Biomedicines

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10 pages, 1118 KiB

Open AccessArticle

Long-Term Outcome of Leptospirosis Infection with Acute Kidney Injury

by Chih-Hsiang Chang, Wei-Chiao Sun, Su-Wei Chang, Cheng-Chia Lee, Pei-Chun Fan, Huang-Yu Yang and Chih-Wei Yang

Biomedicines 2022, 10(10), 2338; https://doi.org/10.3390/biomedicines10102338 - 20 Sep 2022

Cited by 3 | Viewed by 3433

Abstract

Acute kidney injury (AKI) is associated with long-term mortality and morbidity outcomes. Severe leptospirosis usually results in AKI and multiple organ failure, but is associated with favorable short-term outcomes, if treatment is initiated early. However, information on long-term outcomes after leptospirosis-associated AKI is [...] Read more.

Acute kidney injury (AKI) is associated with long-term mortality and morbidity outcomes. Severe leptospirosis usually results in AKI and multiple organ failure, but is associated with favorable short-term outcomes, if treatment is initiated early. However, information on long-term outcomes after leptospirosis-associated AKI is limited. The effects of leptospirosis on resulting chronic kidney disease (CKD), as well as mortality, were evaluated in this study. We studied 2145 patients with leptospirosis from the National Health Insurance Research Database over an 8-year follow-up period. Patient demographics and characteristics were analyzed for AKI and dialysis. The risk factors for renal outcomes were analyzed using multivariate logistic regression. In total, 443 (20.6%) patients had AKI. Among them, 77 (3.6%) patients received replacement therapy (AKI-RRT group). Long-term mortality was higher in the AKI-RRT group than in the AKI group and non-AKI group, based on a multivariate logistic regression model. Similarly, the incidence rate of CKD was highest in the AKI-RRT group, followed by the AKI and non-AKI groups. Leptospirosis, complicated with AKI, may play a critical role in the long-term outcomes, resulting in CKD. The severity of AKI determines the incidence of CKD. Additional prospective investigations for the early detection of AKI in leptospirosis are warranted. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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16 pages, 2565 KiB

Open AccessEditor’s ChoiceArticle

Distinct Subtyping of Successful Weaning from Acute Kidney Injury Requiring Renal Replacement Therapy by Consensus Clustering in Critically Ill Patients

by Heng-Chih Pan, Chiao-Yin Sun, Thomas Tao-Min Huang, Chun-Te Huang, Chun-Hao Tsao, Chien-Heng Lai, Yung-Ming Chen and Vin-Cent Wu

Biomedicines 2022, 10(7), 1628; https://doi.org/10.3390/biomedicines10071628 - 7 Jul 2022

Cited by 4 | Viewed by 1933

Abstract

Background: Clinical decisions regarding the appropriate timing of weaning off renal replacement therapy (RRT) in critically ill patients are complex and multifactorial. The aim of the current study was to identify which critical patients with acute kidney injury (AKI) may be more likely [...] Read more.

Background: Clinical decisions regarding the appropriate timing of weaning off renal replacement therapy (RRT) in critically ill patients are complex and multifactorial. The aim of the current study was to identify which critical patients with acute kidney injury (AKI) may be more likely to be successfully weaned off RRT using consensus cluster analysis. Methods: In this study, critically ill patients who received RRT at three multicenter referral hospitals at several timepoints from August 2016 to July 2018 were enrolled. An unsupervised consensus clustering algorithm was used to identify distinct phenotypes. The outcomes of interest were the ability to wean off RTT and 90-day mortality. Results: A total of 124 patients with AKI requiring RRT (AKI-RRT) were enrolled. The 90-day mortality rate was 30.7% (38/124), and 49.2% (61/124) of the patients were successfully weaned off RRT for over 90 days. The consensus clustering algorithm identified three clusters from a total of 45 features. The three clusters had distinct features and could be separated according to the combination of urinary neutrophil gelatinase-associated lipocalin to creatinine ratio (uNGAL/Cr), Sequential Organ Failure Assessment (SOFA) score, and estimated glomerular filtration rate at the time of weaning off RRT. uNGAL/Cr (hazard ratio [HR] 2.43, 95% confidence interval [CI]: 1.36–4.33) and clustering phenotype (cluster 1 vs. 3, HR 2.7, 95% CI: 1.11–6.57; cluster 2 vs. 3, HR 44.5, 95% CI: 11.92–166.39) could predict 90-day mortality or re-dialysis. Conclusions: Almost half of the critical patients with AKI-RRT could wean off dialysis for over 90 days. Urinary NGAL/Cr and distinct clustering phenotypes could predict 90-day mortality or re-dialysis. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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13 pages, 2994 KiB

Open AccessArticle

A Single Oral Dose of Diclofenac Causes Transition of Experimental Subclinical Acute Kidney Injury to Chronic Kidney Disease

by Johanna Störmer, Wilfried Gwinner, Katja Derlin, Stephan Immenschuh, Song Rong, Mi-Sun Jang, Nelli Shushakova, Hermann Haller, Faikah Gueler and Robert Greite

Biomedicines 2022, 10(5), 1198; https://doi.org/10.3390/biomedicines10051198 - 22 May 2022

Cited by 4 | Viewed by 8980

Abstract

Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI [...] Read more.

Nephrotoxic drugs can cause acute kidney injury (AKI) and analgesic nephropathy. Diclofenac is potentially nephrotoxic and frequently prescribed for pain control. In this study, we investigated the effects of single and repetitive oral doses of diclofenac in the setting of pre-existing subclinical AKI on the further course of AKI and on long-term renal consequences. Unilateral renal ischemia–reperfusion injury (IRI) for 15 min was performed in male CD1 mice to induce subclinical AKI. Immediately after surgery, single oral doses (100 mg or 200 mg) of diclofenac were administered. In a separate experimental series, repetitive treatment with 100 mg diclofenac over three days was performed after IRI and sham surgery. Renal morphology and pro-fibrotic markers were investigated 24 h and two weeks after the single dose and three days after the repetitive dose of diclofenac treatment using histology, immunofluorescence, and qPCR. Renal function was studied in a bilateral renal IRI model. A single oral dose of 200 mg, but not 100 mg, of diclofenac after IRI aggravated acute tubular injury after 24 h and caused interstitial fibrosis and tubular atrophy two weeks later. Repetitive treatment with 100 mg diclofenac over three days aggravated renal injury and caused upregulation of the pro-fibrotic marker fibronectin in the setting of subclinical AKI, but not in sham control kidneys. In conclusion, diclofenac aggravated renal injury in pre-existing subclinical AKI in a dose and time-dependent manner and already a single dose can cause progression to chronic kidney disease (CKD) in this model. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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14 pages, 2225 KiB

Open AccessArticle

Urinary KIM-1 Correlates with the Subclinical Sequelae of Tubular Damage Persisting after the Apparent Functional Recovery from Intrinsic Acute Kidney Injury

by Cristina Cuesta, Isabel Fuentes-Calvo, Sandra M. Sancho-Martinez, Floris A. Valentijn, Annette Düwel, Omar A. Hidalgo-Thomas, Consuelo Agüeros-Blanco, Adalberto Benito-Hernández, María A. Ramos-Barron, Carlos Gómez-Alamillo, Manuel Arias, Tri Q. Nguyen, Roel Goldschmeding, Carlos Martínez-Salgado and Francisco J. López-Hernández

Biomedicines 2022, 10(5), 1106; https://doi.org/10.3390/biomedicines10051106 - 10 May 2022

Cited by 8 | Viewed by 2658

Abstract

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, [...] Read more.

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, structural sequelae pass largely unnoticed due to the absence of specific diagnostic tools. The urinary kidney injury molecule 1 (KIM-1) participates in renal tissue damage and repair and is proposed as a biomarker of early and subclinical AKI. Thus, we study in this paper the evolution of KIM-1 urinary excretion alongside renal tissue sequelae after an intrinsic AKI episode induced by cisplatin in Wistar rats. Creatinine clearance, pCr, proteinuria and the fractional excretion of Na⁺ and glucose were used to monitor renal function. Renal tissue damage was blindly scored in kidney specimens stained with hematoxylin–eosin and periodic acid–Schiff. KIM-1 urinary excretion and renal mRNA expression were also assessed. Finally, we analyzed urinary KIM-1 in patients apparently recovered from AKI. Our results show that, after the normalization of the standard markers of glomerular filtration and tubular function, the extent of persistent histological findings of tissue repair correlates with the renal expression and urinary level of KIM-1 in rats. In addition, KIM-1 is also elevated in the urine of a significant fraction of patients apparently recovered from an AKI. Besides its potential utility in the early and subclinical diagnosis of renal damage, this study suggests a new application of urinary KIM-1 in the non-invasive follow-up of renal repair after AKI. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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14 pages, 1128 KiB

Open AccessArticle

Predictors of Acute Kidney Disease Severity in Hospitalized Patients with Acute Kidney Injury

by Pai-Chin Hsu, Chih-Han Liu, Wen-Chin Lee, Chien-Hsing Wu, Chien-Te Lee, Chien-Hao Su, Yu-Chin Lily Wang, Kai-Fan Tsai and Terry Ting-Yu Chiou

Biomedicines 2022, 10(5), 1081; https://doi.org/10.3390/biomedicines10051081 - 6 May 2022

Cited by 4 | Viewed by 2401

Abstract

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them [...] Read more.

Acute kidney disease (AKD) forms part of the continuum of acute kidney injury (AKI) and worsens clinical outcomes. Currently, the predictors of AKD severity have yet to be established. We conducted a retrospective investigation involving 310 hospitalized patients with AKI and stratified them based on the AKD stages defined by the Acute Dialysis Quality Initiative criteria. Demographic, clinical, hematologic, and biochemical profiles, as well as 30-day outcomes, were compared between subgroups. In the analysis, the use of offending drugs (odds ratio, OR (95% confidence interval, CI), AKD stage 3 vs. non-AKD, 3.132 (1.304–7.526), p = 0.011, AKD stage 2 vs. non-AKD, 2.314 (1.049–5.107), p = 0.038), high AKI severity (OR (95% CI), AKD stage 3 vs. non-AKD, 6.214 (2.658–14.526), p < 0.001), and early dialysis requirement (OR (95% CI), AKD stage 3 vs. non-AKD, 3.366 (1.008–11.242), p = 0.049) were identified as independent predictors of AKD severity. Moreover, a higher AKD severity was associated with higher 30-day mortality and lower dialysis-independent survival rates. In conclusion, our study demonstrated that offending drug use, AKI severity, and early dialysis requirement were independent predictors of AKD severity, and high AKD severity had negative impact on post-AKI outcomes. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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11 pages, 1204 KiB

Open AccessArticle

Predictive Value of Urinary Aquaporin 2 for Acute Kidney Injury in Patients with Acute Decompensated Heart Failure

by Ming-Jen Chan, Yung-Chang Chen, Pei-Chun Fan, Cheng-Chia Lee, George Kou and Chih-Hsiang Chang

Biomedicines 2022, 10(3), 613; https://doi.org/10.3390/biomedicines10030613 - 6 Mar 2022

Cited by 3 | Viewed by 2206

Abstract

Acute kidney injury (AKI) is frequently encountered in people with acute decompensated heart failure (ADHF) and is associated with increased morbidity and mortality. Early detection of a urinary biomarker of kidney injury might allow a prompt diagnosis and improve outcomes. Levels of urinary [...] Read more.

Acute kidney injury (AKI) is frequently encountered in people with acute decompensated heart failure (ADHF) and is associated with increased morbidity and mortality. Early detection of a urinary biomarker of kidney injury might allow a prompt diagnosis and improve outcomes. Levels of urinary aquaporin 2 (UAQP2), which is also associated with several renal diseases, are increased with ADHF. We aimed to determine whether UAQP2 predicted AKI in patients with ADHF. We conducted a prospective observation study in the coronary care unit (CCU) in a tertiary care university hospital in Taiwan. Individuals with ADHF admitted to the CCU between November 2009 and November 2014 were enrolled, and serum and urinary samples were collected. AKI was diagnosed in 69 (36.5%) of 189 adult patients (mean age: 68 years). Area under the receiver operating characteristic curve (AUROC) of biomarkers was evaluated to evaluate the diagnostic power for AKI. Both brain natriuretic peptide and UAQP2 demonstrated acceptable AUROCs (0.759 and 0.795, respectively). A combination of the markers had an AUROC of 0.802. UAQP2 is a potential biomarker of AKI in CCU patients with ADHF. Additional research on this novel biomarker is required. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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13 pages, 3029 KiB

Open AccessArticle

Artificial Intelligence for Risk Prediction of End-Stage Renal Disease in Sepsis Survivors with Chronic Kidney Disease

by Kuo-Hua Lee, Yuan-Chia Chu, Ming-Tsun Tsai, Wei-Cheng Tseng, Yao-Ping Lin, Shuo-Ming Ou and Der-Cherng Tarng

Biomedicines 2022, 10(3), 546; https://doi.org/10.3390/biomedicines10030546 - 24 Feb 2022

Cited by 9 | Viewed by 2680

Abstract

Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. [...] Read more.

Sepsis may lead to kidney function decline in patients with chronic kidney disease (CKD), and the deleterious effect may persist in patients who survive sepsis. We used a machine learning approach to predict the risk of end-stage renal disease (ESRD) in sepsis survivors. A total of 11,661 sepsis survivors were identified from a single-center database of 112,628 CKD patients between 2010 and 2018. During a median follow-up of 3.5 years, a total of 1366 (11.7%) sepsis survivors developed ESRD after hospital discharge. We adopted the random forest, extra trees, extreme gradient boosting, light gradient boosting machine (LGBM), and gradient boosting decision tree (GBDT) algorithms to predict the risk of ESRD development among these patients. GBDT yielded the highest area under the receiver operating characteristic curve of 0.879, followed by LGBM (0.868), and extra trees (0.865). The GBDT model revealed the strong effect of estimated glomerular filtration rates <25 mL/min/1.73 m² at discharge in predicting ESRD development. In addition, hemoglobin and proteinuria were also essential predictors. Based on a large-scale dataset, we established a machine learning model computing the risk for ESRD occurrence among sepsis survivors with CKD. External validation is required to evaluate the generalizability of this model. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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12 pages, 1406 KiB

Open AccessArticle

Chemokine CCL9 Is Upregulated Early in Chronic Kidney Disease and Counteracts Kidney Inflammation and Fibrosis

by Christian Hemmers, Corinna Schulte, Julia Wollenhaupt, Dickson W. L. Wong, Eva Harlacher, Setareh Orth-Alampour, Barbara Mara Klinkhammer, Stephan H. Schirmer, Michael Böhm, Nikolaus Marx, Thimoteus Speer, Peter Boor, Joachim Jankowski and Heidi Noels

Biomedicines 2022, 10(2), 420; https://doi.org/10.3390/biomedicines10020420 - 10 Feb 2022

Cited by 4 | Viewed by 3533

Abstract

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early [...] Read more.

Inflammation and fibrosis play an important pathophysiological role in chronic kidney disease (CKD), with pro-inflammatory mediators and leukocytes promoting organ damage with subsequent fibrosis. Since chemokines are the main regulators of leukocyte chemotaxis and tissue inflammation, we performed systemic chemokine profiling in early CKD in mice. This revealed (C-C motif) ligands 6 and 9 (CCL6 and CCL9) as the most upregulated chemokines, with significantly higher levels of both chemokines in blood (CCL6: 3–4 fold; CCL9: 3–5 fold) as well as kidney as confirmed by Enzyme-linked Immunosorbent Assay (ELISA) in two additional CKD models. Chemokine treatment in a mouse model of early adenine-induced CKD almost completely abolished the CKD-induced infiltration of macrophages and myeloid cells in the kidney without impact on circulating leukocyte numbers. The other way around, especially CCL9-blockade aggravated monocyte and macrophage accumulation in kidney during CKD development, without impact on the ratio of M1-to-M2 macrophages. In parallel, CCL9-blockade raised serum creatinine and urea levels as readouts of kidney dysfunction. It also exacerbated CKD-induced expression of collagen (3.2-fold) and the pro-inflammatory chemokines CCL2 (1.8-fold) and CCL3 (2.1-fold) in kidney. Altogether, this study reveals for the first time that chemokines CCL6 and CCL9 are upregulated early in experimental CKD, with CCL9-blockade during CKD initiation enhancing kidney inflammation and fibrosis. Full article

(This article belongs to the Special Issue Acute Kidney Injury to Chronic Kidney Disease: Pathophysiology and Therapy Targets)

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