Nanae Matsuo

Serum beta2 microglobulin (beta2MG) level is a potential predictor for encapsulating peritoneal sclerosis (EPS) in peritoneal dialysis patients.

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). The aim of this study was to find a predictor for EPS. METHODS Patients with EPS who were detected by a historical cohort study using clinical data of 219 CAPD patients at our hospital. We recruited 25 patients with EPS who were compared with the patients without EPS who were matched for age and dialysis period as controls. Differences between the two groups (non-EPS group and EPS group) with respect to age, gender, primary disease, dialysis period, serum urea nitrogen, serum creatinine, beta2MG, CRP and PET (peritoneal equilibration test) category (determined by the peritoneal function testing) were analyzed. RESULTS According to multiple regression analysis, a high beta2MG level was an independent risk factor for EPS (odds ratio 1.162, 95% confidence interval 1.026 - 1.317, p = 0.018). Other clinical markers did not show positive significance. A ROC (receiver operating characteristic) curve was prepared to evaluate the suitability of I(2)2MG measurement as a screening test. The sensitivity was 64% and the specificity was 80% when a beta2MG level of 37.0 mg/dl was taken as the cut-off value. The odds ratio for occurrence of EPS was 8.8 when beta2MG level was in the range of 35 - 40 mg/dl, 13.5 when I(2)2MG level was > 40 mg/dl and 1 when beta2MG level was < 30 mg/dl. CONCLUSION These findings suggest that beta2MG is useful as a screening test for the onset of EPS, and that beta2MG and accumulation of middle-molecular uremic substances may be related to the pathophysiology of EPS.

Relationship Between the −374T/A Receptor of Advanced Glycation End Products Gene Polymorphism and Peritoneal Solute Transport Status at the Initiation of Peritoneal Dialysis

Abstract:  An increased peritoneal solute transport rate (PSTR) at baseline is well known to be associated with decreased patient and technique survival in patients undergoing peritoneal dialysis (PD). Recently, angiogenesis has been recognized to be associated with PSTR and peritoneal deterioration. To investigate genetic variations in genes related to angiogenesis, 30 incident PD patients were studied. Several single nucleotide polymorphisms of the vascular endothelial growth factor (VEGF), the endothelial nitric oxide synthase (eNOS) and the receptor for advanced glycation end product (RAGE) were analyzed by the pyrosequencing method. The dialysate‐to‐plasma ratio of creatinine (D/P Cr) obtained from a peritoneal equilibrium test (PET) during the first 12 months after initiation of PD was used for a marker of PSTR. The D/P Cr was assessed both as a continuous and as a categorical variable including high (H), high‐average (HA), low‐average (LA), and low (L). Baseline D/P Cr was 0.645 ± 0.083. The RAGE −374 TA genotype had a significantly lower prevalence of the H/HA transporters than the TT genotype (20% vs 63%; P = 0.03). Genetic polymorphisms of the VEGF and eNOS were not associated with initial peritoneal transport type. The RAGE polymorphism may have a considerable effect on the basal PSTR. Further studies will be needed to confirm this hypothesis.

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan

Peritoneal dialysis‐associated peritonitis (PD‐associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin‐bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection‐causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single‐bag and conventional PD solutions (S+C group, N = 145), twin‐bag and conventional PD solutions (T+C group, N = 171) and twin‐bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD‐associated peritonitis incidences. Incidences of PD‐associated peritonitis (times per patient‐months) and peritonitis‐free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin‐bag system has made a greater contribution to reductions in PD‐associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis.

Successful treatment of BK virus nephropathy using therapeutic drug monitoring of mycophenolic acid.

We report the successful management of BK virus nephropathy (BKVN) using therapeutic drug monitoring (TDM) of mycophenolic acid (MPA). A 40‐year‐old woman was admitted for a protocol biopsy 3 months following primary kidney transplantation. Histological features were distributed in mainly two sections: the corticomedullary junction and cortical area. In the former, massive interstitial mononuclear cell infiltration and mild to moderate tubulitis with nuclear inclusion bodies were found. SV40 staining was positive in the injured tubules. These findings were compatible with BKVN. In the latter, focal interstitial inflammation and severe tubulitis without cytopathic changes were identified outside of SV40‐positive areas. Based on the histological findings, we diagnosed BKVN and we also suspected of the complication with acute T‐cell‐mediated rejection. We started steroid pulse therapy and reduced the dosage of immunosuppressive therapy under careful monitoring, using not only a trough level of tacrolimus but also a 12‐h area under the curve (AUC0–12) of MPA. After the treatment, the patient maintained kidney function. This case report demonstrates the usefulness of MPA AUC0–12 for more accurate adjustment of immunosuppressive therapy and the difficulty of pathological differentiation of BKVN and acute cellular rejection.

Acute vascular rejection during antituberculosis therapy in a kidney transplant patient.

We report a case of acute vascular rejection occurring during antituberculosis therapy in a patient who had received a kidney transplant. A 29 year‐old man was admitted for a protocol biopsy; he had a serum creatinine (S‐Cr) level of 1.5 mg/dL 1 year after primary kidney transplantation. Histological examination yielded no evidence of rejection but a routine chest CT scan revealed typical lung tuberculosis and his serum was positive for QFT. We commenced antituberculosis therapy, including rifampicin, on June 29 2012. We paid close attention to the weekly trough tacrolimus (TAC) level but the S‐Cr concentration increased to 3.7 mg/dL on October 16 2012, and he was admitted for biopsy. Histological examination revealed, first, a diffuse aggressive infiltration of tubulointerstitial inflammatory cells accompanied by severe tubulitis and mild intimal arteritis and, second, peritubular capillary infiltration by inflammatory cells (including neutrophils). Laboratory data revealed that our patient did not express donor‐specific antibody and the peritubular capillaries did not exhibit C4d immunoreactivity. Upon consideration of both histological and laboratory findings, we diagnosed acute vascular rejection of Banff 2007 class ACR IIA. We commenced 3‐day sessions of intravenous steroid pulse therapy twice weekly and adjusted the trough TAC level to 5–8 ng/mL by varying the TAC dose. We next performed an allograft biopsy and found no evidence of rejection (the S‐Cr level was 2.7 mg/dL on April 1 2013). The present case report demonstrates the difficulties associated with management of TAC‐based regimens in kidney transplant patients undergoing antituberculosis therapy. We also review the relevant literature.

Successful treatment of recurrent focal segmental glomerulosclerosis combined with calcineurin inhibitor nephrotoxicity four yr after kidney transplantation

Mitome J, Yamamoto H, Maruyama Y, Kobayashi A, Yaginuma T, Matsuo N, Tanno Y, Hayakawa H, Miyazaki Y, Yokoyama K, Utsunomiya Y, Yamaguchi Y, Hosoya T. Successful treatment of recurrent focal segmental glomerulosclerosis combined with calcineurin inhibitor nephrotoxicity four yr after kidney transplantation.
Clin Transplant 2010: 24 (Suppl. 22): 48–53.

Risk factors for encapsulating peritoneal sclerosis: analysis of a 36-year experience in a University Hospital.

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid.

Combined therapy using peritoneal dialysis and hemodialysis may increase the indications for peritoneal dialysis in the United States

To the Editor: The survival of propensity-matched incident peritoneal dialysis (PD) and hemodialysis (HD) patients in the United States health-care system has been investigated.1 The cumulative hazard ratio for death at 1 year was higher for the HD patients, compared with the PD patients, in as-treated and intent-to-treat analyses, respectively. However, the cumulative risk of death, as estimated using the cumulative hazard ratio, favored PD for nearly 3 years of follow-up in the as-treated analysis, based on the decline in residual renal function.

Successful treatment of adult IgA nephropathy with nephrotic-level proteinuria by combination therapy including long-term coadministration of mizoribine.

A 41-year-old male patient was admitted to our hospital due to massive proteinuria and hematuria. His 24-hour urinary protein excretion and the number of urinary erythrocytes were 3.91 g/day and 50–99/high-power field, respectively. A renal biopsy showed a severe pathological pattern of immunoglobulin A nephropathy (IgAN) that involved marked endocapillary proliferation and segmental sclerosis (Oxford-MEST score: M0, E1, S1, T0). Because he had nephrotic-level proteinuria with severe pathological findings, which are tonsillectomy and corticosteroid pulse therapy-resistant characteristics, he received mizoribine for a long period as part of the combination therapy using corticosteroid, tonsillectomy, dipyridamole, warfarin and renin-angiotensin-aldosterone system blockers. Twelve months after the beginning of treatment, his urinary findings were normal. In this report, we describe the pathological findings and successful treatment course, and discuss the potential effects of long-term coadministration of mizoribine for adult IgAN treatment.