Reverse epidemiology in patients with chronic kidney disease who are not yet on dialysis

Many traditional risk factors show a seemingly paradoxical, inverse association with mortality in patients on dialysis. In spite of their larger numbers, patients with chronic kidney disease (CKD) who are not yet on dialysis are less well studied. Preliminary studies indicate that "reverse epidemiology" is also present in patients with CKD who are not yet on dialysis. Studying patients with CKD offers hope to further our understanding of this phenomenon.     

Association between medication adherence and clinical outcomes in patients with chronic kidney disease: a prospective cohort study

Background

There is limited evidence of medication adherence related to progression of chronic kidney disease (CKD) worldwide. The aim of this study was to determine associations between medication adherence and the progression of CKD in outpatients with CKD.

Methods

This cohort study recruited 339 Thai patients with stages 3–5 CKD. Patients with a glomerular disease or receiving renal replacement therapy before recruitment were excluded. 295 were followed up regarding their serum creatinine, blood pressure, glycated hemoglobin, and low-density lipoprotein cholesterol over 12 months. Medication adherence was measured at baseline using the Thai version of the 8-Item Morisky Medication Adherence Scale^®. The primary outcome was the progression of CKD. The progression of CKD was defined as either a decline in estimated glomerular filtration rate of at least 3 ml/min/1.73 m²/year or initiation of renal replacement therapy. Univariate and multivariate analyses were performed using Chi-squared tests and multiple logistic regressions.

Results

Twenty-one percent had poor adherence. Younger patients were more likely to have poor adherence (adjusted OR 2.81, 95 % CI 1.45–5.43). Anti-hypertensive agents were the most frequently reported as not being taken (52 %). Patients with poor adherence were associated with the progression of CKD (adjusted OR 1.96, 95 % CI 1.02–3.76). Those with poor adherence were less likely to control their blood pressure, than moderate-to-high adherence group (p < 0.01).

Conclusion

The findings suggest that CKD patients with poor medication adherence are more likely to have progression of CKD. Health care providers should acknowledge these findings and provide effective strategies to deal with this issue.

     

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.

     

J-shaped association of platelet-to-lymphocyte ratio with 5-year mortality among patients with chronic kidney disease in a prospective cohort study

International Urology and Nephrology - To examine whether platelet-to-lymphocyte ratio (PLR) is associated with 5-year mortality in patients with chronic kidney disease (CKD), we performed this...     

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study

Background

Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)—an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m²—has remained largely unexamined.

Methods

We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event.

Results

Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan.

Conclusions

Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

     

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

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

Effect of antitubercular medications on blood pressure control in chronic kidney disease patients with tuberculosis: a prospective cohort study

BACKGROUND: Previous anecdotal reports suggested a decrease in antihypertensive medication potency after starting antitubercular medications. This interaction could be unpredictable in presence of renal failure due to increased half-lives of most commonly used antihypertensive medications. METHODS: In a cohort study involving 135 patients with chronic kidney disease (CKD), 62 patients with tuberculosis star-ted on antitubercular medications (TB group) were prospectively compared with 73 CKD controls (with no TB and not on antitubercular medications) for a change in antihypertensive medications. Antihypertensive dose was converted to unit score. RESULTS: The TB group had a greater increase in antihypertensive medication dose as compared with controls (89% vs. 54%, p<0.0001). In absolute terms an overall increase in antihypertensive medications was observed in 60% of pa-tients in the TB group, with a 2-fold dose increase from the baseline (p<0.0001). Four patients from the TB group de-veloped a hypertensive emergency. In multivariate linear regression, the association between TB group and increase in antihypertensives remained significant ( beta =0.38; p<0.0001). CONCLUSIONS: In CKD patients, antihypertensive medication potency is reduced in TB patients on antitubercular the-rapy in a significant number of patients, to a clinically significant degree with a potential risk for hypertensive emergency.     

Left ventricular systolic function monitoring in asymptomatic dialysis patients: a prospective cohort study

Although it is well established that compromised systolic function predicts cardiovascular (CV) complications in symptomatic and asymptomatic patients with ESRD, it still is unknown whether repeated echocardiographic measurements of systolic function in asymptomatic patients with ESRD is useful for monitoring the evolution of cardiomyopathy in these patients. The prognostic value for CV events of changes in systolic function, as measured by midwall fractional shortening (mwFS) in a cohort of 191 dialysis patients, was tested. Echocardiography was performed twice, 17 +/- 2 mo apart. Changes in mwFS (ch-mwFS) that occurred between the second and the first echocardiographic studies then were used to predict CV events during the ensuing 27 +/- 13 mo. After the second echocardiographic study, 85 patients had incident CV events. In a Kaplan-Meier analysis, there was a graded increase in the risk for fatal and nonfatal CV events across ch-mwFS quartiles (P = 0.005). On multivariate Cox regression analysis, ch-mwFS maintained an independent association with CV outcomes. In this analysis, the risk for CV events was 51% lower in patients who manifested an increase in mwFS (hazard ratio 0.49; 95% confidence interval 0.27 to 0.88; P = 0.02) than in those who had a decrease in mwFS. Changes in mwFS have an independent prognostic value for CV events, and periodic echocardiographic studies of systolic function are useful for monitoring asymptomatic dialysis patients.     

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.     

Hypercalcemia in patients with advanced chronic renal failure not yet requiring dialysis

Six patients with progressive chronic renal failure not yet requiring dialysis and not consuming supplemental calcium or vitamin D developed hypercalcemia. Three had proven and 1 suspected tertiary hyperparathyroidism, 1 parathyroid carcinoma and 1 aplastic bone. None of the 3 patients who underwent bone biopsy had heavy bone aluminum staining. The patients with proven parathyroid-mediated hypercalcemia had marked elevation of C-terminal parathyroid hormone and alkaline phosphatase values and, when performed, radiographs consistent with osteitis fibrosa. When these findings are absent or the diagnosis is otherwise uncertain, a bone biopsy may provide a definitive diagnosis and guide management.     

Association of magnesium abnormalities at intensive care unit admission with kidney outcomes and mortality: a prospective cohort study

Clinical and Experimental Nephrology - Magnesium abnormalities have been associated with adverse kidney outcomes and mortality in critically ill patients, however, this association remains...     

Association of physical activity with mortality in chronic kidney disease

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for all-cause mortality. In the general population, physical activity is associated with reduced mortality. We examined the association of level of physical activity with mortality in patients with predominantly nondiabetic CKD stage 3-4. METHODS: We studied 811 patients with CKD enrolled in the Modification of Diet in Renal Disease (MDRD) Study, a multicenter clinical trial conducted between 1989 and 1993. Patients completed a survey of their physical activity at baseline, from which we derived 3 physical activity variables: indoor activity, exercise and outdoor activity, using standardized scores. We used Cox proportional hazards modeling to examine the relationship between baseline physical activity and all-cause mortality with long-term outcome ascertained through 2000. RESULTS: The mean age of the study population was 52 years, and 61% were male. The mean glomerular filtration rate was 32.5 ml/min per 1.73 m2. A total of 24.6% died during follow-up. After adjustment for other factors significantly associated with mortality, the hazard ratio for all-cause mortality for indoor activity was 0.94 (95% confidence interval [95% CI], 0.77-1.14), exercise 1.01 (95% CI, 0.84-1.10) and outdoor activity 0.94 (95% CI, 0.80-1.10). CONCLUSIONS: Higher levels of physical activity were not significantly associated with a reduction in long-term mortality in patients with CKD in this cohort. Additional prospective studies are needed to confirm our finding and determine whether physical activity improves outcomes in patients with CKD.     

Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome

High total cholesterol is associated with lower mortality in dialysis patients, but the relationship between lipid levels and mortality in patients who have chronic kidney disease (CKD) and are not yet on dialysis is poorly described. This study examined the association between lipid levels and all-cause and cardiovascular mortality in 986 male patients (age 67.4 +/- 10.9 yr; race 23.7% black) who had CKD and were not yet on dialysis. Associations were determined in fixed-covariate and time-dependent Cox models, before and after adjustment for components of case mix and surrogates for malnutrition-inflammation-cachexia syndrome (MICS). Lower total cholesterol quartiles were associated with higher all-cause mortality in a fixed-covariate model that was adjusted for age, race, and body mass index (hazard ratio [95% confidence interval] for cholesterol <153, 153 to 182, and 183 to 215 versus >215 mg/dl: 1.91 [1.35 to 2.69], 1.36 [0.96 to 1.92], 1.10 [0.78 to 1.57]; P < 0.001 for trend), but this association was attenuated after adjustment for case mix (P = 0.023 for trend) and abolished after additional adjustment for MICS (P = 0.14 for trend), with time-dependent Cox models showing similar results. Similar tendencies also were detected in the association between levels of LDL cholesterol with total and cardiovascular mortality and triglycerides with all-cause mortality in both fixed-covariate and time-dependent analyses. Lower lipid levels are associated with higher mortality in patients who have moderate and advanced CKD and are not yet on dialysis. This inverse association is explained in part by case-mix characteristics and the presence of surrogates for MICS.     

Association of pre-transplant dialysis duration with outcome in kidney transplant recipients: a prevalent cohort study

Introduction  

Dialysis treatment prior to transplantation may contribute to premature mortality and graft loss in kidney-transplanted patients. In this prevalent cohort study (TransQol-HU Study), we analyzed the association between pre-transplant dialysis duration versus mortality and death-censored graft loss in kidney-transplanted patients.     

Fetuin-A is not associated with mortality in chronic kidney disease

Fetuin-A is a serum protein that inhibits vascular calcification such that lower levels are associated with a higher prevalence of vascular calcification and mortality risk among end-stage renal disease populations. We analyzed data of 822 persons in the Modification of Diet in Renal Disease study, a randomized, controlled trial of persons with predominantly non-diabetic stage 3-4 chronic kidney disease (CKD). Serum fetuin-A levels were measured in baseline serum. Survival status and cause of death were determined by the National Death Index. Cox proportional hazard models evaluated the association of fetuin-A levels with all-cause and cardiovascular mortality. Glomerular filtration ranged from 13 to 55 ml per min per 1.73 m(2). During a median follow-up of 9.5 years, 25% of persons died from any cause and 12% died from a cardiovascular cause. Compared to the lowest tertile, no association was found between the highest fetuin-A tertile and all-cause or cardiovascular mortality. Similarly, no association was found between fetuin-A as a continuous variable and all-cause or cardiovascular mortality. Our study shows that serum fetuin-A levels are not related to all-cause or cardiovascular mortality among persons with predominantly non-diabetic stage 3 or 4 CKD.