Asymptomatic atherosclerosis and hypertension in nondiabetic patients with chronic kidney disease

Abstract:  Atherosclerosis is accelerated in dialysis patients, but less is known about asymptomatic atherosclerosis and major risk factors in patients with different stages of chronic kidney disease (CKD). We compared intima media thickness (IMT) and plaque occurrence in the carotid arteries in 104 nondiabetic patients (stages 1–5 of CKD; mean age: 51.6 years) with those in 40 healthy control subjects. The IMT values (0.69 vs. 0.59 mm; P  < 0.002) were higher in patients. More patients had plaques (46.2 vs. 17.5%; P  < 0.002), and number of plaques was higher ( P  < 0.003). Negative correlation between IMT ( P  < 0.0001), presence of plaques ( P  < 0.0001), their number ( P  < 0.040), and chromium 51-labeled ethylenediaminetetraacetate (⁵¹Cr-EDTA) clearance were found in patients. With multiple regression analysis, relationship between IMT and ⁵¹Cr-EDTA clearance ( P  < 0.001) and presence of hypertension ( P  < 0.001) was found. Nondiabetic patients with CKD showed advanced atherosclerosis and IMT, plaque occurrence, and number increased directly with the level of renal dysfunction. Another important risk factor was hypertension.       

Adiponectin and mortality in patients with chronic kidney disease

Adiponectin is presumed to possess antiatherogenic and cardioprotective properties. Limited data exist on the relationship between adiponectin and mortality in the earlier stages of chronic kidney disease. The Modification of Diet in Renal Disease study was a randomized, controlled trial that was conducted between 1989 and 1993. Adiponectin was measured in frozen samples that were obtained at baseline (N = 820). Survival status and cause of death, up to December 31, 2000, were obtained from the National Death Index. Multivariable Cox models were used to examine the relationship of adiponectin with all-cause and cardiovascular mortality. Mean +/- SD age was 52 +/- 12 yr, and mean +/- SD glomerular filtration rate (GFR) rate was 33 +/- 12 ml/min per 1.73 m2. Eighty-five percent of participants were white, and 60% were male. Mean +/- SD adiponectin was 12.8 +/- 8.0 mug/ml. Triglycerides, insulin resistance, glucose, body mass index, GFR, C-reactive protein, and albumin were inversely related and proteinuria and HDL cholesterol were directly related to adiponectin. During the 10-year follow-up period, 201 (25%) participants died of any cause, and 122 (15%) from cardiovascular disease. In multivariable adjusted Cox models, a 1-mug/ml increase in adiponectin was associated with a 3% (hazard ratio 1.03; 95% confidence interval 1.01 to 1.05; P = 0.02) increased risk for all-cause and 6% (hazard ratio 1.06; 95% confidence interval 1.03 to 1.09; P < 0.001) increased risk for cardiovascular mortality. High, rather than low, adiponectin is associated with increased mortality in this cohort of patients with chronic kidney disease stages 3 to 4. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.     

Mineral metabolism and mortality in patients with chronic kidney disease

Chronic kidney disease is associated with profound alterations in mineral metabolism. A growing body of evidence, based largely on observational studies, indicates that patient mortality is associated with altered mineral metabolism. Evidence is reviewed concerning the association between mortality and high concentrations of serum phosphorus, calcium, calcium-phosphate product, and parathyroid hormone. In addition, mortality may be independently associated with dialysate calcium concentration, type of phosphate binder therapy, and use of vitamin D analogs. Practices related to management of altered mineral metabolism may prove to be a promising means of improving outcomes for patients with chronic kidney disease.     

Glycosylated hemoglobin in patients treated by chronic dialysis

A glycosylated hemoglobin (HbA₁) test was used to evaluate the role of dialysate glucose in the development of carbohydrate intolerance and hyperlipidemia in chronic hemodialysis patients and chronic peritoneal dialysis patients. HbA₁ levels were significantly elevated in all groups of patients. HbA₁ levels were not ameliorated with 8 weeks of glucose-free hemodialysis. There was no correlation between HbA₁ and serum glucose, triglycerides, or cholesterol.Thus, HbA₁ elevation cannot be explained solely by glucose reabsorption from dialysate. This test is helpful in the detection of carbohydrate intolerance, but its usefulness in evaluation of hyperlipidemia of dialysis patients is uncertain.     

Long-term outcomes in nondiabetic chronic kidney disease

The Modification of Diet in Renal Disease (MDRD) Study examined the effects of strict blood pressure control and dietary protein restriction on the progression of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic participants with stages 2-4 chronic kidney disease (CKD) from randomized and nonrandomized cohorts of the MDRD Study. Kidney failure and survival status through December of 2000, were obtained from the US Renal Data System and the National Death Index. Event rates were calculated for kidney failure, death, and a composite outcome of death and kidney failure. In the 1666 patients, rates for kidney failure were four times higher than that for death. Kidney failure was a more likely event than death in subgroups based on baseline glomerular filtration rate, proteinuria, kidney disease etiology, gender, and race. It was only among those older than 65 that the rate for death approximated that for kidney failure. In contrast to other populations with CKD, our study of relatively young subjects with nondiabetic disease has found that the majority of the participants advanced to kidney failure with a low competing risk of death. In such patients, the primary emphasis should be on delaying progression of kidney disease.     

Vitamin D status and mortality risk in patients with chronic kidney disease

Several studies have shown that mineral metabolism disorders play a major role in determining a higher mortality rate for end-stage renal disease patients. Vitamin D deficiency is associated with cardiovascular events in hemodialysis patients. Recently, an association between vitamin D insufficiency and cardiovascular or renal events has been found, in patients with chronic renal failure who have not started renal replacement therapy yet. To further investigate this issue, we evaluated the relationship between blood levels of 25-hydroxyvitamin D (25-OH D; > or ≤30 ng/mL) and mortality or dialysis dependence in 104 incident consecutive patients with chronic kidney disease stages 3-5, over a period of 17 months, with a follow-up of 2 years in a cross-sectional analysis. The correlation between different levels of vitamin D and the risk of events has been estimated by using a probit model. Explanatory variables employed concerned age, sex, blood pressure, BMI, and number of co-morbid factors. The average 25-OH D concentration was of 30.13 ng/mL. During follow-up (>16 months), each patient experienced an average of 1.28 events. Vitamin D has been shown to reduce the probability of cardiovascular or renal events. Vitamin D intake for more than 12 months can reduce the probability of such events by 11.42%. Each co-morbid factor, instead, raises the probability of events by 29%. Lower probabilities of experiencing an adverse cardiovascular event might depend on higher levels of vitamin D. The influence of 25-OH D on survival in chronic kidney disease patients may be related to unrecognized factors that need to be further explored.     

Delayed gastric emptying in nondiabetic patients with end-stage kidney disease

ObjectiveThis study aimed to assess the gastric emptying capacity in nondiabetic patients with end-stage kidney disease (ESKD) by ultrasound.MethodsConsecutive hemodialysis patients with ESKD (n = 37) and healthy controls (n = 37) were enrolled. All ESKD patients underwent ultrasound examinations on the day of hemodialysis (dialysis day) and the day after hemodialysis (nondialysis day). Standard ultrasound examinations were performed after overnight fasting, immediately after a light meal, and at 6 h after a meal. The antral cross-sectional area and gastric emptying according to the Perlas grading system were evaluated.ResultsCompared with the controls, patients with ESKD, on both dialysis and non-dialysis days, had significantly larger antral areas when examined in the supine position (p = 0.002 and p = 0.003, respectively), but not in the right lateral decubitus position (p = 0.452 and p = 0.512, respectively). In the supine position, the antral area of ESKD patients before dialysis (8 a.m. on the dialysis day) was larger than that at the same time on the nondialysis day (p = 0.028). The controls had a Perlas grade of either 0 or 1 at 6 h after a meal, whereas five patients (13.5%) and 11 patients (29.7%) in the ESKD group had Perlas grade 2 on the dialysis and non-dialysis days, respectively. Among patients with or without delayed gastric emptying, no differences were detected in the dialysis duration or levels of biochemical markers, except blood urea nitrogen (p = 0.038) and serum creatinine (p = 0.003).ConclusionNondiabetic patients with ESKD had significantly delayed gastric emptying. Hemodialysis might improve gastric emptying and reduce gastric emptying delay.     

Effect of pitavastatin on urinary liver-type fatty-acid-binding protein in patients with nondiabetic mild chronic kidney disease

BACKGROUND/AIM: Urinary liver-type fatty-acid-binding protein (L-FABP) is a useful clinical marker in the monitoring of chronic kidney disease (CKD) associated with tubulointerstitial damage. Statins have been shown to be effective in the treatment of renal disease. The aim of the present study was to determine whether pitavastatin, a newly developed statin, modulates the urinary L-FABP levels in normolipidemic patients with CKD. METHODS: Thirty normolipidemic mild CKD patients (18 males and 12 females, mean age 40 years, mean serum creatinine level 1.0 mg/dl) were randomly assigned to two groups: (1) pitavastatin (1 mg/day, n = 15) and (2) placebo (n = 15). Urinary protein and urinary L-FABP levels were measured before the initiation of treatment and 3 and 6 months thereafter. Twenty age-matched healthy subjects were also studied as controls. RESULTS: Before treatment, the urinary L-FABP levels in 30 CKD patients (84.0 +/- 68.5 microg/g creatinine) were significantly higher than those of healthy subjects (6.4 +/- 4.2 mug/g creatinine; p < 0.001). Pitavastatin slightly reduced serum total cholesterol and triglyceride levels, but this was not statistically significant. However, pitavastatin reduced the urinary protein excretion from 1.8 to 1.0 g/day (p < 0.01), while the urinary L-FABP levels fell from 88.5 +/- 70.5 to 28.0 +/- 16.5 mug/g creatinine (p < 0.01). CONCLUSION: The present data suggest that pitavastatin ameliorates tubulointerstitial damage in CKD patients independent of the lipid-lowering effect.     

Darbepoetin alfa administered once monthly maintains hemoglobin concentrations in patients with chronic kidney disease

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin (rHuEPO), but has a three-fold longer serum half-life. Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers. This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease (CKD) not receiving dialysis. METHODS: This study was a multicenter, open-label study of 97 patients with CKD not on dialysis. Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks. The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated. Safety measurements (e.g. adverse events, laboratory parameters, blood pressure) and seroreactivity were assessed. RESULTS: Hemoglobin concentration was maintained within the target range in 79% (95% confidence interval (CI) = 71% to 87%) of all patients receiving darbepoetin alfa and in 85% (95% Cl = 78% - 93%) of patients who completed the study period. The mean +/- standard deviation monthly darbepoetin alfa dose was similar between baseline (88.7 +/- 49.9 microg) and the evaluation period (86.6 +/- 78.8 microg). The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration. CONCLUSION: Patients with CKD who are clinically stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly.     

Association of adiposity with hemoglobin levels in patients with chronic kidney disease not on dialysis

Background

In the general population, adiposity influences erythropoiesis and iron metabolism. We aimed to assess the relationships between adiposity [estimated by body mass index (BMI) and abdominal circumference (AC)] and biomarkers of erythropoiesis in patients with chronic kidney disease (CKD) not on dialysis.

Methods

A total of 2322 patients from the Chronic Kidney Disease Japan Cohort study were included. Patients were grouped according to BMI (low: < 18.5 kg/m², normal: 18.5–24.5 kg/m², and high: ≥ 25 kg/m²) and AC categories (large: ≥ 90 cm for men and ≥ 80 cm for women; small: < 90 cm and < 80 cm, respectively). Body composition and laboratory data were assessed at baseline, and at 1 and 2 years of follow-up.

Results

Multivariate regression analysis of the 3 time-points showed that high BMI and large AC in male patients were significantly associated with higher hemoglobin levels. Hemoglobin levels were lower in female patients with low BMI and small AC than that in female patients with normal BMI and large AC, respectively; however, hemoglobin levels plateaued above a threshold of 25 kg/m² for BMI and 80 cm for AC. While BMI and AC were positively associated with C-reactive protein levels, they were not associated with levels of transferrin saturation, ferritin, and erythropoietin in multivariate models.

Conclusions

Body composition appears to be associated with erythropoiesis; however, adiposity may be only associated with increased erythropoiesis in male patients. In addition, body composition does not appear to hamper iron metabolism in CKD patients not on dialysis.

     

血红蛋白靶目标值对慢性肾脏病患者生存影响的荟萃分析

目的 探讨血红蛋白(Hb)水平对慢性肾脏病(CKD)患者生存时间的影响,为明确CKD患者最佳Hb靶目标值提供参考依据.方法 采用荟萃分析的方法,利用Medline、Embase和Cochrane数据库检索国内外公开发表的有关Hb水平对CKD患者生存影响的临床试验,通过Cochrane协作网提供的Revman软件对检索结果进行荟萃分析.结果 纳入本次荟萃分析的文献共23篇,随访样本总量10 204例.综合分析后发现,与低Hb(Hb＜100 g/L)水平组患者相比,维持高Hb(Hb＞127 g/L)水平可增加患者死亡及发生高血压、中风及住院治疗的风险,相对危险度(RR)值分别为1.10、1.40、1.73和1.07,两组比较差异均有统计学意义(P＜ 0.05).但两组非致命性心肌梗死(RR=1.13,95％CI 0.79～1.62)及肾脏替代治疗(RR=1.00,95％CI 0.85～1.18)的发生率差异均无统计学意义.结论 在纠正CKD患者贫血过程中,维持低Hb水平可以降低患者发生高血压、中风、入院治疗和死亡的风险,但不能改善心肌梗死发生及肾脏替代治疗的风险.     

High-normal albuminuria and incident chronic kidney disease in a male nondiabetic population

Background

High-normal albuminuria is an important risk factor for incident chronic kidney disease in diabetic populations, in contrast to an uncertain association in nondiabetic populations. This study aimed to reveal the relationship between high-normal albuminuria and incident chronic kidney disease in a Japanese nondiabetic population.

Methods

A 10-year follow-up retrospective cohort study was performed involving 1378 Japanese men (mean age 44?±?5.3 years) without chronic kidney disease and diabetes mellitus. Chronic kidney disease was diagnosed as either estimated glomerular filtration rate <?60 mL/min/1.73 m² or a urine albumin-to-creatinine ratio ≥?30 mg/g.

Results

At baseline, age, estimated glomerular filtration rate, and the presence of hematuria, hypertension, and dyslipidemia were independently associated with the albumin-to-creatinine ratio. Among the 1378 participants, 185 (13.4%) fulfilled diagnostic criteria for chronic kidney disease over the 10-year follow-up period. Median annual estimated glomerular filtration rate decline showed a deterioration with increasing quartiles of baseline albumin-to-creatinine ratio (P?=?0.004). Participants who had a baseline albumin-to-creatinine ratio in the highest quartile (5.9–28.9 mg/g) were more likely to develop micro- or macroalbuminuria (odds ratio: 16.23, 95% confidence interval 6.56–54.03), chronic kidney disease (odds ratio: 2.48, 95% confidence interval 1.64–3.82), and hypertension (odds ratio 2.06, 95% confidence interval 1.30–3.31), but not diabetes mellitus compared with those who had an albumin-to-creatinine ratio in the lowest quartile (1.3–3.6 mg/g) after adjustment for potential confounders.

Conclusions

High-normal albuminuria was associated with incident chronic kidney disease in this Japanese nondiabetic male population.