Incident Chronic Kidney Disease Stage Research Articles

Performance of a Genetic Risk Score for CKD Stage 3 in the General Population

Recent genome-wide association studies have identified multiple genetic loci that increase the risk of chronic kidney disease (CKD) in the general population. We hypothesized that knowledge of these loci might permit improved CKD risk prediction beyond that provided by traditional phenotypic risk factors. Observational cohort study. Participants who attended the 15th (1977-1979) and 24th (1995-1998) examination cycles of the original cohort or the 6th (1995-1998) and 8th cycles (2005-2008) of the offspring cohort of the Framingham Heart Study (n = 2,489). Single-nucleotide polymorphisms at 16 stage 3 CKD loci were genotyped and used to construct a genetic risk score. Standard clinical predictors of incident stage 3 CKD also were used. Incident stage 3 CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m(2) at follow-up. Participants with baseline stage 3 CKD were excluded. Logistic regression was used to generate C statistics, which measured the power of the genetic risk score to discriminate risk of incident CKD stage 3 with and without traditional risk factors. There were 270 new stage 3 CKD cases during an average of 10.8 years of follow-up. Mean genetic risk score was 17.5 ± 2.8 (SD) for those who developed stage 3 CKD and 17.3 ± 2.6 for those who did not (P for genotype score difference = 0.2). The OR for stage 3 CKD was 1.06 (95% CI, 1.01-1.11; P = 0.03) per additional risk allele, adjusting for age and sex. In the age- and sex-adjusted model, the C statistic was 0.748 without the genotype score and 0.751 with the score (P difference = 0.3). The risk score was not statistically significant in a multivariable model adjusted for standard stage 3 CKD risk factors (P = 0.07). All participants were of European ancestry; the genotype score may not be valid in different ancestral groups. A genetic score generated from 16 known CKD risk alleles did not predict new cases of stage 3 CKD in the community beyond knowledge of common clinical risk factors alone.

Retinal Arteriolar Narrowing and Subsequent Development of CKD Stage 3: The Multi-Ethnic Study of Atherosclerosis (MESA)

Microvascular disease is a major pathogenic factor for chronic kidney disease (CKD) in persons with diabetes, but the role of microvascular disease in the development of CKD in the general population is unclear. The aim of this study is to examine whether microvascular disease precedes the development of CKD stage 3 in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Population-based cohort study. MESA is a prospective cohort study of adults aged 45-84 years living in 6 US communities; 4,594 adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) when they underwent retinal photography (visit 2: in 2002-2004) were examined. Retinal microvascular caliber measured from fundus photographs. Incident CKD stage 3 (ie, eGFR <60 mL/min/1.73 m(2)) at 2 subsequent follow-up examinations (visit 3 in 2004-2005, and visit 4 in 2005-2007) and an annual eGFR decrease >1 mL/min/1.73 m(2) computed using the CKD Epidemiology Collaboration (CKD-EPI) equation. After a median follow-up of 4.8 years, there were 232 incident CKD stage 3 cases. Overall, retinal microvascular caliber was not associated with incident CKD stage 3. However, in race-stratified analysis, narrower arterioles in whites was associated with a higher risk of developing CKD stage 3 after adjusting for age, sex, blood pressure, diabetes, and other factors (HR, 1.78; 95% CI, 1.01-3.15; P = 0.04, lowest vs highest arteriolar caliber tertile). This association was seen even in whites without hypertension and diabetes (HR, 2.95; 95% CI, 1.10-7.98; P = 0.03). Retinal arteriolar caliber was not associated with incident CKD stage 3 in African Americans, Chinese, or Hispanics. Analyses were based on a single eGFR measurement, and retinal microvascular caliber and eGFR measurements were not ascertained concurrently. Microvascular changes as manifest in the eye may contribute to the development of CKD stage 3 in whites.

Cystatin C and Albuminuria as Risk Factors for Development of CKD Stage 3: The Multi-Ethnic Study of Atherosclerosis (MESA)

The growing burden and morbidity of chronic kidney disease (CKD) warrant effective strategies for identifying those at increased risk. We examined the association of cystatin C level and albuminuria with the development of CKD stage 3. Prospective observational study. 5,422 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2). Participants were categorized into 4 mutually exclusive groups: the presence or absence of microalbuminuria (albumin-creatinine ratio >17 and >25 μg/mg in men and women, respectively) in those with or without cystatin C level ≥1.0 mg/L. Incident CKD stage 3 was defined as eGFR <60 mL/min/1.73 m(2) at the third or fourth visit and an annual decrease >1 mL/min/1.73 m(2). Poisson regression was used to evaluate incident rate ratios in unadjusted and adjusted analyses that include baseline eGFR. Mean age was 61 years, 49% were men, 38% were white, 11% had diabetes, 13.7% had cystatin C level ≥1 mg/L, 8.4% had microalbuminuria, and 2.7% had cystatin C level ≥1 mg/L with microalbuminuria. 554 (10%) participants developed CKD stage 3 during a median follow-up of 4.7 years, and adjusted incidence rate ratios were 1.57 (95% CI, 1.19-2.07), 1.37 (95% CI, 1.13-1.66), and 2.12 (95% CI, 1.61-2.80) in those with microalbuminuria, cystatin C level ≥1 mg/L, and both, respectively, compared with those with neither. Relatively short follow-up and absence of measured GFR. Cystatin C level and microalbuminuria are independent risk factors for incident CKD stage 3 and could be useful as screening tools to identify those at increased risk.

Early Withdrawal of Calcineurin Inhibitors and Everolimus Monotherapy in de novo Liver Transplant Recipients Preserves Renal Function

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novo liver transplantation (LT) patients would result in superior renal function compared to a CsA-based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy-eight patients were randomized (Evr n = 52; CsA n = 26). The 1-year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥ 3 (estimated glomerular filtration rate < 60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novo LT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

Patient INformation about Options for Treatment (PINOT): a prospective national study of information given to incident CKD Stage 5 patients

Informed decision-making requires the presentation of all possible courses of action; however, it is unclear what proportion of Stage 5 chronic kidney disease (CKD) patients are routinely informed of all their treatment options. The aim of this study was to determine the effect of patient and unit characteristics on the type and timing of information provided. A prospective national multi-centre study of information was given to incident pre-emptive transplant, dialysis and conservatively managed patients in Australian renal units, over a 3-month period. Sixty-six of 73 renal units participated in the study. Seven hundred and twenty-one incident CKD Stage 5 patients including 102 who chose not to dialyse were identified. Of these, 603 (84%) were presented with information about their options prior to commencing treatment. Three quarters (n = 543) were presented with home dialysis, one-third (n = 230) pre-emptive transplantation and 65% (n = 470) were informed about conservative care as an option. Patients were more likely to receive information prior to commencing treatment if they were known to a nephrologist for more than 3 months (OR 7.29, 95% CI 3.86-13.79) or were treated in small units with < 100 dialysis patients (OR 2.40, 95% CI 1.26-4.60). The mean estimated glomerular filtration rate at the time information was first presented was 13.3 mL/min/1.73 m(2) (95% CI 12.7-13.8) and mean serum creatinine was 449 μmol/L (95% CI 431-467). Most Australian patients were informed of their treatment options prior to starting treatment, albeit in late stage CKD. Earlier education and support for informed decision-making may help optimize the uptake of pre-emptive transplantation and home dialysis therapies.

Visfatin is increased in chronic kidney disease patients with poor appetite and correlates negatively with fasting serum amino acids and triglyceride levels

Anorexia is a common complication of chronic kidney disease (CKD), while novel animal and human data suggest a role for visfatin in regulating feeding behavior. We hypothesized that increased visfatin levels in CKD patients may be involved in the regulation of appetite and nutrient homeostasis. This is a cross-sectional study where circulating visfatin levels were analysed in 246 incident CKD stage 5 patients starting dialysis therapy. The associations between visfatin (enzyme-linked immunosorbent assay, ELISA) and anthropometric and biochemical nutritional status, self-reported appetite, fasting serum amino acids (high-performance liquid chromatography) and circulating cytokine levels (ELISAs) were assessed. We also performed genotyping (Pyrosequencing(R)) of two polymorphisms (rs1319501 and rs9770242) in the visfatin gene. Serum visfatin concentrations were not associated with either body mass index or serum leptin. Across groups with worsening appetite, median visfatin levels were incrementally higher (P < 0.05). With increasing visfatin tertiles, patients proved to be more often anorectic (P < 0.05) and to have incrementally lower serum albumin, cholesterol and triglycerides as well as lower essential and non-essential serum amino acids (P < 0.05 for all). A polymorphism in the visfatin gene was associated with increased circulating visfatin levels and, at the same time, a higher prevalence of poor appetite (P < 0.05 for both). Our study suggests novel links between visfatin and anorexia in CKD patients. Based on recent studies, we speculate that high visfatin in CKD patients may constitute a counter-regulatory response to central visfatin resistance in uremia. Future studies should examine a putative role of visfatin as a regulator of nutrient homeostasis in uremia.

Temporal discrepancies in the association between the apoB/apoA‐I ratio and mortality in incident dialysis patients

In the general population, a high apoB/apoA-I ratio is a strong risk factor for cardiovascular disease and mortality. However, whether this is the case in chronic kidney disease (CKD) patients is currently unknown. The apoB/apoA-I ratio was evaluated in 391 incident CKD stage 5 patients examined close to dialysis initiation, and again after 1 year of dialysis in a subgroup of 182 patients, subsequently followed for up to 3 years. Baseline values of the apoB/apoA-I ratio as well as changes in the ratio during the first year of dialysis correlated with body mass index (BMI) and fat mass. The baseline apoB/apoA-I ratio showed no association with 4-year mortality. However, after adjustment for confounders, a high apoB/apoA-I ratio (>0.9) predicted short-term (first year) survival [hazard ratio (HR): 0.35; 95% confidence interval (CI): 0.13-0.85)] and long-term (next 3 years) mortality (HR: 1.72; 95% CI: 1.01-2.96). An increase in the apoB/apoA-I ratio during the first year of dialysis was linked to a survival advantage thereafter (HR: 0.48; 95% CI: 0.22-0.98). However, this association lost its significance (HR: 0.62; 95% CI: 0.26-1.36) after adjustment for indices of protein-energy wasting. A high apoB/apoA-I ratio and an increase in this ratio during the first year on dialysis were associated with short-term survival advantage in CKD patients. This paradoxical relationship represents an example of the so-called reverse epidemiology phenomenon in CKD patients and suggests that the apoB/apoA-I ratio should always be interpreted with caution in this patient population.

The impact of BMI on outcome in incident chronic kidney disease stage 5 patients

The impact of BMI on outcome in incident chronic kidney disease stage 5 patients