Troponin I at admission in the intensive care unit predicts the need of dialysis in septic patients.

BACKGROUND: In a previous study we showed that troponin I (TnI) > 0.42 ng/mL predicted the need of dialysis in a group of 29 septic patients admitted to the intensive care unit (ICU). We aimed to confirm such finding in a larger independent sample. METHODS: All septic patients admitted to an ICU from March 2016 to February 2017 were included if age between 18 and 90 years, onset of sepsis < 24 h, normal left ventricular ejection fraction, and no previous coronary or kidney diseases. TnI was measured on day 1. Patients were followed by 30 days or until death. RESULTS: A total of 120 patients were included (51% male, 74 ± 13 years old). At ICU admission, 70 patients had TnI > 0.42 ng/mL. These patients had serum creatinine slightly higher (1.66 ± 0.34 vs. 1.32 ± 0.39 mg/dL; P <  0.0001) than those with lower TnI and similar urine output (1490 ± 682 vs. 1406 ± 631 mL; P = 0.44). At the end of the follow-up period, 70.0% of the patients with lower TnI were alive in comparison with 38.6% of those with higher TnI (p = 0.0014). After 30 days, 69.3 and 2.9% of the patients with lower and higher TnI levels remained free of dialysis, respectively (p <  0.0001). In a Cox regression model, after adjustment for gender, age, Charlson comorbidity index, serum creatinine, potassium, pH, brain natriuretic peptide and urine output, TnI > 0.42 ng/mL persisted as a strong predictor of dialysis need (hazard ratio 3.48 [95%CI 1.69-7.18]). CONCLUSIONS: TnI levels at ICU admission are a strong independent predictor of dialysis need in sepsis.

Creatinine measurement on dry blood spot sample for chronic kidney disease screening.

INTRODUCTION: Chronic kidney disease (CKD) screening is advisable due to its high morbidity and mortality and is usually performed by sampling blood and urine. OBJECTIVE: Here we present an innovative and simpler method, by measuring creatinine on a dry blood spot on filter paper. METHODS: One-hundred and six individuals at high risk for CKD were enrolled. The creatinine values obtained using both tests and the demographic data of each participant allowed us to determinate the eGFR. The adopted cutoff for CKD was an eGFR < 60 ml/min. RESULTS: Mean age was 57 ± 12 years, 74% were female, 40% white, and 60% non-white. Seventy-six percent were hypertensive, 30% diabetic, 37% had family history of CKD, and 22% of smoking. The BMI was 29.5 ± 6.9 kg/m2, median systolic blood pressure was 125 mmHg (IQR 120-140 mmHg) and median diastolic blood pressure was 80 mmHg (IQR 70-80 mmHg). According to MDRD equation, sensitivity was 96%, specificity 55%, predictive positive value 96%, predictive negative value 55% and accuracy 92%. By the CKD-EPI equation the sensitivity was 94%, specificity 55%, predictive positive value 94%, predictive negative value 55% and accuracy 90%. A Bland and Altman analysis showed a relatively narrow range of creatinine values differences (+ 0.68mg/dl to -0.55mg/dl) inside the ± 1.96 SD, without systematic differences. CONCLUSION: Measurement of creatinine on dry blood sample is an easily feasible non-invasive diagnostic test with good accuracy that may be useful to screen chronic kidney disease.

Detecção de disfunção renal através da dosagem de creatinina em amostra de gota de sangue seca no papel filtro / Creatinine measurement on dry blood spot sample for chronic kidney disease screening

Resumo Introdução: A identificação precoce da doença renal crônica (DRC) por meio de amostras de sangue e urina é preconizada em populações de risco devido à elevada morbimortalidade. Objetivo: Apresentamos um teste simples e inovador para dosar a creatinina coletada em gota de sangue seca em papel filtro (PF). Métodos: Cento e seis pessoas em risco de DRC foram rastreadas com avaliação de dados clínicos, exame físico e coleta de sangue de forma convencional e em PF. Com os dados obtidos, foi estimada a taxa de filtração glomerular (e-TFG). Foi considerado diagnóstico de DRC a e-TFG < 60 ml/min. Resultados: A idade dos participantes foi de 57 ± 12 anos, 78 (73,5%) eram mulheres, 43 brancos (40,5%), 36 pardos (34%) e 27 negros (25,5%). O índice de massa corpórea foi de 29,5 ± 6,9 kg/m2, a pressão arterial sistólica foi de 125 mmHg (120-140 mmHg) e a pressão arterial diastólica de 80 mmHg (70-80 mmHg). A sensibilidade pela equação CKD-EPI foi de 94%, a especificidade 55%, o valor preditivo positivo foi de 94%, o valor preditivo negativo de 55% e a acurácia de 90%. A estatística de Bland-Altman mostrou que as diferenças entre os valores de creatinina dos dois testes estão numa faixa relativamente estreita (+ 0,68 mg/dL e -0,55mg/dL) para um desvio padrão de ± 1,96 mg/dL. Conclusão: A dosagem da creatinina coletada em gota de sangue em PF é um teste diagnóstico simples de ser realizado, pouco invasivo e que apresentou uma ótima acurácia, podendo ser útil para rastrear DRC.

Abstract Introduction: Chronic kidney disease (CKD) screening is advisable due to its high morbidity and mortality and is usually performed by sampling blood and urine. Objective: Here we present an innovative and simpler method, by measuring creatinine on a dry blood spot on filter paper. Methods: One-hundred and six individuals at high risk for CKD were enrolled. The creatinine values obtained using both tests and the demographic data of each participant allowed us to determinate the eGFR. The adopted cutoff for CKD was an eGFR < 60 ml/min. Results: Mean age was 57 ± 12 years, 74% were female, 40% white, and 60% non-white. Seventy-six percent were hypertensive, 30% diabetic, 37% had family history of CKD, and 22% of smoking. The BMI was 29.5 ± 6.9 kg/m2, median systolic blood pressure was 125 mmHg (IQR 120-140 mmHg) and median diastolic blood pressure was 80 mmHg (IQR 70-80 mmHg). According to MDRD equation, sensitivity was 96%, specificity 55%, predictive positive value 96%, predictive negative value 55% and accuracy 92%. By the CKD-EPI equation the sensitivity was 94%, specificity 55%, predictive positive value 94%, predictive negative value 55% and accuracy 90%. A Bland and Altman analysis showed a relatively narrow range of creatinine values differences (+ 0.68mg/dl to -0.55mg/dl) inside the ± 1.96 SD, without systematic differences. Conclusion: Measurement of creatinine on dry blood sample is an easily feasible non-invasive diagnostic test with good accuracy that may be useful to screen chronic kidney disease.

Proof of concept study: Improvement of echocardiographic parameters after renal sympathetic denervation in CKD refractory hypertensive patients.

AIM: Evaluation of the effectiveness of the renal sympathetic denervation (RSD) in reducing lesions of target organs such as the heart and kidneys, in resistant hypertensive CKD patients. METHODS AND RESULTS: Forty-five patients were included and treated with an ablation catheter with open irrigated tip. RSD was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n=22), 3 (n=16), and 4 (n=7). Data were obtained at baseline and monthly until the 6th month of follow-up. Twenty-six out of the 45 patients had LVH and nineteen did not present LVH. The LV mass index decreased from 123.70±38.44g/m(2) at baseline to 106.50±31.88g/m(2) at the 6th month after RSD, P<0.0001. The end-diastolic left ventricular internal dimension (LVIDd) reduced from 53.02±6.59mm at baseline to 51.11±5.85mm 6months post procedure, P<0.0001. The left ventricular end-diastolic posterior wall thickness (PWTd) showed a reduction from 10.58±1.39mm at baseline to 9.82±1.15mm at the 6th month of follow-up, P<0.0001. The end-diastolic interventricular septum thickness (IVSTd) also decreased from 10.58±1.39mm at baseline to 9.82±1.15mm 6months post procedure, P<0.0001. The left ventricular ejection fraction (LVEF) improved from 58.90±10.48% at baseline to 62.24±10.50% at the 6th month of follow-up, P<0.0001. When the ∆ between baseline and the 6th month post RSD in LVH patients and non LVH patients were compared to the same parameters no significant difference was found. CONCLUSIONS: The RSD seemed to be feasible, effective, and safe resulting in an improvement of echocardiographic parameters in LVH and non LVH CKD refractory hypertensive patients.

Long-Term Effects of Renal Sympathetic Denervation on Hypertensive Patients With Mild to Moderate Chronic Kidney Disease.

Thirty patients who underwent percutaneous renal denervation, which was performed by a single operator following the standard technique, were enrolled in this study. Patients with chronic kidney disease (CKD) stage 2 (n=19), 3 (n=6), and 4 (n=5) were included. Data were obtained at baseline and at monthly intervals for the first 6 months. At 7 months, follow-up data were collected bimonthly until month 12, after which data were collected on a quarterly basis. Baseline blood pressure values (mean±standard deviation) were 185±18/107±13 mm Hg in the office and 152±17/93±11 mm Hg through 24-hour ambulatory blood pressure monitoring (ABPM). Three patients with stage 4 CKD required chronic renal replacement therapy (one at the 13-month follow-up and two at the 14-month follow-up) after episodes of acute renal injury; their follow-up was subsequently discontinued. The office blood pressure values at the 24-month follow-up were 131±15/87±9 mm Hg (P<.0001, for both comparisons); the corresponding ABPM values were 132±14/84±12 mm Hg (P<.0001, for both comparisons). The mean estimated glomerular filtration rate increased from 61.9±23.9 mL/min/1.73 m(2) to 88.0±39.8 mL/min/1.73 m(2) (P<.0001). The urine albumin:creatinine ratio decreased from 99.8 mg/g (interquartile range, 38.0-192.1) to 11.0 mg/g (interquartile range, 4.1-28.1; P<.0001 mg/g). At the end of the follow-up period, 21 patients (70% of the initial sample) were no longer classified as having CKD.

Troponin I serum levels predict the need of dialysis in incident sepsis patients with acute kidney injury in the intensive care unit.

INTRODUCTION: Sepsis, an extremely prevalent condition in the intensive care unit, is usually associated with organ dysfunction, which can affect heart and kidney. OBJECTIVE: To determine whether the cardiac dysfunction and the Troponin I forecast the occurrence of acute renal failure in sepsis. METHODS: Cardiac dysfunction was assessed by echocardiography and by the serum troponin I levels, and renal impairment by AKIN criteria and the need of dialysis. Twenty-nine patients with incident sepsis without previous cardiac or renal dysfunction were enrolled. RESULTS AND DISCUSSION: Patients averaged 75.3 ± 17.3 years old and 55% were male. Median APACHE II severity score at ICU admission was 16 (9.7 - 24.2) and mortality rate in 30 days was 45%. On the fifth day, 59% had ventricular dysfunction. Troponin serum levels on day 1 in the affected patients were 1.02 ± 0.6 ng/mL compared with 0.23 ± 0.18 ng/mL in patients without heart dysfunction (p = 0.01). Eighteen out of 29 patients (62%) underwent renal replacement therapy (RRT) and the percent of patients with ventricular dysfunction who required dialysis was higher (94% vs. 16%, p = 0.0001). Values of troponin at day 1 were used to develop a ROC curve to determine their ability to predict the need of dialysis. The area under the curve was 0.89 and the cutoff value was 0.4 ng/mL. CONCLUSION: We found that an elevation in serum troponin levels, while guarding a relationship with ventricular dysfunction, can be a precious tool to predict the need for dialysis in sepsis patients.

Troponin I serum levels predict the need of dialysis in incident sepsis patients with acute kidney injury in the intensive care unit / Níveis séricos de troponina predizem a necessidade de diálise em pacientes sépticos com injúria renal aguda renal na unidade de terapia intensiva

Abstract Introduction: Sepsis, an extremely prevalent condition in the intensive care unit, is usually associated with organ dysfunction, which can affect heart and kidney. Objective: To determine whether the cardiac dysfunction and the Troponin I forecast the occurrence of acute renal failure in sepsis. Methods: Cardiac dysfunction was assessed by echocardiography and by the serum troponin I levels, and renal impairment by AKIN criteria and the need of dialysis. Twenty-nine patients with incident sepsis without previous cardiac or renal dysfunction were enrolled. Results and Discussion: Patients averaged 75.3 ± 17.3 years old and 55% were male. Median APACHE II severity score at ICU admission was 16 (9.7 - 24.2) and mortality rate in 30 days was 45%. On the fifth day, 59% had ventricular dysfunction. Troponin serum levels on day 1 in the affected patients were 1.02 ± 0.6 ng/mL compared with 0.23 ± 0.18 ng/mL in patients without heart dysfunction (p = 0.01). Eighteen out of 29 patients (62%) underwent renal replacement therapy (RRT) and the percent of patients with ventricular dysfunction who required dialysis was higher (94% vs. 16%, p = 0.0001). Values of troponin at day 1 were used to develop a ROC curve to determine their ability to predict the need of dialysis. The area under the curve was 0.89 and the cutoff value was 0.4 ng/mL. Conclusion: We found that an elevation in serum troponin levels, while guarding a relationship with ventricular dysfunction, can be a precious tool to predict the need for dialysis in sepsis patients.

Resumo Introdução: Sepse é uma condição extremamente prevalente na unidade de terapia intensiva, geralmente associada com disfunção orgânica que pode afetar o coração e os rins. Objetivo: Determinar se a disfunção cardíaca e a troponina I preveem a ocorrência de lesão renal aguda na sepse. Métodos: A disfunção cardíaca foi avaliada por ecocardiografia e pelos níveis de troponina I sérica; e a lesão renal aguda pelos critérios AKIN e necessidade de diálise. Vinte e nove pacientes com sepse foram recrutados. Resultados e Discussão: Os pacientes tinham em média 75,3 ± 17,3 anos e 55% eram do sexo masculino. O escore de gravidade APACHE II médio de internação na UTI foi de 16 (9,7-24,2) e taxa de mortalidade em 30 dias foi de 45%. No quinto dia, 59% tinham disfunção ventricular. O nível sérico de troponina no dia 1 nos pacientes afetados foi de 1,02 ± 0,6 ng/mL em comparação com 0,23 ± 0,18 ng/mL em pacientes sem disfunção cardíaca (p = 0,01). Dezoito dos 29 pacientes (62%) foram submetidos à terapia renal substitutiva e a porcentagem de pacientes com disfunção ventricular que necessitou de diálise foi maior (94% vs. 16%, p = 0,0001) nesse grupo. A área sob uma curva ROC desenhada para prever a necessidade de diálise de acordo com o nível sérico de troponina no dia 1 foi de 0,89 e o valor de corte foi de 0,4 ng/mL. Conclusão: Verificou-se que uma elevação nos níveis séricos de troponina pode prever a necessidade de diálise em pacientes sépticos com lesão renal aguda.

Renal sympathetic denervation in patients with hypertension and chronic kidney disease: does improvement in renal function follow blood pressure control?

Twenty-seven patients with resistant hypertension and chronic kidney disease were treated by renal sympathetic denervation (RSD) and followed for 12 months. Patients were retrospectively divided into controlled and uncontrolled blood pressure (BP) groups. Increases in mean estimated glomerular filtration rate (eGFR) were found at months 1, 3, 6, and 12 in the controlled group (P < .0001, for every time point). The mean change in eGFR after 12 months was 18.54 ± 8.15 mL/min/1.73 m(2) higher in the controlled group (P=.0318). In patients in the controlled group with baseline eGFR < 45 mL/min/1.73 m(2), responders (with an increase in eGFR > 6.2%) corresponded to 50% at 6 months and 83% at 12 months. In the patients with baseline eGFR ≥ 45 mL/min/1.73 m(2), all patients were labeled as responders at months 6 and 12. Median albumin:creatinine ratio after 12 months was lower than baseline only in the controlled group (P = .0003). Our results suggest that patients with this profile who reached BP control by RSD also experienced a significant improvement in renal function.

Effects of renal denervation with a standard irrigated cardiac ablation catheter on blood pressure and renal function in patients with chronic kidney disease and resistant hypertension.

AIMS: Evaluation of the safety and efficacy of renal denervation with a standard irrigated cardiac ablation catheter (SICAC) in chronic kidney disease (CKD) patients with refractory hypertension. METHODS AND RESULTS: Twenty-four patients were included and treated with a SICAC. Denervation was performed by a single operator following the standard technique. Patients included with CKD were on stages 2 (n = 16), 3 (n = 4), and 4 (n = 4). Data were obtained at baseline and monthly until 180th day of follow-up. Baseline values of blood pressure (mean ± SD) were 186 ± 19 mmHg/108 ± 13 mmHg in the office, and 151 ± 18 mmHg/92 ± 11 mmHg by 24 h ambulatory blood pressure monitoring (ABPM). Office blood pressure values at 180th day after the procedure were 135 ± 13 mmHg/88 ± 7 mmHg (P < 0.0001, for both comparisons). The mean ABPM decreased to 132 ± 15 mmHg/85 ± 11 mmHg at the 180th day after the procedure (P < 0.0001 for systolic and P = 0.0015 for diastolic). Estimated glomerular filtration (mean ± SD) increased from baseline (64.4 ± 23.9 mL/min/1.73 m(2)) to the 180th day (85.4 ± 34.9 mL/min/1.73 m(2), P < 0.0001) of follow-up. The median urine albumin:creatinine ratio decreased from baseline (48.5, IQR: 35.8-157.2 mg/g) to the 180th day after ablation (ACR = 15.7, IQR: 10.3-34.2 mg/g, P = 0.0017). No major complications were seen. CONCLUSION: The procedure using SICAC seemed to be feasible, effective, and safe resulting in a better control of BP, a short-term increase in estimated glomerular filtration rate, and reduced albuminuria. Although encouraging, our data are preliminary and need to be validated in the long term.

Intrarenal Renin-Angiotensin system is upregulated in experimental model of progressive renal disease induced by chronic inhibition of nitric oxide synthesis.

Locally generated angiotensin II (AngII) may be involved in the pathogenic mechanisms of chronic renal diseases. Renal expression of AngII and other components of the renin-angiotensin system (RAS) were analyzed by immunohistochemistry and Western blot in a model of chronic progressive nephropathy induced by inhibition of nitric oxide synthesis. Renal injury was evaluated by histology and albumin excretion. Systemic RAS status was evaluated through plasma renin activity (PRA) and plasma AngII concentration. In addition, the effects of enalapril, losartan, and mycophenolate mofetil (MMF) on AngII expression in animals with chronic renal disease was also analyzed. Plasma renin activity and plasma AngII were not different between rats with nephropathy and controls (2.08 +/- 0.7 versus 2.03 +/- 0.5 ng/ml/h and 94.3 +/- 18 versus 78.9 +/- 16 fmol/ml, respectively). However, rats with chronic progressive nephropathy showed augmented renal content of angiotensinogen protein (13.5 +/- 3.5 versus 2.2 +/- 0.4 pixels in control rats; P < 0.05), enhanced expression of cathepsin D-a renin-like enzyme-in cortical collecting tubules (103.5 +/- 27.0 versus 66.2 +/- 3.6 cells/mm2 in controls; P < 0.01), and increased expression of AT1 receptor in interstitium (54.7 +/- 7.8 versus 1.3 +/- 0.4 cells/mm2 in controls; P < 0.001). Kidney angiotensin-converting enzyme content did not differ among the groups. Notably, an increased number of interstitial cells expressing AngII was detected in the renal interstitium (9.5 +/- 1.6 versus 1.7 +/- 0.6 cells/mm2 in controls; P < 0.05). Rats treated with Nomega-nitro-L-arginine-methyl-esther and losartan presented a decreased local AngII formation, in contrast to its known effect on plasma AngII. Moreover, mycophenolate mofetil lowered interstitial AngII expression, suggesting that inflammatory signaling may be involved in interstitial AngII generation. This study demonstrates the upregulation of local RAS in the kidney in a model of chronic progressive nephropathy.

Estudo do sistema renina-angiotensina intrarenal em modelo experimental de nefropatia crônica progressiva / A study of the intrarenal renin-angiotensin system in a experimental model of progressive chronic nephropathy

A Ang II é um agente fibrogênico que contribui para a progressão de doenças renais crônicas que possivelmente é produzida localmente no rim. Foram estudados ratos com doença renal por depleção de óxido nítrico. Os principais achados foram: 1) os animais doentes, com hipertensão, albuminúria e lesão renal histológica têm renina e Ang II plasmáticas normais; 2) o rim apresenta toda a maquinaria necessária à produção local de Ang II; 3) há aumento da expressão de Ang II e de seu receptor AT1 no interstício renal de animais doentes; 4) a regulação da Ang II local é diferente da sistêmica, uma vez que o losartan diminui a Ang II local e aumenta a sistêmica; 5) a catepsina D pode contribuir para a geração local de Ang II; e 6) Os fibroblastos podem participar da geração local de Ang II e esta produção pode ser influenciada por TNF-a e IL-1b.Ang II is an well known fibrogenic agent that contributes to the progression of chronic renal disease and seems to be locally produced inside the kidney. Rats with renal disease caused by nitric oxide depletion were studied. The main results are: 1) the rats were hypertensive, albuminuric and with histologic renal damage but had normal plasma renin and Ang II; 2) the kidney has a complete machinery to produce Ang II; 3) Ang II and AT1 receptor were highly expressed in injured kidneys; 4) the regulation of local Ang II production differs from the systemic one, since losartan diminishes local while increases systemic Ang II; 5) cathepsin D may contribute to local Ang II generation; and 6) fibroblasts may produce Ang II locally under the stimuli of TNF-a and IL-1b...