Chronic nicotine exposure reduces klotho expression and triggers different renal and hemodynamic responses in klotho-haploinsufficient mice.

The klotho gene, which encodes a single-pass transmembrane protein and a secreted protein, is expressed predominantly by the distal renal tubules and is related to calcium phosphorus metabolism, ion channel regulation, intracellular signaling pathways, and longevity. Klotho deficiency aggravates acute kidney injury and renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we investigated renal Klotho protein expression in a mouse model of chronic (28-day) nicotine exposure, in which mice received nicotine or vehicle (saccharine) in drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+) mice, and their respective controls, in terms of the effects of that exposure. Nicotine exposure was associated with a significant decline in renal Klotho expression in WT and kl/+ mice as well as a reduction in the glomerular filtration rate in WT mice. Although plasma electrolytes were similar among the groups, fractional excretion of sodium was reduced in both nicotine-exposed groups. The nicotine-WT mice presented augmented baroreflex sensitivity to nitroprusside and augmented sympathetic cardiac modulation. However, nicotine- kl/+ mice presented higher plasma levels of urea and aldosterone together with a higher α-index (spontaneous baroreflex) and higher peripheral sympathetic modulation, as evaluated by spectral analysis. We can conclude that nicotine downregulates Klotho expression as well as that renal and autonomic responses to nicotine exposure are modified in kl/+ mice.

The utility of point-of-care ultrasound in critical care nephrology.

Point-of-care ultrasonography (POCUS) is gaining heightened significance in critical care settings as it allows for quick decision-making at the bedside. While computerized tomography is still considered the standard imaging modality for many diseases, the risks and delays associated with transferring a critically ill patient out of the intensive care unit (ICU) have prompted physicians to explore alternative tools. Ultrasound guidance has increased the safety of invasive procedures in the ICU, such as the placement of vascular catheters and drainage of collections. Ultrasonography is now seen as an extension of the clinical examination, providing quick answers for rapidly deteriorating patients in the ICU. The field of nephrology is increasingly acknowledging the value of diagnostic point-of-care ultrasound (POCUS). By employing multi-organ POCUS, nephrologists can address specific queries that arise during the diagnosis and treatment of patients with acute kidney injury. This approach aids in ruling out hydronephrosis and offers immediate information on hemodynamics, thereby consolidating patient data and facilitating the development of personalized treatment strategies.

Predicting intradialytic hypotension in critically ill patients undergoing intermittent hemodialysis: a prospective observational study.

BACKGROUND: Hypotension during dialysis arises from vasomotor tone alterations and hypovolemia, with disrupted counterregulatory mechanisms in acute kidney injury (AKI) patients. This study investigated the predictive value of preload dependency, assessed by the passive leg raising (PLR) test, and arterial tone, measured by dynamic elastance (Eadyn), for intradialytic hypotension (IDH). METHODS: In this prospective observational study conducted in a tertiary hospital ICU, hemodynamic parameters were collected from critically ill AKI patients undergoing intermittent hemodialysis using the FloTrac/Vigileo system. Baseline measurements were recorded before KRT initiation, including the PLR test and Eadyn calculation. IDH was defined as mean arterial pressure (MAP) < 65 mmHg during dialysis. Logistic regression was used to identify predictors of IDH, and Kaplan-Meier analysis assessed 90-day survival. RESULTS: Of 187 patients, 27.3% experienced IDH. Preload dependency, identified by positive PLR test, was significantly associated with IDH (OR 8.54, 95% CI 5.25-27.74), while baseline Eadyn was not predictive of IDH in this cohort. Other significant predictors of IDH included norepinephrine use (OR 16.35, 95% CI 3.87-68.98) and lower baseline MAP (OR 0.96, 95% CI 0.94-1.00). IDH and a positive PLR test were associated with lower 90-day survival (p < 0.001). CONCLUSIONS: The PLR test is a valuable tool for predicting IDH in critically ill AKI patients undergoing KRT, while baseline Eadyn did not demonstrate predictive value in this setting. Continuous hemodynamic monitoring, including assessment of preload dependency, may optimize patient management and potentially improve outcomes. Further research is warranted to validate these findings and develop targeted interventions to prevent IDH.

Physico-chemical characterization of acid base disorders in patients with COVID-19: A cohort study.

BACKGROUND: Acid-base imbalance has been poorly described in patients with coronavirus disease 2019 (COVID-19). Study by the quantitative acid-base approach may be able to account for minor changes in ion distribution that may have been overlooked using traditional acid-base analysis techniques. In a cohort of critically ill COVID-19 patients, we looked for an association between metabolic acidosis surrogates and worse clinical outcomes, such as mortality, renal dialysis, and length of hospital stay. AIM: To describe the acid-base disorders of critically ill COVID-19 patients using Stewart's approach, associating its variables with poor outcomes. METHODS: This study pertained to a retrospective cohort comprised of adult patients who experienced an intensive care unit stay exceeding 4 days and who were diagnosed with severe acute respiratory syndrome coronavirus 2 infection through a positive polymerase chain reaction analysis of a nasal swab and typical pulmonary involvement observed in chest computed tomography scan. Laboratory and clinical data were obtained from electronic records. Categorical variables were compared using Fisher's exact test. Continuous data were presented as median and interquartile range. The Mann-Whitney U test was used for comparisons. RESULTS: In total, 211 patients were analyzed. The mortality rate was 13.7%. Overall, 149 patients (70.6%) presented with alkalosis, 28 patients (13.3%) had acidosis, and the remaining 34 patients (16.2%) had a normal arterial pondus hydrogenii. Of those presenting with acidosis, most had a low apparent strong ion difference (SID) (20 patients, 9.5%). Within the group with alkalosis, 128 patients (61.0%) had respiratory origin. The non-survivors were older, had more comorbidities, and had higher Charlson's and simplified acute physiology score 3. We did not find severe acid-base imbalance in this population. The analyzed Stewart's variables (effective SID, apparent SID, and strong ion gap and the effect of albumin, lactate, phosphorus, and chloride) were not different between the groups. CONCLUSION: Alkalemia is prevalent in COVID-19 patients. Although we did not find an association between acid-base variables and mortality, the use of Stewart's methodology may provide insights into this severe disease.

Evaluation of urine SARS-COV-2 RT-PCR as a predictor of acute kidney injury and disease severity in patients with critical COVID-19.

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began as an outbreak in Wuhan, China and has spread rapidly across the globe. Although most infections are mild, patients with severe and critical COVID-19 infections face deterioration of respiratory function and may also have extrapulmonary manifestations, mostly affecting the kidney, digestive tract, heart, and nervous system. Here, we prospectively evaluated the presence of SARS-CoV-2 genetic material using reverse-transcription polymerase chain reaction in urine samples obtained from patients with COVID-19 receiving critical care. Among 51 included patients, we found higher serum creatinine levels, a longer hospital stay, and more frequent need for dialysis in urine-positive patients. These findings could suggest that, in predisposed patients, a direct viral cytopathic effect may contribute to a more severe disease phenotype.

Evaluation of hemodynamic variations during anesthetic induction in treated hypertensive patients.

BACKGROUND AND OBJECTIVES: Due to the high prevalence of hypertension, the increase in life expectancy, and improvement of diagnostic methods and surgical techniques, this comorbidity will be increasingly more common in surgical patients. The objective of this study was to evaluate the behavior of the hemodynamic variables during anesthetic induction in treated hypertensive patients. METHODS: This is an observational study on the behavior of hemodynamic parameters (systolic blood pressure, diastolic blood pressure, and heart rate) during the anesthetic induction of hypertensive and normotensive patients scheduled for elective surgeries under general anesthesia, at four moments: preparation (MP), drug (MD), laryngoscopy/intubation (ML), and 5 minutes after laryngoscopy/intubation (ML5). RESULTS: The sample was composed of 128 patients divided into two groups: hypertensive (GH) and normotensive (GN). Diastolic blood pressure was reduced at MD in both groups, with a smaller percentage reduction in GH (18.3 +/- 14.0% versus 23.0 +/- 11.4%, p = 0.04). There was an increase in SBP and DBP at ML in both groups, with smaller percentage reductions in GH (8.2 +/- 16.3% versus 18.2 +/- 21.2%, p < 0.01; 8.6 +/- 20.2% versus 25.0 +/- 27.9%, p < 0.01, respectively for DBP and SBP). As for ML5, HR, SBP and DBP did not show significant differences between both groups. CONCLUSIONS: Hypertensive patients under treatment and with controlled blood pressure levels demonstrated greater hemodynamic stability during anesthetic induction.

Parathyroidectomy improves survival in patients with severe hyperparathyroidism: a comparative study.

BACKGROUND AND OBJECTIVES: Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. METHODS: This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. RESULTS: Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. CONCLUSIONS: Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.

Efeitos renais da exposição crônica a nicotina em camundongos com deficiência de Klotho / Renal effects of chronic nicotine exposure in klotho deficient mice

A nicotina é o principal componente do tabaco e dos cigarros eletrônicos. A exposição crônica a nicotina, em quantidades semelhantes às atingidas pelo tabagismo humano, é responsável por piora da lesão renal aguda e da doença renal crônica. O gene klotho, predominantemente expresso no rim, foi descoberto após uma mutação insercional, com o surgimento de um fenótipo semelhante ao envelhecimento humano nos camundongos homozigotos para esse transgene. A proteína Klotho transmembrana tem ação de co-receptor do fator de crescimento fibroblástico 23 (FGF-23) e sua forma secretada atua em diversas vias intracelulares e em órgãos a distância. A deficiência de Klotho ocorre no envelhecimento, em situações que levam a lesão renal aguda e na doença renal crônica. A expressão reduzida de Klotho também agrava lesão renal aguda e participa da progressão da doença renal crônica, enquanto o seu aumento, ou a sua reposição, protegem dos processos inflamatórios e do estresse oxidativo. Neste estudo, objetivamos avaliar os efeitos renais, hemodinâmicos e sobre a expressão de Klotho da exposição crônica a nicotina e quais os efeitos dessa exposição nos animais haploinsuficientes para o transgene klotho (Kl+/-). Utilizamos para estas avaliações camundongos Kl+/- e seus controles wild type (Kl+/+), que foram expostos a nicotina (200 mcg/mL) ou veículo (sacarina 2%) diluídos em água por 28 dias. Ao final do estudo foram avaliados diurese, eletrólitos plasmáticos e urinários, ureia, aldosterona, ADH, FGF-23 e PTH intactos plasmáticos, expressão protéica renal de Klotho, alfa7-nAchR, NHE3, ENaC, NKCC2, AQP2, e-NOS, VEGF, MnSOD e renina, expressão genica renal de klotho, interleucinas, TBARS e GSH em tecido renal, taxa de filtração glomerular por FITC-inulina, pressão arterial e frequência cardíaca invasivas, sensibilidade baroreflexa e modulação autonômica cardíaca e periférica por análise espectral. Após a exposição a nicotina, os animais Kl+/+ apresentaram redução da expressão...

Nicotine is a major compound of tobacco and electronic cigarettes. Chronic exposure to nicotine concentrations that are similar to human smoke worsens acute kidney injury and chronic kidney disease. The klotho (Kl) gene is expressed predominantly by the kidney and was discovered after an unintentional insertional mutation that resulted, in transgenic homozygous mice, in a phenotype similar to human aging. Klotho transmembrane protein acts as a co-receptor to fibroblastic growth factor 23 (FGF-23) and the secreted form interacts in multiple intracellular pathways, with effects in distant organs. Klotho deficiency occurs in aging and in multiple acute kidney injury and chronic kidney disease etiologies, whereas klotho upregulation and replacement protect from inflammation and oxidative stress. Here, we investigated renal and hemodynamic effects of chronic nicotine exposure, its effects over renal expression of Kl, and compared wild type (Kl+/+) and Kl haploinsufficient mice (Kl+/-) in terms of the effects of that exposure. Kl+/- and Kl+/+ mice received nicotine (200 ?g/ml) or vehicle (saccharine 2%) in drinking water for 28 days. We evaluated diuresis, ions in serum and urine, urea, plasma and urinary levels of cotinine, aldosterone, plasma antidiuretic and parathyroid hormone, plasma FGF-23, protein expression of (immunoblotting for) Klotho and ?7 nicotinic acetylcholine receptor, NHE3, NKCC2, ENaC, aquaporin-2, e-NOS, VEGF and renin, klotho mRNA, kidney interleukines, TBARS and GSH, glomerular filtration rate by fluorescein isothiocyanate-inulin clearance, mean arterial pressure, heart rate, baroreflex sensitivity and autonomic cardiac and peripheral modulation by spectral analysis. After nicotine exposure, Kl+/+ mice showed decreased Klotho protein and mRNA and a tendency towards an elevation in plasma FGF-23, which were associated with both diuresis and glomerular filtration rate reductions, without modifications in ADH levels. Besides that, Kl+/+ animals...

Avaliação das variações hemodinâmicas durante a indução anestésica em pacientes hipertensos tratados / Evaluation of hemodynamic variations during anesthetic induction in treated hypertensive patients / Evaluación de las variaciones hemodinámicas durante la inducción anestésica en pacientes hipertensos tratados

JUSTIFICATIVA E OBJETIVOS: Devido à alta prevalência da hipertensão arterial sistêmica, ao aumento da expectativa de vida e ao aprimoramento dos métodos diagnósticos e das técnicas cirúrgicas, essa comorbidade tornar-se-á comum em pacientes cirúrgicos. O objetivo deste estudo foi avaliar o comportamento das variáveis hemodinâmicas dos pacientes hipertensos tratados durante a indução anestésica. MÉTODO: Estudo observacional sobre o comportamento das variáveis hemodinâmicas (pressão arterial sistólica, pressão arterial diastólica e freqüência cardíaca) durante a indução anestésica dos pacientes hipertensos e normotensos, escalados para operações eletivas submetidos à anestesia geral em quatro momentos consecutivos durante a indução anestésica: preparo (MP), fármaco (MF), laringoscopia/intubação (ML) e laringoscopia/intubação 5 min (ML5). RESULTADOS: A amostra foi composta por 128 pacientes distribuídos nos grupos de pacientes hipertensos (GH) e normotensos (GN). Houve diminuição da PAD no momento MF em ambos os grupos, com menor redução percentual no GH (18,3 ± 14,0 por cento versus 23,0 ± 11,4 por cento, p = 0,04). Houve aumento das PAS e PAD no momento ML em ambos os grupos, com menores elevações percentuais no GH (8,2 ± 16,3 por cento versus 18,2 ± 21,2 por cento, p < 0,01; 8,6 ± 20,2 por cento versus 25,0 ± 27,9 por cento, p < 0,01; respectivamente para PAS e PAD). Quanto à PAS e PAD, após ML5, e à FC não houve diferença entre os grupos. CONCLUSÕES: Os pacientes hipertensos tratados com níveis pressóricos controlados apresentaram maior estabilidade hemodinâmica durante a indução anestésica.

BACKGROUND AND OBJECTIVES: Due to the high prevalence of hypertension, the increase in life expectancy, and improvement of diagnostic methods and surgical techniques, this comorbidity will be increasingly more common in surgical patients. The objective of this study was to evaluate the behavior of the hemodynamic variables during anesthetic induction in treated hypertensive patients. METHODS: This is an observational study on the behavior of hemodynamic parameters (systolic blood pressure, diastolic blood pressure, and heart rate) during the anesthetic induction of hypertensive and normotensive patients scheduled for elective surgeries under general anesthesia, at four moments: preparation (MP), drug (MD), laryngoscopy/intubation (ML), and 5 minutes after laryngoscopy/intubation (ML5). RESULTS: The sample was composed of 128 patients divided into two groups: hypertensive (GH) and normotensive (GN). Diastolic blood pressure was reduced at MD in both groups, with a smaller percentage reduction in GH (18.3 ± 14.0 percent versus 23.0 ± 11.4 percent, p = 0.04). There was an increase in SBP and DBP at ML in both groups, with smaller percentage reductions in GH (8.2 ± 16.3 percent versus 18.2 ± 21.2 percent, p < 0.01; 8.6 ± 20.2 percent versus 25.0 ± 27.9 percent, p < 0.01, respectively for DBP and SBP). As for ML5, HR, SBP and DBP did not show significant differences between both groups. CONCLUSIONS: Hypertensive patients under treatment and with controlled blood pressure levels demonstrated greater hemodynamic stability during anesthetic induction.

JUSTIFICATIVA Y OBJETIVOS: Debido a la alta prevalencia de la hipertensión arterial sistémica, al aumento de la expectativa de vida y al perfeccionamiento de los métodos diagnósticos y de las técnicas quirúrgicas, esa comorbidad se hará común en pacientes quirúrgicos. El objetivo de este estudio fue el de evaluar el comportamiento de las variables hemodinámicas de los pacientes hipertensos tratados durante la inducción anestésica. MÉTODO: Estudio de observación sobre el comportamiento de las variables hemodinámicas (presión arterial sistólica, presión arterial diastólica y frecuencia cardíaca) durante la inducción anestésica de los pacientes hipertensos y normotensos, para operaciones electivas sometidos a anestesia general en cuatro momentos consecutivos durante la inducción anestésica: preparación (MP), fármaco (MF), laringoscopía/intubación (ML) y laringoscopía/intubación 5 min (ML5). RESULTADOS: La muestra se compuso de 128 pacientes distribuidos en los grupos de pacientes hipertensos (GH) y normotensos (GN). Hubo una disminución de la PAD en el momento MF en ambos grupos, con menor reducción porcentual en el GH (18,3 ± 14,0 por ciento versus 23,0 ± 11,4 por ciento, p = 0,04). Hubo un aumento de las PAS y PAD en el momento ML en ambos grupos, con menores elevaciones de porcentaje en el GH (8,2 ± 16,3 por ciento versus 18,2 ± 21,2 por ciento, p < 0,01; 8,6 ± 20,2 por ciento versus 25,0 ± 27,9 por ciento, p < 0,01; respectivamente para PAS y PAD). En cuanto a la PAS y PAD, después de la ML5, y a la FC no hubo diferencia entre los grupos. CONCLUSIONES: Los pacientes hipertensos tratados con niveles de presión controlados presentaron una mayor estabilidad hemodinámica durante la inducción anestésica.