Colistimethate sodium and acute kidney injury: Incidence,risk factors,outcome and prognosis of renal function

BackgroundColistimethate sodium (CMS) treatment has increased over the last years, being acute kidney injury (AKI) its main drug-related adverse event. Therefore, this study aimed to evaluate the incidence and risk factors associated with AKI, as well as identifying the factors that determine renal function (RF) outcomes at six months after discharge.Materials and methodsThis retrospective study included adult septic patients receiving intravenous CMS for at least 48 h (January 2007–December 2014). AKI was assessed using KDIGO criteria. The glomerular filtration rate (GFR) was estimated by the 4-variable MDRD equation. Logistic and linear models were performed to evaluate the risk factors for AKI and chronic kidney disease (CKD).ResultsAmong 126 patients treated with CMS; the incidence of AKI was 48.4%. Sepsis–severe sepsis (OR 8.07, P = 0.001), sepsis–septic shock (OR 42.9, P < 0.001), and serum creatinine (SCr) at admission (OR 6.20, P = 0.009) were independent predictors.Eighty-four patients survived; the main factors for RF evolution at the 6-month follow-up was baseline eGFR (0.58, P < 0.001) and at discharge (0.34, P < 0.001). Fifty-six percent (34/61) of the patients that developed AKI survived. At six months, 32% had CKD.ConclusionsThe development of AKI in septic patients with CMS treatment was associated with sepsis severity and SCr at admission. Baseline eGFR and eGFR at discharge were and important determinant of the RF at the 6-month follow-up. These predictors may assist in clinical decision making for this patient population.     

Interacción cardiorrenal y evolución de la insuficiencia cardiaca. ¿Tiene un papel la proteína de unión del factor de crecimiento de tipo insulina 2?

Introduction and objectivesPreliminary results suggest that high circulating insulin-like growth factor binding protein 2 (IGFBP2) levels are associated with mortality risk in heart failure (HF) patients. As IGFBP2 levels are increased in patients with chronic kidney disease (CKD), which is associated with a higher mortality risk in HF patients, we examined whether IGFBP2 is associated with CKD in HF patients, and whether CKD modifies the prognostic value of this protein in HF patients.MethodsHF patients (n = 686, mean age 66.6 years, 32.7% women) were enrolled and followed up for a median of 3.5 (min-max range: 0.1-6) years. Patients were classified as having CKD with decreased estimated glomerular filtration rate (eGFR < 60 mL/min/1.73 m²) or as having CKD with nondecreased eGFR (≥ 60 mL/min/1.73 m²). Serum IGFBP2 was detected by ELISA.ResultsIGFBP2 was increased (P < .001) in CKD patients with decreased eGFR (n = 290, 42.3%) compared with patients with nondecreased eGFR. IGFBP2 was directly associated with NT-proBNP (P < .001) and inversely associated with eGFR (P < .001), with both associations being independent of confounding factors. IGFBP2 was directly and independently associated with cardiovascular and all-cause death (P < .001) in the whole group of patients, but showed a stronger association with cardiovascular death in CKD patients with decreased eGFR (P for interaction < .05), improving risk prediction in these patients over clinically relevant risk factors.ConclusionsSerum IGFBP2 is associated with impaired renal function and prognosticates cardiovascular death in patients with HF and CKD with decreased eGFR. Thus, there is an effect modification of CKD on circulating IGFBP2 and on its association with cardiovascular mortality in HF patients.     

Does uric acid-lowering treatment slow the progression of chronic kidney disease? A meta-analysis of randomized controlled trials

IntroductionHyperuricemia has been proposed as an independent factor in the development and progression of chronic kidney disease (CKD). However, the effect of uric acid-lowering therapies on delaying CKD progression is still uncertain. Therefore, this systemic review aims to assess the effect of uric acid-lowering therapies on renal outcomes in pre-dialysis CKD patients.MethodsPubMed, Cochrane Library, and Lilacs databases were searched until April 24, 2021, for randomized clinical trials of CKD patients on uric acid-lowering treatment with xanthine-oxidase (XO) inhibitors. The weighted mean difference (WMD) or standard mean difference (SMD) with confidence interval (CI) were pooled using a random-effects model.ResultsAmong 567 studies found, eighteen met the inclusion criteria (n = 2463 participants). Compared to the patient's control group, the WMD for the glomerular filtration ratio (GFR) and serum creatinine changes of the treated group was 2.02 ml/min/1.73 m² (95%CI 0.41 to 3.63, P = 0.014) and −0.19 mg/dl (95%CI −0.34 to −0.04, I² = 86.2%, P = 0.011), respectively. Subgroup analyses showed that the difference in follow-up time and CKD population type in the studies may explain the controversy about the role of uric acid-lowering therapies in CKD progression. The GFR and creatinine outcomes analysis by types of XO inhibitors showed no difference between the control and treated groups. Uric acid-lowering therapies were strongly associated with decreased serum uric acid and urinary protein–creatinine ratio and urinary albumin–creatinine ratio.ConclusionsThese findings suggest that uric acid-lowering treatment may slow CKD progress and reduce protein and albumin excretion. However, larger and properly powered randomized clinical trials with specific CKD populations are needed to confirm these findings.     

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study

BackgroundAcute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI.MethodsIn a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m², renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available.ResultsAmong 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16–1.53], 1.43 [1.33–1.54], 1.23 [1.14–1.34], 1.38 [1.18–1.62] for eGFR ≥90, 60–89, 30–59 and 15–29 ml/min/1.73 m², respectively. When omitting the outcome heart failure, these results were 1.24 [1.06–1.45], 1.22 [1.11–1.33], 1.05 [0.95–1.16], 1.25 [1.02–1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria.ConclusionNon-selected patients aged 50 years or above with AKI during admission had significantly higher one-year risk of cardiovascular event or death, especially, but not only due to heart failure, independent of age and eGFR.     

High-normal serum uric acid predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus and preserved kidney function

AimsWe evaluated whether high-normal serum uric acid (SUA) levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus and preserved kidney function at baseline.MethodsThis was a retrospective observational longitudinal study of patients presenting at the Department of Endocrinology and Metabolism, Pusan National University Hospital. A total of 512 patients with type 2 diabetes mellitus and preserved kidney function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m²) and normouricemia were included. The main outcome was development of CKD of stage 3 or greater. The patients were divided into four groups according to quartiles of SUA levels.ResultsDuring the follow-up period, 62 (12.1%) patients had progressed to CKD 3 or greater. The group with the highest-normal range of SUA (Q4) showed a higher cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q4 vs. Q3; P = 0.037, Q4 vs. Q2; P < 0.001, Q4 vs. Q1; P < 0.001). In a univariate analysis, Q4 was significantly associated with the development of CKD 3 or greater (log-rank statistic, 31.93; P < 0.001). In a multivariate analysis, Q4 (hazard ratio, 2.97; 95% confidence interval, 1.15–7.71; P = 0.025) showed a significant association with CKD 3 or greater.ConclusionsHigh-normal SUA may predict the occurrence of CKD stage 3 or greater in patients with type 2 diabetes mellitus and preserved kidney function.     

Severity of coronary artery disease is an independent risk factor for decline in kidney function

Background and aimChronic kidney disease (CKD) and cardiovascular disease are closely interrelated and the presence of one condition synergistically affects the prognosis of the other, in a negative manner. There are surprisingly very few data on the relationship between baseline coronary artery disease (CAD) severity and subsequent decline in kidney function. We aimed to evaluate for the first time whether baseline coronary artery lesion severity predicts the decline in kidney function.Materials and methodsThe study population was derived from a series of consecutive patients presenting with stable angina pectoris or angina equivalents, who underwent coronary angiography. SYNTAX score for each patient was calculated to define severity of CAD. Change in kidney function was defined by calculating the rates of change in eGFR.ResultsAmong the 823 patients included in our study, the mean age was 59.2 ± 10.7 years, 78.4% were males, and 32% had diabetes. The mean baseline eGFR was 87.3 ± 24.9 ml/min/1.73 m² and the median Syntax score was 14 (IQR = 10–20). The median length of follow-up was 2.75 years (IQR = 2.42–3.50). The mean yearly change for eGFR in the entire study population was 4.06 (95% CI: 3.59–4.51) ml/min/1.73 m². A higher Syntax score was associated with a significantly faster decline in eGFR in all (unadjusted and adjusted) models. During the follow-up, 103 patients developed CKD. A higher Syntax score, analyzed both as continuous and categorical variable, was associated with incident CKD in all models.ConclusionWe have demonstrated for the first time that severity of CAD is an independent risk factor for the decline in kidney function. Studies are needed to highlight the potential mechanisms regarding the association between severity of CAD and decline in kidney function.     

Epidemiology,clinical profile,management, and two-year risk complications among patients with chronic kidney disease in Spain

ObjectivesTo describe the epidemiology, clinical profile, treatments, and to determine cardiovascular and renal outcomes after two years of follow-up in a contemporary chronic kidneay disease (CKD) population in Spain. This was also analyzed among the DAPA-CKD-like population (patients who met most inclusion criteria of DAPA-CKD trial).MethodsObservational, retrospective, population-based study using BIG-PAC database. The CKD population was defined as patients ≥18 years, with at least one diagnostic code of CKD prior to the index date (January 1st, 2018). CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² (CKD-EPI), or albuminuria >30 mg/g.ResultsWe identified 56,435 CKD patients after exclusions (76.4 years, 52.2% men, urine albumin-to-creatinine ratio 390.8 mg/g, eGFR 49.7 mL/min/1.73 m²). CKD prevalence was 4.91% and incidence 2.10 per 1000 patient-years. Regarding treatments, 69.2% were taking renin-angiotensin system inhibitors (only 4.2% at maximal doses) and 3.5% of diabetic patients SGLT-2 inhibitors. During the two years of follow-up, rates of heart failure, all-cause death, myocardial infarction, stroke, and CKD were 17.9, 12.1, 7.2, 6.3, and 5.9 events per 100 patient-years, respectively. During this period, 44% of patients were hospitalized, and 6.8% died during hospitalization. Cardiovascular outcomes were more common in the DAPA-CKD-like population.ConclusionsIn Spain, CKD population is older and comorbidities, including diabetes and heart failure, are common. Cardiovascular and renal outcomes are frequent. There is room for improvement in CKD management, particularly through the use of drugs with proven cardiovascular and renal benefit.     

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT.Study designMulticentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24–120).ResultsIn 69 patients (42 males, 27 females, mean age 44.6 ± 13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242–128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤ 60 ml/min/1.73 m² (log Rank 12.423, p = 0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p = 0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models.ConclusionsGFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.     

Acute kidney injury after allogeneic hematopoietic stem cell transplantation – Predictors and survival impact: A single center retrospective study

Introduction and objectivesAcute kidney injury (AKI) is a frequent complication of hematopoietic stem cell transplantation (HSCT) and appears to be linked to increased morbidity and mortality. The aim of this study was to evaluate the incidence, etiology, predictors and survival impact of early AKI in the post-allogeneic HSCT setting.Patients and methodsWe performed a retrospective single center study that included 155 allogeneic transplant procedures from June 2017 through September 2019.ResultsAKI was observed in 50 patients (32%). In multivariate analysis, age (OR 31.55, 95% CI [3.42; 290.80], p = 0.002), evidence of disease at the time of transplant (OR 2.54, 95% CI [1.12; 5.75], p = 0.025), cytomegalovirus reactivation (OR 5.77, 95% CI [2.43; 13.72], p < 0.001) and hospital stay >35 days (OR 2.66, 95% CI [1.08; 6.52], p = 0.033) were independent predictors for AKI. Increasing age (HR 1.02, 95% CI [1.00; 1.04], p = 0.029), increasing length of hospital stay (HR 1.02, 95% CI [1.01; 1.03], p = 0.002), matched unrelated reduced intensity conditioning HSCT (HR 1.91, 95% CI [1.10; 3.33], p = 0.022), occurrence of grade III/IV acute graft-versus-host disease (HR 2.41, 95% CI [1.15; 5.03], p = 0.019) and need for mechanical ventilation (HR 3.49, 95% CI [1.54; 7.92], p = 0.003) predicted an inferior survival in multivariate analysis. Early AKI from any etiology was not related to worse survival.ConclusionPatients submitted to HSCT are at an increased risk for AKI, which etiology is often multifactorial. Due to AKI incidence, specialized nephrologist consultation as part of the multidisciplinary team might be of benefit.     

Acute kidney injury in hospitalized patients with COVID-19: A Portuguese cohort

IntroductionThe incidence of acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients ranges from 0.5% to 35% and has been associated with worse prognosis. The purpose of this study was to evaluate the incidence, severity, duration, risk factors and prognosis of AKI in hospitalized patients with COVID-19.MethodsWe conducted a retrospective single-center analysis of 192 hospitalized COVID-19 patients from March to May of 2020. AKI was diagnosed using the Kidney Disease Improving Global Outcome (KDIGO) classification based on serum creatinine (SCr) criteria. Persistent and transient AKI were defined according to the Acute Disease Quality Initiative (ADQI) workgroup definitions.ResultsIn this cohort of COVID-19 patients, 55.2% developed AKI (n = 106). The majority of AKI patients had persistent AKI (n = 64, 60.4%). Overall, in-hospital mortality was 18.2% (n = 35) and was higher in AKI patients (28.3% vs. 5.9%, p < 0.001, unadjusted OR 6.03 (2.22–16.37), p < 0.001). In this multivariate analysis, older age (adjusted OR 1.07 (95% CI 1.02–1.11), p = 0.004), lower Hb level (adjusted OR 0.78 (95% CI 0.60–0.98), p = 0.035), duration of AKI (adjusted OR 7.34 for persistent AKI (95% CI 2.37–22.72), p = 0.001) and severity of AKI (adjusted OR 2.65 per increase in KDIGO stage (95% CI 1.32–5.33), p = 0.006) were independent predictors of mortality.ConclusionAKI was frequent in hospitalized patients with COVID-19. Persistent AKI and higher severity of AKI were independent predictors of in-hospital mortality.     

Prediction of cardiovascular events in pre-dialysis chronic kidney disease patients with normal SPECT myocardial perfusion imaging

PurposePatients with normal stress myocardial perfusion imaging (MPI) results generally have an excellent prognosis with <1% cardiovascular events/year. Chronic kidney disease (CKD) is an established risk factor for cardiovascular events. However, the estimated glomerular filtration rate (eGFR) varies considerably among patients with CKD. We evaluated the prognostic value of eGFR for patients with CKD who did not undergo hemodialysis and had no evidence of coronary artery disease (CAD).Methods and subjectsPatients with CKD (n = 108; 58 males; mean age: 74 years) with no CAD [no previous CAD and normal stress MPI results; summed stress score (SSS) <4] and with no history of hemodialysis were followed-up (mean duration: 24 months). CKD was defined by eGFR of <60 ml/min/1.73 m² and/or persistent proteinuria. Cardiovascular events included cardiac death, non-fatal myocardial infarction, and unstable angina.ResultsCardiovascular events were observed in 8 patients with CKD (7%). The following were determined as significant predictors of these events: age (hazard ratio = 1.14; p = 0.019), hemoglobin levels (hazard ratio = 0.69; p = 0.021), eGFR (hazard ratio = 0.94; p = 0.008), SSS (hazard ratio = 2.31; p = 0.012), and summed difference score (hazard ratio = 2.33; p = 0.014).ConclusionsPatients with CKD and with no previous CAD and normal stress MPI results (SSS < 4) may not exhibit an excellent cardiovascular prognosis. Further, a lower eGFR and stress MPI results may be the predictors of cardiovascular events. Thus, patients with a lower eGFR and/or normal stress MPI results (SSS < 4) may require continuous follow-up.     

An association of metabolic syndrome and chronic kidney disease from a 10-year prospective cohort study

ObjectiveAlthough metabolic abnormalities have been considered important risk factors of chronic kidney disease (CKD), the impact of metabolic syndrome (MS) and insulin resistance on renal function deterioration is poorly understood. We investigated the association between MS and incident CKD/rapid decline of estimated glomerular filtration rate (eGFR) in a 10-year population-based longitudinal study.Material and MethodsAmong 10,030 subjects, 6065 without history of CKD or cardiovascular disease at baseline were analyzed using data generated from the Ansan–Ansung cohort of the Korean Genome Epidemiology Study. Participants were categorized into two groups based on the presence of MS at baseline. Incident CKD was defined as eGFR < 60 ml/min per 1.73 m², and rapid decline of eGFR was defined as > 3 ml/min per 1.73 m²/yr over 10 years.ResultsDuring the 10-year follow-up period, CKD developed in 893 subjects (14.7%). Compared to subjects without MS, the odds ratio (OR; 95% confidence interval, CI) of incident CKD in those with MS was 1.38 (1.16–1.64) after controlling for confounding factors. The risk of rapid decline of eGFR was also higher in subjects with MS than those without MS (OR: 1.20, 95% CI: 1.04–1.39). In addition, we found that higher levels of homeostatic model assessment of insulin resistance (HOMA-IR) were associated with incident CKD and rapid decline of eGFR independently of traditional CKD risk factors (OR: 1.24, 95% CI: 1.04–1.47).ConclusionBoth MS and insulin resistance were independent risk factors of incident CKD and rapid decline of eGFR in healthy Korean population.     

Novel predictive biomarkers for acute injury superimposed on chronic kidney disease

Introduction and objectivesChronic kidney disease (CKD) is a risk factor for the development of acute kidney injury (AKI). Recent studies have revealed numerous biomarkers eligible for AKI prediction. However, the expression and performance of AKI biomarkers in acute injury superimposed on preexisting CKD (AonC) remain elusive. The aim of this study was to evaluate whether biomarkers which robustly expressed in acute kidney injury could predict acute injury based on CKD.Materials and methodsMice were classified into cohorts: AKI, CKD, AonC and sham. The AonC model mice were subjected to renal bilateral ischemia/reperfusion (I/R) injury fourteen days after intraperitoneally administrated with 20 mg/kg aristolochic acid. Severity of acute ischemic injury was stratified by clamping the dissected bilateral renal arteries with non-traumatic microvascular clips for 20 or 35 min. The AKI mice were induced with renal bilateral I/R injury and CKD mice were crafted with 20 mg/kg aristolochic acid administrated intraperitoneally. Histology, genetic and protein expression of biomarkers were measured in three cohorts.ResultsWe found that serum creatinine dramatically increased in severe (sAonC) but not in moderate (mAonC) injury mice. Upregulation of Kidney injury molecule-1 (KIM-1) mRNA, tissue inhibitor of metalloproteinase-2 (TIMP-2), Syndecan-1 (SDC-1) mRNA and insulin-like growth factor binding protein-7 (IGFBP7) protein indicated the onset of mAonC. An increase in neutrophil gelatinase-associated lipocalin (NGAL), rhomboid-like protein 2 (RHBDL2), Syndecan-1 (SDC-1) mRNA and protein, and a decrease in IGFBP7 protein were associated with sAonC.ConclusionsOur study revealed the variational expression of AKI biomarkers in AonC kidneys, and uncovered IGFBP7 protein can be used as a sensitive biomarker to predict and differentiate AonC severity. The performance of RHBDL2 and SDC-1 in predicting severe AonC was promising, providing new biomarkers for predicting AonC.     

The economic burden of progressive chronic kidney disease among patients with type 2 diabetes

AimsTo estimate the rate of progression of chronic kidney disease (CKD) among patients with type 2 diabetes (T2D) and calculate medical costs associated with progression.MethodsWe conducted a retrospective cohort study of 25,576 members at Kaiser Permanente who had T2D and at least one serum creatinine measurement in 2005. Using estimated glomerular filtration rate (eGFR), we assigned patients to baseline stages of kidney function (stage 0–2, > 60 ml/min/1.73 m², n = 21,008; stage 3, 30–59, n = 3,885; stage 4, 15–29, n = 683). We examined all subsequent eGFRs through 2010 to assess progression of kidney disease. Medical costs at baseline and incremental costs during follow-up were assessed.ResultsMean age of patients was 60.6 years, 51% were men, and mean diabetes duration was 5.3 years. At baseline, 17.9% of patients with T2D also had stage 3 or 4 CKD. Incremental adjusted costs that occurred over follow-up (from baseline) was on average $4569, $12,617, and $33,162 per patient per year higher among patients who progressed from baseline stage 0–2, stage 3, and stage 4 CKD, respectively, compared to those who did not progress. Across all stages of CKD, those who progressed to a higher stage of CKD from baseline had follow-up costs that ranged from 2 to 4 times higher than those who did not progress.ConclusionsProgression of CKD in T2D drives substantial medical care costs. Interventions designed to minimize decline in progressive kidney function, particularly among patients with stage 3 or 4 CKD, may reduce the economic burden of CKD in T2D.     

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass

Background and objectives

Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass.

Influence of mild pulmonary congestion on diaphragmatic mobility and activities of daily living in chronic kidney disease: An experimental and clinical study

BackgroundPulmonary congestion is a strong predictor of mortality and cardiovascular events in chronic kidney disease (CKD); however, the effects of the mild form on functionality have not yet been investigated. The objective of this study was to assess the influence of mild pulmonary congestion on diaphragmatic mobility (DM) and activities of daily living (ADL) in hemodialysis (HD) subjects, as well as compare ADL behavior on dialysis and non-dialysis days. In parallel, experimentally induce CKD in mice and analyze the resulting pulmonary and functional repercussions.MethodsThirty subjects in HD underwent thoracic and abdominal ultrasonography, anthropometric assessment, lung and kidney function, respiratory muscle strength assessment and symptoms analysis. To measure ADL a triaxial accelerometer was used over seven consecutive days. Twenty male mice were randomized in Control and CKD group. Thoracic ultrasonography, TNF-α analysis in kidney and lung tissue, exploratory behavior and functionality assessments were performed.ResultsMild pulmonary congestion caused a 26.1% decline in DM (R² = .261; P = .004) and 20% reduction in walking time (R² = .200; P = .01), indicating decreases of 2.23 mm and 1.54 min, respectively, for every unit increase in lung comet-tails. Regarding ADL, subjects exhibited statistically significant differences for standing (P = .002), walking (P = .034) and active time (P = .002), and number of steps taken (P = .01) on days with and without HD. In the experimental model, CKD resulted in increased levels of TNF-α on kidneys (P = .037) and lungs (P = .02), attenuation of exploratory behavior (P = .01) and significant decrease in traveled distance (P = .034). Thoracic ultrasonography of CKD mice showed presence of B-lines.ConclusionThe mild pulmonary congestion reduced DM and walking time in subjects undergoing HD. Individuals were less active on dialysis days. Furthermore, the experimental model implies that the presence of pulmonary congestion and inflammation may play a decisive role in the low physical and exploratory performance of CKD mice.     

Progresión de la enfermedad renal crónica en pacientes con hipertensión resistente sometidos a 2 estrategias terapéuticas: intensificación con diuréticos de asa vs. antagonistas de la aldosterona

IntroductionActualy, there are few data about glomerular filtration rate (eGFR) drop in patients with resistant hypertension and how diferent therapies can modify chronic kidney disease progression (CKD).ObjectiveTo evaluate CKD progression in patients with resistant hypertension undergoing 2 diferent therapies: treatment with spironolactone or furosemide.MethodsWe included 30 patients (21 M, 9 W) with a mean age of 66.3 ± 9.1 years, eGFR 55.8 ± 16.5 ml/min/1.73 m², SBP 162.8 ± 8.2 and DBP 90.2 ± 6.2 mmHg: 15 patients received spironolactone and 15 furosemide and we followed up them a median of 32 months (28-41).ResultsThe mean annual eGFR decrease was -2.8 ± 5.4 ml/min/1.73 m². In spironolactone group was –2.1 ± 4.8 ml/min/1.73 m² and in furosemide group was -3.2 ± 5.6 ml/min/1.73 m², P<0.01. In patients received spironolactone, SBP decreased 23 ± 9 mmHg and in furosemide group decreased 16 ± 3 mmHg, P<.01. DBP decreased 10 ± 8 mmHg and 6 ± 2 mmHg, respectively (P<.01). Treatment with spironolactone reduced albuminuria from a serum albumin/creatine ratio of 210 (121-385) mg/g to 65 (45-120) mg/g at the end of follow-up, P<.01. There were no significant changes in the albumin/creatinine ratio in the furosemide group. The slower drop in kidney function was associated with lower SBP (P=.04), higher GFR (P=.01), lower albuminuria (P=.01), not diabetes mellitus (P=.01) and treatment with spironolactone (P=.02). Treatment with spironolactone (OR 2.13, IC 1.89-2.29) and lower albuminuria (OR 0.98, CI 0.97-0.99) maintain their independent predictive power in a multivariate model.ConclusionTreatment with spironolactone is more effective reducing BP and albuminuria in patients with resistant hypertension compared with furosemide and it is associated with a slower progression of CKD in the long term follow up.     

Obesity,chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3

Introduction and aimsObesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression.MethodsPatients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered).Results81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1 ± 23.8 vs 84.5 ± 6.2; p = 0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4 ± 24.7 vs 106 ± 24.7; p < 0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p = 0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p = 0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96–1.06).ConclusionsCTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.     

Efficacy and safety of direct-acting antiviral agents for HCV in mild-to-moderate chronic kidney disease

Background and aimsThe advent of direct-acting antiviral agents promises to change the management of hepatitis C virus infection (HCV) in patients with chronic kidney disease (CKD), a patient group in which the treatment of hepatitis C was historically challenging. We investigated the safety and efficacy of all-oral, interferon-free direct-acting antiviral agents for the treatment of hepatitis C in a ‘real-world’ cohort of patients with CKD.MethodsWe performed an observational single-arm multi-centre study in a large (n = 198) cohort of patients with stage 1–3 CKD who underwent antiviral therapy with DAAs for the treatment of HCV. The primary end-point was sustained virologic response (serum HCV RNA <15 IU/mL, 12 weeks after treatment ended) (SVR12). We collected data on on-treatment adverse events (AEs), severe AEs, and laboratory abnormalities.ResultsThe average baseline eGFR (CKD-EPI equation) was 70.06 ± 20.1 mL/min/1.72 m²; the most common genotype was HCV 1b (n = 93, 51%). Advanced liver scarring was found in 58 (46%) patients by transient elastography. Five regimens were adopted: elbasvir/grazoprevir (n = 5), glecaprevir/pibrentasvir (n = 4), ritonavir-boosted paritaprevir/ombitasvir/dasabuvir (PrOD) regimen (n = 40), simeprevir ± daclatasvir (n = 2), and sofosbuvir-based combinations (n = 147). The SVR12 rate was 95.4% (95% CI, 93.8%; 96.8%). There were nine virological failures – eight being relapsers. Adverse events occurred in 30% (51/168) of patients, and were managed clinically without discontinuation of therapy or hospitalization. One of the most common AEs was anaemia (n = 12), which required discontinuation or dose reduction of ribavirin in some cases (n = 6); deterioration of kidney function occurred in three (1.7%).ConclusionsAll-oral, interferon-free therapy with DAAs for chronic HCV in mild-to-moderate CKD was effective and well-tolerated in a ‘real–world’ clinical setting. Studies are in progress to address whether sustained viral response translates into better survival in this population.     

Serum sclerostin in acute kidney injury patients

BackgroundMany of the mineral metabolite abnormalities encountered in chronic kidney disease (CKD) patients were found also associated with acute kidney injury (AKI). In the last decade, sclerostin was found to intimately affect bone mineral metabolism in CKD patients. Nothing is known about sclerostin in AKI.ObjectiveWe looked for serum level of sclerostin in AKI patients in comparison to normal control subjects and if there is an impact on metabolic derangement, endothelial function or clinical outcome.Cases and methodsThis is a cross sectional case control observational study of 219 AKI cases (group I) beside 219 age matched normal control subjects (group II). All cases of group I were in the intensive care because of sepsis; 86 had acute on CKD (group Ib), while 133 had de novo AKI (group Ia). All studied subjects underwent estimation of serum sclerostin, parathyroid hormone (PTH), 25 hydroxy vitamin D (25 OH vit D), fibroblast growth factor 23 (FGF23), C-reactive protein (CRP), interleukin 6 (IL6), Homeostatic Model Assessment for Insulin Resistance (Homa IR), beside the routine CBC, kidney and liver function tests, serum calcium, and phosphorus, and flow mediated vasodilation of brachial artery (FMD). Follow-up of group I cases was done till they recovered or passed away.ResultsSerum sclerostin, PTH, FGF23, phosphorus, CRP, IL6, HOMA IR, creatinine, urea, uric acid, ALT, AST and white blood cell count (WBC) were significantly higher while serum calcium, 25 OH vit D, hemoglobin, platelet count and FMD were significantly lower in group I compared to group II (P < 0.001 in all). On the other hand, there was no significant difference in serum sclerostin, PTH, FGfF23, 25 OH vit D, CRP, IL6, Homa IR and FMD between group Ia and Ib. Survivors were younger in age (median 55.5 vs. 60 years, P < 0.04), had lower AST (30.5 vs. 58 units, P < 0.001), had higher platelet count (206 vs 162 × 10⁹/L, P < 0.001), otherwise, there was no significant difference in any of the other parameters between survivors and patients that were lost. Serum sclerostin had strong correlation with FGF23 in group I (r = 0.99, P < 0.001) and group II (r = 1, P < 0.001). Homa IR had positive correlation with serum sclerostin (r = 0.148, P = 0.014) and serum FGF23 (r = 0.142, P = 0.018) in group I.ConclusionSclerostin is intimately related to FGF23. Sclerostin level increases in AKI patients. Both sclerostin and FGF23 might increase insulin resistance but have no impact on FMD. Neither sclerostin nor FGF23 interfere with AKI outcome.