Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease

Summary

Background and objectives

The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients.

Design, setting, participants, & measurements

We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan–Meier survival curves, and time-dependent analysis.

Results

Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality.

Conclusions

Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.     

Síndrome de desgaste proteico energético en la enfermedad renal crónica avanzada: prevalencia y características clínicas específicas

Introduction

Protein-energy wasting (PEW) is associated with increased mortality and differs depending on the chronic kidney disease (CKD) stage and the dialysis technique. The prevalence in non-dialysis patients is understudied and ranges from 0 to 40.8%.

Chronic Kidney Disease Stage Progression in Liver Transplant Recipients

Summary

Background and objectives

There is little information on chronic kidney disease (CKD) stage progression rates and outcomes in liver transplant recipients. Identifying modifiable risk factors may help prevent CKD progression in liver transplant recipients.

Design, setting, participants, & measurements

We performed a retrospective review of 1151 adult, deceased-donor, single-organ primary liver transplants between July 1984 and December 2007 and analyzed kidney outcomes and risk factors for CKD stage progression. Seven hundred twenty-nine patients had an available estimated GFR at 1 year posttransplant to establish a baseline stage. The primary end point was the CKD progression from one stage to a higher stage (lower GFR).

Results

Kaplan–Meier estimates of patient survival were 91%, 74%, and 64% at 5, 10, and 15 years, respectively. Estimates of liver allograft survival were 89%, 71%, and 60% at the same time points. At 1 year, 7%, 34%, 56%, 3%, and 1% of patients were in CKD stages 1, 2, 3, 4, and 5. The incidence of stage progression was 28%, 40%, and 53% at 3, 5, and 10 years. The incidence of ESRD was 2.6%, 7.5%, and 18% at 5, 10, and 20 years. Multivariable Cox regression analyses demonstrated that CKD stage at 1 year, pretransplant diabetes and urinary tract infections/hypercholesterolemia in the first year proved to be independent risk factors for stage progression (hazard ratio 1.9, 0.28, 1.39, and 1.46, respectively, P < 0.05).

Conclusions

Future studies will determine whether treatment of risk factors in the first posttransplant year prevent CKD progression in liver transplant recipients.     

Prognosis of CKD Patients Receiving Outpatient Nephrology Care in Italy

Summary

Background and objectives

Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated.

Design, setting, participants, & measurements

We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach.

Results

Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P < 0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome.

Conclusions

In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population.     

Warfarin in atrial fibrillation patients with moderate chronic kidney disease

Summary

Background and objectives

The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown.

Design, setting, participants, & measurements

Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%).

Results

Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively).

Conclusions

Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.     

Sex Differences in High Sensitivity C-Reactive Protein in Subjects with Risk Factors of Metabolic Syndrome

Background

Metabolic syndrome (MetS) is associated with a higher risk of all-cause mortality. High-sensitivity C-reactive protein (hsCRP) is a prototypic marker of inflammation usually increased in MetS. Women with MetS-related diseases present higher hsCRP levels than men with MetS-related diseases, suggesting sex differences in inflammatory markers. However, it is unclear whether serum hsCRP levels are already increased in men and/or women with MetS risk factors and without overt diseases or under pharmacological treatment.

Objective

To determine the impact of the number of MetS risk factors on serum hsCRP levels in women and men.

Methods

One hundred and eighteen subjects (70 men and 48 women; 36 ± 1 years) were divided into four groups according to the number of MetS risk factors: healthy group (CT; no risk factors), MetS ≤ 2, MetS = 3, and MetS ≥ 4. Blood was drawn after 12 hours of fasting for measurement of biochemical variables and hsCRP levels, which were determined by immunoturbidimetric assay.

Results

The groups with MetS risk factors presented higher serum hsCRP levels when compared with the CT group (p < 0.02). There were no differences in hsCRP levels among groups with MetS risk factors (p > 0.05). The best linear regression model to explain the association between MetS risk factors and hsCRP levels included waist circumference and HDL cholesterol (r = 0.40, p < 0.01). Women with MetS risk factors presented higher hsCRP levels when compared with men (p_sex < 0.01).

Conclusions

Despite the absence of overt diseases and pharmacological treatment, subjects with MetS risk factors already presented increased hsCRP levels, which were significantly higher in women than men at similar conditions.     

Elevated Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Predicts Atherosclerotic Cardiovascular Events in Hemodialysis Patients

Summary

Background and objectives

Dialysis patients show “reverse causality” between serum cholesterol and mortality. No previous studies clearly separated the risk of incident cardiovascular disease (CVD) and the risk of death or fatality after such events. We tested a hypothesis that dyslipidemia increases the risk of incident atherosclerotic CVD and that protein energy wasting (PEW) increases the risk of fatality after CVD events in hemodialysis patients.

Design, setting, participants, & measurements

This was an observational cohort study in 45,390 hemodialysis patients without previous history of myocardial infarction (MI), cerebral infarction (CI), or cerebral bleeding (CB) at the end of 2003, extracted from a nationwide dialysis registry in Japan. Outcome measures were new onsets of MI, CI, CB, and death in 1 year.

Results

The incidence rates of MI, CI, and CB were 1.43, 2.53, and 1.01 per 100 person-years, and death rates after these events were 0.23, 0.21, and 0.29 per 100 person-years, respectively. By multivariate logistic regression analysis, incident MI was positively associated with non-HDL cholesterol (non–HDL-C) and inversely with HDL cholesterol (HDL-C). Incident CI was positively associated with non–HDL-C, whereas CB was not significantly associated with these lipid parameters. Among the patients who had new MI, CI, and/or CB, death risk was not associated with HDL-C or non–HDL-C, but with higher age, lower body mass index, and higher C-reactive protein levels.

Conclusions

In this hemodialysis cohort, dyslipidemia was associated with increased risk of incident atherosclerotic CVD, and protein energy wasting/inflammation with increased risk of death after CVD events.     

Echocardiographic parameters are independently associated with rate of renal function decline and progression to dialysis in patients with chronic kidney disease

Summary

Background and objectives

Cardiac abnormalities were frequently noted in patients with chronic kidney disease (CKD). This study is designed to assess whether echocardiographic parameters are associated with rate of renal function decline and progression to dialysis in CKD stage 3 to 5 patients.

Design, setting, participants, & measurements

This longitudinal study enrolled 415 patients. The renal end point was defined as commencement of dialysis. The change in renal function was measured by estimated GFR (eGFR) slope.

Results

Progression to dialysis was predicted by wide pulse pressure, low albumin, low hemoglobin, high calcium-phosphorous product, proteinuria, diuretics use, and concentric left ventricular hypertrophy (LVH) (hazard ratio, 2.03; 95% confidence interval [CI], 1.00 to 4.10; P = 0.05). The eGFR slope was negatively associated with total cholesterol, uric acid, proteinuria, diuretics use, and left atrial (LA) diameter (change in slope, −0.50; 95% CI, −0.89 to −0.11; P = 0.01) and positively associated with albumin and left ventricular ejection fraction (LVEF) (change in slope, 0.06; 95% CI, 0.03 to 0.08; P < 0.001).

Conclusions

Our study in patients of CKD stage 3 to 5 demonstrated that concentric LVH was associated with progression to dialysis, and that increased LA diameter and decreased LVEF were associated with faster renal function decline. Echocardiography may help identify high-risk groups with progressive decline in renal function to dialysis and rapid progression of renal dysfunction in CKD stage 3 to 5 patients.     

Upper Gastrointestinal Bleeding in Patients with CKD

Background and objectives

Patients with CKD receiving maintenance dialysis are at risk for upper gastrointestinal bleeding. However, the risk of upper gastrointestinal bleeding in patients with early CKD who are not receiving dialysis is unknown. The hypothesis was that their risk of upper gastrointestinal bleeding is negatively linked to renal function. To test this hypothesis, the association between eGFR and risk of upper gastrointestinal bleeding in patients with stages 3–5 CKD who were not receiving dialysis was analyzed.

Design, setting, participants, & measurements

Patients with stages 3–5 CKD in the CKD program from 2003 to 2009 were enrolled and prospectively followed until December of 2012 to monitor the development of upper gastrointestinal bleeding. The risk of upper gastrointestinal bleeding was analyzed using competing-risks regression with time-varying covariates.

Results

In total, 2968 patients with stages 3–5 CKD who were not receiving dialysis were followed for a median of 1.9 years. The incidence of upper gastrointestinal bleeding per 100 patient-years was 3.7 (95% confidence interval, 3.5 to 3.9) in patients with stage 3 CKD, 5.0 (95% confidence interval, 4.8 to 5.3) in patients with stage 4 CKD, and 13.9 (95% confidence interval, 13.1 to 14.8) in patients with stage 5 CKD. Higher eGFR was associated with a lower risk of upper gastrointestinal bleeding (P=0.03), with a subdistribution hazard ratio of 0.93 (95% confidence interval, 0.87 to 0.99) for every 5 ml/min per 1.73 m² higher eGFR. A history of upper gastrointestinal bleeding (P<0.001) and lower serum albumin (P=0.004) were independently associated with higher upper gastrointestinal bleeding risk.

Conclusions

In patients with CKD who are not receiving dialysis, lower renal function is associated with higher risk for upper gastrointestinal bleeding. The risk is higher in patients with previous upper gastrointestinal bleeding history and low serum albumin.     

Estimated Glomerular Filtration Rate Is a Poor Predictor of Concentration for a Broad Range of Uremic Toxins

Summary

Background and objectives

The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD.

Design, setting, participants, & measurements

Associations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas.

Results

There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR > 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R² values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R² are mainly due to discrepancies in solute handling apart from GFR.

Conclusions

eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.     

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.     

Chronic kidney disease and coronary artery vulnerable plaques

Summary

Background and objectives

Chronic kidney disease (CKD) is a risk factor of cardiovascular disease. The number of yellow plaques is a predictor of future cardiovascular events. We assumed that CKD might raise the risk of cardiovascular events by increasing the number of yellow plaques. Therefore, we compared the number of yellow plaques between patients with and without CKD.

Design, setting, participants, & measurements

Consecutive 136 patients with acute myocardial infarction who received percutaneous coronary intervention (PCI) and angioscopic examination were analyzed. The infarct-related artery was angioscopically examined. The number of yellow plaques, maximum yellow color grade of detected yellow plaques, and prevalence of disrupted yellow plaques in nonculprit segments were compared between patients with and without CKD.

Results

The number of yellow plaques was significantly larger in CKD than in non-CKD patients (median [interquartile range]: 4.0 [2.0 to 6.0] versus 2.0 [1.0 to 4.0], P = 0.001). Maximum yellow color grade and prevalence of disrupted plaques in the nonculprit segments were not different between patients with and without CKD. Multivariate logistic regression analysis revealed CKD as an independent risk of multiple yellow plaques per vessel (odds ratio 3.49, 95% confidence interval 1.10 to 11.10, P = 0.03).

Conclusion

CKD was an independent risk factor of multiple coronary yellow plaques, suggesting that patients with CKD would have a higher risk of coronary events because they had more yellow plaques than patients without CKD.     

Presence and Outcomes of Kidney Disease in Patients with Pulmonary Hypertension

Background and objectives

Pulmonary hypertension is associated with higher mortality rates. The associations of nondialysis-dependent CKD and all-cause mortality in patients with pulmonary hypertension were studied.

Design, setting, participants, & measurements

The study population included those patients who underwent right heart catheterization for confirmation of pulmonary hypertension between 1996 and January 2011. Pulmonary hypertension was defined as the presence of mean pulmonary artery pressure≥25 mmHg at rest measured by right heart catheterization. CKD was defined as the presence of two measurements of eGFR<60 ml/min per 1.73 m² 90 days apart. The risk factors associated with CKD as well as the association between CKD and death in those patients with pulmonary hypertension using logistic regression and Cox proportional hazard models were examined.

Results

Of 1088 patients with pulmonary hypertension, 388 (36%) patients had CKD: 340 patients had stage 3 CKD, and 48 (4%) patients had stage 4 CKD. In the multivariable analysis, older age, higher hemoglobin, and higher mean right atrial pressures were independently associated with CKD. During a median follow-up of 3.2 years (interquartile range=1.5–5.6 years), 559 patients died. After adjusting for relevant covariates, presence of stage 3 CKD (hazard ratio, 1.37; 95% confidence interval, 1.14 to 1.66) and stage 4 CKD (hazard ratio, 2.69; 95% confidence interval, 1.88 to 3.86) was associated with all-cause mortality in those patients with pulmonary hypertension. When eGFR was examined as a continuous measure, a 5 ml/min per 1.73 m² lower eGFR was associated with a 5% (95% confidence interval, 1.03 to 1.07) higher hazard for death. This higher risk with CKD was similar irrespective of demographics, left ventricular function, and pulmonary capillary wedge pressure.

Conclusion

In a clinical population referred for right heart catheterization, presence of CKD was associated with higher all-cause mortality in those patients with pulmonary hypertension. Mechanisms that may underlie these associations warrant additional studies.     

Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease

Summary

Background and objectives

Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD).

Design, setting, participants, & measurements

In 48 stage 2 to 4 CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry.

Results

CKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r = 0.32, P = 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P < 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P = 0.003) in a model including the same covariates.

Conclusions

Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients.     

Patterns and Prognostic Value of Total and Differential Leukocyte Count in Chronic Kidney Disease

Summary

Background and objectives

The purpose of this study was to evaluate the levels and patterns of total and differential leukocyte counts and their prognostic importance in a cohort of people with and without chronic kidney disease (CKD).

Design, setting, participants, & measurements

Among 153 veterans without CKD and 267 with, blood leukocyte count was measured at baseline and then repeatedly over a decade. The patterns of change in leukocyte count between the two groups were compared. In the CKD cohort, the spikes in leukocyte counts were compared to the combined endpoint of ESRD and death.

Results

Patients with CKD had more granulocytes and eosinophils and fewer lymphocytes. Over time, granulocytes increased and lymphocytes decreased in those with and without CKD. In addition, in those with CKD, over time eosinophils fell and monocytes increased. Compared with their non-CKD counterparts, patients with CKD had between 1.5- and 3.0-fold more spikes in leukocyte counts. Independent risk factors for the combined endpoint were associated with spikes in the leukocyte counts of absolute and percent eosinophil count, percent granulocyte, and percent monocyte counts. In a multivariate adjusted joint model, both granulocyte and monocyte spikes were independently associated with ESRD and death (hazard ratio 1.67 and 1.52 respectively, P < 0.05).

Conclusions

Compared with those without CKD, patients with CKD have more eosinophils and granulocytes and fewer lymphocytes. Greater variation in leukocytes is seen. Spikes in granulocyte and monocyte percentages among patients with CKD are of independent prognostic importance.     

Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKD

Background and objectives

Ultrasonographic detection of subclinical atheromatosis is a noninvasive method predicting cardiovascular events. Risk factors predicting atheromatosis progression in CKD are unknown. Predictors of atheromatosis progression were evaluated in patients with CKD.

Design, setting, participants, & measurements

Our multicenter, prospective, observational study included 1553 patients with CKD (2009–2011). Carotid and femoral ultrasounds were performed at baseline and after 24 months. A subgroup of 476 patients with CKD was also randomized to undergo ultrasound examination at 12 months. Progression of atheromatosis was defined as an increase in the number of plaque territories analyzed by multivariate logistic regression.

Results

Prevalence of atheromatosis was 68.7% and progressed in 59.8% of patients after 24 months. CKD progression was associated with atheromatosis progression, suggesting a close association between pathologies. Variables significantly predicting atheromatosis progression, independent from CKD stages, were diabetes and two interactions of age with ferritin and plaque at baseline. Given that multiple interactions were found between CKD stage and age, phosphate, smoking, dyslipidemia, body mass index, systolic BP (SBP), carotid intima-media thickness, plaque at baseline, uric acid, cholesterol, 25-hydroxy vitamin D (25OH vitamin D), and antiplatelet and phosphate binders use, the analysis was stratified by CKD stages. In stage 3, two interactions (age with phosphate and plaque at baseline) were found, and smoking, diabetes, SBP, low levels of 25OH vitamin D, and no treatment with phosphate binders were positively associated with atheromatosis progression. In stages 4 and 5, three interactions (age with ferritin and plaque and plaque with smoking) were found, and SBP was positively associated with atheromatosis progression. In dialysis, an interaction between body mass index and 25OH vitamin D was found, and age, dyslipidemia, carotid intima-media thickness, low cholesterol, ferritin, and uric acid were positively associated with atheromatosis progression.

Conclusions

Atheromatosis progression affects more than one half of patients with CKD, and predictive factors differ depending on CKD stage.     

Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus

Summary

Background and objectives

Prior studies have examined long-term outcomes of a single acute kidney injury (AKI) event in hospitalized patients. We examined the effects of AKI episodes during multiple hospitalizations on the risk of chronic kidney disease (CKD) in a cohort with diabetes mellitus (DM).

Design, setting, participants, & measurements

A total of 4082 diabetics were followed from January 1999 until December 2008. The primary outcome was reaching stage 4 CKD (GFR of <30 ml/min per 1.73 m²). AKI during hospitalization was defined as >0.3 mg/dl or a 1.5-fold increase in creatinine relative to admission. Cox survival models examined the effect of first AKI episode and up to three episodes as time-dependent covariates, on the risk of stage 4 CKD. Covariates included demographic variables, baseline creatinine, and diagnoses of comorbidities including proteinuria.

Results

Of the 3679 patients who met eligibility criteria (mean age = 61.7 years [SD, 11.2]; mean baseline creatinine = 1.10 mg/dl [SD, 0.3]), 1822 required at least one hospitalization during the time under observation (mean = 61.2 months [SD, 25]). Five hundred thirty of 1822 patients experienced one AKI episode; 157 of 530 experienced ≥2 AKI episodes. In multivariable Cox proportional hazards models, any AKI versus no AKI was a risk factor for stage 4 CKD (hazard ratio [HR], 3.56; 95% confidence interval [CI], 2.76, 4.61); each AKI episode doubled that risk (HR, 2.02; 95% CI, 1.78, 2.30).

Conclusions

AKI episodes are associated with a cumulative risk for developing advanced CKD in diabetes mellitus, independent of other major risk factors of progression.     

Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Chronic Kidney Disease and Hemodialysis

Summary

Background and objectives

Sleep-disordered breathing (SDB) and excessive daytime sleepiness (EDS) are highly prevalent among hemodialysis (HD) patients. It is unclear to what extent SDB is associated with advanced chronic kidney disease (CKD; stages 4 to 5). This paper describes and compares the prevalence, severity, and patterns of SDB and EDS among patients with advanced CKD, HD-dependent patients, and community individuals without known renal disease.

Design, setting, participants, & measurements

Eighty-nine CKD and 75 HD patients were compared with 224 participants from the Sleep-Strategies Concentrating on Risk Evaluation Sleep-SCORE study of sleep and cardiovascular risk. Participants had in-home unattended polysomnography for quantifying SDB. EDS was defined by a score ≥10 on the Epworth Sleepiness Scale.

Results

The sample had a median age 58.1 years, was predominantly male (57.4%) and white (62.5%), and had a median body mass index of 28.1 kg/m². Controls and Sleep-SCORE Study CKD patients had significantly higher median total sleep time and sleep efficiency compared with HD patients. The adjusted odds of severe SDB were higher for CKD and HD groups compared with the controls. Nocturnal hypoxemia was significantly elevated in the HD group compared with the CKD group. There were similar proportions of participants with EDS between the controls (33%), the CKD patients (29.3%), and the HD patients (40.6%).

Conclusions

Severe SDB (predominantly obstructive) and EDS are common among advanced CKD and HD patients. EDS correlated modestly with severe SDB and its obstructive and mixed patterns in the HD group.     

Bone mineral densities in individuals with Gilbert’s syndrome: A cross-sectional,case-control pilot study

BACKGROUND

Unconjugated bilirubin inhibits osteoblastic proliferative activity in vitro, raising the possibility that Gilbert’s syndrome (GS) patients are at increased risk of osteoporosis.

OBJECTIVES

To compare bone mineral density (BMD), serum parathyroid hormone (PTH), C-telopeptide (CTX) and osteocalcin levels in GS subjects versus matched controls in a cross-sectional, case-control study.

METHODS

BMD determinations were obtained with central dual-energy x-ray absorptiometry. Serum PTH, CTX and osteocalcin levels were measured by enzyme immunoassay.

RESULTS

A total of 17 GS and 30 control subjects were studied. Overall, there were no significant differences in BMD, PTH, CTX or osteocalcin levels between the two groups. However, when older (older than 40 years of age) and younger (40 years of age and younger) cohorts were considered separately, the older GS cohort had significantly decreased total hip BMD, T scores and Z scores, and femoral neck BMD, T scores and Z scores (P<0.005 for each parameter, respectively) compared with older control subjects. Serum osteocalcin levels were lower in the older versus younger GS cohort (P=0.006). An inverse correlation existed between all subjects’ serum unconjugated bilirubin levels and total body BMD determinations (r=−0.42; P=0.04). On univariate analysis, the association between serum unconjugated bilirubin and total body BMD was not significant (P=0.066), nor was serum unconjugated bilirubin identified as a risk factor for low BMD when entered into multivariate analyses.

CONCLUSIONS

The results of the present pilot study warrant further research involving larger numbers of subjects and longitudinal measurements to determine whether GS is associated with decreased BMD, particularly in older GS subjects.     

Vision-Threatening Retinal Abnormalities in Chronic Kidney Disease Stages 3 to 5

Summary

Background and objectives

Retinal abnormalities are common in inherited and acquired renal disease. This study determined the prevalence of retinal abnormalities in chronic kidney disease (CKD) stages 3 to 5.

Design, setting, participants, & measurements

One hundred fifty patients with CKD stages 3 to 5 and 150 age- and gender-matched hospital patients with CKD stages 1 to 2 underwent bilateral retinal photography. These images were reviewed for incidental abnormalities, microvascular (Wong and Mitchell classification) and diabetic retinopathy (Airlie House criteria), and macular degeneration (Seddon classification).

Results

Three (2%) patients with CKD stages 3 to 5 had retinal features characteristic of inherited renal disease (atrophy in Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes [MELAS] syndrome; and 2 with drusen in dense deposit disease). Fifty-nine (39%) patients had moderate-severe microvascular retinopathy (hemorrhages, exudates, etc.) compared with 19 (13%) with CKD stages 1 to 2. Forty-one (28%) had moderate-severe diabetic retinopathy (microaneurysms, exudates, etc.) compared with 16 (11%) with CKD stages 1 to 2. Ten (7%) had severe macular degeneration (geographic atrophy, hemorrhage, exudates, membranes) compared with one (1%) with CKD stages 1 to 2. Renal failure was an independent risk factor for microvascular retinopathy, diabetic retinopathy, and macular degeneration. Eleven (7.3%) patients with renal failure and one (0.7%) with CKD stages 1 to 2 had previously unrecognized vision-threatening retinal abnormalities that required immediate ophthalmologic attention.

Conclusions

Retinal abnormalities are common in CKD stages 3 to 5, and are more severe and more likely to threaten vision than in hospital patients with CKD stages 1 to 2.