Long-term cardio-vascular risk assessment in chronic kidney disease and kidney transplanted patients following SARS-COV-2 disease: protocol for multi-center observational match controlled trial.

BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced a pandemic since March 2020 by affecting more than 243 million people with more than 5 million deaths globally. SARS-CoV-2 infection is produced by binding to angiotensin-converting enzyme, which among other sites is highly expressed in the endothelial cells of the blood vessels, pericytes and the heart, as well as in renal podocytes and proximal tubular epithelial cells. SARS-CoV-2 and cardiovascular disease (CVD) are interconnected by risk factors association with an increased incidence of the disease and by determining de novo cardiac complications. At the same time, COVID-19 disease can lead to acute kidney injury directly, or due to sepsis, multi-organ failure and shock. Therefore, the pre-existence of both CVD and chronic kidney disease (CKD) is linked with a higher risk of severe disease and worse prognosis. METHODS: The main aim of this study is to assess the CV risk in a CKD (stage 3 to 5), dialysis and kidney transplanted population, following SARS-CoV-2 infection, with focus on the endothelial dysfunction as compared to a control group of matched patients. By using clinical evaluation, flow-mediated dilatation, carotid-femoral pulse wave velocity, intima-media thickness, echocardiographic parameters, lung ultrasound, bioimpedance spectroscopy and a series of novel biomarkers, the investigators will determine the long-term impact of this disease on CV and renal outcomes. DISCUSSION: This study will address the challenges and implications in long-term CV sequeale of COVID-19 and focus on a better understanding of the underlying mechanisms and possible therapeutic options. TRIAL REGISTRATION: Patient enrolment in the trial started in January 2021 and is expected to finish at the end of 2022. The study can be found on ClinicalTrials.gov database with NCT05125913 identifier. Registered on 18 November 2021 - Retrospectively registered.

An analysis of the impact of fluid overload and fluid depletion for all-cause and cardiovascular mortality.

BACKGROUND: Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. METHODS: In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre-post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. RESULTS: According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between -1.1 and 1.1 L, fluid depletion with an AFO below -1.1 L, moderate FO with an AFO compartment >1.1 but <2.5 L and severe FO with the AFO compartment >2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22-1.93], HR 2.04 (95% CI 1.59-2.60) and HR 1.88 (95% CI 1.07-3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57-0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11-1.75); severe FO: HR 2.29 (95% CI 2.01-3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05-1.70); severe FO: HR 2.34 (95% CI 1.67-3.28)] as compared with normohydrated patients. Using pre-post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO <-1.1 L pre- and post-dialysis; Group 2, AFO between -1.1 and 1.1 L pre-dialysis and <-1.1 L post-dialysis (the reference group); Group 3, AFO between -1.1 and 1.1 L pre- and post-dialysis; Group 4, AFO >1.1 L pre-dialysis and <-1.1 L post-dialysis; Group 5, AFO >1.1 L pre-dialysis and between -1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29-5.84)]. CONCLUSION: We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

Use of Lung Ultrasound for the Assessment of Volume Status in CKD.

Adequate assessment of fluid status is an imperative objective in the management of all types of patients in cardiology, intensive care, and especially nephrology. Fluid overload is one of the most common modifiable risk factors directly associated with hypertension, heart failure, left ventricular hypertrophy, and eventually, higher morbidity and mortality risk in these categories of patients. Different methods are commonly used to determine fluid status (eg, clinical assessment, natriuretic peptide concentrations, echocardiography, inferior vena cava measurements, or bioimpedance analysis). In recent years, lung ultrasonography (LUS), through the assessment of extravascular lung water, has received growing attention in clinical research. This article summarizes available studies that compare LUS with other methods for fluid status assessment in patients with kidney diseases. At the same time, it also presents the association of LUS with different outcomes (physical functioning, mortality, and cardiovascular events) in the same population. It appears that this simple bedside noninvasive technique has significant clinical potential in nephrology.

Primary Prevention of Stroke in Chronic Kidney Disease Patients: A Scientific Update.

BACKGROUND: Although chronic kidney disease (CKD) is an independent risk factor for stroke, official recommendations for the primary prevention of stroke in CKD are generally lacking. SUMMARY: We searched PubMed and ISI Web of Science for randomised controlled trials, observational studies, reviews, meta-analyses and guidelines referring to measures of stroke prevention or to the treatment of stroke-associated risk factors (cardiovascular disease in general and atrial fibrillation (AF), arterial hypertension or carotid artery disease in particular) among the CKD population. The use of oral anticoagulation in AF appears safe in non-end stage CKD, but it should be individualized and preferably based on thromboembolic and bleeding stratification algorithms. Non-vitamin K antagonist oral anticoagulants with definite dose adjustment are generally preferred over vitamin K antagonists in mild and moderate CKD and their indications have started being extended to severe CKD and dialysis also. Aspirin, but not clopidogrel, has limited indications for reducing the risk for atherothrombotic events in CKD due to its increased bleeding risk. Carotid endarterectomy has shown promising results for stroke risk reduction in CKD patients with high-grade symptomatic carotid stenosis. The medical treatment of arterial hypertension in CKD often fails to efficiently lower blood pressure values, but recent data regarding the use of interventional procedures such as renal denervation, baroreflex activation therapy or renal artery stenting are encouraging. Key Messages: In the absence of clear guidelines and protocols, primary prevention of stroke in CKD patients remains a subtle art in the hands of the clinicians. Nevertheless, refraining CKD patients from standard therapies often worsens their prognosis.

Overhydration, underhydration, and total body sodium: A tricky "ménage a trois" in dialysis patients.

Overhydration is a frequent complication in dialysis patients. It has been linked with hypertension, left ventricular hypertrophy, arterial stiffness, atherosclerosis uremic cardiomyopathy, and all-cause mortality or cardiovascular morbidity. In addition, predialysis underhydration is also associated with increased risk of death in ESRD patients. In this context, the optimal evaluation of hydration status is a must. However, this mission is not easy or accurate. In the last 10 years, several new methods have been tested in dialysis patients, particularly bioimpedance and lung ultrasonography. The precise clinical value of these techniques in the daily care of hemodialysis patients is not obvious yet. Sodium is also an important piece of this puzzle. Salt intake and/or removal of sodium during dialysis are essential determinants of optimal hydration status. Recent studies have revealed that salt and water homeostasis is also dependent of tissue sodium storage-increased in hemodialysis patients. However, the significance of increased sodium tissue storage as a cardiovascular risk factor and the relationship between tissue sodium content and hard CV endpoint have not yet been elucidated yet.

Lipids, blood pressure and kidney update 2014.

This paper is an effort to review all the most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2014. Irrespective of advances, the options for improving simultaneous hypercholesterolemia and hypertension management (as well as its complication - chronic kidney disease) remain a problem. Recommending hypolidemic, hypotensive and kidney disease drugs to obtain therapy targets in cardiovascular, diabetic, elderly and kidney disease (=high risk) patients might strengthen risk factor control, improve compliance and the therapy efficacy, and in the consequence reduce the risk of cardiovascular events and mortality rate. That is why the authors have decided to summary and discuss the recent scientific achievements in the field of lipid, blood pressure and kidney.

Lipids, blood pressure and kidney update 2015.

The most important studies and guidelines in the topics of lipid, blood pressure and kidney published in 2015 were reviewed. In lipid research, the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial revalidated the concept "lower is better" for low density lipoprotein (LDL)-cholesterol as a target for therapy, increasing the necessity of treatment the high-risk patients to achieve LDL-C goals. After these results, ezetimibe might become the preferred additional drug in the combination therapy of lipid disorders because of oral dosage form and lower acquisition cost. However, for the statin-intolerant patients and those patients requiring essential reductions in LDL-C to achieve their goals, new therapies, including PCSK9 inhibitors remain promising drugs. In blood pressure research, American Heart Association (AHA)/American College of Cardiology (ACC) 2015 guidelines recommended a target for blood pressure below 140/90 mmHg in stable or unstable coronary artery disease patients and below 150/90 mmHg in patients older than 80 years of age, however the recent results of the Systolic Blood Pressure Intervention Trial (SPRINT) trial have suggested that there might be significant benefits, taking into account cardiovascular risk, for hypertensive patients over 50 without diabetes and blood pressure levels <120/80. In kidney research, reducing the progression of chronic kidney disease and related complications such as anemia, metabolic acidosis, bone and mineral diseases, acute kidney injury and cardiovascular disease is still a goal for clinicians.

Bioimpedance-guided fluid management in maintenance hemodialysis: a pilot randomized controlled trial.

BACKGROUND: Chronic subclinical volume overload happens very frequently in hemodialysis patients and is associated directly with hypertension, increased arterial stiffness, left ventricular hypertrophy, and ultimately higher mortality. STUDY DESIGN: Randomized controlled parallel-group trial. SETTING & PARTICIPANTS: 131 patients from one hemodialysis center, randomly assigned into 2 groups. INTERVENTION: Dry weight prescription using results derived from repeated 3-month bioimpedance measurements to guide ultrafiltration for strict volume control (bioimpedance group; n=62) compared with clinical judgment without bioimpedance measures (clinical-methods group; n=69) for 2.5 years. OUTCOMES: The primary outcome was all-cause mortality over 2.5 years (the duration of the intervention). Secondary outcomes were change in relative arterial stiffness, fluid overload, and blood pressure (BP) over 2.5 years. MEASUREMENTS: Bioimpedance measurements were performed using a Body Composition Monitor device. Pulse wave velocity analysis was performed at baseline, 2.5 years (end of intervention), and 3.5 years (end of study). Relative fluid overload and BP were assessed at 3-month intervals. RESULTS: The unadjusted HR for all-cause death in the bioimpedance group (vs the clinical-methods group) was 0.100 (95% CI, 0.013-0.805; P=0.03). After 2.5 years, we found a greater decline in arterial stiffness, relative fluid overload, and systolic BP in the bioimpedance group than the clinical-methods group. Between-group differences in change from baseline to the end of intervention were -2.78 (95% CI, -3.75 to 1.80)m/s for pulse wave velocity (P<0.001), -2.99% (95% CI, -5.00% to -0.89%) for relative fluid overload (P=0.05), and -2.43 (95% CI, -7.70 to 2.84)mmHg for systolic BP (P=0.4). LIMITATIONS: Echocardiography was not performed as cardiovascular assessment and the caregivers were not masked to the intervention. CONCLUSIONS: Our study showed improvement in both surrogate and hard end points after strict volume control using bioimpedance to guide dry weight adjustment. These findings need to be confirmed in a larger trial.

Routine bioimpedance-derived volume assessment for all hypertensives: a new paradigm.

Hypertension is one of the most common worldwide diseases. Is linked with increased morbidity and mortality and amplified costs to society; in this context, preventing and treating hypertension is an imperative public health challenge. Unidentified, clinically unapparent volume expansion is an important cause for hypertension. Optimization of fluid status was associated with an improvement in BP control, a substantial regression of the left ventricular mass index, arterial stiffness and better survival rate in several cohorts. Clinical assessment of hydration status is an inaccurate clinical science. Bioimpedance provides a noninvasive and reliable, simple, reproducible technology for diagnosing subclinical fluid accumulation. Several small studies and a recent meta-analysis performed in patients with resistant hypertension reported an improved BP control in the impedance treated group compared with the group of patients treated as per clinical judgment alone. A combined approach (using both sphygmomanometers and bioimpedance) and individualized antihypertensive treatment in hypertensive's patients it seems probable to improve BP control and possibly end organ damage.

Superior predictive value for NTproBNP compared with high sensitivity cTnT in dialysis patients: a pilot prospective observational study.

BACKGROUND/AIMS: The clinical utility of the new biomarker, high sensitivity cardiac T troponin (hs-cTnT) is still unclear in dialysis patients. Furthermore, the prognostic value of combining N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and hs-cTnT has not been explored so far. The objective of this pilot study was to determine the utility of hs-cTnT alone versus hs-cTnT in combination with NT-proBNP for predicting death in a stable hemodialysis cohort. METHODS: A prospective observational pilot study including 98 chronic asymptomatic hemodialysis patients with a follow up period of 24 months was designed. The cut-off values for NT-proBNP and hs-cTnT were calculated using receiver operating characteristic (ROC) analysis, using mortality as an end-point. Based on the cut-off values, the cohort was divided into four groups. Group 1--NT-proBNP < 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 2--NT-proBNP < 14275 pg/ml and hs-cTnT > 69.48 ng/l; group 3--NT-proBNP > 14275 pg/ml and hs-cTnT < 69.48 ng/l; group 4--NT-proBNP > 14275 pg/ml and hs-cTnT > 69.48 ng/l. Survival for each group was determined using the Kaplan-Meier method and Cox regression analysis. RESULTS: During the follow-up period 16 patients died. According to the ROC curves analysis, the cut-off point for hs-cTnT and for NT-proBNP were 69.43 ng/l (AUC = 0.618; p = 0.04) and 14275 pg/ml (AUC = 0.722; p = 0.003), respectively. In univariate Cox analysis, both hs-cTnT (HR = 3.34; p = 0.016) and NT-proBNP (HR = 5.94; p = 0.01) were predictors of death. In the multivariable Cox proportional hazards model, only NT-pro-BNP levels above the cut-off value remained an independent predictor of all-cause mortality. The combined elevation of both biomarkers did not improve significantly the prognostic value compared with NT-proBNP alone (HR = 6.15 versus HR =4 .78; p = 0.338). CONCLUSION: NT-pro-BNP is a strong predictor of overall mortality in asymptomatic hemodialysis patients. The addition of hs-cTnT did not improve the prognostic accuracy compared with NT proBNP alone.

Tricuspid Regurgitation Associated with Implantable Cardiac Devices: A Double-Edged Sword.

The use of cardiac implantable electronic devices (CIEDs) has increased considerably, becoming a cornerstone of management for patients with brady- or tachyarrhythmia or for the prevention of sudden cardiac death. On the other hand, tricuspid regurgitation (TR) associated with CIEDs is progressively accepted as a serious clinical issue; the prognostic impact of TR is profound, as it is independently associated with increased mortality and a higher risk of heart failure hospitalization. Additionally, the management of established CIED-related TR continues to be challenging, with limited options for intervention once significant TR has developed. The balance between the lifesaving benefits of CIEDs and the risk of TR underlines the necessity for cautious patient selection and innovative approaches to device implantation and management. This review highlights the clinical importance, underlying mechanisms and challenges associated with lead-related tricuspid regurgitation in patients with CIEDs.

The Impact of Frailty and Severe Cognitive Impairment on Survival Time and Time to Initiate Dialysis in Older Adults With Advanced Chronic Kidney Disease: A Prospective Observational Cohort Study.

Background and objectives Frailty and cognitive impairment significantly impact survival time and time to initiate dialysis in older adults with advanced chronic kidney disease (CKD). This study aims to evaluate the effects of frailty and cognitive impairment on these outcomes and determine the most effective assessment tool for predicting early dialysis initiation and short survival time. Materials and methods This prospective observational cohort study involved 240 patients aged ≥65 years with stage 4 or 5 CKD, recruited from a nephrology outpatient department (ambulatory care) between March 2020 and March 2021. Frailty was assessed using the Physical Frailty Phenotype (PFP), PRISMA-7, Clinical Frailty Scale (CFS), and FRAIL scale. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). The primary outcomes were time to initiate dialysis and survival time, with secondary outcomes including hospitalization rates, length of stay, and mortality after dialysis initiation. Results Frail patients only showed significantly shorter time to dialysis initiation when identified by the PFP and FRAIL scale (28.3 months for frail vs. 31.2 months for non-frail, p = 0.028; 26.9 months for frail vs. 30.9 months for non-frail, p = 0.038). The PFP, FRAIL, and CFS tools indicated significantly shorter survival times for frail patients compared to non-frail patients (26.8 months for frail vs. 30.6 months for non-frail, p = 0.003). Frailty is strongly correlated with severe cognitive impairment, as 45.5% of frail patients (according to the FRAIL scale) have dementia compared to 15.1% of non-frail patients (p<0.001). However, cognitive impairment did not significantly affect the time to dialysis initiation or survival time. Hospitalization rates and length of stay in the hospital were significantly higher only for frail patients identified by PRISMA-7, with a median hospital length of stay of 9.15 days for frail patients vs 6.37 days for non-frail patients (p = 0.044). Overall, 37.5% of the patients did not survive during the study follow-up, with frail patients having a higher mortality rate. Conclusion Frailty, mainly when assessed by PFP and FRAIL, is a significant predictor of early dialysis initiation and reduced survival time in older adults with advanced CKD. Cognitive impairment, while prevalent, did not independently predict these outcomes. Regular frailty screening should be incorporated into CKD management to tailor interventions and improve patient outcomes.

Predicting mortality in haemodialysis patients: a comparison between lung ultrasonography, bioimpedance data and echocardiography parameters.

BACKGROUND: The use of lung ultrasonography to evaluate extravascular lung water and its consequences has received growing attention in different clinical areas, including, in recent years, end-stage renal disease patients treated by haemodialysis (HD). Lung congestion is a direct consequence of either overall overhydration and/or cardiac dysfunction, but the exact contribution of each of these tests to mortality is unknown. METHODS: In this prospective observational study, we enrolled 96 patients from a single HD unit undergoing thrice weekly HD. We used three different methods of evaluation: lung ultrasonography (pre- and post-dialysis), bioimpedance spectroscopy (pre- and post-dialysis) and echocardiography (pre-dialysis). The objective of the study was to test for the first time the prognostic value of ultrasound lung comets (ULC) combined with bioimpedance-derived data [total body water (TBW), extravascular water, hydration status-ΔHS] and several echocardiographic parameters. Mortality was analysed after a median of 405.5-day follow-up. RESULTS: Pre-dialysis lung congestion was classified as moderate (ULC = 16-30) in 19.8% of the patients and severe in 12.5% of patients (ULC > 30), while only 19.8% appear to be hyperhydrated (ΔHS > 15%). The pre-dialysis ultrasound lung congestion score correlated significantly with all of the bioimpedance-derived parameters. In a multivariate Cox model that included ULC score, demographic, ecocardiographic and bioimpedance parameters, the factors that remained significantly associated with survival time were the pre-dialysis ULC score and left ventricular mass index. The pre-HD ULC score has a significant discriminating power for survival, while the bioimpedance-derived hydration status has no discriminatory abilities in terms of survival. CONCLUSIONS: To our knowledge, this study is the first one that compares three different strategies to predict mortality in haemodialysed patients. The lung comet score emerged as the best predictor for the relationship hydration status-mortality, independently of bioimpedance-derived parameters in this population.

Changes in the histological spectrum of glomerular diseases in the past 16 years in the North-Eastern region of Romania.

BACKGROUND: The aim of this study was to describe the findings of renal biopsies from a large nephrology center in Iasi, Romania, performed between 2005 and 2010. We compared these findings with our previous ones, from 1995 to 2004, as well as with similar reports. METHODS: We studied retrospectively 239 renal biopsies. The indications for renal biopsy were categorized into: nephrotic syndrome, acute nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. RESULTS: During the past 16 years, a gradual increase in the annual number of renal biopsies/per million population (p.m.p.)/year was observed, although this incidence remained lower than in other European countries. Nephrotic syndrome was the indication for renal biopsy in over 50% of cases. Glomerulonephritis (GN) was the main histological diagnosis in 91% of cases, of which 56% were primary GN and 35% were secondary GN. The frequency of various types of primary GN was: membranoproliferative GN (MPGN) - 29.3%, membranous nephropathy (MN) -27.5%, focal segmental glomerulosclerosis (FSGS) - 17.2%, mesangial GN (including IgAN) -13.7%, crescentic GN - 9.4%, and minimal change disease (MCD) - 2.5%. Compared to the previously reported period (1994-2004), we observed a significant decrease in the frequency of MPGN and significant increases in the frequency of FSGS and, particularly MN - which more than doubled. CONCLUSION: We report significant changes in the histological spectrum of GN in North-Eastern Romania in 2005-2010, compared to the previously reported 10-yrs. These changes seem to be following a trend that has also been observed in Western countries a few decades ago, and which may have a socioeconomic explanation.

Cisplatin and AKI: an ongoing battle with new perspectives-a narrative review.

Acute kidney injury (AKI) is a growing global health problem with increased mortality and morbidity. Cisplatin is achemotherapy drug first introduced in 1978, and since then, it became one of the most widely used and successful anti-cancer medication. However, there are risks associated with cisplatin administration, such as nephrotoxicity. Mechanisms of nephrotoxicity include proximal tubular injury, DNA damage, apoptosis, inflammation, oxidative stress, and vascular injury. Although various protocols are being used in clinical practice in nephrotoxicity prevention due to cisplatin, there are no clear guidelines regarding this approach. Most recommendations include hydration and avoiding additional nephrotoxic drugs. To prevent nephrotoxicity, future perspectives could rely on natural products, such as flavonoids or saponins or pharmacological products, such as aprepitant, but data are scarce in this direction. Repetitive administration of cisplatin could cause subclinical kidney injury, which over time, leads to chronic kidney disease (CKD). Therefore, more studies are needed to determine possible ways to prevent nephrotoxicity and avoid the burden of CKD worldwide.

Gut Microbiota in Chronic Kidney Disease: From Composition to Modulation towards Better Outcomes-A Systematic Review.

BACKGROUND: A bidirectional kidney-gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. MATERIALS AND METHODS: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. RESULTS: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. CONCLUSIONS: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Revisiting risk prediction tools for death and end-stage renal disease in older patients with advanced chronic kidney disease: a prospective study.

BACKGROUND: Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking. METHODS: In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management. RESULTS: Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score < 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P < 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P < 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE. CONCLUSIONS: Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

Epidemiology of biopsy-proven glomerulonephritis in the past 25 years in the North-Eastern area of Romania.

PURPOSE: The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. METHODS: We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. RESULTS: During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994-2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. CONCLUSION: The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.