Anemia as a risk factor for chronic kidney disease

Chronic kidney disease (CKD) is an important and leading cause of end-stage renal disease (ESRD) and moreover, plays a role in the morbidity and mortality due to cardiovascular disease, infection, and cancer. Anemia develops during the early stages of CKD and is common in patients with ESRD. Anemia is an important cause of left ventricular hypertrophy and congestive heart failure. Correction of anemia by erthyropoiesis-stimulating agent (ESA) has been shown to improve survival in patients with congestive heart failure. Anemia is counted as one of the non-conventional risk factors associated with CKD. Hypoxia is one of the common mechanisms of CKD progression. Treatment by ESA is expected to improve quality of life, survival, and prevent the CKD progression. Several clinical studies have shown the beneficial effects of anemia correction on renal outcomes. However, recent prospective trials both in ESRD and in CKD stages 3 and 4 failed to confirm the beneficial effects of correcting anemia on survival. Similarly, treatment of other risk factors such as hyperlipidemia by statin showed no improvement in the survival of dialysis patients. Given the high prevalence of anemia in ESRD and untoward effects of anemia in CKD stages 3 and 4, appropriate and timely intervention on renal anemia using ESA is required for practicing nephrologists and others involved in the care of high-risk population. Lessons from the recent studies are to correct renal anemia (hemoglobin <10 g/dl not hemoglobin > or =13 g/dl). Early intervention for renal anemia is a part of the treatment option in the prevention clinic. In this study, clinical significance of anemia management in patients with CKD is discussed.     

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.     

Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study

In animal models, inflammatory processes have been shown to have an important role in the development of kidney disease. In humans, however, the independent relation between markers of inflammation and the risk of chronic kidney disease (CKD) is not known. To clarify this, we examined the relationship of several inflammatory biomarker levels (high-sensitivity C-reactive protein, tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6) with the risk of developing CKD in a population-based cohort of up to 4926 patients with 15 years of follow-up. In cross-sectional analyses, we found that all these inflammation markers were positively associated with the outcome of interest, prevalent CKD. However, in longitudinal analyses examining the risk of developing incident CKD among those who were CKD-free at baseline, only tumor necrosis factor-α receptor 2, white blood cell count, and interleukin-6 levels (hazard ratios comparing highest with the lowest tertile of 2.10, 1.90, and 1.45, respectively), and not C-reactive protein (hazard ratio 1.09), were positively associated with incident CKD. Thus, elevations of most markers of inflammation predict the risk of developing CKD. Each marker should be independently verified.     

Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort

Background Disturbances in lipid metabolism are often observed in patients with renal failure and could be a risk factor for end-stage renal disease (ESRD). However, few studies have examined abnormal lipid metabolism as a risk factor for the development of ESRD in the general population.Methods We examined the cumulative incidence of ESRD based on the results of a community-based mass screening in Okinawa, Japan, which was conducted in 1993 by the Okinawa General Health Maintenance Association. Screenees who developed ESRD by the end of 2000 were identified through the Okinawa Dialysis Study registry.Results Total cholesterol (TC) data were available for 133338 (92.6%) of the total 143948 screenees) and triglyceride (TG) data were available for 132094 (91.8%). Dyslipidemia was defined as TC 220mg/dl or TG 150mg/dl. The cumulative incidences of ESRD, per 1000 screenees, were 1.12 for those without dyslipidemia and 2.53 for those with dyslipidemia. The adjusted hazard ratio (95% confidence interval) for dyslipidemia was 0.856 (0.484–1.516) for men and 1.260 (0.661–2.400) for women; neither was significant when adjustment was made for age, systolic blood pressure, diastolic blood pressure, body mass index, creatinine clearance, diabetes mellitus, and proteinuria.Conclusions The present study showed dyslipidemia to be an insignificant predictor of development of ESRD in the general Okinawa population.     

Anemia as a risk factor for all-cause mortality: obscure synergic effect of chronic kidney disease

Background

Anemia is common in chronic kidney disease (CKD) and may be associated with mortality in CKD patients. However, few studies have examined this relationship in Asian populations.

Methods

A total of 62,931 Japanese people (age 64.0 ± 8.0 years; men 38.5%) were followed up from 2008 to 2012. Participants were divided into six groups in accordance with their estimated glomerular filtration rate (eGFR) (<45, 45–59, ≥60 mL/min/1.73 m²) and by hemoglobin levels (13.0 g/dL for men; 12.0 g/dL for women). Hazard ratio and confidence interval (CI) for mortality with a combination of eGFR and anemia were calculated. After matching using propensity score (PS) for anemia, survival analysis between anemic and non-anemic people, independent from some variables, including eGFR, was performed.

Results

A total of 828 (1.3%) participants died (non-anemic vs. anemic, 1.2 vs. 2.3%, p < 0.01). Multivariable Cox analysis showed that, independent of eGFR levels, anemic people had significantly higher mortality. Anemic people were found to have significantly poorer survival than non-anemic people as per a log-rank test (p < 0.01) for the PS-matching cohort. Further stratified logistic analysis using PS in the overall cohort odds ratio (95% CI) showed 2.25 (1.89–2.67) with p < 0.01.

Conclusion

The results of the present study showed that anemia was an independent risk factor of all-cause mortality.

     

The longitudinal chronic kidney disease study: a prospective cohort study of predialysis renal failure

Chronic kidney disease (CKD) is a significant public health problem: every year the number of Americans living with CKD and requiring renal replacement therapy increases. In addition, individuals with CKD have substantially increased morbidity and mortality compared to the general population. The Longitudinal Chronic Kidney Dialysis (LCKD) Study is a multicenter, prospective, observational study of patients with moderate to severe CKD that was designed to better describe the course of the disease and the determinants of patient outcomes. Patients with moderate to severe CKD (glomerular filtration rate [GFR] < 60 ml/min/m2) from four academic nephrology clinics were enrolled between 2000 and 2002. Special cardiac and vascular testing has recently commenced as phase II of this study. Areas that have been or are currently being studied include anemia management, health-related quality of life (HRQOL), medication use, and markers of cardiovascular disease. This article describes the LCKD Study in the context of current knowledge of CKD.     

Fructose intake as a risk factor for kidney stone disease

Taylor and Curhan report that consumption of fructose is independently associated with an increased risk of incident kidney stones. What could be the mechanisms underlying the relation between fructose intake and stone risk? And how should we incorporate this finding into the dietary advice that we give to our patients to prevent kidney stone formation?     

Anemia as a risk factor for cardiovascular disease and all-cause mortality in diabetes: the impact of chronic kidney disease

Anemia is a potential nontraditional risk factor for cardiovascular disease (CVD). This study evaluated whether anemia is a risk factor for adverse outcomes in people with diabetes and whether the risk is modified by the presence of chronic kidney disease (CKD). Persons with diabetes from four community-based studies were pooled: Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Anemia was defined as a hematocrit <36% in women and <39% in men. CKD was defined as an estimated GFR of 15 to 60 ml/min per 1.73 m(2). Study outcomes included a composite of myocardial infarction (MI)/fatal coronary heart disease (CHD)/stroke/death and each outcome separately. Cox regression analysis was used to study the effect of anemia on the risk for outcomes after adjustment for potential confounders. The study population included 3015 individuals: 30.4% were black, 51.6% were women, 8.1% had anemia, and 13.8% had CKD. Median follow-up was 8.6 yr. There were 1215 composite events, 600 MI/fatal CHD outcomes, 300 strokes, and 857 deaths. In a model with a CKD-anemia interaction term, anemia was associated with the following hazard ratios (95% confidence intervals) in patients with CKD: 1.70 (1.24 to 2.34) for the composite outcome, 1.64 (1.03 to 2.61) for MI/fatal CHD, 1.81 (0.99 to 3.29) for stroke, and 1.88 (1.33 to 2.66) for all-cause mortality. Anemia was not a risk factor for any outcome in those without CKD (P > 0.2 for all outcomes). In persons with diabetes, anemia is primarily a risk factor for adverse outcomes in those who also have CKD.     

Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies

Chronic kidney disease (CKD) is a major public health problem. Conflicting evidence exists among community-based studies as to whether CKD is an independent risk factor for adverse cardiovascular outcomes. After subjects with a baseline history of cardiovascular disease were excluded, data from four publicly available, community-based longitudinal studies were pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels were indirectly calibrated across studies. CKD was defined by a GFR between 15 and 60 ml/min per 1.73 m(2). A composite of myocardial infarction, fatal coronary heart disease, stroke, and death was the primary study outcome. Cox proportional hazards models were used to adjust for study, demographic variables, educational status, and other cardiovascular risk factors. The total population included 22,634 subjects; 18.4% of the population was black, and 7.4% had CKD. There were 3262 events. In adjusted analyses, CKD was an independent risk factor for the composite study outcome (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.32), and there was a significant interaction between kidney function and race. Black individuals with CKD had an adjusted HR of 1.76 (95% CI, 1.35-2.31), whereas whites had an adjusted HR of 1.13 (95% CI, 1.02-1.26). CKD is a risk factor for the composite outcome of all-cause mortality and cardiovascular disease in the general population and a more pronounced risk factor in blacks than in whites. It is hypothesized that this effect may be due to more frequent or more severe subclinical vascular disease secondary to hypertension or diabetes in black individuals.     

Acute kidney injury as a risk factor for chronic kidney diseases in disadvantaged populations

Acute kidney injury (AKI) is considered to be a potential cause for developing chronic kidney disease (CKD); on the other hand, CKD predisposes to AKI. The lack of adequate epidemiological data makes it difficult to determine if AKI induces CKD in less developed countries. The etiology of AKI in rich populations, in whom sophisticated surgery, interventional radiology and oncology treatments are usually the cause of AKI, is very different from that of disadvantaged populations, where the origin of AKI is associated with endemic infections, obstetric problems, poisons, toxins and natural disasters. Any conclusions extrapolated from these two settings should be treated with caution. Moreover, people living in disadvantaged conditions are usually much younger than those in rich areas and this age factor could facilitate total recovery of renal function after AKI if treatment based on an adequate supply of water, rehydration and anti-infectious measures were provided. In the small segment of the population of less developed countries having an income per capita similar to that observed in the developed countries, the long-term outcome of AKI should also be expected to be similar. New data coming from two single centers analyzing only the long-term outcome of acute tubular necrosis (ATN) patients, with a normal or near normal renal function prior to the AKI episode, coincide in reporting a requirement for chronic dialysis among the surviving patients of 2%. If these data are confirmed, the importance of AKI as cause of CKD should be reconsidered, both in developed and less developed countries.     

Chronic kidney disease as a risk factor for Clostridium difficile infection

Introduction: Clostridium difficile‐associated diarrhoea (CDAD) is the most common cause of nosocomial diarrhoea in the USA. In this study, we sought to determine the association between chronic kidney disease (CKD) and CDAD. Methods: A case–control study was designed to determine the association between CKD and CDAD in an urban hospital. Over a 2‐year period, all patients diagnosed with CDAD (n = 188) were included as cases and the prevalence of CKD was calculated. Age‐ and sex‐matched patients without CDAD were considered as controls with a ratio of 2:1 controls to cases. The prevalence of different stages of advanced CKD (stages 3–5) was determined and compared between groups. Also the calculated odds ratios (OR) were adjusted for multiple possible confounding variables using logistic regression analysis. Results: There was no significant difference in prevalence of advanced CKD between cases and controls (OR = 1.38, 95% confidence intervals (CI) = 0.90–2.12, P = 0.1365). The association between CKD and CDAD remained insignificant in subjects with CKD stages 3–5 who were not on dialysis (OR = 1.07, 95% CI = 0.65–1.77), P = 0.7970). However, the group with end‐stage renal disease on dialysis showed a significant association (OR = 2.60, 95% CI = 1.25–5.41, P = 0.0165). Controlling for antibiotics as a possible confounding variable, yielded an OR that was not statistically significant (OR = 2.05, 95% CI = 0.94–4.47, P = 0.07), but still showing a trend towards increased risk. Conclusion: End‐stage renal disease may increase the risk of acquiring CDAD through unknown mechanisms. This suggests implementing better surveillance strategies for these patients and eliminating the known risk factors for CDAD.     

Former smoking is a risk factor for chronic kidney disease after lung transplantation

Chronic kidney disease (CKD) is a common complication after lung transplantation (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking cessation for >6 months is required for LTx enlistment. However, the impact of smoking history on CKD development after LTx remains unclear. We investigated the effect of former smoking on CKD and mortality after LTx. CKD was based on glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was measured before and repeatedly after LTx. One hundred thirty-four patients never smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5 years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were 68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]= 1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR = 0.99 [0.71-1.38]). Adjustment for potential confounders did not change results. Thus, despite cessation, smoking history remained a risk factor for CKD in LTx recipients. Considering the increasing acceptance for LTx of older recipients with lower baseline renal function and an extensive smoking history, our data suggest that the problem of post-LTx CKD may increase in the future.     

Stabilization of glomerular filtration rate in advanced chronic kidney disease: a two-year follow-up of a cohort of chronic kidney disease patients stages 4 and 5

This study examines whether stabilization of the glomerular filtration rate (GFR) is possible in patients with advanced chronic kidney disease (CKD), managed in a CKD clinic. A cohort of 82 patients with stages 4 and 5 CKD was followed for a period of 2 years after initiation of erythropoietin for anemia to determine the GFR and the frequency of primary outcomes (dialysis, transplantation, or death). GFR, calculated by the abbreviated Modification of Diet in Renal Disease formula, was determined every 3 months. After 24 months, 35 subjects (43%) developed a primary outcome. Controlled for other risk factors, the risk of having a primary outcome increased 19.7% for every unit that the GFR decreased (95% confidence interval [CI], 11.9%-26.8%, P < .001) and decreased 21.7% for every unit that the hemoglobin increased (95% CI, 0.5%-38.4%, P < .001). Blacks had a 3.1 times higher risk (95% CI, 1.4-6.9, P = .006) of developing a primary outcome than other ethnicities. In subjects who did not develop primary outcomes (n = 47 or 57%), GFR remained unchanged (19.5 +/- 9.1 at the end of the study v 20.8 +/- 5.3 mL/min/1.73 m(2) at baseline, P = .16). The standardized mortality rate was 4.75 and 9.77 per 100 person-year for stages 4 and 5, respectively. We conclude that stabilization of GFR over a 2-year period can be achieved in many patients with advanced CKD treated with erythropoietin in a CKD clinic. Although the precise reason for the stabilization of GFR cannot be elucidated from this study, our data are "proof of concept" that CKD outcomes can be improved in a CKD clinic setting.