Effects of preoperative plasma exchange therapy with albumin replacement fluid on blood coagulation in patients undergoing ABO-incompatible living-donor kidney transplantation using rotational thromboelastometry.

BACKGROUND: ABO-incompatible living-donor kidney transplantation (LDKT) requires immunotherapy and plasma exchange therapy (PEX). PEX with albumin replacement fluid reportedly decreases fibrinogen levels. However, no reports have described the effects of PEX with albumin replacement fluid on blood coagulation parameters and blood loss during the perioperative period. Therefore, we investigated the effects of preoperative PEX on blood coagulation parameters and blood loss during the perioperative period in patients undergoing ABO-incompatible LDKT as measured by rotational thromboelastometry (ROTEM®). METHODS: Twenty-eight patients undergoing LDKT were divided into the PEX group (ABO incompatible with PEX, n = 13) and non-PEX group (ABO compatible without PEX, n = 15). ROTEM® parameters, standard laboratory test parameters, bleeding volume, and transfusion volume were compared between PEX and non-PEX group. MCEplatelet, which represents platelet contribution to clot strength and where "MCE" stands for maximum clot elasticity, was calculated from the difference in MCE between EXTEM and FIBTEM. RESULTS: The bleeding volume during surgery and the intensive care unit (ICU) stay was significantly higher in the PEX than non-PEX group (p < 0.01). Maximum clot firmness (MCF) of EXTEM (MCFEXTEM), MCFFIBTEM, and MCEplatelet was significantly lower in the PEX than non-PEX group (p < 0.01). In the PEX group, the bleeding volume during surgery was very strongly correlated with the baseline MCFEXTEM and MCEplatelet, and the bleeding volume during the ICU stay was strongly correlated with the postoperative MCFEXTEM and MCEplatelet. CONCLUSIONS: These results suggest that the increased blood loss in the PEX group during surgery and the ICU stay was associated with decreased platelet contribution to clot strength as measured by ROTEM®. TRIAL REGISTRATION: UMIN-Clinical Trial Registry UMIN000018355 . Registered 21 July 2015.

The potential role of perivascular lymphatic vessels in preservation of kidney allograft function.

BACKGROUND: Lymphangiogenesis occurs in diseased native kidneys and kidney allografts, and correlates with histological injury; however, the clinical significance of lymphatic vessels in kidney allografts is unclear. METHODS: This study retrospectively reviewed 63 kidney transplant patients who underwent protocol biopsies. Lymphatic vessels were identified by immunohistochemical staining for podoplanin, and were classified according to their location as perivascular or interstitial lymphatic vessels. The associations between perivascular lymphatic density and kidney allograft function and pathological findings were analyzed. RESULTS: There were no significant differences in perivascular lymphatic densities in kidney allograft biopsy specimens obtained at 0 h, 3 months and 12 months. The groups with higher perivascular lymphatic density showed a lower proportion of progression of interstitial fibrosis/tubular atrophy grade from 3 to 12 months (P for trend = 0.039). Perivascular lymphatic density was significantly associated with annual decline of estimated glomerular filtration rate after 12 months (r = -0.31, P = 0.017), even after adjusting for multiple confounders (standardized ß = -0.30, P = 0.019). CONCLUSIONS: High perivascular lymphatic density is associated with favourable kidney allograft function. The perivascular lymphatic network may be involved in inhibition of allograft fibrosis and stabilization of graft function.

Temporal serum creatinine increase and exacerbation of tubulointerstitial inflammation during the first two months in resolving polyomavirus BK nephropathy.

AIM: Polyomavirus BK nephropathy (BKVN) is an important complication in kidney transplantation. After immunosuppressive agents are reduced, some patients experience a temporal increase in serum creatinine (sCr) before viral clearance. The histological characteristics of re-biopsies were therefore investigated to evaluate the time course of remission. METHODS: sCr was measured and urinary cytology evaluated periodically in 14 patients with biopsy-proven BKVN. Remission of BKVN was defined as re-biopsies negative for SV40 large T antigen (SV40-TAg) or for decoy cells on at least three consecutive cytology tests. Early changes in sCr were correlated with re-biopsy findings. RESULTS: Mean sCr was 1.6 ± 0.6 mg/dL at diagnosis, increasing during the first 2 months to 2.6 ± 2.0 mg/dL, and decreasing thereafter, to 2.3 ± 1.2 mg/dL at 3-4 months. Two patients who experienced further increases in sCr at 3 months showed early graft loss, while the others showed clinical or histological remission. Nineteen re-biopsies were obtained from eight patients over 4 months. Banff i-scores were higher in re-biopsies obtained during the first 2 months than the index biopsies and re-biopsies at 2-4 months (P = 0.02). SV40-TAg positivity was common in re-biopsies during the first 2 months (10/11 biopsies), but rarer at 2-4 months (2/8 biopsies, P = 0.001). CONCLUSIONS: Temporal graft dysfunction and increased inflammation, called immune reconstitution, were observed at 2 months. Later sCr reversal is associated with remission.

Renal interstitial fibrosis in 0-hour biopsy as a predictor of post-transplant anemia.

BACKGROUND/AIMS: Anemia is common in kidney transplant patients and may cause adverse cardiovascular events. Several studies have reported some predictors of post-transplant anemia. However, associations between the pathological findings in the 0-hour biopsy and anemia have not been well described. METHODS: 258 consecutive kidney transplant patients were enrolled in this retrospective study. The patients were divided into two groups, according to the presence or absence of interstitial fibrosis and tubular atrophy (IF/TA) in the 0-hour biopsy: the IF/TA group with fibrotic area ≥5% (n = 131) and the non-IF/TA group with fibrotic area <5% (n = 127). We examined the association between IF/TA and post-transplant anemia. RESULTS: Serial changes in hemoglobin levels in the IF/TA group were lower than in the non-IF/TA group (p = 0.007). Anemia at 12 months was found in 53% of the IF/TA group, and 35% of the non-IF/TA group (p = 0.004). Even after adjustment for several confounders including graft function, the presence of IF/TA was independently associated with post-transplant anemia at 12 months (odds ratio 1.88, 95% confidence interval 1.06-3.36, p = 0.031). This association was still significant in a subgroup with normal graft function. CONCLUSIONS: IF/TA in the 0-hour biopsy specimen is one of the predictors for post-transplant anemia and can be used to identify patients who need the treatment with erythropoiesis-stimulating agents.

Pancreas transplantation: a single-institution experience in Japan.

PURPOSE: We herein report our experience with pancreas transplantation in 26 patients at a single institution in Japan between August 2001 and December 2011. METHODS: We reviewed the medical records of 26 pancreas transplantations performed in our institute. RESULTS: The early complications (within 2 weeks) included one graft venous thrombosis, one arterial thrombosis, and two reoperations for bleeding. Of the 26 pancreas transplant recipients, five lost pancreas graft function. Of 24 simultaneous pancreas-kidney recipients, three lost kidney graft function due to noncompliance. The patient, pancreas, and kidney survival rates were 100, 96 and 93 % at 1 year; 100, 80 and 93 % at 5 years; and 100, 67 and 68 % at 10 years, respectively. Of all these complications, venous thrombosis after pancreas transplantation was the most critical. CONCLUSIONS: As the largest series of pancreas transplantations in a single institution in Japan, our series yielded better results than the worldwide data recorded by the International Pancreas Transplant Registry. Routine postoperative anticoagulation therapy is not necessary for the prevention of graft thrombosis if sufficient fluid infusion is strictly controlled and the graft blood flow is frequently monitored. When graft thrombosis occurs, both early detection and appropriate intervention are extremely important if the pancreas graft is to survive.

Performance of the Japanese GFR equation in potential kidney donors.

BACKGROUND: Japanese GFR equation was developed from mainly chronic kidney disease (CKD) subjects. Only a small number of healthy subjects were included in the development and validation of the GFR equation. We assessed the performance of the equation in potential kidney donors. METHODS: A total of 113 potential kidney donors was included. The data of CKD subjects that were previously reported were also included for comparison. GFR (mGFR) was measured by inulin clearance. The estimated GFR (eGFR) was calculated by the Japanese GFR equation. Bias of the equation (eGFR - mGFR) and urinary creatinine excretion were evaluated. RESULTS: There was no significant difference between eGFR and mGFR in 340 CKD subjects (54.2 ± 31.6 and 55.7 ± 33.2 ml/min/1.73 m(2), respectively). Contrarily, the eGFR was significantly lower than mGFR in 113 potential kidney donors (78.9 ± 16.2 and 93.6 ± 19.2 ml/min/1.73 m(2), respectively). The biases in potential kidney donors with eGFR 30-59 and 60-89 ml/min/1.73 m(2) were significantly greater than those in CKD subjects (-19.2 ± 12.2 and -18.3 ± 16.4 ml/min/1.73 m(2) in potential kidney donors and -3.8 ± 15.6 and -3.4 ± 17.6 ml/min/1.73 m(2) in CKD subjects, respectively). Creatinine excretion per body weight of potential kidney donors was significantly higher than that of CKD subjects, suggesting higher creatinine generation in potential kidney donors. CONCLUSION: The Japanese GFR equation underestimated GFR in potential kidney donors. Higher creatinine generation compared with CKD subjects may contribute to the underestimation of GFR by the Japanese GFR equation in potential kidney donors.

Usefulness of 3-month protocol biopsy of kidney allograft to detect subclinical rejection under triple immunosuppression with basiliximab: a single center experience.

BACKGROUND: Theoretically, an early protocol biopsy (PB) serves to detect subclinical rejection (SCR), allowing early treatment and prevention of acute rejection (AR) and chronic graft injuries. In this retrospective study, we investigated the incidence of biopsy-proven AR (BPAR) and the usefulness of a 3-month PB in detecting SCR in kidney transplant (KT) and simultaneous pancreas-kidney transplant (SPKT) recipients who received triple immunosuppression and basiliximab. METHODS: Between January 2007 and September 2009, 116 patients received transplantation (KT = 112, SPKT = 4). In August 2008, we changed our PB policy and started to collect PB after 3 months instead of a pre-discharge biopsy performed 1 month after transplantation. Here we compare the incidence of SCR (defined as Banff grade Ia or higher) between the pre-discharge PB group and the 3-month PB group. PB was obtained from 41 patients before discharge (pre-discharge PB group), and from 49 patients 3 months after transplantation (3-month PB group). RESULTS: Among all recipients, 21 patients were diagnosed with BPAR (estimated incidence of BPAR 20.1%); including 13 (62.0%) diagnosed from 31 to 180 postoperative days (POD), and only 3 (14.3%) within 30 POD. The incidence of BPAR was not different between the two groups (19.5 and 20.8%, respectively); however, 4 of 8 recipients in the 3-month PB group were diagnosed with SCR, compared to none in the pre-discharge PB group (P < 0.05). CONCLUSION: Since the use of triple immunosuppression and basiliximab delayed the onset of AR, we recommend that in order to detect SCR, PB should be obtained 3 months postoperatively.

Progressive interstitial fibrosis of kidney allograft early after transplantation from a non-heart beating donor: possible role of persistent ischemic injury.

The donor was 63-yr-old woman with subarachnoid hemorrhage. As she developed severe hypotension for more than four h before cardiac arrest, we biopsied the grafts and decided to transplant those kidneys. Recipient 1 was a 23-yr-old man on 13-yr dialysis program. After 19 d of delayed graft function (DGF), we discontinued hemodialysis (HD). However, the decrease in serum creatinine (sCr) was poor. The minimum sCr was 4.3 mg/dL on post-operative day (POD) 40, and increased to 6.5 mg/dL. The contralateral graft was transplanted to a 61-yr-old man (recipient 2) with 18-yr HD. After 15 d of DGF period, sCr decreased gradually and has been stable at 1.9 mg/dL. In recipient 1, graft biopsies performed on POD 15, 69, and 110, revealed progressive interstitial fibrosis and tubular atrophy (IF/TA) without evidences of acute rejection, tacrolimus associated injury, reflux nephropathy, or viral nephropathy. The second biopsy on POD 69 showed typical findings of acute tubular necrosis. We compared the clinical courses of the two recipients because certain features of recipient 1, such as age, duration of HD, total ischemic time, and body size were advantageous, whereas graft function was poorer than that in recipient 2. Recipient 1 developed severe anemia following the dissociation of graft function from recipient 2. In this case, posttransplant anemia and lower blood pressure might promote IF/TA through persistent ischemic tubular damage, and positive CMV antigenemia and its treatment could promote anemia. Especially in the kidney allograft from a marginal donor, we should consider various factors to obtain a better graft outcome.

[Current situation of pancreas transplantation in Japan].

Pancreas transplantation has been recognized as the best treatment for advanced type 1 diabetic patients. In Japan, we have performed 64 SPK, PAK or PTA from 62 brain-dead donors and two non-heart beating donors since the enforcement of Organ Transplant Act in 1997. In addition, 18 cases have been performed from living related donors. The patient survival, pancreas graft survival and kidney graft survival rate of the cadaveric transplantation at five years are 97.5%, 73.9% and 71.0%, respectively. The QOL of the recipients in both mental and physical aspects has been wonderfully improved leading to the happy second life. In front of the revised low in this year, the number of the donor and the transplantation are expected to increase.

Subclinical peritubular capillaritis in serial graft biopsies in cadaveric kidney transplant recipient with pre-transplant anti-HLA antibodies.

National Fukuoka-Higashi Medical Center, Koga, Japan A 63-yr-old Japanese woman on 18-yr hemodialysis (HD) program underwent cadaveric kidney transplantation from non-heart beating donor. Pre-transplant lymphocytotoxicity test was negative, but flow cytometric cross-match and flow-cytometric panel reactive antibody (PRA) screening tests were positive. Flow-PRA single-antigen test revealed several anti-HLA antibodies including donor-specific antibody (DSA). She was treated with plasma exchange (PEX) and rituximab to prevent antibody-mediated rejection (AMR). Urinary output increased from post-operative day (POD) 5 and HD was discontinued from POD8. Graft biopsy performed on POD11 showed severe peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was negative, the case was diagnosed as subclinical AMR based on the presence of pre-transplant DSA and PTCitis with predominant PMNs. The patient was treated with additional PEX and rituximab, which increased urinary output and reduced serum creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was negative again. The patient was discharged from the hospital on POD40. During the seven months follow-up at the outpatient clinic, the sCr level has shown a slight increase. In this case, the patient had DSA, which can be detected only by flow-PRA. In both graft biopsies, C4d on PTC was negative despite the presence of severe PTCitis, and thus the diagnosis of AMR could not be established. However, the significance of subclinical PTCitis is reported perhaps as an early marker for chronic AMR and to emphasize the importance of close follow-up.

Prevention of iatrogenic bile duct injuries in difficult laparoscopic cholecystectomies: is the naso-biliary drain the answer?

BACKGROUND: Prevention of iatrogenic injuries is of paramount importance in difficult laparoscopic cholecystectomies (LC). The objective of this study was to analyze the effectiveness of cholangiography using a pre-inserted endoscopic naso-biliary drain (ENBD) for navigation during difficult cholecystectomies. METHODS: The study design was a retrospective case analysis. In 508 patients who underwent LC in a tertiary referral university hospital from 1996 through 2007, difficult cholecystectomy was anticipated in 26 patients due to possibly aberrant biliary anatomy (four patients), unclear cystic duct anatomy during magnetic resonance cholangiopancreatography (MRCP) and/or endoscopic retrograde cholangiopancreatography (ERCP) (three patients), and acute cholecystitis (19 patients). An ENBD was inserted during ERCP prior to LC for cholangiography (ENBDC) to facilitate safe dissection during LC. Prevalence of biliary complications was assessed as the main outcome measurement. RESULTS: The majority (68%) of the patients who underwent ENBDC had complicated cholecystitis. Advanced technical expertise was not required for insertion of an ENBD. In retrospect, ENBDC was useful in prevention of a possible catastrophe in 69% of cases. Open conversion was necessary in five patients and biliary complications occurred in five patients only in the non-ENBD group. There were no procedure-related complications. One limitation of the study was that it was not randomized and there was no comparison with patients without ENBDC. CONCLUSIONS: ENBDC is a useful and safe tool in the prevention of iatrogenic bile duct injuries in LC.

Treatment of arteriovenous shunts after renal transplantation.

PURPOSE: Immunosuppressive drugs have improved the results of renal transplantation dramatically in recent years; however, there is still no consensus on the treatment of arteriovenous (A-V) shunts after successful transplantation. We evaluated the treatment of A-V shunts after transplantation. METHODS: We reviewed all patients who underwent shunt closure at our hospital between 2005 and 2007 assessing surgical methods, operative time, blood loss, and complications. RESULTS: Fifty-two patients underwent shunt closure, as a simple transection in 5 patients, resection of the anastomotic site in 16, resection and reconstruction of the artery in 26, and graftectomy in 5. Graftectomy was associated with copious blood loss and a long operative time. The most frequent complication was phlebitis, but there were no nerve complications. CONCLUSIONS: An A-V shunt after renal transplantation may result in an aneurysm, severe venous dilatation, pain, bloating of the arm, infection, and cardiac problems. Thus, after successful transplantation, shunt closure should be performed to prevent these complications and to improve quality of life.

LIM only 4 is overexpressed in late stage pancreas cancer.

BACKGROUND: LIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, was initially reported to have an oncogenic role in breast cancer. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer. METHODS: We measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and microdissected target cells (normal ductal cells; pancreatic intraepithelial neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC] cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB] cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: 9 of 14 pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples, expression of LMO4 was higher in pancreatic carcinoma than in intraductal papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas (p < 0.0001 for both). We carried out microdissection-based analyses. IDC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B cells (p < 0.001 for both) or PanIN-2 cells (p = 0.014). IPMC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia (p < 0.001), IPMA (p < 0.001) and IPMB cells (p = 0.003). CONCLUSION: Pancreatic carcinomas (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer.

Histological Analysis in ABO-Compatible and ABO-Incompatible Kidney Transplantation by Performance of 3- and 12-Month Protocol Biopsies.

BACKGROUND: ABO-incompatible (ABO-I) kidney transplantation (KTx) is an established procedure to expand living donor sources. Although graft and patient survival rates are comparable between ABO-compatible (ABO-C) and ABO-I KTx, several studies have suggested that ABO-I KTx is associated with infection. Additionally, the histological findings and incidence of antibody-mediated rejection under desensitization with rituximab and plasmapheresis remain unclear. METHODS: We reviewed 327 patients who underwent living-donor KTx without preformed donor-specific antibodies (ABO-C, n = 226; ABO-I, n = 101). Patients who underwent ABO-I KTx received 200 mg/body of rituximab and plasmapheresis, and protocol biopsy (PB) was planned at 3 and 12 months. We compared the PB findings, cumulative incidence of acute rejection in both PBs and indication biopsies, infection, and patient and graft survivals. RESULTS: The 3- and 12-month PBs were performed in 85.0% and 79.2% of the patients, respectively. Subclinical acute rejection occurred in 6.9% and 9.9% of patients in the ABO-C and ABO-I groups at 3 months (P = 0.4) and in 12.4% and 10.1% at 12 months, respectively (P = 0.5). The cumulative incidence of acute rejection determined by both PBs and indication biopsies was 20.5% and 19.6%, respectively (P = 0.8). The degrees of microvascular inflammation and interstitial fibrosis/tubular atrophy were comparable. Polyomavirus BK nephropathy was found in 2.7% and 3.0% of patients in the ABO-C and ABO-I groups, respectively (P = 1.0). The incidence of other infections and the graft/patient survival rates were not different. CONCLUSIONS: Analyses using 3- and 12-month PBs suggested comparable allograft pathology between ABO-C and ABO-I KTx under desensitization with low-dose rituximab and plasmapheresis.

S100P in Duodenal Fluid Is a Useful Diagnostic Marker for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: The development of an effective screening method for pancreatic ductal adenocarcinoma (PDAC) is of paramount importance. This study assessed the diagnostic utility in pancreatic diseases of duodenal markers during upper gastrointestinal endoscopy (GIE) or endoscopic ultrasonography. METHODS: This study prospectively enrolled 299 consecutive participants, including 94 patients with PDACs, 144 patients with other pancreatic diseases, and 61 normal individuals as control subjects. All subjects underwent upper GIE or endoscopic ultrasonography either at Kyushu University Hospital (Fukuoka, Japan) or the Mayo Clinic (Jacksonville, Fla) from October 2011 to July 2014. Duodenal fluid (DF) was collected without secretin stimulation and of carcinoembryonic antigen and S100 calcium-binding protein P (S100P) concentrations were measured. RESULTS: Concentrations of S100P in DF were significantly higher in patients with PDAC and chronic pancreatitis than in control subjects (P < 0.01). A logistic regression model that included age found that the sensitivity and specificity of S100P concentration in diagnosing stages 0/IA/IB/IIA PDAC were 85% and 77%, respectively, with an area under the receiver operating characteristic curve of 0.82. Carcinoembryonic antigen concentrations in DF of patients with pancreatic disease did not differ significantly from control subjects. CONCLUSIONS: Analysis of S100P concentration in DF, in combination with routine screening upper GIE, may facilitate the detection of PDAC.

Effect of synthetic protease inhibitor gabexate mesilate on the attenuation of ischemia/reperfusion injury in canine kidney autotransplantation.

BACKGROUND: Kidneys from non-heart-beating donors are associated with delayed graft function and a high rejection rate due to the long period of warm ischemia. Gabexate mesilate (GM), a synthetic serine protease inhibitor, has been shown to improve organ function by suppressing cytokine activity and neutrophil function after ischemia/reperfusion. In this study, we evaluated the effect of GM on renal function after warm ischemia in a canine kidney autotransplantation model. METHODS: After 60 minutes of warm ischemia, the left kidney was transplanted into the iliac fossa, and the right kidney was removed. The control group (n = 7) and GM group (n = 7) were evaluated for serum creatinine and blood urea nitrogen (BUN) concentrations, renal tissue blood flow, resistive index, pulsatility index, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha mRNA expression levels in peripheral blood mononuclear cells, apoptotic index, CD10 immunolabeling as an indicator of brush border injury, and standard histopathology. RESULTS: Compared with controls, administration of GM resulted in lower serum creatinine concentrations (11.3 +/- 2.4 vs 5.2 +/- 3.3 mg/dL at 72 hours; P = .04) and BUN concentrations (188 +/- 26 mg/dL vs 98 +/- 41 mg/dL at 72 hours; P = .04), as well as better tissue blood flow, improvement of brush border injury and apoptotic index (each P < .05). The expression of IL-1beta and TNF-alpha mRNA did not change after administration of GM. CONCLUSIONS: The present study shows that GM protected renal function after warm ischemia/reperfusion by inhibition of serine proteases, maintenance of tissue blood flow, and amelioration of tubular apoptosis.

De novo myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis 31 years after living-donor kidney transplantation.

A 61-year-old woman was admitted to our hospital because of an unexpected rise in serum creatinine (sCr) level with proteinuria and microhematuria. She had undergone living-donor kidney transplantation 31 years before for end-stage renal disease caused by chronic glomerulonephritis (GN). On admission, her sCr was 1.27 mg/dL which was increased from 0.6 mg/dL, urinary protein/creatinine ratio was 1.39 g/gCr, and urinary red blood cell count was more than 100 per high power field. The allograft biopsy revealed crescentic glomerulonephritis with moderate to severe tubulointerstitial inflammation. Immunofluorescence staining yielded only a minimal staining for immunoglobulin A, and negative C4d in peritubular capillary. Since increased myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer of 45.5 U/mL was detected, we made the diagnosis of post-transplant MPO-ANCA-associated GN. She was treated with three doses of bolus methylprednisolone (500 mg) followed by oral prednisolone therapy. Her sCr was stable at 1.20 mg/dL thereafter. ANCA-associated GN should be considered in older kidney transplant patients with new-onset urinary abnormalities because typical systemic symptoms and vasculitis in other organs might be masked by maintenance immunosuppression.

Attenuation of renal ischemia-reperfusion injury by FR167653 in dogs.

BACKGROUND: Inflammatory cytokines are known to contribute to ischemia-reperfusion injury. We investigated the effect of FR167653 (FR), a suppressor of interleukin-1beta and tumor necrosis factor-alpha, on ischemia-reperfusion injury of the kidney in dogs. METHODS: The left kidney was subjected to ischemia for 60 minutes followed by removal of the right kidney. A control group (n = 10) and an FR group (n = 8) were evaluated for tissue blood flow; resistive index, pulsatility index, arterial oxygen pressure, serum creatinine, blood urea nitrogen, aspartate transaminase, and alanine transaminase levels; interleukin-1beta messenger RNA expression in the peripheral blood; apoptotic index; and histopathology. RESULTS: The FR group showed lower creatinine, serum urea nitrogen, aspartate transaminase, and alanine transaminase levels (P <.038 each) and lower interleukin-1beta mRNA expression and apoptotic index (P <.041 each) than did the control group. Arterial oxygen pressure during the 120 minutes after reperfusion in the FR group decreased but recovered quickly (P =.024). Renal tissue damage in the FR group was less than that in the control group (P =.036). CONCLUSIONS: FR ameliorates ischemia-reperfusion injury of the kidney potentially by reduced production of inflammatory cytokines that may contribute to damage to the ischemic kidney and the distant organs.

Subclinical nephrosclerosis is linked to left ventricular hypertrophy independent of classical atherogenic factors.

Recently, cardio-renal interactions have been considered to be important and it has been demonstrated that mild renal dysfunction is associated with left ventricular hypertrophy (LVH). However, the correlation between LVH and subclinical renal damage is unclear. We investigated this association by assessing pretransplant biopsies from living kidney donors with normal renal function. We retrospectively categorized 238 living kidney donors into tertiles according to the percentage of global glomerulosclerosis (%GGS) observed in pretransplant biopsies (low, 0-3.45% (n=80); moderate, 3.46-11.76% (n=78); high, ⩾11.77% (n=80)) to analyze trends in their left ventricular mass index (LVMI) measured by echocardiography and baseline factors. LVH was defined as LVMI >110 g m(-2) in female and >125 g m(-2) in male subjects. We used a logistic regression model to evaluate any correlations between %GGS and LVH. LVMI increased significantly with increasing tertiles of %GGS, as did the prevalence of left ventricular remodeling and LVH. According to multivariate logistic regression analysis, subjects with high %GGS tertiles had a sevenfold greater risk of LVH than did those with low tertiles, even after adjusting for age, sex, systolic blood pressure, history of diabetes mellitus, total serum cholesterol and glomerular filtration rate (GFR) measured by a radioisotopic technique. There is an association between GGS and LVH in subjects with normal renal function. This association is significant after adjustment for age, sex, blood pressure, GFR and other atherogenic factors.