The impact of acute kidney damage in the community.

BACKGROUND AND HYPOTHESIS: Assess incidence of Acute Kidney Diseas and Disorders (AKD) and Acute Kidney Injury (AKI) episodes and impact on progression of renal dysfunction and risk of all-cause mortality in the community. METHODS: Community of 1 863 731 aged > 23 years with at least two serum creatinine measurements. eGFR was calculated using CKD-EPI formula. CKD, AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The sCr values and RIFLE scale was used to classify episodes. Progression of renal dysfunction and mortality were evaluated. RESULTS: 56 850 episodes of AKD in 47 972 patients in 4.8 years were identified. AKD incidence of AKD was 3.51 and 12.56/1000 patients/year in non-CKD and CKD, respectively. One AKD episode was observed in 87.3% patients, two in 9.3% and three or more in 3.4%. A second episode was less common in patients without CKD (10.3%) compared to those with CKD (18.4%). Among patients without CKD a total of 43.8% progressed to CKD, and those with previous CKD 63.1% had eGFR decline of > 50%. The risk of progression to CKD was higher in women, older, overweight-obesity and heart failure, as was the risk of eGFR decline > 50% in CKD patients, although the number of AKD episodes was also a risk factor. AKI episodes were observed in 5646 patients with or without CKD. Of these, 12.7% progressed to CKD and of those with pre-existing CKD, 43.2% had an eGFR decline of > 20%. In the toal population mortality within 3 months of detection of AKD episode occurred in 7% patients, and was even higher in patients with AKI, 30.1%. CONCLUSION: Acute elevations in serum creatinine in the community may pose a health risk and contribute to the development of CKD. Identification of therapeutic targets and provision of appropriate follow-up for those who survive an episode is warranted.

Hypercalcemia as a rare manifestation of immune reconstitution inflammatory syndrome (IRIS) in a person living with Human Immunodeficiency Virus (HIV) with disseminated nontuberculous mycobacteriosis.

INTRODUCTION: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). CASE PRESENTATION: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. CONCLUSION: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.

Prion Protein Overexpression in Adipose-Derived Mesenchymal Stem Cells (ADMSCs) Effectively Protected Rodent Kidney Against Ischemia-Reperfusion Injury Via Enhancing ATP/Mitochondrial Biogenesis-Role of ADMSC Rejuvenation and Proliferation.

BACKGROUND: We tested the hypothesis that overexpression of cellular-prion-protein in adipose-derived mesenchymal stem cells (PrPCOE-ADMSCs) effectively protected the kidney against ischemia-reperfusion (IR) injury in rat. METHODS: Part I of cell culture was categorized into A1(ADMSCs)/A2(ADMSCs+p-Cresol)/A3(PrPCOE in ADMSCs)/A4 (PrPCOE in ADMSCs+p-Cresol). Part II of cell culture was divided into B1(ADMSCs)/B2[ADMSCs+lipopolysaccharide (LPS)]/B3(PrPCOE in ADMSCs)/B4(PrPCOE in ADMSCs+LPS). Sprague-Dawley (SD) rats (n = 50) were equally categorized into groups 1 (sham-operated-control)/2 (IR)/3 (IR+ADMSCs/6.0 × 105 equally divided into bilateral-renal arteries and 6.0 × 105 intravenous administration by 1 h after IR)/4 [IR+PrPCOE-ADMSCs (identical dosage administered as group 3)]/5 [IR+silencing PRNP -ADMSCs (identical dosage administered as group 3)], and kidneys were harvested post-day 3 IR injury. RESULTS: Part I results demonstrated that the cell viability at 24/48/72 h, BrdU uptake/number of mitDNA/APT concentration/mitochondrial-cytochrome-C+ cells and the protein expressions of ki67/PrPC at 72 h-cell culturing were significantly higher in PrPCOE-ADMSCs than in ADMSCs (all P < 0.001). The protein expressions of oxidative-stress (NOX-1/NOX2/NOX4/oxidized protein)/mitochondrial-damaged (p22-phox/cytosolic-cytochrome-C)/inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers were lowest in A1/A3 and significantly higher in A2 than in A4 (all P < 0.001). Part II result showed that the protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/IL-6)/apoptotic (cleaved caspase-3/cleaved-PARP) biomarkers exhibited an identical pattern of part I among the groups (all P < 0.001). The protein expressions of inflammatory (p-NF-κB/IL-1ß/TNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized-protein)/mitochondrial-damaged (cytosolic-cytochrome-C/p22-phox)/apoptotic (cleaved caspase-3/cleaved-PARP/mitochondrial-Bx)/autophagic (beclin-1/ratio of LC3B-II/LC3B-I)/fibrotic (Smad3/TGF-ß) biomarkers and kidney-injury-score/creatinine level were lowest in group 1, highest in group 2, significantly higher in group 5 than in groups 3/4 (all P < 0.0001). CONCLUSION: PrPCOE in ADMSCs rejuvenated these cells and played a cardinal role on protecting the kidney against IR injury.

Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?

The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.

Case Report and Supporting Documentation: Acute Kidney Injury Manifested as Oliguria Is Reduced by Intravenous Magnesium Before Cisplatin.

After more than four decades of post-approval, cisplatin is still an important treatment for numerous cancers. However, acute kidney injury (AKI), defined as significant impairment of renal filtration as discussed below, is the major limiting side effect of cisplatin, occurring in approximately 30% of patients (25-33% after the first course). Cisplatin also damages the kidneys' ability to reabsorb magnesium in 40-100% of patients, with collateral health risks due to subsequent hypomagnesemia. Multiple methods and drugs have been proposed for preventing cisplatin-induced AKI, including saline infusion with or without mannitol, which has not always prevented AKI and has been found to activate a cellular stress response in renal tubular cells. While numerous reports and trials, as well as the National Comprehensive Cancer Network (NCCN), support premedication with magnesium and hydration, this practice has not been universally accepted. Many clinics administer intravenous magnesium (IV) only after identification of hypomagnesemia post-cisplatin treatment, thus placing patients at risk for AKI and chronic renal loss of magnesium. We present the following case report and additional supporting evidence identifying the immediate effect of IV magnesium prior to intraperitoneal cisplatin for cycle 4 because of documented hypomagnesemia resulting in normalization of oliguria, which had been experienced for the first three cycles. The patient subsequently requested and received IV magnesium before cisplatin for the next two cycles with continuation of normal urinary output. The effect of pretreatment with IV magnesium on urine output following cisplatin has not been previously reported and further supports pre-cisplatin administration. In addition, two recent meta-analyses of clinical trials and pre-clinical research are reviewed that demonstrate effectiveness of magnesium pretreatment to preventing AKI without reducing its chemotherapeutic efficacy. This case report with additional evidence supports the adoption of administration of 1-3 g IV magnesium before cisplatin as best practice to prevent cisplatin induced AKI and hypomagnesemia regardless of patient baseline serum magnesium levels.

Outcomes of COVID-19 Among Hospitalized Patients With Non-dialysis CKD.

Background: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Corona Virus 2 has generated significant impact on global health worldwide. COVID-19 can cause pneumonia and organ injury. Chronic kidney disease (CKD) has been associated with increased mortality in previous epidemics, but there is a paucity of data regarding actual risks for non-dialysis CKD patients with COVID-19. Methods: Multicenter, observational cohort study including 136 non-dialysis CKD patients and 136 age- and sex-matched controls that required hospitalization due to COVID-19. Patients with end-stage renal disease, a kidney transplant or without registered baseline glomerular filtration rate prior to COVID-19 infection were excluded. CKD and acute kidney injury (AKI) were defined according to KDIGO criteria. Results: CKD patients had higher white blood cell count and D-dimer and lower lymphocyte percentage. No differences were found regarding symptoms on admission. CKD was associated with higher rate of AKI (61 vs. 24.3%) and mortality (40.4 vs. 24.3%). Patients with AKI had the highest hazard for death (AKI/non-CKD HR:7.04, 95% CI:2.87-17.29; AKI/CKD HR:5.25, 95% CI: 2.29-12.02), followed by CKD subjects without AKI (HR:3.39, 95% CI:1.36-8.46). CKD status did not condition ICU admission or length of in-hospital stay. Conclusions: CKD patients that require hospitalization due to COVID-19 are exposed to higher risk of death and AKI.

Daño renal agudo en pacientes con ventilación mecánica invasiva, Guantánamo 2018-2019 / Acute kidney injury in patients with invasive mechanical ventilation in Guantanamo, 2018-2019

RESUMEN Introducción: El daño renal agudo es una complicación frecuente en las Unidades de Terapia Intensiva, sobre todo en pacientes con ventilación mecánica. Objetivo: Caracterizar el daño renal agudo en los pacientes tratados con ventilación mecánica invasiva en la Unidad de Terapia Intensiva del Hospital General Docente "Dr. Agostinho Neto" durante el periodo 2108-2019. Método: Se realizó un estudio descriptivo, retrospectivo y longitudinal, que se aprobó por el Comité de Ética. El universo de estudio se constituyó por el total de pacientes con este diagnóstico según la clasificación Acute Kidney Injury Network (AKIN). Se estudiaron las características de los pacientes (necesidad y duración de la VAM, necesidad de hemodiálisis, estado al egreso) y del daño renal agudo (estadio y etiología). Resultados: El 47,5 % de los pacientes tratados con este soporte vital presentó un daño renal agudo, sobre todo los que la demandaron por siete o más días (68,4 %). El riesgo de muerte fue superior en los pacientes que requirieron ventilación mecánica o hemodiálisis. En los pacientes con daño renal estadio 2 y 3 de la clasificación que se utilizó presentaron un riesgo tres veces o más superior comparado con los que no necesitaron estas terapias. La sepsis (69,4 %) fue la principal causa del daño renal agudo. Conclusiones: El uso de ventilación mecánica invasiva y la presentación de un daño renal agudo son condiciones con una fuerte asociación, juntas y separadas se correlacionan con la mortalidad.

ABSTRACT Introduction: Acute kidney injury is a very common complication in the intensive care units, especially in patients with invasive mechanical ventilation. Objective: To characterize acute kidney damage in patients with invasive mechanical ventilation in the intensive care unit at the General Teaching Hospital ¨Dr. Agostinho Neto¨ within the period 2018-2019. Method: A descriptive, retrospective and longitudinal study approved by the Ethics Committee was carried out. The study population was constituted by the total of patients with the diagnosis, according to the Acute Kidney Injury Network (AKIN). Characteristics and variables like: reason for the invasive mechanical ventilation, its duration, hemodialysis, and status of the patient at time of discharge were taken into account, along with the characteristics of the kidney injury (stages and etiology). Results: 47.5 % of the patients treated with life support showed acute kidney injury, especially the ones with more than a week of mechanical ventilation (68.4 %). The risk of death was higher in the patients with mechanical ventilation and hemodialysis. In the patients with stage 2 and 3 of the scale used for kidney injury presented 3 times more risk compared to those who did not require these treatments. Sepsis was the main cause of acute kidney injury (69.4 %). Conclusions: the use of invasive mechanical ventilation and acute kidney injury are deeply related to each other, both of them constitute main issues in the variables of mortality.

The Impact of Versatile Macrophage Functions on Acute Kidney Injury and Its Outcomes.

Acute kidney injury (AKI) is a common and devastating clinical condition with a high morbidity and mortality rate and is associated with a rapid decline of kidney function mostly resulting from the injury of proximal tubules. AKI is typically accompanied by inflammation and immune activation and involves macrophages (Mϕ) from the beginning: The inflamed kidney recruits "classically" activated (M1) Mϕ, which are initially poised to destroy potential pathogens, exacerbating inflammation. Of note, they soon turn into "alternatively" activated (M2) Mϕ and promote immunosuppression and tissue regeneration. Based on their roles in kidney recovery, there is a growing interest to use M2 Mϕ and Mϕ-modulating agents therapeutically against AKI. However, it is pertinent to note that the clinical translation of Mϕ-based therapies needs to be critically reviewed and questioned since Mϕ are functionally plastic with versatile roles in AKI and some Mϕ functions are detrimental to the kidney during AKI. In this review, we discuss the current state of knowledge on the biology of different Mϕ subtypes during AKI and, especially, on their role in AKI and assess the impact of versatile Mϕ functions on AKI based on the findings from translational AKI studies.

Protective effects of N-acetyl-cysteine in mitochondria bioenergetics, oxidative stress, dynamics and S-glutathionylation alterations in acute kidney damage induced by folic acid.

Folic acid (FA)-induced acute kidney injury (AKI) is a widely used model for studies of the renal damage and its progression to chronic state. However, the molecular mechanisms by which FA induces AKI remain poorly understood. Since renal function depends on mitochondrial homeostasis, it has been suggested that mitochondrial alterations contribute to AKI development. Additionally, N-acetyl-cysteine (NAC) can be a protective agent to prevent mitochondrial and renal dysfunction in this model, given its ability to increase mitochondrial glutathione (GSH) and to control the S-glutathionylation levels, a reversible post-translational modification that has emerged as a mechanism able to link mitochondrial energy metabolism and redox homeostasis. However, this hypothesis has not been explored. The present study demonstrates for the first time that, at 24 h, FA induced mitochondrial bioenergetics, redox state, dynamics and mitophagy alterations, which are involved in the mechanisms responsible for the AKI development. On the other hand, NAC preadministration was able to prevent mitochondrial bioenergetics, redox state and dynamics alterations as well as renal damage. The protective effects of NAC on mitochondria and renal function could be related to its observed capacity to preserve the S-glutathionylation process and GSH levels in mitochondria. Taken together, our results support the idea that these mitochondrial processes can be targets for the prevention of the renal damage and its progression in FA-induced AKI model.

Acetobacter indonesiensis Pneumonia after Lung Transplantation.

We report a case of Acetobacter indonesiensis pneumonia in a 51-year-old woman after bilateral lung transplantation. We found 2 other A. indonesiensis pneumonia cases reported in the literature. All 3 cases involved complex patients exposed to broad-spectrum antimicrobial drugs, suggesting that this pathogen may be opportunistic and highly drug-resistant.

Dexmedetomidine ameliorates the inflammatory immune response in rats with acute kidney damage.

It has been demonstrated that dexmedetomidine (Dex) can protect patients with acute kidney injury from experiencing further tissue damage, however its mechanism of action remains unclear. The present study investigated the immune modulatory functions of Dex in rats with acute kidney injury (AKI) induced via injection of lipopolysaccharide into the tail vein. ELISA analysis showed that Dex reduced the levels of inflammatory cytokines in rats with AKI in a dose dependent manner. Furthermore, the regulatory effects of Dex on cytokine production disappeared when the α-2 adrenergic receptor antagonist Yohimbine (YOH) was added. For a detailed investigation on how Dex regulates the immune response in rats with AKI, the impact of Dex on the viability of splenocytes and lymphocytes was determined and it was determined that Dex did not influence splenocyte and lymphocyte viability. In addition, ELISA tests showed that Dex regulated the production of the T-helper (Th) 17 cytokines interleukin (IL)-17 and IL-23, but not the Th1 cytokine tumor necrosis factor α, in splenocytes and lymphocytes. To confirm whether Dex functioned as an α-2-adrenergic receptor in these immune regulations, YOH was administered together with Dex. When Dex and YOH were administered together, the regulatory functions of Dex were reduced, confirming that Dex acted as an agonist on the α-2-adrenergic receptor. Thus the results of the current study may provide novel insights regarding how Dex modulates immune functions in AKI.

Nephroprotective Effect of EDL Peptide at Acute Injury of Kidneys of Different Genesis.

EDL peptide produced a nephroprotective effect on experimental models gentamycin-induced nephropathy and ischemia/reperfusion kidney injury in rats. The nephroprotective effect of EDL peptide manifested in prevention of oliguria and retention azotemia, a decrease in proteinuria and sodium excretion, prevention of critical decrease in activities of antioxidant enzymes, suppression of LPO, and normalization of energy supply to kidneys cells. Our findings confirm the prospects of further studies of the nephroprotective properties of peptide EDL in various pathologies of the kidneys.