METHODS: Kidney IRI was performed with bilateral pediculus clamping in Swiss Background mice (3 months, 30-40g). Mice were euthanised on day one (I/R1, n=6), day eight (I/R8, n=6), and day twelve (I/R12, n=6) to exam acute and chronic episodes. Sham operation procedure was performed in the control. Tubular injury was assessed based on periodic acid- Schift (PAS) staining. Reverse transcriptase PCR (RT-PCR) was done to quantify mRNA expression of Bax, Bcl-2, and p16. Immunohistostaining (IHC) was performed to examine localisation of apoptosis (p53) and proliferation (Bcl-2).
RESULTS: RT-PCR analysis showed upregulation of mRNA expression of Bcl-2, Bax, and p16 (p<0.05). The data showed that ischemia/reperfusion induces upregulation of Bax (p=0.20), Bcl-2 (p=0.45), p16 (p=0.18). Apoptosis and proliferation occurred in the epithelial cells in acute episodes, but occurred in interstitial areas in chronic episodes.
CONCLUSIONS: Ischemia/reperfusion injury induces upregulation proliferation, apoptosis, and cellular senescence in acute kidney injury. Apoptosis reached its peak on day 1, proliferation on day 8, and cellular senescence on day 12.
METHODS: This prospective observational study included patients requiring CRRT in a tertiary intensive care unit (ICU) from February 2022 to January 2023. They were classified to either the RCA or usual care groups based on the anticoagulation technique chosen by the treating physician, considering contraindications. The CRRT prescription follows the institutional protocol. All relevant data were obtained from the ICU CRRT-RCA charts and electronic medical records. A cost analysis was performed.
RESULTS: A total of 54 patients (27 per group) were included, with no demographic differences. Sequential Organ Failure Assessment score and lactate levels were significantly higher in the usual care group. The number of filters used were comparable (p = .108). The median filter duration in the RCA group was numerically longer (35.00 [15.50-56.00] vs. 23.00 [17.00-29.00] h), but not statistically significant (p = .253). The duration of mechanical ventilation, vasopressor requirement, and mortality were similar, but the RCA group had a significantly longer ICU stay. The rate of adverse events was similar, with four severe metabolic alkalosis cases in the RCA group. The RCA group had higher total cost per patient per day (USD 611 vs. 408; p = .013).
CONCLUSION: In this resource-limited setting, RCA for CRRT appeared safe and had clinically longer filter lifespan compared with usual care, albeit the increased cost.
DESIGN: This was a single-center double-blind randomized controlled trial comparing continuous venovenous hemofiltration-high cutoff to continuous venovenous hemofiltration-standard.
SETTING: Tertiary care hospital in Australia.
PATIENTS: Vasopressor-dependent patients in acute kidney injury who were admitted to the ICU.
INTERVENTIONS: Norepinephrine-free time were calculated in critically ill vasopressor-dependent patients in acute kidney injury, randomized to either continuous venovenous hemofiltration-high cutoff or continuous venovenous hemofiltration-standard.
MEASUREMENT AND MAIN RESULTS: A total of 76 patients were randomized with the following characteristics (continuous venovenous hemofiltration-high cutoff vs continuous venovenous hemofiltration-standard); median age of 65 versus 70 year, percentage of males 47% versus 68%, and median Acute Physiology and Chronic Health Evaluation scores of 25 versus 23.5. The median hours of norepinephrine-free time at day 7 were 32 (0-110.8) for continuous venovenous hemofiltration-high cutoff and 56 hours (0-109.3 hr) (p = 0.520) for continuous venovenous hemofiltration-standard. Inhospital mortality was 55.6% with continuous venovenous hemofiltration-high cutoff versus 34.2% with continuous venovenous hemofiltration-standard (adjusted odds ratio, 2.49; 95% CI, 0.81-7.66; p = 0.191). There was no significant difference in time to cessation of norepinephrine (p = 0.358), time to cessation of hemofiltration (p = 0.563), and filter life (p = 0.21). Serum albumin levels (p = 0.192) were similar and the median dose of IV albumin given was 90 grams (20-212 g) for continuous venovenous hemofiltration-high cutoff and 80 grams (15-132 g) for continuous venovenous hemofiltration-standard (p = 0.252).
CONCLUSIONS: In critically ill patients with acute kidney injury, continuous venovenous hemofiltration-high cutoff did not reduce the duration of vasopressor support or mortality or change albumin levels compared with continuous venovenous hemofiltration-standard.
METHODS: Proton Nuclear Magnetic Resonance (1H NMR) and Liquid Chromatography Mass Spectroscopy (LCMS) coupled with multivariate data analysis were employed to characterize the metabolic variations of intracellular metabolites and the compositional changes of the corresponding culture media in rat renal proximal tubular cells (NRK-52E).
RESULTS: NMR and LCMS analysis highlighted choline, creatine, phosphocholine, valine, acetic acid, phenylalanine, leucine, glutamic acid, threonine, uridine and proline as the main metabolites which differentiated the cisplatin-induced group of NRK-52E from control cells extract. The corresponding media exhibited lactic acid, glutamine, glutamic acid and glucose-1-phosphate as the varied metabolites. The altered pathways perturbed by cisplatin nephrotoxic on NRK-52E cells included changes in amino acid metabolism, lipid metabolism and glycolysis.
CONCLUSION: The C. nutans aqueous extract (1000 μg/mL) exhibited the most potential nephroprotective effect against cisplatin toxicity on NRK-52E cell lines at 89% of viability. The protective effect could be seen through the changes of the metabolites such as choline, alanine and valine in the C. nutans pre-treated samples with those of the cisplatin-induced group.
METHODS: We conducted a before-and-after trial with 5008 consecutive ED-treated hospital admissions in the control period and 5146 consecutive admissions in the intervention period. During the control period (18 February 2008 to 17 August 2008), patients received standard i.v. fluids. During the intervention period (18 February 2009 to 17 August 2009), we restricted all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes (KDIGO) staging to define AKI.
RESULTS: Stage 3 of KDIGO-defined AKI decreased from 54 (1.1%; 95% confidence interval [CI] 0.8-1.4) to 30 (0.6%; 95% CI 0.4-0.8) (P = 0.006). The rate of renal replacement therapy did not change, from 13 (0.3%; 95% CI 0.2-0.4) to 8 (0.2%; 95% CI 0.1-0.3) (P = 0.25). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stage 3 (hazard ratio 1.82; 95% CI 1.13-2.95; P = 0.01). On sensitivity assessment after removing repeat admissions, KDIGO stage 3 remained significantly lower in the intervention period compared with the control period (P = 0.01).
CONCLUSION: In a before-and-after trial, a chloride-restrictive strategy in an ED was associated with a significant decrease in the incidence of stage 3 of KDIGO-defined AKI.