Clinical Impacts of Allograft Biopsy in Renal Transplant Recipients 10 Years or Longer After Transplantation.

We aimed to investigate the clinical value of allograft biopsy performed long after renal transplantation. We retrospectively evaluated 99 allograft biopsies in recipients with transplantation vintages of 10 years or longer. Mixed-effects model showed that 1-year estimated glomerular filtration rate (eGFR) slopes after biopsy were significantly greater than those before biopsy [-3.13, -4.42 mL/min/1.73 m2/year, p = 0.01]. Renal biopsy changed the treatment strategies in more than half of the patients. Improvement in eGFR slopes was pronounced in 51 patients with treatment modification based on the biopsy results [2.27 (95% confidence interval (CI): 0.66, 3.89) mL/min/1.73 m2/year], whereas no improvement was observed in those without [0.33 (95% CI: -1.05, 1.71) mL/min/1.73 m2/year, Pinteraction = 0.001]. Among the treatment modifications, enhancement of immunosuppression (IS) led to the most remarkable improvement in eGFR slope. Patients with g scores ≥2 were more likely to receive IS enhancement than those with g scores = 0 [odds ratio; 15.0 (95% CI: 1.65, 136)]. Patients with active glomerulitis (g ≥ 1) without chronicity (cg ≤ 1) showed the most significant improvement in eGFR slope. Given the prevalence of active glomerulitis (g ≥ 1, 21%), which is responsive to treatment even long after transplantation, and the observed magnitude of eGFR slope improvement, renal biopsy can indeed improve allograft prognosis.

Fluoroquinolone resistance and clinical characteristics of acute bacterial prostatitis in Japan: A multicenter study by the Japanese research group for urinary tract infection.

OBJECTIVE: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan. METHODS: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed. RESULTS: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥37.5 °C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48 % (51/106). FQ-resistant E. coli was detected in 33 % (17/51), and extended-spectrum beta-lactamase-producing E. coli in 12 % (6/51). TRBx (odds ratio [OR] = 48.60, 95 % confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95 % CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria. CONCLUSIONS: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category.

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.

[A Case of Remission of Metastatic Germ Cell Tumor in an Elderly Patient by Multimodal Treatment].

There have been few reports of multimodal treatment such as chemotherapy and surgical resection for testicular tumors over 40 years old. In this case, a 64-year-old man with nonseminoma, pT2N2M1aS1, stage IIIb, IGCCC good prognosis completed induction chemotherapy, followed by retroperitoneal lymph node dissection and resection of lung metastases. Chemotherapy (4 courses of etoposide and cisplatin therapy) was completed without serious adverse events other than grade 4 neutropenia. Resection of the residual tumor confirmed no viable tumor cells. There was no evidence of recurrence or elevation of tumor markers in the following 6 months. Similar cases could increase with the increase of testicular tumors in the elderly.

[Ectopic Ureterocele of Adult Male with Urination Difficulty : A Case Report].

Ectopic ureteroceles is sometimes noted in children as an incidental finding in antenatal ultrasonography results or because of symptoms related to a urinary tract infection. In contrast, it is rarely noted in adults, with only 18 cases in Japan presented in literature. We report here a 30-year-old adult male with an ectopic ureterocele discovered due to urination difficulty. The patient noted a poor urine stream and macroscopic hematuria after exercise, and over time needed manual compression on the lower abdomen for urination. Computed tomography results revealed a 35 mm right ureterocele containing a 7.0 mm stone. Cystoscopy showed the ureterocele protruding into the prostatic urethra, which was thought to be the cause of urination difficulty. Transurethral resection of the ureterocele and lithotripsy for the stone were performed. The right ureteral orifice was not visualized during the operation. Resection was performed from the bladder neck side so that the ureterocele wall did not interfere with urination and the calculus was crushed with a pneumatic lithotripter (LithoClast®). Urination difficulty was improved following the procedures. Urinary cystourethrography performed two weeks postoperatively confirmed no vesicoureteral reflux. No symptoms of dysuria or fever were noted at a follow-up visit two months after the operation.

Difference in IgA1 O-glycosylation between IgA deposition donors and IgA nephropathy recipients.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and disease recurrence often occurs after transplantation. On the other hands, Asymptomatic IgA deposition (IgAD) is occasionally observed in donated kidney. It is recognized that IgAD does not progress to IgAN, but the mechanism has not demonstrated yet. In IgAN, aberrant IgA1 O-glycan structure in the hinge region (HR) of serum IgA is suggested as one of the most convincing key mediators. However, little is known about IgA1 O-glycan structure in IgAD patients. Herein, we investigated the prevalence of IgAD in living renal transplant donors in our cohort. IgAD was observed in 21(13.0%) among 161 renal transplant donors and have statistically significant blood relationship with IgAN recipients (28.6% in relatives vs. 9.8% in non-relatives, respectively; p = 0.0073). Next, we evaluated the IgA1 O-glycan structure of serum IgA from IgAN recipients (n = 26), IgAD donors (n = 17), and non-IgAD helthy donors (n = 27) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The numbers of GalNAc and Gal and the Gal/GalNAc ratio in the HR of the IgAN recipients had significantly lower comparing to the IgAD and non-IgAD healthy donors. The decreased Gal/GalNAc ratio in IgAN recipients means the increased ratio of galactose-deficient IgA1. To the best of our knowledge, this is the first report to compare the O-glycan structures in IgAN recipients and IgAD donors using MALDI-TOF MS. We concluded that IgAD was more common in IgAN related donors. Overall, decreased GalNAc and Gal contents in HR could play a material pathogenic role in IgAN.

[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.

[Disturbance of Consciousness in a Patient with an Indwelling Lumbar-Peritoneal Shunt Following Retroperitoneal Laparoscopic Radical Right Nephrectomy : A Case Report].

An 83-year-old man with an indwelling lumbar-peritoneal (L-P) shunt (for idiopathic normal-pressure hydrocephalus) underwent retroperitoneal laparoscopic radical right nephrectomy for renal cell carcinoma (pT1aN0M0). Peritoneal perforation occurred intraoperatively, and he developed postoperative disturbance of consciousness. Computed tomography showed mild ventricular enlargement, which was attributed to L-P shunt failure secondary to increased pneumoperitoneum pressure. His level of consciousness was improved when we raised his head. Few reports have discussed complications observed during retroperitoneal laparoscopic surgery in patients with an indwelling L-P shunt. This case report discusses this topic along with a discussion of previously reported findings.

[A Case of Hypoplastic Kidney and an Ectopic Ureter Treated by Laparoscopic Nephroureterectomy in an Adult Woman].

A 20-year-old woman had urinary incontinence since childhood. She self-managed her symptoms by using incontinence pads and she admitted never having been to a urologist. When she consulted a urologist for cystitis, ultrasonography could not locate the presence of a right kidney. She was suspected of having a contracted kidney and was referred to our hospital for further examinations and treatment. An enhanced computed tomography scan showed a contracted right kidney, which was located on the surface of the inferior vena cava. Magnetic resonance imaging showed that the right ureter extended into the vagina. Cystoscopy showed the absence of a right ureteral orifice, and an ectopic orifice was identified in the vagina. Laparoscopic nephroureterectomy was performed based on the diagnosis of a hypoplastic kidney with an ectopic ureter. We removed the ureter as far as the vagina because a residual ureteral segment could cause infection. Postoperatively, the patient had no complications, and her uterine artery was successfully saved. The patient achieved complete continence after the operation.

The impact on graft survival of interstitial inflammation in borderline change of allograft kidneys.

AIM: In kidney transplantation cases, borderline change (BL) can lead to a progressive course. However, factors related to outcome and the progress of BL are not well defined. In this study, we focused specifically on interstitial inflammation as a factor influencing outcome after diagnosis of BL. METHODS: We followed 252 recipients who underwent renal transplantation between 1998 to 2012 at our hospital. Of those, we retrospectively studied 40 diagnosed with BL from allograft biopsy findings, and then classified them as BL1 and BL2 according to the level of interstitial inflammation (i) (BL1: i < 10%, BL2: i ≥ 10%). RESULTS: There were 21 BL1 and 19 BL2 cases, of whom 7 developed rejection during the follow-up period. There were no significant differences for graft survival rate and the rate leading to acute rejection between the 2 groups (P = 0.44, P = 0.69). Univariate analysis showed that the grade of interstitial inflammation was not a significant risk factor for developing acute rejection (P = 0.816). CONCLUSION: Our results show that the level of interstitial inflammation does not have an effect on a progressive BL course.

[A case of urachal carcinoma with multiple lung metastases treated by TS-1/CDDP chemotherapy].

A 67-year-old woman presented with macroscopic hematuria and lower abdominal pain. Cystoscopy revealed a broad-stalk non-papillary tumor at the bladder dome. Computed tomography (CT) showed a tumor extending from the umbilicus to the bladder dome, together with multiple lung metastases. Serum carcinoembryonic antigen and cancer antigen (CA19-9) levels were elevated at 7.0 ng/ml and 180 U/ml, respectively. Transurethral resection of the tumor was performed and histopathology revealed adenocarcinoma. Therefore, the tumor was diagnosed as a stage IVB (Sheldon's category) urachal carcinoma. En bloc segmental resection of the urachal carcinoma with the bladder dome was performed, followed by chemotherapy with tegafur, gimestat, and otastat potassium (TS-1) and cisplatin. The disease remained stable for 8 months. However, a follow up CT scan after 11 chemotherapy cycles showed progression of the lung metastases. In spite of the change to a second-line gemcitabine and cisplatin chemotherapy regimen, the disease continued to progress after 4 cycles.

Assessment of Tumor Markers in Renal Transplant Recipients.

Background/Aim: Malignant tumors are diagnosed using various methods, including diagnostic imaging methods. The measurement of tumor markers is commonly used because of its noninvasiveness and convenience. Furthermore, it is known that the excretion and metabolism of some tumor markers are affected by impaired renal function. In the present study, we investigated the effect of improved renal function on pre-and post-transplantation changes in tumor marker levels [carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and prostate-specific antigen (PSA)] in renal transplant recipients. Patients and Methods: A total of 116 renal transplant recipients, who had not been diagnosed with malignancies between January 2012 and December 2019, were included, and tumor markers were investigated. Results: CEA showed a significant decrease after kidney transplantation, regardless of the dialysis type (3.6→2.6 ng/ml, p<0.001), while other tumor markers showed a significant increase (AFP: 3.6→3.7 ng/ml; CA19-9: 16.2→19.5 U/ml; PSA: 0.95→1.05 ng/ml; all p<0.05). Pre- and postoperative eGFR ratios and postoperative liver function were identified as factors influencing the postoperative CEA and CA19-9 values, while PSA was influenced by the duration of dialysis. No statistically significant factors were found for AFP levels. Conclusion: Caution should be exercised when investigating tumor markers in patients with renal dysfunction, as tumor marker levels may vary depending on the pathophysiology of each patient.

A retroperitoneal primary undifferentiated pleomorphic sarcoma.

A 52-year-old male had pain in the right back and right hypochondrium, and an abdominal CT scan revealed a 49-mm tumor in the right upper perirenal space. Additional MRI and PET-CT suggested that the tumor may be a primary adrenal carcinoma and could invade the liver and diaphragmatic leg. The tumor was completely removed by laparotomy and histopathologically diagnosed as retroperitoneal primary undifferentiated pleomorphic sarcoma. The patient has remained recurrence-free for 1.5 years after the surgery.

MYH9-related disorder with sole presentation of end-stage kidney disease and long-term, recurrence-free living after living donor renal transplantation: a case report.

MYH9-related disorders are a group of autosomal dominant disorders caused by mutations in MYH9, and are characterized by thrombocytopenia, sensorineural hearing loss, cataracts, and renal failure. Here, we report a case of chronic renal failure due to MYH9-related disorder with renal symptoms in a patient who underwent living-donor renal transplantation. The patient was diagnosed with proteinuria during a health checkup at the age of 12 years. Her renal function gradually deteriorated, and hemodialysis was initiated at 34 years of age. No definitive diagnosis of renal disease was made through renal biopsy. At the age of 35, she underwent living-donor renal transplantation from her mother as the donor. Six years after transplantation, her renal function remained stable, and no evidence of recurrent nephritis was found during renal biopsies. The family history revealed that her father, uncle, and younger brother had end-stage kidney disease. Genetic testing revealed a mutation (p.E1653D) related to the MYH9 gene. As her father had a history of renal biopsy and was diagnosed with focal segmental glomerulosclerosis (FSGS), we diagnosed chronic renal failure due to FSGS associated with MYH9 disorder. There were no findings suggestive of hearing loss, cataracts, or thrombocytopenia in the recipient or their family members with renal failure, and no symptoms other than renal failure were noted.

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.

Performance of the New CKD-EPI Creatinine-and Cystatin C-based Glomerular Filtration Rate Estimation Equation in Living Kidney Donor Candidate.

Background: Accurate preoperative evaluation of renal function in living kidney donor candidates (LKDCs) is crucial to prevent kidney failure after nephrectomy. We examined the performance of various estimated glomerular filtration rate (eGFR) equations, including the new chronic kidney disease epidemiology collaboration (CKD-EPI) equation in LKDCs. Methods: We analyzed 752 LKDCs who were assessed for measured GFR by inulin clearance as part of routine pretransplant examination from 2006 to 2020. CKD-EPI2012 from cystatin C (CKD-EPI12cys), CKD-EPI2021 from creatinine (CKD-EPI21cr), CKD-EPI21cr-cys, Japanese modified (JPN) eGFRcr, and JPN eGFRcys were compared in determining the suitability for LKDCs. Results: CKD-EPI12cys had the lowest absolute and relative biases, with higher P30 and P10, followed by JPN eGFRcys, CKD-EPI21cr, and CKD-EPI21cr-cys. The root mean square error was least for CKD-EPI12cys, then JPN eGFRcys, CKD-EPI21cr-cys, CKD-EPI21cr, and JPN eGFRcr. CKD-EPI21cr, CKD-EPI12cys, and CKD-EPI21cr-cys estimated GFR higher, whereas JPN eGFRcr estimated GFR lower. At the threshold of 90 mL/min/1.73 m2, CKD-EPI21cr had the highest percentage of misclassification at 37.37%, whereas JPN eGFRcr had the lowest percentage of misclassification at 6.91%. Using the age-adapted approach, JPN eGFRcr had the lowest percentage of misclassification into overestimation at 7.31%. All eGFR had >5.0%, and CKD-EPI21cr had the highest percentage of misclassification at 21.94%. Conversely, CKD-EPI21cr-cys had the lowest percentage of misclassification into underestimation at 3.19%, both at the threshold of 90 mL/min/1.73 m2 and the age-adapted approach. JPN eGFRcr had the highest percentage at 33.38% and 40.69%, respectively. Conclusions: In evaluating the renal function of Japanese LKDCs, the new CKD-EPI equation had a lower rate of underestimation but a relatively high rate of overestimation. New GFR estimation formulas are needed to be tailored to each ethnic group to enhance the accuracy and reliability of donor selection processes.

Seronegative rheumatoid arthritis after combination therapy with ipilimumab and nivolumab for postoperative pancreatic and liver metastases from renal cell carcinoma.

Introduction: Since the approval of immune checkpoint inhibitors for renal cell carcinoma treatment, therapeutic efficacy has been enhanced. However, although autoimmune-related side effects may occur, rheumatoid immune-related adverse events seldom develop. Case presentation: A 78-year-old Japanese man with renal cell carcinoma developed pancreatic and liver metastases after bilateral partial nephrectomy and was treated with ipilimumab and nivolumab. After 22 months, he developed arthralgia in limbs and knee joints, accompanied by limb swelling. The diagnosis was seronegative rheumatoid arthritis. Nivolumab was discontinued, and prednisolone was initiated, quickly improving symptoms. Although nivolumab was resumed after 2 months, arthritis did not recur. Conclusion: Immune checkpoint inhibitors may cause a wide variety of immune-related adverse events. When arthritis is encountered during immune checkpoint inhibitor administration, seronegative rheumatoid arthritis should be differentiated from other types of arthritis, despite being less frequent.

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.

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.