Effect of pre-transplantation use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in kidney transplant recipients-propensity score-matched analysis.

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARBs) can cause acute kidney injury under dehydratation or in hemodynamically unstable conditions. Regarding kidney transplantation (KT), the risk of using ACEi/ARBs before surgery is not well established. Therefore, we evaluated the clinical outcomes to determine the effect of preoperative use of ACEi/ARBs on KT. METHODS: We retrospectively collected 1187 patients who received living-donor KT between January 2017 and December 2021. We conducted a propensity score-matched analysis between the ACEi/ARB(+) and ACEi/ARB(-) groups and evaluated the effects of ACEi/ARBs on delayed graft function, post-KT renal function, hyperkalemia events, rejection, and graft survival. RESULTS: The ACEi/ARB(+) group showed a similar incidence of delayed graft function as the ACEi/ARB(-) group (1.8% vs. 1.0%, P = 0.362). The risk of delayed graft function was not upregulated in the ACEi/ARB(+) group after propensity score-matching (odds ratio: 0.50, 95% confidence interval (CI) 0.13-2.00). Postoperative creatinine levels and the slope of creatinine levels after KT also were not significantly different between the two groups (creatinine slope from POD#0 to POD#7: - 0.73 ± 0.35 vs. - 0.75 ± 0.32 mg/dL/day, P = 0.464). Hyperkalemia did not occur more often in the ACEi/ARB(+) group than in the ACEi/ARB(-) group during perioperative days. Rejection-free survival (P = 0.920) and graft survival (P = 0.621) were not significantly different between the two groups. CONCLUSIONS: In KT, the preoperative use of ACEi/ARBs did not significantly affect clinical outcomes including delayed graft function, postoperative renal function, hyperkalemia events, incidence of rejection, and graft survival rates compared to the patients who did not receive ACEi/ARBs.

Association of ketone bodies with incident CKD and death: A UK Biobank study.

AIMS: Although cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. METHODS: This was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of ß-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. RESULTS: During a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05-1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11-1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01-1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07-1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02-1.24) and 26 % (aHR 1.26; 95 % CI 1.15-1.37) higher risk of incident CKD and all-cause mortality, respectively. CONCLUSIONS: Higher KB levels were independently associated with higher risk of incident CKD and death.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank.

RATIONALE & OBJECTIVE: The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. EXPOSURE: Estimated GFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFRdiff was also categorized as negative (<-15mL/min/1.73m2), midrange (-15 to 15mL/min/1.73m2), or positive (≥15mL/min/1.73m2). OUTCOME: Incident AF. ANALYTICAL APPROACH: Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. RESULTS: During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFRdiff had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10mL/min/1.73m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF. LIMITATIONS: A single measurement of baseline serum creatinine and cystatin C levels. CONCLUSIONS: The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF. PLAIN-LANGUAGE SUMMARY: The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Fibrotic Burden in Patients With Hepatitis B Virus-Related Cirrhosis Is Independently Associated With Poorer Kidney Outcomes.

BACKGROUND: We investigated whether higher fibrotic burden was independently associated with poorer kidney outcomes in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: A total of 1691 patients with radiologically diagnosed HBV-related cirrhosis but without baseline chronic kidney disease (CKD) who underwent transient elastography (TE) between March 2012 and August 2018 were selected. The study outcome was the composite of development of incident CKD, defined as the occurrence of estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 or proteinuria (≥1+ on dipstick test) on 2 consecutive measurements during follow-up, 50% decline in eGFR or onset of end-stage kidney disease (initiation of chronic dialysis), or all-cause mortality. RESULTS: The mean age was 53.4 years and 1030 (60.9%) patients were male. During 8379 person-years of follow-up (median 5.2 years), 60 (3.5%) patients experienced study outcomes. When stratified according to TE-defined fibrotic burden, multivariable Cox models revealed that risk of poorer kidney outcomes was 2.77-fold (95% confidence interval, 1.16-6.63; P < .001) higher in patients with liver stiffness range indicating cirrhosis (≥11.7 kPa), compared to those without significant liver fibrosis (<7.9 kPa). These associations remained significant even after adjusting for vigorous confounders. CONCLUSIONS: Higher fibrotic burden assessed using TE was independently associated with poorer kidney outcomes in patients with HBV-related cirrhosis.

Effectiveness of a Smartphone Application for Dietary Sodium Intake Measurement.

Accurate estimation of sodium intake is a key requirement for evaluating the efficacy of interventional strategies to reduce salt intake. The effectiveness of a smartphone application in measuring dietary sodium intake was assessed. This study included 46 participants who consented to register in Noom's food-logging program. All participants were followed up for six months from the day of enrollment. The mean age of the participants was 40.2 ± 12.3 years, and 22 (48%) participants were male. The average number of times/weeks the meals were logged was 16.2 ± 10.3. At baseline, the mean 24-h urine sodium was 124.3 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 2020.9 mg/24 h and 2857.6 mg/24 h, respectively. During the second visit, the mean 24-h urine sodium was 117.4 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 1456.0 mg/24 h and 2698.3 mg/24 h, respectively. Sodium intake measured using the smartphone application positively correlated with that calculated using the 24-h urine sodium at baseline (r = 0.464; p < 0.001) and follow-up (r = 0.334; p= 0.023). Dietary sodium intake measured using a smartphone application correlated well with that estimated using 24-h urine sodium level.

Association of Plant Protein Intake With Risk of Incident CKD: A UK Biobank Study.

RATIONALE & OBJECTIVE: Data suggest that various dietary interventions slow kidney disease progression and improve clinical outcomes for those with chronic kidney disease (CKD). However, the association between plant protein intake and incident CKD has been uncertain. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 117,809 participants who completed at least 1 dietary questionnaire and had an estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2, a urinary albumin-creatinine ratio (UACR)<30mg/g, and no history of CKD. EXPOSURE: Daily plant protein intake in g/kg/day. OUTCOME: Incident CKD based on the International Classification of Diseases, 10th Revision (ICD-10) or the Office of Population Censuses and Surveys Classification of Interventions and Procedures, version 4 (OPCS-4) codes. ANALYTICAL APPROACH: A cause-specific proportional hazards analysis incorporating competing risks that treated death occurring before incident CKD as a competing event. RESULTS: During a median follow-up period of 9.9 years, incident CKD occurred in 3,745 participants (3.2%; incidence rate, 3.2 per 1,000 person-years). In a multivariable model, the adjusted hazard ratio (AHR) for the second, third, and highest quartiles of plant protein intake was 0.90 (95% CI, 0.82-0.99), 0.83 (95% CI, 0.75-0.92), and 0.82 (95% CI, 0.73-0.93), respectively, compared with the lowest quartile. Modeled as a continuous variable, the AHR per 0.1g/kg/day plant protein intake increase was 0.96 (95% CI, 0.93-0.99). This beneficial association was also consistent in secondary analyses for which CKD was defined based on codes or 2 consecutive measures of eGFR<60mL/min/1.73m2 or UACR>30mg/g. Various sensitivity analyses demonstrated consistent findings. LIMITATIONS: Potential incomplete dietary assessments; limited generalizability due to the characteristics of participants in the UK Biobank Study. CONCLUSIONS: In this large, prospective cohort study, greater dietary plant protein intake was associated with a lower risk of incident CKD. Further interventional studies demonstrating the kidney-protective benefits of plant protein intake are warranted. PLAIN-LANGUAGE SUMMARY: Plant-based diets confer various health benefits, including lowering the risk of cardiovascular disease and certain cancers. However, the relationship between plant protein intake and the risk of chronic kidney disease (CKD) remains unclear. Our study investigated the association between plant protein intake and the development of CKD. Using the UK Biobank Study data, we found that participants with a higher plant protein intake had a lower risk of developing CKD. Our finding suggests that a higher dietary intake of plant-based protein may be beneficial for kidney health and provides insight into dietary interventions to prevent CKD in primary care settings.

An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD. However, to date, there is no appropriate guidance on CKD in individuals with MAFLD. Furthermore, there has been little attention paid to the link between MAFLD and CKD in the Nephrology community. Methods and Results: Using a Delphi-based approach, a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD. Conclusions: This Delphi-based consensus statement provided guidance on the epidemiology, mechanisms, management and treatment of MAFLD and CKD, as well as the relationship between the severity of MAFLD and risk of CKD, which establish a framework for the early prevention and management of these two common and interconnected diseases.

Proteinuria Modifies the Relationship Between Urinary Sodium Excretion and Adverse Kidney Outcomes: Findings From KNOW-CKD.

Introduction: High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). Methods: In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a ≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. Results: During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P = 0.006). In patients with proteinuria of <0.5 g/d, sodium excretion was not associated with the primary outcome. However, in patients with proteinuria of ≥0.5 g/d, a 1.0 g/d increase in sodium excretion was associated with a 29% higher risk of adverse kidney outcomes. Moreover, in patients with proteinuria of ≥0.5 g/d, the hazard ratios (HRs) (95% confidence intervals[CIs]) for sodium excretion of <3.4 and ≥3.4 g/d were 2.32 (1.50-3.58) and 5.71 (3.58-9.11), respectively, compared with HRs for patients with proteinuria of <0.5 g/d and sodium excretion of <3.4 g/d. In sensitivity analysis with 2 averaged values of sodium and protein excretion at baseline and third year, the results were similar. Conclusion: Higher urinary sodium excretion was more strongly associated with an increased risk of adverse kidney outcomes in patients with higher proteinuria levels.

Comparison of decline in renal function between patients with chronic hepatitis B with or without antiviral therapy.

BACKGROUND AND AIMS: Renal function can deteriorate in patients with chronic hepatitis B (CHB). We compared the risk of renal function decline between patients with untreated and treated CHB receiving antiviral therapy. METHODS: This retrospective study included 1061 untreated CHB patients, and 366 on tenofovir alafenamide (TAF), 190 on besifovir dipivoxil maleate (BSV), and 2029 on entecavir (ETV). The primary outcome was renal function decline, a ≥ one-stage increase in chronic kidney disease for ≥3 consecutive months. RESULTS: The incidence and risk of renal function decline were significantly higher in the 1:1 propensity score-matched treated group (588 pairs) than in the untreated (2.7 per 1000 person-years [PYs] vs. 1.3 per 1000 PYs, adjusted hazard ratio [aHR] = 2.29, all p < 0.001). The matched TAF group (222 pairs) showed a similar risk for the primary outcome (aHR = 1.89, p = 0.107) despite a significantly higher incidence thereof, compared to the untreated (3.9 vs. 1.9 per 1000 PYs, p = 0.042). The matched BSV and untreated groups (107 pairs) showed no significant differences in the incidence and risk. However, ETV users (541 pairs) carried a significantly higher outcome incidence and risk than the matched untreated (3.6 vs. 1.1 per 1000 PYs, aHR = 1.05, all p < 0.001). Compared to each matched untreated group, changes in the estimated glomerular filtration rate over time were greater in the ETV group (p = 0.010), despite being similar in the TAF (p = 0.073) and BSV groups (p = 0.926). CONCLUSIONS: Compared with untreated patients, TAF or BSV users showed similar risk, whereas ETV users showed a higher risk of renal function decline.

Hepatorenal syndrome: Current concepts and future perspectives.

Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.

Association of coronary artery calcium with adverse cardiovascular outcomes and death in patients with chronic kidney disease: results from the KNOW-CKD.

BACKGROUND: In East Asian countries, patients with chronic kidney disease (CKD) have lower cardiovascular risk profiles and experience fewer cardiovascular events (CVEs) than those in Western countries. Thus the clinical predictive performance of well-known risk factors warrants further testing in this population. METHODS: The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) is a multicenter, prospective observational study. We included 1579 participants with CKD G1-G5 without kidney replacement therapy between 2011 and 2016. The main predictor was the coronary artery calcium score (CACS). The primary outcome was a composite of nonfatal CVEs or all-cause mortality. Secondary outcomes included 3-point major adverse cardiovascular events (MACEs; the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), all CVEs and all-cause mortality. RESULTS: During a median follow-up of 5.1 years, a total of 123 primary outcome events occurred (incidence rate 1.6/100 person-years). In the multivariable Cox model, a 1-standard deviation log increase in the CACS was associated with a 1.67-fold [95% confidence interval (CI), 1.37-2.04] higher risk of the primary outcome. Compared with a CACS of 0, the hazard ratio associated with a CACS >400 was 4.89 (95% CI 2.68-8.93) for the primary outcome. This association was consistent for secondary outcomes. Moreover, inclusion of the CACS led to modest improvements in prediction indices of the primary outcome compared with well-known conventional risk factors. CONCLUSIONS: In Korean patients with CKD, the CACS was independently associated with adverse cardiovascular outcomes and all-cause death. The CACS also showed modest improvements in prediction performance over conventional cardiovascular risk factors.

Risk improvement and adverse kidney outcomes in patients with chronic kidney disease: findings from KNOW-CKD.

BACKGROUND: Many trials have attempted to slow the progression of chronic kidney disease (CKD) by modifying specific risk factors, but without achieving satisfactory results. We aimed to evaluate the association between the degree of improvement in multiple risk factors and adverse kidney outcomes. METHODS: This was a prospective observational study of 839 patients with CKD G3-G4. The main predictors were the number of improved risk factors between baseline and year one as follows: a decrease in proteinuria, systolic blood pressure, phosphate, and uric acid, and an increase in hemoglobin and bicarbonate from the baseline status to out of the target range. The primary outcome was a composite one, including CKD progression (50% decline in eGFR or kidney replacement therapy) and all-cause death. RESULTS: Patients whose risk factors eventually improved had more unfavorable baseline profiles of the six considered factors. During 3097.8 person-years of follow-up (median 3.5 years per patient), the composite outcome occurred in 48.0% of patients (incidence rate, 13.0 per 100 person-years). Compared with an improvement of no risk factors, the adjusted HRs (95% CI) for improvement of 1 and ≥ 2 risk factors were 0.96 (0.76-1.22) and 0.53 (0.37-0.75), respectively. The association was not affected by diabetic status or CKD severity. Among the risk factors, proteinuria accounted for the greatest contribution to CKD progression. CONCLUSIONS: In patients with CKD G3-G4, improvement in multiple factors was associated with a decreased risk of CKD progression, suggesting the importance of multifactorial risk management.

Novel biomarkers for diabetic kidney disease.

Although diabetic kidney disease (DKD) remains one of the leading causes of reduced lifespan in patients with diabetes mellitus; its prevalence has failed to decline over the past 30 years. To identify those at high risk of developing DKD and disease progression at an early stage, extensive research has been ongoing in the search for prognostic and surrogate endpoint biomarkers for DKD. Although biomarkers are not used routinely in clinical practice or prospective clinical trials, many biomarkers have been developed to improve the early identification and prognostication of patients with DKD. Novel biomarkers that capture one specific mechanism of the DKD disease process have been developed, and studies have evaluated the prognostic value of assay-based biomarkers either in small sets or in combinations involving multiple biomarkers. More recently, several studies have assessed the prognostic value of omics- based biomarkers that include proteomics, metabolomics, and transcriptomics. This review will first describe the biomarkers used in current practice and their limitations, and then summarize the current status of novel biomarkers for DKD with respect to assay- based protein biomarkers, proteomics, metabolomics, and transcriptomics.

Similar risk of kidney function decline between tenofovir alafenamide and besifovir dipivoxil maleate in chronic hepatitis B.

BACKGROUND AND AIMS: Although tenofovir alafenamide (TAF) and besifovir dipivoxil maleate (BSV) are potent antiviral agents in the treatment of chronic hepatitis B (CHB) infection, their renal safety profiles have not been previously compared. This study compared the risk of kidney function decline among patients with treatment-naïve CHB treated with TAF or BSV. METHODS: This multicenter, retrospective, longitudinal cohort study included 556 patients with treatment-naïve CHB treated with TAF (n = 366) or BSV (n = 190) between November 2017 and August 2021. The primary outcome was chronic kidney disease (CKD) progression, defined as an increase in CKD stage by at least one stage for at least three consecutive months. RESULTS: 1:1 Propensity score matching yielded 154 patients in each treatment group. The mean estimated glomerular filtration rate (eGFR) was 100.4 vs. 100.3 ml/min/1.73 m2 in the TAF and BSV groups respectively. A total of 25 patients developed a progression in CKD stage ≥1, of which 13 and 12 patients were from the TAF and BSV treated groups respectively (3.1 vs. 3.3 per 1000 person-years; p = .751). The unadjusted hazard ratio for risk of progression in CKD stage ≥1 of the BSV group (vs. the TAF group) was 1.13 (95% confidence interval, 0.50-2.58; p = .758). This association persisted even after adjusting for potential confounders. Virological, serological and biochemical responses were also similar between the two treatment groups (all p > .05). CONCLUSIONS: TAF and BSV showed a similar risk of kidney function decline in patients with treatment-naïve CHB. Further prospective randomized studies are warranted for validation.

Exercise reduces the risk of chronic kidney disease in individuals with nonalcoholic fatty liver disease: A nationwide cohort study.

AIMS: Recent studies of individuals with nonalcoholic fatty liver disease (NAFLD) have indicated benefits of exercise in improving outcomes. We investigated whether exercise reduces the risk of chronic kidney disease (CKD) in individuals with NAFLD. METHODS: A total of 7275 participants from the Korea National Health and Nutrition Examination Survey (KNHANES) cohort, and 40,418 participants with NAFLD from the National Health Insurance Service (NHIS) cohort were included for the cross-sectional and longitudinal analyses, respectively. For the cross-sectional analysis, the primary outcome was prevalent CKD, defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. For the longitudinal analysis, the primary outcome was incident CKD, defined as the occurrence of eGFR <60 mL/min/1.73m2 or proteinuria (≥ trace) on two consecutive measurements during follow-up. RESULTS: In the KNHANES cohort, prevalent CKD was observed in 229 (6.1%), 48 (2.6%), and 36 (2.1%) participants in the 0, 1-2, and ≥ 3 exercise sessions/week groups, respectively. The likelihood of prevalent CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted OR 0.49; 95% CI, 0.33-0.71; P < 0.001). During a median follow-up of 5.0 years in the NHIS cohort, incident CKD occurred in 1,047 (9.7/1,000 person-years), 188 (7.3/1,000 person-years), and 478 (7.4/1,000 person-years) participants in the 0, 1-2, and ≥ 3 sessions/week groups, respectively. The risk of incident CKD was lowest in participants allocated to the ≥ 3 sessions/week group (adjusted HR 0.85; 95% CI, 0.76-0.95; P = 0.004). CONCLUSIONS: Exercise was significantly associated with a reduced risk of both prevalent and incident CKD in individuals with NAFLD.

Nationwide Implementation of Nonpharmaceutical Interventions During the Coronavirus Disease 2019 Pandemic Is Associated With Decreased Incidence of Pneumocystis jirovecii Pneumonia in Kidney Transplant Recipients.

This study aimed to investigate the impact of nationwide nonpharmaceutical interventions against coronavirus disease 2019 (COVID-19) on the incidence of Pneumocystis jirovecii pneumonia (PCP) in kidney transplant recipients. The monthly incidence of PCP during the COVID-19 period decreased significantly compared to that of the pre-COVID-19 period in kidney transplant recipients.

A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy.

BACKGROUND: It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. METHODS: We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20-50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. RESULTS: Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in the combination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of -4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and -5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was -0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. CONCLUSION: In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.

Preoperative Ionized Magnesium Levels and Risk of Acute Kidney Injury After Cardiac Surgery.

RATIONALE & OBJECTIVE: Although postoperative acute kidney injury (AKI) is a serious complication after cardiac surgery, preventive measures are limited. Despite the known association of preoperative low magnesium levels with cardiac surgery-related atrial fibrillation, the association between preoperative magnesium concentration and postoperative AKI has not been fully elucidated. This study evaluated the association between preoperative serum magnesium level and the development of AKI after cardiac surgery. STUDY DESIGN: Retrospective observational cohort study. SETTING & PARTICIPANTS: Patients aged≥18 years who underwent cardiac surgery at 2 South Korean tertiary hospitals between 2006 and 2020 were identified from medical records. Patients with missing information, an estimated glomerular filtration rate<15mL/min/1.73m2, receiving maintenance dialysis, or a history of AKI treated by dialysis within 1 year before surgery were excluded. EXPOSURE: Preoperative serum magnesium levels. OUTCOME: Postoperative AKI within 48 hours after surgery, defined using the Acute Kidney Injury Network (AKIN) criteria, and dialysis-treated AKI within 30 days after surgery. ANALYTICAL APPROACH: Multivariable logistic regression analysis. RESULTS: Among the 9,766 patients (median age, 64.0 years; 60.1% male), postoperative AKI and dialysis-treated AKI were observed in 40.1% and 4.3% patients, respectively. Postoperative AKI was more prevalent in patients with lower serum magnesium levels (44.9%, 41.4%, 39.4%, and 34.8% in quartiles 1-4, respectively). Multivariable logistic regression analysis revealed that the odds ratios (ORs) for postoperative AKI were progressively larger across progressively lower quartiles of serum magnesium concentration (adjusted ORs of 1.53 [95% CI, 1.33-1.76], 1.29 [95% CI, 1.12-1.48], 1.15 [95% CI, 1.01-1.31] for quartiles 1-3, respectively, relative to quartile 4, P for trend<0.001). Preoperative hypomagnesemia (serum magnesium level<1.09mg/dL) was also significantly associated with AKI (adjusted OR, 1.39 [95% CI, 1.10-1.77]) and dialysis-treated AKI (adjusted OR, 1.67 [95% CI, 1.02-2.72]). LIMITATIONS: Causality could not be evaluated in this observational study. CONCLUSIONS: Lower serum magnesium levels were associated with a higher incidence of AKI in patients undergoing cardiac surgery.

Creatinine-cystatin C ratio and mortality in cancer patients: a retrospective cohort study.

BACKGROUND: Muscle wasting is prevalent in cancer patients, and early recognition of this phenomenon is important for risk stratification. Recent studies have suggested that the creatinine-cystatin C ratio may correlate with muscle mass in several patient populations. The association between creatinine-cystatin C ratio and survival was assessed in cancer patients. METHODS: A total of 3060 patients who were evaluated for serum creatinine and cystatin C levels at the time of cancer diagnosis were included. The primary outcome was 6-month mortality. The 1-year mortality, and length of intensive care unit (ICU) and hospital stay were also evaluated. RESULTS: The mean age was 61.6 ± 13.5 years, and 1409 patients (46.0%) were female. The median creatinine and cystatin C levels were 0.9 (interquartile range [IQR], 0.6-1.3) mg/dL and 1.0 (IQR, 0.8-1.5) mg/L, respectively, with a creatinine-cystatin C ratio range of 0.12-12.54. In the Cox proportional hazards analysis, an increase in the creatinine-cystatin C ratio was associated with a significant decrease in the 6-month mortality (per 1 creatinine-cystatin C ratio, hazard ratio [HR] 0.35; 95% confidence interval [CI], 0.28-0.44). When stratified into quartiles, the risk of 6-month mortality was significantly lower in the highest quartile (HR 0.30; 95% CI, 0.24-0.37) than in the lowest quartile. Analysis of 1-year mortality outcomes revealed similar findings. These associations were independent of confounding factors. The highest quartile was also associated with shorter lengths of ICU and hospital stay (both P < 0.001). CONCLUSIONS: The creatinine-cystatin C ratio at the time of cancer diagnosis significantly associates with survival and hospitalization in cancer patients.