Peritoneal dialysis-related infections in elderly patients.

This review outlines the epidemiology, characteristics, risk factors, and prognosis of peritoneal dialysis (PD)-related peritonitis, PD catheter-related infections, and the effects of assisted PD in elderly patients from the Japanese perspective. Based on the literature, the incidence of peritonitis is likely to be higher in elderly patients than in younger patients. The most frequent causative bacteria in elderly patients are Gram-positive bacteria, as in adult PD patients, most commonly due to transcatheter infection. However, elderly patients may have difficulty recognizing cloudy drainage fluid due to decreased visual acuity. Hypokalemia, the use of gastric acid suppressants, prophylactic antibiotic use before endoscopy, biocompatible fluids and hypoalbuminemia considered modifiable risk factors for peritonitis. However, the mechanism by which treatment of hypokalemia prevents peritonitis is unknown. Currently, the relationship between gastric acid suppression therapy and peritonitis in elderly patients is debatable, with no evidence to strongly recommend uniform discontinuation of gastric acid suppression therapy. Exit-site infection (ESI) is a major risk factor for the development of peritonitis, and appropriate prevention and management of ESI may reduce infection-related hospitalizations in PD patients. Currently, no randomized, controlled trials have verified the effectiveness of antibiotic application for ESI in Japan, but results from other countries are awaited. In assisted PD, it is extremely important that family members, caregivers, and nurses who support the procedure receive sufficient education and training from medical professionals familiar with PD. Early detection and treatment of PD-related infections are required because the risk of death increases in elderly patients.

Pathophysiology of encapsulating peritoneal sclerosis: lessons from findings of the past three decades in Japan.

Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS.

The Transfer of the Hepatocyte Growth Factor Gene by Macrophages Ameliorates the Progression of Peritoneal Fibrosis in Mice.

Growing evidence indicates that hepatocyte growth factor (HGF) possesses potent antifibrotic activity. Furthermore, macrophages migrate to inflamed sites and have been linked to the progression of fibrosis. In this study, we utilized macrophages as vehicles to express and deliver the HGF gene and investigated whether macrophages carrying the HGF expression vector (HGF-M) could suppress peritoneal fibrosis development in mice. We obtained macrophages from the peritoneal cavity of mice stimulated with 3% thioglycollate and used cationized gelatin microspheres (CGMs) to produce HGF expression vector-gelatin complexes. Macrophages phagocytosed these CGMs, and gene transfer into macrophages was confirmed in vitro. Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) for three weeks; seven days after the first CG injection, HGF-M was administered intravenously. Transplantation of HGF-M significantly suppressed submesothelial thickening and reduced type III collagen expression. Moreover, in the HGF-M-treated group, the number of α-smooth muscle actin- and TGF-ß-positive cells were significantly lower in the peritoneum, and ultrafiltration was preserved. Our results indicated that the transplantation of HGF-M prevented the progression of peritoneal fibrosis and indicated that this novel gene therapy using macrophages may have potential for treating peritoneal fibrosis.

Comparison of the 2013 and 2019 Nationwide Surveys on the Management of Chronic Kidney Disease by General Practitioners in Japan.

In 2019, the Japan Physicians Association conducted a second nationwide survey on the management of chronic kidney disease (CKD) among the Japanese general practitioners (GPs). We aimed to clarify the changes in the state of CKD medical care by GPs since the 2013 survey. The 2013 and 2019 surveys included 2214 and 601 GPs, respectively, who voluntarily participated. The two surveys were compared, using propensity score matching to balance the background of the responded GPs. For the medical care of CKD, the frequency of urine or blood examination, use of estimated glomerular filtration rate (eGFR) value for CKD management, and continuous use of renin-angiotensin system inhibitors for their reno-protective effects were significantly higher in 2019 than in 2013 (all: p < 0.001). The medical cooperation in CKD management, the utilization of the clinical path for CKD management and the measurement of the eGFR during the medical health checkup were significantly increased in 2019, compared to those in 2013. More GPs felt dissatisfied with the components of CKD treatment by nephrologists (p < 0.001). The two surveys confirmed improvements in the level of medical care for CKD and a strengthening in cooperation. However, the dissatisfaction with the consultation with nephrologists did not necessarily improve.

Nationwide questionnaire survey on the management of chronic kidney disease for general practitioners in Japan.

BACKGROUND: In 2019, a nationwide questionnaire survey on the management of chronic kidney disease (CKD) was circulated to general practitioners (GPs) throughout Japan by The Japan Physicians Association. The aim was to assess the current state of CKD medical care in the country and evaluate the utilization of CKD-specific guidelines in the treatment by GPs. METHODS: The voluntary survey targeted all members of Japan Physicians Association, a nationwide organization consisting primarily of 15,000 GPs in clinics throughout the country. GPs were divided into groups: 171 GPs using and 414 GPs not using the guidelines. Comparisons between the groups' responses were made using propensity score matching and component cluster analysis. RESULTS: Overall responses revealed that the estimated glomerular filtration rate's utilization rate was high (95.1%). However, evidence-practice gaps in urine protein quantification and anemia remedy were prominent. There were significantly favorable answers in terms of CKD management in the user group compared with those in the non-user group, except for the questions about a urine check at the first visit, stopping the use of renin-angiotensin system inhibitors, and the target blood pressure for elderly CKD patients. The differences suggest that utilization of the CKD guidelines has improved CKD management practices by GPs. CONCLUSIONS: Further promotion of CKD guidelines utilization (28% in this survey) is considered valid for CKD medical education.

An inhibitor of Krüppel-like factor 5 suppresses peritoneal fibrosis in mice.

BACK GROUND: Krüppel-like transcription factor 5 (KLF5) is a transcription factor regulating cell proliferation, angiogenesis and differentiation. It has been recently reported that Am80, a synthetic retinoic acid receptor α-specific agonist, inhibits the expression of KLF5. In the present study, we have examined the expression of KLF5 in fibrotic peritoneum induced by chlorhexidine gluconate (CG) in mouse and evaluated that Am80, as an inhibitor of KLF5, can reduce peritoneal fibrosis. METHODS: Peritoneal fibrosis was induced by intraperitoneal injection of CG into peritoneal cavity of ICR mice. Am80 was administered orally for every day from the start of CG injection. Control mice received only a vehicle (0.5% carboxymethylcellulose solution). After 3 weeks of treatment, peritoneal equilibration test (PET) was performed and peritoneal tissues were examined by immunohistochemistry. RESULTS: The expression of KLF5 was less found in the peritoneal tissue of control mice, while KLF5 was expressed in the thickened submesothelial area of CG-injected mice receiving the vehicle. Am80 treatment reduced KLF5 expression and remarkably attenuated peritoneal thickening, accompanied with the reduction of type III collagen expression. The numbers of transforming growth factor ß-positive cells, α-smooth muscle actin-positive cells and infiltrating macrophages were significantly decreased in Am80-treated group. PET revealed the increased peritoneal permeability in CG mice, whereas Am80 administration significantly improved the peritoneal high permeability state. CONCLUSIONS: These results indicate the involvement of KLF5 in the progression of experimental peritoneal fibrosis and suggest that Am80 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of KLF5 expression.

Usefulness of the quantitative measurement of urine protein at a community-based health checkup: a cross-sectional study.

BACKGROUND: The dipstick urinalysis for proteinuria has been used for chronic kidney disease (CKD) screening at community-based health checkups; however, it has major drawbacks in that the result is only semi-quantitative and is influenced by urine concentration. METHODS: We conducted urine protein/creatinine ratio (UPCR) measurements of 590 participants who showed a result of more than trace proteinuria on a dipstick analysis and evaluated the usefulness of UPCR measurements in community-based health checkups. RESULTS: The UPCR values increased in accordance with the severity of the dipstick test findings, but statistical significance was only obtained between (±) and (1+), between (±) and (2+), and between (±) and (3+) groups. When the participants with (±) proteinuria were subjected to CGA classification (a classification of CKD by cause, glomerular filtration rate category, and albuminuria category) according to their UPCR data, a significant proportion of subjects (277, 77.0%) moved from the A2 category into A1, which is a less severe category. Conversely, 21 subjects (5.8%) were reclassified into a more severe category (A3). Thus, a dipstick test may produce a non-negligible number of false negatives as well as a large number of false positives. Similarly, the classifications of more than half of the subjects with (1+) or more severe proteinuria were changed based on their UPCR results. CONCLUSION: The dipstick urinalysis for proteinuria appears less reliable than expected, suggesting that the quantitative measurement of urine protein should be performed even during mass health checkups to ensure the early detection and prevention of CKD.

Impact of tonsillectomy combined with steroid pulse therapy on immunoglobulin A nephropathy depending on histological classification: a multicenter study.

BACKGROUND: In addition to corticosteroids and inhibition of the renin-angiotensin-aldosterone system, tonsillectomy with steroid pulse therapy (TSP) may have a beneficial impact on the clinical course of IgA nephropathy (IgAN). However, there is still much uncertainty regarding the indications for therapy, treatment protocol, and therapeutic options for IgAN. METHODS: In this multicenter retrospective cohort study, we enrolled 284 patients with biopsy-proven IgAN who received TSP or corticosteroid therapy or conservative therapy. The effects of TSP on clinical remission (CR) were evaluated after a median follow-up period of 4.1 years in relation to histological classifications. RESULTS: Among the 284 participants, 161 patients received TSP. During the observation time, 141 patients (49.6%) achieved CR, with a median time to remission of 397 days. In multivariate Cox regression analyses, TSP had an impact on achieving CR in only the group with histological grade 3 defined as glomerulosclerosis, crescent formation or adhesion to Bowman's capsule in 10-30% of all biopsied glomeruli, or mild cellular infiltration in the interstitium (hazard ratio (HR) 4.29, 95% confidence interval (95%CI) 1.88-11.19, P < 0.001). TSP independently contributed to a higher incidence of CR, particularly in the patient group showing evident mesangial hypercellularity (HR 2.54, 95%CI 1.38-5.08, P = 0.002). CONCLUSIONS: TSP may have a beneficial effect on the clinical course in IgAN patients with mild to moderate glomerular and interstitial lesions, particularly with distinct mesangial cell proliferation.

Significance of tonsillectomy combined with steroid pulse therapy for IgA nephropathy with mild proteinuria.

BACKGROUND: Medical intervention for patients with IgA nephropathy and mild proteinuria (<1.0 g/day) is controversial, and the effectiveness of tonsillectomy plus steroid pulse therapy (TSP) for such patients remains obscure. METHODS: Among 323 patients in our multicenter cohort study, 79 who had mild proteinuria (0.4-1.0 g/day) at diagnosis were eligible to participate in this study. We compared the clinicopathological findings at diagnosis, a decline in renal function defined as a 50 or 100% increase in serum creatinine (sCr) and clinical remission (CR) defined as the disappearance of hematuria and proteinuria (<0.3 g/day) among groups given TSP (n = 46), steroid therapy (ST) (n = 9), and non-ST (n = 24). Factors contributing to CR were also evaluated using multivariate analysis. RESULTS: Background factors at diagnosis including age, ratio (%) of patients with hypertension, sCr, proteinuria, and histological severity did not significantly differ among the groups. Only two patients each in the TSP (4.3%) and non-ST (8.3%) groups achieved a 50% increase in sCr during a mean follow-up period of 4.7 years. At the final observation, 71.7, 44.4, and 41.7% of patients in the TSP, ST, and non-ST groups, respectively, achieved CR (p = 0.032). Cox proportional hazards models revealed that TSP led to CR more effectively than non-TSP by a factor of about threefold (hazard ratio, 2.74; p = 0.008). CONCLUSION: TSP therapy has potential for inducing CR in patients with IgAN and mild proteinuria (<1.0 g/day).

Morphological characteristics in peritoneum in patients with neutral peritoneal dialysis solution.

Peritoneal dialysis solution (PDS) plays a role in functional and morphological damage to the peritoneum. This study aimed to clarify the effect of neutral PDS in preventing morphological changes by assessing peritoneal damage and comparing morphological alterations between PD patients treated with neutral PDS and acidic PDS. Sixty-one patients participated from seven hospitals. All patients were treated with neutral PDS excluding icodextrin, during their entire PD treatment, and experienced no episode of peritonitis. The thickness of submesothelial compact (SMC) zone and the presence of vasculopathy in the anterior parietal abdominal peritoneum were assessed. The impact of icodextrin, hybrid therapy, and peritoneal rest and lavage in morphological alterations were determined. There was no significant difference in the average SMC thickness between neutral and acidic PDS. The vessel patency in patients using neutral PDS was significantly higher compared to that in acidic PDS at any time during PD. There were no significant suppressive effects from interventions or use of icodextrin with respect to peritoneal morphological injury. A monolayer of mesothelial cell was observed in approximately half the patients, especially in their receiving lavage patients. Neutral PDS, accompanied by other preventive approaches against peritoneal injury, might suppress the development of peritoneal morphological alterations.

Encapsulating peritoneal sclerosis in the era of a multi-disciplinary approach based on biocompatible solutions: the NEXT-PD study.

INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD). Over the past decade in Japan, a multidisciplinary approach has been adopted to minimize the incidence and improve outcomes of EPS. This strategy includes planned PD discontinuation for high-risk patients and the introduction of biocompatible solutions. This study examined the current clinical status of EPS in representative PD centers in Japan. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Patients (n = 1,338) from 55 PD centers in Japan who were using neutral-pH solutions from the initiation of therapy (mean age, 62 years; median PD duration, 32 months; concomitant use of icodextrin, 35.2%; PD and hemodialysis combination therapy, 12.2%) were assessed every 6 months to ascertain the reasons for PD discontinuation and the development of EPS development. Outcomes were also recorded. The study period was from November 2008 to March 2012. RESULTS: There were 727 patients who discontinued PD, including 163 deaths. Among all causes of PD withdrawal except for death, planned PD discontinuation to avoid EPS was utilized in 58 cases (7.1% in total). The strategy was increasingly utilized in proportion to the duration of PD: 0.5% for patients undergoing PD for < 3 years, 0.6% for patients undergoing PD for 5 years, 14.7% for patients undergoing PD for 8 years, and 35.5% for patients undergoing PD for > 8 years. Fourteen patients developed EPS (three cases after PD), which corresponded with an overall incidence of 1.0%. The incidence according to the duration of PD was 0.3% for PD < 3 years, 0.6% for PD = 5 years, 2.3% for PD = 8 years, and 1.2% for PD > 8 years. In terms of therapy, 11 patients were treated with prednisolone (PSL), and surgical enterolysis was utilized in two cases. Complete remission of abdominal symptoms was achieved in twelve patients (85.7%), and three died due to EPS (mortality rate of 21.4%). CONCLUSIONS: Use of the multidisciplinary approach described above reduces the risk of the development of EPS according to PD duration. In cases of de novo EPS cases in Japan, this strategy can also attenuate the clinical course of the condition.

Involvement of leptin in the progression of experimentally induced peritoneal fibrosis in mice.

Leptin is a hormone mainly produced by white adipose cells, and regulates body fat and food intake by acting on hypothalamus. Leptin receptor is expressed not only in the hypothalamus but in a variety of peripheral tissues, suggesting that leptin has pleiotropic functions. In this study, we investigated the effect of leptin on the progression of peritoneal fibrosis induced by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 2 or 3 weeks in mice. This study was conducted in male C57BL/6 mice and leptin-deficient ob/ob mice. Peritoneal fluid, blood, and peritoneal tissues were collected 15 or 22 days after CG injection. CG injection increased the level of leptin in serum and peritoneal fluid with thickening of submesothelial compact zone in wild type mice, but CG-injected ob/ob mice attenuate peritoneal fibrosis, and markedly reduced the number of myofibroblasts, infiltrating macrophages, and blood vessels in the thickened submesothelial area. The 2-week leptin administration induced a more thickened peritoneum in the CG-injected C57BL/6 mice than in the PBS group. Our results indicate that an upregulation of leptin appears to play a role in fibrosis and inflammation during peritoneal injury, and reducing leptin may be a therapeutically potential for peritoneal fibrosis.

Recombinant human erythropoietin attenuates renal tubulointerstitial injury in murine adriamycin-induced nephropathy.

BACKGROUND: Erythropoietin (EPO) has been found to provide cytoprotection against acute ischemic and toxic renal tubulointerstitial injury. This study aimed to elucidate the mechanism(s) underlying EPO protection while examining whether EPO provides tubulointerstitial protection in a mouse model with adriamycin (ADR)-induced tubulointerstitial injury. METHODS: Adriamycin nephropathy (AN) was induced by a single injection of ADR in the 2 experimental groups on day 0. The saline-control group and the AN-saline group were administered saline at days 7, 14, and 21, while the EPO-control group and the AN-EPO group were administered EPO at days 7, 14, and 21. Kidneys were harvested at days 14 and 28 after ADR injection to measure the expression levels of the EPO receptor (EPO-R), CD34, and phosphorylated Akt by immunohistochemistry; to determine the extent of apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and active caspase-3 staining; and to map the hypoxic area by pimonidazole staining. RESULTS: EPO-R was detected in glomerular, tubular epithelial, and endothelial cells. EPO administration significantly improved tubulointerstitial injury, decreased the number of TUNEL-positive and active caspase-3-positive cells, and increased the phosphorylated-Akt-positive area in the tubulointerstitial area without increasing the hemoglobin or hematocrit levels. CONCLUSIONS: EPO provides renoprotection against AN by reducing apoptotic cell death and preserving peritubular capillaries, possibly by exerting pleiotropic effects independently of its hemopoietic effects.

22-Oxacalcitriol prevents progression of peritoneal fibrosis in a mouse model.

OBJECTIVE: Vitamin D plays an important role in calcium homeostasis and is used to treat secondary hyperparathyroidism among dialysis patients. The biologic activity of vitamin D and its analogs is mediated by vitamin D receptor (VDR), which is distributed widely throughout the body. Recent papers have revealed that low vitamin D levels are correlated with severe fibrosis in chronic diseases, including cystic fibrosis and hepatitis. The aim of the present study was to evaluate the protective effects of vitamin D against the progression of peritoneal fibrosis. METHODS: Peritoneal fibrosis was induced by injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. An analog of vitamin D, 22-oxacalcitriol (OCT), was administered subcutaneously daily from initiation of the CG injections. The peritoneal tissue was excised at 3 weeks. Changes in morphology were assessed by hematoxylin and eosin staining. Expression of VDR, alpha smooth muscle actin (as a marker of myofibroblasts), type III collagen, transforming growth factor ß(TGF-ß), phosphorylated Smad2/3, F4/80 (as a marker of macrophages), and monocyte chemoattractant protein-1 (MCP-1) was examined by immunohistochemistry. Southwestern histochemistry was used to detect activated nuclear factor κB (NF-κB). RESULTS: In the CG-injected mice, immunohistochemical analysis revealed expression of VDR in mesothelial cells, myofibroblasts, and macrophages in the thickened submesothelial zone. Treatment with OCT significantly prevented peritoneal fibrosis and reduced the accumulation of type III collagen in CG-treated mice. Among the markers of fibrosis, the numbers of myofibroblasts, cells positive for TGF-ß, and cells positive for phosphorylated Smad2/3 were significantly decreased in the OCT-treated group compared with the vehicle-treated group. Furthermore, OCT suppressed inflammatory mediators of fibrosis, as shown by the reduced numbers of activated NF-κB cells, macrophages, and MCP-1-expressing cells. CONCLUSIONS: Our results indicate that OCT attenuates peritoneal fibrosis, an effect accompanied by reduced numbers of myofibroblasts, infiltrating macrophages, and TGF-ß-positive cells, suggesting that vitamin D has potential as a novel therapeutic agent for preventing peritoneal sclerosis.

[Current status of and regional differences in CKD management and medical cooperation in Japan: from the results of a nationwide questionnaire survey for primary care physicians].

OBJECTIVE: The goal of this study was to figure out the current status of and regional differences in CKD management and medical cooperation in Japan. METHODS: We conducted a nationwide questionnaire survey on CKD management for primary care physicians (PCPs) from December 2012 to March 2013. The questionnaire included 36 items about CKD management and medical cooperation. In order to compare the current status of CKD care and cooperation, we divided the country into 11 areas; Hokkaido, Tohoku, Kanto, Koshin-etsu, Hokuriku, Chubu-Tokai, Kinki, Chugoku, Shikoku, Kyushu and Okinawa. RESULTS: 28,200 sets of questionnaires were delivered to PCPs throughout Japan, and 2,287 (8.1%) doctors responded. Doctors at clinics accounted for 86.5%, and 90.9% were non-nephrologists. Regional differences were evident in the following items regarding CKD management; urinalysis at the first examination, measurement of urinary protein/albumin excretion, frequency of blood testing, counselling with eGFR, prescription of erythropoiesis stimulating agents (ESA). Urinalysis at the first examination was relatively rare in Koshin-etsu and Kanto (p < 0.01), and counseling with eGFR was relatively rare in Tohoku, Shikoku and Koshin-etsu (p = 0.05). Regional differences regarding medical cooperation were evident in the following items; functional level of cooperation, critical path, presence of consulting nephrologist, personal relationship, satisfaction with the nephrologists' reaction to referral, CKD involvement in Specific Medical Checkup/Specific Medical Guidance. Functional level of cooperation was higher in Chugoku, Okinawa, Chubu-Tokai and Hokuriku, and lower in Shikoku, Koshin-etsu and Kinki (p < 0.05). Serum creatinine measurement in the Specific Medical Checkup was involved more frequently in Okinawa, Shikoku, Kanto, Chubu-Tokai, Kyushu and Hokuriku, and less frequently in Tohoku, Chugoku and Kinki (p < 0.01). CONCLUSION: We elucidated the current status of CKD management by PCPs and medical cooperation in Japan. Effective actions to improve CKD care must be proposed on the basis of these data, especially the existing regional differences.

[Influence of physicians' subspecialty and training history on CKD management and medical cooperation: from the results of a nationwide questionnaire survey for primary care physicians].

OBJECTIVE: The goal of this study was to elucidate how the subspecialty and training history of primary care physicians(PCPs) influence CKD management and medical cooperation in Japan. METHODS: We conducted a nationwide questionnaire survey on CKD management for PCPs from December 2012 to March 2013. The questionnaire included 32 items about CKD management and medical cooperation. PCPs' subspecialties were categorized as follows: general internal medicine, nephrology, cardiology, diabetology/endocrinology, gastroenterology, pulmonology, neurology, neurosurgery, hematology, collagen disease/rheumatology, allergology. The PCPs' training history of nephrology was classified into three categories: none, experienced, active-nephrologist. Response distributions for each question were compared between the PCPs' subspecialties and the three categories of training history. RESULTS: 2,287 out of 28,200 PCPs (8.1%) of all 47 prefectures responded. The majority (86.5%) of responders were PCPs at clinics, and 90.9% were non-nephrologists. The PCPs' subspecialty influenced the response distributions in the following questions: utilization of the CKD guidebook, urinalysis at the first and follow-up examinations, frequency of blood testing, counselling with eGFR, self-monitoring of blood pressure, prescription and cessation of renin-angiotensin system (RAS) inhibitors, anemia treatment with erythropoiesis stimulating agents (ESA). The PCPs' training history of nephrology had a strong impact on various aspects of CKD management. The PCPs' subspecialties also influenced the responses regarding medical cooperation of CKD: relationship with nephrologists, utilization of critical path, criterion of patient referral, requests for nephrologists, discontent with the nephrologists' response. CONCLUSION: We elucidated that the PCPs' subspecialty and training history of nephrology substantially influenced CKD management and medical cooperation in Japan. Effective promotion activities to improve CKD management and medical cooperation should be proposed on the basis of these data.

Production and degradation of extracellular matrix in reversible glomerular lesions in rat model of habu snake venom-induced glomerulonephritis.

We investigated the mechanism of development and repair process of glomerular injury in a rat model of habu snake (Trimeresurus flavoviridis) venom (HSV)-induced glomerulonephritis. Glomerulonephritis was induced in rats by intravenously injecting HSV at 3 mg/kg. Renal tissue was isolated and subjected to immunohistochemical analysis for expression levels of type IV collagen, heat shock protein 47 (HSP47), transforming growth factor-ß (TGF-ß), and matrix metalloproteinase-3 (MMP-3), as well as its transcription factor Ets-1. Expression levels of HSP47, TGF-ß, and type IV collagen began to increase in the mesangial area starting from day 14 and peaked on day 21, followed by a gradual decrease. Expression levels of MMP-3 and Ets-1 started to increase coinciding with peak production of mesangial matrix on day 21, peaking on day 35, followed by gradual decrease. Expression of MMP-3 and Ets-1 persisted until day 63, whereas that of HSP47 and type IV collagen returned to baseline level at this time point. Time-course changes of extracellular matrix (ECM) accumulation in glomeruli in the HSV-induced glomerulonephritis model were correlated with those of factors involved in both ECM production and degradation systems. Continued expression of factors in the degradation system seems particularly important for the repair process. These findings might lead to new therapies that prevent and repair glomerular injury.

Involvement of lymphocyte infiltration in the progression of mouse peritoneal fibrosis model.

Peritoneal fibrosis is a serious complication in patients with severe chronic kidney disease who are undergoing peritoneal dialysis (PD). One of the pathological characteristics of peritoneal fibrosis is the infiltration of macrophages in the thickened submesothelial compact zone. In addition, infiltration of lymphocytes, including T and B lymphocytes, is observed in the fibrotic peritoneum. However, the relationship between lymphocyte infiltration and progression of peritoneal fibrosis remains unclear. In this study, we investigated the role of lymphocytes in the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG) by comparing the histological changes observed in severe combined immunodeficient (SCID) mice (largely lacking functional T and B lymphocytes) with those observed in wild-type (WT) mice. As expected, CG-injected WT mice showed a thickening of the submesothelial compact zone together with massive collagen deposition accompanied by increased numbers of infiltrating macrophages and T and B lymphocytes. In the peritoneum of SCID mice, the submesothelial compact zone was thicker and the number of macrophages and B lymphocytes was significantly higher than that observed in control immunodeficient and WT mice. In contrast, the number of T lymphocytes in the peritoneum of SCID mice was significantly lower than that in the peritoneum of WT mice. These results suggest that T and B lymphocytes modulate the process of peritoneal fibrosis via macrophage infiltration.