The clinicopathological relevance of pretransplant anti-angiotensin II type 1 receptor antibodies in renal transplantation.

BACKGROUND: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been suggested as a risk factor for graft failure and acute rejection (AR). However, the prevalence and clinical significance of pretransplant AT1R-Abs have seldom been evaluated in Asia. METHODS: In this multicenter, observational cohort study, we tested the AT1R-Abs in pretransplant serum samples obtained from 166 kidney transplant recipients. Statistical analysis was used to set a threshold AT1R-Abs level at 9.05 U/mL. RESULTS: Pretransplant AT1R-Abs were detected in 98/166 (59.0%) of the analyzed recipients. No graft loss or patient death was reported during the study period. AT1R-Abs (+) patients had a significantly higher incidence of biopsy-proven AR than AT1R-Abs (-) patients (27.6 versus 10.3%, P = 0.007). Recipients with pretransplant AT1R-Abs had a 3.2-fold higher risk of AR within a year of transplantation (P = 0.006). Five study subjects developed microcirculation inflammation (score ≥2). Four of them were presensitized to AT1R-Abs. In particular, three patients had a high titer of anti-AT1R-Abs (>22.7 U/mL). CONCLUSIONS: Pretransplant AT1R-Abs is an independent risk factor for AR, especially acute cellular rejection, and is possibly associated with the risk of antibody-mediated injury. Pretransplant assessment of AT1R-Abs may be useful for stratifying immunologic risks.

KNOW-KT (KoreaN cohort study for outcome in patients with kidney transplantation: a 9-year longitudinal cohort study): study rationale and methodology.

BACKGROUND: Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients. METHODS: KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January 20th, 2014. CONCLUSION: The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.

Association between sclerostin levels and vascular outcomes in kidney transplantation patients.

BACKGROUND: The impact of circulating sclerostin levels on vascular calcification has shown conflicting results depending on the target population and vascular anatomy. This study investigated the associations of sclerostin levels with vascular outcomes in kidney transplant patients. METHODS: In a prospective observational study of the Korean Cohort Study for Outcome in Patients with Kidney Transplantation, 591 patients with serum sclerostin level data prior to transplantation were analyzed. The main predictor was the pre-transplant sclerostin level. Vascular outcomes were the abdominal aortic calcification score and brachial-ankle pulse wave velocity measured at pre-transplant screening and three and five years after kidney transplantation. RESULTS: In linear regression analysis, sclerostin level positively correlated with changes in abdominal aortic calcification score between baseline and five years after kidney transplantation (coefficient of 0.73 [95% CI, 0.11-1.35] and 0.74 [95% CI, 0.06-1.42] for second and third tertiles, respectively, vs the first tertile). In a longitudinal analysis over five years, using generalized estimating equations, the coefficient of the interaction (sclerostin × time) was significant with a positive value, indicating that higher sclerostin levels were associated with faster increase in post-transplant abdominal aortic calcification score. Linear regression analysis revealed a positive association between pre-transplant sclerostin levels and changes in brachial-ankle pulse wave velocity (coefficient of 126.7 [95% CI, 35.6-217.8], third vs first tertile). Moreover, a significant interaction was identified between sclerostin levels and brachial-ankle pulse wave velocity at five years. CONCLUSIONS: Elevated pre-transplant sclerostin levels are associated with the progression of post-transplant aortic calcifications and arterial stiffness.

Organ procurement in a deceased donor.

With the increasing demand for organ transplantation, organ procurement from a deceased donor is an essential step for deceased donor organ transplantation. A proper surgical technique for the procurement of an organ graft from a deceased donor must be carried out to avoid any damage to it. Moreover, how to manage deceased donors until they enter the operating room in a stable condition is a critical point to be considered. The establishment of a surgical technique and preoperative management for organ procurement is encouraged to achieve a nationwide standard and consistency for organ graft sharing among the transplant units.

Tacrolimus trough levels higher than 6 ng/mL might not be required after a year in stable kidney transplant recipients.

BACKGROUND: Little is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs. METHODS: KTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections. RESULTS: A total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups. CONCLUSIONS: TAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Characteristics of Anemia and Iron Deficiency After Kidney Transplant.

BACKGROUND: Numerous studies have shown that iron deficiency is common in patients with end-stage renal disease. However, change of iron deficiency after kidney transplant (KT) is not fully understood. This study was undertaken to examine sequential changes of iron level after KT. METHODS: A total of 1080 KT recipients enrolled in a multicenter observational cohort study between July 2012 and August 2018. A total of 786 patients with transferrin saturation and ferritin level at pretransplant and 1 year after KT were reviewed. Iron deficiency was defined as ferritin <200 ng/mL and total saturation of transferrin (TSAT) < 20%. Anemia was defined as hemoglobin (Hb) < 13 g/dL (male) or <12 g/dL (female). RESULTS: Hemoglobin at 1 year after KT was higher than Hb at KT (13.64 [SD, 1.87] g/dL vs 10.53 [SD, 1.63] g/dL; P < .001). The TSAT decreased from baseline at 1 year after KT (33.89% [SD, 18.73%] vs 29.09% [SD, 14.54%]; P < .001), and ferritin level decreased from baseline at 1 year (190.63 [SD, 217.43] ng/mL vs 141.39 [194.25] ng/mL; P < .001). In patients with anemia at pretransplant, the group with anemia at 1 year after KT (persistent group) and the group without anemia at 1 year after KT (improved group) were compared. The persistent group showed higher pretransplant TSAT, lower 1-year TSAT, and lower estimated glomerular filtration rate at 1 year after KT than the improved group. In multivariate analysis, low ferritin at KT, low TSAT at 1 year, and high ferritin at 1 year were the risk factors for low Hb level at 1 year after adjusting multiple variables. CONCLUSION: Anemia improved within 1 year after KT, although patients with iron deficiency increased. While ferritin reflected the inflammatory status, low TSAT at 1 year after KT was a risk factor for anemia at 1 year after KT.

Pretransplant Osteoporosis and Osteopenia are Risk Factors for Fractures After Kidney Transplantation.

BACKGROUND: There is a high risk of fracture after kidney transplantation (KT). Recipients of KT are susceptible to persistent hyperparathyroidism and other disorders of bone and mineral metabolism. However, the risk factors for fractures after KT remain uncertain. The aim of the present study was to investigate the risk factors for fracture after KT. METHODS: A total of 941 recipients of KT were enrolled from a multicenter observational cohort study in Korea from 2012 to 2016. The biochemical markers were measured at the time of KT, then annually for 5 years following KT. All fracture events were recorded. A Cox proportional hazards analysis was performed to calculate hazard ratios (HR) for the association of risk factors with fractures. RESULTS: Twenty-two fractures had occurred in 20 patients during the study period. Baseline and serial changes of mineral and bone biochemical markers were similar between fracture and nonfracture patient groups. Among the total study population, 104 patients were diagnosed with osteoporosis and 422 patients were diagnosed with osteopenia in a pretransplant bone mineral density test. In a multivariate Cox analysis, pretransplant osteoporosis (HR = 11.76; 95% confidence interval [CI], 2.28-60.69; P = .003) and pretransplant osteopenia (HR = 5.21; 95% CI, 1.15-23.57; P = .032) were independent risk factors for fracture in recipients of KT. CONCLUSIONS: Pretransplant osteoporosis and osteopenia were independent risk factors for fracture after KT. More careful monitoring of bone mineral density before and after KT might be beneficial to predict the risk for fracture after KT.

Use of early postoperative MAG3 renal scan to predict long-term outcomes of renal transplants.

OBJECTIVES: A Tc-99m mercaptoacetyltriglycine renal scan has been used to evaluate perfusion and excretory function of renal allografts. A Tc-99m mercaptoacetyltriglycine renal scan has been reported to correlate with early allograft outcomes. This study was done to determine whether a Tc-99m mercaptoacetyltriglycine renal scan has any relation with long-term renal transplant outcomes. MATERIALS AND METHODS: A total of 311 consecutive kidney transplant recipients were included in the study. All had Tc-99m mercaptoacetyltriglycine renal scans on posttransplant days 3 and 7. Patterns of the renography curve was graded as follows: 0=normal perfusion and excretion; 1=normal perfusion, reduced excretion; 2=normal perfusion, flat excretion; and 3=reduced perfusion and rising curve. Early postoperative Tc-99m mercaptoacetyltriglycine scintigraphy findings were correlated with serum creatinine values, acute rejection episodes, and long-term graft survival. RESULTS: A Tc-99m mercaptoacetyltriglycine renography of a deceased-donor kidney transplant showed a significantly higher grade on both days 3 and 7 than did live-donor kidney transplant (P < .001). Serum creatinine was positively correlated with the renography grades on days 3 and 7. The acute rejection rate was higher in the renography on days 3 and 7. Grade 2 renography on day 3 showed a significantly higher graft failure rate compared with the other grades (8.8% vs 8.6% vs 31.6% vs 7.3%; P = .014). Also, the renography showed the worst 5-year graft survival rate (95.9% vs 93.3% vs 89.5% vs 94.1%; P = .019). There were no differences in the graft failure rate or in graft survival rate according to the Tc-99m mercaptoacetyltriglycine renography grades on day 7. CONCLUSIONS: Our data show that a Tc-99m mercaptoacetyltriglycine renography grade correlate not only with early postoperative kidney function and incidence of acute rejection, but also with long-term outcomes of a renal allograft. A grade 2 renography pattern, with normal uptake and flat excretion, indicates a dismal prognosis for the long-term allograft survival.

The Effect of Low-dose Ketamine on Post-caesarean Delivery Analgesia after Spinal Anesthesia.

BACKGROUND: Ketamine, an N-methyl-D-aspartate receptor antagonist, might play a role in postoperative analgesia, but its effect on postoperative pain after caesarean section varies with study design. We investigated whether the preemptive administration of low-dose intravenous ketamine decreases postoperative opioid requirement and postoperative pain in parturients receiving intravenous fentanyl with patient-controlled analgesia (PCA) following caesarean section. METHODS: Spinal anesthesia was performed in 40 parturients scheduled for elective caesarean section. Patients in the ketamine group received a 0.5 mg/kg ketamine bolus intravenously followed by 0.25 mg/kg/h continuous infusion during the operation. The control group received the same volume of normal saline. Immediately after surgery, the patients were connected to a PCA device set to deliver 25-µg fentanyl as an intravenous bolus with a 15-min lockout interval and no continuous dose. Postoperative pain was assessed using the cumulative dose of fentanyl and visual analog scale (VAS) scores at 2, 6, 24, and 48 h postoperatively. RESULTS: Significantly less fentanyl was used in the ketamine group 2 h after surgery (P = 0.033), but the difference was not significant at 6, 12, and 24 h postoperatively. No significant differences were observed between the VAS scores of the two groups at 2, 6, 12, and 24 h postoperatively. CONCLUSIONS: Intraoperative low-dose ketamine did not have a preemptive analgesic effect and was not effective as an adjuvant to decrease opioid requirement or postoperative pain score in parturients receiving intravenous PCA with fentanyl after caesarean section.

Polyomavirus nephropathy after renal transplantation: a single centre experience.

BACKGROUND: Polyomavirus associated nephropathy (PVN) in renal transplant recipients has been observed with increasing frequency recently and has emerged as a cause of allograft failure linked to highly potent new immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). METHODS: Polyomavirus associated nephropathy was identified in nine out of 182 patients who received renal transplantation between October 1998 and July 2003. PVN was confirmed by allograft biopsy. The clinical records of these nine patients were reviewed, as were all of the allograft biopsies. Electron microscopy was performed in all nine cases. After the diagnosis of PVN, maintenance immunosuppression was reduced. The clinical course and outcome of the PVN patients were reviewed in relation to manipulation of immunosuppressive agents. RESULTS: There were nine cases of PVN in renal transplant recipients and the incidence of PVN was 4.9%. All patients with PVN were under triple immunosuppression comprising tacrolimus and MMF. The mean time to a diagnosis of PVN was 7.8 months after transplantation. Three of the nine patients received antirejection therapy prior to PVN. Seven out of nine PVN patients presenting acute allograft dysfunction were initially treated with high-dose intravenous steroid pulse or OKT3 before reduction of the immunosuppression. After reduction of the immunosuppression, seven patients stabilized their renal function. Two (22%) lost their grafts due to persistent PVN and chronic rejection. Two (22%) patients later developed acute rejection after reduction of the immunosuppression. CONCLUSION: PVN can cause allograft dysfunction and graft loss. Renal allograft recipients who are at risk of PVN should be routinely screened with urine cytology and quantitative measurements of viral load in the blood, particularly patients who had graft dysfunction. Early diagnosis and judicious alteration of immunosuppressive agents might permit a superior prognosis and reduce the graft loss from PVN in renal transplant recipients.