Subsequent Chronic Kidney Disease Research Articles

Risk factors for severe COVID-19 infection and the impact of COVID-19 infection on disease progression among patients with AAV

To identify risk factors for COVID-19 infection and investigate the impact of COVID-19 infection on chronic kidney disease (CKD) progression and vasculitis flare in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This cohort study retrospectively analyzed the prevalence and severity of COVID-19 infection in 276 patients with AAV who were followed up. Logistic regression was employed to estimate the risk of COVID-19 infection as well as CKD progression and vasculitis flare upon COVID-19 infection. During the 6-month observation period, 213 (77.2%) of 276 patients were diagnosed with COVID-19 infection. Of these 213 patients, 49 (23.0%) had a COVID-19-related inpatient admission, including 17 patients who died of COVID-19 infection. AAV patients with severe COVID-19 infection were more likely to be male (OR 1.921 [95% CI 1.020–3.619], P = 0.043), suffered from worse kidney function (serum creatinine [Scr], OR 1.901 [95% CI 1.345–2.687], P < 0.001), had higher C-reactive protein (CRP) (OR 1.054 [95% CI 1.010–1.101], P = 0.017) and less likely to have evidence of initial vaccination (OR 0.469 [95% CI 0.231–0.951], P = 0.036), and Scr and COVID-19 vaccination were proven to be significantly associated with severe COVID-19 infection even after multivariable adjustment. Severe COVID-19 infection was significantly associated with subsequent CKD progression (OR 7.929 [95% CI 2.030–30.961], P = 0.003) and vasculitis flare (OR 11.842 [95% CI 1.048–133.835], P = 0.046) among patients with AAV. AAV patients who were male, and with worse kidney function were more susceptible to severe COVID-19 infection, which subsequently increased the risk of CKD progression and vasculitis flare.

A short treatment with resveratrol after a renal ischaemia-reperfusion injury prevents maladaptive repair and long-term chronic kidney disease in rats.

Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30min (IR) or IR+RSV. The RSV treatment commenced 24h after IRI and continued for 10days. The rats were studied for either 10days or 5months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury-related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI. KEY POINTS: Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. In this study, we found that histological tubular injury persists 10days after ischaemia-reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells. Short-term RSV intervention influenced the post-ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes. Resveratrol effectively prevented AKI-to-CKD transition even 5 months after the intervention. The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI-to-CKD transition.

Advances in metabolic reprogramming of renal tubular epithelial cells in sepsis-associated acute kidney injury.

Sepsis-associated acute kidney injury presents as a critical condition characterized by prolonged hospital stays, elevated mortality rates, and an increased likelihood of transition to chronic kidney disease. Sepsis-associated acute kidney injury suppresses fatty acid oxidation and oxidative phosphorylation in the mitochondria of renal tubular epithelial cells, thus favoring a metabolic shift towards glycolysis for energy production. This shift acts as a protective mechanism for the kidneys. However, an extended reliance on glycolysis may contribute to tubular atrophy, fibrosis, and subsequent chronic kidney disease progression. Metabolic reprogramming interventions have emerged as prospective strategies to counteract sepsis-associated acute kidney injury by restoring normal metabolic function, offering potential therapeutic and preventive modalities. This review delves into the metabolic alterations of tubular epithelial cells associated with sepsis-associated acute kidney injury, stressing the importance of metabolic reprogramming for the immune response and the urgency of metabolic normalization. We present various intervention targets that could facilitate the recovery of oxidative phosphorylation-centric metabolism. These novel insights and strategies aim to transform the clinical prevention and treatment landscape of sepsis-associated acute kidney injury, with a focus on metabolic mechanisms. This investigation could provide valuable insights for clinicians aiming to enhance patient outcomes in the context of sepsis-associated acute kidney injury.

Mediation analysis of chronic kidney disease risk factors using kidney biomarkers in women living with HIV.

Novel urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in persons living with HIV. However, it is unknown whether these biomarkers provide mechanistic insight into the associations between clinical risk factors for CKD and subsequent CKD risk. Among 636 women living with HIV in the Women's Interagency HIV Study with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m 2 , we used a counterfactual approach to causal mediation analysis to evaluate the extent to which systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin a1c (Hba1c) and serum albumin associations with incident CKD were mediated by eight urine proteins. These biomarkers reflect proximal tubular reabsorptive dysfunction (α1-microglobulin [a1m], β2-microglobulin, trefoil factor 3); tubular injury (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1]); kidney repair (epidermal growth factor); tubular reserve (uromodulin); and glomerular injury (urinary albumin). Incident CKD was defined as eGFR <60 ml/min/1.73 m 2 measured at two consecutive 6-month visits with an average annual eGFR decline ≥3% per year. During a median follow-up of 7 years, 11% developed CKD. Urinary albumin and KIM-1 mediated 32% (95% CI: 13.4%, 76.6%) and 23% (6.9%, 60.7%) of the association between SBP and incident CKD, respectively; and 19% (5.1%, 42.3%) and 22% (8.1%, 45.7%) of the association between DBP and incident CKD, respectively. Urinary albumin, α1m, and IL-18 were significant mediators of the association between Hba1c and incident CKD. None of the eight biomarkers mediated the association between serum albumin and incident CKD. Among women living with HIV, several urinary biomarkers reflecting distinct dimensions of kidney health may partially explain the associations between SBP, DBP, and Hba1c and subsequent CKD risk.

Outcomes of Proton Therapy to Infradiaphragmatic Sites in Pediatric Hodgkin Lymphoma Patients

Purpose: When treating pediatric patients with radiotherapy (RT), an important area of optimization is reducing integral dose with the goal of minimizing toxicity. As a result, proton radiation (PT) is a well-established RT modality for certain clinical indications within pediatrics. However, there is limited data on outcomes of PT in pediatric patients with Hodgkin lymphoma who receive RT to infradiaphragmatic targets. We report on radiation planning details, doses achieved to organs at risk (OARs), and outcomes for this population, and additionally provide comparative dosimetric data between photon and proton plans for a patient subset. Methods: This is a single-institution retrospective study of pediatric patients with Hodgkin lymphoma who received curative intent PT to infradiaphragmatic targets between 2011-2022. Demographic and clinical factors were collected from the electronic medical record, and toxicity was reported using CTCAE version 5.0. Dosimetric and clinical factors associated with toxicity and oncologic outcomes were assessed via Cox regression, while the paired t-test or Wilcoxon signed rank sum test was used for dosimetric analyses. Photon comparison plans were generated for a subset of 10 patients who received PT to a range of infradiaphragmatic subsites, and doses to key OARs were compared across modalities via the Wilcoxon signed rank sum test. Results: Twenty-one patients comprising 22 PT courses were included. Median follow-up was 4.8 years. Mean age at the time of RT was 14.2 years (range 4-22 years) and 48% were male. Median dose was 21 Gray equivalent (GyE) over 14 fractions. 50% of patients received PT to multiple subdiaphragmatic sites, and top locations treated in single-target PT courses included spleen (32%), retroperitoneum (14%), and pelvis (3%). Most common acute grade 1 (G1) toxicities were fatigue (59%) and anorexia (36%). Rates of acute G2 and G3+ toxicity were 18% and 0%, respectively. The average maximum dose (Dmax) to the spinal cord was 15.3 Gy and bowel bag (BB) was 19.9 Gy. Multiple BB metrics were significantly different between patients who developed nausea and those who did not: V5 Gy (median 42% vs. 2%, p=.0068), V15 Gy (median 30% vs. 1%, p=.0056), V20 Gy (median 26% vs. 0%, p=.0038), mean (median 949 vs. 35 cGy, p=.0063), and Dmax (median 2295 vs. 2184 cGy, p=.0301). Rectum Dmax also significantly varied between those who did or did not develop abdominal discomfort (median 119 vs. 0 cGy, p=.0071). No other OAR metrics were significantly different based on acute toxicity. Following PT, two patients developed persistent gastrointestinal issues of unclear etiology, and one patient developed chronic kidney disease (CKD). No statistically significant differences in doses to BB (V5 Gy, V15 Gy, V20 Gy, Dmax, or mean) or kidney (mean or V5 Gy) were detected between these patients and those without chronic abdominopelvic sequelae. Kidney V18 Gy and V20 Gy for the patient with subsequent CKD was 2% and 0%, respectively. No patients developed a second malignancy after PT, and 0% experienced progression of disease (POD) after final course of PT. In our 10 patient subset with photon comparison plans, protons achieved numerically lower averages for all OARs assessed with the exception of spinal cord Dmax (889 vs. 851 cGy), although these differences were not statistically significant (all p&amp;gt;0.05). Conclusions: PT is well-tolerated when utilized to target single or multiple infradiaphragmatic locations in pediatric Hodgkin lymphoma patients and leads to excellent oncologic and toxicity outcomes with long-term follow-up. PT may confer dosimetric advantages when compared to photons, although larger patient subsets are needed.

The renal outcome post contrast exposure in patient with diabetes and SGLT2 inhibitor

Abstract Introduction Contrast-induced nephropathy (CIN) is increasingly prevalent as the increased age and comorbidities. Though most CIN can be reversible, some may progress to acute kidney disease (AKD) and subsequent chronic kidney disease (CKD)1-3. Sodium–glucose cotransporter-2 (2SGLT) inhibitor has been known to bring better renal outcomes 4-7. However, whether it affect contrast-induced kidney injury is not known well. we Purpose We aimed to investigate the renal outcomes post-contrast exposure in patients with diabetes and SGLT2 inhibitor. Materials and methods We used the Taipei Medical University Clinical Research Database (TMUCRD), composed of clinical data from 3 teaching hospitals. which stores electronic health data of 3 million patients. Patients with diabetes and exposure to contrast in CT-imaging studies or catheter-based angiography from 2016 to 2020 were included. The primary outcome was major kidney adverse event (MAKE), which included acute kidney disease (AKD), chronic kidney disease (CKD), renal replacement therapy (RRT), new onset of urinary albumin-creatinine ratio (uACR), eGFR decline ≥ 40% and all-cause mortality. We used overlap weighting to reduce confounding factors, as in observational studies. Results A total of 12,421 patients were included in this study, of them, 920 and 11501 patients were categorized to SGLT2 inhibitor users and non SGLT2 inhibitor users, respectively. SGLT2 inhibitor user had lower MAKE risk as compared with non-SGLT2 inhibitor i user (incidence rate: 37.9 v.s. 53.4 per 1,000 person months, P value = 0.0002) after exposure to contrast media. The incidence rate of AKD, CKD, and eGFR decline ≥ 40% were significantly lower in SGLT2 inhibitor user. However, there were no significantly different in the risk of RRT, new onset of uACR or all-cause mortality. Conclusions In this retrospective cohort study, we found that SGLT2 inhibitor user was associated with lower MAKE comparing with non-SGLT2 inhibitor user after contrast exposure in patients with diabetes.Outcomes of DM patients with PCI or contKaplan-Meier plot of major adverse kidne

Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.

Acute kidney injury (AKI) is one of the main conditions responsible for chronic kidney disease (CKD), including end-stage renal disease (ESRD) as a long-term complication. Besides short-term complications, such as electrolyte and acid-base disorders, fluid overload, bleeding complications or immune dysfunctions, AKI can develop chronic injuries and subsequent CKD through renal fibrosis pathways. Kidney fibrosis is a pathological process defined by excessive extracellular matrix (ECM) deposition, evidenced in chronic kidney injuries with maladaptive architecture restoration. So far, cited maladaptive kidney processes responsible for AKI to CKD transition were epithelial, endothelial, pericyte, macrophage and fibroblast transition to myofibroblasts. These are responsible for smooth muscle actin (SMA) synthesis and abnormal renal architecture. Recently, AKI progress to CKD or ESRD gained a lot of interest, with impressive progression in discovering the mechanisms involved in renal fibrosis, including cellular and molecular pathways. Risk factors mentioned in AKI progression to CKD are frequency and severity of kidney injury, chronic diseases such as uncontrolled hypertension, diabetes mellitus, obesity and unmodifiable risk factors (i.e., genetics, older age or gender). To provide a better understanding of AKI transition to CKD, we have selected relevant and updated information regarding the risk factors responsible for AKIs unfavorable long-term evolution and mechanisms incriminated in the progression to a chronic state, along with possible therapeutic approaches in preventing or delaying CKD from AKI.

A population-based longitudinal study on glycated hemoglobin levels and new-onset chronic kidney disease among non-diabetic Japanese adults

Chronic kidney disease (CKD) is a major global public health problem. Recent studies reported that diabetes and prediabetes are risk factors for developing CKD; however, the exact glycated hemoglobin (HbA1c) cut-off value for prediabetes remains controversial. In this study, we aimed to examine the relationship between HbA1c levels and subsequent CKD development in greater detail than previous studies. Longitudinal data of annual checkups of 7176 Japanese non-diabetic people (male: 40.4%) from 1998 to 2022 was analyzed. HbA1c values were categorized into < 5.0%, 5.0–5.4%, 5.5–5.9%, and 6.0–6.4%. CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. The descriptive statistics at study entry showed that higher HbA1c values were associated with male, older, overweight or obese, hypertensive, or dyslipidemic people. During a mean follow-up of 7.75 person-years, 2374 participants (male: 40.0%) developed CKD. The Weibull accelerated failure time model was selected because the proportional hazards assumption was violated. The adjusted time ratios of developing CKD for HbA1c levels of 5.5–5.9% and 6.0–6.4% compared with 5.0–5.4% were 0.97 (95% confidence interval: 0.92–1.03) and 1.01 (95% confidence interval: 0.90–1.13), respectively. There was no association between HbA1c in the prediabetic range and subsequent CKD development.

A single administration of FGF2 after renal ischemia-reperfusion injury alleviates post-injury interstitial fibrosis.

Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At an early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by ischemia-reperfusion (I/R) injury. Unilateral renal I/R with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined. Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with the I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1)-mediated inflammatory response, the inhibition of transforming growth factor beta (TGF-β1)/Smads signaling-induced epithelial-mesenchymal transition and the maintenance of peritubular capillary structure. A single dose of exogenous FGF2 administration 1 h or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI-to-CKD progression and underscored the potential of FGF-based therapy for this devastating disease.

Incidence of Chronic Kidney Disease Following Acute Coronavirus Disease 2019 Based on South Carolina Statewide Data

BackgroundCoronavirus disease 2019 (COVID-19) was associated with severe acute illness including multiple organ failure. Acute kidney injury (AKI) was a common finding, often requiring dialysis support.ObjectiveDefine the incidence of new clinically identified chronic kidney disease (CKD) among patients with COVID-19 and no pre-existing kidney disease.Design ParticipantsThe South Carolina (SC) Department of Health and Environmental Control (DHEC) COVID-19 mandatory reporting registry of SC residents testing for COVID-19 between March 2020 and October 2021 was included.Design Main MeasuresThe primary outcome was a new incidence of a CKD diagnosis (N18.x) in those without a pre-existing diagnosis of CKD during the follow-up period of March 2020 to January 14, 2022. Patients were stratified by severity of illness (hospitalized or not, intensive care unit needed or not). The new incidence of CKD diagnosis was examined using logistic regression and cox proportional hazards analyses.Key ResultsAmong patients with COVID-19 (N = 683,958) without a pre-existing CKD diagnosis, 8322 (1.2 %) were found to have a new diagnosis of CKD. The strongest predictors for subsequent CKD diagnosis were age ≥ 60 years hazard ratio (HR) 31.5 (95% confidence interval [95%CI] 25.5–38.8), and intervening (between COVID-19 and CKD diagnoses) AKI diagnosis HR 20.7 (95%CI 19.7–21.7). The presence of AKI was associated with an HR of 23.6, 95% CI 22.3–25.0, among those not hospitalized, and HR of 6.2, 95% CI 5.7–6.8 among those hospitalized, for subsequent CKD. COVID-19 was not significantly associated with subsequent CKD after accounting for the severity of illness and comorbidities.ConclusionAmong SC residents, COVID-19 was not associated with CKD independent from indicators of the severity of illness, especially AKI diagnosis. Kidney-specific follow-up testing may be reserved for those high-risk for CKD development. Further prospective registries should examine the long-term kidney consequences to confirm these findings.

Association of intraabdominal fat with the risk of incident chronic kidney disease according to body mass index among Korean adults.

The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48-14.30) and 7.50 (2.33-24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35-37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26-4.27) among subjects with normal weight and central obesity and 1.81 (1.03-3.15) among subjects with obesity and central obesity. Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.

Risk of Chronic Kidney Disease in Pneumoconiosis: Results from a Retrospective Cohort Study (2008-2019).

Pneumoconiosis has considerable comorbidities, most notably pulmonary and cardiovascular diseases. However, the relationship between pneumoconiosis and chronic kidney disease (CKD) is largely unknown. The present study aimed to use a retrospective cohort study design to further clarify the association between pneumoconiosis and subsequent CKD risk. This is a nationwide, population-based, retrospective cohort study that used data from Taiwan's National Health Insurance Database. Between 2008 and 2018, 17,952 newly diagnosed patients were included in the pneumoconiosis cohort, while 71,808 individuals without pneumoconiosis were included in the comparison cohort, with a propensity score matching for age, gender, and date of pneumoconiosis diagnosis. The development of CKD was monitored until the end of 2019. The risk was assessed using Cox proportional hazard regression models. After controlling for age, gender, and comorbidity, the overall incidence of CKD was 1.69-fold higher in the pneumoconiosis cohort than in the comparison cohort (19.71 vs. 11.76 per 1000 person-years, respectively, p &lt; 0.001), with an adjusted hazard ratio of 1.83 (95% confidence interval: 1.73-1.93). Stratified analyses by age group, gender, and presence of comorbidity revealed that the adjusted hazard ratios of CKD associated with pneumoconiosis remained significant (8/9). Furthermore, pneumoconiosis and tri-high (hypertension, hyperglycemia, and hyperlipidemia) interact positively with CKD development (p &lt; 0.001). Patients with pneumoconiosis had a significantly higher risk of developing CKD than those without. Pneumoconiosis combined with hypertension, hyperglycemia, or hyperlipidemia would increase the risk even further. More studies are required to understand the possible pathophysiological mechanisms.

Association of Chronic Kidney Disease with Prior Tinnitus: A Case-Control Study.

This population-based, case−control study aims to explore the relationship between prior tinnitus and the occurrence of chronic kidney disease (CKD) using a nationwide, population-based cohort study. We used data from the Taiwan National Health Insurance Research Database to explore the association of CKD with tinnitus. We identified 15,314 patients aged ≥40 years old with a first-time diagnosis of CKD as the cases. We used propensity-scored matching to select 45,942 controls (1:3 ratio). We performed multivariate logistic regression to estimate the odds ratio (OR) of a prior tinnitus diagnosis among the CKD group vs. the control group. Analysis showed that 770 (1.26%) out of the 61,256 sampled patients had previously diagnosed tinnitus. Chi-square testing revealed a significant difference in the rate of previously diagnosed tinnitus between cases and controls (3.86% vs. 0.93%, p < 0.001). Univariate logistic regression analysis showed an OR of prior tinnitus for cases of 10.249 (95% confidence interval (CI): (8.662~12.126)) relative to controls. In adjusted analysis, cases were more likely than controls to have a prior diagnosis of tinnitus (OR = 10.970, 95% CI = 9.255~13.004, p < 0.001) after adjusting for age, sex, monthly income, geographic location, urbanization level, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity, and autoimmune disease. Our study shows that CKD patients have a higher likelihood of having suffered from tinnitus before CKD was diagnosed, but we have no data suggesting that tinnitus is a predictor of subsequent CKD. Patients diagnosed with tinnitus may benefit from proactive measures to prevent CKD and detect it early through lifestyle modifications and regular renal function examinations, regardless of CKD-related symptoms.

Associations of New-Onset Atrial Fibrillation With Risks of Cardiovascular Disease, Chronic Kidney Disease, and Mortality Among Patients With Type 2 Diabetes.

Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7-11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59-2.16), heart failure (HR 4.40; 95% CI 3.67-5.28), CKD (HR 1.68; 95% CI 1.41-2.01), all-cause mortality (HR 2.91; 95% CI 2.53-3.34), and CVD mortality (HR 3.75; 95% CI 2.93-4.80) compared with those without incident AF. Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.

Non-Renal Risk Factors for Chronic Kidney Disease in Liver Recipients with Functionally Intact Kidneys at 1 Month.

Chronic kidney disease (CKD) is a critical complication of liver transplants, of which non-renal risk factors are not fully understood yet. This study aimed to reveal pre- and post-transplant risk factors for CKD (<60 mL/min/1.73 m2), examining liver recipients with functionally intact kidneys one month after grafting using nationwide cohort data. Baseline risk factors were analyzed with multivariable Cox regression analyses and post-transplant risk factors were investigated with the time-dependent Cox model and matched analyses of time-conditional propensity scores. Of the 2274 recipients with a one-month eGFR ≥ 60 mL/min/1.73 m2, 494 (22.3%) developed CKD during a mean follow-up of 36.6 ± 14.4 months. Age, female sex, lower body mass index, pre-transplant diabetes mellitus, and lower performance status emerged as baseline risk factors for CKD. Time-dependent Cox analyses revealed that recurrent hepatocellular carcinoma (HR = 1.93, 95% CI 1.06–3.53) and infection (HR = 1.44, 95% CI 1.12–1.60) were significant post-transplant risk factors for CKD. Patients who experienced one of those factors showed a significantly higher risk of subsequent CKD compared with the matched controls who lacked these features (p = 0.013 for recurrent hepatocellular carcinoma, and p = 0.003 for infection, respectively). This study clarifies pre- and post-transplant non-renal risk factors, which lead to renal impairment after LT independently from patients’ renal functional reserve.

Admission Lysophosphatidic Acid Is Related to Impaired Kidney Function in Acute Aortic Dissection: 2-Year Retrospective Follow-Up Study.

BackgroundDelayed treatment of acute aortic dissection (AAD)-related acute kidney injury (AKI) significantly increases the burden of chronic kidney disease (CKD) and mortality. Lysophosphatidic acid (LPA) is a shared mediator of kidney disease and AAD. Here, we evaluated the relationship between LPA and kidney injury in AAD patients.MethodsWe measured the plasma concentration of LPA in a cohort of 80 patients with AAD. Least Absolute Shrinkage and Selection Operator (LASSO) regression and Logistic regression were used to evaluate the effect and interaction of LPA on AKI. Additive generalized model and penalized spline method were used to describe the non-linear association. Multivariable analyses with the Cox proportional-hazards model were used for subgroup analysis and interaction in LPA and subsequent CKD.ResultsThe participant’s average age was 54.27 ± 11.00 years, 68.75% of them were males, and the incidence of AKI was 43.75%. Patients with AKI had higher levels of LPA on admission, and the more significant the increase, the higher the risk of AKI. There was a non-linear positive correlation between admission LPA and AKI, and the premeditated inflection point was 346.33 (μg/dL) through two-piecewise linear regression and recursive algorithm. Subgroup analysis identified a stronger association between admission LPA and AKI in the elder, female and medically treated patients. The incidence of CKD was 22.67% in the 2-year follow-up. Patients with subsequent CKD had higher LPA levels on admission in the follow-up cohort, and a similar interaction trend was also observed through Cox proportional—hazards model.ConclusionAdmission LPA levels show a non-linear positive correlation with AKI and increase the risk of subsequent CKD, which is more pronounced in elderly, female, and medically treated patients.

Insufficient early renal recovery and progression to subsequent chronic kidney disease in living kidney donors.

Background/AimsRenal recovery of a kidney donor after undergoing nephrectomy though challenging is essential. We aimed to examine the effect of estimated glomerular filtration rate (eGFR) percent change at 1-month post-donation on insufficient kidney function after kidney donation.MethodsA total of 3,952 living kidney donors who underwent donor nephrectomy from 1982 to 2019 from eight different tertiary hospitals in Korea were initially screened. Percent changes in the eGFR from baseline to 1-month post-donation were calculated. The degree of percent changes was categorized by quartile, and the 1st quartile was regarded as the group with the lowest decreased eGFR at 1-month after donation. The remaining eGFR less than 60 mL/min/1.73 m2 was the end-point. The Cox proportional hazard model was used for evaluating the impact of initial eGFR and eGFR percent change at 1-month post-donation on the condition with remaining eGFR < 60 mL/min/1.73 m2. In the multivariate analysis, we used variables with a p < 0.1 in the univariate analysis.ResultsA total of 1,585 donors were included in the analysis. During 62.2 ± 49.3 months, 13.7% of donors showed renal insufficiency. The 4th (adjusted hazard ratio [aHR], 10.41; 95% confidence interval [CI], 5.15 to 21.04) and the 3rd (aHR, 4.29; 95% CI, 2.15 to 8.56) quartiles of percent change in eGFR and the pre-donation eGFR (aHR, 0.90; 95% CI, 0.88 to 0.92) were associated with the development of renal insufficiency.ConclusionsThe impact of worse initial renal recovery on renal insufficiency was pronounced in donors with lower pre-donation eGFRs. Additionally, worse initial renal recovery of remaining kidney affected the long-term development of renal insufficiency in kidney donors.

Neonatal Acute Kidney Injury.

Acute kidney injury (AKI) is a common occurrence in the neonatal intensive care unit (NICU). In recent years, our knowledge of the incidence and impact of neonatal AKI on outcomes has expanded exponentially. Neonatal AKI has been shown to be associated with adverse outcomes including increased length of mechanical ventilation, prolonged length of stay, and rise in mortality. There has also been increasing work suggesting that neonates with AKI are at higher risk of chronic kidney disease (CKD). In the past, AKI had been defined multiple ways. The utilization of the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria as the standard definition for neonatal AKI in research and clinical care has driven the advances in our understanding of neonatal AKI over the last 10 years. This definition has allowed researchers and clinicians to better understand the incidence, risk factors, and outcomes associated with neonatal AKI across populations through a multitude of single-center studies and the seminal, multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study. As the impacts of neonatal AKI have become clear, a shift in efforts toward identifying those at highest risk, protocolizing AKI surveillance, improving prevention and diagnosis, and expanding kidney support therapy (KST) for neonates has occurred. These efforts also include improving risk stratification (identifying high risk populations, including those with nephrotoxic medication exposure) and diagnostics (novel biomarkers and diagnostic tools). Recent work has also shown that the targeted use of methylxanthines may prevent AKI in a variety of high-risk populations. One of the most exciting developments in neonatal AKI is the advancement in technology to provide KST to neonates with severe AKI. In this comprehensive review we will provide an overview of recent work and advances in the field of neonatal AKI. This will include a detailed review of (1) the definition of neonatal AKI, (2) the epidemiology, risk factors, and outcomes associated with neonatal AKI, (3) improvements in risk stratification and diagnostics, (4) mitigation and treatment, (5) advancements in the provision of KST to neonates, and (6) the incidence and risk of subsequent CKD.

Results of a community-based screening programme for chronic kidney disease and associated risk factors, (obesity, diabetes and hypertension) in a Samoan cohort

ObjectivesIn 2019, under the World Kidney Day theme of ‘Kidney health for everyone everywhere’, the National Kidney Foundation of Samoa undertook an extensive community screening campaign to detect the estimated...

Extracellular Vesicles Derived from Human Liver Stem Cells Attenuate Chronic Kidney Disease Development in an In Vivo Experimental Model of Renal Ischemia and Reperfusion Injury.

The potential therapeutic effect of extracellular vesicles (EVs) that are derived from human liver stem cells (HLSCs) has been tested in an in vivo model of renal ischemia and reperfusion injury (IRI), that induce the development of chronic kidney disease (CKD). EVs were administered intravenously immediately after the IRI and three days later, then their effect was tested at different time points to evaluate how EV-treatment might interfere with fibrosis development. In IRI-mice that were sacrificed two months after the injury, EV- treatment decreased the development of interstitial fibrosis at the histological and molecular levels. Furthermore, the expression levels of pro-inflammatory genes and of epithelial–mesenchymal transition (EMT) genes were significantly reverted by EV-treatment. In IRI-mice that were sacrificed at early time points (two and three days after the injury), functional and histological analyses showed that EV-treatment induced an amelioration of the acute kidney injury (AKI) that was induced by IRI. Interestingly, at the molecular level, a reduction of pro-fibrotic and EMT-genes in sacrificed IRI-mice was observed at days two and three after the injury. These data indicate that in renal IRI, treatment with HLSC-derived EVs improves AKI and interferes with the development of subsequent CKD by modulating the genes that are involved in fibrosis and EMT.