Shunji Narumi

De Novo Anti-HLA DSA Characteristics and Subclinical Antibody-Mediated Kidney Allograft Injury.

Background It is unclear whether all donor-specific antibodies (DSA) can cause chronic antibody-mediated rejection (AMR). Subclinical stage before manifestation of renal dysfunction may be a critical period for reversing AMR. The aim of our study was to identify factors related to the development of subclinical AMR and to clarify the characteristics of de novo DSA. Methods Eight hundred ninety-nine renal transplants were screened for HLA antibody. De novo DSA were detected in 95 patients. Forty-three patients without renal dysfunction who underwent renal biopsies were enrolled in this study. Eighteen patients (41.9%) were diagnosed with biopsy-proven subclinical AMR and treated with plasmapheresis and rituximab-based therapy, whereas 25 showed no findings of AMR. Results Significant subclinical AMR-related factors were younger recipients, history of acute T cell–mediated rejection and DSA class II, especially DR-associated DSA. Mean fluorescence intensity (MFI) values of DR-DSA were significantly higher, whereas DQ-DSA was not different between subclinical AMR and no AMR. The &Dgr;MFI (>50%), DSA-MFI values greater than 3000, and C1q binding DSA were also significant subclinical AMR-related factors (P < 0.05). Among 18 patients treated for subclinical AMR, 8 patients (44.4%) obtained over 50% reduction of DSA-MFI and/or improvement or no deterioration of pathological findings. In contrast, 25 patients without subclinical AMR did not show renal dysfunction clinically. Moreover, all of the 8 patients with rebiopsy after 2 years continued to demonstrate no AMR. Conclusions About 40% of patients with de novo DSA demonstrated biopsy-proven subclinical AMR, leading to progressive graft injury. To validate the intervention and treatment for de novo DSA-positive patients without renal dysfunction, further study is necessary.

Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism.

BackgroundReoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated.MethodsWe retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue.ResultsOf 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146).ConclusionsIn patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX.

Association of Dialysis Duration with Outcomes after Transplantation in a Japanese Cohort

BACKGROUND AND OBJECTIVESnEvidence regarding the differences in clinical outcomes after preemptive kidney transplantation (PKT) and non-PKT in Japan is lacking.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnWe conducted a retrospective cohort study at a single center in Japan. Consecutive patients ages >18 years old who had received a kidney transplant from a living donor between November of 2001 and December of 2013 at our institution (n=786) were enrolled. The primary study outcome was the occurrence of clinical events before the end of 2014. Clinical events were defined as any of the following: death with functioning graft (DWFG), graft loss, or post-transplant cardiovascular disease (CVD).nnnRESULTSnThe median follow-up period was 61.0 (35.3-94.0) months. PKT was performed in 239 patients (30.4%). Clinical events occurred in 78 (9.9%). In the Cox proportional hazard model for univariate analysis, factors found to be associated with higher risk of clinical events included older age, men, ABO incompatibility, longer dialysis duration, diabetes, pretransplant CVD, and large ventricular mass index. PKT was associated with lower risk. Clinical event rate in patients who received a PKT was 3.3% compared with 10.8%, 11.1%, 10.4%, 10.2%, 16.7%, and 16.2% among patients who were on dialysis for <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, and ≥5 years before transplant, respectively (P=0.002). The multivariate analysis showed that ABO incompatibility (hazard ratio [HR], 2.98; 95% confidence interval [95% CI], 1.89 to 4.71), duration of dialysis per year (HR, 1.07; 95% CI, 1.03 to 1.11), and diabetes (HR, 3.54; 95% CI, 2.05 to 6.12) were only three independent risk factors for the incidence of clinical events.nnnCONCLUSIONSnEven in Japan, where the long-term outcomes of patients on hemodialysis are excellent, PKT could be beneficial to reduce DWFG, graft loss, and post-transplant CVD.

Characteristics of Persistent Hyperparathyroidism After Renal Transplantation

BackgroundPersistent hyperparathyroidism (HPT) after renal transplantation (RTx), termed tertiary HPT (THPT), is not uncommon. However, risk factors and appropriate operative procedures for THPT are poorly understood.MethodsA retrospective study of patients who underwent RTx without pre-transplant parathyroidectomy (PTx) was performed at our hospital between January 2001 and March 2011. Risk factors for the development of THPT were investigated by comparing THPT and non-THPT groups. We retrospectively analyzed patients with THPT who underwent total PTx with forearm autograft. Pre- and postoperative (1xa0year after PTx) laboratory results were analyzed for PTx efficacy.ResultsData for 520 patients were analyzed. On multivariate analysis, long dialysis duration (pxa0=xa00.009, hazard ratio (HR) 1.01), large maximum parathyroid gland size before RTx (pxa0=xa00.003, HR 1.23), pre-RTx high intact parathyroid hormone (iPTH) (pxa0=xa00.041, HR 1.01), post-RTx (<2xa0weeks) high calcium (Ca) (pxa0<xa00.001, HR 25.04), and post-RTx high alkaline phosphatase (ALP) (pxa0=xa00.027, HR 0.99) were identified as risk factors for THPT. Patients who underwent PTx showed significant improvement compared with baseline for serum Ca, phosphorus, iPTH, and ALP. Serum creatinine showed no significant difference.ConclusionsSeveral risk factors for THPT development were identified. PTx for patients with THPT significantly improved serum Ca, iPTH, ALP, and phosphorous levels. There was no significant difference in renal function after PTx. Therefore, total PTx with forearm autograft may be an appropriate surgical approach for patients with THPT.

Death and kidney allograft dysfunction after bacteremia

BackgroundSome studies have reported causal associations between bacteremia and mortality or allograft loss in kidney transplant recipients (KTR). However, few studies have assessed the clinical course of kidney function and the risk of acute allograft rejection after bacteremia.MethodsWe retrospectively reviewed 902 kidney transplants performed at Nagoya Daini Red Cross Hospital between January 1, 2002 and March 31, 2014. Forty-five living donor kidney transplant recipients with single bacteremia were included. We analyzed death, change in kidney function, and development of acute allograft rejection 12xa0months after bacteremia according to the following groups: primary source of bacteremia (urinary tract or other sources), site of acquisition (community acquired or nosocomial), severity (not meeting the systemic inflammatory response syndrome criteria and sepsis or severe sepsis and septic shock), empiric antibiotic use (appropriate or inappropriate), and baseline kidney function (estimated glomerular filtration rate ≤44.7 or ≥44.8xa0ml/min).ResultsUrinary tract infection (UTI) was the leading cause of bacteremia (68.9xa0%), and Escherichia coli was the most common pathogen. Three cases (6.7xa0%) died of infection that caused bacteremia within 12xa0months. Pneumonia accounted for two-thirds. Kidney function declined 1xa0week after bacteremia (Pxa0<xa00.05), particularly in severe cases. Thereafter, kidney function was comparable to baseline level in each group (Pxa0≥xa00.05). Severe UTI was associated with subsequent acute allograft rejection (Pxa0=xa00.03).ConclusionsPneumonia in KTR should be managed with caution. Kidney function generally returned to baseline level after bacteremia. However, severe UTI may be associated with subsequent acute allograft rejection.

Impact of Arterial Reconstruction With Recipient's Own Internal Iliac Artery for Multiple Graft Arteries on Living Donor Kidney Transplantation: Strobe Study.

AbstractThe aim of this study is to investigate the usefulness of arterial reconstruction using the recipients own internal iliac artery for multiple kidney graft arteries.The safety and efficacy of various arterial reconstruction methods have been demonstrated. Although some reports have documented arterial reconstruction with the recipients own internal iliac artery for multiple kidney graft arteries using the interposition method, usefulness of this technique has not yet been investigated compared with other arterial reconstruction methods.Between January 2008 and April 2014, 532 living donor kidney transplants in adult recipients were performed at 1 center. Of these, 389 kidney grafts had a single artery and did not need arterial reconstruction (nonarterial reconstruction group). Among the bench surgery patients, 19 kidney grafts for multiple arteries were performed using the interposition method with the recipients own internal iliac artery (interposition group). Seventy-nine kidney grafts were performed using conjoined reconstruction (conjoined group) and 15 kidney grafts were performed using end-to-side reconstruction (end-to-side group). Total ischemic time (the period between arterial clamp and blood reperfusion), time to initial urination, perioperative and postoperative estimated glomerular filtration rate (eGFR), and complication rates between the interposition group and other 3 groups were retrospectively investigated. This study was based on the STROBE compliant.Warm ischemic time (the period between arterial clamp and beginning of the cold perfusion) of interposition group was significantly longer than that of nonarterial reconstruction group. Total ischemic time of the interposition group was significantly longer than those of other 3 groups. But time to initial urination, perioperative and postoperative eGFR, and complications were similar to other 3 groups.The interposition method was shown to be a useful standard method for multiple kidney graft arteries of living donor kidney transplantation in carefully selected recipients without calcification of the iliac arteries.

Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak

The outbreak of Pneumocystis jirovecii pneumonia (PJP) among kidney transplant recipients is emerging worldwide. It is important to control nosocomial PJP infection. A delay in diagnosis and treatment increases the number of reservoir patients and the number of cases of respiratory failure and death. Owing to the large number of kidney transplant recipients compared to other types of organ transplantation, there are greater opportunities for them to share the same time and space. Although the use of trimethoprim-sulfamethoxazole (TMP-SMX) as first choice in PJP prophylaxis is valuable for PJP that develops from infections by trophic forms, it cannot prevent or clear colonization, in which cysts are dominant. Colonization of P. jirovecii is cleared by macrophages. While recent immunosuppressive therapies have decreased the rate of rejection, over-suppressed macrophages caused by the higher levels of immunosuppression may decrease the eradication rate of colonization. Once a PJP cluster enters these populations, which are gathered in one place and uniformly undergoing immunosuppressive therapy for kidney transplantation, an outbreak can occur easily. Quick actions for PJP patients, other recipients, and medical staff of transplant centers are required. In future, lifelong prophylaxis may be required even in kidney transplant recipients.

Virus-Associated Hemophagocytic Syndrome in Renal Transplant Recipients: Report of 2 Cases from a Single Center

Virus-associated hemophagocytic syndrome (HPS) is a potentially fatal complication of immunosuppression for transplantation. However, it presents with heterogeneous clinical symptoms (fever, disturbed consciousness, and hepatosplenomegaly) and laboratory findings (pancytopenia, elevated hepatic enzyme levels, abnormal coagulation, and hyperferritinemia), impeding diagnosis. Case 1: A 39-year-old female developed fever 4 years after ABO-incompatible living-related renal transplantation. Laboratory findings revealed thrombocytopenia, elevated hepatic enzymes, Epstein-Barr virus (EBV) DNA seropositivity, and hyperferritinemia. EBV-associated HPS was confirmed by bone marrow aspiration. Steroid pulse therapy and etoposide were ineffective. Disseminated intravascular coagulation resulted in multiple organ failure, and the patient died 32 days after disease onset. Case 2: A 67-year-old male was admitted with rotavirus enteritis a month after living-unrelated renal transplantation. He developed sudden-onset high fever, disturbance of consciousness, and tachypnea 8 days after admission. Laboratory findings revealed elevated hepatic enzyme levels, hyperkalemia, and hyperferritinemia. Emergency continuous hemodiafiltration ameliorated the fever, and steroid pulse therapy improved abnormal laboratory values. Varicella-zoster virus meningitis was confirmed by spinal tap. Acyclovir improved consciousness, and he was discharged 87 days after admission. Fatal virus-associated HPS may develop in organ transplant patients receiving immunosuppressive therapy. Pathognomonic hyperferritinemia is useful for differential diagnosis.

Lifelong Prophylaxis With Trimethoprim-Sulfamethoxazole for Prevention of Outbreak of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients

Background Outbreaks of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients are frequently reported worldwide. However, the general guidelines propose only short-term prophylaxis with trimethoprim-sulfamethoxazole after kidney transplantation. We experienced 3 PCP outbreaks in the last 10 years despite providing the recommended prophylaxis. The purpose of this study was to find a prophylaxis regimen that could successfully prevent future PCP outbreaks in immunosuppressed kidney transplant recipients. Methods Occurrence of PCP at our hospital since 2004 was reviewed. A total of 48 cases were diagnosed from July 2004 through December 2014. Genotypes of P. jirovecii were determined in these cases. Results Three PCP outbreaks by 3 different genotypes of P. jirovecii in each outbreak occurred with 2-year intervals in last 10 years. Molecular analysis showed that each intraoutbreak was caused by identical P. jirovecii, whereas interoutbreaks were caused by different genotypes. Although short-term prophylaxis was provided to all kidney recipients after each outbreak after identification of a single PCP case, additional outbreaks were not prevented because the universal prophylaxis had already been completed when new case of PCP emerged. Conclusions The contagious nature of P. jirovecii allows easy development of outbreaks of PCP in immunosuppressed kidney transplant recipients. Although the universal short-term prophylaxis is effective in controlling ongoing outbreak, lifelong prophylaxis of kidney transplant recipients should be considered to prevent new outbreaks.

Beneficial effects of preemptive kidney transplantation on calcium and phosphorus disorders in early post-transplant recipients

BackgroundRecently, preemptive kidney transplantation (PKT) has increased in Japan; however, the effects of PKT on calcium (Ca) and phosphorus (Pi) metabolism are poorly understood.MethodsThirty-two consecutive patients were enrolled in this study at Nagoya Daini Red Cross Hospital. Fifteen patients were in the PKT group and 17 patients were in the non-PKT group. Parameters of Ca and Pi metabolism, including fibroblast growth factor (FGF) 23 and intact parathyroid hormone, were measured before transplantation and 1, 3, and 24xa0weeks after transplantation.ResultsFGF 23 decreased dramatically in both groups after transplantation; however, FGF 23 before transplantation and at 1 and 3xa0weeks after transplantation was significantly lower in the PKT group than in the non-PKT group (pxa0<xa00.05). Although iPTH levels were higher in the PKT group than in the non-PKT group before transplantation, these levels were lower in the PKT group at 24xa0weeks after transplantation (pxa0<xa00.05). Corrected Ca was lower at 24xa0weeks in the PKT group (pxa0<xa00.05), whereas Pi was lower in the non-PKT group at 1 and 3xa0weeks (pxa0<xa00.05), but not significantly different at 24xa0weeks. Multivariate linear regression analysis revealed that FGF 23 before transplantation was the strongest predictor of Ca and Pi disorders in early post-transplant recipients.ConclusionsThis study suggests that PKT has beneficial effects on Ca and Pi metabolism and pre-transplant FGF 23 levels are a good marker of post-transplant Ca and Pi metabolism disorders.