Incidence and mortality of post-transplant lymphoproliferative disorders after kidney transplantation: A real-world retrospective analysis in Japan.

OBJECTIVES: Post-transplant lymphoproliferative disorder is a potentially life-threatening complication that has a greater risk of occurrence in the setting of immunosuppression and oncogenic viral infections after transplant surgery. Few studies have reported the cumulative incidence, histological subtypes and clinical outcomes of this disorder in kidney transplant recipients. METHODS: We retrospectively investigated 34 post-transplant lymphoproliferative disorder patients diagnosed out of the 1210 kidney transplant recipients who had undergone the surgery at the two largest centers in Japan between January 1983 and December 2017. RESULTS: A total of 32 patients (94.1%) developed late-onset post-transplant lymphoproliferative disorder (diagnosed 1 year after transplantation). The cumulative incidence rates were 0.76% and 1.59% at 5 and 10 years post-transplantation, respectively. The central nervous system was the most common site (35.3%, 12/34). Overall survival was similar between patients with and without central nervous system lesions (P = 0.676). Of all of the cases, 23.5% (8/34) were detected through cancer screening. Importantly, patients with screening-detected post-transplant lymphoproliferative disorder had better overall survival than those with the disorder who had been symptom detected (P = 0.0215). Overall survival was significantly reduced in patients who developed the disorder compared with those who did not (P = 0.0001). CONCLUSIONS: Post-transplant lymphoproliferative disorder was more likely to occur in the late post-transplantation period, which showed that long-term medical examination for transplant recipients is required. Based on our findings, we propose vigilant, long-term, cancer screening in kidney transplant recipients.

Efficacy of a Si-based agent against developing renal failure in a rat remnant kidney model.

Chronic renal failure is exacerbated by oxidative stress, and this condition is difficult to treat in advanced stages. Because of the lack of effective treatments, the disease is a global public health concern. We developed a Si-based agent that continuously generates hydrogen for more than 24 h by reacting with water under conditions similar to those in the gastrointestinal tract. Given the efficacy of hydrogen in the treatment of conditions associated with oxidative stress, we examined whether the Si-based agent had beneficial effects on the development of renal failure. The Si-based agent was orally administered to rats that were developing renal failure. Rats underwent 5/6 nephrectomy to establish a remnant kidney model. Specifically, on day -7, rats underwent right 2/3 nephrectomy, followed by light nephrectomy on day 0. Starting on day -3, the rats were administered a control or Si-based agent-containing diet for 8 weeks. Compared with the findings in control rats, the Si-based agent greatly suppressed the increases of both serum creatinine and urinary protein levels. All analyzed parameters of oxidative stress were significantly suppressed in the Si-based agent groups. Histopathological examination illustrated that glomerular hypertrophy was suppressed by the treatment. Quantitative real-time reverse transcription-polymerase chain reaction revealed that sirtuin 1 and heme oxygenase-1 expression was increased in the Si-based agent groups, suggesting improved antioxidant activity and reduced hypoxia. In addition, caspase-3 and interleukin-6 expression was suppressed in the Si-based agent groups, indicating the alleviation of apoptosis and inflammation. In conclusion, oral administration of a Si-based agent resulted in renoprotective effects, presumably by suppressing oxidative stress via hydrogen generation.

[Empyema in Left Ureteral Stump Following Bilateral Nephrectomy and Living Renal Transplant-Case Report].

A 34-year-old male came to us with congenital spina bifida, vesicoureteral reflux and scoliosis. He had been on hemodialysis for chronic renal failure caused by reflux nephropathy since the age of 23 years. At the age of 24, he received bilateral nephrectomy and underwent living renal transplantation from his mother. Hemodialysis was started again at the age of 26, because the renal graft was not functioning. At the age of 34, the patient developed a fever that persisted for a few days. He received antibiotic medication from his physician, but since his condition did not improve he was refered to our hospital. A computed tomography scan examination revealed abscess formation in the left retroperitoneum. Magnetic resonance imaging findings also showed the abscess in the left retroperitoneum. The patient was diagnosed with empyema of the residual ureter and underwent a left ureterectomy procedure.

[A Case of Perivascular Epithelioid Cell Tumor (PEComa) of the Uterus Associated with Tuberous Sclerosis Complex Diagnosed by Intra-Abdominal Bleeding from the Uterus].

We report a case of perivascular epithelioid cell tumor (PEComa) of the uterus associated with tuberous sclerosis complex discovered as a result of intraabdominal bleeding. A 54-year-old woman visited the department of obstetrics and gynecology with chief complaints of genital bleeding and abdominal pain lasting three weeks. Abdominal computed tomography (CT) revealed intraabdominal bleeding from the uterine corpus. She had a history of bilateral renal angiomyolipoma, which was treated with partial bilateral nephrectomy at age 25. Moreover, pulmonary lymphangioleiomyomatosis was diagnosed at age 43. Both conditions were detected by the CT scan during this hospitalization. Immediately after the CT scans, the patient entered a state of hemorrhagic shock, and we performed an emergency simple total hysterectomy. Histopathological examination on the resected specimen yielded a diagnosis of uterine perivascular epithelial cell tumor (PEComa). After making a definitive diagnosis of tuberous sclerosis complex (TSC), systemic evaluation was performed. As a result, multiple skin and intracranial lesions characteristic of TSC were identified and we stated administration of everolimus.

[A Case of Adrenal Leiomyosarcoma].

A 61-year-oldman presentedwith a chief complaint of abdominal pain. Enhancedcomputed tomography andmagnetic resonance imaging showeda left adrenal mass with a diameter of 7 cm with heterogeneous enchancement. He was referredto our hospital for further treatment. No endocrinological abnormality was detected. The tumor showed abnormal uptake on fludeoxyglucose positron emission tomography scan. Preoperative diagnosis was left adrenocortical carcinoma (cT2N0M0). Tumor excision was performedandpathological findings on the resectedspecimen revealedleiomyosarcoma of the left adrenal grand. The patient has been followed up for 16 months with no additional treatment. No evidence of local recurrence or metastasis was seen.

Impact of prior abdominal surgery on the outcomes after robotic - assisted laparoscopic radical prostatectomy: single center experience.

PURPOSE: To evaluate the influence of prior abdominal surgery on the outcomes after robotic-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We retrospectively analyzed patients with prostate cancer who underwent RALP between June 2012 and February 2015 at our institution. Patients with prior abdominal surgery were compared with those without prior surgery while considering the mean total operating, console, and port-insertion times; mean estimated blood loss; positive surgical margin rate; mean duration of catheterization; and rate of complications. RESULTS: A total of 203 patients who underwent RALP during the study period were included in this study. In all, 65 patients (32%) had a prior history of abdominal surgery, whereas 138 patients (68%) had no prior history. The total operating, console, and port-insertion times were 328 and 308 (P=0.06), 252 and 242 (P=0.28), and 22 and 17 minutes (P=0.01), respectively, for patients with prior and no prior surgery. The estimated blood losses, positive surgical margin rates, mean durations of catheterization, and complication rates were 197 and 170 mL (P=0.29), 26.2% and 20.2% (P=0.32), 7.1 and 6.8 days (P=0.74), and 12.3% and 8.7% (P=0.42), respectively. Furthermore, whether prior abdominal surgery was performed above or below the umbilicus or whether single or multiple surgeries were performed did not further affect the perioperative outcomes. CONCLUSIONS: Our results suggest that RALP can be performed safely in patients with prior abdominal surgery, without increasing the risk of complications.

[A Case of Steroid Sulfatase Deficiency Complicated by Bilateral Undescended Testis].

Steroid sulfatase (STS) deficiency is one of the causes of ichthyoses. STS genes on the X chromosome is responsible for this disease. Therefore, STS deficiency is also called X-linked ichthyosis. Herein we report a case of STS deficiency complicated by bilateral undescended testis. A5-year-old-boy with STS deficiency was referred to our hospital because of bilateral undescended testis. We performed bilateral orchiopexy.

[Removal of a Foreign Body in the Urinary Bladder in a Patient Four Times in the Past Thirty Years].

We report a case of recurring foreign bodies in the urinary bladder. A 67-year-old male inserted a foreign body into the urinary bladder during masturbation. Eight months later, he experienced a fever and went to a hospital where ultrasonography revealed a foreign body in his urinary bladder. Then, he was referred to our hospital for surgical treatment. The patient's surgical record indicated that he had undergone the same operation 3 times in the past thirty years. The inserted foreign body was successfully removed by suprapubic cystotomy, and he was discharged 13 days after the operation. He was also evaluated by psychiatrists, but they diagnosed that he had no mental disorder. To our knowledge, this is the first report on the removal of a foreign body in the urinary bladder four times in the same patient.

[The Vaginal Metastasis of Ureteral Carcinoma after Left Nephroureterectomy: A Case Report].

69-year-old woman underwent left nephroureterectomy for left ureteral cancer (urothelial carcinoma (UC), high grade, pT3pN0) in September 2013. She returned to our hospital presenting with asymptomatic macrohematuria in July 2014. Cystoscopy showed tiny papillary tumors in the bladder. We also found genital bleeding from multiple papillary tumors on the vaginal wall. We performed transurethral resection of the bladder tumor and a biopsy of the vaginal wall demonstrated non-invasive UC, high grade. Pelvic magnetic resonance imaging after the operation showed no infiltration outside the bladder wall and vaginal wall. Therefore, we performed endoscopic excision of the vaginal tumor. However we could not resect all vaginal tumors. Irradiation of the vagina and uterus was performed under the diagnosis of metastasis of UC tovagina. Vaginal UC is extremely rare and this is the 26th case report in the literature.

[Emphysematous Cystitis and Acute Focal Bacterial Nephritis: A Case Report].

A 96-year-old woman was diagnosed with colitis in our hospital. Her past history was breast cancer and lung cancer but no diabetes mellitus. She suddenly complained of lower abdominal pain. Abdominal computed tomography (CT) revealed intramural gas in the bladder wall and multiple poor contrasting area in her right kidney, which suggested emphysematous cystitis and acute focal bacterial nephritis. Indwelling urethral catheter was performed for bladder drainage and the treatment with antibiotics started. Urine culture revealed Klebsiella pneumoniae and blood culture was negative. After 3 weeks, the abdominal CT confirmed the decrease of gas within the bladder wall and improvement of contrasting area in the right kidney.

[Traumatic Testicular Rupture Complicated with Hydrocele: A Case Report].

A 17-year-old man presented with right hydrocele because of an athletic injury. His scrotum was hit with a ball 2 months ago while playing baseball. He was diagnosed with post-traumatic hydrocele and underwent needle puncture at another hospital 1 month after the trauma. However, the hydrocele did not improve. Therefore, he was referred to our hospital for surgical treatment. For diagnosis of the traumatic hydrocele testis, a hydrocelectomy was scheduled. When we opened the tunica vaginalis, we realized that the tunica albuginea had been ruptured and the testicular parenchyma had gushed out. We tried to replace all the escaped testicular parenchyma into the tunica albuginea, but it was impossible. Therefore were moved some of the redundant testicular parenchyma, and replaced the remnants into the tunica albuginea. After the operation, right hydrocele and testicular atrophy did not occur. Traumatic testicular rupture complicated with hydrocele is rare.

[A Case of Perirenal Inflammatory Liposarcoma].

A 65-year-old man had been hospitalized for examination of melena at a separate facility. Computed tomography (CT) showed left renal mass and he was referred to our hospital. Magnetic resonance imaging (MRI) revealed a tumor without adipose components in the perirenal space. Preoperative diagnosis was retroperitoneal malignant tumor. Tumor excision and left nephrectomy were performed. Pathologic evaluation revealed inflammatory liposarcoma. He has been followed up for 10 months with no additional treatment and no evidence of local recurrence was seen.

Remarkable Improvement of Diabetic Nephropathy in Transplanted Allograft after Kidney Transplantation.

Although glomerular damage caused by diabetic nephropathy was thought to be irreversible, in recent years, there have been reports on improvement in glomerular damage with strict glycemic control. However, few reports are available on the pathologic course after renal transplantation of donor-derived grafts with findings of diabetic nephropathy. A 53-year-old woman underwent an ABO blood-type compatible living-donor renal transplant. The recipient had no history of diabetes, and fasting blood glucose and hemoglobin A1c levels were both normal. The donor was a 57-year-old male who had received treatment for type 2 diabetes mellitus for 10 years. Transplant renal biopsy performed 1 h after revascularization showed mesangial matrix expansion and arterial hyalinosis due to diabetic nephropathy. The blood glucose level was within the normal range after transplantation. Mesangial matrix expansion and arterial hyalinosis disappeared in allograft biopsy samples 7 years after transplantation. We observed significant improvement in the pathological findings of donor-derived diabetic nephropathy after renal transplantation in the subsequent follow-ups.

Single-cell transcriptome analysis of a rat model of bilateral renal ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) causes massive tissue damage. Renal IRI is the most common type of acute renal injury, and the defects caused by it may progress to chronic kidney disease (CKD). Rodent models of renal IRI, with various patterns, have been used to study the treatment of human kidney injury. A rat model of bilateral IRI, in which the bilateral kidney blood vessels are clamped for 60 min, is widely used, inducing both acute and chronic kidney disease. However, the molecular mechanisms underlying the effects of bilateral IRI on kidney cells have not yet been fully elucidated. This study aimed to perform a whole-transcriptome analysis of the IRI kidney using single-cell RNA sequencing. We found renal parenchymal cells, including those from the proximal tubule, the loop of Henle, and distal tubules, to be damaged by IRI. In addition, we observed significant changes in macrophage population. Our study delineated the detailed cellular and molecular changes that occur in the rat model of bilateral IRI. Collectively, our data and analyses provided a foundation for understanding IRI-related kidney diseases in rat models.

D-Asparagine is an Ideal Endogenous Molecule for Measuring the Glomerular Filtration Rate.

Introduction: An ideal endogenous molecule for measuring glomerular filtration rate (GFR) is still unknown. However, a rare enantiomer of serine, d-serine, is useful in GFR measurement. This study explored the potential of other d-amino acids for kidney function assessment. Methods: This was a cross-sectional observational study of 207 living kidney transplant donors and recipients, for whom GFR was measured using clearance of inulin (C-in). Associations between levels of d-amino acids and GFR were analyzed using multivariate factor analysis. Fractional excretion (FE), a ratio of the clearance of a substance to C-in as a standard molecule, was calculated to monitor the excretion ratio after glomerular filtration. Dissociation from an ideal FE of 100% was assessed as a bias. Proportional bias against C-in was calculated using Deming regression. Results: Multivariate analysis identified the blood level of d-asparagine to reflect GFR. Means of blood d-asparagine and clearance of d-asparagine (C-d-Asn) were 0.21 µM and 65.0 ml/min per 1.73 m2, respectively. Inulin-based FE (FEin) of d-asparagine was 98.67% (95% confidence interval [CI]: 96.43-100.90%) and less biased than those of known GFR markers, such as FEin of creatinine (147.93 [145.39-150.46]; P < 0.001) and d-serine (84.84 [83.22-86.46]; P < 0.001). A proportional bias of C-d-Asn to C-in was -7.8% (95% CI, -14.5 to -0.6%), which was minor compared to those of clearance of creatinine (-34.5% [-37.9 to -31.0%]) and d-serine (21.2% [13.9-28.9]). Conclusion: D-Asparagine acts similar to inulin in the kidney. Therefore, d-asparagine is an ideal endogenous molecule that can be used for GFR measurement.

A Case Report of a Kidney Transplant Recipient With Organizing Pneumonia After Graft Loss.

We present a case of a 68-year-old male patient who underwent ABO-incompatible living kidney transplantation from his wife because of immunoglobulin A nephropathy 13 years ago. Over time, the patient showed a gradual decline in graft function and required reinitiation of hemodialysis because of fluid overload, which led to his admission to our hospital. An arteriovenous fistula was created, and subsequently, hemodialysis therapy was started. Because he had chronic cytomegalovirus retinopathy and thrombotic microangiopathy due to immunosuppressive therapy at admission, mycophenolate mofetil and tacrolimus were discontinued during hemodialysis initiation. Only low-dose prednisolone was continued. One week later, the patient had a fever, and chest computed tomography revealed bilateral pneumonia, which was not improved by antibiotics. The patient was diagnosed with organized pneumonia. After ruling out opportunistic infection, including pneumocystis pneumonia, increased doses of prednisolone resulted in the remission of organizing pneumonia.

[Extranodal marginal zone lymphoma of the dura: a case report].

The authors present the case of a 65-year-old woman who initially was diagnosed as having intracranial dural B-cell malignant lymphoma. She survived more than 9 years after surgery and radiation. We re-examined the specimens pathologically. Histological findings confirmed an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) that showed numerous IgG4-positive plasma cells. MALT lymphomas are already recognized as a distinct clinico-pathological entity. A primary dural MALT lymphoma is very rare and has a favorable clinical outcome, and patients are expected to have an excellent long-term survival with local therapy alone.

Rapid deterioration of renal function following coronavirus disease 2019 in a renal transplant recipient.

Introduction: The coronavirus disease 2019 pandemic emerged in December 2019. Renal transplant recipients receiving chronic immunosuppression are considered to be at a high risk of infection. Aside from upper respiratory tract symptoms, coronavirus disease 2019 has also been reported to cause acute kidney injury in 20-50% of infected cases. Case presentation: A 62-year-old male renal transplant recipient presented with high fever, diarrhea, and cough, concurrent with rapid deterioration of graft function. The patient tested positive for coronavirus disease 2019. The pathological findings of the graft biopsy revealed diffuse flattening of tubular epithelial cells and extensive loss of the brush border in proximal tubular cells. Mycophenolate mofetil was discontinued and sotrovimab, remdesivir, intravenous immunoglobulin, and intravenous methylprednisolone were administered, resulting in gradual improvements in clinical symptoms and renal function. Conclusion: We describe a case of a coronavirus disease 2019-infected kidney transplant recipient who developed severe acute kidney injury caused by severe acute tubular necrosis.

Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study.

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Measurement of glomerular filtration rate using endogenous d-serine clearance in living kidney transplant donors and recipients.

BACKGROUND: Endogenous molecules that provide an unbiased and a precise evaluation of kidney function are still necessary. We explored the potential of clearance of d-serine, a rare enantiomer of serine and a biomarker of kidney function, as a measure of glomerular filtration rate (GFR). METHODS: This was a cross-sectional observational study of 200 living kidney transplant donors and recipients enrolled between July 2019 and December 2020 in a single Japanese center, for whom GFR was measured by clearance of inulin (C-in). Clearance of d-serine (C-dSer) was calculated based on blood and urine levels of d-serine, as measured by two-dimensional high-performance liquid chromatography. Analytical performance was assessed by calculating biases. Utilizing data from 129 participants, we developed equations for C-in based on C-dSer and C-cre using a linear regression model, and the performance was validated in 68 participants. FINDINGS: The means of C-in and C-dSer were 66.7 and 55.7 mL/min/1.73 m2 of body surface area, respectively, in the entire cohort. C-dSer underestimated C-in with a proportional bias of 22.0% (95% confidence interval, 14.2-29.8%) and a constant bias of -1.24 (-5.78-3.31), whereas the proportional bias was minor to that of C-cre (34.6% [31.1-38.2%] and 2.47 (-1.18-6.13) for proportional and constant bias, respectively). Combination of C-dSer and C-cre measured C-in with an equation of 0.391 × C-dSer + 0.418 × C-cre + 3.852, which reduced the proportional bias (6.5% [-0.2-13.1%] and -4.30 [-8.87-0.28] for proportional and constant bias, respectively). In the validation dataset, this equation performed well with median absolute residual of 3.5 [2.3-4.8], and high ratio of agreement (ratios of 30% and 15% different from C-in [P30 and P15] of 98.5 [91.4-100] and 89.7 [80.0-95.2], respectively). INTERPRETATION: The smaller proportional bias compared to that of C-cre is an advantage of C-dSer as a measure of C-in. Combinational measurement of d-serine and creatinine, two endogenous molecules, has the potential to serve as a measure of GFR with precision and minor biases and can support important clinical decisions. FUNDING: Japan Society for the Promotion of Science (JSPS, grant number 17H04188), Japan Agency of Medical Research and Development (AMED, JP20gm5010001), Osaka Kidney Bank (OKF19-0010), Shiseido Co., Ltd and KAGAMI Inc.