Multiple blood gas variables predict AKI survival in an independent manner.

BACKGROUND AND AIM: Acute kidney injury (AKI) is becoming increasingly prevalent among hospitalized patients and carries a poor prognosis. While new biomarkers show promise in identifying early stages of AKI, accurately predicting severe outcomes such as the need for kidney replacement therapy (KRT) or death remains a challenge. However, blood gas analyses (BGA) can be used to diagnose life-threatening complications associated with AKI. The objective of this study was to assess the role of BGA as a biomarker panel in both emerging and established cases of AKI. METHODS: Retrospective observational study examining subjects with newly developed acute kidney injury (AKI). The study will document venous and arterial pH, pCO2, and actual bicarbonate levels upon hospital admission and at the onset of AKI. The primary endpoints include in-hospital mortality, the need for kidney replacement therapy (KRT), and the recovery of kidney function (ROKF). RESULTS: A total of 202 individuals were included in the study. Three variables were found to be independent predictors of in-hospital survival: admission arterial pH, arterial pH at acute kidney injury (AKI) onset, and arterial pCO2 at AKI onset. Additionally, venous pCO2 at AKI onset was identified as an independent predictor for the need of kidney replacement therapy (KRT). CONCLUSIONS: Our study suggests that blood gas analysis may have a potential role in predicting severe outcome variables in acute kidney injury (AKI). The associated costs are minimal.

Electronic Acute Kidney Injury Alert at the Brandenburg Medical School: Implementation and Follow-Up.

INTRODUCTION: Acute kidney injury (AKI) substantially worsens the prognosis of hospitalized patients worldwide. In order to optimize early AKI recognition and therapeutic intervention, AKI alert systems have been implemented and evaluated in the past. Herein, we aimed to analyze outcome variables of AKI patients under the conditions of a de novo-established AKI alert system at the Brandenburg Hospital of the Brandenburg Medical School. METHODS: Automated e-mail messages were generated and sent to the nephrologist with responsibility based on an electronic algorithm. The message was exclusively generated if one of the two first KDIGO criteria was fulfilled. During period 1, all alerts were ignored. During the second period, every alert was followed up, coupled with therapeutic management of respective individuals according to an AKI care bundle. Endpoints were in-hospital death, need for dialysis, and renal recovery. RESULTS: In periods 1 and 2, 200 and 112 patients were included. In period 1, 150 out of 200 AKI alerts were identified as correct (75%); in the second period, 93 out of 112 AKI alerts were accepted as correct (83%) (p = 0.16). Kidney replacement therapy was initiated in 21 (14%) of all period 1 patients and in 32 (34.4%) of the period 2 patients (p = 0.017). In-hospital mortality of affected patients was 24 (16%) in period 1 and 21 (22.5%) in period 2 (p = 0.4). Restoration of kidney function was 69 (46%) in period 1 and 45 (48.3%) in period 2 (p = 0.71). CONCLUSIONS: We finally conclude that an AKI alert system, as implemented and followed-up in our study, did not significantly improve clinically relevant endpoints in AKI patients. Potential weaknesses were the lack of documentation of the time between receiving the alert and patient contact, and physicians in responsibility were not particularly informed about the alert system.

Biomarker-Based Prediction of Survival and Recovery of Kidney Function in Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) affects increasing numbers of hospitalized patients; the prognosis remains poor. The diagnosis is still based on the 2012 published KDIGO criteria. Numerous new AKI biomarkers have been identified in recent years; they either reflect impaired excretory function or structural damage. The majority of markers are useful for AKI recognition under certain circumstances. Fewer data are available on the role of biomarkers in the prediction of in-hospital survival and renal recovery post-AKI. The current article is intended to provide information about these two aspects. SUMMARY: The following databases were screened: PubMed, Web of Science, Cochrane Library, Scopus. The period lasted from 2000 until 2022. The following terms were applied: "AKI" AND "biomarker" AND "survival" OR "mortality" OR "recovery of kidney function" OR "renal recovery" OR "kidney recovery". The following terms were used for additional literature search: "TIMP-2" AND "IGFBP7" and "RNA biomarker" AND "hematology". Regarding mortality, exclusively those studies were selected that addressed the in-hospital mortality. Nine (9) studies were identified that evaluated biomarker-based prediction of in-hospital mortality and/or of recovery of kidney function (ROKF). A homogenous definition of ROKF is however missing yet. Currently, some biomarkers, measured early during the course of the disease, are associated with increased mortality risk and/or with a higher chance of renal recovery. KEY MESSAGES: The literature provides only a few biomarker-related studies that address the issues of mortality and recovery. The definition of ROKF needs to be homogenized.

Secondary Prevention of Potentially Life-Threatening Arrhythmia Using Implantable Cardioverter Defibrillators in Patients with Biopsy-Proven Viral Myocarditis and Preserved Ejection Fraction.

BACKGROUND: Arrhythmia and sudden cardiac death (SCD) are known complications of acute viral myocarditis, regardless of ejection fraction (EF) at presentation. Whether such complications confer long-term risk is unknown, especially in those who present with preserved left ventricular (LV) function. No guidelines exist to the long-term reduction of arrhythmic death in such patients. METHOD: In this retrospective study, we analyzed the long-term results of implantable cardioverter defibrillator (ICD) treatment in patients after an acute phase of myocarditis with life-threatening arrhythmia. RESULTS: We identified 51 patients who had ICDs implanted following life-threatening arrhythmia presentation of confirmed acute viral myocarditis, despite preserved LVEF. Overall, 72.5% of patients had a clinical history of chest pain and viral infection with fever. Viral myocarditis was confirmed by cardiac magnetic resonance imaging (all had late enhancement) plus endomyocardial biopsies (most frequent were Epstein-Barr virus 29.4%, adenovirus 17.6%, and Coxsackie 17.6%), and 88.2% were discharged on anti-arrhythmic drugs. Overall, 12 patients (23.5%) required ICD intervention within the first 3 months, a further 7 patients (37.3% overall) between 3 and 12 months, and a further 12 patients (60.8% overall) until 58 months. During the follow-up, 3 of 51 patients (5.9%) died-deaths were due to cardiac events (n = 1), fatal infection (n = 1), and car accidents (n = 1). Of the 31 patients who had ventricular tachycardias after the acute phase of myocarditis, 11 needed radiofrequency ablation due to a high number of events or electrical storm. No baseline variables were identified that would serve as a basis for risk stratification. CONCLUSION: Malignant arrhythmic events due to viral myocarditis are potential predictors of future SCD in patients not only with a reduced but also with a preserved EF.

Chronic Metabolic Acidosis in Chronic Kidney Disease.

BACKGROUND: Metabolic acidosis may be diagnosed as chronic (cMA) if it persists for at least 5 days, although an exact definition has not been provided by any guidelines yet. The most common cause is CKD; numerous less-known diseases can also account for cMA. SUMMARY: In recent years, CKD-associated cMA has been proposed to induce several clinical complications. The aim of the article was to assess the current clinical evidence for complications and the respective management of CKD-associated cMA. In summary, cMA in CKD most likely promotes protein degradation and loss of bone mineral density. It aggravates CKD progression as indicated by experimental and (partly) clinical data. Therefore, cMA control must be recommended. Besides oral bicarbonate, dietary interventions potentially offer an alternative. Veverimer is a future option for cMA control; further systematic data are needed. CONCLUSIONS: The most common cause of cMA is CKD. CKD-associated cMA most likely induces a negative protein balance; the exact role on bone metabolism remains uncertain. It presumably aggravates CKD progression. cMA control is recommendable; the serum bicarbonate target level should range around 24 mEq/L. Veverimer may be established as future option for cMA control; further systematic data are needed.

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.

Oral health-related quality of life in different rheumatic diseases.

OBJECTIVES: Aim of this cross-sectional study was to investigate oral health-related quality of life (OHRQoL) of patients with different rheumatic diseases. SUBJECTS AND METHODS: Patients with rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematodes (SLE), systemic sclerosis (SSc), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and vasculitis were included. OHRQoL was assessed with the German short form of oral health impact profile (OHIP G14). Age, disease duration, leukocytes, c-reactive protein (CRP) and haemoglobin counts were considered as disease related parameters. RESULTS: A total of 356 patients, assigned to the groups RA (n = 218), SLE (n = 36), AS (n = 36), PsA (n = 33), vasculitis (n = 19) and SSc (n = 14) were included. The OHIP G14 sub-scale psychosocial impact differed significantly between groups (p = .02). The OHIP G14 sum score was also significantly different between groups (p < .01). A medium-sized correlation was found for CRP with OHIP G14 sum score within SLE group (r = .344, p = .04). A large correlation was detected for leukocytes within PsA group (r = .525, p < .01). The reliability of the applied OHIP G14 was high. CONCLUSION: Patients with rheumatic disease show a reduced OHRQoL, with several differences between the entities. Psychosocial aspects appear to be of relevance and should be considered in multidisciplinary dental care of these patients.

Oral health-related quality of life in adult patients with end-stage kidney diseases undergoing renal replacement therapy - a systematic review.

BACKGROUND: The oral health of patients undergoing renal replacement therapy (RRT) is insufficient. Poor oral health and its components can affect the oral health-related quality of life (OHRQoL) of these patients. The aim of this systematic review was to assess the OHRQoL of adult patients under RRT. METHODS: A systematic literature search was performed using the terms: dialysis OR "renal disease" OR kidney OR "renal failure" OR "kidney transplantation" OR hemodialysis OR "peritoneal dialysis" OR "renal replacement therapy" AND "oral health-related quality of life", complemented by manual search. Clinical studies including adults (age ≥ 18 years) that were published between 2009 and 2019 were included in qualitative analysis. RESULTS: Twelve out of 20 studies were included in the qualitative analysis. The majority (11/12 studies) included patients undergoing haemodialysis (HD), with a sample size between 47 and 512 participants. Two studies included patients after kidney transplantation. Only one-quarter of the investigations included a healthy control group. The overall OHRQoL was found to be reduced. The majority of studies found relationships between OHRQoL and different oral health parameters. Furthermore, several relationships between OHRQoL and general quality of life as well as disease related parameters including age, gender, diabetes, blood parameters and dialysis duration were found. OHRQoL subscales psychological/psychosocial impairment and pain were predominantly affected. CONCLUSIONS: Patients under RRT suffer from a reduced OHRQoL, which is potentially influenced by oral health and disease related parameters. Interdisciplinary dental care is needed and should consider both physical and psychosocial issues.

Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury.

BACKGROUND: Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy. METHODS: Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later. RESULTS: Both, native and transfected EPCs (EPCsAtg5) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCsAtg5. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCsAtg5 completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells. CONCLUSIONS: Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.

Disease activity, morning stiffness and missing teeth are associated with oral health-related quality of life in individuals with rheumatoid arthritis.

OBJECTIVES: The aim of this cross-sectional study was to assess oral health-related quality of life (OHRQoL) in patients with rheumatoid arthritis (RA) and its relation to specific RA characteristics. MATERIAL AND METHODS: Within the oral examination, the need for dental (carious teeth showing cavitation) and periodontal treatment (presence of a probing depth ≥ 3.5 mm) and the number of missing teeth (M-T) were recorded. OHRQoL was assessed with the German short version of the Oral Health Impact Profile (OHIP G14). The disease activity score (DAS28-ESR), disease duration, number of swollen/painful joints and duration of morning stiffness were retrieved from the patient records. RESULTS: A total of 176 patients with a mean age of 62.5 ± 10.2 years were included. The overall OHIP G14 sum score was 5.4 ± 7.1. The M-T showed a significant correlation with the dimensions of oral function (r = 0.25, p = 0.001) and psychosocial impact (r = 0.20, p = 0.009) and the sum score (r = 0.26, p = 0.001). The DAS28-ESR showed a significant correlation with psychosocial impact (r = 0.19, p = 0.012) and the sum score (r = 0.16, p = 0.041). The duration of morning stiffness was correlated with oral function (r = 0.19, p = 0.019), psychosocial impact (r = 0.18, p = 0.024) and the sum score (r = 0.22, p = 0.006). The effect size of these correlations was interpreted as small. CONCLUSION: Disease activity, morning stiffness and missing teeth are associated to OHRQoL of patients with RA. Accordingly, multidisciplinary dental care appears necessary for these patients. CLINICAL RELEVANCE: The prevention of tooth loss as well as the consideration of psychosocial and disease-specific parameters in the multidisciplinary dental care of RA patients is necessary.

Loop Diuretics in Acute Kidney Injury Prevention, Therapy, and Risk Stratification.

BACKGROUND: Loop diuretics (LD) are widely used in emergency and intensive care medicine. SUMMARY: The substances increase the clearance of electrolytes and water; thus, they allow us to control hypervolemia and to prevent patients from pulmonary edema. LD are also frequently applied to patients with an acute decrease in glomerular filtration rate, namely, acute kidney injury (AKI). Nevertheless, volume depletion may be associated with reduced renal perfusion and possibly slower restitution or even aggravation of kidney dysfunction. Several trials on the preventive or therapeutic efficacy of LD have been published since the early 1970s. Our review article is intended to summarize the most important references related to this topic. In addition, we discuss the diagnostic value of the so-called furosemide stress test. The currently available data indicate that LD may act in a beneficial manner as long as euvolemia is maintained (matched hydration). Key Massages: LD are not beneficial for AKI treatment if kidney-related endpoints are considered. In certain situations, AKI prevention with LD can be associated with favorable outcomes as long as euvolemia is maintained. LD can help to identify AKI subjects at a higher risk of AKI progression, but the exact clinical consequences need to be determined.

Cytokine profiling in anti neutrophil cytoplasmic antibody-associated vasculitis: a cross-sectional cohort study.

ANCA-associated vasculitides (AAV) are severe diseases, potentially affecting lungs, kidney, and other organs. Nevertheless, risk profiling remains difficult. Aim of the current study was to analyze serological characteristics in AAV. The principal goal was to identify diagnostic markers that potentially allow a more sophisticated risk profiling in AAV. AAV subjects were recruited and evaluated for disease activity, disease stage, medication, and laboratory findings. Serum concentrations of the following parameters were measured: IL-1ß, IL-6, IL-17 A, IL-17 F, IL-21, IL-22, IL-23, TNF-α, sCD40L, IL-4, IL-10, IL-25, IL-31, IL-33, and INF-γ. A total number of 62 AAV subjects was included in the study (39 females; 23 males). Forty-five subjects were PR3+, 17 subjects showed ANCA specificity for MPO. The majority of all cytokines fell under the lower detection limit of the assay. Serum IL-10 was higher in both, AAV and SSc as compared to controls; it was also higher in early systemic AAV. Serum IL-33 was elevated in AAV and SSc; in AAV, higher levels were found in non-necrotizing GN and RTX untreated subjects. Serum CD40L was raised in AAV as well; higher concentrations were also found in PR3+ and MPO+ patients and early systemic, generalized, and refractory AAV. IL-10 may potentially serve as a marker of early systemic AAV. IL-33 may help to identify subjects with a higher risk for necrotizing GN in AAV.

Cell-Based Therapies in Acute Kidney Injury (AKI).

Acute kidney injury frequently occurs in hospitalized patients all over the world. The prognosis remains poor since specific therapies for promoting kidney regeneration/repair are still missing. In recent years cell-based strategies have improved AKI outcomes under experimental circumstances. Four groups of cells, each of them displaying certain biological and functional characteristics have been evaluated in AKI, induced Pluripotent Stem Cells (iPSCs), Spermatagonial Stem Cells (SSCs), Proangiogenic Cells (PACs) and Endothelial Colony Forming Cells (ECFCs), and Mesenchymal Stem Cells (MSCs). All of these have been documented to stabilize either parameters of kidney excretory dysfunction and/or certain morphological parameters. The mechanisms responsible for AKI protection include direct (cell incorporation) and indirect processes, the latter being mediated by humoral factors and particularly by the production of so-called extracellular vesicles. Cell-derived vesicular organelles have been shown to carry pro-regenerative micro-RNA molecules which stabilize the vascular and tubular function. The first trials in humans have been initiated, the majority of such trials employs MSCs. However, any transfer of cell-based strategies in the clinical practice is potentially associated with significant difficulties. These include cell availability, tolerance and competence. The article intends to summarize essential informations about all of the four populations mentioned above and to discuss implications for the management of human AKI.

Periodontal condition is associated with disease duration and motoric disabilities in patients with ankylosing spondylitis: results of a cross-sectional study.

OBJECTIVE: Recent literature reveals worse periodontal health condition in ankylosing spondylitis (AS). However, roles of AS-related parameters, periodontal condition, and their association appear unclear. This cross-sectional study aimed at investigating dental and periodontal health as well as potentially periodontal pathogenic bacteria in patients with AS compared to healthy control subjects (HC). METHODS: Dental examination comprised dental findings (DMF-T), periodontal probing depth (PPD), bleeding on probing, clinical attachment loss (CAL), papillary bleeding index, and microbiological analysis based on polymerase chain reaction of selected potentially periodontal pathogenic bacteria. Classification of periodontitis severity was based on PPD and/or CAL and divided into no/mild, moderate, and severe periodontitis. RESULTS: 52 participants with AS and 52 HC were included. 96% of the AS group and 75% of HC had moderate to severe periodontitis (moderate: AS = 26, HC = 34; severe: AS = 23, HC = 5; p < 0.01). Furthermore, a higher number of decayed teeth (D-T) were found in AS compared to HC (p = 0.02). A significant difference between AS und HC was detected for the prevalences of Parvimonas micra (AS = 92%, HC = 71%; p = 0.01), Eubacterium nodatum (AS = 35%, HC = 17%; p = 0.05), and Eikenella corrodens (AS = 96%, HC = 77%; p = 0.01). Bath Ankylosing Spondylitis Metrology Index (BASMI) and disease duration showed significant associations to PPD and CAL (p < 0.01). CONCLUSION: Patients with AS show worse dental and periodontal conditions compared to HC. Thereby, prevalence of bacteria related to insufficient oral hygiene was higher in AS. BASMI and duration of AS affect periodontal burden. Accordingly, particular attention considering dental care and oral hygiene in AS patients seems to be reasonable.

Oral health-related quality of life is associated with disease specific parameters in patients with ankylosing spondylitis.

BACKGROUND: The aim of this cross-sectional study was to investigate oral health-related quality of life (OHRQoL) in patients with ankylosing spondylitis (AS) and its association to oral health as well as AS specific parameters. METHODS: Patients with AS and a healthy control group (HC) were included and examined. The oral examination included decayed-, missing-, and filled-teeth index (DMF-T) as well as assessment of periodontal probing depth and clinical attachment loss to classify patients into healthy/mild, moderate, or severe periodontitis. Furthermore, the German short form of the oral health impact profile (OHIP G14) was used. RESULTS: A total of 50 patients each group (age: AS, 47.18 ± 15.67; HC, 55.82 ± 10.56; p < 0.01, gender male: AS, 52%; HC, 46%; p = 0.69) was included. AS patients showed worse D-T (p < 0.01) and periodontal condition (p = 0.01). The OHIP G14 score was clinically relevant and statistically significant higher in AS compared to HC (AS, 6.2 [2; 0-10.75]; HC, 1.7 [0; 0-2.0]; < 0.01). Only in HC, an association of OHIP G14 to DMF-T (p = 0.01) and M-T (p = 0.01) was found, while the OHIP G14 in AS group was not associated to oral health parameters. Within the AS group, the majority of investigated AS specific parameters were statistically significant and clinically relevant associated to OHIP G14 scores (pi < 0.05). CONCLUSION: Patients with AS show worse OHRQoL compared to HC, irrespective of oral status. The high general disease burden might affect OHRQoL, making an increased attention of these patients in dental care, especially considering psychological aspects, necessary. CLINICAL RELEVANCE: Increased consideration of psychosocial and disease related aspects in dental care of AS patients appear recommendable.

CD4+ lymphocyte adenosine triphosphate--a new marker in sepsis with acute kidney injury?

BACKGROUND: AKI frequently develops in sepsis patients, significantly decreasing the overall prognosis. There are currently no diagnostic markers available which reliably predict the prognosis of sepsis-associated AKI. Recently, ATP content of CD4+ T cells (ATP_CD4) has been shown to correlate with survival in sepsis. The aim of the study was to determine ATP_CD4 in sepsis-associated AKI. METHODS: Thirty-three patients with sepsis were prospectively analyzed for ATP_CD4 at three different time points. Results were related to survival, renal recovery, and further clinical/laboratory findings. RESULTS: ATP_CD4 tended to lower in concentration at 48 h after onset of sepsis in those patients with complete renal recovery. There were no differences between patients with no AKI and those with AKI of different severity (AKIN 1-3). Urinary NGAL did not correlate with renal prognosis. CONCLUSION: ATP_CD4 may serve as risk predictor in sepsis-associated AKI. Lower concentrations may indicate a higher chance of complete renal recovery in sepsis.

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.

Serum Nostrin-A risk factor of death, kidney replacement therapy and acute kidney disease in acute kidney injury.

BACKGROUND: The prediction of Acute Kidney Injury (AKI)-related outcomes remains challenging. Persistent kidney excretory dysfunction for longer than 7 days has been defined as Acute Kidney Disease (AKD). In this study, we prospectively quantified serum Nostrin, an essential regulator of endothelial NO metabolism, in hospitalized patients with AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University Hospital. Serum Nostrin, and serum NGAL and KIM-1 were measured within a maximum of 48 hours from the timepoint of initial diagnosis of AKI. The following endpoints were defined: in-hospital death, need of kidney replacement therapy (KRT), recovery of kidney function (ROKF) until discharge. RESULTS: AKI patients had significantly higher serum Nostrin levels compared to Controls. The level of serum Nostrin increased significantly with the severity of AKI. Within the group of AKI patients (n = 150) the in-hospital mortality was 16.7%, KRT was performed in 39.3%, no ROKF occurred in 28%. Patients who required KRT had significantly higher levels of serum Nostrin compared to patients who did not require KRT. Significantly higher levels of serum Nostrin were also detected in AKI patients without ROKF compared to patients with ROKF. In addition, low serum Nostrin levels at the timepoint of AKI diagnosis were predictive of in-hospital survival. For comparison, the serum concentrations of NGAL and KIM-1 were determined in parallel to the Nostrin concentrations and the results confirm the prognostic properties of serum Nostrin in AKI. CONCLUSIONS: The current study suggests serum Nostrin as novel biomarker of AKI-associated mortality, KRT and Acute Kidney Disease.

Clinically Evident Cardiopulmonary Congestion Does Not Significantly Impact the Prognosis of Patients With Septic Acute Kidney Injury.

Background: Acute kidney injury (AKI) is a common issue among in-hospital patients, with high mortality rates. Sepsis is a primary cause of AKI, particularly in the intensive care unit. Patients with septic AKI often experience cardiovascular congestion, leading to the formal classification of cardiorenal syndrome type 5. The study aimed to evaluate the prognosis of septic AKI patients with and without clinical evidence of cardiovascular congestion. Methods: This was a retrospective observational study. AKI patients were identified using the in-hospital AKI alert system. Sepsis was diagnosed based on laboratory, clinical, and hemodynamic characteristics, with additional consideration of the quickSOFA score. Cardiovascular congestion was diagnosed by assessing clinical (edema), radiographic (pulmonary congestion), echocardiographic (e.g., wall motion abnormalities), and laboratory variables (e.g., N-terminal pro-B-type natriuretic peptide). Endpoints included in-hospital survival, the need for kidney replacement therapy (KRT), and recovery of kidney function (ROKF). Results: In total, 102 patients were included, and cardiopulmonary congestion was diagnosed in 78.4%. Individuals with congestion did not differ from patients without congestion in any of the pre-defined endpoints. Conclusions: It is justified not to consider clinically apparent cardiovascular congestion in septic AKI patients as a risk factor for death per se. Rather, especially in the case of sepsis, clinically apparent positive fluid balance does not seem to be a disadvantage in terms of survival, KRT, and ROKF.

Bone morphogenetic protein-5 and early endothelial outgrowth cells (eEOCs) in acute ischemic kidney injury (AKI) and 5/6-chronic kidney disease.

Early endothelial outgrowth cells (eEOCs) reproducibly have been shown to act protectively in acute ischemic kidney injury (AKI) and chronic kidney injury. Bone morphogenetic protein-5 (BMP-5) acted antifibrotically in human hypertensive nephropathy. The aim of the current study was to analyze effects of BMP-5 treatment in an eEOC-based therapy of murine AKI and 5/6-nephrectomy. Male C57/Bl6N mice were either subjected to unilateral renal artery clamping postuninephrectomy or to 5/6-nephrectomy. Untreated or BMP-5-pretreated murine eEOCs were injected into recipient animals at the time of reperfusion (AKI) or at 2 and 5 days after 5/6-nephrectomy. Analysis of renal function and morphology was performed at 48 h and at 6 wk (AKI) or at 8 wk (5/6 model). Cellular consequences of eEOC treatment were evaluated using different in vitro assays. AKI was mitigated significantly by injecting BMP-5-pretreated eEOCs. Renal function was improved at 48 h [corrected] after cell therapy. In 5/6-nephrectomy, the cells failed to act renoprotectively, [corrected] but proteinuria was reduced after administering untreated eEOCs." Next, the original version read as "BMP-5 acts as a potent eEOC agonist in murine AKI in the short [corrected] term. Cell effects in 5/6-nephrectomy are heterogenous, but untreated cells act antifibrotically [corrected] without any impact on EnMT.