Effects of chronic kidney disease on cognitive function and α-klotho expression in hippocampus

BackgroundAlpha-klotho (α-KL) is not only related to the regulation of calcium-phosphorus metabolism, and fibrosis in chronic kidney disease (CKD), it is also involved in the regulation of many cognitive disorders. We conducted this study to investigate the effects of CKD on cognitive dysfunction and α-KL.MethodsDoxorubicin was used to induce a CKD model, which was validated by weight, 24-hour urine protein quantification, serum creatinine (Cr), blood urea nitrogen (BUN), and kidney hematoxylin-eosin (HE) staining. The Morris water maze (MWM) paradigm was used to assess the effects of CKD on cognitive behavior. The expression of α-KL in the hippocampus was detected using real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry (IHC).Results(I) In the CKD group, the weight of the rats increased slowly (P<0.001), 24-hour urine protein increased (P<0.05), and Cr (P=0.026) and BUN levels (P=0.003) increased; (II) HE staining showed that in the CKD group there were changes in the structure, fibrosis, and inflammatory infiltration of the renal tissues, and changes in the structure, cell necrosis, and neuronal degeneration of the hippocampus; (III) in the MWM experiment, the escape latency of the CKD group was prolonged compared to that of the control group (P=0.043, 0.023), and the number of crossing the platform was reduced (P=0.003); (IV) in the CKD group, the expressions of α-KL messenger ribonucleic acid (P=0.0005) and α-KL protein (P=0.0005) in the hippocampus were downregulated. The IHC results showed that the expression of α-KL protein in the hippocampal region III cornus ammonis (CA3) of the CKD group region was also downregulated, and the α-KL-positive cells (P=0.019) and mean optical density (P=0.015) were decreased.ConclusionsThe expression of α-KL appears to effect the cognitive function of CKD rats; thus, it may be a valuable target in the treatment of CKD with cognitive impairment.     

Effects of Intensive Blood Pressure Treatment on Acute Kidney Injury Events in the Systolic Blood Pressure Intervention Trial (SPRINT)

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Estrogen and estrogen receptors in kidney diseases

Acute kidney injury (AKI) and chronic kidney disease (CKD) are posing great threats to global health within this century. Studies have suggested that estrogen and estrogen receptors (ERs) play important roles in many physiological processes in the kidney. For instance, they are crucial in maintaining mitochondrial homeostasis and modulating endothelin-1 (ET-1) system in the kidney. Estrogen takes part in the kidney repair and regeneration via its receptors. Estrogen also participates in the regulation of phosphorus homeostasis via its receptors in the proximal tubule. The ERα polymorphisms have been associated with the susceptibilities and outcomes of several renal diseases. As a consequence, the altered or dysregulated estrogen/ERs signaling pathways may contribute to a variety of kidney diseases, including various causes-induced AKI, diabetic kidney disease (DKD), lupus nephritis (LN), IgA nephropathy (IgAN), CKD complications, etc. Experimental and clinical studies have shown that targeting estrogen/ERs signaling pathways might have protective effects against certain renal disorders. However, many unsolved problems still exist in knowledge regarding the roles of estrogen and ERs in distinct kidney diseases. Further research is needed to shed light on this area and to enable the discovery of pathway-specific therapies for kidney diseases.     

非透析慢性肾脏病患者心率变异性的特点及其影响因素分析

目的：分析非透析慢性肾脏病（CKD）患者心率变异性（HRV）的特点及相关因素。方法：对263例住院且尚未行肾脏替代治疗CKD患者进行HRV（包括SDNN、RMSSD、pNN50、LF、HF、LF/HF）检测,并分析影响CKD患者HRV的因素。结果：CKD1～5期患者HRV下降的比例为57.79%,在CKD1、2、3、4、5期的比例分别为30.77%、42.00%、52.94%、72.73%和87.27%,各组间差异具有统计学意义（P〈0.05）。CKD患者SDNN均值为（110.8±33.5）ms,除CKD1与2期J间、CKD3与4间差异无统计学意义（P〉0.05）,其他各组间比较差异具有统计学意义（P〈0.05）;RMSSD均值为（30.2±18.7）ms,CKD5期明显低于其他4组,且与其他4组间比较差异具有统计学意义（P〈0.05）,但其他4组间比较差异无统计学意义（P〉0.05）;pNN50均值为9.4±5.3,CKD1、2、3、4、5期患者的pNN50呈递减趋势,且各组间比较差异均具有统计学意义（P〈0.05）;LF均值为（1014.3±609.2）ms,CKD3、4期间比较差异无统计学意义（P〉0.05）,其他各组间比较差异均具有统计学意义（P〈0.05）;HF均值为（806.9±318.3）ms,CKD3、4期间比较差异无统计学意义（P〉0.05）,其他各组间比较差异均具有统计学意义（P〈0.05）;LF/HF均值为2.1±0.9,CKD1、2期间,CKD3、4期间比较差异无统计学意义（P〉0.05）,其他各组间比较差异均具有统计学意义（P〈0.05）。血红蛋白、性别、血钠及血钾水平与HRV显著相关。结论：非透析CKD患者HRV下降的比例较高,且随着CKD分期增加,发生HRV下降的比例增加。     

Psychosocial factors in people with chronic kidney disease prior to renal replacement therapy

Increasing evidence implicates psychosocial factors including depression, anxiety, perceived social support and health‐related quality of life in the pathophysiology of various chronic diseases. Research examining the psychosocial aspects of kidney disease has focussed predominantly on depressive disorders in dialysis patients where they are independently associated with increased risk of mortality and poor health‐related quality of life. In contrast, studies examining the influence of psychosocial factors in people with chronic kidney disease (CKD) prior to the initiation of renal replacement therapy are sparse. Limited data indicate that clinical depression and depressive symptoms are common and may independently predict progression to dialysis, hospitalization and death. In contrast, the influence of anxiety disorders, lower perceived social support and impaired health‐related quality of life on the clinical course of CKD have received little attention. Large‐scale prospective cohort studies are needed to clarify the burden and prognostic impact of these factors in this vulnerable population. Given the escalating burden of CKD worldwide examining the role of these potentially modifiable risk factors is crucial. Identifying and implementing targeted interventions in order to prevent or delay the progression of CKD and improve quality of life will be a major challenge.     

Decreased body mass index as an independent risk factor for developing chronic kidney disease

BACKGROUND: Obesity and metabolic syndrome are risk factors for the development of chronic kidney disease (CKD). Few studies have examined the effect of change in body mass index (DeltaBMI) on CKD incidence in a general screening setting. METHODS: Subjects of this study were screenees that participated in the screening program of the Okinawa General Health Maintenance Association in 1993 and 2003 in Okinawa, Japan. Using identification number, birth date, sex, and other recorded identifiers, we identified 33,389 subjects among the 1993 screening participants (N = 143,948) who also participated in the 2003 screening. CKD was defined as estimated glomerular filtration rate <60 ml/min/1.73 m(2), according to the modification of diet in renal disease study equation. Obesity was defined as BMI > or = 25 kg/m(2). RESULTS: CKD prevalence was 13.8% in 1993 and 22.4% in 2003. The incidence of developing CKD in 10 years was 15.5%. The effect of DeltaBMI on CKD incidence was evaluated after considering other confounding factors such as age, sex, blood pressure, BMI, fasting plasma glucose, and proteinuria. Median DeltaBMI was 1.0%. The adjusted odds ratio (95% CI) for the effect of DeltaBMI on CKD incidence was 1.111 (1.026-1.204, P < 0.01; entire study population), 1.271 (1.116-1.448, P = 0.0030; men), and 1.030 (0.931-1.139, NS; women), when DeltaBMI > or = 1% was taken as a reference. DeltaBMI was an independent predictor of CKD incidence. CONCLUSIONS: The present results suggest that there was an inverse relationship between DeltaBMI and CKD incidence among screened subjects. The reasons for this observation are not clear, but careful follow-up for DeltaBMI is necessary, particularly in obese men with proteinuria.     

Urinary UMOD Excretion and Chronic Kidney Disease in Gout Patients: Cross-Sectional Case–Control Study

Patients with gout often have concurrent chronic kidney disease (CKD); the relationship between the two conditions is still unclear. Previous studies have identified an association between low level of urinary uromodulin (UMOD) and CKD within the setting of diabetes and lupus. The aim of this study was to examine the association between urinary UMOD excretion and CKD in patients with gout. A total of 53 Taiwanese gout patients with stable disease activity were enrolled. Patients were divided into a CKD group (n = 25) and a non-CKD group (n = 28). Using Pearson correlation analysis, urinary UMOD excretion was positively correlated with estimated glomerular filtration rate (Ha: ρ > 0, p = 0.004). Using multivariate analysis, patients with CKD and gout were associated with lower urinary UMOD excretion than those who have gout alone [odds ratio (95% CI): 0.826 (0.694–0.985), p < 0.001]. Patients with CKD and gout were also more likely to be older (p < 0.001) and have higher uric acid levels (p < 0.001). This study implicates that UMOD might play a role in the relationship between gout and CKD. Further studies with animal models of gout and CKD would be recommended.     

Phosphate in early chronic kidney disease: associations with clinical outcomes and a target to reduce cardiovascular risk

There is an intimate association between mineral and bone disorders in chronic kidney disease (CKD) and the extensive burden of cardiovascular disease (CVD) in this population. High phosphate levels in CKD have been associated with increased all-cause mortality and cardiovascular morbidity and mortality. Observational studies have also shown a consistent relationship between serum phosphate in the normal range and all-cause and cardiovascular mortality, left ventricular hypertrophy (LVH) and decline in renal function. Furthermore, fibroblast growth factor-23 (FGF-23), a phosphaturic hormone, increases very early in the course of CKD and is strongly associated with death and CVD, including LVH and vascular calcification. Few studies have addressed outcomes using interventions to reduce serum phosphate in a randomized controlled fashion; however, strategies to address cardiovascular risk in early CKD are imperative and phosphate is a potential therapeutic target. This review outlines the epidemiological and experimental evidence highlighting the relationship between excess phosphate and adverse outcomes, and discusses clinical studies required to address this problem.