Long-term Chronic Kidney Disease Research Articles

Long-Term Kidney Outcomes after Pediatric Acute Kidney Injury.

Acute kidney injury (AKI) is common in hospitalized children. Pediatric AKI receiving acute kidney replacement therapy (KRT) is associated with long-term chronic kidney disease (CKD), hypertension, and death. We aim to determine the outcomes after AKI in children who did not receive acute KRT, since these remain uncertain. Retrospective cohort study of all hospitalized children (0-18 years) surviving AKI without acute KRT between 1996-2020 in Ontario, Canada, identified by validated diagnostic codes in provincial administrative health databases. Children with prior KRT, CKD, or AKI were excluded. Cases were matched with up to four hospitalized comparators without AKI by age, neonatal status, sex, intensive care unit admission, cardiac surgery, malignancy, hypertension, hospitalization era, and a propensity score for AKI. Patients were followed until death, provincial emigration, or censoring in March 2021. The primary outcome was long-term major adverse kidney events (MAKE-LT; a composite of all-cause mortality, long-term KRT, or incident CKD). We matched 4,173 pediatric AKI survivors with 16,337 hospitalized comparators. Baseline covariates were well-balanced following propensity score matching. During median 9.7-year follow-up, 18% of AKI survivors developed MAKE-LT vs. 5% of hospitalized comparators (hazard ratio [HR] 4.0, 95% confidence interval [CI] 3.6-4.4). AKI survivors had higher rates of long-term KRT (2% vs. <1%; HR 11.7, 95%CI 7.5-18.4), incident CKD (16% vs. 2%; HR 7.9, 95%CI 6.9-9.1), incident hypertension (17% vs. 8%; HR 2.3, 95%CI 2.1-2.6), and AKI during subsequent hospitalization (6% vs. 2%; HR 3.7, 95%CI 3.1-4.5), but no difference in all-cause mortality (3% vs. 3%; HR 0.9, 95%CI 0.7-1.1). Children surviving AKI without acute KRT were at higher long-term risk of CKD, long-term KRT, hypertension, and subsequent AKI vs. hospitalized comparators.

Podocyte involvement in the pathogenesis of preterm-related long-term chronic kidney disease.

With the continuous advancement of neonatal intensive care technology, the survival rate of preterm infants is gradually increasing. However, this improvement in survival is accompanied by long-term prognostic implications in various systems. In the field of renal diseases, current epidemiological data indicate that preterm birth is a significant risk factor for the development of long-term chronic kidney disease (CKD). This not only imposes an economic burden on patients families but also severely impacts their quality of life. Understanding the underlying mechanisms involved in this process could offer potential strategies for early prevention and management of CKD. Although the nephron number hypothesis is currently widely accepted as a mechanism, there has been limited exploration regarding podocytes - one of the most important structures within nephrons - in relation to long-term CKD associated with preterm birth. Therefore, this review aims to summarize current knowledge on how prematurity influences CKD development overall, while specifically focusing on our current understanding of podocytes in relation to prematurity.

Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). Patients with TT showed lower BMI (24 vs. 26kg/m2) and preoperative Hb (11 vs. 14g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

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.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study

ObjectiveThe Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan (FROM-J) study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease (ESKD) and CVD. This study aimed to measure health-related quality of life (HRQOL) in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured QOL scores. MethodsThe EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the FROM-J study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. ResultsThe response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880–0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.806–1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767–0.881), and the median was 0.828 (IQR, 0.755–1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811–0.943), and the median was 1.000 (IQR, 0.723–1.000). The mean QOL score in participants with 50% decline in eGFR was 0.893 (95% CI, 0.860–0.926), and the median was 0.889 (IQR, 0.825–1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere–Terpstra test for trend (P = 0.002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. ConclusionWe suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of ESKD/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future HRQOL in patients with CKD.

Pulmonary, circulatory and renal considerations in the early postoperative management of the lung transplant recipient.

Lung transplantation volumes and survival rates continue to increase worldwide. Primary graft dysfunction (PGD) and acute kidney injury (AKI) are common early postoperative complications that significantly affect short-term mortality and long-term outcomes. These conditions share overlapping risk factors and are driven, in part, by circulatory derangements. The prevalence of severe PGD is up to 20% and is the leading cause of early death. Patients with pulmonary hypertension are at a higher risk. Prevention and management are based on principles learned from acute lung injury of other causes. Targeting the lowest effective cardiac filling pressure will reduce alveolar edema formation in the setting of increased pulmonary capillary permeability. AKI is reported in up to one-half of lung transplant recipients and is strongly associated with one-year mortality as well as long-term chronic kidney disease. Optimization of renal perfusion is critical to reduce the incidence and severity of AKI. In this review, we highlight key early post-transplant pulmonary, circulatory, and renal perturbations and our center's management approach.

#5309 MODELLING LONG-TERM OUTCOMES FOR PATIENTS WITH IMMUNOGLOBULIN A NEPHROPATHY (IGAN) FROM SHORT-TERM PROTEINURIA DATA

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is rare kidney disease that leads to glomerular injury, progressive loss of kidney function and progression to kidney failure. Pre-specified interim proteinuria data from ongoing clinical trials is being used as the basis of regulatory approval of new therapies but little is known about the translation of these results to long-term patient outcomes; a topic of particular interest to heath technology assessment (HTA) groups looking to inform decisions on reimbursement before final renal outcome data are available. The objective of this study was to model long-term outcomes for patients with IgAN based on short-term proteinuria data. Method We developed a de novo model including a short-term (36-week) decision tree and a long-term Markov model to capture expected lifetime outcomes associated with treatment for IgAN. We used achievement of proteinuria &amp;lt;1 g/day as a clinically relevant treatment target. The short-term model included data on proteinuria level and distribution of chronic kidney disease (CKD) health states (CKD 1/2, 3, 4, and 5). At the end of 36 weeks of treatment, patients were categorized into groups based on their proteinuria level (&amp;lt;1g/day and ≥1 g/day) and CKD stage before transitioning to the long-term Markov model. In the long-term model, proteinuria level-based, CKD health state transition matrices derived from analysis of UK National Registry of Rare Kidney Disease (RaDaR) data, and transition matrices to dialysis and transplant derived from the US Renal Data System (USRDS) were used. Other included clinical inputs of complications and mortality were derived from extension of US Optum data analyses and literature. Health-related quality of life (HRQoL) was assessed as health state utilities and disutility associated with complications. Hypothetic scenarios of improvement in short-term proteinuria and impact on long term outcomes were tested. Model outputs included life years (LYs) and quality-adjusted life years (QALYs). Effectiveness was discounted at 3% annually. Deterministic sensitivity analysis was conducted. Results Over a lifetime, patients receiving treatment that increased the probability of achieving proteinuria &amp;lt;1 g/day by 10% in the short-term, were modelled to have gained an additional 0.388 LYs from reduced CKD/transplant/dialysis-related mortality and 0.633 QALYs from delaying CKD progression to kidney failure. As expected, results improved when the probability of achieving proteinuria &amp;lt;1 g/day increased; with a 30% increase in the probability of achieving proteinuria &amp;lt;1 g/day, LYs gained were 0.562 (Figure 1) and QALYs 0.968 (Figure 2). Results were most sensitive to time horizon and long-term extrapolation of CKD health state transition matrices. Conclusion Despite challenges inherent in the translation of surrogate endpoints to long-term outcomes, combining short-term proteinuria from clinical trials and long-term CKD data from real-world registry and claims-based data provides a solution. Based on modelling, treatments that increase the probability of achieving &amp;lt;1 g/day in the short-term, are expected to provide benefits to patients with IgAN in the long-term including less time with advanced kidney disease, less time on dialysis and avoiding the need for kidney transplant resulting in improved survival, and better quality of life. Refinement and customization of country-specific model inputs will help ensure outputs are relevant for different jurisdictions and as representative of anticipated real-world outcomes as possible.

Integrated Analysis of Blood and Urine Biomarkers to Identify Acute Kidney Injury Subphenotypes and Associations With Long-term Outcomes

Acute kidney injury (AKI) is a heterogeneous clinical syndrome with varying causes, pathophysiology, and outcomes. We incorporated plasma and urine biomarker measurements to identify AKI subgroups (subphenotypes) more tightly linked to underlying pathophysiology and long-term clinical outcomes. Multicenter cohort study. 769 hospitalized adults with AKI matched with 769 without AKI, enrolled from December 2009 to February 2015 in the ASSESS-AKI Study. 29 clinical, plasma, and urinary biomarker parameters used to identify AKI subphenotypes. Composite of major adverse kidney events (MAKE) with a median follow-up period of 4.7 years. Latent class analysis (LCA) and k-means clustering were applied to 29 clinical, plasma, and urinary biomarker parameters. Associations between AKI subphenotypes and MAKE were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Among 769 AKI patients both LCA and k-means identified 2 distinct AKI subphenotypes (classes 1 and 2). The long-term risk for MAKE was higher with class 2 (adjusted HR, 1.41 [95% CI, 1.08-1.84]; P=0.01) compared with class 1, adjusting for demographics, hospital level factors, and KDIGO stage of AKI. The higher risk of MAKE among class 2 was explained by a higher risk of long-term chronic kidney disease progression and dialysis. The top variables that were different between classes 1 and 2 included plasma and urinary biomarkers of inflammation and epithelial cell injury; serum creatinine ranked 20th out of the 29 variables for differentiating classes. A replication cohort with simultaneously collected blood and urine sampling in hospitalized adults with AKI and long-term outcomes was unavailable. We identify 2 molecularly distinct AKI subphenotypes with differing risk of long-term outcomes, independent of the current criteria to risk stratify AKI. Future identification of AKI subphenotypes may facilitate linking therapies to underlying pathophysiology to prevent long-term sequalae after AKI. Acute kidney injury (AKI) occurs commonly in hospitalized patients and is associated with high morbidity and mortality. The AKI definition lumps many different types of AKI together, but subgroups of AKI may be more tightly linked to the underlying biology and clinical outcomes. We used 29 different clinical, blood, and urinary biomarkers and applied 2 different statistical algorithms to identify AKI subtypes and their association with long-term outcomes. Both clustering algorithms identified 2 AKI subtypes with different risk of chronic kidney disease, independent of the serum creatinine concentrations (the current gold standard to determine severity of AKI). Identification of AKI subtypes may facilitate linking therapies to underlying biology to prevent long-term consequences after AKI.

MP58-16 SIGNIFICANCE OF GLUCOSE CONTROL FOR PERIOPERATIVE AND LONG-TERM RENAL FUNCTIONS AFTER NEPHRON-SPARING SURGERY FOR RENAL CANCER IN PATIENTS WITH DIABETES

You have accessJournal of UrologyCME1 Apr 2023MP58-16 SIGNIFICANCE OF GLUCOSE CONTROL FOR PERIOPERATIVE AND LONG-TERM RENAL FUNCTIONS AFTER NEPHRON-SPARING SURGERY FOR RENAL CANCER IN PATIENTS WITH DIABETES Do Gyeong Lim, Jeong Hoon Oh, Jiwon Ryu, Seong Hyeon Yu, Ho Seok Chung, Kyung Jin Oh, Sun-Ouck Kim, Seung Il Jung, Taek Won Kang, Dong Deuk Kwon, Kwangsung Park, and Eu Chang Hwang Do Gyeong LimDo Gyeong Lim More articles by this author , Jeong Hoon OhJeong Hoon Oh More articles by this author , Jiwon RyuJiwon Ryu More articles by this author , Seong Hyeon YuSeong Hyeon Yu More articles by this author , Ho Seok ChungHo Seok Chung More articles by this author , Kyung Jin OhKyung Jin Oh More articles by this author , Sun-Ouck KimSun-Ouck Kim More articles by this author , Seung Il JungSeung Il Jung More articles by this author , Taek Won KangTaek Won Kang More articles by this author , Dong Deuk KwonDong Deuk Kwon More articles by this author , Kwangsung ParkKwangsung Park More articles by this author , and Eu Chang HwangEu Chang Hwang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003311.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aimed to evaluate the predictive factors for perioperative and long-term renal functions after nephron-sparing surgery (NSS). METHODS: The clinical records of 379 patients who underwent NSS for a single renal tumor with a normal contralateral kidney between 2009 and 2016 were retrospectively analyzed. After surgery, the occurrence of acute kidney injury (AKI) within 7 days and the progression of chronic kidney disease (CKD) 5 years later were assessed using serum creatinine (S-Cr) levels. Perioperative AKI was defined as an increase in the S-Cr level by ≥ 0.3 mg/dL or 1.5–1.9 times the baseline value. CKD was defined as the estimated glomerular filtration rate (eGFR) decreasing from > 60 mL/min/1.73 m2 to <60 mL/min/1.73 m2. RESULTS: Changes in the eGFR were assessed during 5 years after surgery. Among 379 patients, 81 (21.4%) patients presented diabetes mellitus (DM), and 30 (7.92%) experienced uncontrolled DM. The AKI occurrence and CKD progression were observed in 50 (13.2%) patients and 79 (20.8%) patients, respectively. Multivariate analyses revealed that female gender (odds ratio [OR] = 0.39, 95% confidence interval [CI]: 0.16–0.91, p=0.029), uncontrolled DM (OR=2.63, 95% CI: 1.05–6.60, p=0.039), and intermediate NePhRO score (OR=2.02, 95% CI: 1.07–3.80, p=0.03) were associated with perioperative AKI. In addition, old age (OR=1.14, 95% CI: 1.10–1.18, p<0.001) and uncontrolled DM (OR=4.57, 95% CI: 1.84–11.4, p=0.001) were associated with long-term CKD progression. CONCLUSIONS: Uncontrolled DM is the only predictive factor for perioperative and long-term renal functions after nephron-sparing surgery. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e802 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Do Gyeong Lim More articles by this author Jeong Hoon Oh More articles by this author Jiwon Ryu More articles by this author Seong Hyeon Yu More articles by this author Ho Seok Chung More articles by this author Kyung Jin Oh More articles by this author Sun-Ouck Kim More articles by this author Seung Il Jung More articles by this author Taek Won Kang More articles by this author Dong Deuk Kwon More articles by this author Kwangsung Park More articles by this author Eu Chang Hwang More articles by this author Expand All Advertisement PDF downloadLoading ...

Significance of Glucose Control for Perioperative and Long-Term Renal Functions after Nephron-sparing Surgery for Renal Cancer in Patients with Diabetes.

This study aimed to evaluate the predictive factors for perioperative and long-term renal functions after nephron-sparing surgery (NSS). The clinical records of 379 patients who underwent NSS for a single renal tumor with a normal contralateral kidney between 2009 and 2016 were retrospectively analyzed. After surgery, the occurrence of acute kidney injury (AKI) within 7 days and the progression of chronic kidney disease (CKD) 5 years later were assessed using serum creatinine (S-Cr) levels. Perioperative AKI was defined as an increase in the S-Cr level by ≥ 0.3 mg/dL or 1.5-1.9 times the baseline value. CKD was defined as the estimated glomerular filtration rate (eGFR) decreasing from > 60 mL/min/1.73 m2 to < 60 mL/min/1.73 m2. Changes in the eGFR were assessed during 5 years after surgery. Among 379 patients, 81 (21.4%) patients presented diabetes mellitus (DM), and 30 (7.92%) experienced uncontrolled DM. The AKI occurrence and CKD progression were observed in 50 (13.2%) patients and 79 (20.8%) patients, respectively. Multivariable analyses revealed that female gender (95% confidence interval [CI]: 0.16-0.91, odds ratio [OR] = 0.39, P = 0.029), uncontrolled DM (95% CI: 1.05-6.60, OR = 2.63, P = 0.039), and intermediate NePhRO score (95% CI: 1.07-3.80, OR = 2.02, P = 0.03) were associated with perioperative AKI. In addition, old age (95% CI: 1.10-1.18, OR = 1.14, P < 0.001) and uncontrolled DM (95% CI: 1.84-11.4, OR = 4.57, P = 0.001) were associated with long-term CKD progression. Uncontrolled DM is the only predictive factor for perioperative and long-term renal functions after nephron-sparing surgery.

Monks: A Population at Risk for Liver Fluke and Skin-Penetrating Helminths.

Monks cannot cook received raw meat dishes and should walk barefoot while working. This population lacks both a survey of parasitic infection and a proper prevention and control policy. Five hundred and fourteen monks from the Ubolratana, Ban Haet, and Ban Phai Districts of Kh on Kaen Province were enrolled in this study. A stool container and questionnaire were collected from each study participant. Stool samples were processed by formalin ethyl acetate concentration and agar plate culture techniques. We then analyzed the results and risk factors to demonstrate associations. The prevalence of overall parasites, liver flukes, and skin-penetrating helminths were 28.8%, 11.1%, and 19.3%, respectively. Raw fish dish offerings were associated with opisthorchiasis (ORcrude 3.32; 95% CI 1.53-7.20). The risk factors for skin-penetrating helminths were older age (ORcrude 5.02; 95% CI 2.2-11.17), being a long-term ordinate (ORcrude 3.28; 95% CI 1.15-9.34), smoking (ORcrude 2.03; 95% CI 1.23-3.36), and chronic kidney disease with other underlying disease (ORcrude 20.7; 95% CI 2.54-190.1). The protective factors for skin-penetrating helminths were secular education above primary education (ORcrude 0.41; 95% CI 0.25-0.65) and having received health education about parasitic infection (ORcrude 0.47; 95% CI 0.28-0.80). Wearing shoes at times other than alms work does not show a protective effect against skin-penetrating helminths (ORcrude 0.86; 95% CI 0.51-1.46). These findings support the recommendation for a strict Rule of Discipline regarding raw meat ingestion and allowing shoes to be worn for protection against skin-penetrating helminths in high-risk situations.

Biomarkers of eGFR decline after cardiac surgery in children: findings from the ASSESS-AKI study.

Children who require surgery for congenital heart disease have increased risk for long-term chronic kidney disease (CKD). Clinical factors as well as urine biomarkers of tubular health and injury may help improve the prognostication of estimated glomerular filtration rate (eGFR) decline. We enrolled children from 1month to 18years old undergoing cardiac surgery in the ASSESS-AKI cohort. We used mixed-effect models to assess the association between urinary biomarkers (log2-transformed uromodulin, NGAL, KIM-1, IL-18, L-FABP) measured 3months after cardiac surgery and cyanotic heart disease with the rate of eGFR decline at annual in-person visits over 4years. Of the 117 children enrolled, 30 (24%) had cyanotic heart disease. During 48months of follow-up, the median eGFR in the subgroup of children with cyanotic heart disease was lower at all study visits as compared with children with acyanotic heart disease (p = 0.01). In the overall cohort, lower levels of both urine uromodulin and IL-18 after discharge were associated with eGFR decline. After adjustment for age, RACHS-1 surgical complexity score, proteinuria, and eGFR at the 3-month study visit, lower concentrations of urine uromodulin and IL-18 were associated with a monthly decline in eGFR (uromodulin β = 0.04 (95% CI: 0.00-0.09; p = 0.07) IL-18 β = 0.07 (95% CI: 0.01-0.13; p = 0.04), ml/min/1.73 m2 per month). At 3months after cardiac surgery, children with lower urine uromodulin and IL-18 concentrations experienced a significantly faster decline in eGFR. Children with cyanotic heart disease had a lower median eGFR at all time points but did not experience faster eGFR decline. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Bone marrow mesenchymal stem cells inhibit ferroptosis via regulating the Nrf2-keap1/p53 pathway to ameliorate chronic kidney disease injury in the rats

Purpose Although bone marrow mesenchymal stem cells (BMMSCs) have been reported to exhibit a protective effect on animal models of chronic kidney disease (CKD), the exact mechanisms involved require further investigation. This study aims to investigate the underlying molecular mechanisms of BMMSCs in inhibiting ferroptosis and preventing an Adriamycin (ADR)-induced CKD injury. Methods A rat model of long-term CKD induced through the injection of ADR administered twice weekly via the tail vein was used in this study. After BMMSCs were systemically administered through the renal artery, pathological staining, western blotting, ELISA, and transmission electron microscopy were used to analyze ferroptosis. Results Analyses of renal function and histopathological findings indicated that ADR-mediated renal dysfunction improved in response to the BMMSC treatment, which was also sufficient to mediate the partial reversal of renal injury and mitochondrial pathological changes. BMMSCs decreased the ferrous iron (Fe2+) and reactive oxygen species and elevated glutathione (GSH) and GSH peroxidase 4. Moreover, the BMMSC treatment activated the expression of ferroptosis-related regulator NF-E2-related factor 2 (Nrf2) and inhibited Keap1 and p53 in CKD rat kidney tissues. Conclusions BMMSCs alleviate CKD, possibly resulting from the inhibition of kidney ferroptosis by regulating the Nrf2–Keap1/p53 pathway.

Are patients with Covid-19 at risk of long-term chronic kidney disease?

The relationship between Coronavirus Disease 2019 (COVID-19) and acute kidney injury (AKI) is well-established. However, a comprehensive evaluation of kidney outcomes in the long-term course of COVID-19 is not yet been performed. The aim of this study is to investigate whether chronic kidney disease (CKD) develops within six months after hospital discharge in COVID-19 patients who did not have kidney damage at the time of admission to the hospital. This single-center retrospective study investigated a total of 1008 participants selected from 7500 COVID-19 patients with real-time reverse transcription-polymerase chain reaction (RT-PCR) positivity. All patients had mild/moderate or severe COVID-19. Patients were randomly selected from inpatient and outpatient settings. Critical COVID-19 patients were not included. The mean age of the patients was 56.57 ± 16.30 years, and 69.9% of them were male. The comorbidity percentages of the participants were as follows; 19.5% coronary artery disease (CAD), 28.6% diabetes mellitus (DM), 36.2% hypertension (HT), 3.1% cerebrovascular obstruction (CVO), 1.7% malignancy, 2.6% chronic obstructive pulmonary disease (COPD), 9.4% asthma, % 1.7 dementia, 9.9% hyperlipidaemia, and 1.7% hepatitis B virus (HBV). Kidney function tests of these patients at first admission and 6 months later were compared to reveal the relationship between COVID-19 and CKD. Serum glucose, sodium estimated glomerular filtration rate (eGFR), and uric acid levels were found to be high in the post-COVID-19 period (P = 0.001). However, there were a decrease in serum albumin, potassium, alanine aminotransferase (ALT), C-reactive protein (CRP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) levels (P = 0.001). The difference between the first measurement of serum urea and creatinine (Cr) levels and the measurement 6 months later was not statistically significant (P = 0.102 and P = 0.300, respectively). Those who survived the mild/moderate and severe clinical manifestations of COVID-19 did not exhibit any risk of kidney outcomes after the acute phase of the disease, suggesting that the kidney can protect itself over a long period of time.

Comparison between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate in the Follow-Up of Patients Recovering from a Stage-3 AKI in ICU.

Acute kidney injury (AKI) in critically ill patients is associated with a significant increase in mortality as well as long-term renal dysfunction and chronic kidney disease (CKD). Serum creatinine (SCr), the most widely used biomarker to evaluate kidney function, does not always accurately predict the glomerular filtration rate (GFR), since it is affected by some non-GFR determinants such as muscle mass and recent meat ingestion. Researchers and clinicians have gained interest in cystatin C (CysC), another biomarker of kidney function. The study objective was to compare GFR estimation using SCr and CysC in detecting CKD over a 1-year follow-up after an AKI stage-3 event in the ICU, as well as to analyze the association between eGFR (using SCr and CysC) and mortality after the AKI event. This prospective observational study used the medical records of ICU patients diagnosed with AKI stage 3. SCr and CysC were measured twice during the ICU stay and four times following diagnosis of AKI. The eGFR was calculated using the EKFC equation for SCr and FAS equation for CysC in order to check the prevalence of CKD (defined as eGFR &lt; 60 mL/min/1.73 m2). The study enrolled 101 patients, 36.6% of whom were female, with a median age of 74 years (30-92), and a median length of stay of 14.5 days in intensive care. A significant difference was observed in the estimation of GFR when comparing formulas based on SCrand CysC, resulting in large differences in the prediction of CKD. Three months after the AKI event, eGFRCysC &lt; 25 mL/min/1.73 m2 was a predictive factor of mortality later on; however, this was not the case for eGFRSCr. The incidence of CKD was highly discrepant with eGFRCysC versus eGFRSCr during the follow-up period. CysC detects more CKD events compared to SCr in the follow-up phase and eGFRCysC is a predictor for mortality in follow-up but not eGFRSCr. Determining the proper marker to estimate GFR in the post-ICU period in AKI stage-3 populations needs further study to improve risk stratification.

Predictive factors for severe long-term chronic kidney disease after acute kidney injury requiring renal replacement therapy in critically ill patients: an ancillary study of the ELVIS randomized controlled trial

BackgroundAcute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown.MethodsWe performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD.ResultsOf the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02–1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77–0.93] per point).ConclusionSevere long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT.Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

Risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people: a retrospective cohort study.

ABSTRACTBACKGROUND:Advanced age, multiple chronic diseases and frailty have been correlated with worse prognosis among coronavirus disease 2019 (COVID-19) inpatients.OBJECTIVE:To investigate potential risk factors for hospitalization and death due to COVID-19 among frail community-dwelling elderly people.DESIGN AND SETTING:Retrospective cohort study of patients followed up at a geriatric outpatient clinic in Belo Horizonte, Minas Gerais, Brazil.METHODS:The associations of demographic characteristics (age and sex) and clinical characteristics (frailty, multimorbidity, number of medications with long-term use, obesity, smoking, diabetes mellitus, pulmonary diseases, cardiovascular diseases, cerebrovascular disease, and chronic kidney disease) with the risk of hospitalization and death due to COVID-19 were explored using a multivariable logistic regression model.RESULTS:5,295 patients (mean age 78.6 ± 9.4 years; 72.6% females) were included. After adjustments, the number of medications with long-term use was found to increase the odds of hospitalization due to COVID-19 (odds ratio, OR: 1.13; 95% confidence interval, CI: 1.06-1.22). Frailty, multimorbidity and diabetes mellitus also increased the odds of hospitalization (OR: 1.06, 95% CI: 1.02-1.09; OR: 1.17, 95% CI: 1.09-1.26; and OR: 2.27, 95% CI: 1.45-3.54, respectively) and the odds of death due to COVID-19 (OR: 1.07, 95% CI: 1.00-1.14; OR: 1.16, 95% CI: 1.03-1.32; and OR: 2.69, 95% CI: 1.79-6.14, respectively).CONCLUSIONS:Multimorbidity, frailty and diabetes mellitus increased the odds of hospitalization and death due to COVID-19 and the number of medications with long-term use increased the odds of hospitalization due to COVID-19 among frail community-dwelling elderly people.

Acute Kidney Injury During Pregnancy and Puerperium

Background and Aim: Acute kidney injury (AKI) is a serious complication in perilous patients substantially related to long-term chronic kidney disease (CKD) with increased morbidity, hospital duration, and mortality. AKI during pregnancy is a life-threatening disease related to maternal and fetal loss contributing to 30% to 60% of mortality. Though a rare cases of AKI during pregnancy has been reported in previous studies. But the present study aimed to assess the acute kidney injury during pregnancy and puerperium. Methodology: This cross-sectional study was conducted on 205 pregnant or puerperium women with acute kidney injury or acute renal failure in the Department of Gynaecology and Obstetrics and Nephrology, Liaquat National Hospital, Karachi from January 2019 to December 2021. All the pregnant women of age 22 to 40 years with no prior co-morbidities were enrolled in this study. Patients with history of autoimmune disease, chronic kidney disease before pregnancy, higher level of serum creatinine, hypertension before gestation and renal stone diseases, renal scarring on ultrasonography or small size of the kidneys were all excluded. An informed consent was taken from all the patients. Patient’s detailed history, laboratory investigations, demographic details, and clinical presentation were recorded. Laboratory examination involve CBC and renal function tests. Each patient had a thorough obstetric examination. Hemodialysis was performed as per standard indications. Acute kidney injury was assessed. SPSS version 25 was used for data analysis. Results: The incidence of acute kidney injury in pregnant and puerperium women was 21.5% (n=44). The overall mean age was 31.42 ± 4.35 years. Mean parity was 3.2. During pregnancy, the most prevalent cause of acute kidney injury was pre-eclampsia with incidence rate of 28 (63.6%) followed by postpartum hemorrhage in 8 (18.2%). About 6 (13.6%) patients had regain renal function and discharged from the hospital. Maternal mortality was found in 2 (4.5%) cases. Of the remaining 161 pregnant women without AKI cases, the prevalence of postpartum hemorrhage, HELLP syndrome, pre-eclampsia/eclampsia, and pregnant fatty liver were 58 (36.02%), 17 (10.6%), 66 (41%), and 20 (12.4%) respectively. Apart from hemorrhagic shock and amniotic fluid embolism, maternal outcomes was good. No significant association was found between acute kidney injury and outcomes with 5% level of significance. Conclusion: The present study found a higher prevalence of acute kidney injury in pregnant women. Pre-eclampsia and postpartum hemorrhage was the prevalent causes for AKI in pregnant women. Postpartum hemorrhage and amniotic fluid embolism were the major causes for mortality of pregnant women with AKI. The mortality of pregnant women with AKI is mostly caused by postpartum hemorrhage and pre-eclampsia. Poor outcome might be predicted by renal therapy need in acute kidney injury. Further studies is required to be conducted in order to improve pregnancy associated AKI outcomes. Keywords: Acute kidney Injury, Pregnant women, Puerperium

Urine podocyte mRNA loss in preterm infants and related perinatal risk factors

BackgroundPreterm birth has been identified as a risk factor for development of long-term chronic kidney disease. Podocyte loss has been reported to contribute to this process in preterm animal models. However, details about podocyte loss in preterm infants and related perinatal risk factors have not been well clarified.MethodsForty full-term infants and 106 preterm infants were enrolled. Urine samples were collected from full-term infants within 4–7 days of birth and preterm infants at 37–40 weeks of corrected age. Levels of urine podocin mRNA, urine protein (UP), and urine microalbumin (UMA) were measured, and the relationship between these markers was evaluated. Clinical information in these infants was collected, and potential correlates that may lead to increased podocyte loss during the perinatal period were identified using linear regression analysis.ResultsUrine podocyte loss indicated by the urine podocin mRNA to creatinine ratio (UpodCR) was higher in preterm infants than in full-term infants. UpodCR was correlated with the levels of UP and UMA. Multiple linear regression analysis also showed that lower gestational age (GA) at birth and small for gestational age (SGA) were high risk factors for urine podocyte loss.ConclusionsIncreasing urine podocyte loss was identified in preterm infants. Moreover, perinatal factors were associated with podocyte loss and may be a potential direction for comprehensive research and intervention in this field.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

MO442: COVID-19 Disease Severity and Risk of 12-Month CKD Progression

Abstract BACKGROUND AND AIMS Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been in our daily practice for almost 2 years now. Since the beginning of the pandemic, we have aimed to study its most immediate effects on patients to find the best line of treatment or, at least, mitigate its worst outcomes. Nevertheless, we also know some long-term health consequences such as fatigue, sleep difficulties, headache, among others, but its long-term kidney effects are not entirely clear yet. The aim of this study was to describe if coronavirus disease's (COVID-19) severity increases the risk of chronic kidney disease (CKD) progression after a previous hospitalization and observe if there are any additional risk factors that could help us predict this outcome. METHOD In this study, a sample of consecutive patients who required admission due to COVID-19 during the first wave of the pandemic (from March to May of 2020) was recruited. Patients were followed for 12 months since initial admission. The composite outcome of the study included either death or CKD progression. CKD progression was defined as incremental progression to a higher KDIGO CKD stage compared to baseline pre COVID-19 renal function [(in mL/min/1.73 m2): estimated glomerular filtration rate (eGFR) ≥60; stage 3a: 45–59; stage 3b: 30–44; stage 4: 15–29; stage 5: &amp;lt;15], or dialysis initiation. Cardiovascular disease was defined as a history of myocardial infarction, stroke, or peripheral vascular disease. Chronic lung diseases included asthma, chronic obstructive pulmonary disease and chronic bronchitis. RESULTS The sample was composed of 93 patients, of which 14 (15.1%) died during follow-up. Of those alive 12 months after initial admission, 17 (21.5%) suffered CKD progression. No patient required renal replacement therapy. Patients that suffered the composite outcome presented a higher prevalence of cancer, tended to be slightly older and suffered from additional comorbidities more frequently (Table). In multivariate logistic regression analysis, previous history of CKD [odds ratio (OR): 1.066 (0.433–2.624); P = 0.889], severe or critical COVID-19 on admission [OR: 0.657 (0.24–1.8); P =0.414] or ICU admission [OR: 0.986 (0.082–11.898); P = 0.991] failed to predict the composite outcome. CONCLUSION Our main hypothesis was that COVID-19 sequelae should be due to an exaggerated activation of the immune system against the virus. Thus, patients that suffered severe COVID-19 should be expected to develop more long-term health consequences of the infection when compared with those with milder disease. However, we failed to prove any link between COVID-19 severity and long-term CKD progression. History of CKD or ICU admission was also unable to predict the composite outcome. Previous studies have described a relationship between COVID-19 severity and adverse renal outcomes, a relationship that we failed to observe. These discrepancies could be due to the small sample size of our study and the different definition of CKD progression applied. In addition, age could act as a potential modifier of CKD progression after admission due to COVID. More studies are required to further clarify the mechanisms and long-term renal consequences of COVID-19 and define potential lines of treatment.