Rise In Serum Creatinine Research Articles

Chronic kidney disease amplifies severe kidney injury and mortality in a mouse model of skin arsenical exposure.

In previously published work, we elucidated the role of cutaneous arsenical exposure in promoting acute kidney injury (AKI) in adult healthy mice. Here, we determine whether pre-existing chronic kidney disease (CKD) increases the severity of AKI. Following exposure to aristolochic acid (AA) (a nephrotoxic phytochemical in humans), mice manifested classical markers of CKD, including robust interstitial fibrosis and loss in kidney function. Skin challenge with phenylarsine oxide (PAO), a surrogate for warfare arsenicals, led to significantly worse kidney injury, as evidenced by tubulointerstitial fibrosis, glomerulosclerosis, a persistent loss of estimated glomerular filtration rate and mortality in AA-induced CKD mice compared to mice without CKD. These PAO-challenged CKD mice exhibited enhanced production of serum/urine NGAL, and a significant rise in serum creatinine along with histological markers of kidney injury, including brush border loss, tubular atrophy, cast formation, glomerular injury, and interstitial inflammatory cell infiltration. Serum cytokines IL-4, IL-6, IFN-γ, IL-12p70, TNF-α, and IL-18 significantly elevated in CKD mice following PAO exposure when compared to animals exposed to PAO alone. Furthermore, we found increased TUNEL-positive tubular cells in the kidneys of CKD mice following PAO exposure, suggesting enhanced PAO-mediated cell death in CKD mice. Mechanistically, we determined that DNA damage-regulated p53 signaling was a major mediator of cellular responses to PAO in CKD mice. In summary, our data demonstrate that CKD significantly increased severity of AKI following exposure to arsenicals and suggest that human populations with preexisting CKD could be highly susceptible to arsenical-mediated kidney injury and associated morbidity and mortality.

Acute Kidney Injury Among Asphyxiated Neonates In Sokoto, North West Nigeria

Background: Birth asphyxia and its attendant complications remain a common problem in our neonatal intensive care units. Compelling evidence from various epidemiologic studies shows that Acute Kidney Injury (AKI) is indeed one of the commonest complications of birth asphyxia. The kidneys are sensitive to oxygen deprivation, renal insult may occur within few hours of hypoxic-ischemic episode, which if prolonged could lead to irreversible cortical and or tubular necrosis. Aim: To determine the prevalence and factors associated with AKI among asphyxiated term neonates in Usmanu Danfodiyo University Teaching Hospital (UDUTH) Sokoto, Nigeria Materials and methods: One hundred and nineteen asphyxiated term neonates admitted into the special care baby unit of UDUTH Sokoto participated in the study. Birth asphyxia was defined as failure to initiate and sustain breathing at birth with Apgar scores ≤ 5 at 5 minutes in the presence of arterial cord blood pH < 7 and base deficit >12mmol. Blood samples were taken for arterial blood gas analysis within one hour of life. Moderately and severely asphyxiated neonates who satisfied the inclusion criteria were consecutively recruited into the study and serum creatinine assay was done on day 3 and day 5 of life. AKI was defined as a rise in serum creatinine ≥ 0.3mg/dl over 48 hours. Quantitative variables such as birth weight, length, occipitofrontal circumference (OFC) were expressed using mean, standard deviation and range, while qualitative variables like gender, mode of delivery and grade of asphyxia were summarised using frequency and percentages. Chisquare and fisher’s exact tests were applied to determine if any relationship exists between sociodemographic/clinical factors and AKI. A p-value of < 0.05 was considered statistically significant. Results: Of the 119 asphyxiated term neonates 74 (62.2%) were males while 45 (37.8%) were females giving a M:F ratio of 1.6:1. Majority 96 (80.7%) of the subjects had normal birth weight with a mean birth weight of 3.1 ± 0.6kg. The mean gestational age recorded was 38.2 ± 1.1 months The prevalence of AKI in the study subjects was 42.9%. The grade of birth asphyxia was significantly associated with AKI with a prevalence odds ratio of 7.2 (95CI 2.8-18). Conclusion: The prevalence of AKI in asphyxiated term neonates in UDUTH Sokoto was high and the grade of birth asphyxia was found to be significantly associated with AKI

Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker.

Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

Empagliflozin mitigates methotrexate-induced nephrotoxicity in male albino rats: insights on the crosstalk of AMPK/Nrf2 signaling pathway

BackgroundThe anti-diabetic drug, empagliflozin (EMPA), has many pleiotropic actions and is challenged recently to possess renoprotective properties. This renoprotective potential is proposed to be mediated via the activation of AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This research investigated the renoprotective potential and the mechanistic pathway of EMPA against methotrexate (MTX)-induced nephrotoxicity and evaluated the role of AMPK by utilizing an AMPK inhibitor, dorsomorphin (Dorso).MethodsThirty male Wistar rats, weighing 180–200 g, were divided equally into five groups. Group I represented the control group. Nephrotoxicity was induced in the remaining rats through the administration of a single intraperitoneal injection of MTX (20 mg/kg). Rats were then randomly assigned to: Group 2 (received MTX injection only); Group 3 (received MTX and EMPA 30 mg/kg/day); Group 4 (received MTX and Dorso 0.2 mg/kg/day), Group 5 (received MTX, Dorso, EMPA). After one week, blood samples were collected, the rats were euthanized, and renal tissues were harvested for biochemical and histomorphometric assessments.ResultsMTX produced a significant rise in serum creatinine and tissue MDA levels; an increase in BAX, p53, cytochrome-c expression; a reduction in Bcl2 level; and disruption of renal microarchitecture. In contrast, EMPA therapy in group 3, resulted in a significant improvement of all these parameters, correlated with significant increase in AMPK phosphorylation and Nrf2 expression. Importantly, the co-administration of Dorso, in group 5, prevented EMPA’s beneficial effects.ConclusionEMPA has a potential protective effect against MTX-induced toxicity through the activation of the AMPK/Nrf2 signaling pathway.

A Case Report on Renal Amyloidosis

Amyloidosis involves the deposition of abnormal proteins in various tissue and result in progressive organ dysfunction, commonly affecting multiple organs. Two types of systemic amyloidosis are AA and AL, the former is associated with acute phase reaction and the later is composed of light chain immunoglobulin. This disease commonly affects the kidneys and is evidenced by massive proteinuria. A biopsy is the gold standard of diagnosis, with Congo Red staining revealing an apple green birefringence under polarized light microscope. We are presenting a 45 years old male who presented with rapid rising serum creatinine with history of multiple myeloma (non secretory). There was also history of spine tuberculosis.

Acute kidney injury in acute heart failure–when to worry and when not to worry?

ABSTRACT Acute kidney injury is common in patients with acute decompensated heart failure. It is more common in patients with acute heart failure who suffer from chronic kidney disease. Worsening renal function is often defined as a rise in serum creatinine of more than 0.3 mg/dL (26.5 µmol/L) which, by definition, is acute kidney injury (AKI) stage 1. Perhaps the term AKI is more appropriate than worsening renal function as it is used universally by nephrologists, internists and other medical practitioners. In health, the heart and the kidney support each other to maintain the body's homeostasis. In disease, the heart and the kidney can adversely affect each other's function, causing further clinical deterioration. In patients presenting with acute heart failure and fluid overload, therapy with diuretics for decongestion often causes a rise in serum creatinine and AKI. However, in the longer term the decongestion improves survival and prevents hospital admissions despite rising serum creatinine and AKI. It is important to realize that renal venous congestion due to increased right-sided heart pressures in acute heart failure is a major cause of kidney dysfunction and hence decongestion therapy improves kidney function in the longer term. This review provides a perspective on the acceptable AKI with decongestion therapy, which is associated with improved survival, as opposed to AKI due to tubular injury related to sepsis or nephrotoxic drugs, which is associated with poor survival.

Comparison Between Retrograde and Antegrade Ureteroscopic Laser Lithotripsy for the Management of Medium-Sized Proximal Ureteral Stones: A Randomized Prospective Study.

This study aimed to present the outcomes of retrograde and antegrade ureteroscopic laser lithotripsy in the treatment of proximal ureteral stones ranging in size from 10 to 20 millimeters in diameter. From March 2023 to December 2023, 70 patients were included in this prospective randomized double-arm interventional study. Patients were divided into two groups: Group 1 (35 patients) had semi-rigid retrograde ureteroscopic laser lithotripsy, and Group 2 (35 patients) had semi-rigid antegrade ureteroscopic laser lithotripsy. In terms of length of hospitalization, there was a statistically significant distinction between the groups that were evaluated (p = 0.001). Group (1) showed a statistically significant distinction in Hb and HCT levels before and after the procedure (p < 0.05), whereas Group (2) showed a similar difference in Hb, creatinine, and HCT levels before and after the operation (p < 0.05). The antegrade group had much more hemorrhage than the retrograde group. Reduced hemoglobin (p = 0.008) and hemoglobin saturation (p = 0.029) were most noticeable in the antegrade group. Regarding stone-free rates (SFRs), no statistically significant difference was noted between the groups (p = 0.643). Both retrograde and antegrade ureteroscopic laser lithotripsy are dependable and successful for the treatment of proximal ureteral stones. For medium-sized proximal ureteral stones (10-20 mm), retrograde ureteroscopic laser lithotripsy may be the first option due to its shorter hospital stays, decreased bleeding rates, blood transfusion needs, and temporary rise in serum creatinine.

#1150 Neutrophil rich infiltrate in immunotherapy induced acute interstitial nephritis

Abstract Background and Aims Acute interstitial nephritis (AIN) is a well-recognized cause of acute kidney injury (AKI) in patients treated with Immune checkpoint inhibitors (ICI). Kidney biopsy typically shows tubular interstitial infiltration with well-differentiated mononuclear cells with occasional granulomas and eosinophils. Neutrophil rich tubular interstitial infiltration is typically associated with pyelonephritis. We report a case series of neutrophil rich ICI induced AIN. Method After obtaining approval from the institutional review board, medical records of the nephrology service at a large cancer center were reviewed. Patients were included in the study if they underwent a kidney biopsy for the diagnosis of ICI associated AKI, the biopsy was consistent with atypical AIN with neutrophil rich infiltrate, there was no glomerular involvement, they exhibited no symptoms of pyelonephritis including but not limited to fever, nausea, vomiting, flank pain and dysuria and had a negative urine culture. Results Forty eight patients who had a biopsy proven ICI associated AIN were identified from the medical records. Four (8.3%) patients met the study criteria (Table 1). There were three males and one female. The mean age was 75.5 years. One patient had a history of pre-existing CKD stage 3. Mean number of ICI therapy cycles prior to the development of AIN was seven with two patients treated with pembrolizumab (2 and 14 cycles), one patient treated with nivolumab (1 cycle) and one patient treated with the combination of nivolumab and ipilimumab (2 cycles). All patients presented with asymptomatic rise in serum creatinine (sCr). Kidney biopsy showed neutrophil rich infiltrate and neutrophilic tubulitis in all patients. Neutrophilic casts were present in three biopsies. One patient had evidence of granulomatous inflammation. All patients had mild to moderate interstitial fibrosis. Three patients were initially treated with flat dose prednisone 60 mg daily and one was treated with weight adjusted dose of prednisone 1 mg/kg at 75 mg/day. Three patients had complete renal recovery (sCr &amp;lt; 0.5 mg/dl above baseline) after steroid taper. One patient developed a relapse but achieved partial recovery (sCr &amp;lt; 2x baseline) after the second taper. Two patients remain alive three and 12 months after the kidney biopsy. Two patients died due to the progression of cancer two and 10 months after the biopsy. Conclusion AIN with neutrophil rich infiltrate likely represents a subset of ICI induced AIN. In the absence of clinical signs of pyelonephritis and with evidence of negative urine cultures the treatment should be geared towards addressing inflammation with systemic corticosteroids which have been shown to be effective in management of ICU induced AIN. Avoidance of antibiotics in this setting would lead to better antibiotic stewardship.

Myeloid-specific ferritin light chain deletion does not exacerbate sepsis-associated AKI.

Sepsis-associated acute kidney injury (SA-AKI) is a key contributor to the life-threatening sequelae attributed to sepsis. Mechanistically, SA-AKI is a consequence of unabated myeloid cell activation and oxidative stress that induces tubular injury. Iron mediates inflammatory pathways directly and through regulating the expression of myeloid-derived ferritin, an iron storage protein comprising ferritin light (FtL) and ferritin heavy chain (FtH) subunits. Previous work revealed that myeloid FtH deletion leads to a compensatory increase in intracellular and circulating FtL and is associated with amelioration of SA-AKI. We designed this study to test the hypothesis that loss of myeloid FtL and subsequently, circulating FtL will exacerbate the sepsis-induced inflammatory response and worsen SA-AKI. We generated a novel myeloid-specific FtL knockout mouse (FtLLysM-/-) and induced sepsis via cecal ligation and puncture or lipopolysaccharide endotoxemia. As expected, serum ferritin levels were significantly lower in the knockout mice, suggesting that myeloid cells dominantly contribute to circulating ferritin. Interestingly, although sepsis induction led to a marked production of pro- and anti-inflammatory cytokines, there was no statistical difference between the genotypes. There was a similar loss of kidney function, as evidenced by a rise in serum creatinine and cystatin C and renal injury identified by expression of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. Finally, RNA sequencing revealed upregulation of pathways for cell cycle arrest and autophagy postsepsis, but no significant differences were observed between genotypes, including in key genes associated with ferroptosis, an iron-mediated form of cell death. The loss of FtL did not impact sepsis-mediated activation of NF-κB or HIF-1a signaling, key inflammatory pathways associated with dysregulated host response. Taken together, while FtL overexpression was shown to be protective against sepsis, the loss of FtL did not influence sepsis pathogenesis.NEW & NOTEWORTHY Hyperferritinemia in sepsis is often associated with a proinflammatory phenotype and poor prognosis. We previously showed the myeloid deletion of FtH results in a compensatory increase in FtL and is associated with reduced circulating cytokines and decreased rates of SA-AKI in animal sepsis models. Here, we show that myeloid deletion of FtL does not impact the severity of SA-AKI following CLP or LPS, suggesting that FtH plays the predominant role in propagating myeloid-induced proinflammatory pathways.

#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians. Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation. In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity. Methods We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs. Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula. Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of &amp;lt; 0.05 was considered statistically significant. All data was analyzed using Stata software. Results A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology. Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL. After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p &amp;lt; 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p &amp;lt; 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use. Conclusion Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified. Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.

#2716 Selenoprotein-P1 (SEPP-1) in human proximal tubule cells after ischemic-reperfusion injury: an in-vitro model

Abstract Background and Aims Novel biomarkers, anticipating serum creatinine rise, are eagerly needed to have a speedy diagnosis of acute kidney injury (AKI) and thus to mitigate and to preserve kidney function with well-timed therapeutic plans. Recently, in a pilot study on patients undergoing elective major cardiac surgery with cardiopulmonary bypass (CPB), selenoprotein-p1 (SEPP-1) has emerged as a promising candidate plasmatic biomarker for an early AKI risk stratification. SEPP-1 increased particularly between 4th to 8th hour after CPB and with a strict relation with ischemia duration (Bolignano et Al. Rev. Cardiovasc. Med. 2022). SEPP1 is primarily secreted from liver and acts as a selenium transporter supplying tissues and organs with this trace mineral which elicits the activity of specific glutathione peroxidase selenoenzymes. Additionally, renal tubular cells are able to synthetize this protein but remain unknown if, during AKI, SEPP1 increases as defeat answer to renal cells damage or if it's hepatic SEPP1 that accumulates for a reduced renal glomerular filtration rate. The primary aim of this study was to investigate the release of SEPP-1 by renal tubular cells in an experimental model of AKI induced by ischemia-reperfusion and secondarily evaluate the effect of selenium supplying on renal cells injury. Method Human proximal tubular cells (PTC), HK2 cells and human embryonic kidney 293 cells (HEK293) were cultured in Keratinocyte-SFM a complete serum-free medium supplemented with human recombinant Epidermal Growth Factor (rEGF) and Bovine Pituitary Extract (BPE) (LGC Standards s.r.l., Milan, Italy) and in Eagle's Minimum Essential Medium (E-MEM) (LGC Standards s.r.l., Milan, Italy) containing 10% fetal bovine serum, respectively. The cells were pre-incubated with medium containing Sodium Selenite 100 nM for 24 h and then were treated for 24 hours with CoCl2 (Sigma Aldrich S.r.l., Milan, Italy) a chemical hypoxia inducer (500 µM for HK-2 and 250 µM for HEK-293). After that cell viability was evaluated by MTT and trypan bleu dye exclusion assay, while, protein expression of HIF (hypoxia marker) and SEPP1 was analyzed by western blot analysis. Results Ischemia-reperfusion was simulated by the exposure of HK-2 and HEK-293 to CoCl2 and confirmed by HIF expression. The expression of SEPP-1 increased significantly in HK-2 and HEK-293 after hypoxia stress (Fig. 1). Furthermore, the treatment with CoCl2 determined a decrease of cell viability (about 50% less) and Sodium selenite alone increased cell proliferation (about 15% more) in both cell lines. Interestingly cell growth after hypoxia augmented significantly if cell lines were pre-treated with sodium-selenite, highly in HK-2 cells (p &amp;lt; 0.001). Conclusion These preliminary data evidenced, in vitro, that AKI is able to induce renal tubular expression of SEPP-1 and probably SEPP-1 release in human after renal injury is not only a result of a reduced filtration of the hepatic released protein. Furthermore, SEPP-1 showed a possible protective role in AKI. In fact, AKI induced by ischemia-reperfusion, in our in vitro cellular model, was able to induce an increased expression of SEPP-1 in renal tubular cells suggesting a shielding mechanism against injury related to selenium transport. This hypothesis was supported by an exalted SEPP-1 expression after Sodium-Selenite adding to cells’ culture. Supplementary experiments, including functional molecular assays in vitro and in vivo studies will allow to better characterize the role of SEPP-1 in AKI.

Sex bias in prediction and diagnosis of cardiac surgery associated acute kidney injury

BackgroundFemale sex has been recognized as a risk factor for cardiac surgery associated acute kidney injury (CS-AKI). The current study sought to evaluate whether female sex is a risk factor for CS-AKI, or modifies the association of peri-operative change in serum creatinine with CS-AKI.MethodsObservational study of adult patients undergoing cardiac surgery between 2000 and 2019 in a single U.S. center. The main variable of interest was registered patient sex, identified from electronic medical records. The main outcome was CS-AKI within 2 weeks of surgery.ResultsOf 58526 patients, 19353 (33%) were female; 12934 (22%) incurred AKI based on ≥ 0.3 mg/dL or ≥ 50% rise in serum creatinine (any AKI), 3320 (5.7%) had moderate to severe AKI, and 1018 (1.7%) required dialysis within 2 weeks of surgery. Female sex was associated with higher risk for AKI in models that were based on preoperative serum creatinine (OR, 1.35; 95% CI, 1.29–1.42), and lower risk with the use of estimated glomerular filtration, (OR, 0.90; 95% CI, 0.86–0.95). The risk for moderate to severe CS-AKI for a given immediate peri-operative change in serum creatinine was higher in female compared to male patients (p < .0001 and p < .0001 for non-linearity), and the association was modified by pre-operative kidney function (p < .0001 for interaction).ConclusionsThe association of patient sex with CS-AKI and its direction was dependent on the operational definition of pre-operative kidney function, and differential outcome misclassification due to AKI defined by absolute change in serum creatinine.

A cohort study of sodium-glucose cotransporter-2 inhibitors after acute kidney injury among Veterans with diabetic kidney disease

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk for several adverse outcomes among patients with diabetic kidney disease. Yet, optimal timing for SGLT2i after acute kidney injury (AKI) is uncertain, as are the providers responsible for post-AKI SGLT2i initiation. Using a retrospective cohort of United States Veterans with diabetes mellitus type 2 and proteinuria, we examined encounters by provider specialty before SGLT2i initiation and subsequent all-cause mortality after hospitalization with AKI, defined by a 50% or more rise in serum creatinine. Covariates included recovery, defined by return to a110% or less of baseline creatinine, and time since AKI hospitalization. Among 21,330 eligible Veterans, 7,798 died (37%) and 6,562 received a SGLT2i (31%) over median follow-up of 2.1 years. Post-AKI SGLT2i use was associated with lower mortality risk [adjusted hazard ratio 0.63 (95% confidence interval 0.58-0.68)]. Compared with neither SGLT2i use nor recovery, mortality risk was similar with recovery without SGLT2i use [0.97 (0.91-1.02)] but was lower without recovery prior to SGLT2i use [0.62 (0.55-0.71)] and with SGLT2i use after recovery [0.60 (0.54-0.67)]. Finally, the effect of SGLT2i was stable over time (P for time-interaction 0.19). Thus, we observed reduced mortality with SGLT2i use after AKI among Veterans with diabetic kidney disease whether started earlier or later or before or after observed recovery. Hence, patients with diabetic kidney disease who receive a SGLT2i earlier after AKI experience no significant harm impacting mortality and experience a lower mortality risk than those who do not.

A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14)(p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.

Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

Acyclovir-Induced Nephrotoxicity in Adults with Viral Encephalitis.

To determine the frequency of parenteral Acyclovir-induced Acute Kidney Injury (AKI) in patients with viral encephalitis. Descriptive study. Place and Duration of the Study: Department of Neurology, Liaquat National Hospital, Karachi, from January to December 2021. A total of 89 suspected and proven cases of encephalitis receiving IV Acyclovir were collated. All had extensive medical histories and underwent CSF studies with +/- brain imaging. CSF routine and viral PCR were done. Acyclovir-induced AKI was defined as a rise in serum creatinine of >0.3 mg/dl in 48 h or by ≥1.5 times the baseline value, and its severity was staged into 1 (risk), 2 (injury), and 3 (failure) according to the KDIGO guidelines (Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group, 2012). Patients' variables, including age, gender, presenting features, comorbid conditions, and CSF findings, were divided into two groups, i.e. with and without AKI. This research included 89 patients with a mean age of 48 years. AKI occurred in 34 patients (38.2%). The frequency of AKI with Stage 1 was 24%, Stage 2 was 44%, and Stage 3 was 32%; approximately two-thirds of cases were in Stage 2 and 3 (p >0.05). Five patients (5.6%) from Stage 3, required dialysis. AKI is an important adverse effect of parenteral acyclovir, which necessitates its early identification and timely management. Renal function monitoring is essential for patients on Acyclovir treatment as they are at risk for AKI. Acyclovir, Acute kidney injury, Viral encephalitis, Creatinine, Kidney Disease Improving Global Outcomes.

Biomarkers vs Machines: The Race to Predict Acute Kidney Injury.

Acute kidney injury (AKI) is a serious complication affecting up to 15% of hospitalized patients. Early diagnosis is critical to prevent irreversible kidney damage that could otherwise lead to significant morbidity and mortality. However, AKI is a clinically silent syndrome, and current detection primarily relies on measuring a rise in serum creatinine, an imperfect marker that can be slow to react to developing AKI. Over the past decade, new innovations have emerged in the form of biomarkers and artificial intelligence tools to aid in the early diagnosis and prediction of imminent AKI. This review summarizes and critically evaluates the latest developments in AKI detection and prediction by emerging biomarkers and artificial intelligence. Main guidelines and studies discussed herein include those evaluating clinical utilitiy of alternate filtration markers such as cystatin C and structural injury markers such as neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloprotease 2 with insulin-like growth factor binding protein 7 and machine learning algorithms for the detection and prediction of AKI in adult and pediatric populations. Recommendations for clinical practices considering the adoption of these new tools are also provided. The race to detect AKI is heating up. Regulatory approval of select biomarkers for clinical use and the emergence of machine learning algorithms that can predict imminent AKI with high accuracy are all promising developments. But the race is far from being won. Future research focusing on clinical outcome studies that demonstrate the utility and validity of implementing these new tools into clinical practice is needed.

Berberine alleviates chlorpyrifos-induced nephrotoxicity in rats via modulation of Nrf2/HO-1 axis

Chlorpyrifos (CPS), an organophosphorus insecticide, is widely used for agricultural and non-agricultural purposes with hazardous health effects. Berberine (BBR) is a traditional Chinese medicine and a phytochemical with anti-inflammatory and anti-oxidative properties. The present study evaluated the effects of BBR against kidney damage induced by CPS and the underlying mechanisms. An initial study indicated that BBR 50 mg/kg was optimal under our experimental conditions. Then, 24 rats (6/group) were randomized into: control, BBR (50 mg/kg/day), CPS (10 mg/kg/day), and CPS + BBR. BBR was administration 1 h prior to CPS. Each treatment was delivered daily for a period of 28 consecutive days using a gastric gavage tube. Compared to CPS-alone treated rats, BBR effectively improved renal function by preventing the rise in serum urea, creatinine, and uric levels. The reno-protective effects of BBR were confirmed through a histological examination of kidney tissues. BBR restored oxidant-antioxidant balance in renal tissues mediated by Keap1/Nrf2/HO-1 axis modulation. In addition, BBR decreased nitric oxide (NO) and myeloperoxidase (MPO) activity. This was paralleled with the potent down-regulation of NF-κB. Furthermore, BBR exhibited anti-apoptotic activities supported by the upregulation of Bcl-2 and down-regulation of Bax and caspase-3 expression. In conclusion, our data suggest that BBR attenuates CPS-induced nephrotoxicity in rats by restoring oxidant-antioxidant balance and inhibiting inflammatory response and apoptosis in renal tissue. This is mediated, at least partly, by modulation of the Nrf2/HO-1 axis.

Endovascular Embolization of Spontaneously Ruptured Renal Artery Pseudoaneurysm in a Post-Partum Woman: A Case Report

Renal artery pseudoaneurysm (RAP) is a rare but potentially life-threatening condition that is often challenging to diagnose. While commonly associated with procedures or trauma, spontaneous cases are exceedingly rare. We present a case of a post-partum woman with a spontaneously ruptured segmental renal artery pseudoaneurysm. We report a 19-year-old post-partum woman presented with an enlarged kidney and rising serum creatinine levels following a caesarean section. Imaging revealed a ruptured renal artery pseudoaneurysm, and endovascular glue embolization was performed successfully.

Cystatin C as an Early Marker of Renal Dysfunction in Patients with Cirrhosis of Liver: A Cross-sectional Study

Introduction: Serum cystatin C has been proposed as a sensitive marker for detecting renal impairment. Renal impairment can often co-exist with liver cirrhosis, as decreased blood flow through the cirrhotic liver can lead to kidney dysfunction. However, its role in patients with liver cirrhosis has not been extensively studied, especially in the detection of early renal impairment. Aim: To investigate whether serum cystatin C could serve as a potential marker for detecting early renal dysfunction in patients with liver cirrhosis. Materials and Methods: This hospital-based cross-sectional study was conducted on 60 patients with liver cirrhosis at Assam Medical College and Hospital, Dibrugarh, Assam, India, from June 2019 to May 2020. All patients were assessed for clinical symptoms and laboratory parameters, focusing on renal function tests, measurement of serum cystatin C levels, and Glomerular Filtration Rate (GFR). A two-tailed p-value &lt;0.05 was considered statistically significant in all calculations. Results: In total, 60 consecutive patients with liver cirrhosis were evaluated during the study period, 85% of whom were males. The mean age was 47.4±9.3 years. The mean values of GFR calculated from the mean values of serum creatinine and serum cystatin C were 59.57±31.48 and 31.25±18.32, respectively, both showing a negative correlation (r=-0.802 and r=-0.817, respectively), indicating that cystatin C has a superior correlation with GFR when compared to serum creatinine. Regression analysis showed a tighter distribution of results around the regression line for cystatin C, as indicated by an R2 value of 0.67, compared to 0.64 for creatinine. It was also observed that for every unit rise in serum creatinine and cystatin C value, GFR decreased by 29.89 and 14.67, respectively. Conclusion: Serum cystatin C is a better predictor of GFR than serum creatinine and can therefore be used as an early marker of renal dysfunction in the course of liver cirrhosis