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Pulmonary hypertension (PH), an acknowledged risk condition at the community level and in patients with heart or lung diseases, is now getting growing attention as a new, potentially modifiable cardiovascular (CV) risk factor also in individuals affected by kidney diseases. PH is highly prevalent in this setting, being about 3 to 6 times more frequent that in the general population and portends a risk excess for mortality, adverse CV outcomes and also worsen graft function in kidney transplant recipients. Several factors might be involved to explain PH in renal patients, including but not limited to volume overload, breath disorders, left heart dysfunction and the presence of highflow artero-venous fistulas. Targeting PH might lead to improved outcomes in renal patients but the lack of specific interventional studies and the need for more accurate evidence adopting standardized ways to assess PH leave the issue open for future research., Competing Interests: All authors declare no conflicts of interest., (© 2018 Bolignano et al. Published by IMR press. All rights reserved.)

Background and Aims: Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment., Methods: 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures., Results: Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001)., Conclusions: Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Background: Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes., Methods: The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of) patients with diabetes and CKD Stage 5., Results: A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis., Conclusions: There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Biomarkers are useful tools for diagnosis and risk assessment of acute kidney injury and acute heart failure, particularly in ICU patients. Most biomarkers are produced or cleared by the kidney, so the presence of chronic kidney disease may affect their clinical reliability, particularly if the putative diagnosis of acute kidney injury or acute heart failure is based on a single measurement/single threshold approach. Better alternatives, such as establishing different diagnostic cutoff values per different chronic kidney disease strata or evaluating the diagnostic performance of a delta value (change from baseline levels) instead of a single threshold, should be carefully considered in critically ill patients with renal impairment and other co-morbidities.

Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60 ml/min/1.73 m2 or urinary albumin:creatinine ratio (UACR) reaches ≥30 mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified as mild, moderate or severe, based on GFR and UACR values, and the latter two classifications convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 European League Against Rheumatism (EULAR)/European Renal Association–European Dialysis and Transplant Association recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk who may benefit from guidance detailed in the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN is considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression. Study design: Systematic review and meta-analysis. Population: Adults with DKD (either secondary to type 1 or 2 diabetes mellitus) Search strategy and sources: Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction. Intervention: Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination. Outcomes: Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function. Results: From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking. Limitations: Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy. Conclusions: In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression. [ABSTRACT FROM AUTHOR]

Background : Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting. Study Design : Systematic review. Population : Diabetes patients with CKD stage 3 to 5. Search Strategy and Sources : Medline, Embase and Central were searched to identify papers. Intervention : Effect of a negative energy balance on hard outcomes in diabetics with CKD. Outcomes : Death, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition. Results : We retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from −0.66 to −1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (−9.2 vs. −20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (−0.51 (−0.87 to −0.14); p = 0.007 and −0.38 (−0.72 to −0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (−0.74% (−1.29 to −0.18); p = 0.009) and body weight (−2.2 kg (−3.9 to −0.6); p = 0.008). Resistance exercise reduces trunk fat mass (−0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001−0,005). In none of the studies did the intervention cause an increase in adverse events. Limitations : All studies used a different intervention type and mixed patient groups. Conclusions : There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed. [ABSTRACT FROM AUTHOR]

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action. [ABSTRACT FROM AUTHOR]

The author reflects on the consideration of the serum creatinine as a decisive marker for diagnosis and staging of acute kidney injury (AKI). The author mentions that the possibility of diagnosing AKI using serum creatinine was only 24-72 hour after cardiopulmonary bypass. He adds that the concentrations serum creatinine are not specific for renal tubular lesions, but rather reflecting the loss of glomerular filtration function, which follows the development of AKI.

Neutrophil gelatinase-associated lipocalin (NGAL) is a small 25-kDa protein released from kidney tubular cells after harmful stimuli. It represents one of the most promising future biomarkers in the diagnostic field of acute kidney injury (AKI), as the increase in NGAL levels is a good predictor of a brief-term onset of AKI, notably anticipating the resulting increase in serum creatinine. However, recent studies also suggest a possible role for NGAL in chronic kidney disease (CKD). For this reason we evaluated serum (sNGAL) and urinary NGAL (uNGAL) in a cohort of CKD patients in order to verify the relationship with the severity of renal impairment. In CKD patients sNGAL, uNGAL and the fractional excretion of this protein were notably increased as compared to controls. Furthermore both sNGAL and uNGAL were correlated with serum creatinine and, inversely, with residual glomerular filtration rate (GFR): this last relationship was found to be even closer than that found between GFR and serum creatinine. Multivariate models validate these correlations as independent, confirming that in these patients NGAL is a better predictor of GFR than serum creatinine. The results confirm NGAL as an important biomarker in clinical nephrology, extending to CKD the pathophysiological role of this protein in tubular adaptations to renal damage. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]