Instituto Reina Sofia Of Investigacion Nefrologica Irsin

Spain

Instituto Reina Sofia Of Investigacion Nefrologica Irsin

Spain

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Rodriguez E.,University of Barcelona | Rodriguez E.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Rodriguez E.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | Elia C.,University of Barcelona | And 35 more authors.
Journal of Hepatology | Year: 2014

Background & Aims Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. Methods Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. Results Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5 mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14 ± 3 vs. 8 ± 1, respectively p <0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ≥11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. Conclusions Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment. © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Sola E.,University of Barcelona | Sola E.,Institute d Investigacions Biomediques August Pi i Sunyer IDIBAPS | Sola E.,CIBER ISCIII | Sola E.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 8 more authors.
Current Hepatitis Reports | Year: 2014

Cirrhosis is associated with high morbidity rates due to complications of portal hypertension. Ascites is the most frequent complication in patients with cirrhosis, and refractory ascites will develop in approximately 10 % of patients during follow-up. Currently, the first-line treatment for patients with refractory ascites is large-volume paracentesis with albumin supplementation. In more advanced stages of the disease, dilutional hyponatremia may develop as the result of nonosmotic hypersecretion of vasopressin. Although vaptans have shown promising results as a potential pharmacologic approach to treating hypervolemic hyponatremia, their results on long-term efficacy and safety in patients with cirrhosis are not conclusive. Moreover, because of concerns regarding side effects, the US Food and Drug Administration recently removed the indication of tolvaptan for use in patients with cirrhosis. Finally, in late stages of the disease, intense renal vasoconstriction occurs and leads to the development of hepatorenal syndrome. The treatment of choice for patients with hepatorenal syndrome is vasoconstrictor drugs followed by liver transplantation. © Springer Science+Business Media New York 2014.


Moreno J.A.,Autonomous University of Madrid | Martin-Cleary C.,Autonomous University of Madrid | Gutierrez E.,Institute Investigacion Hospital 12 Of Octubre | Rubio-Navarro A.,Autonomous University of Madrid | And 5 more authors.
Nephrology Dialysis Transplantation | Year: 2012

Haematuria is a frequent manifestation of glomerular disease. However, nephrologists devote more attention to the monitoring and therapeutic targeting of another key manifestation of glomerular injury, proteinuria. Recent reports have propelled haematuria to the forefront of clinical nephrology. Thus, glomerular macroscopic haematuria is associated with the development of acute kidney injury (AKI) with predominant tubular cell damage and there is increasing evidence for the negative impact of glomerular haematuria-associated AKI on long-term renal function outcome both in the context of IgA nephropathy and in anticoagulated patients. In addition, an epidemiological association between isolated microscopic haematuria in young adults and long-term incidence of end-stage renal disease has been described. Finally, a clearer understanding of how haematuria may cause tubular injury is emerging through detailed histological assessment of human biopsies and experimental models of haemoglobin-mediated nephrotoxicity. © 2011 The Author.


Elia C.,University of Barcelona | Elia C.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS | Elia C.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas Ciberehed | Elia C.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 52 more authors.
Journal of Hepatology | Year: 2015

Background & Aims Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs. Methods Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients. Results Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4 ± 3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953 ± 1,198 vs. 83 ± 79 μg/g of creatinine, respectively, p = 0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p = 0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI. Conclusions Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome. © 2015 European Association for the Study of the Liver.


Rodriguez E.,University of Barcelona | Rodriguez E.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | Henrique Pereira G.,University of Barcelona | Henrique Pereira G.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 14 more authors.
Liver Transplantation | Year: 2015

There is little information on the effects of treatment with vasoconstrictors plus albumin in patients with type 2 hepatorenal syndrome (HRS), particularly those awaiting liver transplantation (LT). This study reports the effects of treatment of type 2 HRS in patients on the waiting list for LT. We included 56 patients with type 2 HRS who were awaiting LT. Out of these 56 patients, 31 were treated with terlipressin and albumin. Nineteen (61%) of these 31 patients had response to therapy, and 11 of them relapsed after treatment withdrawal. There were no differences in mortality on the waiting list between responders and nonresponders. Among the 46 (82%) patients who underwent transplantation, 15 underwent transplantation with reversal of type 2 HRS, whereas the remaining 31 underwent transplantation with type 2 HRS. There were no significant differences in serum creatinine or estimated glomerular filtration rate between the 2 cohorts of patients at 3, 6, and 12 months after transplantation. There were no significant differences regarding development of acute kidney injury, need for renal replacement therapy, frequency of chronic kidney disease 1 year after transplant, length of hospitalization, and survival. In conclusion, treatment of patients with type 2 HRS with terlipressin and albumin does not appear to have beneficial effects either in pretransplantation or in posttransplantation outcomes. Liver Transpl 21:1347-1354, 2015. © 2015 AASLD. © 2015 American Association for the Study of Liver Diseases.


Nazar A.,University of Barcelona | Nazar A.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS | Nazar A.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Nazar A.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 24 more authors.
Journal of Hepatology | Year: 2013

Background & Aims: The current study aimed at assessing the potential role of cardiac abnormalities in the pathogenesis of circulatory and renal dysfunction in cirrhosis. Methods: One hundred and fifty-two patients (34 without ascites, 95 with ascites without renal failure and 21 with hepatorenal syndrome) were evaluated using Doppler echocardiography. In 102 patients, diastolic function was assessed by measuring parameters related to ventricular filling velocity, mitral annulus velocity and left atrial dimensions. Cardiopulmonary pressures were also measured by cardiac catheterization in 54 patients. In 50 additional patients, left ventricular myocardial strain was performed to estimate myocardial contractility and systolic function. Results: Grade 1 and 2 diastolic dysfunction was present in 41% and 16% of the patients, respectively. There was no patient with severe grade 3 diastolic dysfunction. Grade 2 diastolic dysfunction was associated with higher cardiopulmonary pressures but values were within the normal limits in all cases. Diastolic dysfunction directly correlated with liver failure but not with the degree of impairment in circulatory and renal function. The proportion of patients without or with grade 1 or 2 diastolic dysfunction was similar in patients with compensated cirrhosis, with ascites without renal failure or with hepatorenal syndrome despite marked differences in the degree of circulatory dysfunction, as indicated by plasma renin activity and noradrenaline concentration. The heart rate and systolic function were normal in all cases. There were no differences between patients without ascites, with ascites without renal failure or with HRS, despite marked differences in the activity of the renin-angiotensin system and sympathetic nervous system. These features indicate an impaired response of cardiac chronotropic and inotropic function to changes in systemic hemodynamics. Conclusions: These data indicates that: (1) diastolic dysfunction is frequent in cirrhosis but in most cases it is of mild degree and does not increase the cardiopulmonary pressure to abnormal levels. This feature, which may be due to the central hypovolemia of cirrhosis, probably accounts for the lack of symptoms associated with this condition. (2) Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. (3) In cirrhosis, there is a lack of response of the left ventricular systolic and chronotropic function to peripheral arterial vasodilation and activation of the sympathetic nervous system and this feature is an important contributory factor to the progression of circulatory dysfunction and the pathogenesis of ascites and HRS. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Guevara M.,University of Barcelona | Guevara M.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS | Guevara M.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Guevara M.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 25 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Treatment with albumin in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) prevents renal failure and improves survival. Whether albumin has similar beneficial effects in patients with infections other than SBP is unknown. Methods: One hundred and ten patients with cirrhosis hospitalized for infections other than SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg bw at diagnosis and 1 g/kg bw at day 3) (albumin group; n = 56) or antibiotics alone (control group; n = 54). The primary end point was survival at 3 months. Secondary end points were effects on renal and circulatory function. Results: The renal function, as evaluated by differences in changes in serum creatinine and estimated glomerular filtration rate between the two groups, improved in patients treated with albumin. The circulatory function improved significantly in patients treated with albumin, but not in those from the control group. There was a trend for a lower frequency of type 1 hepatorenal syndrome in the albumin group compared to the control group (1 vs. 4 patients, respectively; p = n.s.). Probability of survival at 3 months was not significantly different among the two groups. However, when adjusted for factors with independent prognostic value, treatment with albumin was an independent predictive factor of survival. Conclusions: As compared with standard antibiotic therapy alone, treatment with albumin together with antibiotics has beneficial effects on the renal and circulatory function and shows a potential survival benefit. Further studies with large sample sizes should be performed to confirm these findings. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Fagundes C.,University of Barcelona | Fagundes C.,Institute dInvestigacions Biomediques August Pi Sunyer IDIBAPS | Fagundes C.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Fagundes C.,Instituto Reina Sofia Of Investigacion Nefrologica Irsin | And 47 more authors.
Journal of Hepatology | Year: 2012

Background & Aims: Impairment of kidney function is common in cirrhosis but differential diagnosis remains a challenge. We aimed at assessing the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage, in the differential diagnosis of impairment of kidney function in cirrhosis. Methods: Two-hundred and forty-one patients with cirrhosis, 72 without ascites, 85 with ascites, and 84 with impaired kidney function, were studied. Urinary levels of NGAL were measured by ELISA. Results: Patients with impaired kidney function had higher urinary NGAL levels compared to patients with and without ascites. Patients with urinary tract infection (n = 25) had higher uNGAL values than non-infected patients. Patients with acute tubular necrosis (ATN) had uNGAL levels markedly higher (417 μg/g creatinine (239-2242) median and IQ range) compared to those of patients with pre-renal azotemia due to volume depletion 30 (20-59), chronic kidney disease (CKD) 82 (34-152), and hepatorenal syndrome (HRS) 76 (43-263) μg/g creatinine (p <0.001 for all). Among HRS patients, the highest values were found in HRS-associated with infections, followed by classical (non-associated with active infections) type-1 and type-2 HRS (391 (72-523), 147 (83-263), and 43 (31-74) μg/g creatinine, respectively; p <0.001). Differences in uNGAL levels between classical type 1 HRS and ATN on the one hand and classical type 1 HRS and CKD and pre-renal azotemia on the other were statistically significant (p <0.05). Conclusions: uNGAL levels may be useful in the differential diagnosis of impairment of kidney function in cirrhosis. Urinary tract infections should be ruled out because they may increase uNGAL excretion. © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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