Association of nutritional status with osteoporosis, sarcopenia, and cognitive impairment in patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Inadequate nutrition in patients on hemodialysis causes various complications. This study aimed to investigate the association between nutritional status and risk of osteoporosis, sarcopenia, and cognitive impairment in patients on hemodialysis. METHODS AND STUDY DESIGN: We enrolled 131 older patients on maintenance hemodialysis. Geriatric Nutrition Risk Index (GNRI) was used to assess nutritional status. Patients were divided into quartile groups according to the GNRI. Dual-energy X-ray absorptiometry, bioimpedance analysis and handgrip strength measurement, and the Korean version of the Montreal Cognitive Assessment were used to assess osteoporosis, sarcopenia, and cognitive impairment, respectively. Biochemical laboratory tests were also performed before mid-week hemodialysis session. RESULTS: Patients from higher GNRI quartiles had a lower prevalence of osteoporosis and sarcopenia. Cognitive impairment was not associated with any GNRI quartile. In the multivariable models, longer dialysis periods (OR 1.696, 95% CI 1.053-2.729, p=0.030) and higher intact parathyroid hormone levels (OR 3.136, 95% CI 1.781-5.518, p<0.001) were significantly associated with osteoporosis risk. GNRI quartile 2 (OR 0.064, 95% CI 0.005-0.883, compared to quartile 1, p=0.040) and higher hemoglobin A1c levels (OR 3.728, 95% CI 1.033-86.4, p=0.043) were associated with a higher sarcopenia risk. Lower hemoglobin levels (OR 0.585, 95% CI 0.360-0.950, p=0.030) were associated with a higher risk of cognitive impairment. CONCLUSIONS: In patients on hemodialysis, inadequate nutrition was associated with the risk of osteoporosis and sarcopenia, but not cognitive impairment. Proper nutritional assessment and management in these patients could prevent complications related to bone and muscle loss.

Risk of overhydration and low lean tissue index as measured using a body composition monitor in patients on hemodialysis: a systemic review and meta-analysis.

Overhydration and sarcopenia, related to an individual's nutritional status, have been associated with increased cardiovascular mortality and poor prognosis in patients on hemodialysis. The purpose of this study was to investigate the prediction of overhydration and sarcopenia on mortality in patients on hemodialysis using a body composition monitor. We conducted a systematic review and meta-analysis using a random-effects model. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published prior to December 9, 2016 and reviewed the reference lists of relevant reviews, registered trials and relevant conference proceedings. The overhydration group (fluid excess, >15% vs. the normohydration group) and the low lean tissue index group ( <10%) were compared with a reference group. Six trials, consisting of 29,469 patients, were included in the pooled analysis. The pooled hazard ratio for overall survival of the overhydration group, compared with the reference normohydration group was 1.798 (95% confidence interval [CI]: 1.53-2.804, p = .001). The hazard ratio for mortality in the low lean tissue index group was 1.533 (95% CI, 1.411-1.644; p = .001) in the random-effects model. The results from the most recent study showed the greatest heterogeneity in the sensitivity analysis. Low lean tissue index and overhydration, measured using a body composition monitor, were associated with a high mortality rate in patients on hemodialysis.

Effect of Induction Therapy Dose on Survival in Abo-Incompatible Kidney Transplantation: A Network Meta-Analysis Using Recent Data.

BACKGROUND: Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. METHODS: Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. RESULTS: Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. CONCLUSIONS: We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.

Effect of Plasmapheresis on the Efficacy of Rituximab in Antibody-Mediated Rejection Patients.

BACKGROUND: Rituximab and plasmapheresis (PP) suppress and eliminate antibody production in patients experiencing antibody-mediated rejection (AMR). Herein, we discuss a case where rituximab was less effective after PP for treating AMR. CASE: A 55-year-old male patient underwent kidney transplantation. His renal function remained normal for 1 year. Subsequently, renal function declined, and (donor-specific antibodies showed positive results. A biopsy of the transplanted kidney revealed AMR. On the day of the biopsy, the medical staff administered 200 mg of rituximab, followed by IV immunoglobulin (IVIg) and PP the next day. The time interval between PP + IVIg treatment and rituximab was 12 h. As a result, the B-cell markers CD19 and CD20 did not decrease sufficiently, and the patient's creatinine and glomerular filtration rate muscles did not recover adequately. CONCLUSION: We report a case in which PP was administered shortly after rituximab injection, resulting in insufficient B-cell inhibition due to the removal of rituximab.

High-Dose Intravenous Immunoglobulin to Treat Anti-Thymocyte Globulin Induction-Related BK Virus and Cytomegalovirus Infection in Patients with ABO-Incompatible Kidney Transplantation.

BACKGROUND: ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. METHODS: A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. CONCLUSIONS: High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and CMV infections.

The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data.

BACKGROUND: Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. METHODS: We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. RESULTS: In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. CONCLUSION: ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.

Real-world evidence of constipation and laxative use in the Korean population with chronic kidney disease from a common data model.

Constipation is a highly prevalent gastrointestinal disorder in patients with chronic kidney disease (CKD). However, our understanding of its epidemiology and management in CKD is limited. We aimed to explore real-world data on constipation and laxative use in patients with CKD in a nationwide population-based cohort from the Korean Health Insurance Review and Assessment-National Patient Sample database. This study analyzed retrospective health claims data in Korea from 2012 to 2017 that were transformed into the Observational Medical Outcomes Partnership Common Data Model. The pooled proportion of constipation diagnoses was 30.5% in all patients with CKD and 15.9%, 16.5%, 17.4%, 29.9%, and 43.3% in patients with CKD stages 1-5, respectively, suggesting a higher prevalence in advanced CKD. Patients receiving peritoneal dialysis or hemodialysis had the highest prevalence of constipation, while transplant recipients showed a prevalence comparable to that of patients with early CKD. Patients with CKD had a significantly higher risk of constipation than age- and sex-matched non-CKD individuals (range of odds ratio [OR]:1.66-1.90). Laxative prescribing patterns differed by CKD severity. Osmotic agents were prescribed in more than half of patients with advanced CKD, while magnesium salts and bulking agents were prescribed less frequently. The CKD patients with constipation were more likely to be prescribed constipation-inducing medications, including antipsychotic and neurological medications. Our findings provide real-world constipation and laxative prescription status in the Korean CKD population, revealing a significantly higher risk of constipation and different laxative prescribing patterns in patients with CKD.

Cumulative impact of hypotension during intermittent hemodialysis on kidney recovery in critically ill patients with AKI-D.

BACKGROUND: Intermittent hemodialysis (IHD) is commonly implemented in patients with AKI-D, irrespective of the initial kidney replacement therapy (KRT) modality. However, concerns remain regarding the hemodynamic instability during IHD. This study aimed to assess the association between hypotensive episodes during IHD and kidney recovery in AKI-D patients. METHODS: We retrospectively enrolled AKI-D survivors who received IHD in the intensive care units of a tertiary care hospital in Korea from January 2018 to February 2024. RESULTS: A total of 1791 IHD sessions from 209 AKI-D survivors were analyzed. The patients underwent a median of 7 IHD sessions (interquartile range [IQR] 3-11), with an incidence of intradialytic hypotension (IDH) of 16.8 % per patient. Of these, 43.1 % were dialysis-dependent at hospital discharge. The number of IDH was a significant predictor of dialysis dependence (odds ratio [OR] 1.56; 95 % confidence interval [CI] 1.16-2.22). Patients experiencing ≥3 IDH episodes had a substantially higher risk of dialysis dependence compared to those without IDH (OR 9.41; 95 % CI 2.41-41.69). In per-session analysis, the target ultrafiltration rate was identified as an independent risk factor for IDH occurrence. CONCLUSIONS: Our study revealed that IHD-related hypotension during hospitalization has a cumulative negative impact on kidney recovery in AKI-D survivors.

Status and trends in epidemiologic characteristics of diabetic end-stage renal disease: an analysis of the 2021 Korean Renal Data System.

Korean Renal Data System (KORDS) is a nationwide end-stage renal disease (ESRD) registry database operated by the Korean Society of Nephrology (KSN). Diabetes mellitus is currently the leading cause of ESRD in Korea; this article provides an update on the trends and characteristics of diabetic ESRD patients. The KORDS Committee of KSN collects data on dialysis centers and patients through an online registry program. Here, we analyzed the status and trends in characteristics of diabetic chronic kidney disease stage 5D (CKD 5D) patients using data from 2001 to 2021. In 2021, the dialysis adequacy of hemodialysis (HD) was lower in diabetic CKD 5D patients than in nondiabetic CKD 5D patients, while that of peritoneal dialysis (PD) was similar. Diabetic CKD 5D patients had a higher proportion of cardiac and vascular diseases and were more frequently admitted to hospitals than nondiabetic CKD 5D patients, and the leading cause of death was cardiac disease. From 2001 to 2020, diabetic CKD 5D patients had a higher mortality rate than nondiabetic CKD 5D patients, but in 2021 this trend was reversed. Diabetic PD patients had the highest mortality rate over 20 years. The mortality rate of diabetic HD patients was higher than that of nondiabetic HD patients until 2019 but became lower starting in 2020. There was a decreasing trend in mortality rate in diabetic CKD 5D patients, but cardiac and vascular diseases were still prevalent in diabetic CKD 5D patients with frequent admissions to hospitals. More specialized care is needed to improve the clinical outcomes of diabetic CKD 5D patients.

Mortality in patients receiving renal replacement therapy in South Korea.

Background: This study analyzed data from the end-stage renal disease patient registry collected by the Korean Society of Nephrology to explore trends in mortality among dialysis patients from 2001 to 2022. Methods: Mortality was analyzed in two ways: firstly, using the annual mortality rate; and secondly, by assessing survivability after a certain period of time since the initiation of dialysis. Additionally, we categorized the causes of death by disease group annually to observe how the proportions changed. Results: Since 2001, annual mortality for dialysis patients generally declined, except for a rise in 2020 and 2021 among hemodialysis patients. Overall mortality rates for all dialysis patients dropped from 74.2/1,000 person-years in 2001 to 42.3/1,000 person-years in 2022, with a more pronounced decrease in peritoneal dialysis. While survival probability over the 5 years following initiation of dialysis has shown a steady increase, short-term mortality from 2018 to 2020 affected by coronavirus disease 2019 (COVID-19) has shown a yearly increase by age group, with a greater effect in those aged 75 years and older. The leading causes of death for all dialysis patients have changed little, in the order of heart disease, infection, and vascular problems. Conclusion: While annual mortality and survival probability after dialysis initiation have generally improved in dialysis patients, there has been a temporary deterioration during the COVID-19 pandemic, most pronounced in the elderly.

Changes in CT-Based Morphological Features of the Kidney with Declining Glomerular Filtration Rate in Chronic Kidney Disease.

Chronic kidney disease (CKD) progression involves morphological changes in the kidney, such as decreased length and thickness, with associated histopathological alterations. However, the relationship between morphological changes in the kidneys and glomerular filtration rate (GFR) has not been quantitatively and comprehensively evaluated. We evaluated the three-dimensional size and shape of the kidney using computed tomography (CT)-derived features in relation to kidney function. We included 257 patients aged ≥18 years who underwent non-contrast abdominal CT at the Inha University Hospital. The features were quantified using predefined algorithms in the pyRadiomics package after kidney segmentation. All features, except for flatness, significantly correlated with estimated GFR (eGFR). The surface-area-to-volume ratio (SVR) showed the strongest negative correlation (r = -0.75, p < 0.0001). Kidney size features, such as volume and diameter, showed moderate to high positive correlations; other morphological features showed low to moderate correlations. The calculated area under the receiver operating characteristic (ROC) curve (AUC) for different features ranged from 0.51 (for elongation) to 0.86 (for SVR) for different eGFR thresholds. Diabetes patients had weaker correlations between the studied features and eGFR and showed less bumpy surfaces in three-dimensional visualization. We identified alterations in the CKD kidney based on various three-dimensional shape and size features, with their potential diagnostic value.

Cancer Diagnosis During Kidney Donor Evaluation.

Donor evaluation is important to ensure that life threatening diseases like cancer can be prevented from getting passed on to the recipient. The donor patient described in our report showed normal parameters in blood and urine biochemistry analysis. Additionally, kidney ultrasonography and renal artery CT showed no indications of any abnormalities. However, endoscopic analysis performed later turned out to be valuable in detection of a protruding mass of 22 to 25 cm in size at the anal verge, and positron emission tomography revealed liver metastasis. Thus, our study highlights that endoscopic techniques can be really valuable in cancer detection and medical centers must consider including these tests in their donor evaluation diagnostic procedures.

Acute Anti-A/B Antibody-Mediated Rejection After ABO-Incompatible Kidney Transplantation Treated With Bortezomib and Plasmapheresis: A Case Report.

BACKGROUND: ABO-incompatible kidney transplantation (KTP) is effective for avoiding transplantation-related issues. It is a viable alternative to ABO-compatible KTP, as both techniques have similar patient and graft survival rates. However, anti-A/B antibody-mediated rejection (AMR) can occur, resulting in poor long-term graft survival. CASE: A 45-year-old man with end-stage renal disease presented with a serum creatinine level of 10.2 mg/dL. We decided to perform KTP with spousal donation. He had panel-reactive antibody class I and II and cross matching test negativity, a 3/6 mismatch on human leukocyte antigen typing, an ABO antibody titer of 1:256, and no donor-specific antibodies. The patient and donor blood types were O+ and A+, respectively. The anti-A/B antibody titer was reduced preoperatively with rituximab (200 mg/body), plasmapheresis, and intravenous immunoglobulin (0.2 mg/kg). Basiliximab and methylprednisolone were used for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisolone were used for maintenance immunosuppression. KTP was successful, and graft function was initially normal. On postoperative day (POD) 5, the serum creatinine level and anti-A/B antibody titer increased from 0.9 mg/dL to 1.9 mg/dL and 1:16 to 1:64, respectively. Graft biopsy revealed acute AMR and tubular injury. We started steroid pulse therapy, plasmapheresis, and subcutaneous bortezomib (2.6 mg, twice a day, every 3 days) with no side effects. The serum creatinine level decreased from 5.7 mg/dL to 1.5 mg/dL on POD 28. Graft biopsy showed no rejection, and normal function was maintained for 40 months. CONCLUSIONS: Acute, early anti-A/B AMR was successfully treated with plasmapheresis and bortezomib.

Multiple Gouty Arthritis With Tophi Formation in a Patient With End-Stage Kidney Disease Treated After Kidney Transplant.

BACKGROUND: Hyperuricemia is a common condition in patients with chronic kidney disease and end-stage kidney disease. It occurs even after kidney transplant because of the use of calcineurin inhibitors and transplanted kidney failure. We describe the case of a patient with end-stage kidney disease who had multiple gouty arthritis with tophi formation despite receiving appropriate treatment but was successfully cured after kidney transplant. CASE REPORT: A 36-year-old male patient undergoing hemodialysis treatment was treated with febuxostat for multiple gouty arthritis and underwent tophi removal twice. He received a deceased donor kidney transplant 10 years after dialysis treatment. He received immunosuppressants (basiliximab, tacrolimus, mycophenolate mofetil) and steroids. Results of renal biopsy performed on days 7 and 21 postoperation showed no specific findings and normal renal function. The uric acid level before transplant was 3.1 mg/dL, and when renal function was normal, it reached 6-7 mg/dL and remained stable. Although hyperuricemia was still present, the tophi disappeared 3 months after transplant. It is presumed that the high-dose steroids interfered with the activation of inflammatory responses during tophi formation, which may have caused the tophi to disappear. It is also presumed that the patient adhered to the diet well after transplant, which suppressed tophi formation. CONCLUSIONS: Our findings suggest that disappearance of multiple tophi and arthritis in patients undergoing hemodialysis can be achieved with kidney transplant, especially when uric acid-lowering drugs are not effective.

Potassium Channel Syndrome Caused by Nicorandil in Chronic Kidney Disease: A Case Report and Literature Review.

Nicorandil is an anti-anginal drug that is commonly used in the treatment of ischemic heart disease. Nicorandil acts as a nitrate donor and ATP-sensitive potassium channel agonist, inducing coronary artery vasodilation. Potassium efflux through ATP-sensitive potassium channels activated by nicorandil can cause refractory hyperkalemia, particularly in patients with chronic kidney disease (CKD). Here, we report the case of an 85-year-old man who presented with severe refractory hyperkalemia, despite proper medical management. His serum potassium level increased from 4.96 to 7.21 mEq/L 7 days after restarting nicorandil. Hyperkalemia resolved shortly after discontinuation of nicorandil, which was presumed to be the offending drug. Previously, a few cases reported nicorandil-induced hyperkalemia called potassium channel syndrome in patients with CKD, and hyperkalemia can be reversed by ceasing nicorandil or using sulfonyl urea drugs. Given that CKD patients may have several contributing factors to this adverse event, clinicians should be aware of the risk of nicorandil-induced hyperkalemia, and medication review and drug discontinuation should be considered.

Efficacy and Safety According to the Dose of Valganciclovir for Cytomegalovirus Prophylaxis in Transplantation: Network Meta-analysis Using Recent Data.

BACKGROUND: Valganciclovir is used to prevent posttransplant cytomegalovirus (CMV) infection among patients undergoing kidney transplant. However, the optimal dose remains controversial because continuous use decreases kidney function and can induce leukopenia. The purpose of this study was to identify the appropriate dose of valganciclovir for preventing CMV using network meta-analysis. METHODS: We searched the Cochrane Central Register, Ovid MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health, and Web of Science databases for studies published through April 15, 2017, evaluating 900-mg and 450-mg valganciclovir. We performed direct and indirect network meta-analysis using Bayesian models and generated rankings of different doses of valganciclovir by generating a mixed-treatment comparison. RESULTS: Twenty-three studies involving 3478 participants were included. Compared with the control group, there was no difference in the incidence of CMV infection between the low-dose (450 mg) (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.50-1.40) and high-dose (900 mg) (OR, 1.0; 95% CI, 0.61-1.60) groups. Low-dose valganciclovir had the best probability (71.1%) for decreasing CMV infection. Leukopenia was significantly more common in the high-dose group than in the control group (OR, 4.3; 95% CI, 2.69-7.10) and in the low-dose group (OR, 2.9; 95% CI, 1.88-4.67), but there was no significant difference in the incidence of leukopenia between the low-dose and control groups (OR, 1.5; 95% CI, 0.99-2.20). CONCLUSIONS: The incidence of CMV was not different based on the dose of valganciclovir, although the tendency for CMV infection was decreased at 450 mg. However, the low dose of valganciclovir significantly reduced the incidence of leukopenia.

Effect of rituximab dose on induction therapy in ABO-incompatible living kidney transplantation: A network meta-analysis.

BACKGROUND: Rituximab is an induction immunosuppressant essential for ABO-incompatible kidney transplantation (ABOi KT). However, studies on its dosing, which differs among countries and transplant centers, are lacking. Therefore, we retrospectively investigated the effectiveness of the induction dose of rituximab against patient mortality, graft failure, and adverse events. METHODS: We included the studies referring to at least 2 of eligible induction doses (200 mg, 200-500 mg, or 500 mg) of rituximab during ABOi KT and relevant outcomes such as patient survival, graft failure, and bacterial and viral infections. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using generation mixed treatment comparison. Publications were retrieved using CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2020 and analyzed. The GRADE of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. RESULTS: Among the 4256 patients from 21 trials, glomerular filtration rate, graft loss, antibody-mediated rejection, T-cell mediated rejection, fungal infection, bacterial infection, and CMV infection did not differ among ABOi groups treated with different rituximab doses. The effect on mortality was significantly higher in rituximab 200 to 500 mg, and rituximab 500 mg groups (odds ratios [OR] 3.5, 95% CrI: 1.3-9.8, and OR 3.0, 95% CrI 1.1-9.8), but not in rituximab 20 mg group (OR 0.45, 95% CrI 0.036-2.5). The incidence of BK virus was significantly lower in the rituximab 200-mg group than in the other groups. DISCUSSION: In ABO-incompatible kidney transplantation, low-dose rituximab is more efficacious than higher doses and reduces serious infection risks. Additional randomized controlled trials might be needed to confirm these findings due to small sample size.

Effects of Sodium-Glucose Cotransporter Inhibitor/Glucagon-Like Peptide-1 Receptor Agonist Add-On to Insulin Therapy on Glucose Homeostasis and Body Weight in Patients With Type 1 Diabetes: A Network Meta-Analysis.

Many patients with type 1 diabetes (T1D) do not achieve the glycemic target goal with insulin treatment. In this study, we aimed to evaluate the efficacy and safety of add-on to insulin therapy in patients with T1D. We conducted direct and indirect network meta-analyses using Bayesian models and ranked hypoglycemic agents via mixed treatment comparison, using data from the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. Randomized controlled trials (RCTs) involving patients with T1D treated with insulin and add-on metformin or sodium-glucose cotransporter inhibitors or glucagon-like peptide-1 receptor agonists from January 1970 to September 2019 were included in this study. Twenty-three RCTs with 5,151 subjects were divided into the following groups: insulin alone, insulin+metformin, insulin+canagliflozin, insulin+dapagliflozin, insulin+empagliflozin, insulin+sotagliflozin, insulin+liraglutide, and insulin+exenatide. HbA1c level in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group (mean difference: -0.43, 95% credible interval: -0.62 to -0.23). Total daily insulin dose in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group. Compared with that in the insulin alone group, body weight in the groups treated with insulin+add-on canagliflozin, sotagliflozin, and exenatide was significantly decreased by 4.5, 2.8, and 5.1 kg, respectively. Hypoglycemic episodes did not differ among the groups. In patients with T1D, insulin+sotagliflozin decreased the HbA1c level, daily insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Insulin+canagliflozin or insulin+exenatide was effective in reducing body weight compared with insulin alone. In conclusion, sotagliflozin treatment decreased not only the HbA1c levels and insulin dose but also the body weight without causing hypoglycemia in patients with T1D. Treatment with canagliflozin and exenatide effectively reduced body weight in patients with T1D. However, ketoacidosis associated with the use of SGLT inhibitors should be considered in these patients. Thus, our results suggest that sotagliflozin has a high probability of being ranked first as an adjunctive therapy to insulin in patients with T1D.

Effect of Rituximab Used as Induction in Patients with ABO Mismatch Kidney Transplant: A Systematic Review and Meta-analysis.

INTRODUCTION: ABO-incompatible living kidney transplantation (ABOILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABOILKT remains uncertain. We aimed to determine the outcomes according to dose of rituximab induction. METHODS: We conducted a systematic review and meta-analysis using random-effects modeling. We searched the following databases for all studies published through May 15, 2019: Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival according to dose of rituximab as induction in kidney transplantation. RESULTS: Five trials with a total of 390 patients were included. Glomerular filtration rates, graft loss, antibody mediated rejection, T cell mediated rejection, fungal infection (Candida), and patient survival rates did not differ between the 200 mg single dose and 375 mg/m2 in rituximab groups. However, incidence rate of infection 0.470 (95% confidence interval [CI], 0.264 to 0.838) had a lower result than the 200 mg rituximab group. CONCLUSIONS: The using of a 200 mg single dose of rituximab induction in ABOILKT has not only the same results for rejection, graft survival, and patient survival but also low incidence of infection after transplantation.

Effect of statins on cardiovascular complications in chronic kidney disease patients: A network meta-analysis.

BACKGROUND: The rates of cardiovascular mortality and morbidity are increased in advanced chronic kidney disease (CKD). Mild to moderate CKD is associated with an increase in cardiovascular events. This study aims to investigate the effects of statins on patient mortality and cardiac events. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies on statins (atorvastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, and simvastatin + ezetimibe) in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2019 were analyzed. Inclusion criteria were randomized control trials and adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have thrombosis as an outcome were excluded. We performed direct and indirect network meta-analysis using Bayesian models and ranked different statins using generation mixed treatment comparison (GeMTC) and Stata version 13. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) of network meta-analysis approach specified 4 levels of certainty for a given result: high, moderate, low, and very low. The outcomes were cardiac events, cardiac mortality, and all-cause mortality. RESULTS: Nineteen studies (45,863 patients) were included. Compared with placebos, pravastatin 40 mg group showed a significantly lower patient mortality (odds ratio 0.66 [95% credible interval, 0.46-0.91]).Atorvastatin 80 mg, fluvastatin 40 mg, lovastatin 20 mg, pravastatin 40 mg, and simvastatin 40 mg showed significant results in reducing cardiac events.In rank probability, pravastatin showed the best effect at all-cause mortality rate. Lovastatin, fluvastatin, and pravastatin showed good effects in the 1st, 2nd, and 3rd ranks in cardiac events. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Pravastatin 40 mg demonstrated the best effect on all-cause mortality, and was observed to be effective with high ranking in cardiac events. We anticipate that the data of this study will assist physicians in making informed decisions when selecting statins, such as pravastatin, as a treatment option for CKD patients.