Although an arteriovenous fistula (AVF) is the hemodialysis access of choice, its prevalence continues to be lower than recommended in the United States. We assessed the association between past peripherally inserted central catheters (PICCs) and lack of functioning AVFs.
Participants & Setting
Prevalent hemodialysis population in 7 Mayo Clinic outpatient hemodialysis units. Cases were without functioning AVFs and controls were with functioning AVFs on January 31, 2011.
History of PICCs.
Lack of functioning AVFs.
On January 31, 2011, a total of 425 patients were receiving maintenance hemodialysis, of whom 282 were included in this study. Of these, 120 (42.5%; cases) were dialyzing through a tunneled dialysis catheter or synthetic arteriovenous graft and 162 (57.5%; controls) had a functioning AVF. PICC use was evaluated in both groups and identified in 30% of hemodialysis patients, with 54% of these placed after dialysis therapy initiation. Cases were more likely to be women (52.5% vs 33.3% in the control group; P = 0.001), with smaller mean vein (4.9 vs 5.8 mm; P < 0.001) and artery diameters (4.6 vs 4.9 mm; P = 0.01) than controls. A PICC was identified in 53 (44.2%) cases, but only 32 (19.7%) controls (P < 0.001). We found a strong and independent association between PICC use and lack of a functioning AVF (OR, 3.2; 95% CI, 1.9–5.5; P < 0.001). This association persisted after adjustment for confounders, including upper-extremity vein and artery diameters, sex, and history of central venous catheter (OR, 2.8; 95% CI, 1.5–5.5; P = 0.002).
Retrospective study, participants mostly white.
PICCs are commonly placed in patients with end-stage renal disease and are a strong independent risk factor for lack of functioning AVFs.
Chronic kidney disease; end-stage renal disease; arteriovenous fistula; hemodialysis; dialysis access
Low vitamin D concentrations are prevalent in chronic kidney disease (CKD) patients. We investigated the relationship between plasma 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations with death, cardiovascular events (CVE) and dialysis initiation in patients with advanced CKD. Study Design: The Homocysteine Study was a randomized double-blind trial evaluating the effects of high doses of folic acid on death and chronic dialysis initiation in patients with advanced CKD (stage 4 and 5 not yet on dialysis). 25(OH)D and 1,25(OH)2D concentrations were measured in stored plasma samples obtained 3 months after trial initiation and evaluated at clinically defined cutoffs (<10, 10-30, and >30 ng/mL) and tertiles (< 15, 15-22, and >22 pg/mL), respectively. Cox-proportional hazard models were used to examine the association between vitamin D concentrations and clinical outcomes.
Setting & Participants
1,099 patients with advanced CKD from 36 Veteran Affairs Medical Centers
25(OH)D and 1,25(OH)2D concentrations
Death, CVE and time to initiation of chronic dialysis.
After a median follow-up period of 2.9 years, 41% (n=453) died, while 56% (n=615) initiated dialysis. Mean 25(OH)D and 1,25(OH)2D concentrations were 21±10 ng/mL and 20±11 pg/mL, respectively. After adjustment for potential confounders, the lowest tertile of 1,25(OH)2D was associated with death (HR, 1.33; 95% CI, 1.01-1.74) and initiation of chronic dialysis (HR, 1.78; 95% CI, 1.40-2.26), compared to the highest tertile. The association with death and initiation of dialysis was moderately attenuated after adjustment for plasma fibroblast growth factor-23 (FGF23) concentrations (HRs of lower tertiles of 1.20 [95% CI, 0.91-1.58] and 1.56 [95% CI, 1.23-1.99], respectively, compared to highest tertile). There was no association between 25(OH)D concentrations and outcomes.
Participants were mostly male.
Low plasma 1,25(OH)2D concentrations are associated with death and initiation of chronic dialysis in advanced CKD. Fibroblast growth factor-23 may attentuate this relationship.
We present the case of a 21-year-old man who developed a renal artery pseudoaneurysm following a 7-foot fall onto his back. He initially presented with gross hematuria, left flank pain, and back pain. He was observed in the hospital for 3 days and discharged. One week later, he was readmitted with headache, nausea, vomiting, seizure activity, and hypertension. Contrast-enhanced computed tomography of the abdomen showed a left renal artery pseudoaneurysm with associated arterial narrowing and delayed ipsilateral renal enhancement. He underwent percutaneous stent-graft placement with resolution of the pseudoaneurysm. He was free of complications and normotensive off antihypertensive medications after 36 months of follow-up. Renal artery pseudoaneurysms are rare and under-recognized complications of blunt abdominal or back trauma that can cause hypertension. Imaging modalities in renovascular hypertension have focused on detecting renal artery stenosis from atherosclerotic disease or fibromuscular dysplasia, with little attention given to renal artery pseudoaneurysms. In addition, first-line treatment for renal artery pseudoaneurysms historically has consisted of angioembolization, yet percutaneous stent-graft placement has emerged as an attractive alternative to preserve vessel patency. We discuss the role of imaging in renovascular hypertension with a focus on renal artery pseudoaneurysms and their prevalence, diagnosis, and treatment.
Pseudoaneurysm; renovascular hypertension; imaging; blunt trauma; renal artery
Antibody response to the inactivated influenza vaccine is not well described in kidney transplant recipients on newer, but commonly used, immunosuppression medications. We hypothesized that kidney transplant recipient participants on tacrolimus-based regimens would have decreased antibody response compared with healthy controls.
Prospective cohort study of 53 kidney transplant recipient and 106 healthy control participants over the 2006–2007 influenza season. All participants received standard inactivated influenza vaccine.
Setting and participants
Kidney transplant recipients on tacrolimus-based regimens at a single academic medical center and healthy controls.
Presence of kidney transplant.
Proportion of participants achieving seroresponse (four-fold rise in antibody titer) and seroprotection (antibody titer greater than 1:32) one month after vaccination.
Antibody titers before vaccination and one month after vaccination using hemagglutinin inhibition assays for influenza types A/H1N1, A/H3N2, and B.
A smaller proportion of the transplantation group compared with the healthy control group developed the primary outcomes of seroresponse or seroprotection for all three influenza types at one month post vaccination. The response to influenza type A/H3N2 was statistically different, with the transplantation group having 69% decreased odds of developing seroresponse (95% CI 0.16 to 0.62, P = 0.001) and 78% decreased odds of developing seroprotection (95% CI 0.09 to 0.53, P = 0.001) compared with healthy controls. When participants less than 6 months from time of transplantation were considered, this group had significantly decreased response to the vaccine as compared with healthy controls.
Decreased sample size; potential for confounders; outcome measure used is the standard but does not give information about vaccine efficacy.
Kidney transplant recipients, especially within 6 months of transplantation, had diminished antibody response to the 2006–07 inactivated influenza vaccine.
influenza; vaccination; immunosuppression; kidney transplant; tacrolimus
Conflicting relationships have been described between anemia correction using erythropoiesis-stimulating agents (ESAs) and progression of chronic kidney disease (CKD). This study was undertaken to examine the impact of target hemoglobin on progression of kidney disease in the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial.
Secondary analysis of a randomized controlled trial
Setting and participants
1432 participants with CKD and anemia
Participants were randomized to target hemoglobin of 13.5 vs 11.3 gm/dL with the use of epoetin-alfa.
Outcomes and measurements
Cox regression was used to estimate hazard ratios for progression of CKD (a composite of doubling of creatinine, initiation of renal replacement therapy (RRT), or death). Interactions between hemoglobin target and select baseline variables (estimated glomerular filtration rate (eGFR), proteinuria, diabetes, heart failure, and smoking history) were also examined.
Participants randomized to higher hemoglobin targets experienced a shorter time to progression of kidney disease in both univariate (HR, 1.25; 95% CI, 1.03–1.52; p=0.02) and multivariable models (HR, 1.22; 95% CI, 1.00–1.48; p=0.05). These differences were attributable to higher rates of RRT and death among participants in the high hemoglobin arm. Hemoglobin target did not interact with eGFR, proteinuria, diabetes, or heart failure (p>0.05 for all). In the multivariable model, hemoglobin target interacted with tobacco use (p=0.04) such that the higher target had a greater risk of CKD progression among participants that currently smoked (HR, 2.50; 95% CI, 1.23–5.09; p=0.01) which was not present among those who did not currently smoke (HR, 1.15; 95% CI 0.93–1.41; p=0.2).
A post-hoc analysis and thus cause- effect cannot be determined.
These results suggest that high hemoglobin target is associated with a greater risk of progression of CKD. This risk may be augmented by concurrent smoking. Further defining the mechanism of injury may provide insight into methods to optimize outcomes in anemia management.
There is a gap of knowledge in the long-term outcomes of patients who have complete recovery of kidney function after an episode of acute kidney injury (AKI). We sought to determine if complete recovery of kidney function after an episode of AKI is associated with development of incident stage 3 chronic kidney disease (CKD) and mortality in patients with normal baseline kidney function.
Retrospective cohort study.
SETTING & PARTICIPANTS
3,809 patients from an integrated healthcare delivery system that had a hospitalization between January 1, 1999 and December 31, 2009 with follow-up through March 31, 2010.
AKI defined by ICD-9 codes and using the Acute Kidney Injury Network (AKIN) definition with complete recovery defined by reduction in serum creatinine to less than 1.10 times the baseline value.
OUTCOMES AND MEASUREMENTS
Incident stage 3 CKD persistent for 3 months and all-cause mortality.
After a median follow-up of 2.5 years, incident stage 3 CKD occurred in 15% and 3% of those with and without AKI, respectively, with an unadjusted HR of 5.93 (95% CI, 4.49-7.84) and a HR of 3.82 (95% CI, 2.81-5.19) in propensity score-stratified analyses. Deaths occurred in 35% and 24% of those with and without AKI, respectively, with an unadjusted HR of 1.46 (95% CI, 1.27-1.68). In the propensity score stratified analyses, HR decreased to 1.08 (95% CI, 0.93-1.27).
Measurements of albuminuria were not available.
Complete recovery of kidney function after an episode of AKI in subjects with normal baseline kidney function is associated with an increased risk of development of incident stage 3 CKD but not all-cause mortality.
Cognitive impairment is common but often undiagnosed in patients with end-stage renal disease, in part reflecting limited validated and easily administered tools to assess cognitive function in dialysis patients. Accordingly, we assessed the utility of the Kidney Disease Quality of Life Cognitive Function (KDQOL-CF) scale in comparison to an extensive neuropsychological battery, building on a prior assessment of this potential cognitive screen.
Setting & Participants
Maintenance hemodialysis patients at 6 Boston area dialysis units were administered an extensive neurocognitive battery and the KDQOL-CF at the beginning of a hemodialysis session.
KDQOL-CF score, depression symptom burden, and demographic and clinical characteristics.
Neurocognitive performance classified into executive function and memory domains, determined using principal components analysis.
Univariate and multivariable linear regression models adjusting for age, sex, race, and end-stage renal disease cause were used to evaluate the association between KDQOL-CF score and cognitive performance, and test metrics were determined for a KDQOL-CF cutoff score of 60 or less from a maximum score of 100.
For 168 prevalent hemodialysis patients, KDQOL-CF score was 76 ± 19 and 40 (24%) had scores of 60 or less, consistent with self-identified worse cognitive performance. There was no significant correlation between KDQOL-CF score and either memory (P = 0.2 and P = 0.3) or executive function (P = 0.1 and P = 0.4) in univariate and multivariable models, respectively. There was a strong correlation between higher KDQOL-CF score and fewer depression symptoms (P <0.001). Sensitivity of the KDQOL-CF was poor (range, 0.28–0.36), with modest specificity (range, 0.77–0.81) for identifying worse executive function and memory.
Cross-sectional study, modest population size, and abbreviated gold-standard cognitive battery.
The KDQOL-CF is a poor determinant of neurocognitive performance in hemodialysis patients, with limited sensitivity. To assess cognitive impairment in hemodialysis patients, better screening tests are essential.
Dialysis; dementia; cognitive impairment; screening; depression; quality of life
The strength and direction of the associations between inflammation and coagulation biomarkers with kidney disease onset and progression remains unclear, especially in a population-based setting.
Prospective observational study.
Setting & Participants
4,966 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with a cystatin C-based estimate of glomerular filtration rate (eGFRcys) > 60 ml/min/1.73m2 and least one follow-up measure of kidney function. All participants were free of cardiovascular disease (CVD) at entry.
We evaluated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, factor VIII, and D-dimer with kidney function decline.
Outcomes and Measurements
Kidney function decline was assessed primarily by repeated measures of eGFRcys over 5 years. Rapid decline of kidney function was defined as an eGFR decrease of more than 3 ml/min/1.73m2 per year. Incident low eGFR was defined as the onset of eGFRcys<60 ml/min/1.73m2 at any follow up exam and eGFRcys decline ≥1 ml/min/1.73m2 per year.
Mean age was 60 years, 39% were white, 52% were women, and 11% had diabetes. Mean eGFRcys was 96 mL/min/1.73 m2 and 7% had albuminuria. Median follow up time was 4.77 years. Higher Factor VIII levels (per 1-standard deviation [SD] of biomarker) had the strongest association with kidney function decline (β= −0.25; 95% CI, −0.38 to −0.12; p<0.001), followed by IL-6 (β= −0.16; 95% CI, −0.29 to −0.03; p=0.01), CRP (β= −0.09; 95% CI, −0.22 to 0.03; p=0.1), and fibrinogen (β= −0.09; 95% CI, −0.22 to 0.04; p=0.2). Each 1-SD higher concentration of IL-6 (OR, 1.15; 95% CI, 1.07–1.23), Factor VIII (OR, 1.11; 95% CI, 1.03–1.18), and CRP (OR, 1.09; 95% CI, 1.02–1.16) at baseline was significantly associated with rapid kidney function decline. Only IL-6 was significantly associated with incident low eGFR (OR, 1.09; 95% CI, 1.00–1.19).
Observational study design and absence of measured GFR.
Inflammation and coagulation biomarkers are associated with declining kidney function in ambulatory adults without established CVD or CKD.
Uninsured adults in the United States have poor access to health care services and worse health outcomes than insured adults. Little is known about the association between lack of insurance and chronic kidney disease (CKD) progression to end-stage renal disease (ESRD) or death in patients at high risk of kidney disease. We used 2000–2011 data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP) to examine this association.
The study population included KEEP participants younger than 65 years. Outcomes were time to ESRD (chronic kidney failure treated by renal replacement therapy) and time to death. Incident ESRD was ascertained by linkage to the US Renal Data System, and vital status, by linkage to the Social Security Administration Death Master File. We used Cox proportional hazard regression to examine the association between insurance and risk of death or ESRD after adjusting for demographic variables.
Of 86,588 participants, 27.8% had no form of insurance, 10.3% had public insurance, and 61.9% had private insurance; 15.0% had CKD (defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urine albumin-creatinine ratio ≥30 mg/g), 63.3% had hypertension, and 27.7% had diabetes. Of participants with CKD, 29.3% had no health insurance. Participants without insurance were younger, more likely to be Hispanic and to have 12 or fewer years of education, and less likely to have seen a physician in the past year. After adjustment for demographic characteristics, uninsured KEEP participants were 82% more likely than privately insured participants to die (HR, 1.82; 95% CI, 1.56–2.12; P < 0.001) and 72% more likely to develop ESRD (HR, 1.72; 95% CI, 1.33–2.22; P < 0.001). The association between insurance and outcomes varied by CKD stage.
Lack of insurance is an independent risk factor for early death and ESRD in this population at high risk of kidney disease. Considering the high morbidity and mortality and increasing cost associated with ESRD, access to appropriate health insurance coverage is warranted.
Chronic kidney disease; end-stage renal disease; health insurance; mortality; public health
The CD14 is a key molecule in innate immunity that mediates cell activation and signaling in response to endotoxin and other bacterial wall-derived components. CD14 protein exists in soluble (sCD14) and membrane bound (mCD14) forms. The correlates of sCD14 in persons undergoing long-term hemodialysis (HD) are not known.
We hypothesized that elevated sCD14 in hemodialysis patients is associated pro-inflammatory cytokine activation and increased mortality in a 33-month cohort
Well defined cohort of 310 long-term HD patients who participated in the Nutritional and Inflammatory Evaluation in Dialysis (NIED) Study.
Predictors and other Measurements
Soluble CD14 in serum.
Predictors and other Measurements
Thirty-three month mortality in the NIED Study cohort.
The mean sCD14 was 7.24±2.45 μg/ml. Tumor necrosis factor-α (TNF-α) was the strongest correlate of sCD14 (r=+0.24, p<0.001) followed by interleukin(IL)-6 (r=+0.18, p=0.002), serum ferritin (r+=0.21, p=<0.001), total iron binding capacity (r=−0.19, p=<0.001), body mass index (r=−0.15, p=0.008), vintage (r=+0.14, p=0.01), low density lipoprotein-C (r=+0.13, p=0.03) and body fat (r=−0.11, p=0.06). Over the 33 months follow-up, 71 (23%) patients died. Multivariable Cox proportional analysis adjusted for case-mix and other nutritional and inflammatory confounders including serum TNF-α, C-Reactive protein, and IL-6 showed that compared to lowest sCD14 tertile, sCD14 levels in the third tertile (>7.8 μg/ml) were associated with higher death risk (hazard ratio, 1.94; 95% confidence interval, 1.01–3.75, p=0.04).
Survivor bias in combined incident/prevalent studies.
Elevated sCD14 is positively related to markers of inflammation, negatively related to nutritional status and an independent predictor of mortality in long-term HD patients. Further studies are needed to examine the usefulness of sCD14 in risk stratification and clinical decision-making process in hemodialysis patients.
Hemodialysis; mortality; inflammation; endotoxin; soluble CD14; mortality; nutritional status
Change in glomerular filtration rate (GFR) is important for clinical decision making. GFR estimates from serum creatinine provide an unbiased but imprecise estimate of GFR at single time points. However, the accuracy of estimated GFR over time is not well known.
Longitudinal study of diagnostic test accuracy
Settings and participants
Four clinical trials with longitudinal measures of GFR and serum creatinine on the same day, including subjects with and without kidney disease, with a wide range of kidney function, diverse racial backgrounds and varied clinical characteristics.
GFR estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
GFR measured using urinary clearance of 125I-iothalamate
Data included 19,735 GFR measurements in 3531 subjects over mean follow up of 2.6 years. Mean at baseline for measured and estimated GFR and error (measured GFR – estimated GFR) were 73.1 (95% CI, 71.6 to 74.5), 72.7 (95% CI, 71.5 to 74.0) and 0.14 (95% CI, −0.35 to 0.63) ml/min/1.73 m2, respectively. The mean rate of change in measured and estimated GFR and error was −2.3 (95% CI, −2.4 to −2.1), −2.2 (95% CI, −2.4 to −2.1) and −0.09 (95% CI, −0.24 to 0.05) ml/min/1.73 m2 per year (p <.001, p <.001, and p = 0.2 respectively). The variability (ie, SD) among subjects in rate of change in measured GFR, estimated GFR and error was 4.3, 3.4 and 3.3 ml/min/1.73 m2 per year, respectively. Only 15% of subjects had a rate of change in error of more than 3 ml/min/1.73 m2 per year, and only 2% had a rate of change in error larger than 5% per year.
Subject characteristics were not available over time.
Accuracy of GFR estimates did not change over time. Clinicians should interpret changes in estimated GFR over time as reflecting changes in measured GFR rather than changes in errors in the GFR estimates in most individuals.
Identifying individuals at risk for chronic kidney disease (CKD) is critical for timely treatment initiation to slow progression of the disease. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) are known biomarkers of acute kidney injury, but it is unknown whether these markers are associated with incident CKD stage 3 in the general population.
Matched case-control study
Setting and Participants
African American and Caucasian participants from the Atherosclerosis Risk in Communities (ARIC) study who at baseline had an estimated glomerular filtration rate ≥ 60 ml/min/1.73 m2 and urinary albumin-creatinine ratio (UACR) ≤ 30 mg/g. A total of 143 controls were matched on age, sex and race to 143 cases of incident CKD stage 3 after 8.6 years of follow-up.
Quartile of NGAL and KIM-1.
Outcomes & Measurements
Incident CKD stage 3 (eGFR < 60 ml/min/1.73 m2 at follow-up and a decrease in eGFR from baseline to follow-up of ≥25%)
Both NGAL (p=0.05) and KIM-1 (p<0.001) were positively correlated with baseline UACR; neither was associated with baseline eGFR. Participants with NGAL concentrations in the fourth quartile had more than 2-fold higher odds (adjusted OR, 2.11, 95% CI, 0.96–4.64) of incident CKD stage 3 compared to participants in the first quartile after multivariable adjustment (p-trend=0.03). Adjustment for urinary creatinine and albumin resulted in a non-significant association (highest quartile adjusted OR. 1.52; 95% CI, 0.64–3.58; p=0.2). No significant association between KIM-1 levels and incident CKD was observed in crude or adjusted models.
The relatively small sample size of the study limits precision and power to detect weak associations.
Higher NGAL levels, but not KIM-1 levels, were associated with incident CKD stage 3. Adjustment for urinary creatinine and albumin concentration attenuated this association. Additional studies are needed to confirm these findings and assess the utility of urinary NGAL as a marker of CKD risk.
Glomerular filtration rate (GFR) is considered the best measure of kidney function, but repeated assessment is not feasible in most research studies.
Cross-sectional study of 1,433 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study (i.e., the GFR subcohort) to derive an internal GFR estimating equation using a split sample approach.
Setting & Participants
Adults from 7 US metropolitan areas with mild to moderate chronic kidney disease; 48% had diabetes and 37% were black.
CRIC GFR estimating equation
Reference Test or Outcome
Urinary 125I-iothalamate clearance testing (measured GFR)
Laboratory measures including serum creatinine and cystatin C, and anthropometrics
In the validation dataset, the model that included serum creatinine, serum cystatin C, age, gender, and race was the most parsimonious and similarly predictive of mGFR compared to a model additionally including bioelectrical impedance analysis phase angle, CRIC clinical center, and 24-hour urinary creatinine excretion. Specifically, the root mean square errors for the separate model were 0.207 vs. 0.202, respectively. The performance of the CRIC GFR estimating equation was most accurate among the subgroups of younger participants, men, non-blacks, non-Hispanics, those without diabetes, those with body mass index <30 kg/m2, those with higher 24-hour urine creatinine excretion, those with lower levels of high-sensitivity C-reactive protein, and those with higher mGFR.
Urinary clearance of 125I-iothalamate is an imperfect measure of true GFR; cystatin C is not standardized to certified reference material; lack of external validation; small sample sizes limit analyses of subgroup-specific predictors.
The CRIC GFR estimating equation predicts measured GFR accurately in the CRIC cohort using serum creatinine and cystatin C, age, gender, and race. Its performance was best among younger and healthier participants.
glomerular filtration rate (GFR); kidney function; GFR estimation
Serum cystatin C level has been shown to have a stronger association with clinical outcomes than serum creatinine level. However, little is known about the combined association of cystatin C–based estimated glomerular filtration rate (eGFRcys) and albuminuria with clinical outcomes, particularly at levels lower than current chronic kidney disease (CKD) cutoffs.
Setting & Participants
10,403 ARIC (Atherosclerosis Risk in Communities) Study participants followed up for a median of 10.2 years.
Mortality, coronary heart disease (CHD), and heart failure, as well as a composite of any of these separate outcomes.
Both decreased eGFRcys and albuminuria were associated independently with the composite outcome, as well as mortality, CHD, and heart failure. Although eGFRcys of 75-89 mL/min/1.73 m2 in the absence of albuminuria (albumin-creatinine ratio [ACR] <10 mg/g) or albuminuria with ACR of 10-29 mg/g with normal eGFRcys (90-104 mL/min/1.73 m2) was not associated significantly with any outcome compared with eGFRcys of 90-104 mL/min/1.73 m2 and ACR <10 mg/g, the risk of each outcome was significantly higher in those with both eGFRcys of 75-89 mL/min/1.73 m2 and ACR of 10-29 mg/g (for mortality, HR of 1.4 [95% CI, 1.1-2.0]; for CHD, HR of 1.9 [95% CI, 1.4-2.6]; for heart failure, HR of 1.8 [95% CI, 1.2-2.7]). Combining the 2 markers improved risk classification for all outcomes (P < 0.001), even in those without overt CKD.
Only one measurement of cystatin C.
Mildly decreased eGFRcys and mild albuminuria independently contributed to the risk of mortality, CHD, and heart failure. Even minimally decreased eGFRcys (75-89 mL/min/1.73 m2) is associated with increased risk in the presence of mild albuminuria. Combining the 2 markers is useful for improved risk stratification even in those without clinical CKD.
Epidemiology; kidney; outcomes
Few studies have examined the impact of childhood obesity on later kidney disease, and consequently, our understanding is very limited.
Longitudinal population-based cohort.
Setting & Participants
The Medical Research Council National Survey of Health and Development, a socially stratified sample of 5,362 singletons born in 1 week in March 1946 in England, Scotland, and Wales, of which 4,340 were analyzed.
Early-life overweight latent classes (never, prepubertal only, pubertal onset, or always), derived from repeated measurements of body mass index between ages 2 and 20 years.
Outcomes & Measurements
The primary outcome was chronic kidney disease (CKD), defined as creatinine- or cystatin C–based estimated glomerular filtration rate (eGFRcr and eGFRcys, respectively) <60 mL/min/1.73 m2 or urine albumin-creatinine ratio (UACR) ≥3.5 mg/mmol measured at age 60-64 years. Associations were explored through regression analysis, with adjustment for socioeconomic position, smoking, physical activity level, diabetes, hypertension, and overweight at ages 36 and 53 years.
2.3% of study participants had eGFRcr <60 mL/min/1.73 m2, 1.7% had eGFRcys <60 mL/min/1.73 m2, and 2.9% had UACR ≥3.5 mg/mmol. Relative to being in the never-overweight latent class, being in the pubertal-onset– or always-overweight latent classes was associated with eGFRcys-defined CKD (OR, 2.04; 95% CI, 1.09-3.82). Associations with CKD defined by eGFRcr (OR, 1.27; 95% CI, 0.71-2.29) and UACR (OR, 1.33; 95% CI, 0.70-2.54) were less marked, but in the same direction. Adjustment for lifestyle and health factors had little impact on effect estimates.
A low prevalence of CKD resulted in low statistical power. No documentation of chronicity for outcomes. All-white study population restricts generalizability.
Being overweight in early life was found to be associated with eGFRcys-defined CKD in later life. The associations with CKD defined by eGFRcr and UACR were less marked, but in the same direction. Reducing or preventing overweight in the early years of life may significantly reduce the burden of CKD in the population.
Childhood obesity; chronic kidney disease; estimated glomerular filtration rate
Current management of ADPKD is focused on managing disease complications, not on slowing cyst development or preventing progression to kidney failure. Tolvaptan, a selective vasopressin V2 receptor antagonist, has proven to inhibit kidney cyst growth and preserve kidney function in multiple animal models of polycystic kidney disease. The TEMPO¾ trial will examine the long-term effectiveness and safety of tolvaptan in ADPKD patients.
A prospective, three-year, multicenter, double-blind, placebo controlled trial.
Setting & Participants
This trial includes ADPKD patients with a relatively preserved kidney function (baseline eCrCl ≥ 60 mL/min) ≤ 50 years of age and total kidney volume (TKV) measured with magnetic resonance imaging (MRI) ≥ 750 mL
Administration of placebo or tolvaptan, a selective V2 receptor antagonist, dose-titrated to tolerance.
Primary outcome is TKV percent change from baseline for tolvaptan relative to placebo. Secondary outcome parameters include time to ADPKD associated complications (renal function decline, blood pressure control, renal pain and albuminuria) and safety endpoints.
Measurements included TKV, kidney function, albuminuria, kidney pain, adverse events and vital signs.
Between March 2007 and January 2009, 1445 ADPKD patients were enrolled. Preliminary baseline median TKV was 1.46 L and eCrCl was 105 ± 34 mL/min. A pre-specified, blinded, sample size re-calculation at 2/3 enrollment confirmed the likely power of the study to detect 20% differences from placebo in the primary and key secondary endpoints at p<0.05.
This is a preselected ADPKD population chosen for its risk for progression to renal failure and may not represent the general ADPKD population. If the study results are positive with regard to the primary endpoint, confirmation among secondary clinical outcomes will be required.
Results from this randomized clinical trial will show whether treatment with a vasopressin V2 receptor antagonist effectively inhibits cyst growth and disease progression defined as a reduction in change in TKV in ADPKD patients.
clinical trial; ADPKD; polycystic kidney disease; vasopressin
The contribution of albuminuria to the increased risk of incident end-stage renal disease (ESRD) in individuals with a family history of ESRD has not been well studied.
Prospective cohort study.
Study Setting & Participants
We analyzed data for family history of ESRD collected from 19,409 participants of the Renal REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study.
Family history of ESRD was ascertained by asking “Has anyone in your immediate family ever been told that he or she had kidney failure? This would be someone who is on or had been on dialysis or someone who had a kidney transplant.”
Incidence rate for ESRD.
Morning urine albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Incident cases of ESRD were identified through the US Renal Data System.
A family history of ESRD was reported by 11.1% of participants. Mean eGFRs for those with and without a family history of ESRD were 87.5 ± 22.2 (SD) and 86.5 ± 19.3 mL/min/1.73 m2, respectively (P = 0.05) and the respective geometric mean ACRs were 12.2 and 9.7 mg/g (P < 0.001). ESRD incidence rates for those with and without a family history of ESRD were 244.3 and 106.1/100,000 person-years, respectively. After adjusting for age, sex, and race, the ESRD HR for those with versus those without a family history of ESRD was 2.13 (95% CI, 1.18-3.83). Adjustment for comorbid conditions and socioeconomic status attenuated this association (HR, 1.82; 95% CI, 1.00-3.28), and further adjustment for baseline eGFR and ACR completely attenuated the association between family history of ESRD and incident ESRD (HR, 1.12; 95% CI, 0.69-1.80).
The report of a family history of ESRD was not validated.
Family history of ESRD is common in older Americans and the increased risk of ESRD associated with a family history reflects lower GFR, higher albuminuria, and comorbid conditions.
Race; albuminuria; end-stage renal disease; chronic kidney disease
Diabetic nephropathy (DN) represents a major burden to public health cost. Tight glycemic and blood pressure control can dramatically slow but not halt the progression of the disease, and a large number of patients progress towards end-stage renal disease despite the currently available multifactorial interventions. An early and key event in the development of DN is the loss of podocyte function (or glomerular visceral epithelial cells) from the kidney glomerulus, where they contribute to the integrity of the glomerular filtration barrier. The recent evidence that podocyte can be the direct target of circulating hormones, lipids and adipokynes that are affected in diabetes, has prompted us to review the clinical and experimental evidence supporting novel endocrine and metabolic pathways in the pathogenesis of podocyte malfunction and in the development of DN.
Chronic kidney disease (CKD) is common, but under-recognized, among patients in the health care system, where improving patient safety is a high priority. Poor disease recognition and several other features of CKD make it a high risk condition for adverse safety events. In this review, we will discuss the unique attributes of CKD, which make it a high risk condition for patient safety mishaps. We will point out that adverse safety events in this disease have the potential to contribute to disease progression; namely, accelerated loss of kidney function and an increased incidence of end-stage renal disease (ESRD). We will also propose a framework in which to consider patient safety in CKD, highlighting the need for disease-specific safety indicators that reflect unsafe practices in this disease. Finally, we will discuss the hypothesis that increased recognition of CKD will reduce disease-specific safety events, and in this way decrease the likelihood of adverse outcomes including an accelerated rate of kidney function loss and an increased incidence of ESRD.
patient safety; chronic kidney disease; disease recognition; medical errors
Depressive symptoms are correlated with poor health outcomes in adults with chronic kidney disease (CKD). The prevalence, severity, and treatment of depressive symptoms and potential risk factors, including level of kidney function, in diverse populations with CKD have not been well studied.
Settings and Participants
Participants at enrollment into the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies. CRIC enrolled Hispanics and non-Hispanics at seven centers from 2003-2007, and H-CRIC enrolled Hispanics at the University of Illinois from 2005-2008.
Depressive symptoms measured by Beck Depression Inventory (BDI)
Demographic and clinical factors
Elevated depressive symptoms (BDI >= 11) and antidepressant medication use
Among 3853 participants, 28.5% had evidence of elevated depressive symptoms and 18.2% were using antidepressant medications; 30.8% of persons with elevated depressive symptoms were using antidepressants. The prevalence of elevated depressive symptoms varied by level of kidney function: 25.2% among participants with eGFR ≥ 60 ml/min/1.73m2, and 35.1% of those with eGFR < 30 ml/min/1.73m2. Lower eGFR (OR per 10 ml/min/1.73m2 decrease, 1.09; 95% CI, 1.03-1.16), Hispanic ethnicity (OR, 1.65; 95% CI, 1.12-2.45), and non-Hispanic black race (OR, 1.43; 95% CI, 1.17-1.74) were each associated with increased odds of elevated depressive symptoms after controlling for other factors. In regression analyses incorporating BDI score, while female sex was associated with a greater odds of antidepressant use, Hispanic ethnicity, non-Hispanic black race, and higher levels of urine albumin were associated with decreased odds of antidepressant use (p<0.05 for each).
Absence of clinical diagnosis of depression and use of non-pharmacologic treatments
Although elevated depressive symptoms were common in individuals with CKD, use of antidepressant medications is low. African Americans, Hispanics, and individuals with more advanced CKD had higher odds of elevated depressive symptoms and lower odds of antidepressant medication use.
Data are scant regarding access to health care in patients with chronic kidney disease (CKD). We performed descriptive analyses using data from the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP), a nationwide health screening program for adults at high risk of CKD.
From 2000–2010, a total of 122,502 adults without end-stage renal disease completed KEEP screenings; 27,927 (22.8%) met criteria for CKD (10,082, stages 1–2; 16,684, stage 3; and 1,161, stages 4–5). CKD awareness, self-rated health status, frequency of physician visits, difficulty obtaining medical care, types of caregivers, insurance status, and medication coverage and estimated costs were assessed.
Participants with CKD were more likely to report fair/poor health status than those without CKD. Health care utilization increased at later CKD stages; ~95% of participants at stages 3–5 had visited a physician during the preceding year compared with 83.7% of participants without CKD. More Hispanic and African American than white participants at all CKD stages reported not having a physician. Approximately 40% of participants younger than 65 years reported fair/poor health status at stages 4–5 compared with ~30% who were 65 years and older. Younger participants at all stages were more likely to report extreme or somewhat/moderate difficulty obtaining medical care. Comorbid conditions (diabetes, hypertension, and prior cardiovascular events) were associated with increased utilization of care. Utilization of nephrology care was poor at all CKD stages; <6% of participants at stage 3 and <30% at stages 4–5 reported ever seeing a nephrologist.
Lack of health insurance and perceived difficulty obtaining medical care with lower health care utilization, both of which are consistent with inadequate access to health care, are more likely for KEEP participants who are younger than 65 years, nonwhite, and without previously diagnosed comorbid conditions. Nephrology care is infrequent in elderly participants with advanced CKD who are nonwhite, have comorbid disease, and have high-risk states for cardiovascular disease.
Chronic kidney disease; health care access; health insurance; medication payment; socioeconomic status; educational status
Evaluating the accuracy of estimated glomerular filtration rate (eGFR) derived from serum creatinine (SCr) and serum cystatin C (SCysC) equations requires gold standard measures of GFR. However, the influence of imprecise measured GFRs (mGFRs) on estimates of equation error is unknown.
Diagnostic test study
Setting & Participants
1995 participants from the Modification of Diet in Renal Disease (MDRD) Study and African American Study of Kidney Disease (AASK) with at least two baseline mGFRs from125I-iothalamate urinary clearances, one standardized Scr value, and one SCysC value.
eGFRs calculated from the 4-variable IDMS-traceable MDRD Study equation, the CKD-EPI SCysC equation, the CKD-EPI SCr-SCysC equation, and mGFRs collected from another pre-randomization visit
A single reference mGFR, average of two, and average of three mGFRs; additional analysis limited to consistent mGFRs (difference fl 25% from the reference mGFR)
We found that mGFRs had stable means but substantial variability across visits. Of all the mGFRs collected a mean of 62 days apart from the reference visit, 8.0% fell outside 30% of the single reference mGFR (1-P30). The estimation equations were less accurate as 12.1%, 17.1% and 8.3% of the eGFR from MDRD Study, CKD-EPI SCysC, and CKD-EPI SCr-SCysC equations fell outside 30% of the same gold standard (1-P30). However, improving the precision of the reference test from a single mGFR to the average of three consistent mGFRs reduced these error estimates (1-P30) to 8.0%, 12.5% and 3.9% respectively.
Study population limited to those with CKD.
Imprecision in gold standard measures of GFR contribute to an appreciable proportion of the cases where estimated and measured GFR differs by more than 30%. Reducing and quantifying errors in gold standard measurements of GFR is critical to fully estimating the accuracy of GFR estimates.
gold standard; measured glomerular filtration rate; kidney function estimation equations; cystatin C; creatinine
The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that higher GFR may be associated with increased mortality.
A meta-analysis of cohort studies and trials.
Setting & Population
Patients with advanced CKD.
Selection Criteria for Studies
We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis initiation and mortality.
estimated or calculated GFR at dialysis initiation.
Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality.
Sixteen cohort studies and one randomized controlled trial were identified (n=1,081,116). By meta-analysis, restricted to the 15 cohorts (n=1,079,917), higher GFR at dialysis initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03–1.05; P<0.001). However, there was significant heterogeneity (I2=97%; P<0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR 1.03; 95% CI 1.02, 1.04; P<0.001; residual I2=97%). The highest mortality risk was observed in hemodialysis cohorts (HR 1.05; 95% CI 1.02, 1.08; P<0.001) whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR 1.04; 95% CI 0.99, 1.08, P=0.11; residual I2=98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR 0.80; 95% CI 0.71, 0.91; P=0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR 1.04; 95% CI 1.03, 1.05; P<0.001; residual I2=97%).
Paucity of randomized controlled trials; different methods for determining GFR; and substantial heterogeneity.
Higher estimated rather than calculated GFR at dialysis initiation is associated with a higher mortality risk among patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study.
ESRD; CKD; hemodialysis; peritoneal dialysis; early initiation; late initiation; GFR; mortality
Recent studies show a survival advantage with kidney transplant amongst elderly patients compared to those on dialysis.
In our present study we examined and compared the association of expanded donor criteria (ECD) kidney and living kidney donation with outcome of kidney transplant across different ages including elderly recipients.
Setting and Participants
Using the Scientific Registry of Transplant Recipients, we identified 145,470 adult kidney transplanted patients. Mortality and death-censored graft failure risks were estimated by Cox proportional regression analyses over a follow-up period with a median of 3.9 years.
ECD kidney and living kidney donation and age compared to others.
Mortality and death-censored graft failure risk.
Patients were 45±16 years old and included 40% women and 19% diabetics. Compared to transplanted patients 55-<65 years old, the fully adjusted death-censored graft failure risk was somewhat higher in patients ≥75 years old (HR, 1.30; 95% CI, 1.09–1.56), 35-<55 years (HR, 1.13; 95% CI, 1.08–1.17) and 18-<35 years (HR, 1.64; 95% CI, 1.57–1.71). Compared to non-ECD kidneys, ECD kidneys were significant predictors of mortality in non-elderly patients (18–<35 years: HR, 1.46 [95% CI, 1.19–1.77]; 35-<55 years: HR, 1.23 [95% CI, 1.14–1.32]; and 55-<65 years: HR, 1.26 [95% CI, 1.15–1.38]) and patients aged 65-<70 years (HR, 1.20; 9% CI, 1.05–1.36); but not in other groups of elderly patients (HRs of 1.12 [95% CI, 0.93–1.36] 70-<75 years and 1.04 [95% CI, 0.74–1.47] for ≥75 years). Similar results were found in risk of graft loss. Compared to deceased donor, living kidney was associated with better survival in all age groups and lower graft loss risk in patients aged <70 years.
Unmeasured confounders cannot be adjusted for.
Among deceased donors, the ECD kidneys are not associated with either increased mortality or graft failure in recipients over 70 years. Among all types of donors, the persistent association between living donor kidneys and lower all-cause mortality across all ages suggests that, if possible, elderly patients gain longevity from living donor kidney transplant.
elderly; kidney transplantation; mortality; graft failure; living donor