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis-experience of a referral centre in Germany. Nephrol Dial Transplant 2013; 28:1021–30. 6. Lo WK, Kawanishi H. Encapsulating peritoneal sclerosis – medical and surgical treatment. Perit Dial Int 2009; 29:S211–4. 7. Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007; 13:688–94. 8. Ohta S. Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications. Curr Pharm Des 2011; 17:2241–52. 9. Huang KC, Yang CC, Lee KT, Chien CT. Reduced hemodialysis-induced oxidative stress in end-stage renal disease patients by electrolyzed reduced
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The authors have no financial conflicts of interest to declare.
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SHORT REPORTS 29. Zhu WJ, Nakayama M, Mori T, Nakayama K, Katoh J, Murata Y, et al. Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats. Nephrol Dial Transplant 2011; 26:2112–8. 30. Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, et al. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutr Res 2008; 28:137–43. 31. Nakao A, Toyoda Y, Sharma P, Evans M, Guthrie N. Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic
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