Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study.

Background: Diabetes mellitus is a common and crucial metabolic complication in kidney transplantation. It is necessary to analyze the course of glucose metabolism in patients who already have diabetes after receiving a transplant. In this study, we investigated the changes in glucose metabolism after transplantation, and a detailed analysis was performed on some patients whose glycemic status improved. Methods: The multicenter prospective cohort study was conducted between 1 April 2016 and 31 September 2018. Adult patients (aged 20 to 65 years) who received kidney allografts from living or deceased donors were included. Seventy-four subjects with pre-transplant diabetes were followed up for 1 year after kidney transplantation. Diabetes remission was defined as the results of the oral glucose tolerance test performed one year after transplantation and the presence or absence of diabetes medications. After 1-year post-transplant, 74 recipients were divided into the persistent diabetes group (n = 58) and the remission group (n = 16). Multivariable logistic regression was performed to identify clinical factors associated with diabetes remission. Results: Of 74 recipients, 16 (21.6%) showed diabetes remission after 1-year post-transplant. The homeostatic model assessment for insulin resistance numerically increased in both groups throughout the first year after transplantation and significantly increased in the persistent diabetes group. The insulinogenic index (IGI30) value significantly increased only in the remission group, and the IGI30 value remained low in the persistent diabetes group. In univariate analysis, younger age, newly diagnosed diabetes before transplantation, low baseline hemoglobin A1c, and high baseline IGI30 were significantly associated with remission of diabetes. After multivariate analysis, only newly diagnosed diabetes before transplantation and IGI30 at baseline were associated with remission of diabetes (34.00 [1.192-969.84], P = 0.039, and 17.625 [1.412-220.001], P = 0.026, respectively). Conclusion: In conclusion, some kidney recipients with pre-transplant diabetes have diabetes remission 1 year after transplantation. Our prospective study revealed that preserved insulin secretory function and newly diagnosed diabetes at the time of kidney transplantation were favorable factors for which glucose metabolism did not worsen or improve 1 year after kidney transplantation.

The Immunomodulating Effects of Thalidomide and Dexamethasone in a Murine Cardiac Allograft Transplantation Model.

PURPOSE: The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. MATERIALS AND METHODS: Intraabdominal transplant of cardiac allografts from BALB/c (H-2d) donors to C57BL/6 (H-2b) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. RESULTS: The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4+FOXP3+/CD4+CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. CONCLUSION: These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk.

High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6-12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42-5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.

Glomerular subepithelial microparticles - a footprint for podocyte injury.

The aim of this study was to clarify the nature and clinical significance of glomerular subepithelial microparticles (SMPs), located between the basal surface of the podocytes and the glomerular basement membrane. Ultrastructural morphology of 79 renal biopsy samples (obtained from 25 native and 54 transplanted kidneys), showing SMPs in the last 3 years, was reevaluated with regard to the podocyte changes and clinical condition of the patients. One hundred and nine SMPs were identified, with 32.9% of the samples having two or more per glomerulus. Overall, they were most frequently located in the open capillary loops (55%). However, in the native kidney samples with mesangial deposits, 64.3% of SMPs were present in the mesangium-bound areas. Each vesicle ranged from 46.9 to 87.1 nm, and vesicles were admixed with curved strands in larger SMPs. Diffuse effacement of the foot processes and condensation of the actin filaments were present in 56.0% and 62.4% of the samples, respectively. SMPs were associated with hematuria, proteinuria of ≥ 1 gm, and immune complex deposition in the patients with native kidneys, whereas they were related to hyperglycemia and elevated serum creatinine levels in the patients with renal allografts. Patients with native and transplanted kidneys most commonly presented with IgA nephropathy and allograft rejection, respectively. Finding SMPs in the renal biopsy samples is not rare and they may act as a footprint of podocyte injury caused by diverse etiologies. Considering their size, podocyte exosomes could be a possible source of SMPs.

Presence of a survival benefit of HLA-incompatible living donor kidney transplantation compared to waiting or HLA-compatible deceased donor kidney transplantation with a long waiting time.

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.

Clinical impact of serum bilirubin levels on kidney transplant outcomes.

Serum bilirubin, a potent endogenous antioxidant, has been associated with decreased risks of cardiovascular disease, diabetes, and kidney disease. However, the effects of serum bilirubin on kidney transplant outcomes remain undetermined. We analyzed 1628 patients who underwent kidney transplantations between 2003 and 2017. Patients were grouped into sex-specific quartiles according to mean serum bilirubin levels, 3-12 months post-transplantation. Median bilirubin levels were 0.66 mg/dL in males and 0.60 mg/dL in females. The intra-individual variability of serum bilirubin levels was low (9%). Serum bilirubin levels were inversely associated with graft loss, death-censored graft failure, and all-cause mortality, independent of renal function, donor status, and transplant characteristics. Multivariable analysis revealed that the lowest serum bilirubin quartile was associated with increased risk of graft loss (HR 2.64, 95% CI 1.67-4.18, P < 0.001), death-censored graft failure (HR 2.97, 95% CI 1.63-5.42, P < 0.001), and all-cause mortality (HR 2.07, 95% CI 1.01-4.22, P = 0.046). Patients with lower serum bilirubin were also at greater risk of rejection and exhibited consistently lower glomerular filtration rates than those with higher serum bilirubin. Serum bilirubin levels were significantly associated with transplantation outcomes, suggesting that bilirubin could represent a therapeutic target for improving long-term transplant outcomes.

Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells.

PURPOSE: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. MATERIALS AND METHODS: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. RESULTS: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. CONCLUSION: Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

Renal tissue elasticity by acoustic radiation force impulse: A prospective study of healthy kidney donors.

BACKGROUND: Some studies reported the correlations between renal parenchymal stiffness measured by transient elastography or acoustic radiation force impulse (ARFI) and the extent of interstitial fibrosis. This study was prospectively designed to evaluate the correlation between clinical, histological findings and the kidney shear wave velocity (SWV, m/s) assessed by ARFI elastography to identify factors affecting the kidney SWV in normal patients. METHODS: Seventy-three adult living kidney transplantation donors were enrolled in our center between September 2010 and January 2013. Before transplantation, all donors were evaluated by ARFI elastography to identify the range of SWV in kidneys. Time-zero biopsies were performed on all graft kidneys before implantation. RESULTS: Mean age of donors was 42.0 ±â€Š11.3 years. The mean SWV and depth were 2.21 ±â€Š0.58 m/s and 5.37 ±â€Š1.06 cm. All histological findings showed mild degree of the Banff score, only grade I. In univariate analyses, the SWV was not associated with all histological parameters. Age (r = -0.274, P = .019) diastolic blood pressure (DBP, r = -0.255, P = .030) and depth for SWV measurement (r = -0.345, P = .003) were significantly correlated with the SWV. In multivariate linear regression analysis, age, gender, body mass index (BMI), and depth for SWV measurement were significantly correlated with the SWV (P = .003, .005, .002, and .004, respectively). CONCLUSIONS: We demonstrated that all histological findings are not correlated with the SWV of donor kidney. Otherwise, factors influencing the kidney SWV assessed by ARFI elastography are age, gender, BMI, and depth for the SWV measurement in donors for kidney transplantation.

Effects of bisphosphonates on long-term kidney transplantation outcomes.

BACKGROUND: Bisphosphonates are administered to post-transplantation patients with mineral and bone disorders; however, the association between bisphosphonate therapy and long-term renal graft survival remains unclear. METHODS: This nested case-control study investigated the effects of bisphosphonates on long-term graft outcomes after kidney transplantation. We enrolled 3836 kidney transplant recipients treated from April 1979 to June 2016 and matched patients with graft failure to those without (controls). Annual post-transplant bone mineral density assessments were performed and recipients with osteopenia or osteoporosis received bisphosphonate therapy. The associations between bisphosphonate use and long-term graft outcomes and graft survival were analyzed using conditional logistic regression and landmark analyses, respectively. RESULTS: A landmark analysis demonstrated that death-censored graft survival was significantly higher in bisphosphonate users than in non-users in the entire cohort (log-rank test, P < 0.001). In the nested case-control matched cohort, bisphosphonate users had a significantly reduced risk of graft failure than did non-users (odds ratio = 0.38; 95% confidence interval 0.30-0.48). Bisphosphonate use, increased cumulative duration of bisphosphonate use >1 year and increased cumulative bisphosphonate dose above the first quartile were associated with a reduced risk of graft failure, after adjustments. CONCLUSIONS: Bisphosphonates may improve long-term graft survival in kidney transplant recipients.

Characteristics of community-acquired respiratory viruses infections except seasonal influenza in transplant recipients and non-transplant critically ill patients.

BACKGROUND/PURPOSE: Transplant recipients are vulnerable to life-threatening community-acquired respiratory viruses (CA-RVs) infection (CA-RVI). Even if non-transplant critically ill patients in intensive care unit (ICU) have serious CA-RVI, comparison between these groups remains unclear. We aimed to evaluate clinical characteristics and mortality of CA-RVI except seasonal influenza A/B in transplant recipients and non-transplant critically ill patients in ICU. METHODS: We collected 37,777 CA-RVs multiplex real-time reverse transcription-polymerase chain reaction test results of individuals aged ≥18 years from November 2012 to November 2017. The CA-RVs tests included adenovirus, coronavirus 229E/NL63/OC43, human bocavirus, human metapneumovirus, parainfluenza virus 1/2/3, rhinovirus, and respiratory syncytial virus A/B. RESULTS: We found 286 CA-RVI cases, including 85 solid organ transplantation recipients (G1), 61 hematopoietic stem cell transplantation recipients (G2), and 140 non-transplant critically ill patients in ICU (G3), excluding those with repeated isolation within 30 days. Adenovirus positive rate and infection cases were most prominent in G2 (p < 0.001). The median time interval between transplantation and CA-RVI was 30 and 20 months in G1 and G2, respectively. All-cause in-hospital mortality was significantly higher in G3 than in G1 or G2 (51.4% vs. 28.2% or 39.3%, p = 0.002, respectively). The mechanical ventilation (MV) was the independent risk factor associated with all-cause in-hospital mortality in all three groups (hazard ratio, 3.37, 95% confidence interval, 2.04-5.56, p < 0.001). CONCLUSIONS: This study highlights the importance of CA-RVs diagnosis in transplant recipients even in long-term posttransplant period, and in non-transplant critically ill patients in ICU with MV.

Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study.

BACKGROUND: We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. METHODS: This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. RESULTS: PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. CONCLUSION: In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

Improvement of medication adherence with simplified once-daily immunosuppressive regimen in stable kidney transplant recipients: A prospective cohort study.

BACKGROUND: Many immunosuppressive drugs are prescribed as twice-daily dosing. A simplified once-daily dosing of immunosuppressive drug regimen may improve medication adherence. We investigated medication adherence of simplified once-daily immunosuppressive regimen consisting of extended-release tacrolimus, sirolimus, and corticosteroids along with the efficacy and safety of this regimen. METHODS: This study was a prospective, multicenter, controlled and cohort trial. Stable kidney transplant recipients who had received transplantation at least 3 months before the study enrollment were eligible for the study. Participants were required to fill-out the self-reported immunosuppressant therapy barrier scale (ITBS) questionnaire before and after the conversion. Other clinical laboratory parameters and adverse events were evaluated until 6 months post-conversion. RESULTS: A total of 160 kidney recipients comprised the intention-to-treat population. The mean total ITBS score was 19.5 ± 4.0 at pre-conversion and 6 months after converting, the mean total ITBS score was 16.6 ± 3.6 (p < 0.001). Particularly, the ITBS scores of 4 questions related to the frequency of medication dosing were significantly different between pre-conversion and post-conversion. Only 1 patient (0.62%) was diagnosed as biopsy-confirmed acute rejection in the study period. There was no significant change in the mean estimated glomerular filtration rate after the conversion. Overall 95 patients (59.4%) had an adverse event and 28 patients (17.5%) had a serious adverse event. No graft loss and 1 death were reported. CONCLUSION: Medication adherence after the conversion to the once-daily immunosuppressive regimen was significantly improved with no additional risks of efficacy failure or adverse events.

Long-term compensation of renal function after donor nephrectomy.

Background: Living donors are the major source of kidneys in countries with a shortage of deceased donors. Kidney donation after careful donor selection is generally accepted as a safe procedure, but the physiologic consequences after donor nephrectomy are not fully verified. In this study we retrospectively reviewed the renal function of the residual kidney in living donors. Methods: Post-nephrectomy laboratory data of 1,175 living donors (60.7%) from 1,933 living donors who received uninephrectomy from January 1999 to December 2017 at Yonsei University, Severance Hospital, Korea were retrospectively collected. Post-nephrectomy renal function was monitored by the relative ratio of estimated glomerular filtration rate (e-GFR; pre-nephrectomy e-GFR ratio vs. post-nephrectomy e-GFR) that was calculated by the Modification of Diet in Renal Disease formula. Results: During 36.3±37.6 months of mean follow-up, two cases (0.17%, 2/1,175) of renal failure developed. The mean e-GFR decreased to 64.3±14.2 mL/min/1.73 m2 immediately after nephrectomy from 99.2±19.9 mL/min/1.73 m2 of the pre-nephrectomy e-GFR. Early decrement of e-GFR was prominent in male and obese donors (body mass index >25 kg/m2, P<0.05). The e-GFR ratio increased according to post-nephrectomy duration, and the mean increment degree of e-GFR ratio after nephrectomy calculated by linear regression analysis was 1.94% per year. Unlike the early decrement of e-GFR ratio after nephrectomy, donor factors such as degree of obesity and donor sex did not affect the late increment of e-GFR ratio after nephrectomy (P>0.05). Conclusions: Our data showed that long-term compensation of the renal function after nephrectomy occurs independently of preoperative donor characteristics.

The feasibility of organ transplantation during the COVID-19 outbreak: experiences from South Korea.

Background: The coronavirus disease 2019 (COVID-19) has forced healthcare systems to reduce transplant activities in order to preserve resources and minimize the risk of nosocomial transmission. Although transplantation societies around the world have proposed interim recommendations, little is known about the safety of transplant surgery under pandemic conditions and how transplant medicine should move forward after the peak of the pandemic. Methods: We describe our experiences regarding the continuation of living and deceased donor transplantation under infection control measures during the COVID-19 outbreak in South Korea. We reviewed consecutive liver and kidney transplantations at Severance Hospital and analyzed national transplantation activities in South Korea. Results: Transplantation activities with living and deceased donors remained stable during the COVID-19 outbreak compared to the same period in 2019. We performed 94 transplantations (58 kidney, 35 liver, and 1 simultaneous liver-kidney) during the COVID-19 outbreak. Twenty-five patients underwent desensitization therapy prior to transplant (nine ABO-incompatible kidney, eight human leukocyte antigen-incompatible kidney, and eight ABO-incompatible liver). No transplant recipients in our center contracted COVID-19. In South Korea, national transplant activities with living and deceased donors remained stable in 2020 compared to 2019. Conclusions: Organ transplantation during pandemics appears to be feasible with appropriate infection prevention measures.

Transplant outcomes in positive complement-dependent cytotoxicity- versus flow cytometry-crossmatch kidney transplant recipients after successful desensitization: a retrospective study.

BACKGROUND: Despite the obvious survival benefit compared to that among waitlist patients, outcomes of positive crossmatch kidney transplantation (KT) are generally inferior to those of human leukocyte antigen (HLA)-compatible KT. This study aimed to compare the outcomes of positive complement-dependent cytotoxicity (CDC) crossmatch (CDC + FC+) and positive flow cytometric crossmatch (CDC-FC+) with those of HLA-compatible KT (CDC-FC-) after successful desensitization. METHODS: We retrospectively analyzed 330 eligible patients who underwent KTs between June 2011 and August 2017: CDC-FC- (n = 274), CDC-FC+ (n = 39), and CDC + FC+ (n = 17). Desensitization protocol targeting donor-specific antibody (DSA) involved plasmapheresis, intravenous immunoglobulin (IVIG), and rituximab with/without bortezomib for positive-crossmatch KT. RESULTS: Death-censored graft survival and patient survival were not different among the three groups. The median estimated glomerular filtration rate was significantly lower in the CDC + FC+ group than in the compatible group at 6 months (P < 0.001) and 2 years (P = 0.020). Biopsy-proven rejection within 1 year of CDC-FC-, CDC-FC+, and CDC + FC+ were 15.3, 28.2, and 47.0%, respectively. Urinary tract infections (P < 0.001), Pneumocystis jirovecii pneumonia (P < 0.001), and cytomegalovirus viremia (P < 0.001) were more frequent in CDC-FC+ and CDC + FC+ than in CDC-FC-. CONCLUSIONS: This study showed that similar graft and patient survival was achieved in CDC-FC+ and CDC + FC+ KT compared with CDC-FC- through DSA-targeted desensitization despite the higher incidence of rejection and infection than that in compatible KT.

Efficacy and Safety of Gemigliptin in Post-Transplant Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Gemigliptin is a potent, selective dipeptidyl peptidase (DPP)-4 inhibitor that does not require any dosage adjustment based on renal function. It is also known to have no apparent interaction with commonly used drugs. In the present study, we aimed to evaluate the glucose-lowering efficacy and safety of gemigliptin in post-transplant patients with type 2 diabetes mellitus (T2D). METHODS: A total of 84 patients who were prescribed gemigliptin for more than 180 days after transplantation were analyzed retrospectively. Six-month changes in blood glucose and glycated hemoglobin (HbA1c) levels were checked to assess glycemic efficacy. Safety was evaluated by examining its influence on immunosuppressive treatment, as determined by the blood trough level and dosage of calcineurin inhibitors, as well as changes in parameters related to liver and renal function. RESULTS: Six months of gemigliptin treatment significantly lowered blood glucose level (HbA1c: 8.16 ± 1.69 to 7.44 ± 1.26%; P < .001). There were no significant changes in blood trough levels of immunosuppressants, including tacrolimus, cyclosporine, and sirolimus. The dosage of immunosuppressants was also stable. In addition, there were no significant changes in the levels of liver enzymes and renal function during 6 months of treatment. CONCLUSION: Gemigliptin robustly lowered blood glucose levels without exerting any significant effect on immunosuppressive treatment, renal function, and liver enzymes in post-transplant patients with T2D.

Rituximab protects against development of atherosclerotic cardiovascular disease after kidney transplantation: a propensity-matched study.

Recent studies have implicated B cells in atherosclerosis and have verified the atheroprotective effect of rituximab. Rituximab is widely used for desensitization in ABO-incompatible or crossmatch-positive kidney transplantation (KT). Using a single-center KT database, we performed propensity-matched analysis to investigate the association between rituximab and posttransplant atherosclerotic cardiovascular disease (ASCVD). Among 1299 eligible patients, 239 given rituximab induction were matched with 401 controls in a 1:2 propensity score matching process. The cumulative rate of ASCVD during 8 years of follow-up was significantly lower in rituximab-treated patients, compared with matched controls (3.7% vs. 11.2%; P = 0.012). However, all-cause mortality did not differ by group (2.9% vs. 4%; P = 0.943). In multivariable Cox analysis, rituximab proved independently protective of ASCVD (hazard ratio = 0.34, 95% confidence interval: 0.14-0.83). The lower risk of ASCVD seen with rituximab induction reached significance only in patient subsets of diabetes mellitus, pretransplant dialysis, or older age (>50 years). Rituximab induction confers a lower risk of ASCVD during the posttransplant period. This atheroprotective effect appears particularly beneficial in patients whose risk of ASCVD is heightened.

Increase in 24-Hour Protein Excretion Immediately After Donation Is Associated With Decreased Functional Recovery in Living Kidney Donors.

OBJECTIVES: In this study, we evaluated the occurrence of proteinuria in living kidney donors during the immediate postdonation period, aiming to determine its clinical significance in renal function recovery. PATIENTS AND METHODS: We enrolled living kidney donors with predonation protein excretion rate (PER) < 150 mg/24 h. Participants were divided into 2 groups according to immediate postdonation PER (4 days after nephrectomy): non-microproteinuria (non-mPr; PER < 150 mg/24 h), n = 244; and immediate postdonation microproteinuria (ImPr; PER ≥ 150 mg/24 h), n = 605. RESULTS: Estimated glomerular filtration rate (eGFR) did not differ significantly between groups immediately after nephrectomy but was consistently lower in the ImPr group 1 week to 1 year postdonation (1-year postdonation eGFR: ImPr group, 63.6 ± 12.1 mL/min/1.73 m2; non-mPr group, 68.6 ± 12.3 mL/min/1.73 m2; P = .001). Immediate postdonation microproteinuria was an independent predictor of eGFR at 1 year postdonation (ß [standard error] = -2.68 [1.15], 95% confidence interval -4.94 to -0.42, P = .02), along with predonation eGFR, age, and sex. Immediate postdonation microproteinuria was more common in donors who were older or male and occurred in 71.3% of kidney donors, suggesting renal injury in this period. CONCLUSIONS: Although proteinuria generally resolves, its impact persists and can impair renal function recovery. Donors who are older and male are more likely to undergo immediate hyperfiltration after donation.

Utilization of HbA1c in Screening Living Kidney Donors With Prediabetes.

OBJECTIVES: To study the outcome of living kidney donors with prediabetes and to evaluate the utilization of baseline HbA1c to identify donors at high risk for developing diabetes during the postdonation follow-up period. PATIENTS AND METHODS: Living kidney donors with prospectively collected preoperative fasting glucose and HbA1c results were included in the study. Donors were categorized to the high-risk group when both results were in the prediabetic range, the low-risk group when only 1 result was in the prediabetic range, and the control group when both results were normal. RESULTS: Ninety-three donors were followed for 75.9 ± 23.3 months. A higher proportion of donors in the high-risk group progressed to diabetes compared with donors in the low-risk and control groups (31.3% vs 6.5% vs 0.0%, respectively; P < .001). Donors with prediabetes were not at a higher risk for new-onset hypertension (4.4% vs 10.0% vs 7.7%, in control, low-risk, and high-risk groups, respectively; P = .519) or microproteinuria (7.3% vs 10.3% vs 0.0%, in control, low-risk, and high-risk groups, respectively; P = .478) and exhibited equivalent postdonation renal function compared with donors with normal glucose metabolism. CONCLUSIONS: HbA1c can identify donors with prediabetes who are at risk for progression to diabetes. Our results indicate that carefully accepted donors with prediabetes are not at increased risk of renal function deterioration in the immediate postdonation period.