Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation

Hyperparathyroidism occurs in most patients during the progression of chronic kidney disease (CKD) and one of its initiating events, reduced serum levels of 1,25-dihydroxyvitamin D, results from a decrease in renal 1alpha hydroxylase activity, which converts 25-hydroxyvitamin D to its activated form. The combination of persistently high parathyroid hormone (PTH) and low 1,25-dihydroxyvitamin D is associated with bone loss, cardiovascular disease, immune suppression and increased mortality in patients with end-stage kidney failure. Recent studies in dialysis patients suggest that paricalcitol, a selective activator of the vitamin D receptor (VDR), is associated with a more favorable efficacy to side effect profile than calcitriol, with less morbidity and better survival. One hypothesis derived from such studies suggests that systemic activation of VDRs may have direct effects on the cardiovascular system to decrease mortality in CKD. Although current guidelines for regulating serum calcium, phosphate and PTH recommend specific interventions at the various stages of CKD to prevent or postpone irreversible parathyroid disease and decrease cardiovascular morbidity and mortality, emerging data suggest that vitamin D therapy may prolong survival in this patient population by mechanisms that are independent of calcium, phosphate and PTH. It is suggested that a re-evaluation of current treatment recommendations is needed and that future research should focus on mechanisms that distinguish potential tissue specific benefits of selective VDR activators in patients with CKD.     

Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events

Background

Besides its effect on calcium metabolism, vitamin D may play a part in preventing the onset and progression of cardiovascular disease (CVD) events. Only a few reports on the studies relating to whether vitamin D may reduce CVD events in patients with predialysis chronic kidney disease (CKD) are available, and many ambiguities remain.

Methods

We conducted a retrospective cohort study of 665 patients with predialysis CKD. With log-rank test using the Kaplan–Meyer survival curve, comparison of incidences of CVD events, CVD-related mortality, and all-cause mortality were made between patients in the alfacalcidol treatment group (107 patients) in the predialysis stage to whom alfacalcidol 0.25–0.5 μg/day was orally administered for at least 24 weeks, and patients in the nontreatment group (558 patients) who received no administration of alfacalcidol or other type of activated vitamin D and its analogues. Patients to whom alfacalcidol administration was discontinued within 24 weeks as well as initiation of dialysis of <24 weeks were excluded for this study. Factors relating to CVD events were examined using Cox’s proportional hazards analysis.

Results

The mean follow-up period was 55.1 ± 38.9 months in the alfacalcidol treatment group and 41.9 ± 38.4 months in the nontreatment group. CVD events occurred in 172 patients during the follow-up period, and 74 of those occurred during the predialysis period. In the alfacalcidol treatment group, the incidence of cumulative CVD events was significantly lower. In relation to all-cause deaths and CVD-related deaths, the cumulative mortality rate was significantly lower in the alfacalcidol treatment group during the follow-up period. Throughout the follow-up period, the association between CVD events and alfacalcidol use was detected when adjusted for age, sex, diabetes, hypertension, use of renin–angiotensin system inhibitors, estimated glomerular filtration rate, and albumin and parathyroid hormone.

Conclusion

These data showed that oral administration of alfacalcidol for predialysis CKD patients was associated with reduced risk for CVD.     

Ergocalciferol and cholecalciferol in CKD

The development of chronic kidney disease (CKD) is accompanied by a progressive decrease in the ability to produce 1,25-dihydroxyvitamin D. Pharmacological replacement with active vitamin D therefore has been a cornerstone of secondary hyperparathyroidism therapy in the end-stage renal disease population treated by long-term dialysis. Recent evidence suggests that extrarenal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D may have significant biological roles beyond those traditionally ascribed to vitamin D. Furthermore, low 25-hydroxyvitamin D levels are common in patients with all stages of CKD. This article focuses on the role of nutritional vitamin D replacement in CKD and aims to review vitamin D biology and summarize the existing literature regarding nutritional vitamin D replacement in these populations. Based on the current state of the evidence, we provide suggestions for clinical practice and address areas of uncertainty that need further research.     

Adynamic bone in patients with chronic kidney disease

Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.     

Serum vitamin D metabolites and nuclear uptake of (3H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: a study of two radiological types

The nuclear uptake of (³H)-1,25 dihydroxyvitamin D₃ in freshly isolated human monocytes and the serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were investigated in 13 patients with autosomal dominant osteopetrosis and in sex- and age-matched controls. Seven patients had type I osteopetrosis characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and increased thickness of the cranial vault. The other six patients had type II with “Rugger Jersey Spine” and “endobones” as characteristic findings. In type I osteopetrosis the serum 1,25-dihydroxy vitamin D was significantly reduced (p < 0.05), whereas serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D receptor binding were normal. In type II osteopetrosis the serum vitamin D metabolites were normal, as was the maximal binding capacity (Bmax) of 1,25-dihydroxyvitamin D to the nuclear receptor. The dissociation constant (Kd), however, was significantly increased (p < 0.01) indicating a modest resistance to 1,25-dihydroxyvitamin D. It is concluded that a general end-organ resistance to 1,25-dihydroxyvitamin D at the receptor level does not exist in type I osteopetrosis, but may contribute to some of the radiological and biochemical findings in type II.     

Serum vitamin D metabolites and nuclear uptake of (H)-1,25-dihydroxyvitamin D3 in monocytes from patients with autosomal dominant osteopetrosis: A study of two radiological types

The nuclear uptake of (³H)-1,25 dihydroxyvitamin D₃ in freshly isolated human monocytes and the serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were investigated in 13 patients with autosomal dominant osteopetrosis and in sex- and age-matched controls. Seven patients had type I osteopetrosis characterized by diffuse, symmetrical osteosclerosis with pronounced sclerosis of the skull and increased thickness of the cranial vault. The other six patients had type II with “Rugger Jersey Spine” and “endobones” as characteristic findings. In type I osteopetrosis the serum 1,25-dihydroxy vitamin D was significantly reduced (p < 0.05), whereas serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D receptor binding were normal. In type II osteopetrosis the serum vitamin D metabolites were normal, as was the maximal binding capacity (Bmax) of 1,25-dihydroxyvitamin D to the nuclear receptor. The dissociation constant (Kd), however, was significantly increased (p < 0.01) indicating a modest resistance to 1,25-dihydroxyvitamin D. It is concluded that a general end-organ resistance to 1,25-dihydroxyvitamin D at the receptor level does not exist in type I osteopetrosis, but may contribute to some of the radiological and biochemical findings in type II.     

Vitamin D insufficiency: implications for the immune system

Chronic kidney disease (CKD) is characterized by a loss of kidney function and dysregulation of vitamin D metabolism. Well known are the defects in final activation of vitamin D to 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], resulting in renal osteodystrophy. However, in recent years, 1,25(OH)₂D₃ has been identified as having effects far beyond calcium and bone metabolism. In this review, specific attention is given to the effects of 1,25(OH)₂D₃ on the immune system and the implications of vitamin D deficiency, a feature of many patients with CKD, on immune function.     

Association of serum magnesium with cardiovascular mortality and all-cause mortality in peritoneal dialysis patients

Objective To investigate the association of serum magnesium with cardiovascular disease (CVD) and all-cause mortality in peritoneal dialysis patients. Methods A retrospective study was performed in patients who initiated peritoneal dialysis from January 1, 2013 to July 31, 2019 in the Shaoxing People's Hospital. According to the standard of serum magnesium, the patients were divided into control group (Mg≥0.7 mmol/L) and low-magnesium group (Mg﹤0.7 mmol/L). The differences in baseline biochemical variables, comorbidities, medications, and clinical outcomes between the two groups were compared. Logistic regression was used to analyze the related factors of hypomagnesemia. Kaplan-Meier survival analysis and Fine-Gray model were used to compare the difference in cumulative survival rate between the two groups. Cox regression model and competitive risk model were used to analyze the risk factors of all-cause mortality and CVD mortality. Results A total of 381 peritoneal dialysis patients were enrolled in this study. Among them, 321 patients were in control group and 60 patients in low-magnesium group. The total median follow-up time was 27(15, 43) months. There were significant differences in serum albumin, magnesium, phosphorus, intact parathyroid hormone, low-density lipoprotein chloesterol, high sensitivity C-reactive protein and 4-hour dialysate-to-plasma creatinine (4 h D/Pcr) between the two groups. CVD was the main cause of death in patients on peritoneal dialysis. Multivariate logistic regression analysis showed that hypoalbuminemia (OR=0.901, 95%CI 0.831-0.976, P=0.011), hypophosphatemia (OR=0.217, 95%CI 0.080-0.591, P=0.003), higher hsCRP (OR=1.276, 95%CI 1.066-1.528, P=0.008), and higher 4 h D/Pcr (OR=1.395, 95%CI 1.014-1.919, P=0.041) were independent risk factors for patients with hypomagnesemia. Kaplan-Meier survival curve analysis showed the cumulative survival rate of patients in low-magnesium group was significantly lower than that of control group (Log-rank χ2=5.388, P=0.020). Fine-Gray model analysis showed the cumulative CVD survival rate of low-magnesium group was significantly lower than that of control group (Gray=6.915, P=0.009). Multivariate-corrected Cox regression model and competitive risk model analysis showed that higher serum magnesium level was a protective factor for all-cause mortality and CVD mortality when serum magnesium was used as a continuous variable (HR=0.137, 95%CI 0.020-0.946, P=0.044; SHR=0.037, 95%CI 0.002-0.636, P=0.023, respectively). Hypomagnesemia was an independent risk factor for all-cause mortality and CVD mortality when serum magnesium was used as categorical variable (HR=1.864, 95%CI 1.044-3.328, P=0.035; SHR=2.117, 95%CI 1.147-3.679, P=0.029, respectively). Conclusions Hypomagnesemia is susceptible to peritoneal dialysis patients with hypoalbuminemia, hypophosphatemia, higher hsCRP and higher peritoneal transport characteristics. Hypomagnesemia is an independent risk factor for CVD mortality and all-cause mortality in peritoneal dialysis patients.     

Ergocalciferol decreases erythropoietin resistance in children with chronic kidney disease stage 5

Background

Vitamin D insufficiency is related to erythropoietin resistance in chronic kidney disease (CKD). This study was conducted to evaluate the effect of ergocalciferol on the dose of erythrocyte-stimulating agent (ESA) administered to children with CKD stage 5 and vitamin D insufficiency.

Methods

Twenty patients aged <18 years with CKD stages 5 or 5D and vitamin D insufficiency were divided into two groups. During the 12-week study, ten patients received oral ergocalciferol (treatment) whereas the other ten patients did not (control). The ESA dosage was recorded monthly.

Results

There were no significant differences in demographic data, ESA dosages, and laboratory data, including corrected calcium, phosphorus, parathyroid hormone, hemoglobin, ferritin, 25-hydroxyvitamin D (25D), and transferrin saturation levels, between the two groups at baseline. At the completion of the study, serum 25D levels in the treatment group were significantly increased from baseline (p?=?0.02) and were significantly higher than the serum 25D levels in the controls (p?<?0.005). The ESA dosage in the treatment group was significantly decreased when compared to baseline (p?=?0.04).

Conclusions

Vitamin D deficiency should be routinely detected and treated. Our results show that the administration of ergocalciferol in conjunction with 1,25-dihydroxyvitamin D3 reduced the dose of ESA required to treat children with CKD stages 5 and 5D and may decrease erythropoietin resistance.     

Influence of atherosclerosis on the relationship between anaemia and mortality risk in haemodialysis patients.

BACKGROUND: Full, as compared with partial, correction of anaemia did not reduce the mortality risk in patients with chronic kidney disease (CKD), although the underlying mechanisms are unknown. Since CKD is a high-risk population for cardiovascular disease (CVD), we tested a hypothesis that the presence of atherosclerosis affects the relationship between anaemia and mortality risk. METHODS: We performed a single-centre 10-year follow-up study with an observational cohort of 505 haemodialysis patients to analyse the relationship between haematocrit and all-cause mortality. Baseline haematocrit levels did not differ between the 153 patients with CVD and the 352 patients without CVD. RESULTS: During the follow-up, 268 patients died. Both Kaplan-Meier and univariate Cox analyses showed that higher haematocrit levels were a significant predictor of lower risk of death in the CVD (-) group, whereas haematocrit did not predict death in the CVD (+) group. In multivariate Cox analyses, the inverse relationship between haematocrit and mortality in the CVD (-) group remained significant and independent of 14 covariates including the use of erythropoietin. In contrast, using the same Cox models, the CVD (+) group did not show such a beneficial effect of higher haematocrit. Similar observations were made when the subjects were divided based on carotid artery intima-media thickness instead of the presence of CVD. CONCLUSIONS: These results support the hypothesis that the presence of atherosclerosis alters the relationship between anaemia and mortality risk in haemodialysis patients.     

The dualistic role of vitamin D in vascular calcifications

Vitamin D is a multifunctional hormone that can affect many essential biological functions, ranging from the immune regulation to mineral ion metabolism. A close association between altered activity of vitamin D and vascular calcification has been reported in various human diseases, including in patients with atherosclerosis, osteoporosis, and chronic kidney disease (CKD). Vascular calcification is a progressive disorder and is a major determinant of morbidity and mortality of the affected patients. Experimental studies have shown that excessive vitamin D activities can induce vascular calcification, and such vascular pathology can be reversed by reducing vitamin D activities. The human relevance of these experimental studies is not clear, as vitamin D toxicity is relatively rare in the general population. Contrary to the relationship between vitamin D and vascular calcification, in experimental uremic models, low levels of vitamin D were shown to be associated with extensive vascular calcification, a phenomenon that is very similar to the vascular pathology seen in patients with CKD. The current treatment approach of providing vitamin D analogs to patients with CKD often poses a dilemma, as studies linked vitamin D treatment to subsequent vascular calcification. Recent genetic studies, however, have shown that vascular calcification can be prevented by reducing serum phosphate levels, even in the presence of extremely high serum 1,25-dihydroxyvitamin D and calcium levels. This article will briefly summarize the dual effects of vitamin D in vascular calcification and will provide evidence of vitamin D-dependent and -independent vascular calcification.     

慢性肾脏病3～5期患者的钙磷代谢影响因素分析

目的分析我院门诊慢性肾脏病（CKD）3-5期患者的钙磷代谢诊疗现状及影响因素。方法分析我院门诊的317例CKD3～5期患者就诊资料,对钙磷代谢诊疗现状及影响因素进行统计学分析。结果CKD3～5期患者血钙、血磷、全段甲状旁腺素（iPTH）检测情况和结果差异有统计学意义（P〈0．05）。规律随诊与血钙、血磷检查与否相关,CKD分期、规律随诊、服用活性维生素D与患者iPTH检查与否相关。CKD分期、合并心血管疾病（CVD）与血钙异常相关。CKD分期与高血磷、高iPTH相关。结论CKD3期即可能出现钙磷代谢异常。CKD分期是影响血钙、血磷和iPTH的共同影响因素。合并CVD与血钙异常相关。规律随诊与钙磷、iPTH检查与否相关。     

Association of serum soluble Klotho with episode of nonfatal cardiovascular disease and mortality in maintenance hemodialysis patients

Objective To explore the association of serum soluble Klotho (sKlotho) with nonfatal cardiovascular disease (CVD) and all-cause/CVD mortality in maintenance hemodialysis (MHD) patients. Methods A total of 132 MHD patients admitted during October 2011 were enrolled. Serum sKlotho was measured by ELISA. Demographic data, including age, gender and comorbid conditions, were obtained from their medical histories, and parameters including calcium, phosphorus and albumin were assessed. The occurrence time of nonfatal CVD and all-cause mortality were recorded during the 60 months follow-up. MHD patients were categorized into four groups according to the quartiles of sKlotho: group Ⅰ (sKlotho＜361.34 ng/L), group Ⅱ (361.34 ng/L≤sKlotho＜398.81 ng/L), group Ⅲ (398.81 ng/L≤sKlotho＜445.99 ng/L) and group Ⅳ (sKlotho≥445.99 ng/L). Spearman correlation analysis and binary Logistic regression analysis were used to test the association between sKlotho and nonfatal CVD events. The impacts of sKlotho on all-cause mortality and CVD mortality were assessed by Kaplan-Meier method with log-rank test. Cox regression model was applied to evaluate the effect of sKlotho on MHD patients outcomes. Results All 132 MHD patients had sKlotho ranging from 304.02 ng/L to 550.62 ng/L. And 87 patients suffered from nonfatal CVD, with 192 episodes of nonfatal CVD during the follow-up period. The sKlotho had negative correlations with coronary artery disease (r=-0.286, P=0.001), congestive heart failure (r=-0.190, P=0.029), cerebrovascular accident (r=-0.240, P=0.006) and peripheral arterial occlusion (r=-0.243, P=0.005). The sKlotho were risk factors of coronary artery disease (OR=0.989, P=0.023) and peripheral artery occlusion (OR=0.988, P=0.046). 35 patients died in the follow-up period, including 27 death from CVD. The all-cause mortality and CVD mortality rates were significantly different among four groups (P=0.036, P=0.047). Survival rates of all-cause death and CVD death varied among four groups (χ2=8.076, P=0.044; χ2=7.866, P=0.049). Patients in group Ⅳhad higher survival rates of all-cause death and CVD death than those in group Ⅰ and group Ⅱ (all P＜0.05). Multivariate Cox regression analyses revealed diabetes and age were independent risk factors for all-cause mortality and CVD mortality (all P＜0.05), but sKlotho was not associated with the poor prognosis (HR=0.996, P=0.256; HR=0.996, P=0.287). Conclusions Patients with lower sKlotho have worse nonfatal CVD ratio, especially coronary artery disease and peripheral arterial occlusion. Reduced serum sKlotho is associated with all-cause and CVD mortality, but sKlotho is still not a predictive indicator of prognosis of MHD patients.     

Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study

Longitudinal studies testing the relationship between repeated measures of vitamin D or fibroblast growth factor 23 (FGF23) and infectious and cardiac hospitalizations and death in hemodialysis patients have not been reported. We examined the association between yearly 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)₂D), and FGF23 serum levels and various clinical outcomes using time-dependent Cox regression models with repeated yearly measures and fixed-covariate Cox models with only baseline values after controlling for important clinical covariates in the HEMO study. During a median follow-up of 3 years, 582 of the 1340 participants died, and 499 and 514 participants had a hospitalization or death attributed to infectious and cardiac causes, respectively. Patients in the highest 25(OH)D quartile had the lowest risk of infectious events (hazard ratio [HR] 0.66 versus the lowest quartile; 95% confidence interval [95% CI], 0.49–0.89), cardiac events (HR, 0.71; 95% CI, 0.53–0.96), and all-cause mortality (HR, 0.46; 95% CI, 0.34–0.62) in time-dependent analyses. No significant associations of 1,25(OH)₂D with clinical outcomes were observed in time-dependent or fixed-covariate Cox models. In contrast, the highest FGF23 quartile was associated with a higher risk of infectious events (HR, 1.57 versus the lowest quartile; 95% CI, 1.13–2.18), cardiac events (HR, 1.49; 95% CI, 1.06–2.08), and all-cause mortality (HR, 1.50; 95% CI, 1.07–2.12) in fixed-covariate Cox models. The addition of inflammation markers into the statistical models did not attenuate these associations. Thus, disordered mineral metabolism may affect outcomes in chronic hemodialysis patients.     

Vitamin D status in children with chronic kidney disease

Background

The role of vitamin D status in patients with renal insufficiency and its relation to dietary intake and parathyroid hormone (PTH) secretion is of utmost interest given the morbidity and mortality associated with the disordered mineral metabolism seen in chronic kidney disease (CKD).

Methods

We conducted a cross-sectional study of 100 pediatric patients with a diagnosis of CKD stage 1–5 at Children's Hospital Boston, measuring blood levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)₂D], and parathyroid hormone and obtaining data on nutrient intake and other variables related to vitamin D status.

Results

Subjects ranged in age from 6 months to 18?years, and 60 were male, 40 female. Of the 100 patients, 16 % were deficient in 25(OH)D (≤20?ng/mL) and another 24 % were insufficient (≤30?ng/mL), with 40 % in the suboptimal range. Serum 25(OH)D and dietary vitamin D intake were not correlated.

Conclusions

We found a high prevalence of hyperparathyroidism in early-stage CKD and a significant relationship between 25(OH)D and PTH regardless of calcitriol level. Our study results support the suggestion that optimization of vitamin D levels may provide additional benefit in preventing or improving hyperparathyroidism in patients with early CKD and likely remains important as an adjunctive therapy in children with advanced CKD.     

The virtues of vitamin D—but how much is too much?

Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population. What was once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a ‘calcaemic hormone’ but plays an important role in the prevention of cardiovascular disease, infectious and auto-immune conditions, renoprotection, glycaemic control and prevention of some common cancers. Most tissues in the body have a vitamin D receptor and the enzymatic machinery to convert ‘nutritional’ 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D; it is estimated that 3% of the human genome is regulated by the vitamin D endocrine system. Although there are few well-conducted studies on the benefits of vitamin D therapy, an exuberant use of vitamin D is now seen in the general population and at all stages of CKD. There is emerging evidence that vitamin D may in fact have a therapeutic window, and at least from the effects on the cardiovascular system, more is not necessarily better. In this review, we discuss the role of nutritional vitamin D (ergocalciferol or cholecalciferol) supplementation in CKD patients, interpreting the clinical studies in the light of the vitamin D metabolic pathway and its pluripotent effects. While nutritional vitamin D compounds clearly have numerous beneficial effects, randomised controlled studies are required to determine the effectiveness and optimal dose at different stages of CKD, its concurrent use with activated vitamin D compounds and its safety profile.     

Prognosis and risk factors of chronic kidney disease progression in patients with diabetic kidney disease and non-diabetic kidney disease: a prospective cohort CKD-ROUTE study

Diabetic kidney disease (DKD) is emerging rapidly as the leading cause of chronic kidney disease (CKD) worldwide. In this 3-year prospective, multicenter cohort study, a total of 1138 pre-dialysis CKD patients were recruited. Patients were categorized into two groups according to the etiologies of DKD and non-diabetic kidney disease (NDKD). Propensity score matching was performed to adjust for confounding factors, resulting in 197 patients being assigned to DKD and NDKD groups, respectively. The primary endpoints were 50% estimated glomerular filtration rate (eGFR) decline and initiation of kidney replacement therapy (KRT). The secondary endpoints were all-cause death and the development of cardiovascular disease (CVD) events. We found that DKD patients have a higher risk to develop 50% eGFR decline endpoint (HR:2.30, 95%CI [1.48–3.58], p < 0.001) and KRT endpoint (HR:1.64, 95%CI [1.13–2.37], p < 0.05) than NDKD patients. The 3-year cumulative incidence of 50% eGFR decline and KRT endpoint was significantly higher in DKD patients (26.90% vs.13.71% and 35.03% vs. 22.34%, respectively). The Cox regression analyses showed that the increased systolic blood pressure (SBP), DKD, decreased serum albumin (Alb), and higher CKD stages were risk factors for the 50% eGFR decline endpoint; the increased SBP, DKD, decreased serum Alb, serum creatinine (Scr), higher CKD stages, presence of proteinuria and CVD were risk factors for KRT endpoint; the increased age, decreased hemoglobin (Hb), decreased serum Alb were risk factors for all-cause death endpoint; the increased age, decreased serum Alb were risk factors for CVD events endpoint. Appropriate preventive or therapeutic interventions should be taken to control these predictive factors to delay the development of CKD complications, thereby improving the prognosis and reducing the disease burden of the high-risk populations.     

Decreased lymphocyte and increased monocyte count in peripheral blood is associated with cardiovascular disease and one - year mortality in maintenance hemodialysis patients

ObjectiveTo investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients. MethodsA total of 371 MHD patients at Zhongshan Hospital, Fudan University between March 2009 and February, 2011 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. All patients were followed for one year to investigate the risks for CVD event and mortality. Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters. Difference in categorical factors between two groups were determined with Chi-square test, Difference in continuous values between two groups were assessed with t test. Kaplan - Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors. ResultsPatients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51, P＜0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15, P＜0.01) than those without CVD event. Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk, 95%CI: 0.136-0.719, P＜0.01) and that an increased monocyte count was associated with increased mortality risk, 95% CI: 2.657 - 74.396, P＜0.01) after adjustment for hsCRP. ConclusionDecreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one - year all - cause mortality risk in MHD patients.     

Serum nitric oxide metabolites and hard clinical endpoints: a population-based prospective study

Objective. Limited data are available regarding prognostic value of nitric oxide metabolites (NOx) for clinical hard end points. In this study, we defined optimum cut-off values of serum NOx for predicting all-cause and cardiovascular disease (CVD) mortality events and prospectively investigated their hazards in the presence of traditional risk factors. Design. Serum NOx concentrations were measured at baseline (2006–2008) and 3520 adult men and women were followed during 7.7 years for all-cause and cardiovascular disease (CVD) mortality. To determine the optimal cut-off points of serum NOx, the receiver operator characteristic (ROC) curve analysis was used. Multivariate Cox proportional hazard models were used to estimate the hazard ratios (HRs) with 95% confidence intervals (95% CIs) of all-cause and CVD mortality below and above the defined optimal cut-off points of serum NOx. Results. Mean age of participants was 44.5?±?16.0 years at baseline and 40.2% were male. Median (inter-quartile range) of serum NOx levels was 25.0 µmol/L (19.0–37.0), at baseline. The optimal cut-off points of serum NOx levels for predicting CVD and all-cause mortality were 30.5 and 32.5 µmol/L, respectively. In the presence of age, sex, body mass index, smoking, type 2 diabetes, hypertension, and history of CVD, a significant increased risk of CVD mortality (HR?=?1.98, 95% CI?=?1.10–3.58) and all-cause mortality (HR?=?1.52, 95% CI?=?1.05–2.21) was observed for serum NOx values higher than their cut-offs. Conclusion. Serum NOx level may be predictor of CVD mortality and death, in general populations.