Takashi Yokoo

Recurrence and graft loss after renal transplantation in adults with IgA vasculitis

BackgroundIgA vasculitis, a rare condition resulting in end-stage renal disease, is a small-vessel vasculitis that affects the kidney in 49–83xa0% of adults. The reported recurrence rate of IgA vasculitis in renal transplant recipients is 11.5–60xa0%, leading to graft loss in 0–50xa0% of these patients. However, limited data are available on recurrence and graft loss after renal transplantation.MethodsWe evaluated renal transplant recipients seen from 1987 to 2015 at the Jikei University School of Medicine and the Department of Urology, Tokyo Women’s Medical University. Using a 1:2 match, 21 patients with IgA vasculitis and 42 controls were selected. The mean post-transplant follow-up was 121xa0±xa069xa0months for IgA vasculitis and 147xa0±xa066xa0months for the controls.ResultsThe 15-year patient survival was 100xa0% in IgA vasculitis and 97.6xa0% in the controls (pxa0=xa00.22). The 5-, 10-, and 15-year graft survival rates were 95.2, 90.5, and 81xa0% in IgA vasculitis and 100, 90.5, and 88.1xa0% in the controls, respectively (pxa0=xa00.63). The recurrence rate was 28.6xa0% (6 of 21 cases) and half of them (3 of 6 cases) showed histological activity (ISKDC III). We treated them with methylprednisolone pulse therapy and/or tonsillectomy. None of the recurrence cases lost the allograft.ConclusionThe long-term patient and graft survival of IgA vasculitis in renal transplantation were comparable with the previous reports. The recurrence rate was 28.6xa0%, but none of the recurrent cases showed allograft loss in this study. We speculate that methylprednisolone pulse therapy and/or tonsillectomy prevent the progression of recurrent IgA vasculitis.

Usefulness of combination therapy with Daclatasvir plus Asunaprevir in chronic hepatitis C patients with chronic kidney disease

AimCombination therapy with Daclatasvir (DCV) plus Asunaprevir (ASV) has been proven effective in patients with chronic hepatitis C virus (HCV) infection. However, little is known as to the effect of this therapy in patients with reduced renal function. Focusing on CKD patients whose renal function has declined, the present trial addresses the efficacy and safety of this combination therapy in CKD patients with reduced estimated glomerular filtration rate (eGFR).Materials and methodsThe study design is a single-center, retrospective longitudinal observational study enrolling 106 patients with (nxa0=xa029) or without (nxa0=xa077) CKD. After the treatment with combined DCV with ASV for chronic HCV genotype 1b, patients were followed for a total of 48xa0weeks and the comparison was made in clinical parameters between the two groups.Results(1) The majority of patients in both groups achieved sustained virological response at 24xa0weeks (90.8xa0% in the non-CKD group, and 93.1xa0% in the CKD). (2)The reduction rate in HCV-RNA levels 2xa0weeks after commencing the treatment was faster in the CKD group than that in the non-CKD group (81.8 vs. 79.2xa0%, pxa0<xa00.01). (3) Three patients in the CKD group and 6 patients in the non-CKD group withdrew from the treatment because of the adverse events.ConclusionCombination therapy with DCV plus ASV for chronic HCV genotype 1b infection is useful and tolerable, not only in patients with normal eGFR, but also in those with CKD with declined eGFR. Viral eradication at an early phase of the treatment appears to be faster in CKD patients.

Risk factors for encapsulating peritoneal sclerosis: analysis of a 36-year experience in a University Hospital.

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication that occurs in peritoneal dialysis (PD) therapy. The present study aimed to identify the risk factors, especially peritonitis and biocompatible PD fluid.

Hypermethylation of the CaSR and VDR genes in the parathyroid glands in chronic kidney disease rats with high-phosphate diet.

Chronic kidney disease (CKD) disrupts mineral homeostasis and its representative pathosis is defined as secondary hyperparathyroidism (SHPT). SHPT occurs during the early course of progressive renal insufficiency, and is associated with mortality and cardiovascular events. SHPT results in reduction of calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in the parathyroid glands during CKD. However, the precise mechanism of CaSR and VDR reduction is largely unknown. CKD was induced through two-step 5/6 nephrectomy, and then CKD rats and sham-operated rats were maintained for 8xa0weeks on diets containing 0.7xa0% phosphorus (normal phosphate) or 1.2xa0% phosphorus (high phosphate). In gene expression analysis, TaqMan probes were used for quantitative real-time polymerase chain reaction. Finally, CaSR and VDR protein expressions were analyzed using immunohistochemistry. DNA methylation analysis was performed using a restriction digestion and quantitative PCR. CaSR and VDR mRNA were reduced only in CKD rats fed the high-phosphorus diets (CKD HP), then CaSR and VDR immunohistochemical expressions were compatible with gene expression assay. SHPT was then confirmed only in CKD HP rats. Furthermore, sole CKD HP rats showed the hypermethylation in CaSR and VDR genes; however, the percentage methylation of both genes was low. Although CaSR and VDR hypermethylation was demonstrated in PTGs of CKD HP rats, the extent of hypermethylation was insufficient to support the relevance between hypermethylation and down-regulation of gene expression because of the low percentage of methylation. Consequently, our data suggest that mechanisms, other than DNA hypermethylation, were responsible for the reduction in mRNA and protein levels of CaSR and VDR in PTGs of CKD HP rats.

The prognostic values of Caveolin‐1 immunoreactivity in peritubular capillaries in patients with kidney transplantation

The low sensitivity of C4d immunoreactivity in peritubular capillaries (PTCs) hinders its use in the diagnosis of chronic active antibody‐mediated rejection (CAAMR). C4d‐negative CAAMR was defined in the 2013 Banff classification, which included the expression of endothelial‐associated transcripts (ENDATs). We previously showed that the ENDAT caveolin‐1 (CAV‐1) is a distinct feature of CAAMR. In this study, we investigated the prognostic value of CAV‐1 immunoreactivity in PTCs in kidney transplant patients. Ninety‐eight kidney transplant recipients were included in this study. The prognostic value of CAV‐1 immunoreactivity in PTCs was evaluated by double immunostaining for CAV‐1 and pathologische Anatomie Leiden endothelium (PAL‐E, a PTC marker) in the PTCs of kidney allograft biopsy samples. The patients were divided into two groups: CAV‐1/PAL‐E<50% and CAV‐1/PAL‐E≥50%. Kaplan‐Meier curves showed that CAV‐1/PAL‐E≥50% patients had a significantly worse prognosis than that of CAV‐1/PAL‐E<50% patients (log‐rank; P<.001). C4d staining of PTCs was not associated with the development of graft failure (log‐rank; P=.345), whereas in a multivariate Cox regression analysis, CAV‐1 immunoreactivity in PTCs was independently associated with graft failure (hazard ratio: 11.1; P=.0324). CAV‐1 immunoreactivity in PTCs may serve as a prognostic marker for kidney allograft survival.

Circadian blood pressure abnormalities in patients with primary nephrotic syndrome.

ABSTRACT Background: Only a few studies have evaluated the abnormalities of ambulatory blood pressure (ABP) in patients with nephrotic syndrome (NS). Methods: The 24-h ABPs were measured in primary NS patients with acute onset of disease and analyzed in relation to the clinical variables. Results: Our subjects comprised 21 patients: 17 with minimal change disease and 4 with focal segmental glomerulosclerosis. Of these patients, 8 (38%) had daytime hypertension, 13 (62%) had nighttime hypertension, and 13 (62%) were non-dippers (nighttime-to-daytime ratio of ABP: NDR > 0.9). The serum sodium level was correlated with the average 24-h ABP and NDR, after adjustment for other clinical variables, such as the increase in body weight, serum albumin level, and urinary protein excretion. The data from repeated ABP measurements, before and after the achievement of remission, showed a marked decrease in the average 24-h ABP after remission. Furthermore, change in the serum sodium level was significantly correlated with the change in NDR. Conclusion: These results suggest that alteration in renal handling of sodium and water, which might be reflected in serum sodium level, is involved in the abnormality of circadian blood pressure in primary NS patients.

Helicobacter cinaedi bacteremia with cellulitis in a living-donor kidney transplant recipient identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a case report

BackgroundHelicobacter cinaedi causes bacteremia and cellulitis, mainly in immunocompromised patients. We report a rare case of H. cinaedi bacteremia with cellulitis in a living-donor kidney transplant recipient identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS).Case summaryA 54-year-old Asian man with IgA nephropathy underwent living-donor kidney transplantation 14xa0years previously. He was admitted to our hospital for evaluation of fever and multifocal cellulitis. H. cinaedi was isolated and identified from the patient’s blood using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and gyrase subunit B-targeted polymerase chain reaction assays. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry has proven over the years to be a rapid and accurate universal method for the identification of microorganisms.ConclusionsThe combined use of these detection methods enabled the appropriate administration of 6xa0weeks of antibiotic therapy. The patient recovered completely, with no recurrence.

Clinicopathologic Impact of Early Medullary Ray Injury in Patients Following Kidney Transplantation

BACKGROUNDnPreviously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases.nnnAIMnWe examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame.nnnMETHODSnWe defined early MRI as tubular degeneration with interstitial edema or mild fibrosis localized to the medullary ray. We divided 53 protocol biopsies into 2 groups, with and without early MRI. Early MRI+ cases with isometric vacuolization were classified as CNI toxicity; those with Tamm-Horsfall protein in the interstitium and a thyroidlike appearance were classified as urinary tract system abnormalities; remaining cases were classified as others. We compared changes in serum levels of creatinine (sCr) over 3 years and fibrosis extent at 1 year.nnnRESULTSnThe sCr levels were significantly higher in the MRI+ group than the MRI- group at 3 years (Pxa0= .024). Examining the 3 MRI+ subgroups, only the MRI+ urinary tract system abnormalities group had significantly high sCr levels compared to the MRI- group (Pxa0=xa0.019). The MRI+ group showed significant signs of IF/TA at 1 year.nnnCONCLUSIONSnEarly MRI after kidney transplantation was significantly more likely to develop IF/TA at 1 year and had higher sCr levels at 3 years. In such cases, intervention might preserve graft function over the long term.

Possible prevention of uremic nausea by vitamin D receptor activators in non-dialysis patients with stage 5 chronic kidney disease

BackgroundNausea is a major uremic symptom and a frequent indication for starting dialysis. However, preventive medication for uremic nausea has not yet been identified. Vitamin D receptor activators (VDRAs) may prevent uremic nausea via their pleiotropic actions. The objective of this study was to explore whether VDRA administration during the predialysis period is associated with a reduced prevalence of uremic nausea just prior to beginning dialysis.MethodsA multicenter, retrospective, cross-sectional study was performed to identify a medication to prevent uremic nausea. Patients with stage 5 CKD who were followed-up over 3xa0months were included. The primary outcomes examined were the prevalence of uremic nausea, congestive heart failure (CHF), and intractable edema at dialysis commencement. The predictor variable was VDRA use during the predialysis period.ResultsOne thousand five hundred and thirty six patients who had just begun dialysis in nine Japanese facilities between January 2006 and October 2013 were included. Two hundred and thirty (15.0%) patients had commenced dialysis because of uremic nausea, and three hundred and ninety two (25.5%) patients had been using VDRAs before initiating dialysis. Logistic regression analysis showed that, among the medications examined in this study, only VDRA use was independently associated with a lower frequency of uremic nausea (OR 0.512, 95% CI 0.347–0.738, Pxa0=xa00.0003). On the other hand, CHF and intractable edema were not associated with VDRA administration.ConclusionUse of VDRAs during the predialysis period was the only factor associated with a lower prevalence of uremic nausea, suggesting that VDRAs may prevent uremic nausea in patients with advanced CKD.

Fluctuation in Serum Sodium Levels Related to Ipragliflozin Administration in a Patient with Diabetic Nephropathy and Sequela of Traumatic Brain Injury.

A 46-year-old diabetic man underwent the removal of a hematoma caused by traumatic brain injury. After surgery, severe hyponatremia occurred. The subsequent administration of NaCl and fludrocortisone improved his laboratory findings. The patient was transferred to our hospital, and his insulin therapy was replaced by teneligliptin. One week later, ipragliflozin treatment was initiated and induced an immediate increase in the serum sodium levels. NaCl and fludrocortisone were therefore discontinued. However, hyponatremia recurred after ipragliflozin withdrawal due to a urinary tract infection. NaCl and fludrocortisone were initiated again, and the laboratory data improved. We herein report a case of serum sodium fluctuation related to ipragliflozin administration.