Body fluid volume calculated using the uric acid kinetic model relates to the vascular event.

PURPOSE: We developed a method to measure the extracellular and intracellular fluid volumes using the kinetics of uric acid in the bodies of Japanese patients undergoing dialysis. In this research, we aimed to assess the prognosis of vascular events using this uric acid kinetic model method. METHODS: We conducted a retrospective cohort study of 1,298 patients who were undergoing hemodialysis or predilution online hemodiafiltration at the end of December 2019 at 13 institutions in Japan. Information on vascular events was acquired in 2020. Vascular event prognosis was defined as the new incidence of one or more of the following four types of vascular events: myocardial infarction, cerebral infarction, cerebral hemorrhage, or limb amputation. We measured the extracellular fluid volume and intracellular fluid volume after dialysis using the uric acid kinetic model method and determined the association between ECV, ICV, and vascular event risk. RESULTS: A high extracellular volume was substantially linked to an increased risk of vascular events. In addition, while a crude analysis revealed that a high intracellular volume was associated with a low risk of vascular events, this was not statistically significant after multifactorial adjustment. This result was partly affected by the low measurement accuracy of the serum urea nitrogen level used for the intracellular volume calculation. CONCLUSIONS: Extracellular volume calculated using the uric acid kinetic model method is a prognostic factor for vascular events in patients undergoing hemodialysis.

A case of unusual renal manifestation in a patient with neuronal intranuclear inclusion disease treated with steroids.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by intranuclear inclusions. Kidney injury involvement and successful treatment for NIID have rarely been reported. A NIID patient developed crescentic IgA nephropathy. Steroid therapy resolved digestive symptoms and recovered renal function. Steroids are considered for concomitant symptoms of NIID.

Novel Capped-Needle Device: A Novel Safety Feature to Eliminate Air Bubbles in Hemodialysis.

INTRODUCTION: Air bubbles in the dialysis circuit are rarely visible after automatic priming; however, they are often visible after the needles are manually connected to the circuit. To prevent this issue, we thought to prime needles with a circuit at automatic priming by the hemodialysis machine. In order to achieve this idea, we designed and manufactured a novel capped needle to connect the needles to the extracorporeal circuit before the automatic priming of the hemodialysis machine. This study investigated the effectiveness of this novel capped needle and compared it with the conventional method for preventing air bubble contamination. METHODS: We tested novel capped needles ten times to evaluate whether the dialysis machine works appropriately and removes air bubbles even with the attached capped needle. Next, we performed 25 trials using the conventional method, in which skilled nurses manually connect the needle. In both methods, we thoroughly counted the air bubbles with our naked eyes. We predicted that the capped needle would leave few bubbles in the circuit. In order to evaluate fewer bubbles, we conducted an additional experiment using a microparticle counter to measure the size and number of the bubbles. RESULTS: We thoroughly searched for air bubbles during each of the ten tests but could not find any bubbles visible to the naked eye. In the conventional method, bubbles were visible in 29 out of 50 cases. The bubble count was significantly lower in the capped-needle method than in the conventional method (p < 0.0001, Pearson's χ2 test). In the additional experiments using the microparticle counter, the average remaining air volume in the extracorporeal circuit was 0.0999 ± 0.2438 nL when the priming was performed using the novel capped needles. CONCLUSION: The novel capped needle eliminated all visible bubbles efficiently and effectively; therefore, it could be a valuable device for hemodialysis treatment. The reduction of air from the dialysis circuit may improve patient prognosis.

Comparison of Body Fluid Volumes Determined by Kinetic Modeling and by Bioimpedance Spectroscopy.

INTRODUCTION: The bioimpedance spectroscopy (BIS) method is used in individual patients requiring body fluid volume measurement. In a hemodialysis facility, however, regular screening of body fluid volumes is also necessary. Such screening, by kinetic modeling, may become possible by calculating distribution volumes of urea and uric acid from regular blood test results. OBJECTIVE: The aim is to compare uric acid distribution volumes with BIS-extracellular volume, urea distribution volume with BIS-total body water, and difference between urea and uric acid distribution volumes with BIS-intracellular volume. METHODS: We reanalyzed stored blood test data of 53 hemodialysis patients obtained together with BIS data of the same patients in our previous study. RESULTS: Significant correlations were found between urea distribution volume and total body water predicted by the BIS method, between uric acid distribution volume and extracellular volume predicted by the BIS method, and between the difference of uric acid distribution volume from urea distribution volume and intracellular volume predicted by the BIS method. In Bland-Altman analysis, comparison of each pair showed no systematic error. The mean difference between each pair was minimal. CONCLUSION: Fluid volumes in different body compartments can be estimated by kinetic modeling as well as by the BIS method.

Recurrent lupus nephritis in renal allograft triggered by pregnancy.

Herein we report the case of a 37-year-old woman with recurrence of lupus nephritis (LN) in a renal allograft during pregnancy. She had developed end-stage renal disease due to LN and was put on hemodialysis at the age of 26 years. She underwent kidney transplantation at the age 28 years. Maintenance immunosuppressants included methylprednisolone, tacrolimus, and mycophenolate mofetil, which were changed to azathioprine when she desired pregnancy. The renal allograft function remained stable and seemingly disease-free until proteinuria and functional decline occurred during the pregnancy (age: 34 years). The baby was delivered by performing a cesarean section at 33 weeks of gestation. Renal allograft biopsy revealed crescent formation. Light microscopy revealed tuft necrosis and endocapillary proliferation. Immunofluorescence microscopy revealed the deposition of immunoglobulin G and C1q. A recurrence of LN (ISN/RPS class IV-G [A/C]) was diagnosed, and the patient was treated with pulse steroid therapy and azathioprine was replaced with mycophenolate mofetil. This treatment improved acute or active lesions of LN and temporarily benefited the renal allograft function. Unfortunately, there were irreversible chronic changes and a gradual decline in the renal allograft function.

Development of strangulation ileus associated with the ureter of the transplanted kidney 18 years after kidney transplantation.

INTRODUCTION: After kidney transplantation, patients should be treated with caution and monitored for surgical complications. Among the possible surgical complications, strangulation ileus after kidney transplantation is rare. CASE PRESENTATION: A 59-year-old woman who had undergone kidney transplantation at 41 years of age presented to our hospital with lower abdominal pain. She was diagnosed with strangulation ileus and underwent emergency surgery. In the lower right abdomen, the small intestine was compressed by cord-like tissue running from the intraperitoneal space to the retroperitoneal space. We confirmed that the cord-like tissue was the ureter of the transplanted kidney. The necrotic small intestine was resected, and ureter-ureteral anastomosis of the ureter of the transplanted kidney was performed. CONCLUSION: All surgical procedures, including ureteroneocystostomy, require careful attention. The occurrence of some postoperative surgical complications can be prevented by carefully performing the kidney transplantation procedure.

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.

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.

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
.

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.

Multiple myeloma derived from a kidney transplant donor who also developed myeloma after kidney donation.

Patients who undergo kidney transplantation are at increased risk of cancer due to the long-term use of immunosuppressive treatment. Postrenal transplant cancers usually originate from recipient cells, but donor-related cancers have been rarely reported. We report the case of 49-year-old woman who developed multiple myeloma of donor origin 7 years after kidney transplantation. The donor was the mother of the recipient and also developed multiple myeloma 1 year after kidney donation. The diagnosis of multiple myeloma was based on IgG lambda monoclonal protein and the infiltration of plasma cells in bone marrow. The renal biopsy did not reveal plasmacytoma in the transplanted kidney. Epstein-Barr virus DNA load was negative in peripheral blood. The patient responded to lenalidomide and dexamethasone, and subsequently received autologous stem cell transplantation. Donor chimerism was detected in the recipient marrow by short tandem repeat analysis; however, studies of Ig gene rearrangement were inconclusive due to insufficient DNA quality. The chromosomal abnormalities in the two myelomas were different. This case suggests that donor cells with myeloma-initiating potential can be transferred to a recipient via a renal graft and can lead to the development of donor-derived multiple myeloma in the recipient under immunosuppression.

Fibrosing cholestatic hepatitis in a kidney transplant recipient with hepatitis C virus.

Fibrosing cholestatic hepatitis (FCH) is a fatal disorder that presents as a progressive deterioration of liver function over a period of several weeks to several months. It is caused by the direct cytotoxic effect of the over-expression of viral antigens on hepatocytes in immunosuppressed patients. Our patient was a 59-year-old man with hepatitis C virus (HCV) infection of genotype 2a who had suffered from end-stage renal disease due to diabetic nephropathy and underwent kidney transplantation. His serum total bilirubin levels gradually increased to 20 mg/dl and liver atrophy progressed during several weeks after kidney transplantation, which was initially difficult to distinguish from drug-induced liver injury. We diagnosed the condition as FCH on the basis of pathological findings and increased HCV viral load, and treated the patient with Glecaprevir/Pibrentasvir. However, the patient died of refractory hemorrhagic gastric ulcer and liver failure. Currently, it is possible to treat infections of all genotypes of HCV, even with end-stage renal disease, with direct acting antivirals. Furthermore, it is preferable to treat HCV before kidney transplantation considering the risk of FCH due to immunosuppressive therapy.

Conversion From Steroid to Everolimus in Maintenance Kidney Transplant Recipients With Posttransplant Diabetes Mellitus.

OBJECTIVES: Although steroid withdrawal has been attempted to ameliorate various complications in kidney transplant recipients, a steroid-sparing strategy has more frequently led to acute rejection. We investigated the use of everolimus to safely overcome steroid withdrawal in kidney transplant recipients with posttransplant diabetes mellitus under maintenance immunosuppressive therapy. MATERIALS AND METHODS: A total of 75 de novo consecutive kidney transplant recipients received conventional immunosuppressive therapy comprising tacrolimus (trough level of 5 ng/mL), mycophenolate mofetil (1000 mg), and methylprednisolone (4 mg). Patients with posttransplant diabetes mellitus underwent simultaneous everolimus administration (trough level of 3-5 ng/mL) and steroid withdrawal at 1 to 15 months after transplant. Graft outcomes were compared between the everolimus and steroid groups. In the everolimus group, renal function and hemoglobin A1c levels at 12 months after administration were compared with values before everolimus administration. RESULTS: The mean posttransplant follow-up period in the everolimus (n = 25) and steroid (n = 50) groups was 672 and 747 days, respectively. All grafts survived in both groups, and biopsy-proven acute rejection rates did not significantly differ between the groups (16% vs 12%; P = .72). Furthermore, no acute rejection occurred after everolimus administration. In the everolimus group, hemoglobin A1c significantly declined at 9 months after everolimus administration (6.94% vs 6.53%; P = .047). In addition, both serum creatinine levels and estimated glomerular filtration rates in the everolimus group were stable for 12 months after everolimus administration. CONCLUSIONS: Steroid withdrawal using everolimus as maintenance immunosuppressive therapy for kidney transplant recipients may safely ameliorate posttransplant diabetes mellitus, achieve better glycemic control, and maintain stable renal function.

Sarcoidosis in the renal allograft of a recipient whose primary disease was autosomal dominant polycystic kidney disease.

We report a 55-year-old man with a renal allograft that developed sarcoidosis. His autosomal dominant polycystic kidney disease (ADPKD) progressed to end-stage stage renal disease when he was 52 years old, and he underwent living-donor kidney transplantation at the age of 53 years. His proteinuria worsened at 19 months post-transplantation, and his renal function began to decline at 29 months post-transplantation. A renal allograft biopsy performed at 31 months post-transplantation revealed non-caseating granulomatous interstitial nephritis. The patient was treated with prednisolone (0.5 mg/kg/day), with gradual reduction in the dose. His proteinuria improved and renal function did not deteriorate any further. To the best of our knowledge, this is the first case of sarcoidosis in a renal allograft recipient whose primary renal disease was ADPKD.