Urinary Epidermal Growth Factor Level as a Noninvasive Indicator of Tubular Repair in Patients with Acute Kidney Injury.

Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary ß-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI.

Wound healing responses of urinary extravasation after urethral injury.

The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.

Vibegron shows high efficacy in pediatric patients with refractory daytime urinary incontinence.

PURPOSE: Sparse published reports exist nowadays on vibegron and pediatric overactive bladder, so its usefulness of this agent remains unclear. The purpose of this study was to clarify the effectiveness of vibegron for pediatric cases of daytime urinary incontinence (DUI), including refractory cases. METHODS: Participants comprised 57 patients treated with vibegron for DUI from March 2019 to April 2022. To investigate treatment outcomes and risk factors for pediatric patients with refractory DUI, the following factors were evaluated: age at initiatial administration; frequency of DUI; duration of vibegron treatment; presence of neurodevelopmental disorders (NDDs); presence of constipation; and anticholinergic medications before and after initiation of treatment. RESULTS: Patients included 38 boys and 19 girls with a median age at initial administration of 111 months (range: 64-202 months) and a median administration term of 6 months (range: 1-33 months). With treatment for 6 months, the response rate (complete response + partial response) was 68.3%. A total of 24 cases with NDD showed a 72.0% response rate at 6 months. As for the relationship between anticholinergic agents and vibegron, 15 cases were treated with vibegron as the first choice without anticholinergics (First-choice cases), and 33 cases were treated with vibegron alone after switching from anticholinergics (Switch cases). Vibegron was used in combination with anticholinergic agents in 9 cases (Add-on cases). Response rates at 6 months were 85.0% in First-choice cases, 66.3% in Switch cases, and 40.7% in Add-on cases. Univariate analyses failed to identify any significant risk factors for refractory cases. CONCLUSIONS: Vibegron was effective in pediatric cases of DUI, with efficacy demonstrated within a short time in many cases. Vibegron is expected to play a significant role in the treatment of DUI in pediatric cases.

Pregnancy in a patient with caudal regression syndrome following continent bladder reconstruction.

Caudal regression syndrome (CRS) is rare congenital malformation, which is characterized by abnormal development of the lower end of the spine and complicated with neurodevelopmental disorders of vesico-rectal functions and the lower extremities. We report the case of a woman with CRS who became pregnant and gave birth following continent bladder reconstruction (CBR) for intractable urinary incontinence. A 25-year-old primigravida woman with CRS became pregnant naturally and was referred to our department. She had undergone CBR in our institute at 14 years old. Emergency cesarean section (CS) was performed at 30 + 5 weeks of gestation due to severe preeclampsia. This is the first report of a woman with CRS who became pregnant and gave birth following CBR. A multidisciplinary team is needed to manage pregnant women with CRS following CBR. Collaboration with a urologist is especially important for managing pregnancy and performing CS. The CBR is performed for the purpose of improving quality of life by gaining urinary continence and may increase sexual behavior in women with CRS, and so obstetricians may encounter pregnancies more frequently in the future.

Novel high-quality and reality biomaterial as a kidney surgery simulation model.

Surgical training using live animals such as pigs is one of the best ways of achieving skilled techniques and fostering confidence in preclinical medical students and surgeon trainees. However, due to animal welfare ethics, laboratory animals' usage for training should be kept to a minimum. We have developed a novel kidney organ model utilizing a simple procedure in which the kidney is first refluxed with N-vinyl-2-pyrrolidone (NVP) solution for 1 hour in its bath, followed by permeation for 23 hours, with a subsequent freshwater refluxed for 48 hours in the washing step. Surgical simulation of the prepared kidney model (NVP-fixed kidney) was compared with three types of other basic known simulation models (fresh kidney, freeze-thaw kidney, and FA-fixed kidney) by various evaluations. We found the NVP-fixed kidney to mimicked fresh kidney function the most, pertaining to the hardness, and strength of the renal parenchyma. Moreover, the NVP-fixed kidney demonstrated successful blood-like fluids perfusion and electrocautery. Further, we confirmed that surgical training could be performed under conditions closer to actual clinical practice. Our findings suggest that our model does not only contribute to improving surgical skills but also inspires the utilization of otherwise, discarded inedible livestock organs as models for surgical training.

Retroperitoneoscopy-Assisted Dismembered Pyeloplasty With Single-Site Plus One Port in Older Children With Congenital Hydronephrosis.

INTRODUCTION: This study aimed to clarify the advantage of retroperitoneoscopy-assisted dismembered pyeloplasty with single-site plus one port (RPSPO) for pediatric congenital hydronephrosis in patients aged ≥7 years. METHODS: We retrospectively compared a group of patients aged ≥7 years (study group) with patients aged <7 years (comparison group), who underwent RPSPO between August 2015 and August 2018, in terms of preoperative patient characteristics, intra- and perioperative results, and postoperative results. RESULTS: The study group consisted of eight patients. The median body weight at surgery was 27 kg (20-38 kg). The median age at surgery was 102.5 m (87-139 m). The severity of hydronephrosis on the affected side graded by the Society for Fetal Urology grade was grade 3 in one case and grade 2 or less in all other cases. All patients underwent a 99m Tc-MAG3 renogram. Comparison between the two groups showed significant differences in body weight at surgery (p = 0.003), age (p < 0.001), and preoperative hydronephrosis grade (p = 0.007), but the median length of the skin incision was 20 mm in both groups, with no significant difference (p = 1.000). Redo pyeloplasty was not required in any patient in either group. CONCLUSION: RPSPO is an advantageous procedure for older children because it allows precise ureteropelvic neoanastomosis under direct vision and the same wound size as in younger children.

Histological and radiological evaluation of thermal denaturation depth using soft coagulation during partial nephrectomy in living pigs.

OBJECTIVES: To evaluate thermal denaturation depth using soft coagulation in kidneys in vivo. METHODS: In experiment 1, nine kidneys from five pigs were cauterized using five soft-coagulation settings at 80 W with effect 7 by VIO300D and one monopolar-coagulation setting. The surface of the kidney was cauterized over a period of 2, 5 and 10 s. The temperature change was measured at depths of 5 and 10 mm. In experiment 2, three kidneys from two pigs were excised in a semicircular shape with a diameter of 5, 10 and 20 mm without clamping the renal artery. Cauterization was carried out until hemostasis was confirmed by soft coagulation at 80 W with effect 7. After completion of the experiments, pathology examinations of the kidneys were carried out. RESULTS: Experiment 1 showed that with proper saline dripping, denaturation spread with increased cauterization time, reaching a depth of 4 mm at 10 s with or without clamps. The depth remained at 2-3 mm at 10 s in the absence or excess of saline. The temperature increased by 15.6°C at a depth of 5 mm and 8.8°C at 10 mm. In experiment 2, the depth was 4.6 mm from the incision surface regardless of the cauterization time or excision size. CONCLUSIONS: These findings suggest that soft coagulation can be useful for preserving renal function and reducing complications in partial nephrectomy.

Mechanism of hypertensive crisis during energy device ablation of the adrenal gland: An experimental animal study.

OBJECTIVE: To elucidate the mechanism of hypertensive crisis during energy device ablation of the adrenal gland. METHODS: Electrocoagulation on the adrenal glands of six pigs was carried out with the same energy device (VIO300D) using four methods: (i) monopolar coagulation; (ii) monopolar soft coagulation using IO-advanced ball-type electrodes; (iii) bipolar soft coagulation by pinching; and (iv) bipolar soft coagulation by non-pinching (surface contact) using Bipolar forceps Premium. After electrocoagulation for 5 s, blood pressure and pulse changes were monitored, and adrenal hormones were measured from a central vein. The adrenal glands were removed, and the degree of tissue damage was scored histologically. RESULTS: Hypertensive crisis occurred with electrocoagulation of the adrenal gland by the monopolar coagulation, monopolar soft coagulation and bipolar soft coagulation pinching methods. Blood pressure did not change with the bipolar soft coagulation non-pinching method. Pathologically, tissue damage to the adrenal medulla was associated with elevated blood pressure and adrenaline and noradrenaline release. CONCLUSIONS: Hypertensive crisis caused by energy device ablation to the adrenal gland is caused by the release of catecholamines due to heat damage to the adrenal medulla rather than the type of energy device. Proper use of an energy device that does not cause thermal degeneration of the medulla is required to prevent hypertensive crisis.

Predictive factors and management of urinary tract infections after kidney transplantation: a retrospective cohort study.

BACKGROUND: Urinary tract infection (UTI) is one of the most common infectious complications in kidney transplant recipients. The aims of our study were to identify possible predictive factors for UTI and advocate for the management of UTI after kidney transplantation (KT). METHODS: Between January 2013 and December 2018, 182 adult patients with end-stage kidney disease who underwent KT were retrospectively analyzed. Patients who had urinary symptoms and positive urine culture were diagnosed with UTI. The types of urinary bacteria causing UTIs were also examined. RESULTS: UTIs occurred in forty-one patients (25.1%), and the median time to UTI onset (UTI-free survival) after KT was 189 days. The Cox hazard regression analysis showed that the predictive factors for UTI onset were as follows: posttransplant urinary catheterization, including indwelling urinary catheterization and clean intermittent catheterization; a maximum bladder capacity before KT of less than 150 ml; and a low serum albumin level at 1 month after KT. The most common causative agent was Escherichia coli (56.6%), followed by Enterococcus spp. (15.6%) and Klebsiella spp. CONCLUSIONS: Kidney transplant recipients with prolonged postoperative malnutrition, posttransplant voiding dysfunction and/or urinary storage disorder had an increased risk of UTI. Bladder function tests, such as uroflowmetry, postvoid residual urine tests, and urodynamic tests, were needed to predict UTI. For patients with malnutrition, care should be taken to ensure sufficient calorie intake. Kidney transplant recipients who develop UTI should be treated as complicated UTI patients.

Acute Interstitial Nephritis and Acute Tubular Injury Due to a Transdermal Loxoprofen Patch.

A transdermal patch formulation of a non-steroidal anti-inflammatory drug (NSAID) used by a 44-year-old man resulted in acute interstitial nephritis and acute tubular injury. This patient also had a history of mild kidney dysfunction and osteoporosis. The NSAID patch had been prescribed after a traffic accident. He was also receiving a vitamin D analog and taking over-the-counter calcium supplements. Two months later, renal dysfunction and hypercalcemia were discovered. A renal biopsy showed acute interstitial nephritis and acute tubular injury. Once these agents were withdrawn, the renal function recovered. This is the first reported occurrence of biopsy-proven acute interstitial nephritis attributable to NSAID patch usage.

Mid-Term Safety and Efficacy of the Modified Double Hydrodistention Implantation Technique (HIT), Termed Systematic Multi-Site HIT (SMHIT), for Patients with Primary Vesicoureteral Reflux.

PURPOSE: To evaluate the treatment outcomes and postoperative complications associated with the systematic multi-site hydrodistention implantation technique (SMHIT) for primary vesicoureteral reflux (VUR) and to determine its mid-term efficacy and safety. PATIENTS AND METHODS: We retrospectively reviewed the data for 17 ureters from 12 consecutive children, aged ≥1 year, with grade II-IV reflux and a history of febrile urinary tract infections (FUTI), who underwent a single-session of SMHIT. The primary outcome was the absence of postoperative FUTI (clinical success). The secondary outcome was improvement in reflux to grade 0-I on postoperative voiding cystourethrography (radiographic success). RESULTS: Five and 7 children had bilateral and unilateral reflux, respectively. Reflux was categorized as grade II, III, and IV reflux in 2, 12, and 3 ureters, respectively. Seven of 10 (70%) toilet-trained children had bladder-bowel dysfunction (BBD) preoperatively. The SMHIT was performed for all patients, after which BBD improved. The mean postoperative follow-up period was 6 years and 9 months. The clinical success rate was 100%. Radiographic success was achieved in 16/17 ureters (94%) at 3-4 months, 17/17 (100%) ureters at 1 year, and 17/17 (100%) ureters at 3 years postoperatively. Major complications did not develop postoperatively. CONCLUSION: When prioritizing treatment of concomitant BBD in children with primary VUR and avoiding dextranomer/hyaluronic acid injection therapy in contraindicated children according to the Food and Drug Administration recommendations, a single-session of SMHIT may be as effective and safe in the mid-term as performing open anti-reflux surgery.

Clinical outcomes in donors and recipients of kidney transplantations involving medically complex living donors - a retrospective study.

We retrospectively compared the post-transplantation graft survival and the donor's estimated glomerular filtration rates (eGFRs) following living donor kidney transplantations (LDKTs) involving medically complex living donors (MCLDs) (the elderly and patients with obesity, hypertension, diabetes mellitus, or reduced renal function) and standard living donors (SLDs). The clinical data on patients who underwent LDKTs at our institution from 2006-2019, including 192 SLDs and 99 MCLDs, were evaluated. Regarding recipients, the log-rank test and multivariable Cox proportional hazards analyses showed a higher incidence of overall and death-censored graft loss in the recipients who received kidneys from MCLDs (Hazard ratio = 2.16 and 3.25, P = 0.015 and 0.004, respectively), after adjusting for recipient-related variables including age, sex, duration of dialysis, ABO compatibility, and donor-specific antibody positivity. Regarding donors, a linear mixed model showed significantly lower postdonation eGFRs (-2.25 ml/min/1.73 m2 , P = 0.048) at baseline in MCLDs than SLDs, but comparable change (difference = 0.01 ml/min/1.73 m2 /year, P = 0.97). In conclusion, although kidneys from MCLDs are associated with impaired graft survival, the donation did not adversely affect the MCLDs' renal health in at least the short-term. LDKTs involving carefully selected MCLDs would be an acceptable alternative for recipients with no SLDs.

Deterioration of presarcopenia and its risk factors following kidney transplantation.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease and is associated with increased mortality; however, limited data are available on whether kidney transplantation can improve muscle wasting. Therefore, the present study aimed to assess changes in body composition before and after kidney transplantation. METHODS: Between April 2015 and January 2018, 80 de novo consecutive adult patients with end-stage kidney disease who underwent kidney transplantation were prospectively enrolled. Muscle and fat masses were measured via bioelectrical impedance analysis using InBody 770 at - 2 and 7 days and 3, 6, and 12 months after transplantation. Presarcopenia is characterized by low muscle mass according to the skeletal muscle mass index. Changes in body composition and prevalence of presarcopenia were compared before and after transplantation. Risk factors for presarcopenia were identified using logistic regression analysis. RESULTS: Muscle mass significantly decreased at 3 months after transplantation. Consequently, the prevalence of presarcopenia was significantly higher after transplantation (3 months: 47.5%, 6 months: 42.5%, and 12 months: 38.8%) than that before transplantation (25.0%). Similarly, the body fat percentage was significantly higher at 3 months after transplantation than that before transplantation. Presarcopenia before transplantation was an independent risk factor for presarcopenia at 12 months after transplantation (odds ratio: 51.8, 95% CI 5.77-464, p < 0.001). CONCLUSIONS: Muscle wasting deteriorated and body fat percentage increased from 3 months after kidney transplantation. Presarcopenia before transplantation led to presarcopenia after transplantation, which may deteriorate with an increase in body fat percentage.

Sunitinib versus sorafenib for patients with advanced renal cell carcinoma with renal impairment before the immune-oncology therapy era.

OBJECTIVES: The efficacy and safety of sunitinib versus sorafenib in patients with advanced renal cell carcinoma with renal impairment remains poorly documented. PATIENTS AND METHODS: We assessed the efficacy and safety of sunitinib and sorafenib in patients with advanced renal cell carcinoma with an estimated glomerular filtration rate of 15-60 mL/min/1.73 m2 by reviewing the medical records of patients treated at Jichi Medical University Hospital, Japan, between May 2008 and August 2016. RESULTS: Twenty-seven patients were treated with sunitinib and 14 with sorafenib. Median progression-free survival in sunitinib- and sorafenib-treated patients was comparable, at 6.6 vs 5.8 months, respectively (HR, 1.618; 95% CI, 0.689-3.798; P = 0.2691). Median overall survival was also comparable, at 65.9 vs 58.0 months (HR, 0.985; 95% CI, 0.389-2.479; P = 0.9748). Grade 3 or higher adverse events were significantly more frequent in the sunitinib-treated than sorafenib-treated patients (P = 0.0357). Compared to pre-treatment values, estimated glomerular filtration rate at the discontinuation of treatment was not decreased in either group. In contrast, estimated glomerular filtration rate was decreased on long-term treatment, particularly in previously nephrectomized patients. CONCLUSIONS: Sunitinib and sorafenib had similar efficacy in patients with advanced renal cell carcinoma and severe renal impairment. Although renal function was not markedly impaired in either group, close attention to decreased renal function may be necessary in previously nephrectomized patients on long-term treatment.

Effect of Rabbit Antithymocyte Globulin on Acute and Chronic Active Antibody-Mediated Rejection After Kidney Transplantation.

BACKGROUND: Rabbit antithymocyte globulin (rATG) induction is associated with reduction in the occurrence of de novo donor-specific antibody (DSA) and antibody-mediated rejection (AMR). Therefore, rATG administration is considered as a treatment for AMR. However, only a few studies have investigated the treatment of AMR with rATG after kidney transplantation. METHODS: Between April 2013 and March 2018, 162 consecutive de novo kidney transplantations were performed with induction immunosuppressive therapy comprising tacrolimus, mycophenolate mofetil, methylprednisolone, and basiliximab. AMR was diagnosed on the basis of the presence of DSA and episode biopsy findings. For DSA-positive recipients, plasmapheresis was performed to remove DSA before rATG administration (1.5 mg/kg for 5 days). Patients treated with rATG against active AMR were retrospectively analyzed for graft function. RESULTS: A total of 13 kidney transplant recipients developed active AMR within 302 days after transplantation. After rATG administration, the mean serum creatinine and urine protein levels significantly declined from 3.03 mg/dL to 1.68 mg/dL (P = .002) within 46 days and from 3.01 g/gCr to 0.54 g/gCr (P = .006) within 106 days, respectively. The peripheral blood lymphocyte count rapidly decreased after rATG administration and remained low for 12 months. With regard to adverse events, fever (84.6%), cytomegaloviremia (84.6%), thrombocytopenia (61.5%), anemia (30.8%), and neutropenia (15.4%) occurred within 3 months after rATG administration. CONCLUSIONS: rATG improved graft function by suppressing peripheral blood lymphocytes in kidney transplant recipients with active AMR. The rATG administration as a treatment for active AMR may contribute to positive graft outcomes after kidney transplantation.

Association Between Peripheral Blood CD19-Positive Rate and Antibody-Mediated Rejection Following Rituximab Administration in Kidney Transplant Recipients.

BACKGROUND: Rituximab is used widely for desensitization in ABO-incompatible and donor-specific antibody-positive kidney transplantation. However, data about the effects of individual differences in rituximab-induced B-cell suppression on antibody-mediated rejection (AMR) remain unknown. We aimed to assess the association between CD19-positive rate and AMR following rituximab administration after kidney transplantation. METHODS: Overall, 42 patients who underwent rituximab therapy for pretransplant desensitization in ABO-incompatible (n = 33) and donor-specific antibody-positive (n = 15) kidney transplantation were observed retrospectively. To predict AMR incidence, the peripheral blood CD19-positive rate was determined and classified into short- and long-acting groups. AMR incidence, allograft function, complications, and rituximab dose were compared. RESULTS: Eight patients (19%) had AMR within 39.2 months after transplantation. The CD19-positive rate cutoff value to predict AMR incidence was 4.4%, 6.4%, and 7.7% at 6, 12, and 18 months after transplantation, respectively. When comparing the short- and long-acting groups stratified according to the CD19-positive rate cutoff value, AMR incidence was significantly higher in the short-acting group than in the long-acting group at 6 (71.4% vs 8.6%), 12 (70.0% vs 3.1%), and 18 (58.3% vs 3.3%) months after transplantation. The CD19-positive rate for all patients with AMR exceeded the cutoff value 6, 12, or 18 months. Conversely, serum creatinine level, tacrolimus trough-level, cytomegalovirus antigenemia-positive rate, neutropenia incidence rate, and total dose of rituximab before transplantation showed no significant differences between the 2 groups. CONCLUSIONS: The risk of AMR was higher in patients with short-term B-cell suppression following rituximab administration. Additional rituximab administration after transplantation may prevent AMR in patients with a CD19-positive rate higher than the cutoff value.

Remission of Epstein-Barr virus-positive post-transplant lymphoproliferative disorder by conversion to everolimus in a kidney transplant recipient.

Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of transplantation. There is no clear consensus on the treatment of PTLD. In most cases, the pathogenetic mechanism of PTLD involves the Epstein-Barr virus (EBV). We report the case of an elderly kidney transplant recipient who developed EBV-positive monomorphic T-cell PTLD 14 years after transplantation. Conversion from conventional immunosuppressants to everolimus induced complete remission of PTLD accompanied by a decrease in blood EBV-DNA level without chemotherapy.

Conversion to Everolimus in Kidney Transplant Recipients With Calcineurin Inhibitor-Induced Nephropathy: 3 Case Reports.

BACKGROUND: Calcineurin inhibitors (CNIs), which remain the most important immunosuppressants in kidney transplant recipients, are a major cause of renal dysfunction due to CNI-induced nephropathy. However, a safe and effective CNI-sparing protocol is yet to be established. Herein, we report a case series of kidney transplant recipients experiencing CNI nephropathy, whose renal function is improved after conversion from CNIs to everolimus. CASES: The 3 kidney transplant recipients included in this study were diagnosed with CNI arteriolopathy by episode biopsy between 9 months and 11 years after transplantation. All patients received triple immunosuppressive therapy consisting of CNI (tacrolimus or cyclosporine), mycophenolate mofetil, and methylprednisolone. All allografts were transplanted from elderly living donors to ABO-compatible and donor-specific antibody-negative recipients. All allograft biopsy specimens exhibited CNI arteriolopathy with alternative quantitative criteria for hyaline arteriolar thickening (aah score: 2 or 3), according to the Banff classification; however, histopathologic assessment did not show any evidence of allograft rejection. Conversely, total dose and blood concentrations of CNIs were within appropriate ranges. After conversion from CNIs to everolimus (1.5 mg/day, twice daily; trough level, 3-5 ng/mL), serum creatinine levels returned to baseline levels measured before the diagnosis of CNI arteriolopathy. In all patients, renal allograft function remained stable, with no evidence of donor-specific antibodies, 1 year after conversion from CNIs to everolimus. CONCLUSION: Conversion from CNIs to everolimus can safely and effectively improve renal function in kidney transplant recipients experiencing CNI-induced nephropathy.

Effects of denosumab on hypercalcemia and bone mineral density loss in kidney transplant recipients
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BACKGROUND: Hypercalcemia and bone mineral density (BMD) loss are serious problems associated with post-transplant chronic kidney disease-mineral and bone disorder. The present study aimed to clarify the effects of denosumab on hypercalcemia complicated with BMD loss in kidney transplant recipients. MATERIALS AND METHODS: Among 100 consecutive adult kidney transplant recipients, 16 patients with serum corrected Ca (cCa) levels ≥ 11.0 mg/dL were included in a severe hypercalcemia group. In 14 patients (excluding 2 patients who underwent parathyroidectomy) with severe hypercalcemia and low BMD at the lumbar spine (T-score < -1.0), 60 mg of denosumab were administered by subcutaneous injection at 6-month intervals. Serum cCa and alkaline phosphatase (ALP) levels were analyzed before and after denosumab administration. Lumbar spinal BMD was compared between, before, and 12 months after denosumab administration. RESULTS: Both serum cCa (11.7 mg/dL) and ALP (525 U/L) levels declined promptly after denosumab administration, with only the cCa level showing rebound. Additionally, serum cCa and ALP levels were significantly lower after denosumab administration (all time points) than before denosumab administration. Lumbar spinal BMD increased significantly 12 months after denosumab administration when compared with the value before denosumab administration in both anterior-posterior (increase rate: 5.0%) and lateral (increase rate: 5.4%) projections. CONCLUSION: Denosumab could improve hypercalcemia and BMD loss in kidney transplant recipients. Therapeutic intervention involving denosumab should be considered for hypercalcemia and BMD loss associated with post-transplant chronic kidney disease-mineral and bone disorder.