Pediatric GFR Estimating Equations Applied to Adolescents in the General Population

Summary

Background and objectives

We examined the distribution of estimated GFR (eGFR) in a healthy cohort of adolescents to inform clinical and research use.

Design, setting, participants, & measurements

Various creatinine-based (n = 3256) and/or cystatin C–based (n = 811) equations, including the recently developed complete and bedside equations from the Chronic Kidney Disease in Children (CKiD) study, were applied to U.S. adolescents 12 to 17 years of age participating in the 1999–2002 National Health and Nutrition Examination Survey (NHANES).

Results

The median serum creatinine and cystatin C were 0.7 mg/dl and 0.83 mg/L, respectively. The distribution of eGFR varied widely, with the median GFR ranging from a low of 96.6 ml/min per 1.73 m² (CKiD) to a high of 140.0 ml/min per 1.73 m² (original Schwartz). The proportions of participants with eGFRs <75 ml/min per 1.73 m² are as follows: bedside CKiD 8.9%, Counahan 6.3%, Leger 0.4%, original Schwartz 0%, Filler 1.3%, Grubb 3.1%, Bouvet 2.5%, CKiD 1.8%, and Zappitelli 5.6%. By any equation examined, no group of participants with eGFR ≤10th percentile had an increased prevalence of comorbid conditions consistent with a low measured GFR.

Conclusions

Most pediatric-specific GFR estimating equations resulted in 25% to 50% of the participants having an eGFR <100 ml/min per 1.73 m². However, participants with eGFR in the lower ranges did not have an increased prevalence of morbidities associated with chronic kidney disease. Clinical validation of creatinine- or cystatin C–based estimated GFRs in healthy children is needed before it is possible to screen the general population for chronic kidney disease.     

GFR in Patients with β-Thalassemia Major

Background and objectives

Patients with β-thalassemia major (TM) may have tubular dysfunction and glomerular dysfunction, primarily hyperfiltration, based on eGFR. Assessment of GFR based on serum creatinine concentration may overestimate GFR in these patients. This study sought to determine GFR by using inulin clearance and compare it with measured creatinine clearance (Ccr) and eGFR.

Design, setting, participants & measurements

Patients followed up in an Israeli thalassemia clinic who had been regularly transfused for years and treated with deferasirox were included in the study. They were studied by inulin clearance, Ccr, the CKD Epidemiology Collaboration and the Modification of Diet in Renal Disease equations for eGFR, and the Cockcroft–Gault estimation for Ccr. Expected creatinine excretion rate and tubular creatinine secretion rate were calculated.

Results

Nine white patients were studied. Results, given as medians, were as follows: serum creatinine was 0.59 mg/dl (below normal limits); GFR was low (76.6 ml/min per 1.73 m²) and reached the level of CKD; Ccr was 134.9 ml/min per 1.73 m², higher than the GFR because of a tubular creatinine secretion rate of 30.3 ml/min per 1.73 m² (this accounted for 40% of the Ccr); and eGFR calculated by the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease equations and Cockcroft–Gault–estimated Ccr were 133, 141, and 168 ml/min per 1.73 m², respectively. These latter values were significantly higher than the GFR, reaching the hyperfiltration range, and indicated that the estimation techniques were clinically unacceptable as a method for measuring kidney function compared with the GFR according to Bland and Altman analyses.

Conclusions

Contrary to previous reports, patients in this study with TM had normal or reduced GFR. The estimating methods showed erroneous overestimation of GFR and were clinically unacceptable for GFR measurements in patients with TM by Bland and Altman analysis. Therefore, more accurate methods should be used for early detection of reduced GFR and prevention of its further decline toward CKD in these patients.     

High Prevalence of Obstructive Sleep Apnea and Its Association with Renal Function among Nondialysis Chronic Kidney Disease Patients in Japan: A Cross-Sectional Study

Summary

Background and objectives

Obstructive sleep apnea (OSA) affects one of five adults in the general population. Although a high prevalence of OSA has been reported among dialysis patients, the association between nondialysis chronic kidney disease (CKD) and OSA has not been fully investigated. This cross-sectional study aimed to investigate the prevalence of OSA among nondialysis CKD patients in Japan and the association between renal function and OSA.

Design, setting, participants, & measurements

Consecutive nondialysis CKD patients hospitalized mainly for CKD educational program, regardless of their sleep complaints, were enrolled. The diagnosis of OSA and its severity were measured using a type 3 portable monitor.

Results

Overall (n = 100, 68.0% male, median age 66.5 years, body mass index [BMI] 23.1 kg/m², estimated GFR [eGFR] 28.5 ml/min per 1.73 m²), 65% were diagnosed as OSA: mild OSA (apnea-hypopnea index [AHI] 5.0 to 14.9) in 32%, moderate OSA (AHI 15.0 to 29.9) in 25%, and severe OSA (AHI ≥ 30.0) in 8%. Multivariate logistic regression analysis revealed that a 10-ml/min per 1.73 m² decrease in eGFR was associated with a 42% increased odds of OSA after adjustment for age, BMI, and diabetes mellitus. Moreover, in a generalized linear model, eGFR was inversely correlated with AHI after adjustment for covariates.

Conclusions

This study demonstrated a high prevalence of OSA among nondialysis CKD patients in Japan and that the increased risk of OSA was significantly associated with decreased GFR among these patients. Further investigations are warranted to determine OSA''s direct influence on cardiovascular disease.     

Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease

Summary

Background and objectives

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

Design, setting, participants, & measurements

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

Results

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

Conclusions

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

Estimating GFR in Adult Patients with Hematopoietic Cell Transplant: Comparison of Estimating Equations with an Iohexol Reference Standard

Background and objectives

Formal evaluation of kidney function before and after hematopoietic cell transplant is important to determine conditioning regimens, type of transplant, and medication dosing. Serum creatinine and estimating equations may not accurately assess kidney function.

Design, study, participants, & measurements

Existing estimating equations for GFR were compared with an iohexol measure of GFR in a prospective cohort study of 50 patients undergoing hematopoietic cell transplant and subsequent care at the Fred Hutchinson Cancer Research Institute from 2009 to 2013. Patients underwent iohexol GFR, serum creatinine, and cystatin C determination at baseline and day 100 posthematopoietic cell transplant. Iohexol GFR measurements were compared with the CKD Epidemiology Collaboration, Inker CKD Epidemiology Collaboration cystatin C with and without serum creatinine, Modification of Diet in Renal Disease, and Cockcroft–Gault estimating equations using Bland–Altman analysis and McNemar’s test. The iohexol measurements were also compared with blood samples collected simultaneously on filter paper.

Results

Mean differences between iohexol GFR and eGFR on the basis of Bland–Altman analyses ranged from −20.6 to +15.4 ml/min per 1.73 m² at baseline and −12.7 to +12.9 ml/min per 1.73 m² at day 100. The CKD Epidemiology Collaboration and Modification of Diet in Renal Disease estimating equations classified 64% of patients with a GFR<90 at baseline compared with 38% by iohexol GFR (P=0.003 and P<0.01, respectively). No statistically significant differences were seen at day 100. The filter paper GFR had a mean difference of 0 at baseline and 5.9 at day 100. Additionally, 21%–37% and 57%–89% of eGFRs were within 10% and 30%, respectively, of the iohexol GFR at baseline, and 16%–34% and 72%–84% were within 10% and 30%, respectively, of the iohexol GFR at day 100; 98% of the filter paper estimates at baseline were within 30%, and 46% were within 10% of iohexol GFR.

Conclusions

The estimating equations are neither accurate nor precise in the hematopoietic cell transplant population, and clinical decision may require measurement of GFR.     

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

Background and objectives

Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship with early progressive renal decline in type 1 diabetes.

Design, setting, participants, & measurements

A subset of participants with normoalbuminuria (n=204) or microalbuminuria (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April 1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) <20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C <−3.3%/year) and incident advanced CKD (stage ≥3, defined by eGFR [calculated by Modification of Diet in Renal Disease method] <60 ml/min per 1.73 m²). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards.

Results

Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68 (18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P<0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P<0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002).

Conclusions

Cardiac autonomic neuropathy was a strong independent predictor of the long-term risk of early progressive renal decline in type 1 diabetes. Future research should explore the mechanisms by which autonomic neuropathy may be associated with renal function loss.     

A Nurse-coordinated Model of Care versus Usual Care for Stage 3/4 Chronic Kidney Disease in the Community: A Randomized Controlled Trial

Summary

Background and objectives

It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD.

Design, setting, participants, & measurements

A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m² identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked.

Results

The average decline in eGFR over 20 months was −1.9 ml/min per 1.73 m². eGFR declined by ≥4 ml/min per 1.73 m² within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year.

Conclusions

Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.     

Age-specific associations of reduced estimated glomerular filtration rate with concurrent chronic kidney disease complications

Summary

Background and objectives

It has been suggested that moderate reductions in estimated GFR (eGFR) among older adults may not reflect chronic kidney disease (CKD).

Design, setting, participants, & measurements

We examined age-specific (<60, 60 to 69, 70 to 79, and ≥80 years) associations between eGFR level and six concurrent CKD complications among 30,528 participants from the National Health and Nutrition Examination Survey (NHANES) 1988 to 1994 and 1999 to 2006 (n = 8242 from NHANES 2003 to 2006 for hyperparathyroidism). Complications included anemia (hemoglobin <12 g/dl women, <13.5 g/dl men), acidosis (bicarbonate <22 mEq/L), hyperphosphatemia (phosphorus ≥4.5 mg/dl), hypoalbuminemia (albumin <3.5 mg/dl), hyperparathyroidism (intact parathyroid hormone ≥70 pg/ml), and hypertension (systolic/diastolic BP ≥140/90 mmHg or antihypertensive use).

Results

Among participants ≥80 years old, compared with those with estimated GFR (eGFR) ≥60 ml/min per 1.73 m², the multivariable adjusted prevalence ratios (95% confidence interval) associated with eGFR levels of 45 to 59 and <45 ml/min per 1.73 m² were 1.39 (1.11 to1.73) and 2.06 (1.59 to 2.67) for anemia, 1.33 (0.89 to 1.98) and 2.47 (1.52 to 4.00) for acidosis, 1.11 (0.70 to 1.76) and 2.16 (1.36 to 3.42) for hyperphosphatemia, 2.04 (1.39 to 3.00) and 2.83 (1.76 to 4.53) for hyperparathyroidism and 1.09 (1.03 to 1.14), and 1.12 (1.05 to 1.19) for hypertension, respectively. Higher prevalence ratios for these complications at lower eGFR levels were also present at younger ages. Reduced eGFR was associated with hypoalbuminemia only for adults <70.

Conclusions

Reduced eGFR was associated with a higher prevalence of several concurrent CKD complications, regardless of age.     

Relationship between blood pressure and incident chronic kidney disease in hypertensive patients

Summary

Background and objectives

Hypertension is an important cause of chronic kidney disease (CKD). Identifying risk factors for progression to CKD in patients with normal kidney function and hypertension may help target therapies to slow or prevent decline of kidney function. Our objective was to identify risk factors for development of incident CKD and decline in estimated GFR (eGFR) in hypertensive patients.

Design, setting, participants, & measurements

Cox proportional hazards models were used to assess the relationship between incident CKD (defined as eGFR <60 ml/min per 1.73 m²) and potential risk factors for CKD from a registry of hypertensive patients.

Results

Of 43,305 patients meeting the inclusion criteria, 12.1% (5236 patients) developed incident CKD. Diabetes was the strongest predictor of incident CKD (hazard ratio, 1.96; 95% confidence interval, 1.84 to 2.09) and was associated with the greatest rate of decline in eGFR (−2.2 ml/min per 1.73 m² per year). Time-varying systolic BP was associated with incident CKD with risk increasing above 120 mmHg; each 10-mmHg increase in baseline and time-varying systolic BP was associated with a 6% increase in the risk of developing CKD (hazard ratio, 1.06; 95% confidence interval, 1.04 to 1.08 for both). Time-weighted systolic BP was associated with a more rapid decline in eGFR of an additional 0.2 ml/min per 1.73 m² per year decline for every 10-mmHg increase in systolic BP.

Conclusions

We found that time-varying systolic BP was associated with incident CKD, with an increase in risk above a systolic BP of 120 mmHg among individuals with hypertension.     

Chronic Kidney Disease in Octogenarians

Summary

Background and objectives

There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).

Design, setting, participants, & measurements

In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m². GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFR_EPI, eGFR_CYS3var) and the one-variable cystatin C equation (eGFR_CYS1var). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.

Results

Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFR_EPI, eGFR_CYS3var, and eGFR_CYS1var were 59, 62, and 70 ml/min per 1.73 m², and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKD_EPI (OR, 1.53; 95% CI, 1.15 to 2.03), CKD_CYS3var (OR, 1.67; 95% CI, 1.25, 2.23), and CKD_CYS1var (OR, 2.09; 95% CI, 1.55, 2.83).

Conclusions

Reduced eGFR is highly prevalent in octogenarians, and the eGFR_CYS1var equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.     

GFR Decline and Mortality Risk among Patients with Chronic Kidney Disease

Summary

Background and objectives

Estimates of the effect of estimated GFR (eGFR) decline on mortality have focused on populations with normal kidney function, or have included limited information on factors previously shown to influence the risk of death among patients with CKD.

Design, setting, participants, & measurements

We retrospectively assessed the effect of rate of eGFR decline on survival of patients with CKD receiving primary care through a large integrated health care system in central Pennsylvania between January 1, 2004, and December 31, 2009.

Results

A total of 15,465 patients were followed for a median of 3.4 years. Median rates of eGFR change by those in the lower, middle, and upper tertiles of eGFR slope were −4.8, −0.6, and 3.5 ml/min per 1.73 m²/yr, respectively. In Cox proportional hazard modeling for time to death, adjusted for baseline proteinuria, changes in nutritional parameters, and episodes of acute kidney injury during follow-up (among other covariates), the hazard ratio for those in the lower (declining) and upper (increasing) eGFR tertiles (relative to the middle, or stable, tertile) was 1.84 and 1.42, respectively. Longitudinal changes in nutritional status as well as episodes of acute kidney injury attenuated the risk only modestly. These findings were consistent across subgroups.

Conclusions

eGFR change over time adds prognostic information to traditional mortality risk predictors among patients with CKD. The utility of incorporating eGFR trends into patient-risk assessment should be further investigated.     

The Impact of Interlaboratory Differences in Cystatin C Assay Measurement on Glomerular Filtration Rate Estimation

Summary

Background and objectives

Cystatin C (CysC) is a promising marker of GFR. Several equations have been derived to estimate GFR from its serum concentration. Heterogeneity in the performance of these equations exists in validation studies even when the same CysC assay from the same manufacturer is utilized. This study was designed to examine the differences in CysC and GFR estimation (eGFR) using Siemens'' nephelometric immunoassay and the Mayo Clinic equation. The ability of the eGFRs to predict measured GFR was also examined.

Design, setting, participants, & measurements

Ninety-seven split samples were sent to laboratories at Children''s Hospital of Eastern Ontario (CHEO) in Ottawa, Canada, and at the Mayo Clinic in Rochester, Minnesota.

Results

The mean CHEO CysC was 0.17 mg/L (10%) lower than the mean Mayo Clinic CysC. Using the Mayo Clinic equation, the mean eGFR difference was 7.2 ml/min per 1.73 m² (15%). Approximately 36% of the results agreed within 10%, while 13% were discordant by greater than 30%. Larger absolute differences in mean eGFR between the two laboratories were found in the subgroup with CysC less than 1.41 mg/L as compared with the subgroup greater than 1.41 mg/L (9.5 versus 5.0 ml/min per 1.73 m²). Correction of CHEO values to the Mayo Clinic did not improve GFR estimation.

Conclusions

Significant differences in CysC measurement exist between laboratories using the same assay by the same manufacturer and these lead to clinically relevant differences in GFR estimation. This interlaboratory variability needs to be recognized when interpreting and comparing CysC and eGFR results.     

NT-ProBNP and Troponin T and Risk of Rapid Kidney Function Decline and Incident CKD in Elderly Adults

Background and objectives

Elevations in N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

Design, setting, participants, & measurements

N-terminal pro–B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR≥30%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

Results

In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro–B-type natriuretic peptide (>237 pg/ml) had an 67% higher risk of rapid decline and 38% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.92 to 1.50).

Conclusions

Elevated N-terminal pro–B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.     

Progression of Pediatric CKD of Nonglomerular Origin in the CKiD Cohort

Background and objectives

Congenital anomalies of the kidney and urinary tract and genetic disorders cause most cases of CKD in children. This study evaluated the relationships between baseline proteinuria and BP and longitudinal changes in GFR in children with these nonglomerular causes of CKD.

Design, setting, participants, & measurements

Urine protein-to-creatinine ratio, casual systolic and diastolic BP (normalized for age, sex, and height), and GFR decline were assessed in the prospective CKD in Children cohort study.

Results

A total of 522 children, median age 10 years (interquartile range, 7, 14 years) with nonglomerular CKD were followed for a median of 4.4 years. The mean baseline GFR in the cohort was 52 ml/min per 1.73 m² (95% confidence interval [95% CI], 50 to 54) and declined 1.3 ml/min per 1.73 m² per year on average (95%CI, 1.6 to 1.1). A 2-fold higher baseline urine protein-to-creatinine ratio was associated with an accelerated GFR decline of 0.3 ml/min per 1.73 m² per year (95% CI, 0.4 to 0.1). A 1-unit higher baseline systolic BP z-score was associated with an additional GFR decline of 0.4 ml/min per 1.73 m² per year (95% CI, 0.7 to 0.1). Among normotensive children, larger GFR declines were associated with larger baseline urine protein-to-creatinine ratios; eGFR declines of 0.8 and 1.8 ml/min per 1.73 m² per year were associated with urine protein-to-creatinine ratio <0.5 and ≥0.5 mg/mg, respectively. Among children with elevated BP, average GFR declines were evident but were not larger in children with higher levels of proteinuria.

Conclusions

Baseline proteinuria and systolic BP levels are independently associated with CKD progression in children with nonglomerular CKD.     

Racial and Ethnic Differences in Mortality among Individuals with Chronic Kidney Disease: Results from the Kidney Early Evaluation Program (KEEP)

Summary

Background and objectives

Chronic kidney disease (CKD) is prevalent in minority populations and racial/ethnic differences in survival are incompletely understood.

Design, setting, participants, & measurements

Secondary analysis of Kidney Early Evaluation Program participants from 2000 through 2008 with CKD, not on dialysis, and without previous kidney transplant was performed. Self-reported race/ethnicity was categorized into five groups: non-Hispanic white, African American, Asian, American Indian/Alaska Native, and Hispanic. CKD was defined as a urinary albumin to creatinine ratio of ≥30 mg/g among participants with an estimated GFR (eGFR) ≥60 ml/min per 1.73 m² or an eGFR of <60 ml/min per 1.73 m². The outcome was all-cause mortality. Covariates used were age, sex, obesity, diabetes, hypertension, albuminuria, baseline eGFR, heart attack, stroke, smoking, family history, education, health insurance, geographic region, and year screened.

Results

19,205 participants had prevalent CKD; 55% (n = 10,560) were White, 27% (n = 5237) were African American, 9% (n = 1638) were Hispanic, 5% (n = 951) were Asian, and 4% (n = 813) were American Indian/Alaska Native. There were 1043 deaths (5.4%). African Americans had a similar risk of death compared with Whites (adjusted Hazard Ratio (AHR) 1.07, 95% CI 0.90 to 1.27). Hispanics (AHR 0.66, 95% CI 0.50 to 0.94) and Asians (AHR 0.63, 95% CI 0.41 to 0.97) had a lower mortality risk compared with Whites. In contrast, American Indians/Alaska Natives had a higher risk of death compared with Whites (AHR 1.41, 95% CI 1.08 to 1.84).

Conclusions

Significant differences in mortality among some minority groups were found among persons with CKD detected by community-based screening.     

Serum Uric Acid and Risk of CKD in Type 2 Diabetes

Background and objective

Serum uric acid may predict the onset and progression of kidney disease, but it is unclear whether uric acid is an independent risk factor for diabetic nephropathy. Our aim was to study the relationship between uric acid levels and the development of CKD components in patients with type 2 diabetes.

Design, setting, participants, & measurements

Longitudinal study of a cohort of patients with type 2 diabetes from the database of the Italian Association of Clinical Diabetologists network. From a total of 62,830 patients attending the diabetes centers between January 1, 2004, and June 30, 2008, we considered those with baseline eGFR values ≥60 ml/min per 1.73 m² and normal albumin excretion (n=20,142). Urinary albumin excretion, GFR, and serum uric acid were available in 13,964 patients. We assessed the association of serum uric acid quintiles with onset of CKD components by multinomial logistic regression model adjusting for potential confounders. We calculated the relative risk ratios (RRRs) for eGFR <60 ml/min per 1.73 m², albuminuria, and their combination at 4 years.

Results

At 4-year follow-up, 1109 (7.9%) patients developed GFR <60 ml/min per 1.73 m² with normoalbuminuria, 1968 (14.1%) had albuminuria with eGFR ≥60 ml/min per 1.73 m², and 286 (2.0%) had albuminuria with eGFR <60 ml/min per 1.73 m². The incidence of eGFR <60 ml/min per 1.73 m² increased in parallel with uric acid quintiles: Compared with the lowest quintile, RRRs were 1.46 (95% confidence interval [CI], 1.14 to 1.88; P=0.003), 1.44 (95% CI, 1.11 to 1.87; P=0.006), 1.95 (95% CI, 1.48 to 2.58; P<0.001), and 2.61 (95% CI, 1.98 to 3.42; P<0.001) for second, third, fourth, and fifth quintiles, respectively. Serum uric acid was significantly associated with albuminuria only in presence of eGFR <60 ml/min per 1.73 m².

Conclusions

Mild hyperuricemia is strongly associated with the risk of CKD in patients with type 2 diabetes.     

Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD

Background and objectives

eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR).

Design, setting, participants, & measurements

GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR.

Results

sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m²; 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m²; 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m²; 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (−1.4 ml/min per 1.73 m²; 95% CI, −2.1 to −0.6 per SD increase in sTNFR2, and −0.76 ml/min per 1.73 m²; 95% CI, −1.4 to −0.1 per SD increase in log CRP).

Conclusions

eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR–related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies.     

The Microvasculature in Chronic Kidney Disease

Summary

Background and objectives

Individuals with chronic kidney disease (CKD) stages 3 to 5 have an increased risk of cardiac and other vascular disease. Here we examined the association of CKD 3 to 5 with small vessel caliber.

Design, setting, participants, & measurements

This was a cross-sectional observational study of 126 patients with CKD stages 3 to 5 (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and 126 age- and gender-matched hospital patients with CKD 1 or 2. Retinal vessel diameters were measured from digital fundus images by a trained grader using a computer-assisted method and summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).

Results

Patients with CKD 3 to 5 had a smaller mean CRAE and CRVE than hospital controls (139.4 ± 17.8 μm versus 148.5 ± 16.0 μm, P < 0.001; and 205.0 ± 30.7 μm versus 217.4 ± 25.8 μm, respectively; P = 0.001). CRAE and CRVE decreased progressively with each stage of renal failure CKD1–2 to 5 (P for trend = 0.08 and 0.04, respectively). CKD and hypertension were independent determinants of arteriolar narrowing after adjusting for age, gender, diabetes, dyslipidemia, and smoking history. Patients with CKD 5 and diabetes had a larger mean CRAE and CRVE than nondiabetics (141.4 ± 14.9 μm versus 132.9 ± 14.2 μm; 211.1 ± 34.4 μm versus 194.8 ± 23.8 μm).

Conclusions

The microvasculature is narrowed in patients with reduced eGFR.     

Relative Performance of the MDRD and CKD-EPI Equations for Estimating Glomerular Filtration Rate among Patients with Varied Clinical Presentations

Summary

Background

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed using both CKD and non-CKD patients to potentially replace the Modification of Diet in Renal Disease (MDRD) equation that was derived with only CKD patients. The objective of our study was to compare the accuracy of the MDRD and CKD-EPI equations for estimating GFR in a large group of patients having GFR measurements for diverse clinical indications.

Design, setting, participants, and measurements

A cross-sectional study was conducted of patients who underwent renal function assessment for clinical purposes by simultaneous measurements of serum creatinine and estimation of GFR using the MDRD and CKD-EPI equations and renal clearance of iothalamate (n = 5238).

Results

Bias compared with measured GFR (mGFR) varied for each equation depending on clinical presentation. The CKD-EPI equation demonstrated less bias than the MDRD equation in potential kidney donors (−8% versus −18%) and postnephrectomy donors (−7% versus −15%). However, the CKD-EPI equation was slightly more biased than the MDRD equation in native CKD patients (6% versus 3%), kidney recipients (8% versus 1%), and other organ recipients (9% versus 3%). Among potential kidney donors, the CKD-EPI equation had higher specificity than the MDRD equation for detecting an mGFR <60 ml/min per 1.73 m² (98% versus 94%) but lower sensitivity (50% versus 70%).

Conclusions

Clinical presentation influences the estimation of GFR from serum creatinine, and neither the CKD-EPI nor MDRD equation account for this. Use of the CKD-EPI equation misclassifies fewer low-risk patients as having reduced mGFR, although it is also less sensitive for detecting mGFR below specific threshold values used to define CKD stages.