Clinical phenotype of anaerobic bacteremia unaccompanied by detectable abscess lesion: a 10-year retrospective, multicenter, observational-cohort study.

PURPOSE: Despite the importance of abscess lesions in clinical decisions regarding anaerobic bacteremia (AB), their impact on clinical characteristics remains unclear. Herein, we aimed to elucidate the clinical factors associated with AB that were unaccompanied by detectable abscess lesions during the initial phase of infection. METHODS: This was a multicenter retrospective observational study involving patients with culture-proven AB at six tertiary hospitals in Japan between January 2012 and March 2022. Data on clinical characteristics, laboratory and radiological findings were collected, and their associations with the absence of detectable abscess lesions were analyzed. RESULTS: In total, 393 participants were included. Abscess lesions were absent in 42.7% of the entire cohort and detectable in the remaining patients. No differences were identified in the malignancy, severity, or 30-day mortality between patients with and without detectable abscess lesions. Multivariate logistic regression analysis adjusted for age and the modified Charlson comorbidity score revealed that the immunosuppressive status (febrile neutropenia or corticosteroid use), C-reactive protein (CRP) level ≤9.8 mg/dL at onset, and the presence of gram-positive anaerobic rods (GPARs) were independently associated with AB unaccompanied by detectable abscess lesions [odds ratios (ORs) 3.24, 3.00, and 2.81, respectively; p < 0.05]. CONCLUSION: This study elucidated distinctive clinical and microbiological characteristics of AB unaccompanied by detectable abscess lesions, with relatively lower CRP elevation, immunosuppressive status, and GPARs as the causative anaerobes.

Development and nationwide validation of kidney graft injury markers using urinary exosomes and microvesicles (complete English translation of the Japanese version).

BACKGROUND: Non-invasive, prompt, and proper detection tools for kidney graft injuries (KGIs) are awaited to ensure graft longevity. We screened diagnostic biomarkers for KGIs following kidney transplantation using extracellular vesicles (EVs; exosomes and microvesicles) from the urine samples of patients. METHODS: One hundred and twenty-seven kidney recipients at 11 Japanese institutions were enrolled in this study; urine samples were obtained prior to protocol/episode biopsies. EVs were isolated from urine samples, and EV RNA markers were assayed using quantitative reverse transcription polymerase chain reaction. Diagnostic performance of EV RNA markers and diagnostic formulas comprising these markers were evaluated by comparison with the corresponding pathological diagnoses. RESULTS: EV CXCL9, CXCL10, and UMOD were elevated in T-cell-mediated rejection samples compared with other KGI samples, while SPNS2 was elevated in chronic antibody-mediated rejection (cABMR) samples. A diagnostic formula developed through Sparse Logistic Regression analysis using EV RNA markers allowed us to accurately (with an area under the receiver operator characteristic curve [AUC] of 0.875) distinguish cABMR from other KGI samples. EV B4GALT1 and SPNS2 were also elevated in cABMR, and a diagnostic formula using these markers was able to distinguish between cABMR and chronic calcineurin toxicity accurately (AUC 0.886). In interstitial fibrosis and tubular atrophy (IFTA) urine samples and those with high Banff chronicity score sums (BChS), POTEM levels may reflect disease severity, and diagnostic formulas using POTEM detected IFTA (AUC 0.830) and high BChS (AUC 0.850). CONCLUSIONS: KGIs could be diagnosed with urinary EV mRNA analysis with relatively high accuracy.

Corrigendum to "Detecting MUC1 Variants in Patients Clinicopathologically Diagnosed With Having Autosomal Dominant Tubulointerstitial Kidney Disease"Kidney International Reports, Volume 7, Issue 4, April 2022, Pages 857-866.

[This corrects the article DOI: 10.1016/j.ekir.2021.12.037.].

Comparison of Humoral Response in Kidney Transplant Recipients and Donors and Healthy Volunteers Following Second Dose of SARS-CoV-2 mRNA Vaccine.

PURPOSE: To investigate the kinetics and durability of anti-spike glycoprotein (S) immunoglobulin G (IgG) after the second dose of mRNA-based SARS-CoV-2 vaccine in kidney transplant recipients (recipients) compared with those in kidney donors (donors) and healthy volunteers (HVs) and identify factors negatively associated with SARS-CoV-2 vaccine effectiveness in recipients. METHODS: We enrolled 378 recipients with no history of COVID-19 and no anti-S-IgG before the first vaccine and who received a second mRNA-based vaccine dose. Antibodies were detected using an immunoassay more than 4 weeks after the second vaccine dose. Anti-S-IgG <0.8, ≥0.8 to 15, and ≥15 U/mL were considered negative, weak positive, and strongly positive, respectively, whereas anti-nucleocapsid protein IgG was negative. Anti-S-IgG titer was determined in 990 HVs and 102 donors. RESULTS: Anti-S-IgG titers were 154, 2475, and 1181 U/mL in the recipient, HV, and donor groups, respectively, with values significantly lower in recipients. The anti-S-IgG-positivity rate of recipients gradually increased following the second vaccination, suggesting that recipients had a delayed response compared with the HV and donor groups, who had a 100% positivity rate at an earlier time point. Anti-S-IgG titers decreased in donors and HVs, whereas they remained stable in recipients, although at a significantly lower level. Independent negative factors associated with anti-S-IgG titers in recipients were age >60 years and lymphocytopenia (odds ratio: 2.35 and 2.44, respectively). CONCLUSIONS: Kidney transplant recipients demonstrate delayed and attenuated responses, with lower SARS-CoV-2 antibody titers after the second dose of the mRNA-based COVID-19 vaccine.

Temporary reduction of immunosuppression enhances production of anti-S antibody against severe acute respiratory syndrome coronavirus 2 after vaccination in kidney transplant recipients.

OBJECTIVES: The study identified factors affecting anti-S immunoglobulin G production after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in kidney transplant recipients. METHODS: Serum samples were prospectively collected from kidney transplant recipients, live kidney donors, and healthy volunteers 1 month after receiving the second dose of SARS-CoV-2 vaccine, and anti-S immunoglobulin G titers were measured. The mycophenolate mofetil dose was reduced before vaccination in some immunologically low-risk recipients. RESULTS: A total of 151 kidney transplant recipients, 74 live kidney donors, and 50 healthy volunteers were included. Kidney transplant recipients had significantly lower titers of anti-S immunoglobulin G than donors and healthy volunteers (1377 ± 246, 8310 ± 932, and 9908 ± 1040 AU/ml, respectively). Only 67.3% of kidney transplant recipients, compared to 100% of donors and healthy volunteers, were positive for anti-S immunoglobulin G. Among the kidney transplant recipients, the anti-S titer was higher in younger recipients, those with higher peripheral blood lymphocyte counts and glomerular filtration rates, those without a history of antithymocyte globulin use, and those who had discontinued or received a reduced dose of mycophenolate mofetil. Younger age, higher lymphocyte count, glomerular filtration rate, and mycophenolate reduction were significantly associated with anti-S immunoglobulin G > 1000 AU/ml in nominal logistic regression analysis. There were no rejection episodes after mycophenolate modification in kidney transplant recipients. CONCLUSIONS: Anti-S immunoglobulin G production after vaccination was attenuated in kidney transplant recipients. Mycophenolate mofetil cessation or reduction is a modifiable means to enhance anti-S immunoglobulin G production in immunosuppressed kidney transplant recipients.

Detecting MUC1 Variants in Patients Clinicopathologically Diagnosed With Having Autosomal Dominant Tubulointerstitial Kidney Disease.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD)-MUC1 is predominantly caused by frameshift mutations owing to a single-base insertion into the variable number tandem repeat (VNTR) region in MUC1. Because of the complexity of the variant hotspot, identification using short-read sequencers (SRSs) is challenging. Although recent studies have revealed the usefulness of long-read sequencers (LRSs), the prevalence of MUC1 variants in patients with clinically suspected ADTKD remains unknown. We aimed to clarify this prevalence and the genetic characteristics and clinical manifestations of ADTKD-MUC1 in a Japanese population using an SRS and an LRS. Methods: From January 2015 to December 2019, genetic analysis was performed using an SRS in 48 patients with clinically suspected ADTKD. Additional analyses were conducted using an LRS in patients with negative SRS results. Results: Short-read sequencing results revealed MUC1 variants in 1 patient harboring a cytosine insertion in the second repeat unit of the VNTR region; however, deeper VNTR regions could not be read by the SRS. Therefore, we conducted long-read sequencing analysis of 39 cases and detected MUC1 VNTR variants in 8 patients (in total, 9 patients from unrelated families). With the inclusion of family-affected patients (n = 31), the median age at the development of end-stage kidney disease (ESKD) was 45 years (95% CI: 40-40 years). Conclusion: In Japan, the detection rate of MUC1 variants in patients with clinically suspected ADTKD was 18.8%. More than 20% of patients with negative SRS results had MUC1 variants detected by an LRS.

A comparison of laparoendoscopic single-site surgery versus conventional procedures for laparoscopic donor nephrectomy: a Japanese multi-institutional retrospective study.

PURPOSE: Laparoendoscopic single-site donor nephrectomy (LESSDN) is a feasible and effective procedure because of its non-invasiveness and better cosmetic outcomes. However, there have been few multi-institutional studies conducted by multiple surgeons on LESSDN. We retrospectively compared the clinical data and outcomes between LESSDN and conventional laparoscopic donor nephrectomy (LDN) at multiple institutes in Japan. MATERIALS AND METHODS: From 2009 to 2015, the clinical data of 223 donors who underwent LESSDN and 151 donors who underwent LDN were collected from 10 institutes. All LESSDNs were performed transperitoneally, whereas LDNs were performed transperitoneally (P-LDN) in 75 patients and retroperitoneally (R-LDN) in 76 patients. RESULTS: In the LESSDN group, the single-incision site was pararectal in 155 (69.5%) patients and umbilical in 65 (29.1%) patients. Multiple surgeons (one to eight per institute) performed the LESSDN. No significant differences were observed between the three groups regarding estimated blood loss and warm ischemic time. The operative time was significantly shorter in the LESSDN group than in the R-LDN group (p = 0.018). No significant differences were observed regarding the rates of blood transfusion, open conversion, visceral injuries, and postoperative complications. Furthermore, no significant differences were observed regarding the dose of analgesic and the rate of delayed graft function. One patient required open conversion due to injury to the renal artery. Selection of LESS procedure was not an independent risk factor for the median serum creatinine level of above 1.27 mg/dL in recipients at 1 year after kidney transplantation. CONCLUSION: The results showed the technical feasibility of LESSDN compared with the standard LDNs in a multi-institutional and multi-surgeon setting. A few observed non-negligible complications and the significantly higher levels of serum creatinine in patients who underwent LESSDN indicate that this procedure should be employed cautiously when performed by surgeons without ample experience in performing LESS procedures.

Atrophic bladder in long-term dialysis patients increases the risk for urological complications after kidney transplantation.

OBJECTIVES: To evaluate the risk for urological complications after kidney transplantation at a single medical center in Japan. METHODS: In the present study, 408 kidney recipients (255 men, 153 women) were enrolled. There were 349 living and 59 deceased donors. The average age of the recipients was 42.5 ± 13.5 years, and the average pretransplant dialysis period was 71.8 ± 88.2 months. Ureteroneocystostomy was carried out on 347 patients, and ureteroureterostomy on 61 patients. We investigated the relationship between pretransplant duration of dialysis and bladder capacity, and examined the risk factors for urological complication. We also evaluated the incidence of vesicoureteral reflux in 191 recipients who underwent ureteroneocystostomy during transplantation. RESULTS: The preoperative duration of dialysis therapy showed a significant negative correlation with bladder capacity (R2  = 0.33, P < 0.001). The overall urological complication rate was 3.4% (14 patients), including urinary leakage (12 patients) and ureteral stricture (two patients). Univariate analysis showed that atrophic bladder, long-term dialysis therapy, deceased donor and ureteroureterostomy were associated with a higher incidence of urological complications (odds ratio 8.05, 4.43, 3.42 and 3.35; P < 0.01, P = 0.01, P = 0.04 and P = 0.04, respectively). Furthermore, multivariate analysis showed that atrophic bladder was the only significant factor associated with urological complications (odds ratio 10.37; P = 0.01). Among 191 recipients, vesicoureteral reflux was observed in 32 (16.8%). The incidence of vesicoureteral reflux was significantly higher in patients with atrophic bladder. CONCLUSIONS: Bladder atrophy in renal transplant recipients after long-term dialysis therapy is associated with a higher risk of urological complications.

Extrarenal Nephroblastoma of the Retroperitoneal Space in Children: A Case Report and Review of the Literature.

Extrarenal nephroblastoma (ERNB) is a rare disease. We report a case of ERNB in a 4-year-old boy complaining of abdominal pain and vomiting. Imaging showed a retroperitoneal mass and left hydronephrosis. The mass was completely removed by surgery. The pathologic diagnosis was ERNB with favorable histology. Postoperative chemotherapy was administered for 24 weeks with actinomycin D, vincristine, and doxorubicin. No signs of recurrence were found for the next 3 years. We consider 53 reports of ERNB and our own. Median age at diagnosis was 42 months. The most common site is the retroperitoneal space (44.4%), followed by the uterus (14.8%).

De novo proliferative glomerulonephritis with monoclonal IgG deposits of the IgG1κ subtype in a kidney allograft.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) has recently been described in cases with glomerular disease. Only 16 cases of recurrent or de novo PGNMID have been reported in the transplanted kidney. Here we report a case of de novo PGNMID in a renal allograft diagnosed in the early stage by protocol biopsy. A 41-year-old male with end-stage kidney disease caused by focal glomerular sclerosis received a living-related kidney transplant. The post-transplantation course was stable, except for an early episode of acute T cell-mediated rejection. Mesangial C1q deposition was found on the 3-year protocol biopsy. On the 4-year protocol biopsy, mild mesangioproliferative changes and deposition of IgG, C1q, C3, IgG1, and κ light chain were evident, confirming the diagnosis of PGNMID of the IgG1κ subtype. Furthermore, mild proteinuria was detected at that time. Because a subsequent haematological examination revealed high copy number Epstein-Barr virus (EBV) DNA and free κ light chain in blood, the post-transplant lymphoproliferative disorder (PTLD) was suspected. Mycophenolate mofetil (MMF) was discontinued and rituximab was administered for the treatment of PTLD; subsequently, the improvement in proteinuria and serum creatinine was found 2 months after rituximab administration.

Tacrolimus reduction with everolimus addition for calcineurin inhibitor-induced arteriolopathy in kidney allografts.

AIM: The aim of this study was to evaluate the effect of tacrolimus (TAC) reduction with everolimus (EVR) addition on the maintenance immunosuppression for the recipients with calcineurin inhibitor arteriolopathy (CNIA). METHODS: This retrospective study consisted of 13 kidney allograft recipients who were found to have CNIA on protocol biopsy specimens. The time of intervention was 9-89 months. All the patients were on TAC, mycophenolate mofetil (MMF). 9 of 13 were on steroid. EVR was added and TAC dose was reduced. MMF dose was not changed. Revaluation biopsy was taken 12 months after the intervention. TAC trough levels (TACC0 , ng/mL), EVR trough levels (EVRC0 , ng/mL), estimated glomerular filtration rate (eGFR, mL/min), and urine protein per creatinine (uP/Cr, g/g creatinine) were compared before and 1 year after intervention. Changes in pathological findings and adverse events were also reviewed. RESULTS: Aah scores improved in 5 patients. Aah scores did not change in the rest of the patients. No deterioration was observed. No improvement was seen in those with aah3. TACC0 reduced from 3.3 to 2.3. EVRC0 at revaluation was 4.1. eGFR improved from 44.3 to 49.8. uP/Cr slightly increased from 0.20 to 0.26. EVR was discontinued in 1 patient due to an adverse event. EVR dose was reduced in 5 patients due to adverse events. CONCLUSION: TAC reduction with EVR addition improves CNIA histologically in selected cases.

De novo proteinuria with pathological evidence of glomerulonephritis after everolimus induction.

A 68-year-old man who underwent living-unrelated kidney transplantation from his spousal donor was immunosuppressed with tacrolimus and mycophenolate mofetil. Despite his uneventful clinical course, protocol biopsy at 2 years post transplant showed de novo CNI tubulotoxicity despite low tacrolimus exposure. Everolimus was added in order to discontinue TACER. However, prominent proteinuria impeded continuation of everolimus since biopsy showed diffuse glomerular endocapillary proliferation without C4d deposition. No donor-specific antibody was detected. Pulse steroids were given and proteinuria returned to normal with histological reversal.

Long-term histopathology of allografts in sensitized kidney recipients.

Successful desensitization therapy has brought satisfying short-term outcomes in the recipients with anti-donor antibody. We analyzed the long-term pathology of the allografts in the sensitized kidney recipients. Eleven stable recipients after desensitization against positive flow cytometry T-cell crossmatch (FTXM) were included. They were divided into two groups, based on the protocol biopsies findings at three to eight yr (group 1: subclinical glomerulitis and/or peritubular capillaritis, n = 5 and group 2: no rejection, n = 6). Estimated glomerular filtration rate (eGFR), presence of donor-specific antibody (DSA), mean channel shift (MCS) of FTXM, urine protein levels, acute antibody-mediated rejection (AAMR) episodes, and protocol biopsy findings were compared. Chronic transplant glomerulopathy was found in final biopsy of all group 1 cases. DSA was positive in 60% but C4d was positive in 20% case of the group 1. The history of AAMR was only found in the group 1. There was no difference in eGFR decline or proteinuria. The MCS of FTXM was higher in the group 1. The recipients with AAMR history, high MCS in FTXM, and subclinical microvascular inflammation in the early protocol biopsies have risk for developing chronic rejection in long term.

A case of progressive thrombotic microangiopathy after ABO-incompatible renal transplantation.

A 21-yr-old man of blood type O receiving hemodialysis for IgA nephropathy underwent living-related ABO-incompatible (ABOI) renal transplantation from his mother, whose blood type is A. He was negative for flow cross-match, anti-human leukocyte antigen (HLA) antibody, and anti-MICA antibody. Pre-treatment anti-A IgG titer was 1:256. Desensitization consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, rituximab, and plasmapheresis. He developed acute antibody rejection at day 2 post-transplant, which was successfully treated. After renal artery reconstruction surgery at day 91 for renovascular hypertension caused by renal artery stricture, the patient suffered from acute prostatitis, which subsequently induced type III acute antibody-mediated rejection. Even after recovery from the rejection after temporary hemodialysis, graft function progressively deteriorated and consecutive allograft biopsy showed progressive thrombotic microangiopathy (TMA) without any evidence of donor-specific antibody other than anti-A antibody. The tacrolimus dose was kept low for fear of tacrolimus-induced TMA. Despite these efforts, the patient resumed hemodialysis six months' post-transplant.

A case of pregnancy-induced thrombotic thrombocytopenic purpura with a kidney allograft recipient.

A 32-yr-old female patient, who had been suffering from diffuse crescentic glomerulonephritis and a consequent end-stage renal disease, successfully underwent living-related ABO-incompatible kidney transplantation after a desensitization therapy including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the recipient became pregnant. At the 17th gestational week, the patient was admitted for the management of pregnancy-induced hypertension and aggressive deterioration of kidney graft function. At the 21st gestational week, the patient lost her kidney graft and was re-induced into regular hemodialysis. The patient was also suffering from progressive hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent with acute T-cell-mediated rejection. The patient immediately underwent plasma exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia and intrauterine growth retardation progressed. The patient underwent a caesarian section at the 24th gestational week. Consequently, her platelet count recovered drastically. However, the patient lost her neonate five d after giving a birth, and the patient's graft function had never recovered.

(99m)Tc-DTPA dynamic SPECT and CT volumetry for measuring split renal function in live kidney donors.

OBJECTIVES: Split renal function (SRF) estimated from the posterior view of (99m)Tc-diethylenetriaminepentaacetic acid planar scintigraphy (DTPA/P) is not sufficiently accurate even after correction for kidney depth by computed tomography (CT). To obtain more accurate SRF using (99m)Tc-DTPA, dynamic SPECT method was carried out for the initial 5 min after bolus injection of (99m)Tc-DTPA (DTPA/SPECT). Also SRF was evaluated from the renal volume measured by CT. We compared the results with (99m)Tc-dimercaptosuccinic acid SPECT (DMSA/SPECT). METHODS: In 60 consecutive live kidney donors, 30 DTPA/P, 30 DTPA/SPECT, 60 (99m)Tc-DMSA/SPECT, and 60 CT studies were performed. In the DTPA/P studies, SRF was calculated from the posterior image recorded during 2-3-min postinjection with attenuation correction for kidney depth measured by CT. In the DTPA/SPECT studies, SPECT images were acquired continuously for 5 min with a dual-headed gamma camera. In (99m)Tc-DMSA scintigraphy, DMSA/SPECT images were acquired 3-h postinjection. The SRF on both SPECT studies was calculated from the total counts of each kidney. In the DTPA/SPECT study, SRF was evaluated on the three images summed for 1 min: 1-2 min (DTPA/SPECT1-2), 2-3 min (DTPA/SPECT2-3), and 1-3 min (DTPA/SPECT1-3). In the CT examination, to assess the global renal volume, the axial images in the excretory phase were chosen. Renal contours were identified on each image, and the areas (cm(2)) of these regions were summed and multiplied by the slice thickness (10 mm) to yield global renal volume (ml). Right renal function from DTPA/P, DTPA/SPECT, and CT were compared with that from DMSA/SPECT as a reference. RESULTS: Correlation coefficients of the right renal function between DMSA/SPECT and DTPA/P, DTPA/SPECT2-3, and CT were 0.663, 0.849 and 0.907, respectively (P < 0.0001). The differences between DMSA/SPECT and DTPA/P, DTPA/SPECT2-3 and CT were 2.42 +/- 3.878, 0.867 +/- 1.672, and -0.421 +/- 1.077% (mean +/- SD), respectively. CONCLUSION: SRF derived from DTPA/SPECT showed a better correlation with DMSA/SPECT and significantly fewer errors (P < 0.05) than DTPA/P. A significant strong correlation was observed between SRF from DMSA/SPECT and CT, indicating the utility of CT renal volumetry for evaluating SRF.