Beta-lactam-associated hypokalemia.

The aim of this narrative review was to discuss the literature on ß-lactam antibiotic-associated hypokalemia, a potentially life-threatening electrolyte disorder. The PubMed, Web of Science, Cochrane Library, and Scopus databases were searched for articles published between 1965 and 2023, using the following terms: 'hypokalemia' OR 'potassium loss' OR 'potassium deficiency' AND 'beta-lactams' OR 'penicillin' OR 'penicillin G' OR 'cephalosporins' OR 'ceftazidime' OR 'ceftriaxone' OR 'flucloxacillin' OR 'carbapenems' OR 'meropenem' OR 'imipenem' OR 'cefiderocol' OR 'azlocillin' OR 'ticarcillin'. Additional search terms were 'hypokalemia' AND 'epidemiology' AND 'ICU' OR 'intensive care unit' OR 'ER' OR 'emergency department' OR 'ambulatory' OR 'old' OR 'ageing population', and experimental (animal-based) studies were excluded. A total of eight studies were selected and discussed, in addition to nine case reports and case series. Both older and currently used ß-lactam antibiotics (e.g., ticarcillin and flucloxacillin, respectively) have been associated with therapy-related hypokalemia. The incidence of ß-lactam antibiotic-associated hypokalemia may be as high as 40%, thus, the issue of ß-lactam-associated hypokalemia remains clinically relevant. Although other causes of hypokalemia are likely to be diagnosed more frequently (e.g., due to diuretic therapy or diarrhea), the possibility of ß-lactam-induced renal potassium loss should always be considered in individuals with so-called 'unexplained hypokalemia'.

Adherence to guidelines for management of acute kidney injury.

BACKGROUND AND AIM: Acute kidney injury (AKI) affects a significant number of patients and the prognosis for this condition remains poor. The aim of this study was to assess adherence to KDIGO clinical practice guidelines and identify areas for improvement. METHODS: For this retrospective study, data were extracted from the medical database of the University Hospital Brandenburg, for patients who had been diagnosed with AKI from January to March 2021. Implementation rates of eight KDIGO AKI therapeutic measures were analyzed in relation to several AKI severity/risk categories. RESULTS: Data from 200 patients were included in the study. Three specific measures were commonly implemented: hyperglycemia control (100%), volume therapy (82%), and fluid balance management (65%). Nephrotoxic medications were discontinued in 51% patients, while iodinated contrast media was used in 35% patients. Patients with an increased risk of complications, such as those requiring ICU therapy or with sepsis, received these measures more frequently. CONCLUSIONS: While some 2012 KDIGO recommended measures were implemented for a substantial number of affected individuals, others were not. Our study highlights the need for improvement in the quality of care for patients with AKI.

Hypernatremia: Epidemiology and Predictive Role in Emerging and Established Acute Kidney Injury.

Hypernatremia (plasma sodium > 145 mmol/L) reflects impaired water balance, and affected patients can suffer from severe neurologic symptoms. Hyponatremia, on the other hand, is the most frequent electrolyte disorder in hospitals. It may be diagnosed in acute kidney injury (AKI), but hyponatremia prior to the diagnosis of AKI has also predictive or prognostic value in the short term. Aim of the article was to summarize data on both, epidemiology and outcomes of in-hospital acquired hypernatremia ("In-hospital acquired" refers to the diagnosis of either hypo- or hypernatremia in patients, who did not exhibit any of these electrolyte imbalances upon admission to the hospital). It also aimed to discuss its predictive role in patients with emerging or established AKI. Five databases were searched for references: PubMed, Medline, Google Scholar, Scopus, and Cochrane Library. Studies published between 2000 and 2023 were screened. The following keywords were used: "hypernatremia", "mortality", "pathophysiology", "acute kidney injury", "AKI", "risk prediction", "kidney replacement therapy", "KRT", "renal replacement therapy", "RRT", "hyponatremia", and "heart failure". A total of 16 studies were deemed eligible for inclusion. Among these, 13 studies had a retrospective design, two investigations were published as secondary analyses from prospective trial cohorts, and one study was prospective in nature. Out of the 16 studies, 11 focused on the epidemiology and outcomes of hypernatremia, while five investigations were related to AKI and/or AKI-associated endpoints. The prevalence of hypernatremia diagnosed during hospitalization varied from 1.9% to 6.8%, with one exception where it was 30.8%. All studies demonstrated associations between hypernatremia and mortality, even over extended periods after discharge. In AKI patients, hypernatremia shows potential for predicting in-hospital death. In conclusion, hypernatremic individuals are at higher risk of death during in-hospital therapy. Also, the electrolyte disorder potentially qualifies as a future biomarker for AKI onset and AKI-associated mortality.

Metabolomics in Acute Kidney Injury: The Experimental Perspective.

Acute kidney injury (AKI) affects increasing numbers of in-hospital patients in Central Europe and the USA, the prognosis remains poor. Although substantial progress has been achieved in the identification of molecular/cellular processes that induce and perpetuate AKI, more integrated pathophysiological perspectives are missing. Metabolomics enables the identification of low-molecular-weight (< 1.5 kD) substances from biological specimens such as certain types of fluid or tissue. The aim of the article was to review the literature on metabolic profiling in experimental AKI and to answer the question if metabolomics allows the integration of distinct pathophysiological events such as tubulopathy and microvasculopathy in ischemic and toxic AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 1940 until 2022. The following terms were utilized: "acute kidney injury" OR "acute renal failure" OR "AKI" AND "metabolomics" OR "metabolic profiling" OR "omics" AND "ischemic" OR "toxic" OR "drug-induced" OR "sepsis" OR "LPS" OR "cisplatin" OR "cardiorenal" OR "CRS" AND "mouse" OR "mice" OR "murine" OR "rats" OR "rat". Additional search terms were "cardiac surgery", "cardiopulmonary bypass", "pig", "dog", and "swine". In total, 13 studies were identified. Five studies were related to ischemic, seven studies to toxic (lipopolysaccharide (LPS), cisplatin), and one study to heat shock-associated AKI. Only one study, related to cisplatin-induced AKI, was performed as a targeted analysis. The majority of the studies identified multiple metabolic deteriorations upon ischemia/the administration of LPS or cisplatin (e.g., amino acid, glucose, lipid metabolism). Particularly, abnormalities in the lipid homeostasis were shown under almost all experimental conditions. LPS-induced AKI most likely depends on the alterations in the tryptophan metabolism. Metabolomics studies provide a deeper understanding of pathophysiological links between distinct processes that are responsible for functional impairment/structural damage in ischemic or toxic or other types of AKI.

Metabolomics in Acute Kidney Injury: The Clinical Perspective.

BACKGROUND: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients worldwide. The diagnosis of AKI is made too late in most individuals since it is still based on dynamic changes in serum creatinine. In recent years, new AKI biomarkers have been identified; however, none of these can reliably replace serum creatinine yet. Metabolomic profiling (metabolomics) allows the concomitant detection and quantification of large numbers of metabolites from biological specimens. The current article aims to summarize clinical studies on metabolomics in AKI diagnosis and risk prediction. METHODS: The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus, and the period lasted from 1940 until 2022. The following terms were utilized: 'AKI' OR 'Acute Kidney Injury' OR 'Acute Renal Failure' AND 'metabolomics' OR 'metabolic profiling' OR 'omics' AND 'risk' OR 'death' OR 'survival' OR 'dialysis' OR 'KRT' OR 'kidney replacement therapy' OR 'RRT' OR 'renal replacement therapy' OR 'recovery of kidney function' OR 'renal recovery' OR 'kidney recovery' OR 'outcome'. Studies on AKI risk prediction were only selected if metabolomic profiling allowed differentiation between subjects that fulfilled a risk category (death or KRT or recovery of kidney function) and those who did not. Experimental (animal-based) studies were not included. RESULTS: In total, eight studies were identified. Six studies were related to the diagnosis of AKI; two studies were performed on metabolic analysis in AKI risk (death) prediction. Metabolomics studies in AKI already helped to identify new biomarkers for AKI diagnosis. The data on metabolomics for AKI risk prediction (death, KRT, recovery of kidney function), however, are very limited. CONCLUSIONS: Both the heterogenous etiology and the high degree of pathogenetic complexity of AKI most likely require integrated approaches such as metabolomics and/or additional types of '-omics' studies to improve clinical outcomes in AKI.

Increased Serum Sodium at Acute Kidney Injury Onset Predicts In-Hospital Death.

Background: Over the last decades, acute kidney injury (AKI) has been identified as a potentially fatal diagnosis which substantially increases in-hospital mortality in the short term and morbidity/mortality in the long term. However, reliable biomarkers for predicting AKI-associated outcomes are still missing. In this study, we assessed whether serum sodium, measured at different time points during the in-hospital treatment period, provided prognostic information in AKI. Methods: This was a retrospective, observational cohort study. AKI subjects were identified via the in-hospital AKI alert system. Serum sodium and potassium levels were documented at five pre-defined time points: hospital admission, AKI onset, minimum estimated glomerular filtration rate, minimum and maximum of the respective electrolyte during the treatment period. In-hospital death, the need for kidney replacement therapy (KRT) and recovery of kidney function were defined as endpoints. Results: Patients who suffered in-hospital death (n = 37, 23.1%) showed significantly higher serum sodium levels at diagnosis of AKI (survivors: 145.7 ± 2.13 vs. non-survivors: 138.8 ± 0.636 mmol/L, P = 0.003). A logistic regression model was significant for serum sodium levels in patients with in-hospital death (X2, P = 0.003; odds ratio = 1.08 (1.022 - 1.141); R2 = 0.082; d = 0.089). This suggests an increase of the relative risk for in-hospital death by 8% with every unit of serum sodium increase. Patients with a sodium above the upper normal range at AKI diagnosis were also more likely to suffer in-hospital death (P = 0.001). Conclusion: In summary, we present evidence that serum sodium, measured at time of AKI diagnosis, potentially serves as a predictor for in-hospital death in patients with AKI.

Stratification of Acute Kidney Injury Risk, Disease Severity, and Outcomes by Electrolyte Disturbances.

Acute kidney injury (AKI) affects up to 30% of all hospitalized patients in Central Europe and the USA. New biomarker molecules have been identified in recent years; most studies performed so far however aimed to identify markers for diagnostic purposes. Serum electrolytes such as sodium and potassium are quantified in more or less all hospitalized patients. Aim of the article is to review the literature on the AKI predictive role of four distinct serum electrolytes in evolving/progressing AKI. The following databases were searched for references: PubMed, Web of Science, Cochrane Library, and Scopus. The period lasted from 2010 until 2022. The following terms were utilized: "AKI" AND "sodium" OR "potassium" OR "calcium" OR "phosphate" AND "risk" OR "dialysis" OR "recovery of kidney function" OR "renal recovery" OR "kidney recovery" OR "outcome". Finally, 17 references were selected. The included studies were mostly retrospective in nature. Particularly, hyponatremia has been shown to be associated with an overall poor clinical outcome. The association between dysnatremia and AKI is anything but consistent. Hyperkalemia and potassium variability are most likely AKI predictive. Serum calcium and AKI risk are associated in a U-shaped manner. Higher phosphate levels potentially predict AKI in non-coronavirus disease 2019 (COVID-19) patients. The literature suggests that admission electrolytes can offer valuable information about AKI onset during follow-up. Limited data are however available on follow-up characteristics such as the need for dialysis or the chance of renal recovery. These aspects are of particular interest from the nephrologist's perspective.

Kidney Replacement Therapy in Cardiorenal Syndromes.

Cardiorenal syndromes (CRS) have increasingly been recognized as distinct disorders that affect the heart and kidneys simultaneously, either with acute or chronic onset. The different types share common pathophysiological characteristics. The concept "cardiorenal" shall emphasize the inter- or even multidisciplinary approach to respective patients. Anticongestive therapy becomes mandatory in many subjects that suffer from CRS. In recent years, the role of dialysis treatment in a broader sense has been investigated in CRS in more detail. We performed a search for studies related to the topic in the following databases: MEDLINE, PROSPERO, and Web of Science. The following keywords were used for reference identification: "CRS", "cardiorenal syndrome", "dialysis", "hemodialysis", "hemofiltration", "renal replacement therapy", "kidney replacement therapy", "peritoneal dialysis", and "aquapheresis". Finally, a total number of 22 studies, partly performed as retrospective cohort studies, and partly designed as prospective investigations, were included. The selected studies evaluated different modes of peritoneal dialysis (PD) or of non-PD procedures including intermittent hemodialysis, continuous procedures, and so-called aquapheresis. Inclusion and outcome parameters were almost not comparable between selected trials. Some studies revealed dialysis as effective, with reasonable tolerability. Particularly so-called "pure" ultrafiltration (e.g., aquapheresis) was associated with higher rates of adverse events. Future studies should be designed in a more homogenous manner, particularly concerning the inclusion criteria, the respective dialysis procedure applied, and endpoints in the short- and long-term.

Etiology and Management of Acute Metabolic Acidosis: An Update.

BACKGROUND: The etiology of acute metabolic acidosis (aMA) is heterogeneous, and the consequences are potentially life-threatening. The aim of this article was to summarize the causes and management of aMA from a clinician's perspective. SUMMARY: We performed a systematic search on PubMed, applying the following search terms: "acute metabolic acidosis," "lactic acidosis," "metformin" AND "acidosis," "unbalanced solutions" AND "acidosis," "bicarbonate" AND "acidosis" AND "outcome," "acute metabolic acidosis" AND "management," and "acute metabolic acidosis" AND "renal replacement therapy (RRT)/dialysis." The literature search did not consider diabetic ketoacidosis at all. Lactic acidosis evolves from various conditions, either with or without systemic hypoxia. The incidence of metformin-associated aMA is actually quite low. Unbalanced electrolyte preparations can induce hyperchloremic aMA. The latter potentially worsens kidney-related outcome parameters. Nevertheless, prospective and controlled data are missing at the moment. Recently, bicarbonate has been shown to improve clinically relevant endpoints in the critically ill, even if higher pH values (>7.3) are targeted. New therapeutics for aMA control are under development, since bicarbonate treatment can induce serious side effects. Key Messages: aMA is a frequent and potentially life-threatening complication of various conditions. Lactic acidosis might occur even in the absence of systemic hypoxia. The incidence of metformin-associated aMA is comparably low. Unbalanced electrolyte solutions induce hyperchloremic aMA, which most likely worsens the renal prognosis of critically ill patients. Bicarbonate, although potentially deleterious due to increased carbon dioxide production with subsequent intracellular acidosis, improves kidney-related endpoints in the critically ill.