Onset Of Kidney Injury Research Articles

Unveiling the antiurolithiatic potentiality of two benzene sulfonamide derivatives against ethylene glycol-induced renal calculi

ObjectiveOxidative stress and inflammation play crucial roles in the onset of kidney injury and crystal formation caused by hyperoxaluria. Indapamide is a potent medication for treating renal calculi, but it has severe side effects such as hypokalemia, hypercalcemia, and hyperuricemia. Therefore, it is advisable to explore alternative treatments that do not have these side effects. The study aimed to reveal the antiurolithiatic potential of two benzene sulfonamide derivatives (SBCl and SBF; A and B, respectively) against ethylene glycol-induced kidney stones. MethodsThe rats were divided into two main groups: the first group consisted of 20 rats with induced kidney stones, and the second group included 15 control rats. This division enabled a comparative analysis between rats with kidney stones and those without, offering insights into the effects of kidney stone induction on various physiological parameters and biochemical markers. The effectiveness of benzene sulfonamide derivatives (compounds A and B) was assessed in rats with induced kidney stones. The treatment was given orally by gavage for 21 days, administered every 48h after inducing kidney stones with 0.12ml of 5% ethylene glycol (EG). ResultsThe influence of compounds A and B on electrolytes, biochemical, antioxidant, and inflammatory reactions in induced kidneys underscores their potential therapeutic advantages in alleviating the advancement of kidney stone disease and related complications. ConclusionBoth compounds were found to possess equal effectiveness in inhibiting the complications of stone formation. However, SBCl-EG showed superior antioxidant and inflammatory parameters effects compared to SBF-EG. Our study's findings underscore the potential benefits of derivatives in treating nephrolithiasis and related oxidative disorders, highlighting their superior effects on antioxidant and inflammatory responses compared to standard treatments.

Clinical and pathological features of omicron variant of SARS-CoV-2-associated kidney injury.

Kidney injury is common in patients with Coronavirus Disease-19 (COVID-19), which is related to poor prognosis. We aim to summarize the clinical features, athological types, and prognosis of COVID-19 associated kidney injury caused by the Omicron strain. In this study, 46 patients with Omicron-associated kidney injury were included, 38 of whom performed renal biopsy. Patients were divided into twogroups: group A for patients with onset of kidney injury after SARS-CoV-2 infection; group B for patients with pre-existing kidney disease who experienced aggravation of renal insufficiency after SARS-CoV-2 infection. The clinical, pathological, and prognostic characteristics of the patients were observed. Acute kidney injury (AKI) (35%) was the mostcommon clinical manifestation in group A. Patients in group B mainly presented with chronickidney disease(CKD)(55%)and nephroticsyndrome (NS)(40%). The pathological type was mainly IgA nephropathy (IgAN) (39% in group A and 45% in group B). Among all of them, one case presenting with thrombotic microangiopathyhad worse kidney function at biopsy time. Mean serum C3 levels were 1.2 ± 0.5 and 1.0 ± 0.2 g/L in group A and group B, respectively. In renal tissues, C3 deposits were observed in 71.1% of patients. 11.8% (n = 2) patients experienced deterioration of renal function after treatment, but no patients developed to end-stage renal disease. In our single-center study in China, the main clinical manifestations were AKI, CKD, and NS, while the main pathological type was IgAN. Compared with previous strains of SARS-CoV-2, patients with the Omicron infection had a favorable prognosis.

Machine Learning Predicts Acute Kidney Injury in Hospitalized Patients with Sickle Cell Disease

Introduction Acute kidney injury (AKI) in hospitalized patients is associated with a high morbidity and mortality. Individuals with sickle cell disease (SCD) frequently experience organ dysfunction, including AKI, during hospitalization for episodes of vaso-occlusive crisis (VOC). AKI can lead to progressive kidney disease and chronic kidney disease (CKD), which is associated with further increased morbidity and mortality. Identifying AKI early during hospitalizations can lessen the risk of progressive CKD and renal replacement therapy. Utilizing machine learning techniques, we hypothesized that risk of AKI can be identified in SCD patients before the onset of kidney injury, leading to earlier recognition of AKI. Methods This is a single-site, retrospective IRB-approved study of 6,278 patient encounters with SCD admitted across five regional hospitals in Memphis, TN, from July 2017 to December 2020. Of these, 1,178 patient encounters were selected for analysis by including encounters with continuous minute-by-minute physiological data availability and excluding dialysis-dependent patient encounters. Each patient admission was considered a separate patient encounter if the interval between admissions was at least 1 month. AKI was defined based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline. Physiomarkers, a set of signal processing features, derived from five physiological data streams from bedside monitors, including heart rate, respiratory rate, and blood pressure (systolic, diastolic, and mean), were used, along with clinical laboratory and demographic data. Missing laboratory values and vital sign measurements were first imputed using the last-one carry forward imputation. The remaining missing values were imputed by the global median of the associated variable in the training dataset. Logistic regression, support vector machine, random forest, and eXtream Gradient Boosting (XGBoost) classifiers were used for classification. Case (AKI) and control records were divided into 12 non-overlapping but consecutive 6-hour analysis time-windows (Figure 1). Prediction horizons (the time in advance each model bundle was asked to predict the AKI event) were increased by 6-hour until the beginning of the record. Controls were balanced with cases using a bootstrap method and randomized across each unique iteration to minimize selection bias. Statistical features were derived from the 6-hour analysis window immediately prior to each prediction horizon. Explainability of models generated at each time window was assessed using averaged Shapley Additive Explanations (SHAP) scores. Results A total of 82 (7%) patient encounters were identified as AKI cases based on the 2012 KDIGO guidelines. The other 1096 SCD patient encounters served as controls (Figure 1). Overall, there were more females (64.6%) than males among AKI cases (Table 1). A history of hypertension, pulmonary hypertension, CKD, and pneumonia were higher in AKI cases than in controls (Table 1). The XGBoost model most accurately predicted AKI up to 60 hours before AKI onset, with an average test sensitivity, specificity, and area under the receiver operating characteristics curve of 0.86, 0.72, and 0.80, respectively. Conclusions In this proof-of-concept study, we found that physio/biomarkers derived from continuous bedside monitoring and laboratory data are temporally and differentially expressed in SCD patients with AKI. A minimalistic artificial intelligence model can be developed using this information to predict AKI earlier in hospitalized SCD patients and may enable the development of innovative prevention strategies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Elevation of preoperative cystatin C as an early predictor of contrast-induced nephropathy in patients receiving percutaneous coronary intervention.

Introduction:Contrast-induced nephropathy (CIN) is a serious complication of percutaneous coronary intervention (PCI). The most important predictor of CIN is renal function before PCI. Serum creatinine (SCr) is a commonly used biomarker of renal function, but an elevation in SCr lags behind the onset of kidney injury and is not viable for early detection of CIN after PCI. Our primary objective was to investigate whether preoperative cystatin C (CysC) before PCI was an early predictor of postoperative CIN. The secondary objective was to evaluate associations between preoperative CysC and renal biomarkers.Methods:From December 2014 to December 2015, 341 patients with normal renal function were enrolled into the study at our medical centre. All patients were apportioned to normal CysC (≤1.03 mg/L) or high CysC (>1.03 mg/L) groups before PCI and were hydrated from four hours prior to PCI to 24 hours after it. Renal function was monitored at 48 hours after PCI. Clinical parameters were recorded before and after PCI.Results:There was no significant difference in preoperative SCr between the CIN and non-CIN groups. However, preoperative CysC demonstrated significant difference between the two groups (p <0.01). Logistic regression analysis showed that elevated CysC before PCI was a risk factor for CIN (p = 0.013). Furthermore, the linear regression models identified an association between CysC before PCI and renal function after PCI.Conclusion:CysC before PCI was viable as a biomarker of renal function after PCI and high preoperative CysC was able to predict CIN earlier than SCr.

Major adverse renal events (MARE): a proposal to unify renal endpoints.

In renal studies, various outcome endpoints are used with variable definitions, making it nearly impossible to perform meta-analyses and deduce meaningful conclusions. Increasing attention is directed towards standardization of renal outcome reporting. A working group was formed to produce a unifying definition of renal outcomes that can be used by all investigators. We propose major adverse renal events (MARE) as the term for a standardized composite of hard renal outcomes. We discuss the components for inclusion in MARE from existing evidence. MARE could include three to five items, considered relevant to patients and regulators. New onset of kidney injury, that is persistent albuminuria/proteinuria and/or decreasing glomerular filtration rate (GFR) <60 ml/min/1.73 m2, persistent signs of worsening kidney disease, development of end-stage kidney disease with estimated GFR <15 ml/min/1.73 m2 without or with initiation of kidney replacement therapy, and death from renal cause are core items of MARE. Additionally, patient reported outcomes should be reported in parallel to MARE as a standard set of primary (or secondary) endpoints in studies on kidney disease of diabetic, hypertensive-vascular, or other origin. MARE as a reporting standard will enhance the ability to compare studies and thus, facilitate meaningful meta-analyses. This will result in standardized endpoints that should result in guideline improvement to better individualize care of patients with kidney disease.

Genipin attenuates cisplatin-induced nephrotoxicity by counteracting oxidative stress, inflammation, and apoptosis

Cisplatin (CP) is a potent and widely used chemotherapeutic agent. However, the clinical benefits of CP are compromised because it elicits nephrotoxicity and ototoxicity. In this study, we investigated the nephroprotective effects of the phytochemical genipin (GP) isolated from the gardenia (Gardenia jasminoides) fruit, using a murine model of CP-induced nephropathy. GP pretreatment attenuated the CP-induced renal tissue injury by diminishing the serum blood urea nitrogen, creatinine, and cystatin C levels, as well as those of kidney injury molecule-1. In addition, GP attenuated the CP-induced oxidative/nitrative stress by suppressing the activation of NADPH oxidase, augmenting the endogenous antioxidant defense system, and diminishing the accumulation of 4-hydroxynonenal and 3-nitrotyrosine in renal tissues. Furthermore, reduced levels of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 beta indicated that CP-induced renal inflammation was mitigated upon the treatment with GP. GP also attenuated the CP-induced activation of mitogen-activated protein kinases, excessive activities of caspase-3/7 and poly(ADP-ribose) polymerase, DNA fragmentation, and apoptosis. When administered 12h after the onset of kidney injury, GP showed a therapeutic effect by ameliorating CP-induced nephrotoxicity. Moreover, GP synergistically enhanced the CP-induced cell death of T24 human bladder cancer cells. Collectively, our data indicate that GP attenuated the CP-induced renal tissue injury by abrogating oxidative/nitrative stress and inflammation and by blocking cell death pathways, thereby improving the renal function. Thus, our results suggest that the use of GP may be a promising new protective strategy against cisplatin-induced nephrotoxicity.

Clinical practice guideline for drug-induced kidney injury in Japan 2016: digest version.

The definition of DKI is a new onset of kidney injury or the worsening of an existing kidney injury due to drug administration. DKI can be classified based on the mechanism of pathogenesis, as well as on the damaged segment of the kidney. The classification based on the mechanism of pathogenesis is as follows: (1) toxic kidney injury (direct toxicity); (2) acute interstitial nephritis (AIN) due to allergic mechanism (hypersensitivity and direct toxicity); (3) indirect toxicity, such as electrolyte abnormalities and decrease of renal blood flow; and (4) obstruction of urinary tract. The classification based on the damaged segment of kidney is as follows: (1) glomerular injury; (2) tubular injury; (3) interstitial injury; and (4) vascular injury. The criteria for diagnosis are as follows: (1) new onset of kidney injury after the start of the administration of the candidate agent and (2) improvement or stoppage of the progression of the kidney injury after the cessation of the candidate agent, and all other causes can be ruled out. The cornerstone of treatment is the identification and cessation of the candidate agent as soon as possible.

Revascularization versus medical therapy for renal-artery stenosis. The ASTRAL Investigators. The New England Journal of Medicine 2009; 361: 1953—1962

Study objective: The objective of ASTRAL was to determine whether percutaneous revascularization combined with medical therapy compared to medical therapy alone improves renal function and other outcomes, such as blood pressure, time to first renal event, time to first major cardiovascular event, and mortality. Study population: ASTRAL enrolled 806 patients with atherosclerotic renovascular disease from 57 centers. Patients were screened if treating clinicians felt they had clinical features suggestive of underlying atherosclerotic renovascular disease (i.e. hypertension refractory to medical therapy, or renal impairment as suggested by laboratory measurements). All patients had to have an imaging modality (i.e. computed tomographic angiography (CTA), magnetic resonance angiography (MRA) or renal artery ultrasound). This imaging had to convey that the patient had ‘substantial’ anatomical atherosclerotic stenosis in at least one renal artery that was suitable for endovascular therapy. Also, the treating clinician had to be ‘uncertain’ that the patient would benefit from revascularization. Fifty-nine percent of patients were reported to have renal artery stenosis of &gt; 70%, and 60% had a serum creatinine of ≥ 150 mmol per liter. Design and methods: ASTRAL was a randomized, unblinded study of patients with atherosclerotic renal artery disease who were assigned to percutaneous revascularization plus best medical therapy or best medical therapy alone. The primary outcome of the ASTRAL trial was the change of renal function over time, as determined by the mean slope of the reciprocal of serum creatinine. Secondary outcomes included blood pressure, time to first renal event (defined as: new onset of kidney injury, dialysis, renal transplantation, nephrectomy, or death from renal failure), time to first major cardiovascular event (defined as: myocardial infarction, stroke, death from cardiovascular cause, hospitalization for angina, fluid overload or congestive heart failure, coronary artery revascularization, or another peripheral arterial procedure), and all-cause mortality. Randomization was 1:1 via computer algorithm and was stratified by serum creatinine, glomerular filtration rate (GFR), severity of renal artery stenosis, kidney length on ultrasound, and rate of progression of renal impairment. Patients who were assigned to the revascularization plus medical therapy arm underwent percutaneous revascularization within 4 weeks. The procedure type (angioplasty alone or with stenting), was left to the discretion of the local operator. Distal protection devices were not used. Medical therapy in both arms consisted of antihypertensive drugs, statins, and antiplatelet agents. The trial was powered to detect a 20% reduction in the mean slope of the reciprocal of serum creatinine. Based on low crossover rates, it was determined that at least 750 patients would have to be enrolled. Analysis was by intention to treat. Continuous variables were subject to repeated measures analysis. Time-to-event data were expressed via Kaplan Meier curves and compared via log-rank testing. Prespecified subgroup analyses included baseline serum creatinine, GFR, severity of renal artery stenosis, kidney length, and progression of renal disease. Results: Of the 806 patients included, 403 were randomized to the revascularization arm and 403 to medical therapy only. The median follow-up was 34 months. Only 337 (83%) patients randomized to revascularization underwent the procedure, whereas 24 patients (6%) randomized to the medical therapy arm underwent revascularization. The number of antihypertensive medications used was greater in the medical therapy group than in the revascularization group at the 12-month follow-up: 2.97 versus 2.77 ( p = 0.03). The mean slope of the reciprocal of the serum creatinine concentration was —0.07 × 10— 3 liters per micromole per year in the revascularization group versus —0.13 × 10—3 liters per micromole per year in the medical-therapy group (difference of 0.06 × 10 —3 liters per micromole per year) (95% confidence interval [CI], —0.002 to 0.13, p = 0.06) with a trend favoring revascularization. After 5 years of follow-up, there was a trend toward lower mean systolic blood pressure (1.6 mmHg lower, p = 0.06) in the revascularization group. However, the mean diastolic blood pressure was significantly lower in the medical therapy group at long-term follow-up (divergence of slope of mean diastolic blood pressure: 0.61 mmHg per year, p = 0.03). There was no significant difference between renal events, time to first renal event, acute kidney injury, or development of end-stage renal disease in either group. Further, there was no difference in major cardiovascular events or overall survival in either group. The periprocedural complication rate within the revascularization group was 9% (31/359 patients). Fifty-five out of 280 patients (20%) had an adverse event by 1 month post procedure. Overall, there were 31 serious complications of revascularization in 23 patients. Per protocol analysis of patients suggested that there was no significant difference in outcomes between patients who received revascularization versus medical therapy. No differences between treatment groups were identified in any of the pre-specified subgroup analyses. Conclusions: Renal artery stenting combined with medical therapy did not improve renal function compared to medical therapy alone in patients with atherosclerotic renal artery disease.