Manabu Okada

Tertiary Hyperparathyroidism Resistant to Cinacalcet Treatment

Cinacalcet hydrochloride (cinacalcet) has been reported to be efficacious for patients with tertiary hyperparathyroidism (THPT). We experienced five patients with THPT requiring parathyroidectomy (PTx) because of resistance to cinacalcet treatment and investigated their clinical characteristics and clinical course. The maximum diameter of the parathyroid gland estimated by ultrasonography before renal transplantation was evaluated. Serum total calcium, phosphorus, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), and creatinine (Cr) levels were investigated every three months after the administration of cinacalcet and at PTx. After surgery, the Cr levels were followed. In all five patients, at least one parathyroid gland had a largest diameter of more than 1 cm, and the mean diameter was 18.7 mm (range 14.9–24.1 mm). Intact PTH and ALP levels gradually increased after the initiation of cinacalcet and the Cr levels transiently increased after PTx. These findings suggest that the existence of a severely enlarged nodular hyperplastic gland is a main factor involved in resistance to cinacalcet.

Location Frequency of Missed Parathyroid Glands After Parathyroidectomy in Patients with Persistent or Recurrent Secondary Hyperparathyroidism.

BackgroundReoperative parathyroidectomy (RPTX) because parathyroid glands have been missed is frequently required in patients with secondary hyperparathyroidism (SHPT). The usual locations of these missed glands in patients with SHPT are yet to be fully elucidated.MethodsWe retrospectively investigated the locations of missed glands in 165 patients who underwent RPTX for persistent or recurrent SHPT at our institution from August 1982 to July 2014. At our institution, total parathyroidectomy with forearm autograft is the routine operative procedure for SHPT. We also routinely resect the thymic tongue.ResultsOf 165 patients, 82 underwent initial parathyroidectomy at our institution (Group A), and the remaining 83 underwent initial parathyroidectomy at other institutions (Group B). A total of 239 parathyroid glands were resected (Group A, 93; Group B, 146). Missed glands were most commonly located in the mediastinum (Group A, 22/93) and the thymic tongue (Group B, 31/146).ConclusionsIn patients with persistent or recurrent SHPT, ectopic parathyroid glands are frequently located in the mediastinum and thymic tongue. Therefore, resecting the thymic tongue during the initial operation may reduce the need for RPTX.

A Retrospective Study of the Impact of Intraoperative Intact Parathyroid Hormone Monitoring During Total Parathyroidectomy for Secondary Hyperparathyroidism: STARD Study

Abstract The study aimed to evaluate the diagnostic accuracy of intraoperative intact parathyroid hormone (IO-iPTH) in patients with secondary hyperparathyroidism (HPT). The cut-off for IO-iPTH monitoring remains unknown. This was a single-center retrospective review of 226 consecutive patients (107 males and 119 females) who underwent parathyroidectomy for secondary HPT between May 2010 and March 2014. The predetermined cut-off for IO-iPTH was a 70% IO-iPTH drop from baseline 10 minutes after total parathyroidectomy and thymectomy. We used <60 pg/mL iPTH value on postoperative day 1 (POD1) as an indicator of successful removal of parathyroid glands and reviewed the frequency of reoperation other than in autografted sites during the observation period. This study was based on the Standards for the Reporting of Diagnositic accuracy compliant. The reoperation rate in patients with >60 pg/mL iPTH value (POD1) was significantly higher than that in patients with <60 pg/mL iPTH value (POD1), (13.0% versus 0.5% P = 0.003). Sensitivity, specificity, and accuracy of >70% IO-iPTH drop were 97.5%, 52.2%, and 92.9%, respectively, this criterion was demonstrated to be beneficial in 26 patients. In 5 patients, <70% IO-iPTH drop was observed and further exploration enabled sufficient removal of parathyroid glands. In 21 patients, although fewer than 4 parathyroid glands were removed after enough explorations, >70% IO-iPTH drop enabled termination of operations and iPTH value (POD1) was <60 pg/mL. An iPTH value of <60 pg/mL (POD1) was a good predictor for successful parathyroidectomy. A 70% IO-iPTH drop from the baseline was appropriate to determine sufficient parathyroid gland removal during parathyroidectomy for patients with secondary HPT.

Association of Dialysis Duration with Outcomes after Transplantation in a Japanese Cohort

BACKGROUND AND OBJECTIVES Evidence regarding the differences in clinical outcomes after preemptive kidney transplantation (PKT) and non-PKT in Japan is lacking. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective cohort study at a single center in Japan. Consecutive patients ages >18 years old who had received a kidney transplant from a living donor between November of 2001 and December of 2013 at our institution (n=786) were enrolled. The primary study outcome was the occurrence of clinical events before the end of 2014. Clinical events were defined as any of the following: death with functioning graft (DWFG), graft loss, or post-transplant cardiovascular disease (CVD). RESULTS The median follow-up period was 61.0 (35.3-94.0) months. PKT was performed in 239 patients (30.4%). Clinical events occurred in 78 (9.9%). In the Cox proportional hazard model for univariate analysis, factors found to be associated with higher risk of clinical events included older age, men, ABO incompatibility, longer dialysis duration, diabetes, pretransplant CVD, and large ventricular mass index. PKT was associated with lower risk. Clinical event rate in patients who received a PKT was 3.3% compared with 10.8%, 11.1%, 10.4%, 10.2%, 16.7%, and 16.2% among patients who were on dialysis for <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, and ≥5 years before transplant, respectively (P=0.002). The multivariate analysis showed that ABO incompatibility (hazard ratio [HR], 2.98; 95% confidence interval [95% CI], 1.89 to 4.71), duration of dialysis per year (HR, 1.07; 95% CI, 1.03 to 1.11), and diabetes (HR, 3.54; 95% CI, 2.05 to 6.12) were only three independent risk factors for the incidence of clinical events. CONCLUSIONS Even in Japan, where the long-term outcomes of patients on hemodialysis are excellent, PKT could be beneficial to reduce DWFG, graft loss, and post-transplant CVD.

Impact of Arterial Reconstruction With Recipient's Own Internal Iliac Artery for Multiple Graft Arteries on Living Donor Kidney Transplantation: Strobe Study.

AbstractThe aim of this study is to investigate the usefulness of arterial reconstruction using the recipients own internal iliac artery for multiple kidney graft arteries.The safety and efficacy of various arterial reconstruction methods have been demonstrated. Although some reports have documented arterial reconstruction with the recipients own internal iliac artery for multiple kidney graft arteries using the interposition method, usefulness of this technique has not yet been investigated compared with other arterial reconstruction methods.Between January 2008 and April 2014, 532 living donor kidney transplants in adult recipients were performed at 1 center. Of these, 389 kidney grafts had a single artery and did not need arterial reconstruction (nonarterial reconstruction group). Among the bench surgery patients, 19 kidney grafts for multiple arteries were performed using the interposition method with the recipients own internal iliac artery (interposition group). Seventy-nine kidney grafts were performed using conjoined reconstruction (conjoined group) and 15 kidney grafts were performed using end-to-side reconstruction (end-to-side group). Total ischemic time (the period between arterial clamp and blood reperfusion), time to initial urination, perioperative and postoperative estimated glomerular filtration rate (eGFR), and complication rates between the interposition group and other 3 groups were retrospectively investigated. This study was based on the STROBE compliant.Warm ischemic time (the period between arterial clamp and beginning of the cold perfusion) of interposition group was significantly longer than that of nonarterial reconstruction group. Total ischemic time of the interposition group was significantly longer than those of other 3 groups. But time to initial urination, perioperative and postoperative eGFR, and complications were similar to other 3 groups.The interposition method was shown to be a useful standard method for multiple kidney graft arteries of living donor kidney transplantation in carefully selected recipients without calcification of the iliac arteries.

Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak

The outbreak of Pneumocystis jirovecii pneumonia (PJP) among kidney transplant recipients is emerging worldwide. It is important to control nosocomial PJP infection. A delay in diagnosis and treatment increases the number of reservoir patients and the number of cases of respiratory failure and death. Owing to the large number of kidney transplant recipients compared to other types of organ transplantation, there are greater opportunities for them to share the same time and space. Although the use of trimethoprim-sulfamethoxazole (TMP-SMX) as first choice in PJP prophylaxis is valuable for PJP that develops from infections by trophic forms, it cannot prevent or clear colonization, in which cysts are dominant. Colonization of P. jirovecii is cleared by macrophages. While recent immunosuppressive therapies have decreased the rate of rejection, over-suppressed macrophages caused by the higher levels of immunosuppression may decrease the eradication rate of colonization. Once a PJP cluster enters these populations, which are gathered in one place and uniformly undergoing immunosuppressive therapy for kidney transplantation, an outbreak can occur easily. Quick actions for PJP patients, other recipients, and medical staff of transplant centers are required. In future, lifelong prophylaxis may be required even in kidney transplant recipients.

Lifelong Prophylaxis With Trimethoprim-Sulfamethoxazole for Prevention of Outbreak of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients

Background Outbreaks of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients are frequently reported worldwide. However, the general guidelines propose only short-term prophylaxis with trimethoprim-sulfamethoxazole after kidney transplantation. We experienced 3 PCP outbreaks in the last 10 years despite providing the recommended prophylaxis. The purpose of this study was to find a prophylaxis regimen that could successfully prevent future PCP outbreaks in immunosuppressed kidney transplant recipients. Methods Occurrence of PCP at our hospital since 2004 was reviewed. A total of 48 cases were diagnosed from July 2004 through December 2014. Genotypes of P. jirovecii were determined in these cases. Results Three PCP outbreaks by 3 different genotypes of P. jirovecii in each outbreak occurred with 2-year intervals in last 10 years. Molecular analysis showed that each intraoutbreak was caused by identical P. jirovecii, whereas interoutbreaks were caused by different genotypes. Although short-term prophylaxis was provided to all kidney recipients after each outbreak after identification of a single PCP case, additional outbreaks were not prevented because the universal prophylaxis had already been completed when new case of PCP emerged. Conclusions The contagious nature of P. jirovecii allows easy development of outbreaks of PCP in immunosuppressed kidney transplant recipients. Although the universal short-term prophylaxis is effective in controlling ongoing outbreak, lifelong prophylaxis of kidney transplant recipients should be considered to prevent new outbreaks.

Impact of grafting using thin upper pole artery ligation on living-donor adult kidney transplantation: The STROBE study.

AbstractThis study aimed to investigate the impact of grafting using thin upper pole artery ligation for living-donor adult kidney transplantation. Few reports have examined the safety of thin upper pole artery ligation.Between January 2008 and May 2015, 613 consecutive living-donor adult kidney transplantations were performed. We excluded 21 recipients who experienced graft loss due to factors that were unrelated to surgical complications and 3 recipients with grafts treated with arterial reconstruction and thin upper pole artery ligation for 3 arteries. We included 439 kidney grafts with single arteries (Single Artery Group), 123 with reconstructed arteries (Arterial Reconstruction Group) and 27 with ligated thin upper pole arteries (Arterial Ligation Group) in this retrospective cohort study. To evaluate the safety of thin upper pole artery ligation, we compared the Arterial Ligation Group with the Single Artery and Arterial Reconstruction groups. We evaluated the characteristics of the enrolled donors, recipients, and their grafts. Thereafter, we investigated recipients’ perioperative and postoperative estimated glomerular filtration rate (eGFR) and complication rates.Significant differences among the 3 groups were identified for donor sex and endoscopic nephrectomy rates. Recipient eGFR and the complication rates were adjusted according to these factors. The perioperative and postoperative eGFR of recipients did not differ significantly in the Arterial Reconstruction and Single Artery groups with low complication rates.Thin upper pole artery ligation is a safe procedure for living-donor adult kidney transplantation and may prevent unnecessary arterial reconstruction and associated complications.

5-year follow-up of a randomized clinical study comparing everolimus plus reduced-dose cyclosporine with mycophenolate mofetil plus standard-dose cyclosporine in de novo kidney transplantation: Retrospective single center assessment.

The aim of this study is to evaluate the efficacy and safety of everolimus plus reduced-dose cyclosporine compared with mycophenolate mofetil plus standard-dose cyclosporine 5years after living donor kidney transplantation. Between March 2008 and August 2009, 24 living donor kidney transplantations were enrolled in a 2-year, multicenter, randomized phase 3 study (RAD001A1202 study). 24 recipients were randomly classified into two groups and closely observed for 5years. 13 recipients were administered steroid, reduced-dose cyclosporine, everolimus and basiliximab (EVR group). 11 recipients were administered steroid, standard-dose cyclosporine, mycophenolate mofetil and basiliximab (STD group). Two groups were compared not only in graft function including estimated glomerular filtration rate (eGFR), and proteinuria, but also in adverse events such as de novo donor-specific antibody (DSA) production, rejection, new-onset diabetes, hyperlipidemia, and cytomegalovirus (CMV) infection. No graft loss was identified in 5years. The incidences of acute T cell rejection, de novo DSA production, hyperlipidemia, and new-onset diabetes were similar. eGFR levels throughout the observation periods were similar. Three cases of proteinuria were identified in STD group. One case of proteinuria observed in EVR group was well controlled with angiotensin receptor blocker. Incidence of CMV infection in CMV antibody-positive recipients was significantly lower in EVR group. The safety and efficacy of reduced-dose cyclosporine and everolimus protocol were similar to those of standard-dose cyclosporine and mycophenolate mofetil other than for superior prevention of CMV infection.

Serum αKlotho as a predictor of graft dysfunction after kidney transplantation

OBJECTIVE To improve the long-term survival rate after kidney transplantation (KTx), allograft injury should be identified as soon as possible. Regardless of aggressive immunosuppressive therapies, recipients of kidney transplants still have a significant risk of graft failure. No specific predictor for the progression of chronic kidney disease (CKD) after KTx has yet been found. Aberrant molecular mechanisms involving the αKlotho-fibroblast growth factor (FGF) 23 axis may be a useful determinant of renal impairment and graft failure over time. METHODS Plasma and spot urine samples were collected from 47 patients 1 year after KTx. Evaluation of renal function after KTx was performed using levels of biomarkers including serum intact FGF23, soluble αKlotho, 25(OH) vitamin D (25(OH)D), and the difference in the estimated glomerular filtration rate (eGFR) between the first and third year after KTx (ΔeGFR). RESULTS The median serum αKlotho, intact FGF23, and 25(OH)D were 516.3 pg/mL, 58.7 pg/mL, and 5.7 ng/mL, respectively. No marked changes in the standard biomarkers that regulate phosphate homeostasis were found. Serum αKlotho levels were associated with ΔeGFR. Multivariate regression analysis revealed that serum αKlotho levels significantly predicted a decrease in eGFR in the graft kidney 2 years after KTx, but serum 25(OH)D and FGF23 levels were not significant. Serum αKlotho levels showed an inverse correlation with fractional excretion of magnesium, which reflects tubular injury in the early stage of CKD. CONCLUSION Measurement of serum αKlotho may serve as a useful predictor of KTx patients who require initiation of pre-emptive medication.