Introduction: Since the breakout of COVID-19 in December 2019, the virus has already affected and taken millions of lives over the past year. There is still much to learn about this disease. It has been postulated that the human kidney is a potential pathway for COVID-19 due to the presence of the ACE2 receptors found in the surfaces of kidney cells. Some studies that demonstrated acute tubular necrosis and lymphocyte infiltration among post mortem COVID-19 patients, concluding that the virus could directly damage the kidney, increasing the risk of the development of Acute Kidney Injury (AKI) among patients with COVID-19. This study investigated the incidence and severity of AKI among hospitalized COVID-19 patients and the association of the degree of AKI with regards to the severity and outcomes of COVID-19 patients. Methods: This was a single-center cross-sectional study retrospective chart review of COVID-19 patients who developed AKI. Descriptive statistics were used to summarize the general and clinical characteristics of the patients. Frequency and proportion were used for categorical variables. Shapiro-Wilk test was used to determine the normality distribution of continuous variables. Continuous quantitative data that met the normality assumption was described using mean and standard deviation, while those that did not were described using median and range. Continuous variables which are normally distributed were compared using the One-way ANOVA, while those variables that are not normally distributed were compared using the Kruskal-Wallis H test. For categorical variables, the Chi-square test was used to compare the outcomes. If the expected percentages in the cells are less than 5%, Fisher's Exact Test was used instead. Results: A total of 1441 COVID-19 in-patients from March 1, 2020 to March 1, 2021 were reviewed, 59 of whom were excluded. Among the adults with COVID-19 who developed AKI, 60% were in stage I, 10% in stage II, and 30% in stage III. The incidence of AKI among COVID-19 in-patients at Makati Medical Center was 13.10% (95% CI 11.36% - 14.99%). Among the 181 patients, 79 (43.65%, 95% CI 36.30 - 51.20) had died. The mortality rate is 22.02% for Stage I, 50% for Stage II, and 85.19% for Stage III. The median length of hospital stay was 12 days, ranging from 1 day up to 181 days. Full renal recovery on discharge was observed only in one-third of the patients. It was observed in 44.95% of those in Stage I, 27.78% of those in Stage II, and 5.56% of those in Stage III. Conclusion The study demonstrated that the incidence of AKI in hospitalized COVID-19 patients was 13.1% (95% CI 11.36% - 14.99%), which was lower than previously reported. This could be attributed to the longer study period wherein, to date, we have a better understanding of the disease and had already established a standard of care for treatment for the disease attributing to the decreased incidence of AKI among COVID-19 patients than what was initially reported. The development of AKI has a direct correlation with the degree of infection. Among patients who developed AKI, 20% required renal replacement therapy. Overall development of AKI increases the risk of mortality among hospitalized COVID-19 patients. The stage of AKI has a direct correlation with regards to mortality and has an indirect relationship with regards to renal recovery.
Acute Kidney Injury ; COVID-19 ; Renal Replacement Therapy ; Mortality

Objective: The objective of the study is to determine the association of renal impairment (AKI or CKD) with IL-6 levels on mortality, intubation, and length of hospitalization among COVID-19 positive patients. Methods: This is a retrospective cohort study involving chart review of COVID-19 patients with IL-6 levels and admitted from May 2020 to April 2021. The KDIGO criteria was used for determining renal impairment. The subsequent data processing and analysis was carried out using the statistical software, Stata 13. Results: A total of 1,120 charts were included with patients classified as having AKI (33%), CKD (14%), and no renal impairment (58%). Overall mortality and need for intubation were 27% and 30%, respectively, with average length of stay at 12 days. The IL-6 values were divided into low (0 to less than 51 pg/mL), intermediate (51 to 251 pg/mL), and high (greater than 251 pg/mL) tertiles, which showed acceptable sensitivity and specificity for mortality and need for intubation. Conclusion The presence of renal impairment (CKD or AKI) with increasing IL-6 levels had an effect of increasing risk of adverse outcomes; however, within tertile groups, the presence of renal impairment did not significantly change the risk of adverse outcomes. The tertile groups have acceptable sensitivity and specificity for clinical use.
Interleukin-6 ; Acute Kidney Injury ; Renal Insufficiency, Chronic

BACKGROUND

Pregnancy-related acute kidney injury (PR-AKI) is an underdiagnosed yet serious public health obstetric complication with high risk of maternal and fetal morbidity and mortality. Several studies have varied reports as to its incidence since there is no validated diagnostic criteria. As of date, there is a lack in published studies on the prevalence and clinical profiles of PR-AKI in the Philippines.

To determine the prevalence of PR-AKI and investigate their clinical profiles and outcomes in a tertiary hospital.

This single-center, cross-sectional, retrospective study included all admitted patients with PR-AKI from January 2019 to December 2021. Prevalence was determined and clinical data and outcomes were obtained and analyzed through review of electronic records.

A total of 49 out of 1374 patients had PR-AKI with a prevalence of 3.57% while prevalence of AKI with underlying CKD was 0.22%. The mean age was at 30 ± 6 years and most were primigravid (51.02%). Most of the patients affected had no pre-existing comorbidities (57.14%) and no known maternal comorbidities (59.18%) prior to the admission. The top causes of PR-AKI were pre-eclampsia/eclampsia (53.06%), blood loss (24.48%) and sepsis/septic shock (22.45%) mostly occurring during the third trimester (69.39%). The mean highest creatinine level was at 1.99 ± 2.01 mg/dL. Only 18.37% had oliguria while hemodialysis was done in only 6.12%. ICU admission rates were at 26.53%. Intrauterine fetal demise was seen in 12.24% of cases. PR-AKI had a 6.12% mortality rate. However, most were discharged with normal creatinine (89.8%).

R-AKI is a serious complication with significant burden even in previously healthy individuals. Prompt diagnosis is essential for a more favorable maternal and fetal outcome as well as improvement of kidney function to baseline.

BACKGROUND AND OBJECTIVES

Acute kidney injury (AKI) is a common complication of critical illness that often leads to increased mortality and morbidity. Biomarkers detect AKI earlier, providing a window of opportunity for timely intervention. Of the recent biomarkers in literature, the cell cycle arrest biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were found to be superior in predicting AKI. Our study aimed to evaluate the diagnostic performance of urine TIMP-2/IGFBP-7 in its ability to predict AKI and major adverse kidney events within 30 days (MAKE30) among high-risk patients for AKI. MAKE30 is a composite outcome comprised of all-cause mortality, use of renal replacement therapy (RRT), or persistent renal dysfunction at hospital discharge truncated at 30 days.

We conducted a prospective, cross-sectional study which included 135 adult, non-COVID ICU patients. Baseline urine TIMP-2/IGFBP-7 results were used to dichotomize the population into low risk (< 0.3 ng/mL) or high risk (≥ 0.3 ng/mL) for AKI. Participants were then observed for 30 days and monitored for MAKE30 outcomes. ROC curves were created to calculate the sensitivity, specificity, NPV, PPV, and the AUC of the 0.3 ng/mL cut-off to predict the AKI and MAKE30.

Urine TIMP-2/IGFBP-7 cutoff of 0.3 ng/mL predicted AKI with a sensitivity of 82.4%, specificity of 79.2%, PPV of 57.1%, NPV of 93% and AUC of 0.81. MAKE30 was detected with a sensitivity of 62.8%, specificity of 76.1%, PPV of 55.1%, NPV of 81.4% and AUC of 0.69. Elevated levels of urine TIMP-2/IGFBP-7 were found to be associated with AKI (p <0.01), MAKE30 (p <0.01) and all of its subcomponents. Survival or discharge after 30 days were found to be associated with lower urine TIMP-2/IGFBP-7 levels (p <0.01).

Urine TIMP-2/IGFBP-7, at its current cutoff at 0.3 ng/mL, can predict the likelihood of developing AKI and major adverse kidney events among high-risk patients for AKI. It can serve as a useful adjunct to existing methods, such as serum creatinine, in the early diagnosis and prognosis of acute kidney injury and expanding the therapeutic window to prevent disease progression and improve outcomes.

OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on renal function after laparoscopic radical nephrectomy. METHODS: We reviewed the clinical data of 282 patients with renal cell carcinoma (RCC), who underwent laparoscopic radical nephrectomy (LRN) in the Department of Urology, Third Medical Center of PLA General Hospital from November, 2020 and June, 2022.According to whether DEX was used during the operation, the patients were divided into DEX group and control group, and after propensity score matching, 99 patients were finally enrolled in each group.The incidence of acute kidney injuries were compared between the two groups.Serum creatinine (sCr) data within 3 months to 1 year after the operation were available in 51 patients, including 26 in DEX group and 25 in the control group, and the incidence of chronic kidney disease (CKD) was compared between the two groups. RESULTS: After propensity score matching and adjustment for significant covariates, there were no significant differences in postoperative levels of sCr, cystatin C (CysC), β2-microglobulin (β2-MG), hemoglobin (Hb), or C-reactive protein (CRP), extubation time, incidence of AKI, or length of hospital stay between the two groups (P>0.05).The intraoperative urine volume was significantly higher in DEX group than in the control group (P < 0.05).A significant correlation between AKI and CKD was noted in the patients (P < 0.05).The incidence of CKD did not differ significantly between the two groups (P>0.05). CONCLUSION DEX can not reduce the incidence of AKI or CKD after LRN.
Humans ; Dexmedetomidine ; Incidence ; Propensity Score ; Renal Insufficiency, Chronic/epidemiology* ; Kidney Neoplasms/surgery* ; Nephrectomy/adverse effects* ; Laparoscopy/adverse effects* ; Acute Kidney Injury/prevention & control* ; Retrospective Studies

OBJECTIVE: To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). METHODS: Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. RESULTS: Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1β (P < 0.01), enhanced renal expressions of TNF-α, IL-1β and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1β (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. CONCLUSION Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.
Animals ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; Lipopolysaccharides ; Sirtuin 1 ; Tumor Necrosis Factor-alpha ; Acute Kidney Injury ; Disease Models, Animal ; Edema

Humans ; Aged ; Acute Kidney Injury ; Risk Factors ; Creatinine

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

OBJECTIVE: This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients. METHODS: This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values. The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycin-associated acute kidney injury (VA-AKI) occurrence. RESULTS: All patients were at least 60 years old (median age = 81 years). The proportion of patients with target trough concentration achievement (≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group (75.8% vs. 42.4%, P = 0.006). Forty-five patients (68.2%) achieved clinical success, the median duration of vancomycin therapy was 10.0 days, and VA-AKI occurred in eight patients (12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration (mg/L) = 17.194 - 0.104 × creatinine clearance rate (mL/min) + 0.313 × vancomycin daily dose [(mg/(kg∙d)]. CONCLUSION A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.
Humans ; Aged ; Aged, 80 and over ; Middle Aged ; Vancomycin/therapeutic use* ; Anti-Bacterial Agents/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Acute Kidney Injury/drug therapy* ; Pneumonia/drug therapy*

Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney injury that occurs after intravascular contrast media is applied. It is the third most common cause for acute renal failure in hospitalized patients and can cause severe renal impairment and adverse cardiovascular outcomes. In severe cases, it can even lead to the death of the patient. Due to its complicated pathogenesis, the pathogenesis of CI-AKI has not yet been elucidated. Therefore, it is of great significance to further study the pathogenesis for the prevention of CI-AKI. Moreover, a good animal model of CI-AKI is an important tool for in-depth research on the pathogenesis of acute kidney injury induced by contrast agents.
Animals ; Acute Kidney Injury/chemically induced* ; Contrast Media/adverse effects* ; Models, Animal