Chronic Kidney Disease Impairment Research Articles

Does Chronic Kidney Disease-Induced Cognitive Impairment Affect Driving Safety?

Purpose of Review:One of the principal mechanisms by which illness can affect driving safety is by impairing cognition. Nevertheless, despite the substantial evidence demonstrating cognitive impairment in chronic kidney disease (CKD), little is known about the effects of CKD on driving safety.Objective:Investigate the current national medical guidelines and research literature with respect to CKD and driving safety.Sources of Information:Medline, CINAHL, PEDro, Scopus as of August 2017. The most up to date national driving guidelines and available information provided by the provincial and territorial ministries of transportation across CanadaFindings:Fives studies of driving fitness in patients with CKD have been published with minimal data available for patients at early stages of the disease. Amongst these studies, only two come from an era when modern end stage renal disease therapies were routinely provided. The first study demonstrated that 40% of 186 surveyed patients on hemodialysis felt uncomfortable driving and that 1/3 of patients were involved in motor vehicle collisions (MVC) since starting dialysis. Of the patients who felt comfortable driving, more than 75% were found to be at increased driving risk. The second study reported that 15% of patients on hemodialysis were involved in MVCs over a three year span and that the “Am I A Safe Driver” assessment tool by the American Medical Association may not capture all patients at high driving risk. Despite these alarming numbers, national guidelines place few driving restrictions on this patient population and only 3 of 11 available provincial or territorial driving forms include kidney disease as a category that physicians should consider when assessing medical fitness to drive.Limitations:Our review is limited by the lack of randomized control studies evaluating the effects of CKD on driving safety.Implications:Our review demonstrates that driving safety in this patient population remains poorly understood. The limited evidence that does exist, however, suggests that these patients are at substantial risk for unsafe driving. Future research is necessary to determine the impact of CKD-associated cognitive impairment on driving risk, and to parse out the contributions of CKD and its various treatments to driving impairment.

Brain Atrophy and Cognitive Impairment in Chronic Kidney Disease.

There is an increasing prevalence of dementia associated with population aging, and anti-dementia measures have now become of increasing importance in Japan. Chronic kidney disease (CKD) is a risk factor for cognitive impairment. We previously demonstrated that hemodialysis patients have a higher prevalence of brain atrophy, even at younger age, than the general population, and also demonstrated the association between frontal lobe atrophy and frequency of rapid decline in blood pressure during the hemodialysis session. Recently, we demonstrated that decline in gray matter volume in CKD patients on peritoneal dialysis was significantly more rapid compared to non-dialysis-dependent CKD patients, and also showed a close association between gray matter atrophy and executive dysfunction in CKD patients, suggesting the importance of preventing brain atrophy for the prevention of cognitive impairment. Our recent epidemiological study demonstrated that both decreased kidney function and albuminuria were identified as independent risk factors for the development of dementia. In addition, it has been reported that possible contributing factors include anemia, oxidative stress, and the renin-angiotensin system (RAS). Previous reports have demonstrated that CKD patients with severe anemia show cognitive impairment, which was recovered by correction of anemia using erythropoiesis-stimulating agents. Then, we examined the role of oxidative stress and RAS using a mouse model of CKD-associated cognitive impairment, and demonstrated that the RAS inhibitor candesartan, as well as the antioxidant tempol, inhibited the development of cognitive impairment through inhibition of oxidative stress in the hippocampus. Key Messages: In CKD patients, progression of brain atrophy is more rapid and cognitive impairment is more common than in non-CKD subjects. Oxidative stress and RAS in the brain are associated with CKD-associated cognitive impairment.

TIME-VARYING RENAL METABOLIC FACTORS ASSOCIATED WITH COGNITIVE DECLINE IN CHRONIC KIDNEY DISEASE: THE BRINK STUDY

The BRain IN Kidney disease (BRINK) study is a longitudinal study of cognitive impairment in chronic kidney disease (CKD). We sought to identify renal- metabolic factors associated with cognitive domain- specific decline in CKD participants over up to 3 years follow-up. Participants were ≥ 45 years old with moderate/severe (non- dialysis) CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) in Minneapolis/St. Paul. Neuropsychological testing was performed using the Modified Mini-Mental State Examination (global); the Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised to measure memory domain; Color Trails 1 and 2, Symbol-Digit-Modalities Test for executive function domain, and Animal List and Controlled Oral Word Association Test for language domain. Linear mixed models for repeated measures were run to test for associations between phosphorus (high vs. normal and hemoglobin (low vs. normal) and baseline to 36-month change in cognitive function domain T scores. Time-varying phosphorus and hemoglobin and eGFR were included in the models along with age, gender, race, education, diabetes and incident stroke. Among 433 CKD participants recruited at baseline (Table 1), mean age was 70 years, mean education 14 years; 16% were non- white; mean eGFR was 34.3 mean hemoglobin 12.6 g/dL and phosphorus 3.6 mg/dL. Median follow- up time was 2.5 years. In adjusted models, time- varying high (≥ 4.5 mg/dL) vs. normal phosphorus was associated with a significantly larger decline in executive function domain T score over 3 years (-4.5; P = 0.01). Low (< 11.0 g/dL) compared to normal hemoglobin was associated with significantly lower executive function domain T score (-1.8: P <0.004), lower memory T score (-1.84; P = 0.03), and lower language T score (-1.8; p = 0.005) across time. Neither phosphorous nor hemoglobin were associated with change in language domain T score. Time varying high phosphorous was significantly associated with decline in executive function, and time-varying low hemoglobin with lower scores in all three domains over 3 years, but longer follow- up of entire cohort is needed. Phosphorus level and anemia are modifiable factors with accessible treatment options to potentially decrease cognitive decline in CKD.

Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance. In a cross-sectional study (n = 130) we investigated 70 male non-diabetic CKD patients (21 CKD stage 2-3a, 27 CKD stage 3b-4 and 22 CKD stage 5) employing specialized cardiopulmonary exercise testing to measure peak cardiac output and cardiac power output non-invasively. Data from 35 age-matched healthy male volunteers were obtained for comparison. In addition, as a positive control, data from 25 age-matched male HF patients in New York Heart Association class II and III were also obtained. The study subjects showed a graded reduction in peak cardiac power, with 6.13 ± 1.11 W in controls, 5.02 ± 0.78 W in CKD 2-3a, 4.59 ± 0.53 W in CKD 3b-4 and 4.02 ± 0.73 W in CKD 5, although not as impaired as in HF, with 2.34 ± 0.63 W (all P < 0.005 versus control). The central haemodynamic characteristics of the cardiac impairment in CKD mirrored that of HF, with reduced flow and pressure-generating capacities, reduced chronotropic reserve and impaired contractility. The study demonstrates for the first time impaired peak cardiac performance and cardiac functional reserve in asymptomatic CKD patients. The evidence of myocardial dysfunction in the absence of comorbid cardiac disease and diabetes warrants further evaluation of current pathophysiological concepts of cardiovascular disease in CKD.

Cognitive Impairment in Chronic Kidney Disease-Prevalence, Mechanisms and Consequences

In ageing populations, chronic kidney disease (CKD) gets an increasing health problem worldwide. While current therapy of CKD mostly focusses on kidney function and cardiovascular comorbidity, cognition, which crucially influences adherence to CKD therapy, is often neglected. Prevalence of cognitive impairment is high in CKD, ranging from 17% to 87%, depending on CKD severity and cognitive domain affected. In contrast to Alzheimer’s disease patients, which often show impairment in memory function, CKD patients present with a broader spectrum of cognitive deficits, namely impairment in executive function, information processing, language and visuoconstruction which is usually mild in early CKD stages but advances with CKD progression and progression of comorbidities. Mechanisms underlying cognitive impairment in CKD are discussed and conclusions are derived how cognitive impairment may be prevented in CKD and, if cognitive deficits are present, how cognitive impairment may be taken into consideration in patient management.

Cognitive Impairment in Chronic Kidney Disease: Vascular Milieu and the Potential Therapeutic Role of Exercise.

Chronic kidney disease (CKD) is considered a model of accelerated aging. More specifically, CKD leads to reduced physical functioning and increased frailty, increased vascular dysfunction, vascular calcification and arterial stiffness, high levels of systemic inflammation, and oxidative stress, as well as increased cognitive impairment. Increasing evidence suggests that the cognitive impairment associated with CKD may be related to cerebral small vessel disease and overall impairment in white matter integrity. The triad of poor physical function, vascular dysfunction, and cognitive impairment places patients living with CKD at an increased risk for loss of independence, poor health-related quality of life, morbidity, and mortality. The purpose of this review is to discuss the available evidence of cerebrovascular-renal axis and its interconnection with early and accelerated cognitive impairment in patients with CKD and the plausible role of exercise as a therapeutic modality. Understanding the cerebrovascular-renal axis pathophysiological link and its interconnection with physical function is important for clinicians in order to minimize the risk of loss of independence and improve quality of life in patients with CKD.

Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study.

Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD. To measure the association between kidney function biomarkers and brain MRI findings in CKD. In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors. We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: eGFR 45-59; 74 controls: eGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity. Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was agreater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

Prognostic significance of NGAL in early stage chronic kidney disease.

Neutrophilgelatinase-associated lipocalin (NGAL) has been proven to be a useful biomarker for early detection of acute kidney injury, but it is not known whether adding NGAL measurements to conventional risk factors will improve the risk assessment in the setting of chronic kidney disease (CKD). The aim of the present study was to examine the correlation of NGAL with early stage renal impairment in CKD and to evaluate its prognostic value in these subjects. This is a prospective observational cohort study of 54 patients with early stage (stage 1-2) CKD. Patients aged between 18 and 65 years with stable disease were enrolled in this study. Patients with a history of primary glomerulonephritis, diabetes mellitus, acute kidney injury, systemic diseases and stage 3-4-5 CKD were excluded from the study group. Estimated glomerular filtration (eGFR) rate was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. The patients were followed for two years to determine the ability of baseline NGAL for prediction of renal outcome. In our study disease progression was defined as changes in eGFR (ΔeGFR) and proteinuria (Δproteinuria). Patients divided into two groups according to NGAL cut-off value as group 1 (N.=23, NGAL ≤98.71 ng/mL) and group 2 (N.=31, NGAL >98.71 ng/mL). Out of 54 patients (mean age: 45.6±7.6 years, 64.8% female, baseline eGFR: 84.6±16.8 mL/min/1.73 m2, baseline NGAL level: 157.47±121.52 ng/mL); 18 patients were stage 1 and 36 patients were stage 2 CKD. In the ROC analysis, we found that the optimal cut-off value of NGAL for predicting stage 2 CKD was 98.71ng/mL (P=0.005) with the 72.2% sensitivity and 72.2% specificity. In correlation analysis, we evaluated significantly positive correlations between NGAL and CKD stage (r=0.389, P=0.004), baseline/last serum creatinine level (r=0.530, P<0.001 and r=0.439, P=0.003; respectively), last proteinuria level (r=0.359, P=0.043). There were significantly negative correlation between NGAL and baseline/last eGFR (r=-0.498, P<0.001 and r=-0.462, P=0.002; respectively). Compared to the group 1, we determined that group 2 patients had further deterioration in renal functions regarding ΔeGFR (-1.12±12.6 mL/min vs. -1.46±12.4 mL/min: respectively, P=0.930) and Δproteinuria (98.1±569.3 mg/day vs. 339±701.6 mg/day; respectively, P=0.305); however these differences were not statistically significant at the end of the two years follow-up period. Altough NGAL has a positive correlation with disease severity, it does not seem to be a marker of disease progression in patients with early stage CKD. But further studies stated in different patient groups may also explain the usability of NGAL in clinical practice.

Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease.

Growth delay is common in children with chronic kidney disease (CKD), often associated with poor quality of life. The role of anemia in uremic growth delay is poorly understood. Here we describe an induction of uremic growth retardation by a 0.2% adenine diet in wild-type (WT) and hepcidin gene (Hamp) knockout (KO) mice, compared with their respective littermates fed a regular diet. Experiments were started at weaning (3 wk). After 8 wk, blood was collected and mice were euthanized. Adenine-fed WT mice developed CKD (blood urea nitrogen 82.8 ± 11.6 mg/dl and creatinine 0.57 ± 0.07 mg/dl) and were 2.1 cm shorter compared with WT controls. WT adenine-fed mice were anemic and had low serum iron, elevated Hamp, and elevated IL6 and TNF-α. WT adenine-fed mice had advanced mineral bone disease (serum phosphorus 16.9 ± 3.1 mg/dl and FGF23 204.0 ± 115.0 ng/ml) with loss of cortical and trabecular bone volume seen on microcomputed tomography. Hamp disruption rescued the anemia phenotype resulting in improved growth rate in mice with CKD, thus providing direct experimental evidence of the relationship between Hamp pathway and growth impairment in CKD. Hamp disruption ameliorated CKD-induced growth hormone-insulin-like growth factor 1 axis derangements and growth plate alterations. Disruption of Hamp did not mitigate the development of uremia, inflammation, and mineral and bone disease in this model. Taken together, these results indicate that an adenine diet can be successfully used to study growth in mice with CKD. Hepcidin appears to be related to pathways of growth retardation in CKD suggesting that investigation of hepcidin-lowering therapies in juvenile CKD is warranted.

Cognitive Changes in Chronic Kidney Disease and After Transplantation.

Cognitive impairment is very common in chronic kidney disease (CKD) and is strongly associated with increased mortality. This review article will discuss the pathophysiology of cognitive impairment in CKD, as well as the effect of dialysis and transplantation on cognitive function. In CKD, uremic toxins, hyperparathyroidism and Klotho deficiency lead to chronic inflammation, endothelial dysfunction and vascular calcifications. This results in an increased burden of cerebrovascular disease in CKD patients, who consistently have more white matter hyperintensities, microbleeds, microinfarctions and cerebral atrophy on magnetic resonance imaging scans. Hemodialysis, although beneficial in terms of uremic toxin clearance, also contributes to cognitive decline by causing rapid fluid and osmotic shifts. Decreasing the dialysate temperature and increasing total dialysis time limits these shifts and helps maintain cognitive function in hemodialysis patients. For many patients, kidney transplantation is the preferred treatment modality, because it reverses the underlying mechanisms causing cognitive impairment in CKD. These positive effects have to be balanced against the possible neurotoxicity of infections and immunosuppressive medications, especially glucocorticosteroids and calcineurin inhibitors. A limited number of studies have addressed the overall effect of transplantation on cognitive function. These have mostly found an improvement after transplantation, but have a limited applicability to daily practice because they have only included relatively young patients.

The Brain in Kidney Disease (BRINK) Cohort Study: Design and Baseline Cognitive Function

The Brain in Kidney Disease (BRINK) Study aims to identify mechanisms that contribute to increased risk for cognitive impairment in patients with chronic kidney disease (CKD). We describe the rationale, design, and methods of the study and report baseline recruitment and cognitive function results. Longitudinal observational cohort study of the epidemiology of cognitive impairment in CKD. The primary aim is to characterize the association between (1) baseline and incident stroke, white matter disease, estimated glomerular filtration rate (eGFR), inflammation, microalbuminuria, and dialysis initiation and (2) cognitive decline over 3 years in a CKD cohort with a mean eGFR<45 mL/min/1.73 m(2). Community-dwelling participants 45 years or older recruited from 4 health systems into 2 groups: reduced eGFR, defined as eGFR<60 mL/min/1.73 m(2) (non-dialysis dependent), and control, defined as eGFR≥60 mL/min/1.73 m(2). eGFR group. Performance on cognitive function tests and structural brain magnetic resonance imaging. Sequential cognitive and physical function testing, serum and urine biomarker measurement, and brain magnetic resonance images over 3 years. Of 554 participants, mean age was 69.3 years; 333, 88, and 133 had eGFRs<45 (non-dialysis dependent, nontransplantation), 45 to <60, and ≥60 (controls) mL/min/1.73 m(2), respectively. Mean eGFR in reduced-eGFR participants was 34.3 mL/min/1.73 m(2). Baseline cognitive performance was significantly associated with eGFR in all domains except language. Participants with eGFRs<30 mL/min/1.73 m(2) performed significantly worse than those with eGFRs≥30 mL/min/1.73 m(2) on tests of memory, processing speed, and executive function. Participants with reduced eGFRs overall scored worst on the Immediate Brief Visual-Spatial Memory Test-Revised. Healthy cohort bias, competing risk for death versus cognitive decline. Cognitive function was significantly worse in participants with eGFRs<30 mL/min/1.73 m(2). Future BRINK analyses will measure risk factors for cognitive decline using the longitudinal data.

Is there any Gender Difference in the Association between Obesity, Chronic Kidney Disease and Anemia

Abstract Introduction. Nowadays, obesity has emerged as one of the most independent risk factors for chronic kidney disease (CKD) in both economically developed and undeveloped countries. The number of patients requiring dialysis as a consequence of obesity-related renal diseases, such as diabetes mellitus and hypertension, is increasing worldwide. Moreover, obesity has been shown to favorize the risk of cardiovascular diseases (CVD) with premature death due to CKD and/or end-stage renal disease (ESRD). The aim of the study was to investigate the association between obesity [e.g. body mass index (BMI)], kidney function [e.g. glomerular filtration rate (GFR)] and renal anemia in CKD patients. Methods. Retrospectively, data from the register of 315 pre-dialysis patients with different stages of CKD not on erythropoiesis stimulation agents (ESAs) during the period between 1 Jan 2013-30 June 2013 were used to assess the association between the degree of CKD impairment with the degree of obesity and anemia. The stage and/or progression of CKD was calculated by GFR, while the degree of obesity by the body mass index (BMI). CKD was defined as a glomerular filtration rate (GFR) &lt;60 mL/min per 1.73 m2. Data analysis was performed by means of the simple Microsoft excel program. Results. Within the study population of 315 CKD patients, 123 were males with mean age of 63.4±1.33 years and 192 females of 57.3±1.2 years. The GFR reduced with the increased BMI in both genders, and majority of patients (n=243) were in CKD stage 3, with a mean GFR of 44.5 ml/min/1.73 m2. The BMI values in female patients with first and second degree of obesity negatively correlated with GFR (r=−0.46, p&lt;0.05). Only female patients with second degree of obesity (BMI of 35-39.9 kg/m2) had a positive correlation between the decreased renal function and reduced Hb levels. Conclusions. Our study provided an unconditional evidence not only for the presence of an association between the degree of obesity (BMI) and the degree of renal function impairment (GFR), but also an association between the higher BMI and the higher degree of kidney anemia seen in women with second degree of obesity. Further larger scale trials and interventional studies are required to see the effect of body weight reduction on renal function and especially anemia.

Prognostic significance of urinary NGAL in chronic kidney disease.

BackgroundChronic kidney disease (CKD) is a worldwide public health problem. Recently urinary NGAL (uNGAL) has been proven to be a useful (potentially ideal) biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects.MethodsThis was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes) guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period.ResultsMultiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P<0.001), Ca×PO4 (β=0.60, P<0.001), hemoglobin (β=0.37, P<0.001), urine protein (β=0.34, P<0.001), serum albumin (β=0.48, P<0.001), and systolic blood pressure (β=0.76, P<0.001). Receiver operator curve for uNGAL considering the progression of CKD showed area under the curve for uNGAL was 0.878 (95% confidence interval: 0.68–0.96). Cut-off value for uNGAL was log 3.5 unit with a sensitivity of 93.08% and specificity of 71.43% for predicting the progression of CKD. Kaplan–Meier survival curve showed that patients with log uNGAL levels <3.51 unit had a survival rate of 71.4% while patients with NGAL level >3.51 unit had a renal survival rate of 14.7%.ConclusionOur study result showed that uNGAL has a positive correlation with disease severity which signifies the prognostic importance of uNGAL in CKD.

Risk factors for prevalent cognitive impairment in chronic kidney disease: The brain in kidney disease (BRINK) study

Risk factors for prevalent cognitive impairment in chronic kidney disease: The brain in kidney disease (BRINK) study

Cognitive and physical function in chronic kidney disease

Both cognitive and physical function are commonly impaired in individuals with chronic kidney disease (CKD), resulting in important impacts on their quality of life and overall health. This review summarizes the burden of cognitive and physical impairment in CKD, focusing on recent research that highlights a possible unifying microvascular cause among these shared comorbid conditions. Multiple small studies have been published recently evaluating cognitive and physical functioning in people with CKD. These studies overall demonstrate a high burden of comorbid conditions in people with CKD, including microvascular disease, that may result in cognitive impairment. Additionally, studies demonstrate that physical function is substantially worse than expected in individuals with CKD, that decreased physical activity is associated with worse outcomes, that frailty is very common and associated with an increased risk of death, and that structured exercise programs have small but tangible short-term effects on markers of physical performance. Impaired cognitive function and physical performance are important factors impacting the lives of people with CKD. Further research is necessary to better treat these important comorbid conditions in people with CKD.

Cognitive impairment in chronic kidney disease: keep vascular disease in mind

Cognitive impairment is a major cause of morbidity in people with chronic kidney disease (CKD) and is associated with lower quality of life, more difficulty adhering to medications, and worse survival. Prior data suggest a relationship between vascular disease and cognitive impairment in individuals with CKD, although overall risk factors remain poorly understood. Critically, clinicians should be aware of the high rates of cognitive impairment that occur in all stages of CKD, which, although sometimes subtle, may impact comprehension and decision making in these individuals and may herald future, more debilitating impairment.

The prevalence, severity, and association with HbA1c and fibrinogen of cognitive impairment in chronic kidney disease

Cognitive impairment is a frequent finding in patients with chronic kidney disease (CKD). We examined cognitive performance in a prospective study of 119 patients with CKD stages 3-5 (including dialysis) and 54 control patients of the same age without CKD but with similar vascular risk profiles. Analysis included a comprehensive test battery evaluating memory, information processing speed, executive function, language, and visuoconstructive function, in addition to depression and anxiety. Thirty percent of patients with CKD had cognitive deficits (one or more s.d. below control patient performance). Cognitive deficits (T-value related to published norm values) were mild but significantly decreased to 48.8 in patients with stage 3-5 CKD not requiring hemodialysis and 47.2 in patients with stage 5D disease requiring hemodialysis, compared with 51.5 in control patients. Linear regressions among patients with CKD (forced entry strategy) showed that age (β=-0.50 per s.d.), HbA1c (β=-0.18 per s.d.), and fibrinogen (β=-0.18 per s.d.) predicted cognitive performance. Interestingly, HbA1c discriminated cognition in all age groups, while fibrinogen differentiated cognition particularly in patients over 70 years of age. Thus, our cross-sectional study suggests the severity of cognitive impairment in CKD is mild. As such, longitudinal studies are required to further characterize the role of cognitive deficits in CKD.

Cognitive impairment in chronic kidney disease: clinical findings, risk factors and consequences for patient care

Cognitive deficits have a high prevalence in elderly patients with chronic kidney disease (CKD). The clinical picture consists of cognitive slowing, executive, memory and language deficits, and is attributed to cerebral white matter disease and clinically often silent brain infarcts. In the meantime, robust evidence exists that low estimated glomerular filtration rate, a measure of CKD severity, predisposes to cognitive deficits, cerebral white matter lesions, and ischemic brain infarcts in addition to demographic factors, vascular risk factors and diseases which also contribute to CKD-related cognitive deficits. In terminal CKD, cerebral blood flow is compromized during hemodialysis sessions, resulting in oxygen desaturation, cognitive deterioration and-in the longer run-brain atrophy. Kidney transplantation improves cognitive deficits in terminal CKD. At all stages, vascular risk factors and associated diseases should stringently be treated according to therapeutic guidelines.

Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease–related growth retardation

Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats. Serum growth hormone did not change in rats with CKD, yet serum IGF-I levels were decreased and growth retarded. The tibial growth plate hypertrophic zone was wider and vascularization at the primary ossification center was reduced in CKD. This was associated with a decrease in growth plate vascular endothelial growth factor (VEGF) mRNA and immunostainable VEGF and IGF-I levels. Growth plate growth hormone receptor and STAT5 protein levels were unchanged, while JAK2 was reduced. Despite comparable growth hormone and growth hormone receptor levels in CKD and control rats, relative STAT5 phosphorylation was significantly depressed in CKD. Of note, the mRNA of SOCS2, an inhibitor of growth hormone signaling, was increased. Thus, linear growth impairment in CKD can in part be explained by impaired long bone growth plate growth hormone receptor signaling through the JAK2/STAT5 pathway, an abnormality that may be caused by an increase in SOCS2 expression.

The reversible part of cognitive impairment in chronic kidney disease: can mice help men break the TEMPOLimit?

Discussing the non-adherence to diet or medication with chronic haemodialysis patients can be an utterly frustrating experience, especially if one does this thrice a week. It is also a reflection of the fact that for more than half a century, nephrologists have been focusing on cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Over the last decade, however, burgeoning evidence has accumulated to show that CKD also affects the patient’s brain. CKD is accompanied by severe cognitive impairment as recently reviewed by Elias et al. [1]. Kurella et al. [2] could show that decreased estimated glomerular filtration rate (GFR) in postmenopausal women is significantly associated with impairment in global cognition, executive function, language and memory. A community-based cross-sectional study found that global performance and specific cognitive functions are negatively affected early in CKD [3]. Interestingly, not only decreases in GFR but also elevated urinary albumin/creatinine ratios are independently associated with faster decline in cognitive function [4]. In a 5-year longitudinal community-based study, change in renal functioning over time was related to change observed in global cognitive ability, verbal episodic memory and abstract reasoning [5]. Moreover, moderate renal impairment has been shown to be associated with an excess risk of incident dementia among individuals in good to excellent health [6]. Naturally, cognitive impairment cannot be revealed during the discussions about phosphate binders and anti-hypertensives. The backbone for detection of cognitive impairment are psychometric tests, first introduced in 1944 by the US Army in the Army Individual Test Battery—Manual of Directions and Scoring. Part of this test battery was the trail making test (TMT), a neuropsychological test of visual attention and task switching. It consists of two parts in which the subject is instructed to connect a set of 25 dots as fast as possible while still maintaining accuracy (TMT A) [7]. It can provide information about visual search speed, scanning, speed of processing, mental flexibility as well as executive functioning that are evaluated in the TMT B [7]. It is more sensitive to detecting decline in cognitive function in different stages of CKD than the Modified Mini-Mental State Examination (3MS) [8]. The severity of cognitive impairment is best epitomized by the fact that a high school educated 50-yearold person is able to finish the TMT B in ∼1 min, whereas ∼20% of dialysis patients in the same age group are not able to finish the TMT B in 5 min [9]. The pathophysiological mechanisms leading to cognitive impairment in CKD are still not clearly understood. They may range from effects of urea to the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA [10, 11]). Of note, there is an irreversible and a reversible component of cognitive impairment in CKD (Figure 1). The underlying diseases causing CKD, mostly arterial hypertension and diabetes, go along with structural cerebral changes. This is best epitomized by the facts that CKD5D patients have a 6-fold age-adjusted relative risk of stroke when compared with the general population [12]. Also, the prevalence of asymptomatic silent cerebral infarction is four to five times higher in dialysis patients than in ageand sex-matched controls [13]. A recent systematic review of structural neuroimaging findings in CKD came to the conclusion that cerebral atrophy and cerebral density changes in patients with CKD are frequently seen along with cerebral vascular disease, including deep white matter