Association of Serum Activin Levels with Allograft Outcomes in Patients with Kidney Transplant: Results from the KNOW-KT.

INTRODUCTION: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT). METHODS: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT. RESULTS: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18). CONCLUSION: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Impact of Blood Pressure on Allograft Function and Survival in Kidney Transplant Recipients.

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP <110; 110-119; 120-129; 130-139; and ≥140 mmHg. SBP trajectories were classified into decreasing, stable, and increasing groups. Primary outcome was composite kidney outcome of ≥50% decrease in eGFR or death-censored graft loss. Compared with the 110-119 mmHg group, both the lowest (adjusted hazard ratio [aHR], 2.43) and the highest SBP (aHR, 2.25) were associated with a higher risk of composite kidney outcome. In time-varying model, also the lowest (aHR, 3.02) and the highest SBP (aHR, 3.60) were associated with a higher risk. In the trajectory model, an increasing SBP trajectory was associated with a higher risk than a stable SBP trajectory (aHR, 2.26). This associations were consistent in the validation set. In conclusion, SBP ≥140 mmHg and an increasing SBP trajectory were associated with a higher risk of allograft dysfunction and failure in KT patients.

Factors Associated With the Development and Severity of Polycystic Liver in Patients With Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Factors related to the development and severity of polycystic liver disease (PLD) have not been well established. We aimed to evaluate the genetic and epidemiologic risk factors of PLD in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: Adult patients with inherited cystic kidney disease were enrolled from May 2019 to May 2021. Demographic, clinical, and laboratory data were collected at the initial study visit. The severity of PLD was graded based on the height-adjusted total liver volume: < 1,000 mL/m (Gr1), 1,000-1,800 mL/m (Gr2), and > 1,800 mL/m (Gr3). Targeted exome sequencing was done by a gene panel including 89 ciliopathy-related genes. We searched out the relative factors to the presence and the severity of PLD using logistic regression analysis. RESULTS: Of 602 patients with typical ADPKD, 461 (76.6%) patients had PLD. The patients with PLD showed female predominance and a higher frequency of other ADPKD-related complications. The genetic variants with truncating mutation of PKD1 (PKD1-protein-truncating [PT]) or PKD2 commonly affected the development and severity of PLD. An older age, female sex, and higher kidney volume with Mayo classification 1C-1E was significantly associated with the development of PLD, but not with the severity of PLD. On the other hand, higher body mass index, lower hemoglobin, and higher alkaline phosphatase (ALP) were the significant risk factors of severe PLD (≥ Gr2). CONCLUSION: Hepatic involvement in ADPKD could be related to kidney manifestations and genetic variants including PKD1-PT or PKD2. Monitoring hemoglobin and ALP and evaluating the genetic variants might help predict severe PLD. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005580.

Pretransplant and Posttransplant Alcohol Consumption and Outcomes in Kidney Transplantation: A Prospective Multicenter Cohort Study.

The impact of pretransplant and posttransplant alcohol consumption on outcomes in kidney transplant recipients (KTRs) is uncertain. Self-reported alcohol consumption was obtained at the time of transplant and 2 years after transplant in a prospective cohort study. Among 907 KTRs, 368 (40.6%) were drinkers at the time of transplant. Compared to non-drinkers, alcohol consumption did not affect the risk of death-censored graft failure (DCGF), biopsy-proven acute rejection (BPAR), cardiovascular events, or all-cause mortality. Compared to persistent non-drinkers, the development of DCGF, BPAR, cardiovascular events, all-cause mortality, or posttransplant diabetes mellitus was not affected by the alcohol consumption pattern (persistent, de novo, or stopped drinking) over time. However, de novo drinkers had a significantly higher total cholesterol (p < 0.001) and low-density lipoprotein cholesterol levels (p = 0.005) compared to persistent non-drinkers 5 years after transplant, and had significantly higher total cholesterol levels (p = 0.002) compared to the stopped drinking group 7 years after transplant, even after adjusting for the use of lipid-lowering agents, age, sex, and body mass index. Although pretransplant and posttransplant alcohol consumption were not associated with major outcomes in KTRs during the median follow-up of 6.0 years, a new start of alcohol use after KT results in a relatively poor lipid profile. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02042963.

Impact of recipient and donor smoking in living-donor kidney transplantation: a prospective multicenter cohort study.

The smoking status of kidney transplant recipients and living donors has not been explored concurrently in a prospective study, and the synergistic adverse impact on outcomes remains uncertain. The self-reported smoking status and frequency were obtained from recipients and donors at the time of kidney transplantation in a prospective multicenter longitudinal cohort study (NCT02042963). Smoking status was categorized as "ever smoker" (current and former smokers collectively) or "never smoker." Among 858 eligible kidney transplant recipients and the 858 living donors, 389 (45.3%) and 241 (28.1%) recipients were considered ever smokers at the time of transplant. During the median follow-up period of 6 years, the rate of death-censored graft failure was significantly higher in ever-smoker recipients than in never-smoker recipients (adjusted HR, 2.82; 95% CI 1.01-7.87; P = 0.048). A smoking history of >20 pack-years was associated with a significantly higher rate of death-censored graft failure than a history of ≤20 pack-years (adjusted HR, 2.83; 95% CI 1.19-6.78; P = 0.019). No donor smoking effect was found in terms of graft survival. The smoking status of the recipients and donors or both did not affect the rate of biopsy-proven acute rejection, major adverse cardiac events, all-cause mortality, or post-transplant diabetes mellitus. Taken together, the recipient's smoking status before kidney transplantation is dose-dependently associated with impaired survival.

Target value of mean arterial pressure in patients undergoing continuous renal replacement therapy due to acute kidney injury.

BACKGROUND: Although patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI) frequently have instability in mean arterial pressure (MAP), no consensus exists on the target value of MAP related to high mortality after CRRT. METHODS: A total of 2,292 patients who underwent CRRT due to AKI in three referral hospitals were retrospectively reviewed. The MAPs were divided into tertiles, and the 3rd tertile group served as a reference in the analyses. The major outcome was all-cause mortality during the intensive care unit period. The odds ratio (OR) of mortality was calculated using logistic regression after adjustment for multiple covariates. The nonlinear relationship regression model was applied to determine the threshold value of MAP related to increasing mortality. RESULTS: The mean value of MAP was 80.7 ± 17.3 mmHg at the time of CRRT initiation. The median intensive care unit stay was 5 days (interquartile range, 2-12 days), and during this time, 1,227 (55.5%) patients died. The 1st tertile group of MAP showed an elevated risk of mortality compared with the 3rd tertile group (adjusted OR, 1.28 [1.03-1.60]; P = 0.029). In the nonlinear regression analysis, the threshold value of MAP was calculated as 82.7 mmHg. Patients with MAP < 82.7 mmHg had a higher mortality rate than those with ≥ 82.7 mmHg (adjusted OR, 1.21 [1.01-1.45]; P = 0.037). CONCLUSIONS: Low MAP at CRRT initiation is associated with a high risk of mortality, particularly when it is < 82.7 mmHg. This value may be used for risk classification and as a potential therapeutic target.

Genetic identification of inherited cystic kidney diseases for implementing precision medicine: a study protocol for a 3-year prospective multicenter cohort study.

BACKGROUND: Inherited cystic kidney disease is a spectrum of disorders in which clusters of renal cysts develop as the result of genetic mutation. The exact methods and pipelines for defining genetic mutations of inherited cystic kidney disease are not clear at this point. This 3-year, prospective, multicenter, cohort study was designed to set up a cohort of Korean patients with inherited cystic kidney disease, establish a customized genetic analysis pipeline for each disease subtype, and identify modifying genes associated with the severity of the disease phenotype. METHODS/DESIGN: From May 2020 to May 2022, we aim to recruit 800 patients and their family members to identify pathogenic mutations. Patients with more than 3 renal cysts in both kidneys are eligible to be enrolled. Cases of simple renal cysts and acquired cystic kidney disease that involve cyst formation as the result of renal failure will be excluded from this study. Demographic, laboratory, and imaging data as well as family pedigree will be collected at baseline. Renal function and changes in total kidney volume will be monitored during the follow-up period. Genetic identification of each case of inherited cystic kidney disease will be performed using a targeted gene panel of cystogenesis-related genes, whole exome sequencing (WES) and/or family segregation studies. Genotype-phenotype correlation analysis will be performed to elucidate the genetic effect on the severity of the disease phenotype. DISCUSSION: This is the first nationwide cohort study on patients with inherited cystic kidney disease in Korea. We will build a multicenter cohort to describe the clinical characteristics of Korean patients with inherited cystic kidney disease, elucidate the genotype of each disease, and demonstrate the genetic effects on the severity of the disease phenotype. TRIAL REGISTRATION: This cohort study was retrospectively registered at the Clinical Research Information Service ( KCT0005580 ) operated by the Korean Center for Disease Control and Prevention on November 5th, 2020.

Two distinct cases with COVID-19 in kidney transplant recipients.

The fatality of novel coronavirus disease 2019 (COVID-19) is precipitously increased in patients with underlying comorbidities or elderly people. Kidney transplant (KT) recipients are one of the vulnerable populations for infection. COVID-19 infection in KT recipients might be a complicated and awkward situation, but there has been a lack of reports concerning this group. Herein, we demonstrated two distinct cases with different clinical progress. The first case was a 36-year-old man who underwent KT 3 years ago. He was diagnosed with COVID-19 expressing relevant symptoms. Following administration of lopinavir/ritonavir and hydroxychloroquine with reduced immunosuppressant, he recovered from COVID-19. However, the unexpected fluctuations in tacrolimus trough levels needed to be managed because of drug-to-drug interaction. The second case was developed in a 56-year-old man without any symptoms. He received a second KT from an ABO-incompatible donor 8 years ago. He was diagnosed with COVID-19 by screening due to exposure history. During the hospitalization period, the chest infiltrative lesion showed a wax and wane, but he successfully recovered by administration of hydroxychloroquine with azithromycin. These apparently different cases suggest that assertive screening and management could improve the clinical course. In addition, antiviral agents should be used cautiously, especially in patients on calcineurin inhibitors.

Biobanking for glomerular diseases: a study design and protocol for KOrea Renal biobank NEtwoRk System TOward NExt-generation analysis (KORNERSTONE).

BACKGROUNDS: Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). METHODS: The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. DISCUSSION: Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. TRIAL REGISTRATION: NCT03929887 .

Impact of acute kidney injury in expanded criteria deceased donors on post-transplant clinical outcomes: multicenter cohort study.

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

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.

Unilateral testicular tuberculosis in a kidney transplant recipient: a case report.

Tuberculosis (TB) of the genitourinary system is a rare form of extrapulmonary TB. Testicular TB is particularly uncommon among kidney transplantation (KT) recipients. Diagnosing testicular TB is challenging due to the nonspecific nature of clinical presentations and ambiguous imaging results. In this report, we describe a case involving a 36-year-old male KT recipient who presented with left scrotal pain. He had undergone a living donor KT 8 years prior and was receiving tacrolimus, mycophenolate mofetil, and prednisolone. Laboratory tests revealed anemia, leukocytosis, and elevated inflammatory markers. Computed tomography showed left scrotal wall thickening and enlargement, suggestive of a left testicular abscess. We discontinued mycophenolate mofetil and administered intravenous antibiotics. Additionally, we performed an incision and drainage of the abscess. However, there was no improvement in his clinical course. Consequently, we performed a radical left orchiectomy. The biopsy revealed extensive chronic granulomatous inflammation with caseous necrosis, consistent with tuberculous orchiepididymitis. A quadruple anti-TB regimen was administered, leading to an improvement in the patient's condition. To the best of our knowledge, this is the first reported case of testicular TB without other organ involvement in KT recipients. Including testicular TB in the differential diagnosis of testicular infections and masses is necessary to avoid unnecessary surgical procedures.

Coexistence of double seropositivity for MPO antibody and anti-GBM antibody in ANCA-associated vasculitis concurrent with multiple myeloma: A case report.

RATIONALE: Immune-mediated vasculitis with 2 or more autoantibodies, for example, anti-proteinase-3, combined with anti-myeloperoxidase (MPO) or anti-glomerular basement membrane (GBM) antibodies, is extremely unusual. Furthermore, the coexistence of autoimmune vasculitis and hematological malignancies is uncommon. Herein, we describe a case of double-seropositive anti-neutrophil cytoplasmic antibody (ANCA) vasculitis with multiple myeloma. PATIENT CONCERNS: A 79-year-old Asian man presented with persistent leg edema and kidney dysfunction. His kidney function rapidly decreased, and serologic test results showed higher titers of the anti-MPO antibody (54.7 IU/mL) and anti-GBM antibodies (>200 IU/mL). Additionally, the clinical features showed the possibility of monoclonal gammopathy with anemia and hyperglobulinemia. We performed kidney and bone marrow biopsy. Serum protein electrophoresis and immunofixation revealed no significant differences, but the results of the bone marrow smear were compatible with those of myeloma with 15% plasmacytosis. However, kidney biopsy showed diffuse crescentic glomerulonephritis without deposition of the immune complex or kappa/lambda chain. DIAGNOSES AND INTERVENTIONS: Finally, the patient was diagnosed with double-seropositive ANCA-associated glomerulonephritis and multiple myeloma. Given the patient's performance status, we initiated low-dose steroid pulse therapy, followed by conservative management. OUTCOMES: While the pulmonary lesions showed improvement, the kidney function did not regain its previous state, prompting the initiation of kidney replacement therapy by hemodialysis. There has been a decrease in the levels of anti-GBM and anti-MPO antibodies since the initial diagnosis. LESSONS: This case elucidates the complex interplay between ANCA-associated glomerulonephritis and hematologic malignancy and emphasizes the need for a nuanced treatment strategy considering its multifaceted clinical presentation.

Acute interstitial nephritis with acute kidney injury after COVID-19 vaccination: a case report.

In the context of the massive spread of coronavirus disease 2019 (COVID-19), the development of a COVID-19 vaccine is urgently needed. The Pfizer-BioNTech COVID-19 vaccine has been widely applied across global populations. Herein, we report a case of acute interstitial nephritis with acute kidney injury in a young healthy subject after administration of the COVID-19 vaccine. A 20-year-old man was admitted with abdominal discomfort and nausea. He had received the Pfizer-BioNTech COVID-19 vaccine 6 days before. At 9 days after vaccination, his kidney function was decreased, with serum creatinine levels of 1.8 mg/dL. Even with supportive care with hydration, his kidney function worsened, and he underwent a kidney biopsy. The pathology findings revealed diffuse interstitial infiltration of inflammatory cells, predominantly comprising lymphocytes, with preservation of the glomerulus. No abnormal findings were noted by immunofluorescence or electron microscopy. Based on a diagnosis of drug-related acute interstitial nephritis, we treated the patient with high-dose prednisolone. After administration of prednisolone, kidney function slowly improved. A close linkage between COVID-19 vaccination and acute interstitial nephritis should be considered in the clinic, despite the low incidence.

Benefits of statin therapy within a year after kidney transplantation.

Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111-0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198-0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT.

Association of Serum Osteoprotegerin With Vascular Calcification, and Cardiovascular and Graft Outcomes in Kidney Transplant Patients: Results From the KNOW-KT.

BACKGROUND: Vascular calcification and stiffness contribute to increased cardiovascular morbidity in patients with chronic kidney disease. This study investigated associations between serum osteoprotegerin (OPG) levels and vascular calcification or stiffness to assess cardiovascular and graft outcomes in kidney transplant patients. METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation was a prospective multicenter cohort study. Serum OPG levels were measured at baseline and 3 y after transplantation in 1018 patients. Patients were classified into high and low OPG groups according to median serum OPG levels. The median follow-up duration was 93.5 mo. RESULTS: The mean age was 45.8 ±â€…11.7 y and 62.9% were men. Patients with high OPG had significantly higher coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities than those with lower OPG; these parameters remained significant for 5 y after transplantation. The 3-y OPG levels were lower than baseline values ( P < 0.001) and were positively correlated ( r = 0.42, P < 0.001). Multivariate Cox regression analysis showed that high OPG levels were significantly associated with posttransplant cardiovascular events ( P = 0.008) and death-censored graft loss ( P = 0.004). Similar findings regarding posttransplant cardiovascular events ( P = 0.012) and death-censored graft loss ( P = 0.037) were noted in patients with high OPG at the 3-y follow-up. Mediation analyses revealed that coronary artery calcium scores, abdominal aortic calcification scores, and brachial-ankle pulse wave velocities could act as mediators between serum OPG levels and posttransplant cardiovascular events. CONCLUSIONS: Serum OPG concentration is associated with vascular calcification and stiffness and could be a significant risk factor for cardiovascular outcomes and graft loss in patients undergoing kidney transplantation.

Impact of hyperuricemia on CKD risk beyond genetic predisposition in a population-based cohort study.

The bidirectional effect of hyperuricemia on chronic kidney disease (CKD) underscores the importance of hyperuricemia as a risk factor for CKD. We evaluated the effect of hyperuricemia on the presence and development of CKD after considering genetic background by calculating polygenic risk scores (PRSs). We employed genome-wide association study summary statistics-excluding the United Kingdom Biobank (UKB) datasets among published CKD Gen Consortium papers-to calculate the PRSs for CKD in white background subjects. To validate PRS performance, we divided the UKB into two datasets to validate and test the data. We used logistic regression analysis to evaluate the association between hyperuricemia and CKD, and performed Kaplan-Meier survival analysis exclusively for subjects with available follow-up data. In total, 438,253 clinical data and 4,307,940 single nucleotide polymorphisms from 459,155 samples were included. We observed a significant positive association between PRS and CKD and the presence and development of CKD. Hyperuricemia significantly increased CKD risk (adjusted odds ratio 1.55, 95% confidence interval 1.48-1.61). The impact of hyperuricemia on CKD was maintained irrespective of PRS range. In addition, negative interaction between hyperuricemia and PRS for CKD was found. Survival analysis indicates that the presence of hyperuricemia significantly increased the risk of CKD development. The PRS for CKD thoroughly reflects the risk of CKD development. Hyperuricemia is a significant indicator of CKD risk, even after incorporating the genetic risk score for CKD. Irrespective of genetic risk, patients with a prospective risk of developing CKD require uric acid monitoring and management.

Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients.

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established. Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1-4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1-4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes. Results: The high CACS group (N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01-17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27-5.92) compared to the low CACS group (N = 225). Similarly, the high AACS group (N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16-4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups. Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients.

Arterial calcification, accumulation of calcium in the arterial walls, vascular stiffness, and loss of elasticity of blood vessels can contribute to the development of cardiovascular diseases. Patients with chronic kidney disease and those undergoing dialysis have a considerably increased risk of vascular calcification. Even after kidney transplantation when kidney function has been restored, the prevalence of vascular calcification and subsequent cardiovascular disease remains high. Coronary artery calcification score and abdominal aortic calcification score are both well-established markers of vascular calcification. However, the impact of pretransplant vascular calcification scores on cardiovascular and renal outcomes in kidney transplant patients has not been established. When we analyzed 944 Korean kidney transplant patients, both vascular calcification scores were significantly associated with cardiovascular outcomes after kidney transplantation, but were not associated with renal outcomes. We also demonstrated that the addition of coronary artery calcification scores led to a modest improvement in the prediction performance for kidney transplant outcomes. Our findings suggest a potential role of pretransplant screening of coronary calcification scores and aortic calcification scores in risk stratification for post-kidney transplant outcomes.

Recent updates in therapeutic approach using tolvaptan for autosomal dominant polycystic kidney disease.

As a genetic disease, there has been a long-standing effort to identify therapeutic options for autosomal dominant polycystic kidney disease (ADPKD). Following the development of tolvaptan, a vasopressin 2 receptor antagonist, the treatment strategy for ADPKD patients with rapid disease progression has been changed with a disease-targeted approach. Tolvaptan showed significant efficacy in preserving kidney function and reducing the total kidney volume (TKV) growth rate. These effects were especially pronounced in patients with more severe clinical phenotypes, such as higher TKV and rapidly declining kidney function. Despite the therapeutic effects of tolvaptan, aquaretic symptoms are unavoidable side effects related to the mechanism of the drug and are also directly related to the quality of life. A shared decision-making process could be a valuable strategy for reducing the incidence of side effects and improving medication adherence. Herein, we aimed to review overall clinical trials for applying tolvaptan and suggest important factors during the shared decision-making process.