The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

Contrast-induced nephropathy (CIN) is a serious complication that occurs subsequent to the administration of contrast media for therapeutic angiographic interventions. As of present, no effective therapy exists to prevent its occurrence. This single-center double-blind randomized controlled trial aimed to evaluate the effect of edaravone, an antioxidant, in a group of high-risk patients undergoing coronary angiography. Ninety eligible patients with chronic kidney disease Stages 3-4 were randomly assigned to either the control group (n = 45) or the intervention group (n = 45). In the intervention group, one dosage of edaravone (60 mg) in 1 L of normal saline was infused via a peripheral vein 1 h prior to femoral artery-directed coronary angiography. Patients in the control group received an equal amount of infusion in their last hour before angiography. Both groups received intravenous hydration with 0.9% sodium 1 mL/kg/h starting 12 h before and continuing for 24 h after angiography. The primary outcome measure was the onset of CIN, defined as a 25% increase in serum creatinine levels 120 h after administration of contrast media. The occurrence of CIN was observed in 5.5% (n = 5) of the studied population: 2.2% of patients in the intervention group (n = 1) and 8.9% of controls (n = 4). However, this difference was not statistically significant. Administration of a single dosage of edaravone 1 h prior to infusion of contrast media led to a reduction in the incidence of CIN. Further investigations, employing larger sample sizes, are warranted to gain a comprehensive understanding of its efficacy.

BACKGROUND: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs).
METHODS: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI + Veh (infarcted, treated with vehicle); and AMI + PY (infarcted, treated with the cholinesterase inhibitor, pyridostigmine bromide (PY)-40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. The clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury.
RESULTS: Seven days post-surgery, the AMI + PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI + Veh group. Furthermore, there was a notable downregulation in pro-inflammatory gene expression and an upregulation in anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers, indicative of subclinical kidney injury.
CONCLUSIONS: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N1-acetyltransferase, Sat1, and spermine oxidase, Smox) and decreased expression of ornithine decarboxylase (Odc1), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC. Upon confirmation of the RNA-seq results, we tested the hypothesis that enhanced polyamine catabolism contributes to the onset of renal injury and development of fibrosis. To test our hypothesis, we compared the severity of RLDC-induced renal injury and fibrosis in wildtype (WT), Sat1-KO, and Smox-KO mice. Our results suggest that the ablation of polyamine catabolic enzymes reduces the severity of renal injury and that modulation of the activity of these enzymes may protect against kidney damage and fibrosis caused by cisplatin treatment.

The article describes major milestones in acknowledgment of pathophysiological relationship between heart and kidneys since Ancient Egypt till our time and history of term \"cardiorenal syndrome\" (CRS). First references about kidney and heart functions could be dated to 13 BC when Hippocrates mentioned them. In the XIV century Gentile da Foligno proposed a hypothesis about functional interconnection between heart and kidneys. In the XVIII century Richard Bright described the link between myocardial hypertrophy and kidneys diseases. Frederic Justin Collet was the first one who used the term \"cardiorenal\" in his article in 1903. In Russia, I.I. Stolnikov conducted his experiments about myocardial hypertrophy and kidneys ischemia in 1880. Famous Russian internist, E.M. Tareev, devoted several paragraphs to cardiorenal interactions in his fundamental manuals \"Anemia in Bright\'s disease\" (1929) and \"Hypertension\" (1948). The research on this topic was continued by Tareev\'s followers: N.A. Mukhin, V.S. Moiseev, more recent successors - Zh.D. Kobalava, S.V. Moiseev, V.V. Fomin, S.V. Villevalde and others. Their contribution resulted in development of first Russian clinical guidelines on cardio and nephroprotection in CRS in 2014. In 2008 consensus of Acute Disease Quality Initiative summarized current experience on CRS. Today, research on controversial classification questions, biomarkers and other aspects of CRS continues.
В статье освещены основные этапы формирования понимания патофизиологических взаимоотношений между сердцем и почками от Древнего Египта до настоящего времени, история термина «кардиоренальный синдром» (КРС). Первые рассуждения о функции сердца и почек встречаются еще в XIII в. до н.э., на эту тему писал Гиппократ. В XIV в. Джентиле да Фолиньо предположил взаимосвязь работы сердца и почек. Ричард Брайт в XVIII в. описывает связь гипертрофии миокарда и повреждения почек. Фридрих Джастин Коллет в 1903 г. впервые употребляет термин «кардиоренальный». В нашей стране Я.Я. Стольников еще в 1880 г. проводил опыты по выявлению связи гипертрофии миокарда и ишемии почек. Е.М. Тареев уделяет наибольшее внимание проблеме взаимодействия почек и сердца в своих работах «Анемия брайтиков» (1929) и «Гипертоническая болезнь» (1948). Изучение данной проблемы активно продолжили ученики научной школы Е.М. Тареева: Н.А. Мухин, В.С. Моисеев и их последователи – Ж.Д. Кобалава, В.В. Фомин, С.В. Моисеев, С.В. Виллевальде и др., что привело к созданию первых российских рекомендаций по стратегии кардио-нефропротекции при КРС в 2014 г. Мировое сообщество впервые употребляет термин КРС в 2008 г. на конференции инициативной группы ADQI (Acute Dialysis Quality Initiative Group), в этом же году опубликованы первые клинические рекомендации по КРС. В настоящий момент проводятся исследования для уточнения ответов на спорные вопросы в отношении классификации, биомаркеров и других аспектов КРС.

BACKGROUND: Our objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation.
METHODS: We populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents. We translated candidate biomarkers to a CF cohort via analysis of urine collected prior to, during and two weeks after antibiotics and patients were followed for a median of 3 years after antibiotic use.
RESULTS: Polymyxin E treatment resulted in a statistically significant increase in the pro-apoptotic Fas gene relative to control in RNAseq of MPS: fold-change = 1.63, FDR q-value = 7.29 × 10-5. Effluent analysis demonstrated an acute rise of soluble Fas (sFas) concentrations that correlated with cellular injury. In 16 patients with CF, urinary sFas concentrations were significantly elevated during antibiotic treatment, regardless of development of AKI. Over a median of three years of follow up, we identified seven cases of incident chronic kidney disease (CKD). Urinary sFas concentrations during antibiotic treatment were significantly associated with subsequent development of incident CKD (unadjusted relative risk = 2.02 per doubling of urinary sFas, 95 % CI = 1.40, 2.90, p < 0.001).
CONCLUSIONS: Using an ex-vivo MPS, we identified a novel biomarker of proximal tubule epithelial cell injury, sFas, and translated these findings to a clinical cohort of patients with CF.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is a secreted and membrane-associated protein, which regulates diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence has revealed that excess SEMA3A expression and the subsequent signaling pathway aggravate kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports have demonstrated that the inhibition of SEMA3A ameliorated kidney injury via a reduction in cell apoptosis, fibrosis and inflammation; thus, SEMA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized the current knowledge regarding the role of SEMA3A in kidney pathophysiology and their potential use in kidney diseases.

Renal pathophysiology is a multifactorial process involving different kidney structures. Acute kidney injury (AKI) is a clinical condition characterized by tubular necrosis and glomerular hyperfiltration. The maladaptive repair after AKI predisposes to the onset of chronic kidney diseases (CKD). CKD is a progressive and irreversible loss of kidney function, characterized by fibrosis that could lead to end stage renal disease. In this review we provide a comprehensive overview of the most recent scientific publications analyzing the therapeutic potential of Extracellular Vesicles (EV)-based treatments in different animal models of AKI and CKD. EVs from multiple sources act as paracrine effectors involved in cell-cell communication with pro-generative and low immunogenic properties. They represent innovative and promising natural drug delivery vehicles used to treat experimental acute and chronic kidney diseases. Differently from synthetic systems, EVs can cross biological barriers and deliver biomolecules to the recipient cells inducing a physiological response. Moreover, new methods for improving the EVs as carriers have been introduced, such as the engineering of the cargo, the modification of the proteins on the external membrane, or the pre-conditioning of the cell of origin. The new nano-medicine approaches based on bioengineered EVs are an attempt to enhance their drug delivery capacity for potential clinical applications.

Chronic allograft dysfunction (CAD), characterized histologically by interstitial fibrosis and tubular atrophy, is the major cause of kidney allograft loss. Here, using single nuclei RNA sequencing and transcriptome analysis, we identified the origin, functional heterogeneity, and regulation of fibrosis-forming cells in kidney allografts with CAD. A robust technique was used to isolate individual nuclei from kidney allograft biopsies and successfully profiled 23,980 nuclei from five kidney transplant recipients with CAD and 17,913 nuclei from three patients with normal allograft function. Our analysis revealed two distinct states of fibrosis in CAD; low and high extracellular matrix (ECM) with distinct kidney cell subclusters, immune cell types, and transcriptional profiles. Imaging mass cytometry analysis confirmed increased ECM deposition at the protein level. Proximal tubular cells transitioned to an injured mixed tubular (MT1) phenotype comprised of activated fibroblasts and myofibroblast markers, generated provisional ECM which recruited inflammatory cells, and served as the main driver of fibrosis. MT1 cells in the high ECM state achieved replicative repair evidenced by dedifferentiation and nephrogenic transcriptional signatures. MT1 in the low ECM state showed decreased apoptosis, decreased cycling tubular cells, and severe metabolic dysfunction, limiting the potential for repair. Activated B, T and plasma cells were increased in the high ECM state, while macrophage subtypes were increased in the low ECM state. Intercellular communication between kidney parenchymal cells and donor-derived macrophages, detected several years post-transplantation, played a key role in injury propagation. Thus, our study identified novel molecular targets for interventions aimed to ameliorate or prevent allograft fibrogenesis in kidney transplant recipients.

BACKGROUND: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN.
METHODS: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR).
RESULTS: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8-14.3) versus 5.9 (5.2-6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (β = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development.
CONCLUSIONS: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.