Avaliação do perfil de mortalidade por síndrome cardiorrenal na última década do Município de São Paulo / Assessment of the mortality profile due to cardiorenal syndrome in the last decade in the city of São Paulo

INTRODUÇÃO: A síndrome cardiorrenal é uma condição complexa que afeta tanto o coração quanto os rins, representando um desafio significativo para a saúde pública devido à associação com complicações graves e alta taxa de mortalidade. A análise dos padrões de mortalidade decorrentes dessa síndrome em São Paulo, no período de 2013 a 2023, é crucial para aprimorar os cuidados clínicos e mitigar óbitos relacionados a essa condição. Compreender a extensão do problema e identificar padrões de mortalidade pode fornecer informações cruciais para melhorar a prestação de cuidados de saúde e direcionar recursos de forma mais eficaz. OBJETIVO: Fornecer um panorama epidemiológico da síndrome cardiorrenal de 2013 a 2023. MÉTODOS: O estudo em consideração empreende uma análise epidemiológica, descritiva e transversal, utilizando os dados provenientes do banco de saúde DATASUS (TABNET) referentes a 2013 até 2023 no município de São Paulo. Este se aprofunda na investigação das variáveis fundamentais: cor, sexo e faixa etária. RESULTADOS: Analisando os dados coletados entre 2013 e 2023, foram registrados 1.293 óbitos por síndrome cardiorrenal no município de São Paulo, sendo 2021 o ano de maior incidência de óbitos (180). No tangente à cor, os brancos representam o maior número (65,82%), seguidos por pardos (20,53%), negros (12,37%), amarelos (1,26%). Quanto ao sexo, há predominância no feminino (54,60%). Em relação à faixa etária, aqueles que possuem 75 anos ou mais são os mais afetados e representam 63,95% do total, sendo o grupo etário mais acometido em 2021 (65,55%). CONCLUSÕES: Analisando os dados coletados, podemos observar: O sexo feminino teve maior mortalidade, variando de 50% a 60%. A etnia branca, variando entre 60% e 70%. Também foi encontrada uma maior mortalidade na faixa etária de 75 anos ou mais, com uma variação entre 51% e 77%. Também podemos notar uma diminuição do número relativo de mortes da faixa etária de 55-64, com uma porcentagem de 17% no ano de 2013 que diminuiu para a metade a partir de 2019. Também é notável a influência da pandemia de COVID-19 em 2021 e sua influência para o aumento de mortes por síndrome cardiorrenal. A elevação na mortalidade nos últimos anos pode ser atribuído ao aumento na incidência populacional de agentes lesivos cardiorrenais (principalmente diabetes e hipertensão) e ao manejo insuficiente de tais fatores de risco. Estudos complementares e incrementos na saúde pública são necessários para melhorar tais parâmetros.

Simultaneous Heart and Kidney Transplantation: A Systematic Review and Proportional Meta-Analysis of Its Characteristics and Long-Term Variables.

Patients with end-stage heart disease who undergo a heart transplant frequently have simultaneous kidney insufficiency, therefore simultaneous heart and kidney transplantation is an option and it is necessary to understand its characteristics and long-term variables. The recipient characteristics and operative and long-term variables were assessed in a meta-analysis. A total of 781 studies were screened, and 33 were thoroughly reviewed. 15 retrospective cohort studies and 376 patients were included. The recipient's mean age was 51.1 years (95% CI 48.52-53.67) and 84% (95% CI 80-87) were male. 71% (95% CI 59-83) of the recipients were dialysis dependent. The most common indication was ischemic cardiomyopathy [47% (95% CI 41-53)] and cardiorenal syndrome [22% (95% CI 9-35)]. Also, 33% (95% CI 20-46) of the patients presented with delayed graft function. During the mean follow-up period of 67.49 months (95% CI 45.64-89.33), simultaneous rejection episodes of both organ allografts were described in 5 cases only. Overall survival was 95% (95% CI 88-100) at 30 days, 81% (95% CI 76-86) at 1 year, 79% (95% CI 71-87) at 3, and 71% (95% CI 59-83) at 5 years. Simultaneous heart and kidney transplantation is an important option for concurrent cardiac and renal dysfunction and has acceptable rejection and survival rates.

Kidney Replacement Therapies and Ultrafiltration in Cardiorenal Syndrome.

BACKGROUND: Some patients with cardiorenal syndrome 1 and congestion exhibit resistance to diuretics. This scenario complicates management and is associated with a worse prognosis. In some cases, rescue treatment may be considered by starting kidney replacement therapies or ultrafiltration. This decision is complex and necessitates a profound understanding of these techniques and the pathophysiology of this syndrome. These modalities are classified into continuous, intermittent, and ultrafiltration therapies, each with its own advantages and disadvantages that are pertinent in selecting the optimal treatment. SUMMARY: In patients with diuretic-resistant cardiorenal syndrome, extracorporeal ultrafiltration and kidney replacement therapies have the potential to relieve congestion, restore the neurohormonal system, and improve quality of life. KEY MESSAGES: (i) In cardiorenal syndrome, the resistance to diuretics is common. (ii) Extracorporeal ultrafiltration and renal replacement therapies are rescue options that may improve the management of these patients. (iii) Better understanding of these modalities will help the development of new devices which are friendlier, safer, and more affordable for patients in these clinical settings.

Effect on Kidney Function Recovery Guiding Decongestion with VExUS in Patients with Cardiorenal Syndrome 1: A Randomized Control Trial.

INTRODUCTION: In cardiorenal syndrome type 1 (CRS1), vascular congestion is central to the pathophysiology of heart failure and thus a key target for management. The venous evaluation by ultrasound (VExUS) system could guide decongestion effectively and thereby improve outcomes. METHODS: In this randomized clinical trial, patients with CRS1 (i.e., increase in creatinine ≥0.3 mg/dL) were randomized to guide decongestion with VExUS compared to usual clinical evaluation. The primary endpoint was to assess kidney function recovery (KFR), and the key secondary endpoint was decongestion evaluated by physical examination and changes in brain natriuretic peptide (BNP) and CA-125. Exploratory endpoints included days of hospitalization and mortality. RESULTS: From March 2022 to February 2023, a total of 140 patients were randomized 1:1 (70 in the VExUS and 70 in the control group). KFR was not statistically different between groups. However, VExUS improved more than twice the odds to achieve decongestion (odds ratio [OR]: 2.6, 95% CI: 1.9-3.0, p = 0.01) and the odds to reach a decrease of BNP >30% (OR: 2.4, 95% CI: 1.3-4.1, p = 0.01). The survival at 90 days, recongestion, and CA-125 were similar between groups. CONCLUSION: In patients with CRS1, we observed that VExUS-guided decongestion did not improve the probability of KFR but improved the odds to achieve decongestion.

Mitochondrial Impairment: A Link for Inflammatory Responses Activation in the Cardiorenal Syndrome Type 4.

Cardiorenal syndrome type 4 (CRS type 4) occurs when chronic kidney disease (CKD) leads to cardiovascular damage, resulting in high morbidity and mortality rates. Mitochondria, vital organelles responsible for essential cellular functions, can become dysfunctional in CKD. This dysfunction can trigger inflammatory responses in distant organs by releasing Damage-associated molecular patterns (DAMPs). These DAMPs are recognized by immune receptors within cells, including Toll-like receptors (TLR) like TLR2, TLR4, and TLR9, the nucleotide-binding domain, leucine-rich-containing family pyrin domain-containing-3 (NLRP3) inflammasome, and the cyclic guanosine monophosphate (cGMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (cGAS-STING) pathway. Activation of these immune receptors leads to the increased expression of cytokines and chemokines. Excessive chemokine stimulation results in the recruitment of inflammatory cells into tissues, causing chronic damage. Experimental studies have demonstrated that chemokines are upregulated in the heart during CKD, contributing to CRS type 4. Conversely, chemokine inhibitors have been shown to reduce chronic inflammation and prevent cardiorenal impairment. However, the molecular connection between mitochondrial DAMPs and inflammatory pathways responsible for chemokine overactivation in CRS type 4 has not been explored. In this review, we delve into mechanistic insights and discuss how various mitochondrial DAMPs released by the kidney during CKD can activate TLRs, NLRP3, and cGAS-STING immune pathways in the heart. This activation leads to the upregulation of chemokines, ultimately culminating in the establishment of CRS type 4. Furthermore, we propose using chemokine inhibitors as potential strategies for preventing CRS type 4.

Immune Cells Are Differentially Modulated in the Heart and the Kidney during the Development of Cardiorenal Syndrome 3.

Cardiorenal syndrome type 3 (CRS 3) occurs when there is an acute kidney injury (AKI) leading to the development of an acute cardiac injury. The immune system is involved in modulating the severity of kidney injury, and the role of immune system cells in the development of CRS 3 is not well established. The present work aims to characterize the macrophage and T and B lymphocyte populations in kidney and heart tissue after AKI induced by renal I/R. Thus, C57BL/6 mice were subjected to a renal I/R protocol by occlusion of the left renal pedicle (unilateral) for 60 min, followed by reperfusion for 3, 8 and 15 days. The immune cell populations of interest were identified using flow cytometry, and RT-qPCR was used to evaluate gene expression. As a result, a significant increase in TCD4+, TCD8+ lymphocytes and M1 macrophages to the renal tissue was observed, while B cells in the heart decreased. A renal tissue repair response characterized by Foxp3 activation predominated. However, a more inflammatory profile was shown in the heart tissue influenced by IL-17RA and IL-1ß. In conclusion, the AKI generated by renal I/R was able to activate and recruit T and B lymphocytes and macrophages, as well as pro-inflammatory mediators to renal and cardiac tissue, showing the role of the immune system as a bridge between both organs in the context of CRS 3.

Consumo de Castanha-do-Brasil reduz o N-óxido de trimetilamina (TMAO) e a inflamação em um paciente com síndrome cardiorrenal: uma comunicação breve / Brazil nut consumption reduces trimethylamine-n-oxide (TMAO) and inflammation in a patient with cardiorenal syndrome: a brief communication

Introdução: A disbiose intestinal é uma característica comum na síndrome cardiorrenal e está associada ao aumento de toxinas urêmicas, como o N-óxido de trimetilamina (TMAO), que estão envolvidas com a inflamação e mortalidade cardiovascular. A castanha-do-Brasil (semente típica brasileira) possui propriedades anti-inflamatórias e antioxidantes, mas não há evidências dos seus efeitos na modulação da microbiota intestinal e redução de toxinas urêmicas. Objetivo: Avaliar o impacto do consumo de castanha-do-Brasil nos níveis de TMAO e marcadores de inflamação em um paciente com síndrome cardiorrenal. Métodos: Um paciente com doença arterial coronariana (66 anos e IMC, 26 kg/m2), estágio 3 da DRC (TFGe 36 mL/min), recebeu uma castanha-do-Brasil por dia durante três meses. Resultados: Os níveis plasmáticos de TMAO e a expressão de mRNA de NF-κB foram reduzidos e a atividade da glutationa peroxidase (GPx) aumentou após esta intervenção. Conclusão: A prescrição de castanha-do-Brasil pode ser uma estratégia promissora para mitigar as complicações relacionadas à síndrome cardiorrenal. Este caso apoia o conceito de "alimento como remédio" visando o fenótipo urêmico na síndrome cardiorrenal.

Introduction: Gut dysbiosis is a common feature in cardiorenal syndrome, and it is linked to increased uremic toxins, like trimethylamine-n-oxide (TMAO), which are involved with inflammation and cardiovascular mortality. Brazil nut (typical Brazilian seed) has anti-inflammatory and antioxidant properties, but there is no evidence of the effects of gut microbiota modulation and reduction of uremic toxins. Objective: To assess the impact of Brazil nut consumption on TMAO levels and inflammation markers in a patient with cardiorenal syndrome. Methods: Acoronary artery disease patient(66 years and BMI, 26 kg/m2),stage-3 of CKD (eGFR 36 mL/min), receivedone Brazil nut per day for three months. Results: TMAO plasma levels and NF-κB mRNA expression were reduced, and glutathione peroxidase (GPx) activity increased after this intervention. Conclusion: Brazil nut prescription may be a promising strategy to mitigate complications related tothe cardiorenal syndrome. This case supports the concept of "Food as medicine" targeting the uremic phenotype in cardiorenal syndrome.

Effect of COVID-19 on cardiorenal axis: known or unknown universe?

Recent findings have confirmed relationships between coronavirus disease (COVID-19) and multiple organ dysfunction. The prevalence of cardiac and renal involvement in COVID-19 has been increasingly reported and is a marker of severe disease that not only directly or indirectly affects the organs, but may also exacerbate the underlying comorbid illness. In addition, patients affected by the new coronavirus present a systemic inflammatory condition that results in damage to several tissues, especially the heart, kidneys, and vessels. It is well known that the heart and kidneys are closely related, so that any change in one of the organs can lead to damage to the other, establishing the so-called cardiorenal syndrome. Herein, we explore some case reports of patients with COVID-19 who had heart and kidney abnormalities, consequently resulting in worse prognosis of the disease. These results highlight the importance of understanding the cause and effect between the cardiac and renal systems and the course of early SARS-CoV-2 infection.

Cardiorenal syndrome: long road between kidney and heart.

Almost 200 years ago, the first evidence described by Robert Bright (1836) showed the strong interaction between the kidneys and heart and, since then, the scientific community has dedicated itself to better understanding the mechanisms involved in the kidney-heart relationship, known in recent decades as cardiorenal syndrome (CRS). This syndrome includes a wide clinical variety that affects the kidneys and heart, in an acute or chronic manner. Moreover, it is well established in the literature that the immune system, the sympathetic nervous system, the renin-angiotensin-aldosterone, and the oxidative stress actively play a strong role in the cellular and molecular processes present in CRS. More recently, uremic molecules and epigenetic factors have been also shown to be key mediators in the development of syndrome. The present review intends to present the state of the art regarding CRS and to show the paths known, until now, in the long road between the kidneys and heart.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Cardiorenal syndrome: classification, pathophysiology, diagnosis and management. Literature review / Síndrome cardiorrenal: clasificación, fisiopatología, diagnóstico y tratamiento. Una revisión de las publicaciones médicas.

The cardiorenal syndrome is a complex entity in which a primary heart dysfunction causes kidney injury (Types 1 and 2) and vice versa (Types 3 and 4), being either acute or chronic events, or maybe the result of a systemic disease that involves both organs (Type 5). Approximately 49% of heart failure cases present some grade of kidney dysfunction, significantly increasing morbidity and mortality rates. Its pathogenesis involves a variety of hemodynamic, hormonal and immunological factors that in the majority of cases produce fluid overload; the diagnosis and treatment of such constitutes the disease's management basis. Currently, a clinical based diagnosis is insufficient and the use of biochemical markers, such as natriuretic peptides, or lung and heart ultrasound is required. These tools, along with urinary sodium levels, allow the evaluation of therapy effectiveness. The preferred initial decongestive strategy is based on a continuous infusion of a loop diuretic with a step-up dosing regimen, aiming for a minimal daily urine volume of 3 liters, with the possibility to sequentially add potassium sparing diuretics, thiazide diuretics and carbonic anhydrase inhibitors to reach the diuresis goal, leaving ultrafiltration as a last resource due to its higher rate of complications. Finally, evidence-based therapy should be given to improve quality of life, decrease mortality, and delay the deterioration of kidney and heart function over the long term.

El síndrome cardiorrenal es una entidad compleja en la que la disfunción primaria cardíaca produce daño renal (tipos 1 y 2) y viceversa (tipos 3 y 4) y los episodios pueden ser agudos o crónicos o bien efecto de una enfermedad sistémica que afecta a ambos órganos (tipo 5). Hasta 49% de los pacientes con insuficiencia cardíaca muestra algún grado de disfunción renal, lo que aumenta de manera significativa la morbilidad y mortalidad. Su patogenia incluye diversos factores hemodinámicos, hormonales e inmunológicos que en la mayor parte de los casos producen sobrecarga hídrica, y cuyo diagnóstico y tratamiento son la base de su atención. En la actualidad, el diagnóstico clínico es insuficiente y se requieren marcadores bioquímicos, como péptidos natriuréticos, o el uso de ultrasonido pulmonar y cardíaco; estas herramientas, junto con la medición del sodio urinario, también permiten vigilar la efectividad terapéutica. De modo inicial se prefieren las medidas descongestivas con diuréticos de asa en infusión continua a dosis escalonadas para alcanzar una diuresis mínima de 3 L por día, con la posibilidad de agregar diuréticos ahorradores de potasio, tiazidas e inhibidores de la anhidrasa carbónica de modo secuencial para alcanzar el objetivo; como último recurso se recurre a la ultrafiltración en virtud de su mayor tasa de complicaciones. Por último, se debe indicar tratamiento con base en la evidencia para mejorar la calidad de vida, reducir la mortalidad y retrasar el deterioro de la función renal y cardíaca a largo plazo.

Amlexanox Exhibits Cardioprotective Effects in 5/6 Nephrectomized Rats

Abstract Cardiorenal syndrome is a life-threatening condition. The aim of the current study was to determine the cardioprotective effects of amlexanox in 5/6 nephrectomized rats. Rats were randomly assigned to three groups: sham, 5/6 nephrectomized rats, and amlexanox-treated 5/6 nephrectomized group. Amlexanox (25 mg/kg/day, i.p.) administration was started just after surgery and continued for 10 weeks. After treatment, kidney function (serum creatinine and urea) and blood pressure (systolic and diastolic) were measured. Heart weight (normalized to tibial length) and fibrosis area percentage were measured. Serum brain natriuretic peptide (BNP, heart failure marker) and cardiac levels of ß1-adrenergic receptor (ß1AR), ß-arrestin-2, phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol (DAG), pS473 Akt (a survival marker), and caspase-3 activity (an apoptosis marker) were also measured. The 5/6 nephrectomy caused renal impairment, cardiac fibrosis, apoptosis, and heart failure indicated by down- regulation of cardiac ß1AR down-stream signals compared with those in the sham group. Interestingly, amlexanox significantly reduced all cardiopathological changes induced after 10 weeks of 5/6 nephrectomy. Amlexanox showed potent cardiac antifibrotic and antiapoptotic effects in 5/6 nephrectomized rats, which were associated with reduced heart failure. To our knowledge, this is the first study that addresses the potent in vivo cardioprotective effects of amlexanox

Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C.

Cardiorenal syndrome (CRS) is a pathological link between the kidneys and heart, in which an insult in a kidney or heart leads the other organ to incur damage. CRS is classified into five subtypes, and type 3 (CRS3) is characterized by acute kidney injury as a precursor to subsequent cardiovascular changes. Mitochondrial dysfunction and oxidative and nitrosative stress have been reported in the pathophysiology of CRS3. It is known that vitamin C, an antioxidant, has proven protective capacity for cardiac, renal, and vascular endothelial tissues. Therefore, the present study aimed to assess whether vitamin C provides protection to heart and the kidneys in an in vivo CRS3 model. The unilateral renal ischemia and reperfusion (IR) protocol was performed for 60 min in the left kidney of adult mice, with and without vitamin C treatment, immediately after IR or 15 days after IR. Kidneys and hearts were subsequently collected, and the following analyses were conducted: renal morphometric evaluation, serum urea and creatinine levels, high-resolution respirometry, amperometry technique for NO measurement, gene expression of mitochondrial dynamic markers, and NOS. The analyses showed that the left kidney weight was reduced, urea and creatinine levels were increased, mitochondrial oxygen consumption was reduced, NO levels were elevated, and Mfn2 expression was reduced after 15 days of IR compared to the sham group. Oxygen consumption and NO levels in the heart were also reduced. The treatment with vitamin C preserved the left kidney weight, restored renal function, reduced NO levels, decreased iNOS expression, elevated constitutive NOS isoforms, and improved oxygen consumption. In the heart, oxygen consumption and NO levels were improved after vitamin C treatment, whereas the three NOS isoforms were overexpressed. These data indicate that vitamin C provides protection to the kidneys and some beneficial effects to the heart after IR, indicating it may be a preventive approach against cardiorenal insults.

Extracellular Vesicles and Their Relationship with the Heart-Kidney Axis, Uremia and Peritoneal Dialysis.

Cardiorenal syndrome (CRS) is described as primary dysfunction in the heart culminating in renal injury or vice versa. CRS can be classified into five groups, and uremic toxin (UT) accumulation is observed in all types of CRS. Protein-bound uremic toxin (PBUT) accumulation is responsible for permanent damage to the renal tissue, and mainly occurs in CRS types 3 and 4, thus compromising renal function directly leading to a reduction in the glomerular filtration rate (GFR) and/or subsequent proteinuria. With this decrease in GFR, patients may need renal replacement therapy (RRT), such as peritoneal dialysis (PD). PD is a high-quality and home-based dialysis therapy for patients with end-stage renal disease (ESRD) and is based on the semi-permeable characteristics of the peritoneum. These patients are exposed to factors which may cause several modifications on the peritoneal membrane. The presence of UT may harm the peritoneum membrane, which in turn can lead to the formation of extracellular vesicles (EVs). EVs are released by almost all cell types and contain lipids, nucleic acids, metabolites, membrane proteins, and cytosolic components from their cell origin. Our research group previously demonstrated that the EVs can be related to endothelial dysfunction and are formed when UTs are in contact with the endothelial monolayer. In this scenario, this review explores the mechanisms of EV formation in CRS, uremia, the peritoneum, and as potential biomarkers in peritoneal dialysis.

Type 1 Cardiorenal Syndrome in Decompensated Heart Failure Patients in a Low-Income Region in Brazil: Incidence of Acute Kidney Injury (AKIN and KDIGO Criteria), Need for Dialysis and Mortality. / Síndrome Cardiorrenal Tipo 1 em Região de Baixo Desenvolvimento: Comparação entre os Critérios AKIN e KDIGO, Necessidade de Diálise e Mortalidade.

BACKGROUND: Type 1 cardiorenal syndrome is associated with higher mortality in heart failure patients. However, few studies have compared the diagnostic criteria of acute kidney injury (AKI) in this population. OBJECTIVE: To assess clinical and functional features and factors associated AKI in patients with heart failure. METHOD: Retrospective, cohort study on patients with decompensated heart failure or recent acute myocardial infarction, conducted in a tertiary hospital in a low-income region of Brazil. Clinical, laboratory and echocardiographic features were compared between patients with and without AKI according to the Acute Kidney Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The level of statistical significance was set at p < 0.05. RESULTS: Of 81 patients, 61.73% had AKI. Mean creatinine and urea levels were 1.79±1.0 mg/dL and 81.5±46.0 mg/dL, respectively, and higher in the group with AKI (p < 0.05). No evidence of a relationship between cardiac changes and reduced renal function. Chronic renal disease was associated with higher prevalence of AKI. Higher mortality was observed in patients with AKI than in patients without AKI (32.0% vs. 9.8%, p = 0.04, OR 8.187 ad 95% confidence interval 1.402-17.190, p = 0.020). CONCLUSION: In this population of patients with heart failure, AKI was highly prevalent and considered an independent risk factor for mortality. Cardiac changes were not associated with AKI, and the KDIGO and AKIN criteria showed similar performance.

FUNDAMENTO: A síndrome cardiorrenal tipo 1 associa-se a maior mortalidade em pacientes com insuficiência cardíaca (IC). No entanto, há escassez de publicações comparando critérios diagnósticos de lesão renal aguda (LRA). OBJETIVOS: Analisar o perfil clinicofuncional de pacientes com IC e fatores associados a ocorrência de lesão renal aguda (LRA). MÉTODOS: Estudo de coorte retrospectivo, em hospital terciário de região com baixo desenvolvimento econômico que incluiu pacientes com IC descompensada ou infarto agudo do miocárdio (IAM) recente, sendo avaliadas características clínicas, laboratoriais e ecocardiográficas comparativamente em pacientes com e sem LRA classificada pelos critérios Acute Kidney Network (AKIN) e Kidney Disease: Improving Global Outcomes (KDIGO). Nível de significância estatística com valor de p < 0,05. RESULTADOS: Entre 81 pacientes, 61,73% evoluíram com LRA. A média de creatinina foi 1,79±1,0 mg/dL e de ureia 81,5±46,0 mg/dL, sendo maior no grupo com LRA (p < 0,05). Não foi evidenciada relação entre alterações cardíacas e redução da função renal. A doença renal crônica se associou a maior ocorrência de LRA (38% x 3,23% sem LRA, p = 0,001). Não houve diferença do KDIGO com relação ao critério AKIN. Os pacientes que desenvolveram LRA apresentaram maior mortalidade (32% x 9,8% no grupo sem LRA, p = 0,04, com odds ratio (OR) de 8,187 e intervalo de confiança 1,402-17,190, p = 0,020). CONCLUSÃO: Nessa casuística de pacientes com IC, a ocorrência de LRA foi elevada e foi fator de risco independente de mortalidade. As alterações cardíacas não se associaram à ocorrência de LRA, e os critérios diagnósticos KDIGO e AKIN apresentaram performance similar.

Heart Disease and the Kidneys.

Clinical Background: The heart can cause kidney disease, and the kidney can cause heart disease. As an example of the first situation, we can mention dilated cardiomyopathies, which can lead to renal failure of the pre-renal type due to the state of renal hypoflow. As an example of the second situation, we can remember that renal failure is a risk factor for cardiovascular diseases, such as coronary heart disease, due to the acceleration in the process of atherosclerosis that it promotes. Epidemiology: In this chapter, we will address what we consider to be the two main aspects of the interrelationships between heart and kidney disease that are "cardiorenal syndrome (CRS)" and "chronic kidney disease (CKD) and coronary heart disease (CHD)." Challenges: For CRS, we discuss its epidemiology, types, pathophysiological mechanisms common to CRS types 1, 2, 3 and 4 and pathogenesis of CSR type 5. Treatment: For "CKD and CHD" we discuss the association of CKD and CHD in community-based populations, traditional risk factor in CKD, non-traditional risk factor in CKD, reduced risk of CHD in patients with CKD, statin treatment, hypertension treatment, anti-platelet aggregation therapy, treatment of CHD in patients with CKD and prognosis of CHDF in CKD patients.

Heat Shock Proteins: Connectors between Heart and Kidney.

Over the development of eukaryotic cells, intrinsic mechanisms have been developed in order to provide the ability to defend against aggressive agents. In this sense, a group of proteins plays a crucial role in controlling the production of several proteins, guaranteeing cell survival. The heat shock proteins (HSPs), are a family of proteins that have been linked to different cellular functions, being activated under conditions of cellular stress, not only imposed by thermal variation but also toxins, radiation, infectious agents, hypoxia, etc. Regarding pathological situations as seen in cardiorenal syndrome (CRS), HSPs have been shown to be important mediators involved in the control of gene transcription and intracellular signaling, in addition to be an important connector with the immune system. CRS is classified as acute or chronic and according to the first organ to suffer the injury, which can be the heart (CRS type 1 and type 2), kidneys (CRS type 3 and 4) or both (CRS type 5). In all types of CRS, the immune system, redox balance, mitochondrial dysfunction, and tissue remodeling have been the subject of numerous studies in the literature in order to elucidate mechanisms and propose new therapeutic strategies. In this sense, HSPs have been targeted by researchers as important connectors between kidney and heart. Thus, the present review has a focus to present the state of the art regarding the role of HSPs in the pathophysiology of cardiac and renal alterations, as well their role in the kidney-heart axis.

Síndrome cardiorrenal tipo 1 em região de baixo desenvolvimento: comparação entre os critérios akin e kdigo, necessidade de diálise e mortalidade / Type 1 cardiorenal syndrome in decompensated heart failure patients in a low-income region in brazil: incidence of acute kidney injury (akin and kdigo criteria), need for dialysis and mortality

Resumo Fundamento: A síndrome cardiorrenal tipo 1 associa-se a maior mortalidade em pacientes com insuficiência cardíaca (IC). No entanto, há escassez de publicações comparando critérios diagnósticos de lesão renal aguda (LRA). Objetivos: Analisar o perfil clinicofuncional de pacientes com IC e fatores associados a ocorrência de lesão renal aguda (LRA). Métodos: Estudo de coorte retrospectivo, em hospital terciário de região com baixo desenvolvimento econômico que incluiu pacientes com IC descompensada ou infarto agudo do miocárdio (IAM) recente, sendo avaliadas características clínicas, laboratoriais e ecocardiográficas comparativamente em pacientes com e sem LRA classificada pelos critérios Acute Kidney Network (AKIN) e Kidney Disease: Improving Global Outcomes (KDIGO). Nível de significância estatística com valor de p < 0,05. Resultados: Entre 81 pacientes, 61,73% evoluíram com LRA. A média de creatinina foi 1,79±1,0 mg/dL e de ureia 81,5±46,0 mg/dL, sendo maior no grupo com LRA (p < 0,05). Não foi evidenciada relação entre alterações cardíacas e redução da função renal. A doença renal crônica se associou a maior ocorrência de LRA (38% x 3,23% sem LRA, p = 0,001). Não houve diferença do KDIGO com relação ao critério AKIN. Os pacientes que desenvolveram LRA apresentaram maior mortalidade (32% x 9,8% no grupo sem LRA, p = 0,04, com odds ratio (OR) de 8,187 e intervalo de confiança 1,402-17,190, p = 0,020). Conclusão: Nessa casuística de pacientes com IC, a ocorrência de LRA foi elevada e foi fator de risco independente de mortalidade. As alterações cardíacas não se associaram à ocorrência de LRA, e os critérios diagnósticos KDIGO e AKIN apresentaram performance similar.

Abstract Background: Type 1 cardiorenal syndrome is associated with higher mortality in heart failure patients. However, few studies have compared the diagnostic criteria of acute kidney injury (AKI) in this population. Objective: To assess clinical and functional features and factors associated AKI in patients with heart failure. Method: Retrospective, cohort study on patients with decompensated heart failure or recent acute myocardial infarction, conducted in a tertiary hospital in a low-income region of Brazil. Clinical, laboratory and echocardiographic features were compared between patients with and without AKI according to the Acute Kidney Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The level of statistical significance was set at p < 0.05. Results: Of 81 patients, 61.73% had AKI. Mean creatinine and urea levels were 1.79±1.0 mg/dL and 81.5±46.0 mg/dL, respectively, and higher in the group with AKI (p < 0.05). No evidence of a relationship between cardiac changes and reduced renal function. Chronic renal disease was associated with higher prevalence of AKI. Higher mortality was observed in patients with AKI than in patients without AKI (32.0% vs. 9.8%, p = 0.04, OR 8.187 ad 95% confidence interval 1.402-17.190, p = 0.020). Conclusion: In this population of patients with heart failure, AKI was highly prevalent and considered an independent risk factor for mortality. Cardiac changes were not associated with AKI, and the KDIGO and AKIN criteria showed similar performance.

Tyrosine and Tryptophan vibrational bands as markers of kidney injury: a renocardiac syndrome induced by renal ischemia and reperfusion study.

Renal injury caused by renal ischemia and reperfusion strongly influences heart morphology, electrophysiology, and redox unbalance. The so-called cardiorenal syndrome is an important class of dysfunction since heart and kidneys are responsible for hemodynamic stability and organ perfusion through a complex network. In the present work we investigate the vibrational spectral features probed by Fourier-Transform Raman (FT-Raman) spectroscopy due to physiological alterations induced by renal ischemic reperfusion aiming to detect molecular markers related to progression of acute to chronic kidney injury and mortality predictors as well. C57BL/6J mice were subjected to unilateral occlusion of the renal pedicle for 60 min and reperfusion for 5, 8, and 15 days. Biopsies of heart and kidney tissues were analyzed. Our findings indicated that cysteine/cystine, fatty acids, methyl groups of Collagen, α-form of proteins, Tyrosine, and Tryptophan were modulated during renal ischemia and reperfusion process. These changes are consistent with fibroblast growth factors and Collagen III contents changes. Interestingly, Tyrosine and Tryptophan, precursor molecules for the formation of uremic toxins such as indoxyl sulfate and p-cresyl sulfate were also modulated. They are markers of kidney injury and their increase is strongly correlated to cardiovascular mortality. Regarding this aspect, we notice that monitoring the Tyrosine and Tryptophan bands at 1558, 1616, and 1625 cm-1 is a viable and and advantageous way to predict fatality in cardiovascular diseases both "in vivo" or "in vitro", using the real-time, multiplexing, and minimally invasive advantages of FT-Raman spectroscopy.