Outcomes Associated with Race in Males with Nondialysis-Dependent Chronic Kidney Disease

Background and objectives: Blacks are over-represented among dialysis patients, but they have better survival rates than whites. It is unclear if the over-representation of blacks on dialysis is due to faster loss of kidney function or greater survival (or both) in predialysis stages of chronic kidney disease (CKD).Design, setting, participants & measurements: We compared predialysis mortality, incidence of end stage renal disease (ESRD), and slopes of estimated GFR (eGFR) in 298 black versus 945 white male patients with moderate and advanced nondialysis-dependent CKD (NDD-CKD) from a single medical center. Mortality and ESRD incidence were compared in parametric survival models, and slopes of eGFR were assessed in mixed-effects models.Results: Blacks had lower crude mortality and higher crude ESRD incidence. The lower mortality in blacks was explained by differences in case mix, especially a lower prevalence of cardiovascular disease, and the higher incidence of ESRD was explained by differences in case mix and baseline kidney function. The slopes of eGFR were similar in blacks and whites.Conclusions: Lower mortality in black versus white patients is also observed in NDD-CKD and can be accounted for by differences in clinical characteristics. Higher mortality of black patients in earlier stages of CKD may result in the selection of a subgroup with fewer comorbidities and better survival in later stages of CKD. The higher crude ESRD rate in blacks appears to result from lower mortality in late stages of CKD, not faster progression of CKD.Among individuals with chronic kidney disease (CKD) receiving maintenance dialysis therapy, the proportion of black patients is significantly higher compared with their white counterparts (1,2). This can be explained by various factors (1): higher incidence of CKD in blacks (2), lower mortality rates in blacks with nondialysis-dependent CKD (NDD-CKD) (3), lower transplantation rates in blacks (4), and faster rates of CKD progression leading to higher end-stage renal disease (ESRD) incidence.Previous studies have suggested that there was a higher population prevalence of CKD (3) or a faster rate of CKD progression in blacks (4). It is unclear, however, if differences in survival between black and white persons with moderate and advanced NDD-CKD can also have an impact on the higher ESRD incidence recorded in blacks. Because mortality and ESRD are competing end-points in NDD-CKD, lower mortality rates in blacks could inflate their ESRD rates independent of any differences in the prevalence or the progression of their kidney disease. Studies examining race-related survival have found paradoxically lower mortality in blacks compared with whites among dialysis patients (5–12), as opposed to the higher mortality seen in blacks with normal kidney function or mild to moderate CKD (13–17).There have been no studies to examine race-related survival and progression of CKD concomitantly in patients with moderate and advanced NDD-CKD. Such studies could provide important information to guide future allocation of resources into areas that promise to best address the reasons behind the discrepant outcomes of racial minorities in the United States. To discern the relative contributions of differences in mortality and CKD progression to race-related outcomes, we examined all-cause mortality, ESRD incidence, and progression of CKD (defined as slopes of estimated GFR [eGFR]) concomitantly in an unselected group of 1243 male veterans with moderate and advanced NDD-CKD from a single medical center.     

Serum Indoxyl Sulfate Is Associated with Vascular Disease and Mortality in Chronic Kidney Disease Patients

Background and objectives: As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients.Design, setting, participants, & measurements: One-hundred and thirty-nine patients (mean ± SD age: 67 ± 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled.Results: Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 ± 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification.Conclusions: The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.Cardiovascular disease (CVD) mortality is significantly higher in patients with chronic kidney disease (CKD) than in the general population (1,2). Vascular calcification and arterial stiffness are considered to be major contributors to this elevated mortality (3). The pathophysiology of CVD in a CKD setting is not completely understood; in addition to the traditional CVD risk factors, uremia-related elements play an important role. Although these elements may differ from one individual to another, the accumulation of toxic compounds is a common scenario in CKD. These compounds are classified according to their molecular weight and protein binding ability and several have been shown to exert adverse biologic effects and thus enhance the potential for cardiovascular damage (4). Interestingly, we recently observed that cardiac and aortic abnormalities were independently associated with the extent of endothelial dysfunction and renal failure in a mouse model of CKD (5), corroborating the hypothesis whereby the accumulation of uremic toxins is involved in the development of CKD-related cardiovascular abnormalities.Indoxyl sulfate (IS) is a protein-bound uremic toxin that results from the metabolism of dietary tryptophan. Briefly, tryptophan is metabolized into indole by intestinal bacteria and after intestinal absorption is further converted to IS in the liver. The kidneys excrete the toxin via proximal tubular secretion. Consequently, IS accumulates in the blood of patients with impaired renal function. Moreover, IS cannot be efficiently removed by conventional hemodialysis because of its high binding affinity for albumin (6). The role of IS as a uremic toxin was first revealed by its accelerating effects on the progression of CKD (7). Recently, it has been reported that IS may also act as a vascular toxin. In endothelial cells, IS has been shown to (1) induce oxidative stress by modifying the balance between pro- and antioxidant mechanisms (8), (2) stimulate the release of endothelial microparticles (9), and (3) blunt endothelial healing ability (10). Furthermore, IS directly stimulates rat vascular smooth muscular cell proliferation in a concentration-dependent manner (11). Accordingly, increased aortic wall thickness and severe aortic calcification with colocalization of osteoblast-specific proteins (e.g., Cbfa-1, osteopontin, and alkaline phosphatase) were observed in Dahl salt-sensitive, hypertensive rats to which IS was administered (12). These findings suggest that IS may play a role in vascular dysfunction in CKD patients.To investigate this hypothesis, we assessed serum IS levels, aortic calcification, and vascular stiffness (as measured by pulse wave velocity, PWV) in a cohort of CKD patients. We further examined whether IS levels might predict mortality in this population.     

Nonprogressive Kidney Dysfunction and Outcomes in Older Adults with Chronic Kidney Disease

OBJECTIVES: To determine whether a subgroup of patients with severe but nonprogressive renal dysfunction exist and to characterize this subgroup. DESIGN: Retrospective longitudinal monocentric cohort study. SETTING: Nephrology clinic for chronic kidney disease (CKD). PARTICIPANTS: Between January 1998 and December 2004, 177 consecutive patients aged 80 and older were referred for the first time to nephrology for CKD. MEASUREMENTS: The characteristics of patients with nonprogressive or progressive CKD (estimated glomerular filtration rate (eGFR) decline of < and ≥1 mL/min per 1.73 m² per year, respectively) were observed and analyzed, and their risk of dying or requiring dialysis was determined. After exclusion of subjects requiring immediate dialysis or followed up for less than 6 months, 138 patients remained eligible for analysis. RESULTS: In the study cohort (initial mean eGFR 31.8 mL/min per 1.73 m², median follow‐up 47 months), patients were more likely to require dialysis than to die; 36% of patients had nonprogressive CKD. This characteristic, predicted by low proteinuria, lack of hypertension, and low cardiovascular comorbidity, was the strongest predictor of global survival. In progressors, two independent covariates (eGFR <30 mL/min per 1.73 m² and hemoglobin ≤11 g/dL at inclusion) predicted the risk of requiring dialysis. CONCLUSION: More than one‐third of subjects aged 80 and older referred to a nephrology center had severe but nonprogressive kidney dysfunction. This subgroup had a lower mortality rate than those with progressive kidney dysfunction. Simple covariates (low proteinuria, lack of hypertension, low cardiovascular comorbidity) predicted nonprogression of CKD. Distant nephrology follow‐up of such patients may be sufficient.     

Serum Phosphate and Mortality in Patients with Chronic Kidney Disease

Background and objectives: Higher phosphate is associated with mortality in dialysis patients but few prospective studies assess this in nondialysis patients managed in an outpatient nephrology clinic. This prospective longitudinal study examined whether phosphate level was associated with death in a referred population.Design, setting, participants & measurements: Patients (1203) of nondialysis chronic kidney disease (CKD) in the Chronic Renal Insufficiency Standards Implementation Study were assessed. Survival analyses were performed for quartiles of baseline phosphate relative to GFR, 12-month time-averaged phosphate, and baseline phosphate according to published phosphate targets.Results: Mean (SD) eGFR was 32 (15) ml/min per 1.73 m², age 64 (14) years, and phosphate 1.2 (0.30) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate. No association was found in CKD stage 5 patients. Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target. The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality.Conclusions: In CKD stages 3 to 4 patients, higher phosphate was associated with a stepwise increase in mortality. As phosphate levels below published targets (as opposed to within them) are associated with better survival, guidelines for phosphate in nondialysis CKD patients should be re-examined. Intervention trials are required to determine whether lowering phosphate will improve survival.Higher serum phosphate is associated with mortality in hemodialysis patients (1–3). There have been three studies in patients with chronic kidney disease (CKD), not on dialysis, evaluating the association of serum phosphate with mortality; two of these found a positive association (4–6). The relationship between serum phosphate and mortality in patients with CKD stages 3 to 5 (eGFR <60 ml/min per 1.73 m²) who are not on dialysis, and who are under regular nephrological review, has not previously been examined in a prospective systematic way. Survival data according to follow-up phosphate results are also lacking in CKD patients.The aims of this single-center study were to investigate whether an association of serum phosphate with all-cause and cardiovascular mortality could be shown prospectively in outpatients with advanced CKD (stage 5) not receiving dialysis and also in those with earlier (stages 3 and 4) CKD. The relationship of 12-month time-averaged phosphate and mortality and the influence upon survival of a serum phosphate within guideline targets was examined in this population.     

Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients With Chronic Kidney Disease

Endocan is a soluble proteoglycan released by the vascular endothelium. The increase of its serum levels is associated with inflammation, endothelial dysfunction and cardiovascular events in patients with chronic kidney disease (CKD). We studied the association of serum endocan with the lipid profile of 105 CKD patients with dyslipidemia, divided in two groups, non‐dialyzed (CKD, N = 57) and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also analyzed endocan in relation with the concentration of two serum HDL‐linked members of the paraoxonase (PON) family, PON1 and PON3, which have been previously found to have antiatherogenic properties. The results showed that endocan levels were significantly higher in HD patients than in CKD patients (P < 0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients compared to NC (P < 0.001), whereas PON3 was significantly increased in both patient groups (P < 0.001). Endocan levels were significantly and positively correlated with total cholesterol and LDL‐C in CKD and additionally were negatively correlated with HDL‐C in HD group. PON1 levels were significantly correlated with endocan in both groups, while no correlation was observed for PON3 in either group. Multiple regression analysis between endocan and the above lipid parameters in the total of patients revealed that endocan was independently associated only with PON1 (β = ?0.513, P = 0.002). It is concluded that the increase of serum endocan levels in patients with CKD may be associated with the decrease of PON1 concentration, irrespective of lipid alterations produced by atherosclerosis development.     

Hyperlipidemia and Long-Term Outcomes in Nondiabetic Chronic Kidney Disease

Background and objectives: Dyslipidemia confers a paradoxical survival advantage in patients with kidney failure. Data are limited in the earlier stages of chronic kidney disease (CKD).Design, setting, participants, and measurements: This was a cohort study in 840 subjects with stage 3 to 4 CKD enrolled in the Modification of Diet in Renal Disease study. Cox models were used to examine the relationship of total cholesterol (TC), non-HDL-cholesterol (NHDL-C), triglycerides (TG), and HDL-cholesterol (HDL-C) with all-cause and cardiovascular disease (CVD) mortality and progression to kidney failure.Results: During a mean follow-up of 10 years, there were 208 deaths, 128 deaths from CVD, and 554 subjects reached kidney failure. There was no association between tertiles of any of the lipid variables and mortality; the lowest HDL-C tertile (1.44, 1.18 to 1.78) had increased risk of kidney failure but covariate adjustment abolished this association. In analyses with lipids as continuous variables, there was a significant association with all-cause mortality for TC (hazard ratio [HR] per 10-mg/dl increase, 95% confidence intervals [CI] = 1.03, 1.0 to 1.06) that disappeared with covariate adjustment; there was no association of TG, HDL-C, and NHDL-C as continuous variables with all-cause or CVD mortality. There was a significant inverse association between HDL-C and kidney failure (HR = 0.93, CI = 0.87 to 0.99) in an unadjusted Cox model that was attenuated after adjustment for covariates (HR = 0.98 CI = 0.91 to 1.06).Conclusions: In this cohort, with predominantly nondiabetic CKD patients, hyperlipidemia is not an independent predictor of long-term outcomes.Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in chronic kidney disease (CKD) (1–3). Patients with CKD are considered in the highest risk group for development of CVD and, from a risk stratification perspective, equivalent to patients with diabetes or existing coronary heart disease (4,5). Hyperlipidemia, a well established risk factor for CVD in the general population (6–8), is highly prevalent in CKD and is estimated to be over 40% in patients with kidney failure (9–11).Several studies in patients with kidney failure suggest that higher cholesterol levels are protective for CVD (12–15). These findings represent a paradoxical association of lipid levels with mortality compared to the general population and have been attributed to the inflammation and malnutrition that are common in this patient population (16,17). Data regarding the relationship between hyperlipidemia and outcomes in the earlier stages of CKD before reaching kidney failure are limited and contradictory. Whereas one study found an inverse association between cholesterol levels and risk of all-cause and CVD mortality (16), another found no association between lipid parameters and CVD mortality (18).Given the high prevalence of hyperlipidemia in CKD, targeting improvement in lipid levels is of particular interest in this high-risk population, especially patients in the earlier stages of CKD who may be most likely to benefit from preventive interventions. We examined the association between lipid levels and mortality in a cohort of patients with predominantly nondiabetic CKD stages 3 to 4.     

慢性肾脏病患者血清瘦素水平与颈动脉内膜-中层厚度的关系

目的 探讨慢性肾脏病患者血清瘦素水平与颈动脉内膜-中层厚度的关系.方法 选择79例慢性肾脏病非透析患者和15例健康对照者,采用放射免疫法测定血清瘦素水平,用高分辨二维颈动脉超声技术测定颈动脉内膜一中层厚度及粥样硬化斑块.结果 慢性肾脏病患者血清瘦素水平、平均颈动脉内膜-中层厚度和动脉粥样斑块检出率明显高于健康对照组(P<0.01).慢性肾脏病伴颈动硬化组(颈动脉内膜-中层厚度≥1.0mm,和/或颈动脉斑块)较无颈动脉硬化组血清瘦素(17.06±1.061ng/L比14.27±0.70ng/L)和C.反应蛋白(3.32±0.19mg/L比2.55±0.17mg/L)水平明显升高(P<0.01);慢性肾脏病患者血清瘦素与尿素氮、肌酐、C-反应蛋白、体质指数呈显著正相关(r=0.293,P<0.01;r=0.324,P<0.01;r=0.539,P<0.01;r=0.312,P<0.05);与肾小球滤过率、血红蛋白、白蛋白呈显著负相关(r=-0.389,P<0.01;r=-0.454,P<0.01;r=-0.246,P<0.05).瘦素(β=1.527,P<0.05)是慢性肾脏病患者并发动脉粥样硬化的独立危险因素.结论 慢性肾脏病患者存在高瘦素血症,高瘦素血症与颈动脉内膜-中层厚度的关系,其可能参与了慢性肾脏病患者动脉粥样硬化的发生和发展.     

Serum Alkaline Phosphatase and Mortality in African Americans with Chronic Kidney Disease

Background and objectives: Serum alkaline phosphatase has been associated with increased mortality in hemodialysis patients but its associations with mortality in chronic kidney disease (CKD) stages III and IV are unknown.Design, settings, participants & measurements: In 1094 participants in the African-American Study of Kidney Disease and Hypertension (AASK) database, the associations of serum alkaline phosphatase with mortality and cardiovascular events were examined in Cox models.Results: The mean (±SD) age was 54 ± 11 yr, and 61% were men. The median alkaline phosphatase was 80 IU/L, and interquartile range was 66 to 97 IU/L. The mean follow-up was 4.6 yr. There were 105 (9.6%) all-cause deaths and 149 (13.6%) cardiovascular events. Each doubling of serum alkaline phosphatase was significantly associated with increased hazard [hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.08 −2.36] of all-cause mortality adjusted for demographics, drug and blood pressure groups, and comorbidity. With further adjustment for liver function tests as well as serum calcium and phosphorus, each doubling of serum alkaline phosphatase remained significantly associated with increased mortality (HR 1.55, 95% CI 1.03 to 2.33). Serum alkaline phosphatase was not significantly associated with increased risk of cardiovascular events.Conclusions: Independent of liver function tests and serum calcium and phosphorus, higher levels of serum alkaline phosphatase are associated with increased mortality in the CKD population. Further studies are warranted to identify the potential mechanisms for this association.Experimental studies suggest alkaline phosphatase might promote vascular calcification (1,2). Indeed, higher levels of serum alkaline phosphatase were independently associated with progressive arterial calcification in a longitudinal study of stage IV and V chronic kidney disease (CKD) patients (3). Furthermore, serum alkaline phosphatase was independently associated with increased mortality in hemodialysis patients (4–6). However, there is a paucity of data on whether serum alkaline phosphatase is an independent predictor of mortality in CKD stages III and IV. Therefore, we examined the associations of serum alkaline phosphatase with cardiovascular events and mortality in the African-American Study of Kidney Disease and Hypertension (AASK) database.     

Impact of Chronic Kidney Disease in Chronic Total Occlusion Management and Clinical Outcomes

BackgroundData on the impact of chronic kidney disease (CKD) on clinical outcomes in chronic total occlusion (CTO) patients is scarce, and the optimal treatment strategy for this population is not well established. This study aims to compare differences in CTO management and long-term clinical outcomes, including all-cause and cardiac mortalities, according to baseline glomerular filtration rate (GFR).MethodsAll patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortalities were assessed during a median follow-up of 4.03 years (IQR 2.6–4.8). Clinical outcomes were compared between patients with CKD (GFR < 60 mL/min/1.73 m²) and without CKD (GFR ≥ 60 mL/min/1.73 m²).ResultsA total of 1248 patients (67.3 ± 10.9 years; 32% CKD) were identified.CKD patients were older and had a higher prevalence of hypertension, type 2 diabetes, peripheral arterial disease, and severe left ventricular dysfunction compared to patients with normal renal function (p < 0.05).Subjects with renal dysfunction were more often treated with MT alone, compared to patients without CKD (63% vs 45%; p < 0.001), who were more likely to undergo PCI or surgery. During follow-up, 386 patients [31%] died. CKD patients had a higher rate of all-cause and cardiac mortalities compared to patients without CKD (p < 0.001). The independent predictors for all-cause mortality were age, GFR < 60 mL/min/1.73 m², Syntax Score I, and successful revascularization of the CTO (CABG or PCI-CTO). Among patients with CKD, advanced age, eGFR <30 mL/min/1.73 m², and CTO successful revascularization were predictors of all-cause mortality.ConclusionsPatients with CKD were more often treated with MT alone. At long-term follow-up, revascularization of the CTO is associated with lower all-cause and cardiac mortalities in this population.     

Cardiorespiratory Fitness Is Independently Associated with 25-Hydroxyvitamin D in Chronic Kidney Disease

Summary

Background and objectives

Vitamin D is an established important contributor to muscle function and aerobic metabolism. Hypovitaminosis D is highly prevalent in CKD patients and is associated with increased cardiovascular (CV) mortality via unknown mechanisms. Because aerobic-exercise capacity strongly predicts future CV events, we hypothesized that vitamin D status could be linked to CV outcomes via an effect on maximum aerobic-exercise capacity in patients with CKD and that this effect may be mediated in part via its actions on muscle strength and functional ability.

Design, setting, participants, & measurements

Baseline demographic, anthropometric, and biochemical data were collected in a cross-sectional study of patients with moderate CKD. Peak aerobic capacity was determined during treadmill stress testing using metabolic equivalence of tasks. Physical activity was assessed using the Active Australia questionnaire, grip strength by dynamometer, and functional capacity by “Up & Go” testing.

Results

The study included 85 participants (age 59.5 ± 9.7 years, 60% male, 44% diabetic, 92% Caucasian; mean serum 25-hydroxyvitamin D [25-OHD] 78.4 ± 29.4 nmol/L). We demonstrated that 25-OHD status was independently associated with aerobic-exercise capacity (β = 0.2; P = 0.008). Aerobic-exercise capacity was also predicted by younger age, white race, smaller waist circumference, absence of a previous angina history, and increasing weekly physical activity. However, neither muscle strength nor functional ability were significantly associated with 25-OHD.

Conclusions

Vitamin D is independently associated with aerobic capacity in CKD patients, and this finding is not explained by changes in muscle strength or functional ability.     

慢性肾脏病患者血清总胆红素水平与颈动脉内膜中膜厚度的关系

目的观察慢性肾脏病患者血清胆红素水平变化与颈动脉内膜中膜厚度的关系。方法选择慢性肾脏病患者48例和对照组16例,测定血清胆红素水平,用高分辨二维颈动脉超声技术测定颈动脉内膜中膜厚度及粥样硬化斑块。结果慢性肾脏病患者血清胆红素水平明显低于对照组(P<0.01);血清胆红素水平随肾功能降低而减低。平均颈动脉内膜中膜厚度和动脉粥样斑块检出率明显高于对照组(P<0.01)。慢性肾脏病伴颈动脉硬化组较无颈动脉硬化组血清胆红素(5.38±1.95μmol/L比9.15±3.53μmol/L)水平明显降低(P<0.01);慢性肾脏病患者血清胆红素与尿素氮、肌酐呈显著负相关(r=-0.611和-0.492,P<0.0001),与肾小球滤过率、血红蛋白呈显著正相关(r=0.693和0.602,P<0.0001)。血清总胆红素(β=0.918,P=0.004)是慢性肾脏病患者并发动脉粥样硬化的独立危险因素。结论慢性肾脏病患者存在低胆红素血症,低胆红素血症可能参与了慢性肾脏病患者动脉粥样硬化的发生和发展。     

Association between Multimorbidity and Kidney Function among Patients with Non-Dialysis-Dependent CKD: The Fukuoka Kidney Disease Registry Study

Aim: Individuals with chronic kidney disease (CKD) have a high prevalence of comorbidities, including cardiovascular disease (CVD) and its risk factors. However, epidemiological results to assess the association between multimorbidity and kidney function among the CKD population remains limited. Methods: We performed a cross-sectional analysis of the association between 23 comorbid conditions and reduced kidney function in 4,476 patients with non-dialysis-dependent CKD enrolled in a multicenter cohort in Japan. Reduced kidney function was defined as an estimated glomerular filtration rate of ≤ 60 mL/min/1.73 m². Results: The mean age of patients was 67 years (male, 56.0%). The prevalence of hypertension, diabetes mellitus, dyslipidemia, prior CVD, cancer, and bone fracture, which are the major comorbidities, was 83.3%, 28.7%, 45.9%, 23.3%, 12.7%, and 6.3%, respectively. Multivariable-adjusted analyses revealed that age, male sex, hypertension, dyslipidemia, prior CVD, body mass index, urinary protein excretion, and underlying kidney disease were independent factors associated with reduced kidney function. Importantly, the odds ratios (ORs) for reduced kidney function increased linearly as the number of major comorbid conditions increased (OR for 1–2 conditions: 2.22, 95% confidence interval [CI]: 1.65–2.97; OR for 3–4 conditions: 3.04, 95% CI: 2.12–4.37; OR for ≥ 5 conditions: 4.37, 95% CI: 1.75–10.9). The upward trend in OR was more pronounced with cardiovascular comorbidities but not significant with non-cardiovascular comorbidities. Conclusions: In conclusion, we observed an independent association between cardiovascular comorbidity and its risk factors and reduced kidney function. The results of this study highlight the importance of managing multimorbidity among patients with CKD.     

Association of Markers of Iron Stores with Outcomes in Patients with Nondialysis-Dependent Chronic Kidney Disease

Background and objectives: Assessments of iron stores by serum iron saturation ratio (ISAT) and ferritin are used to direct anemia therapy in chronic kidney disease (CKD) and are associated with clinical outcomes in patients on dialysis. The association of ISAT and ferritin with outcomes in patients with nondialysis-dependent CKD (NDD-CKD) has not been studied.Design, setting, participants, & measurements: All-cause mortality and progression of CKD [slopes of estimated GFR (eGFR)] were examined in 453 men with NDD-CKD. Mortality and the composite of mortality and ESRD were studied in Cox models. Slopes of eGFR were examined in mixed-effects models.Results: Lower ISAT was associated with higher mortality; adjusted hazard ratio [95% confidence interval (CI)] with ISAT of <12%, 13 to 17%, and >23% versus 18 to 23%; 1.40 (0.99 to 1.98), 1.20 (0.82 to 1.76), and 0.97 (0.67 to 1.41), P = 0.025 for trend. ISAT was also associated with steeper slopes of eGFR (one log-unit higher ISAT associated with a slope of −0.89 ml/min/1.73m² /yr (95% CI: −1.75, −0.02, P = 0.044). Serum ferritin level showed no significant association with outcomes overall, but a trend for higher mortality was observed in patients with a serum ferritin level >250 ng/ml.Conclusions: Higher ISAT is associated with lower mortality and with more progressive CKD. Clinical trials are needed to examine if correction of low iron levels can improve mortality without affecting kidney function in NDD-CKD.Iron is an essential trace element which plays an important role in the catalysis of oxidative reactions and in the transport of soluble gases (1). Assessment of iron stores is done routinely in everyday nephrology practice (2), through measurement of total iron saturation (ISAT; also known as transferrin saturation) and serum ferritin (3).Iron deficiency is common in patients with nondialysis-dependent chronic kidney disease (NDD-CKD) (4,5), but it is unclear to what extent levels of ISAT and ferritin are associated with outcomes in this population. Examining hard endpoints is especially important given the concern that exceeding certain limits of ISAT or ferritin may be deleterious through excess iron deposition and induction of oxidative stress (6–9). We examined the associations of these iron markers with all-cause mortality, the composite of predialysis mortality or ESRD, and the slopes of estimated GFR (eGFR) in 453 men with moderate and advanced NDD-CKD.