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Background: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized., Methods: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria., Results: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59)., Conclusions: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria., Competing Interests: Potential conflicts of interest. A. L. C. reports being a member of the XXV pediatric Acute Dialysis Quality Initiative on Setting the Landscape and Designing the Future of Pediatric Critical Care Nephrology. C. C. J. reports participation on FEVER DSMB (Birbeck, principal investigator) and Treating Brain Welling in Cerebral Malaria (Taylor, principal investigator). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: This study evaluated potential risk factors associated with acute kidney injury (AKI) in infants undergoing bedside open laparotomy in the neonatal intensive care unit (NICU), and analyzed the association between postoperative AKI and outcomes., Methods: Retrospective data, including neonatal characteristics, perioperative findings (i.e. vital signs and fluid status), postoperative AKI incidence, and postoperative mortality rate of infants who underwent bedside open laparotomy in the NICU between May 2013 and May 2018 were collected and analyzed., Results: A total of 53 cases (26 in AKI group vs 27 in non-AKI group) were analyzed. On univariable analysis, transfusion, pre- and postoperative blood gas analysis and number of inotropic agents, cumulative postoperative percentage fluid overload (48 h), and preoperative hourly urine output were associated with the development of postoperative AKI. On multivariable logistic regression analysis, preoperative acidosis (pH <7.15 or base deficit >10; P = 0.002; OR, 11.067; 95%CI: 2.499-49.017) and preoperative urine output (P = 0.035; OR, 0.548; 95%CI: 0.314-0.959) were significant factors associated with postoperative AKI. Postoperative mortality rate 30 days after surgery was higher in the AKI group, but the difference was not significant., Conclusions: Preoperative metabolic acidosis and urine output are important factors potentially associated with the development of postoperative AKI in neonates undergoing bedside open laparotomy. Strategies such as alkali therapy, which protect the kidney from further injury, should be validated in future studies. A decreasing urine output may suggest deteriorating kidney function prior to surgery, potentially amplifying the risk of postoperative AKI., (© 2019 Japan Pediatric Society.)

Varying degrees of cardiac and kidney dysfunction commonly are observed in hospitalized patients. As a demonstration of the significant interplay between the heart and kidneys, dysfunction or injury of one organ often contributes to dysfunction or injury of the other. The term cardiorenal syndrome (CRS) was proposed to describe this complex organ cross-talk. Type 3 CRS, also known as acute renocardiac syndrome, is a subtype of CRS that occurs when acute kidney injury contributes to or precipitates the development of acute cardiac dysfunction. Acute kidney injury may directly or indirectly produce acute cardiac dysfunction by way of volume overload, metabolic acidosis, electrolyte disorders such as hyperkalemia and hypocalcemia, and other mechanisms. In this review, we examine the definition, epidemiology, pathophysiology, and treatment options for CRS with an emphasis on type 3 CRS., (Copyright © 2018. Published by Elsevier Inc.)

Metabolic acid-base disorders, especially metabolic acidosis, are common in critically ill patients who require renal replacement therapy. Continuous veno-venous hemodiafiltration (CVVHDF) achieves profound changes in acid-base status, but metabolic acidosis can remain unchanged or even deteriorate in some patients. The objective of this study is to understand the changes of acid-base variables in critically ill patients with septic associated acute kidney injury (SA-AKI) during CVVHDF and to determine how they relate to clinical outcome.Observational study of 200 subjects with SA-AKI treated with CVVHDF for at least 72 hours. Arterial blood gases and electrolytes and other relevant acid-base variables were analyzed using quantitative acid-base chemistry.Survivors and nonsurvivors had similar demographic characteristics and acid-base variables on day one of CVVHDF. However, during the next 48 hours, the resolution of acidosis was significantly different between the 2 groups, with an area under the ROC curve for standard base excess (SBE) and mortality of 0.62 (0.54-0.70), this was better than APACHE II score prediction power. Quantitative physicochemical analysis revealed that the majority of the change in SBE was due to changes in Cl and Na concentrations.Survivors of SA-AKI treated with CVVHDF recover hyperchloremic metabolic acidosis more rapidly than nonsurvivors. Further study is needed to determine if survival can be improved by measures to correct acidosis more rapidly.

Metabolic acidosis often results from chronic kidney disease; in turn, metabolic acidosis accelerates the progression of kidney injury. The mechanisms for how acidosis facilitates kidney injury are not fully understood. To investigate whether low pH directly affects the expression of genes controlling local homeostasis in renal tubules, we performed transcription start site sequencing (TSS-Seq) using IN-IC cells, a cell line derived from rat renal collecting duct intercalated cells, with acid loading for 24 h. Peak calling identified 651 up-regulated and 128 down-regulated TSSs at pH 7.0 compared with those at pH 7.4. Among them, 424 and 38 TSSs were ≥ 1.0 and ≤ -1.0 in Log2 fold change, which were annotated to 193 up-regulated and 34 down-regulated genes, respectively. We used gene ontology analysis and manual curation to profile the up-regulated genes. The analysis revealed that many up-regulated genes are involved in renal fibrosis, implying potential molecular mechanisms induced by metabolic acidosis. To verify the activity of the ubiquitin-proteasome system (UPS), a candidate pathway activated by acidosis, we examined the expression of proteins from cells treated with a proteasome inhibitor, MG132. The expression of ubiquitinated proteins was greater at pH 7.0 than at pH 7.4, suggesting that low pH activates the UPS. The in vivo study demonstrated that acid loading increased the expression of ubiquitin proteins in the collecting duct cells in mouse kidneys. Motif analysis revealed Egr1, the mRNA expression of which was increased at low pH, as a candidate factor that possibly stimulates gene expression in response to low pH. In conclusion, metabolic acidosis can facilitate renal injury and fibrosis during kidney disease by locally activating various pathways in the renal tubules.

Continuous renal replacement therapy (CRRT) is used to manage electrolyte and acid-base imbalances in critically ill patients with acute kidney injury. Although a standard solution and prescription is acceptable in most clinical circumstances, specific disorders may require a tailored approach such as adjusting fluid composition, regulating CRRT dose, and using separate intravenous infusions to mitigate and correct these disturbances. Errors in fluid prescription, compounding, or delivery can be rapidly fatal. This article provides an overview of the principles of acid-base and electrolyte management using CRRT., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: Ischemia/reperfusion (I/R) injury and metabolic acidosis (MA) are two critical conditions that may simultaneously occur in clinical practice. The result of this combination can be harmful to the kidneys, but this issue has not been thoroughly investigated. The present study evaluated the influence of low systemic pH on various parameters of kidney function in rats that were subjected to an experimental model of renal I/R injury., Main Methods: Metabolic acidosis was induced in male Wistar rats by ingesting ammonium chloride (NH4Cl) in tap water, beginning 2 days before ischemic insult and maintained during the entire study. Ischemia/reperfusion was induced by clamping both renal arteries for 45 min, followed by 48 h of reperfusion. Four groups were studied: control (subjected to sham surgery, n=8), I/R (n=8), metabolic acidosis (MA; 0.28 M NH4Cl solution and sham surgery, n=6), and MA+I/R (0.28 M NH4Cl solution plus I/R, n=9)., Key Findings: Compared with I/R rats, MA+I/R rats exhibited higher mortality (50 vs. 11%, p=0.03), significant reductions of blood pH, plasma bicarbonate (pBic), and standard base excess (SBE), with a severe decline in the glomerular filtration rate and tubular function. Microscopic tubular injury signals were detected. Immunofluorescence revealed that the combination of MA and I/R markedly increased nuclear factor κB (NF-κB) and heme-oxygenase 1 (HO-1), but it did not interfere with the decrease in endothelial nitric oxide synthase (eNOS) expression that was caused by I/R injury., Significance: Acute ischemic kidney injury is exacerbated by acidic conditions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: In acute kidney injury patients, metabolic acidosis is common. Its severity, duration, and associated changes in mean arterial pressure (MAP) and vasopressor therapy may be affected by the intensity of continuous renal replacement therapy (CRRT). We aimed to compare key aspects of acidosis and MAP and vasopressor therapy in patients treated with two different CRRT intensities., Methods: We studied a nested cohort of 115 patients from two tertiary intensive care units (ICUs) within a large multicenter randomized controlled trial treated with lower intensity (LI) or higher intensity (HI) CRRT., Results: Levels of metabolic acidosis at randomization were similar [base excess (BE) of -8 ± 8 vs. -8 ± 7 mEq/l; p = 0.76]. Speed of BE correction did not differ between the two groups. However, the HI group had a greater increase in MAP from baseline to 24 h (7 ± 3 vs. 0 ± 3 mmHg; p < 0.01) and a greater decrease in norepinephrine dose (from 12.5 to 3.5 vs. 5 to 2.5 μg/min; p < 0.05). The correlation (r) coefficients between absolute change in MAP and norepinephrine (NE) dose versus change in BE were 0.05 and -0.37, respectively., Conclusions: Overall, LI and HI CRRT have similar acid-base effects in patients with acidosis. However, HI was associated with greater improvements in MAP and vasopressor requirements (clinical trial no. NCT00221013).

Purpose: Urinary excretion of chloride corrects metabolic acidosis, but this may be hampered in patients with impaired renal function. We explored the effects of renal function on acid-base characteristics and urinary strong ion excretion using the Stewart approach in critically ill patients with metabolic acidosis., Materials and Methods: We examined the plasma and urine chemistry in 65 critically ill (mixed medical and surgical) patients with metabolic acidosis. The apparent strong ion difference, effective strong ion difference, strong ion gap, and urinary simplified strong ion difference (urinary SID) were calculated. Linear regression analyses were used (1) to assess whether plasma creatinine concentrations were related to urinary SIDs values, adjusted for blood pH levels, and (2) to determine whether urinary SID values were associated with blood pH levels., Results: Creatinine concentrations were positively and significantly (P < .001) associated with urinary SIDs values, adjusted for pH levels. Urinary simplified strong ion difference values were inversely and significantly (P < .001) related to pH levels., Conclusions: In critically ill patients with metabolic acidosis, impaired renal function was associated with greater urinary SIDs. Subsequently, the higher urinary SIDs values were related to lower pH levels, illustrating the importance of renal chloride excretion to correct for acidosis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine mortality rates in patients with acute renal failure during the past decades., Methods: We performed a MEDLINE search using the keywords "acute renal failure" crossed with "outcome," "mortality," "ICU," "critically ill" or "prognosis" in the period from January 1970 to December 2004. Abstracts and full articles were eligible if mortality rates were reported. We also reviewed the bibliographies of available studies for further potentially eligible studies. The dates of the observation period for each study and not the publication dates were considered for the analysis, so the earliest data were from 1956., Results: Of 85 articles fulfilling the criteria, 5 were excluded because of duplicate publications using the same database, so that 80 were included in our review with a total of 15897 patients. Mortality rates in most studies exceeded 30%, and there was no consistent change over time., Conclusion: Despite technical progress in the management of acute renal failure over the last 50 years, mortality rates seem to have remained unchanged at around 50%.

We report our experience with 11 children treated by continuous veno-venous hemodiafiltration. The median age was 5.0 years (range 3 days to 14 years). Access was via dual-lumen subclavian or femoral vein catheters. Hemofilters were chosen on the basis of patient size and dialysis requirements. Bicarbonate-buffered dialysis solution was prepared shortly before use by supplementation of a specially prepared base solution with commercially available electrolyte solutions. The mean ultrafiltration rate was 37.4 +/- 27 ml/kg body weight per hour. Urea and creatinine clearances were 15.1 +/- 6.4 ml/kg body weight per min and 16.4 +/- 8.4 ml/kg body weight per min, respectively. Metabolic acidosis was readily controlled in all patients. Of the 11 patients, 7 ultimately recovered normal renal function.

Myoglobin induces renal injury by mechanisms that remain incompletely defined. Acidosis has been suggested as an important factor in myoglobinuric renal failure, and urine alkalization is routinely recommended for its prevention. We tested this hypothesis by exploring the effects of acid-base balance upon myoglobin nephrotoxicity in vivo and in vitro. In isolated rat kidneys at normal pH, myoglobin at concentrations of 25-250 mg/dl minimally affected renal perfusion flow, glomerular filtration rate (GFR) and tubular sodium reabsorption (TRNa). By contrast, at pH 7.1 myoglobin induced vasoconstriction, reduced GFR and TRNa and increased hypoxic injury to medullary thick ascending limbs. These changes were largely reproduced by perfusing kidneys with hematin, suggesting its release from myoglobin in acidosis. Chronic alkalosis or acidosis was induced in rats by supplementing drinking water with 0.28 M NaHCO3 or NH4Cl, respectively. Acute renal failure, produced in control animals by myoglobin infusion (38 mg/100 g body weight), was comparably prevented by both chronic alkalosis and acidosis. Acute intravenous or oral acid load provided similar protection. Thus, although acidosis exacerbates myoglobin toxicity in isolated perfused kidneys, acute or chronic exogenous acid load prevents renal damage in vivo. This may underscore the protective properties of solute load, a consequence of preconditioning, and suggests that, in the crush syndrome, endogenous acidosis rather than being an independent risk factor is a marker of tissue hypoperfusion and organism susceptibility to myoglobin renal toxicity.

Acute ingestion of ibuprofen commonly results in no symptoms, or minor gastrointestinal or central nervous system manifestations. While most cases of ibuprofen overdose do well, serious toxicity may occur, and is difficult to predict. A case of ibuprofen overdose is presented in which the course was complicated by metabolic acidosis, adult respiratory distress syndrome, and renal failure necessitating prolonged dialysis.

Background: A variety of metabolic and renal disturbances have been described in patients with Acquired Immunodeficiency Syndrome (AIDS) but their influence on the clinical outcome has not been reported. The present study was undertaken in order to evaluate the prevalence of fluid and electrolyte, acid-base, and renal function disturbances in AIDS patients. The influence of these abnormalities on the clinical outcome was studied as well., Material and Methods: Following to a previously established protocol, the charts of all patients hospitalized during the first semester of 1989 were reviewed., Results: The prevalence of hyponatremia was 45% and 80.7% at admission and during hospitalization respectively of 99 patients. Hypokalemia was present in 23.1% of the patients. Metabolic acidosis and renal failure were 20.1% and 28.4% prevalent. The relative risk for mortality in patients with hypokalemia was 4.4. Metabolic acidosis and acute renal failure had relative risks of 12.9 and 21.4., Conclusions: There is an elevated prevalence of fluid and electrolyte, acid-base and renal function disturbances in these patients. The presence of hypokalemia, metabolic acidosis, and renal failure are significantly associated with mortality in AIDS.

Acute urate nephropathy during starvation for weight reduction has been observed in 2 patients. Under these conditions ketoacidosis causes impaired renal uric acid excretion and hyperuricemia. Uricosuric agents or sudden intake of normal calorie diet induces massive uricosuria and kidney damage. Uricosuric agents should be avoided and steps taken to promote abundant diuresis, while allopurinol should be prescribed.

Acute renal failure (ARF) following cardiac surgery under extra-corporeal circulation is a grave but infrequent complication. Numerous physiopathological factors accounting for its origin are analyzed, those related to ECC and those of the immediate post-operative period. The course of these cares of ARF and the elements of the treatment are looked at.