Izumi Yamamoto

Glomerular Expression of Plasmalemmal Vesicle-Associated Protein-1 in Patients with Transplant Glomerulopathy

Transplant glomerulopathy (TG) is a prominent feature of chronic rejection that is characterized by double contours of the glomerular capillaries (GC). In this report, we demonstrate that one of the histopathological features of TG is a phenotypic change of glomerular endothelial cells which is illustrated by increased caveolae formation. To verify the endothelial changes in this disease, we examined the expression of plasmalemmal vesicle‐associated protein‐1 (PV‐1), a glycoprotein associated with plasmalemmal vesicles (caveolae), in the glomeruli of TG patients using pathologische anatomie Leiden‐endothelium (PAL‐E) antibody. Twenty‐six cases of chronic allograft nephropathy (CAN) with TG were examined, compared with 16 cases of CAN without TG, type I MPGN (4 cases), and transplant glomerulitis (8 cases). Overall, 24 of 26 (92.3%), 4 of 16 (25%), 0 of 4, 0 of 8 cases were PAL‐E‐positive for GC, respectively. Further, the extent of glomerular PAL‐E expression was positively correlated with both the grade of TG (rs= 0.72, p = 0.0003) and proteinuria (g/day) (rs= 0.51, p = 0.02). A correlation was not observed between glomerular PAL‐E positivity and peritubular capillary C4d deposits (Yetes chi = 0.23, p = 0.89). In summary, the present study demonstrates expression of PV‐1 in the GC of TG which is correlated with the grade of TG and proteinuria.

Caveolin‐1 Expression Is a Distinct Feature of Chronic Rejection‐Induced Transplant Capillaropathy

Peritubular capillary basement membrane multilayering (PTCBMML) is a pathological landmark of chronic rejection‐induced transplant capillaropathy (TC), but its cellular mechanisms are not fully understood. We observed de novo caveolae formation in endothelial cells in TC under electron microscopy. To examine the role of caveolae and their structural components in TC, biopsy samples from cases of chronic rejection were double‐immunostained for Caveolin‐1 (Cav‐1) and Pathologische Anatomie Leiden‐endothelium (PAL‐E; a marker of peritubular capillary [PC]). Thirty‐two cases of chronic rejection (group I) were compared with 18 cases of interstitial fibrosis and tubular atrophy with no evidence of any specific etiology (IF/TA; group II) and eight cases of peritubular capillaritis (group III). The Cav‐1/PAL‐E immunoreactivities in groups I–III (%Cav‐1/PAL‐E) were 41.8±23.1%, 8.1±7.3% (p < 0.01 vs. group I) and 12.7±7.4% (p < 0.01 vs. group I), respectively. Furthermore, multiple linear regression models demonstrated that %Cav‐1/PAL‐E was independently associated with the PTCBMML grade and reduced PC number. No correlation was observed between %Cav‐1/PAL‐E and PC C4d deposition in group I. We conclude that de novo caveolae formation in PC endothelia is involved in TC in chronic rejection.

Malakoplakia of the Kidney

b alakoplakia is a rare inflammatory disease associated with Escherichia coli nfection. Despite some characteristic histoogical features, including the presence of large istiocytes with clusters of Michaelis-Gutann (MG) bodies, malakoplakia of the kidey is difficult to diagnose because of its rarity nd varying histological picture. We report the ase of a 57-year-old man who had granulomaous interstitial nephritis caused by kidney arenchymal malakoplakia. Of note, using olymerase chain reaction (PCR), we were ble to site-specifically amplify E coli DNA rom his kidney biopsy specimens. Malakoplaia of the kidney should be considered in the ifferential diagnosis of granulomatous intertitial nephritis, and application of molecular iological approaches to the analysis of kidney issues may be useful in the diagnosis of this isease.

Plasma cell-rich rejection accompanied by acute antibody-mediated rejection in a patient with ABO-incompatible kidney transplantation

We report a case of plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection in a patient with ABO‐incompatible kidney transplantation. A 33‐year‐old man was admitted for an episode biopsy; he had a serum creatinine (S‐Cr) level of 5.7 mg/dL 1 year following primary kidney transplantation. Histological features included two distinct entities: (1) a focal, aggressive tubulointerstitial inflammatory cell (predominantly plasma cells) infiltration with moderate tubulitis; and (2) inflammatory cell infiltration (including neutrophils) in peritubular capillaries. Substantial laboratory examination showed that the patient had donor‐specific antibodies for DQ4 and DQ6. Considering both the histological and laboratory findings, we diagnosed him with plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection. We started 3 days of consecutive steroid pulse therapy three times every 2 weeks for the former and plasma exchange with intravenous immunoglobulin (IVIG) for the latter histological feature. One month after treatment, a second allograft biopsy showed excellent responses to treatment for plasma cell‐rich rejection, but moderate, acute antibody‐mediated rejection remained. Therefore, we added plasma exchange with IVIG again. After treatment, allograft function was stable, with an S‐Cr level of 2.8 mg/dL. This case report demonstrates the difficulty of the diagnosis of, and treatment for, plasma cell‐rich rejection accompanied by acute antibody‐mediated rejection in a patient with ABO‐incompatible kidney transplantation. We also include a review of the related literature.

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.

Increased Lymphatic Vessels in Patients with Encapsulating Peritoneal Sclerosis

♦ Background: The angiogenic response is partly involved in the progression of encapsulating peritoneal sclerosis (EPS). However, the details of the angiogenic response, especially for lymphatic vessels in patients with EPS, remain unclear. In addition, because of technical limitations, morphology studies reported to date have examined only the parietal peritoneum. The morphologies of parietal and visceral lymphatic vessels in patients with EPS both need to be analyzed. ♦ Methods: We examined peritoneal samples from 18 patients with EPS who underwent enterolysis of the visceral peritoneum and compared them with samples from 17 autopsy cases (controls). To examine the angiogenic response, we performed immunohistochemistry for the endothelial markers CD34 (blood vessels) and podoplanin (lymphatic vessels) and for the cell proliferation marker Ki-67. Immunogold electron microscopy analysis for podoplanin was also performed. In 7 of 18 cases, we compared differences in the angiogenic response of the parietal and visceral peritoneal membranes. ♦ Results: Angiogenic responses were more frequent in the compact zone than in regenerated layers. The number of capillaries positive for anti-CD34 and anti-podoplanin monoclonal antibodies per unit area of visceral peritoneal tissue was, respectively, 41.1 ± 29.3/mm2 in EPS patients and 2.7 ± 4.4/mm2 in controls (p ≤ 0.01) and 48.1 ± 43.9/mm2 in EPS patients and 4.1 ± 5.4/mm2 in controls (p ≤ 0.01). The percentage of capillaries positive for anti-Ki-67, CD34, and podoplanin was 4.6% in EPS patients (p ≤ 0.01) and 0.8% in controls (p = 0.09). The immunogold electron microscopy analysis revealed that podoplanin was localized to endothelial cells with anchoring filaments, a specific feature of lymphatic vessels. Furthermore, compared with parietal peritoneal membrane, visceral peritoneal membrane had a more prominent podoplanin-positive capillary profile, but not a prominent CD34-positive capillary profile. In addition, fibroblast-like cells double-positive for podoplanin and smooth muscle actin were markedly increased in the degenerated layer, as previously reported. ♦ Conclusions: Our study demonstrated that lymphatic vessels are increased in the visceral peritoneum of patients with EPS.

Medullary ray injury in renal allografts.

Non‐immune injury leading to interstitial fibrosis and tubular atrophy (IF/TA) in renal allografts has various etiologies, but pathological means of verification have yet to be developed. Medullary ray injury (MRI) is a pathological feature of many non‐immune injuries inducing IF/TA and pathological determination of calcineurin inhibitor (CNI) toxicity proceeding to striped fibrosis. We investigated the contribution of CNI toxicity to MRI and other non‐immune etiologies related to IF/TA. In this study MRI is defined as fibrosis and inflammation localized exclusively to the medullary ray. Thirty‐six protocol biopsies showing MRI were analyzed and classified histopathologically as following: MRI related to CNI toxicity; chronic obstruction or reflux nephropathy; and acute or chronic pyelonephritis. The etiology of MRI was CNI toxicity (n= 16, 44.4%), chronic obstruction (n= 13, 36.1%), acute or chronic pyelonephritis (n= 2, 5.6%), and other (n= 5, 13.9%). We performed cystography in seven cases of MRI related to chronic obstruction or reflux nephropathy and six cases showing vesicoureteral reflux. The ci+ct score showed significant progression after one year in 30 of the 36 cases (1.53 ± 1.04 vs. 3.03 ± 1.13, P < 0.01). MRI has various etiologies and may also predict changes in urological complications. The classification of MRI may be useful to determine the non‐immune etiology leading to IF/TA.

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 nephrotic syndrome caused by recurrent IgA nephropathy with chronic active antibody-mediated rejection three years after kidney transplantation.

Yaginuma T, Yamamoto H, Mitome J, Kobayashi A, Yamamoto I, Tanno Y, Hayakawa H, Miyazaki Y, Yokoyama K, Utsunomiya Y, Miki J, Yamada H, Furuta N, Yamaguchi Y, Hosoya T. Successful treatment of nephrotic syndrome caused by recurrent IgA nephropathy with chronic active antibody‐mediated rejection three years after kidney transplantation.
Clin Transplant 2011: 25 (Suppl. 23): 28–33.
© 2011 John Wiley & Sons A/S.

Secondary focal segmental glomerulosclerosis following kidney transplantation in a patient with type I diabetes mellitus

Abstract:  Although recurrent diabetic nephropathy is common in patients with type I diabetes after kidney transplantation, the development of focal segmental glomerulosclerosis (FGS) is rare, and its development generally takes several years. We report here a case of type I diabetes mellitus with secondary FGS accompanied by proteinuria 10 months following kidney transplantation. Episode biopsy showed secondary FGS, evidenced by glomerular capillary collapse and large epithelial cells with ballooning degeneration. Exudative dense deposition of IgM in a diffuse global mesangial pattern and enlarged glomerular diameters were observed, suggestive of glomerular hyperfiltration which can lead to secondary FGS. An imbalance in body size between donor and recipient and/or uncontrolled diabetes are potential causes of glomerular hyperfiltration. We administered angiotensin‐converting enzyme inhibitor and angiotensin II receptor blocker to reduce hyperfiltration‐induced renal damage; the combination therapy reduced proteinuria from 2346 to 258 mg/d. Secondary FGS should be a consideration after kidney transplantation in patients with type I diabetes mellitus.