The prevalence of kidney diseases has been increasing worldwide due to the aging population and has results in an increased socioeconomic burden as well as increased morbidity and mortality. A deep understanding of the mechanisms underlying the physiological regulation of the kidney and the pathogenesis of related diseases can help identify potential therapeutic targets. The farnesoid X receptor (FXR, NR1H4) is a primary nuclear bile acid receptor that transcriptionally regulates bile acid homeostasis as well as glucose and lipid metabolism in multiple tissues. The roles of FXR in tissues other than hepatic and intestinal tissues are poorly understood. In studies over the past decade, FXR has been demonstrated to have a protective effect against kidney diseases through its anti-inflammatory and antifibrotic effects; it also plays roles in glucose and lipid metabolism in the kidney. In this review, we discuss the physiological role of FXR in the kidney and its pathophysiological roles in various kidney diseases, including acute kidney injury and chronic kidney diseases, diabetic nephropathy, and kidney fibrosis. Therefore, the regulatory mechanisms involving nuclear receptors, such as FXR, in the physiology and pathophysiology of the kidney and the development of agonists and antagonists for modulating FXR expression and activation should be elucidated to identify therapeutic targets for the treatment of kidney diseases.

Severe falciparum malaria is a medical emergency and a leading cause of death and neurodisability in endemic areas. Common complications include acute kidney injury (AKI) and cerebral malaria, and recent studies have suggested links between kidney and brain dysfunction in Plasmodium falciparum infection. Here, we review these new findings and present the hypothesis of a pivotal pathogenic crosstalk between the kidneys and the brain in severe falciparum malaria. We highlight the evidence of a role for distant organ involvement in the development of cerebral malaria and subsequent neurocognitive impairment post-recovery, describe the challenges associated with current diagnostic shortcomings for both AKI and brain involvement in severe falciparum malaria, and explore novel potential therapeutic strategies.

Uric acid is the end product of purine metabolism. Uric acid transporters in the renal proximal tubule plays a key role in uric acid transport. Functional abnormalities in these transporters could lead to high or low levels of uric acid in the blood plasma, known as hyperuricemia and hypouricemia, respectively. GLUT9 has been reported as a key transporter for uric acid reuptake in renal proximal tubule. GLUT9 mutation is known as causal gene for renal hypouricemia due to defective uric acid uptake, with more severe cases resulting in urolithiasis and exercise induced acute kidney injury (EIAKI). However, the effect of mutation is not fully investigated and hard to predict the change of binding affinity. We comprehensively described the effect of GLUT9 mutation for uric acid transport using molecular dynamics and investigated the specific site for uric acid binding diffeferences. R171C and R380W showed the significant disruption of the structure not affecting transport dynamics whereas L75R, G216R, N333S, and P412R showed the reduced affinity of the extracellular vestibular area towards urate. Interestingly, T125M showed a significant increase in intracellular binding energy, associated with distorted geometries. We can use this classification to consider the effect mutations by comparing the transport profiles of mutants against those of chemical candidates for transport and providing new perspectives to urate lowering drug discovery using GLUT9.

Acute kidney injury (AKI) is a serious and frequently observed disease associated with high morbidity and mortality. Weighted gene co-expression network analysis (WGCNA) is a research method that converts the relationship between tens of thousands of genes and phenotypes into the association between several gene sets and phenotypes. We screened potential target genes related to AKI through WGCNA to provide a reference for the diagnosis and treatment of AKI. Key biomolecules of AKI were investigated based on transcriptome analysis. RNA sequencing data from 39 kidney biopsy specimens of AKI patients and 9 normal subjects were downloaded from the GEO database. By WGCNA, the top 20% of mRNAs with the largest variance in the data matrix were used to construct a gene co-expression network with a p-value < 0.01 as a screening condition, showing that the blue module was most closely associated with AKI. Thirty-two candidate biomarker genes were screened according to the threshold values of |MM|≥0.86 and |GS|≥0.4, and PPI and enrichment analyses were performed. The top three genes with the most connected nodes, alanine-glyoxylate aminotransferase 2(AGXT2), serine hydroxymethyltransferase 1(SHMT1) and aconitase 2(ACO2), were selected as the central genes based on the PPI network. A rat AKI model was constructed, and the mRNA and protein expression levels of the central genes in the model and control groups were verified by PCR and immunohistochemistry experiments. The results showed that the relative mRNA expression and protein levels of AGXT2, SHMT1 and ACO2 showed a decrease in the model group. In conclusion, we inferred that there is a close association between AGXT2, SHMT1 and ACO2 genes and the development of AKI, and the down-regulation of their expression levels may induce AKI.

Renal vein thrombosis after kidney transplant is a rare but potentially graft-threatening event. As sequelae of this complication can range from brief acute kidney injury to total graft failure, it is necessary to maintain close clinical observation postoperatively. If posttransplant renal vein thrombosis does occur, recanalization may be attempted with mechanical thrombectomy, suction thrombectomy, or explantation and reimplantation of the allograft. This is a novel report of the successful use of suction thrombectomy to treat renal vein thrombosis in a pediatric kidney transplant.

Iron recycling prevents the development of anemia under homeostatic conditions. Whether iron recycling was co-opted as a defense strategy to prevent the development of anemia in response to infection is unclear. We find that in severe Plasmodium falciparum malaria, the onset of life-threatening anemia is associated with acute kidney injury (AKI), irrespective of parasite load. Using a well-established experimental rodent model of malaria anemia, we identify a transcriptional response that endows renal proximal tubule epithelial cells (RPTECs) with the capacity to store and recycle iron during P. chabaudi chabaudi (Pcc) infection. This response encompasses the induction of ferroportin 1/SLC40A1, which exports iron from RPTECs and counteracts AKI while supporting compensatory erythropoiesis and preventing the onset of life-threatening malarial anemia. Iron recycling by myeloid cells is dispensable to this protective response, suggesting that RPTECs provide an iron-recycling salvage pathway that prevents the pathogenesis of life-threatening malarial anemia.

Acute heart failure (AHF) is one of the main causes of unplanned hospitalization in patients >65 years of age and is associated with adverse outcomes in this population. Observational studies suggest that intravenous diuretic therapy given in the first hour of presentation for AHF was associated with favorable outcomes. To study the short-term prognostic associations of the timing of intravenous diuretic therapy in patients admitted to the emergency department (ED) for acute AHF. Patients treated in the ED with intravenous diuretics were selected from the Estratificação de Doentes com InsuFIciência Cardíaca Aguda (EDIFICA) registry, a prospective study including AHF hospitalized patients. Early and non-early furosemide treatment groups were considered using the 1-h cutoff: door-to-furosemide ≤1 h and >1 h. Primary outcomes were a composite of heart failure re-hospitalizations or cardiovascular death at 30- and 90-days. Four-hundred ninety-three patients were included in the analysis. The median (interquartile range) door-to-furosemide time was 85 (41-220) min, and 210 (43%) patients had diuretics in the first hour. Patients in the ≤1 h group had higher evaluation priority according to the Manchester Triage System, presented more often with acute pulmonary edema, warm-wet clinical profile, higher blood pressure, and signs of left-side heart failure, while >1 h group had higher Get With the Guidelines-heart failure risk score, more frequent signs of right-side heart failure, higher circulating B-type natriuretic peptides and lower albumin. Door-to-furosemide ≤ 1 h was independently associated with lower 30-day heart failure hospitalizations and composite of heart failure hospitalizations or cardiovascular death (adjusted analysis Heart Failure Hospitalizations: odds ratios (OR) 3.65; 95% confidence interval (CI), 1.22-10.9; P = 0.020; heart failure hospitalizations or cardiovascular death: OR 3.15; 95% CI, 1.49-6.64; P < 0.001). These independent associations lost significance at 90 days. Door-to-furosemide ≤1 h was associated with a lower short-term risk of heart failure hospitalizations or cardiovascular death in AHF patients. Our findings add to the existing evidence that early identification and intravenous diuretic therapy of AHF patients may improve outcomes.

Heat stroke (HS) can cause several physiological changes in the body. In its most severe form, it can cause multi-organ failure including encephalopathy, circulatory shock, liver failure, renal failure, disseminated intravascular coagulation, and rhabdomyolysis among others. HS is a preventable condition; however, it can be life-threatening in severe forms. We present a case of HS in a 54-year-old male, with rapidly progressive multi-organ failure and a fatal outcome along with a brief literature review.

A 72-year-old man underwent hemodialysis because of end-stage renal failure. The patient often suffered acute pancreatitis and was diagnosed with main duct type intraductal papillary mucinous neoplasm(IPMN). Moreover, skin erythema with pain occurred and was treated as cellulitis using antibiotics; however, the skin lesions did not improve. Skin pathological findings indicated subcutaneous nodular fat necrosis due to pancreatitis. Subtotal stomach-preserving pancreaticoduodenectomy was performed, and the skin erythema with pain symptoms were relieved. The final diagnoses were ampullary carcinoma and intraductal papillary mucinous adenoma(IPMA). We experienced a rare case of subcutaneous nodular fat necrosis due to IPMN.

A female patient in her early 30s was treated with imatinib and high-dose methotrexate (HD-MTX) for Philadelphia chromosome-positive acute lymphoblastic leukaemia. The patient developed delayed MTX clearance and grade 3 acute kidney injury characterised by elevated creatinine (114% increase from baseline). After intensified calcium folinate rescue therapy and hydration, the MTX serum level was appropriately decreased 72 hours after the start of MTX infusion, and renal function returned to normal. Medication analysis by a clinical pharmacist suggested that the concomitant treatment with imatinib likely contributed to the delayed MTX clearance and caused the acute kidney injury.

This study aims to provide pooled estimates for the incidence of AKI in overweight, obese and normal BMI patients and to assess impact of BMI on mortality and CKD rates. We conducted literature search using online databases to analyse outcomes of BMI. This meta-analysis included 22 studies. Compared to normal BMI, underweight, overweight or obese patients had higher risk of having AKI. Underweight individuals had 17% lower CKD risk [RR 0.83, 95% CI: 0.75, 0.90] while patients that were overweight [RR 1.15, 95% CI: 1.08, 1.22] and obese [RR 1.21, 95% CI: 1.10, 1.33] had higher risk of having CKD. Lower than normal BMI was associated with higher mortality risk [RR 1.58, 95% CI: 1.35, 1.85], while being overweight or obese correlated with the decreased risk of mortality. An increased risk of AKI combined with an increased risk of mortality calls for renal protective strategies in subjects who are underweight at the time of hospital admission.

Multisystem inflammatory syndrome adult type (MIS-A) is a rare type of post-acute COVID-19 syndrome which more frequently occurred in younger population. Here we present a 78-year-old Chinese female, the oldest case reported, diagnosed with MIS-A who had severe SARS-CoV-2 infection. She was diagnosed with severe COVID-19 and experienced an unexpected sudden hemodynamic collapse in the recovery period within three weeks. Her platelet count was sharply dropped, accompanied with sustained cardiac, kidney and liver injury. She was diagnosed with MIS-A according to criteria established by Center of Disease Control and Prevention. Though her condition was improved under administrating with high dose of methylprednisolone and intravenous immunoglobulin, methylprednisolone was unable to withdraw till two weeks as her partial pressure of oxygen/fraction of inspiration oxygen ratio and platelet count dropped on the heels of decreasing dosage. Unfortunately, the patient's condition gradually deteriorated with the development of severe nosocomial pneumonia. We presented this rare case in order to emphasize that MIS-A could occur in the elderly and the management of this population might be more difficult as the condition of the elderly with SARS-CoV-2 infection and MIS-A might be more severe.

As a damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1) is well-studied and is released from injured tubular epithelial cells to trigger cell death. However, the role of intracellular HMGB1 induced cell death during acute kidney injury (AKI) is poorly understood. We showed that cytosolic HMGB1 induced ferroptosis by binding to acyl-CoA synthetase long-chain family member 4 (ACSL4), the driver of ferroptosis, following renal ischemia/reperfusion (I/R). Both mouse and human kidneys with acute tubular injury were characterized by nucleocytoplasmic translocation of HMGB1in tubular cells. Pharmacological inhibition of HMGB1 nucleocytoplasmic translocation and deletion of HMGB1 in tubular epithelial cells in mice inhibited I/R-induced AKI, tubular ferroptosis, and inflammation compared to those in controls. Co-immunoprecipitation and serial section staining confirmed the interaction between HMGB1 and ACSL4. Taken together, our results demonstrated that cytoplasmic HMGB1 is essential for exacerbating inflammation-associated cellular injury by activating renal tubular ferroptosis via ACSL4 after I/R injury. These findings indicate that cytoplasmic HMGB1 is a regulator of ferroptosis and a promising therapeutic target for AKI.

We applied the Society for Cardiovascular Angiography and Interventions (SCAI) schema to cardiogenic shock (CS) patients treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) to assess performance in this high acuity group of patients. Records of adult patients receiving VA-ECMO for CS at our institution from 01/2015 to 12/2019 were reviewed. Post-cardiotomy and noncardiogenic shock patients were excluded. A total of 245 patients were included, with a median age of 59 years [IQR: 48-67]; 159 (65%) were male. There were 34 (14%) patients in Stage C, 82 (33%) in D, and 129 (53%) in E. Of E patients, 88 (68%) were undergoing cardiopulmonary resuscitation. Median ECMO duration decreased with stage (C:7, D:6, E:4 days, P < 0.001). In-hospital mortality increased (C:35%, D:56%, E:71%, P < 0.001) and myocardial recovery decreased with stage (C:65%, D:35%, E:30%, P < 0.001). Acute kidney injury (C:35%, D:45%, E:54%, P = 0.045), acute liver failure (C:32%, D:66%, E:76%, P < 0.001), and infection (C:35%, D:28%, E:16%, P = 0.004) varied among groups. Multivariable analysis revealed age (HR=1.02), male sex (HR=0.62), and E classification (HR=2.69) as independently associated with 1-year mortality. Competing-risks regression identified D (SHR=0.53) and E classification (SHR=0.45) as inversely associated with myocardial recovery. In patients treated with VA-ECMO for CS, the SCAI classification provided robust risk stratification.