The Association between a Mediterranean-Style Diet and Kidney Function in the Northern Manhattan Study Cohort

Background and objectives

Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function.

Design, setting, participants, & measurements

This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m²using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥2.5 ml/min per 1.73 m² per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors.

Results

Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m². Incident eGFR<60 ml/min per 1.73 m² developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m² (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98).

Conclusions

A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m² and upper quartile of eGFR decline in a multiethnic cohort.     

Long-Term Renal Function after Endovascular Aneurysm Repair

Background and objectives

Endovascular repair (EVAR) is a common treatment for abdominal aortic aneurysm (AAA). However, its long-term effects on renal function remain unclear. We aimed to assess long-term renal dysfunction after EVAR using a contemporary estimate of GFR and to compare long-term renal outcomes in patients after EVAR with open aneurysm repair (OAR) and in patients without an AAA.

Design, settings, participants, & measurements

We performed a nested case-matched analysis of 726 patients (using a prospectively maintained database for repairs that took place between January 2000 and May 2010 in a tertiary center): 121 patients undergoing OAR (with data at baseline and 5 years postrepair) were case matched (age, sex, smoking, diabetes, baseline eGFR) to patients undergoing suprarenal and infrarenal fixation EVAR (242 in each group) and to 121 patients undergoing carotid endarterectomy (CEA) without AAA. Changes in eGFR were compared (1 and 5 years).

Results

The OAR patients lost an average of 7.4 ml/min per 1.73 m² at 5 years (95% confidence interval [95% CI], 4.8 to 10.6), compared with 8.2 ml/min per 1.73 m² (95% CI, 6.5 to 10.8; P<0.001) for infrarenal-fixation EVAR, 16.9 ml/min per 1.73 m² (95% CI, 13.0 to 21.9, P<0.001) for suprarenal-fixation EVAR, and 5.4 ml/min per 1.73 m² (95% CI, 1.7 to 7.5; P<0.001) for CEA. The decrease in eGFR was steeper during the first postoperative year, with each group losing −2.2 ml/min per 1.73 m² (infrarenal-fixation EVAR), −10.7 ml/min per 1.73 m² (suprarenal-fixation EVAR), and −4.6 ml/min per 1.73 m² (OAR), compared with −1.9 ml/min per 1.73 m² for CEA.

Conclusions

Elective EVAR is associated with a significant decline in eGFR after 5 years, which is steeper in the first postoperative year and more pronounced compared with a similar population with atherosclerotic disease.     

Albuminuria and Estimated Glomerular Filtration Rate as Predictors of Diabetic End-Stage Renal Disease and Death

Summary

Background and objectives

We investigated predictive value of albuminuria and estimated GFR (eGFR) for ESRD in Pima Indians with type 2 diabetes.

Design, setting, participants and measurements

Beginning in 1982, 2420 diabetic Pima Indians ≥18 years old were followed until they developed ESRD or died or until December 31, 2005. Individuals were classified at baseline by urinary albumin-to-creatinine ratio (ACR) and by eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation. Predictors of ESRD and mortality were examined by proportional hazards regression.

Results

During a mean follow-up of 10.2 years, 287 individuals developed ESRD. Incidence of ESRD among individuals with macroalbuminuria (ACR ≥ 300 mg/g) was 9.3 times that of those with normoalbuminuria (ACR < 30 mg/g), controlled for age, gender, and duration of diabetes. Incidence among individuals with eGFR 15 to 29 ml/min per 1.73 m² was 81.9 times that of those with eGFR 90 to 119 ml/min per 1.73 m². Models that combined albuminuria and eGFR added significant predictive information about risk of ESRD or death compared with models containing eGFR or albuminuria alone. The hazard ratio for ESRD associated with a 10-ml/min per 1.73 m² lower eGFR was 1.36, whereas that associated with an increase in albuminuria category was 2.69; corresponding hazard ratios for death were 1.15 and 1.37.

Conclusions

These results suggest that incorporation of quantitative information about albuminuria into staging systems based on eGFR adds significant prognostic information about risk for diabetic ESRD and death.     

Serum 25-Hydroxyvitamin D Level and Kidney Function Decline in a Swiss General Adult Population

Background and objectives

Molecular evidence suggests that levels of vitamin D are associated with kidney function loss. Still, population-based studies are limited and few have considered the potential confounding effect of baseline kidney function. This study evaluated the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline, and incidence of CKD and albuminuria.

Design, setting, participants, & measurements

Baseline (2003–2006) and 5.5-year follow-up data from a Swiss adult general population were used to evaluate the association of serum 25-hydroxyvitamin D with change in eGFR, rapid eGFR decline (annual loss >3 ml/min per 1.73 m²), and incidence of CKD and albuminuria. Serum 25-hydroxyvitamin D was measured at baseline using liquid chromatography–tandem mass spectrometry. eGFR and albuminuria were collected at baseline and follow-up. Multivariate linear and logistic regression models were used considering potential confounding factors.

Results

Among the 4280 people included in the analysis, the mean±SD annual eGFR change was −0.57±1.78 ml/min per 1.73 m², and 287 (6.7%) participants presented rapid eGFR decline. Before adjustment for baseline eGFR, baseline 25-hydroxyvitamin D level was associated with both mean annual eGFR change and risk of rapid eGFR decline, independently of baseline albuminuria. Once adjusted for baseline eGFR, associations were no longer significant. For every 10 ng/ml higher baseline 25-hydroxyvitamin D, the adjusted mean annual eGFR change was −0.005 ml/min per 1.73 m² (95% confidence interval, −0.063 to 0.053; P=0.87) and the risk of rapid eGFR decline was null (odds ratio, 0.93; 95% confidence interval, 0.79 to 1.08; P=0.33). Baseline 25-hydroxyvitamin D level was not associated with incidence of CKD or albuminuria.

Conclusions

The association of 25-hydroxyvitamin D with eGFR decline is confounded by baseline eGFR. Sufficient 25-hydroxyvitamin D levels do not seem to protect from eGFR decline independently from baseline eGFR.     

Metabolic Syndrome and Kidney Disease: A Systematic Review and Meta-analysis

Summary

Background and objectives

Observational studies have reported an association between metabolic syndrome (MetS) and microalbuminuria or proteinuria and chronic kidney disease (CKD) with varying risk estimates. We aimed to systematically review the association between MetS, its components, and development of microalbuminuria or proteinuria and CKD.

Design, setting, participants and measurements and population

We searched MEDLINE (1966 to October 2010), SCOPUS, and the Web of Science for prospective cohort confidence interval (CI) studies that reported the development of microalbuminuria or proteinuria and/or CKD in participants with MetS. Risk estimates for eGFR <60 ml/min per 1.73 m² were extracted from individual studies and pooled using a random effects model. The results for proteinuria outcomes were not pooled because of the small number of studies.

Results

Eleven studies (n = 30,146) were included. MetS was significantly associated with the development of eGFR <60 ml/min per 1.73 m² (odds ratio, 1.55; 95% CI, 1.34, 1.80). The strength of this association seemed to increase as the number of components of MetS increased (trend P value = 0.02). In patients with MetS, the odds ratios (95% CI) for development of eGFR <60 ml/min per 1.73 m² for individual components of MetS were: elevated blood pressure 1.61 (1.29, 2.01), elevated triglycerides 1.27 (1.11, 1.46), low HDL cholesterol 1.23 (1.12, 1.36), abdominal obesity 1.19 (1.05, 1.34), and impaired fasting glucose 1.14 (1.03, 1.26). Three studies reported an increased risk for development of microalbuminuria or overt proteinuria with MetS.

Conclusions

MetS and its components are associated with the development of eGFR <60 ml/min per 1.73 m² and microalbuminuria or overt proteinuria.     

Comparison of Fracture Risk Prediction among Individuals with Reduced and Normal Kidney Function

Background and objectives

The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function.

Design, setting, participants, & measurements

The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m² [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m²) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus).

Results

There were 320 individuals with an eGFR<60 ml/min per 1.73 m² and 1787 with an eGFR≥60 ml/min per 1.73 m². The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m², which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m² versus ≥60 ml/min per 1.73 m² (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38).

Conclusions

This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function.     

eGFR and Outcomes in Patients with Acute Decompensated Heart Failure with or without Elevated BUN

Background and objectives

In patients with heart failure, the association of renal dysfunction and BUN levels with outcomes is unclear. The aim of our study was to investigate the association between the eGFR at discharge and outcomes in patients with heart failure with or without an elevated BUN level at discharge.

Design, setting, participants, & measurements

Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes Registry, 4449 patients discharged alive after hospitalization for acute decompensated heart failure were investigated to assess the association of eGFR in the context of serum BUN level at discharge with all-cause mortality. The enrolled patients were divided into four groups on the basis of the discharge levels of eGFR (<45 or ≥45 ml/min per 1.73 m²) and BUN (≥25 or <25 mg/dl). The median follow-up period after discharge was 517 (381–776) days.

Results

The all–cause mortality rate after discharge was 19.1%. After adjustment for multiple comorbidities, an eGFR<45 ml/min per 1.73 m² was associated with a significantly higher risk of all-cause mortality in patients with a BUN≥25 mg/dl (hazard ratio, 1.58; 95% confidence interval, 1.33 to 1.88; P<0.001) but not in patients with a BUN<25 mg/dl (hazard ratio, 0.97; 95% confidence interval, 0.76 to 1.26; P=0.84) relative to those with an eGFR≥45 ml/min per 1.73 m² and a BUN<25 mg/dl. Among patients with an eGFR≥45 ml/min per 1.73 m², a BUN≥25 mg/dl was associated with a significantly higher risk of all-cause mortality than a BUN<25 mg/dl (hazard ratio, 1.34; 95% confidence interval, 1.04 to 1.73; P=0.02).

Conclusions

We showed that elevation of BUN at discharge significantly modified the relation between eGFR at discharge and the risk of all-cause mortality after discharge, suggesting that the association between eGFR and outcomes may be largely dependent on concomitant elevation of BUN.     

Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney Neoplasms

Background and objectives

Partial nephrectomy or radical nephrectomy is the standard of care for patients with kidney neoplasms, but surgery may result in loss of renal function. We sought to identify patient characteristics associated with renal functional recovery following radical nephrectomy.

Design, setting, participants, & measurements

We performed a retrospective study among 572 patients with kidney neoplasms who underwent RN between 2006 and 2013. The primary endpoint was recovery of postoperative eGFR to the preoperative level. We plotted the trajectory of each patient’s eGFR from their first postoperative visit up to 3 years after surgery. Cumulative incidence and competing risks regression estimated associations between patient and clinical characteristics and eGFR recovery, stratified by preoperative eGFR.

Results

Median age was 61.5 years; 68% of patients were male, and 89% were white. Overall, eGFR increased over time following an initial postoperative decrease. Median postoperative follow-up among survivors was 10.8 (minimum, 0.03; maximum, 36.0) months; during follow-up, 263 patients achieved eGFR recovery. Median time to eGFR recovery was 25.3 months. Two-year cumulative incidence of eGFR recovery was 49% overall and 44% and 58% among those with preoperative eGFR≥60 and <60 ml/min per 1.73 m², respectively (P<0.001). On multivariable analysis, younger age at surgery and female sex were significantly associated with a higher chance of eGFR recovery among patients with preoperative eGFR<60 ml/min per 1.73 m². Among patients with preoperative eGFR≥60 ml/min per 1.73 m², hypertension was significantly associated with a lower chance of eGFR recovery, whereas increased tumor size was significantly associated with a higher chance of eGFR recovery.

Conclusions

Overall, almost half of the patients in this study recovered to their preoperative eGFR by 2 years following surgery. Distributions of preoperative risk factors differed by preoperative eGFR, leading to distinct factors that were significantly associated with chance of eGFR recovery.     

Screening for Chronic Kidney Disease Complications in US Adults: Racial Implications of a Single GFR Threshold

Background and objectives: An ideal and effective screening tool should perform equally across ethnic groups. The objective of this study was to determine whether the widely advocated creatinine-based estimated GFR (eGFR) threshold of 60 ml/min per 1.73 m² identifies the typical metabolic abnormalities related to chronic kidney disease equally well in minority and nonminority adults.Design, setting, participants, & measurements: This objective was addressed using data for 8918 minority and nonminority adult participants in the National Health and Nutrition Examination Survey 2003 through 2006, which used stratified, multistage, probability sampling methods to assemble a nationwide probability sample of the noninstitutionalized population of the United States. Metabolic abnormalities including BP, potassium, hemoglobin, bicarbonate, uric acid, calcium, phosphorus, and parathyroid hormone were defined by fifth or 95th percentile values.Results: Among participants with eGFR <60 ml/min per 1.73 m², black individuals were more likely than white individuals to have low hemoglobin (adjusted odds ratio [aOR] 3.76; 95% confidence interval [CI] 1.94 to 7.28), elevated uric acid (aOR 2.15; 95% CI 1.26 to 3.68), and elevated parathyroid hormone (aOR 3.93; 95% CI 2.33 to 6.66).Conclusions: Metabolic consequences of reduced eGFR are more common in black individuals and seem to be present at levels well above 60 ml/min per 1.73 m²; thus, black individuals should be screened for the metabolic complications of chronic kidney at higher GFR levels.Creatinine-based estimates of GFR (eGFR) are widely used to define chronic kidney disease (CKD), because they are believed to offer the combination of acceptable accuracy, convenience, and low cost (1–3). Current guidelines recommend that physicians begin screening for the metabolic disturbances of CKD once the creatinine-based eGFR reaches 60 ml/min per 1.73 m². Recent data, however, suggest that a strategy of using this single eGFR threshold, 60 ml/min per 1.73 m², may disadvantage minority populations. Using the US Third National Health and Nutrition Examination Survey (NHANES III; 1988 through 1994) database, we found that a case definition of CKD with a single eGFR value of 60 ml/min per 1.73 m² seemed to disadvantage minority populations, because metabolic abnormalities such as high BP, anemia, and elevated phosphorus and uric acid were already considerably more prevalent at higher eGFR values in black than in white participants (4). We believe that confirmation of these findings in a more recent, nationally representative population is of public health relevance, not least because of the changes in the demographic profile that have occurred since the conclusion of NHANES III (5). In addition, unlike more recent iterations of NHANES, parathyroid hormone (PTH) levels were not measured in NHANES III, preventing assessment of a classic metabolic complication of CKD. The objective of this study, therefore, was to determine whether a creatinine-based eGFR threshold of 60 ml/min per 1.73 m², as calculated by the re-expressed Modification of Diet in Renal Disease (MDRD) Study formula and the African American Study of Kidney Disease and Hypertension (AASK) formula, identifies metabolic abnormalities equally well in minority and nonminority adult NHANES participants studied between 2003 and 2006 (n = 8918).     

Hospital-acquired Acute Kidney Injury: An Analysis of Nadir-to-Peak Serum Creatinine Increments Stratified by Baseline Estimated GFR

Summary

Background and objectives

Serum creatinine (sCr) increments currently used to define acute kidney injury (AKI) do not take into consideration the baseline level of kidney function. The objective of this study was to establish whether baseline estimated GFR (eGFR) provides additional risk stratification to sCr-based increments for defining AKI.

Design, setting, participants, & measurements

29,645 adults hospitalized at an acute care facility were analyzed. Hospital-acquired AKI was defined by calculating the difference between the nadir and subsequent peak sCr.

Results

Different thresholds of nadir-to-peak sCr were found to be independently associated with increased in-hospital mortality according to baseline eGFR strata. A nadir-to-peak sCr minimum threshold of ≥0.2, ≥0.3, and ≥0.5 mg/dl was required to be independently associated with increased in-hospital mortality among patients with baseline eGFR ≥60 ml/min per 1.73 m² (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.13 to 2.47), 30 to 59 ml/min per 1.73 m² (OR 2.69; 95% CI, 1.82 to 3.97), and <30 ml/min per 1.73 m² (OR 2.15; 95% CI 1.02 to 4.51), respectively. There was a significant interaction between the nadir-to-peak sCr and baseline eGFR for in-hospital mortality (P < 0.001). Using these thresholds, survivors of AKI episodes had an increased hospital length of stay and were more likely to be discharged to a facility rather than home. Sensitivity analyses showed a significant interaction between baseline eGFR strata and relative increases in sCr, as well as absolute and relative decreases in eGFR for in-hospital mortality (P < 0.001).

Conclusions

This study suggests that future sCr-based definitions of AKI should take into consideration baseline eGFR.     

Decreased eGFR as a Risk Factor for Heart Failure in 13 781 Individuals With Type 1 Diabetes

Background:

Impaired renal function is a well-known risk factor of cardiovascular disease, but its relation to heart failure in individuals with type 1 diabetes has been sparsely studied. The aim of our study was to quantify the risk increase for development of heart failure with decreasing kidney function in individuals with type 1 diabetes.

Methods:

Three equations were used to calculate eGFR (estimated glomerular filtration rate) for individuals with T1D and no known heart failure in the Swedish National Diabetes Registry. Proportional hazards regression models were constructed to evaluate the association between eGFR and hospitalization for heart failure (HF).

Results:

Among 13 781 individuals (mean age 41.1 [SD 13.3] years at baseline), 330 (2.4%) were hospitalized for HF over median follow-up of 7.0 years. Renal function was normal (eGFR > 90 mL/min/1.73 m²) in 67% of individuals according to the Cockcroft-Gault formula, compared to 51% and 41% according to the Chronic Kidney Disease Epidemiology (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulas. For eGFR 45-60 ml/min/1.73 m², hazard ratios (HRs) for hospitalization (reference >90 mL/min/1.73 m²) were 3.18 (95% CI 2.17, 4.65), 2.12 (1.16, 3.08), and 2.44 (1.69, 3.55) using the Cockcroft-Gault, MDRD, and CKD-EPI formulas. With eGFR <30 ml/min/1.73 m² there was a HR of 3.78 (2.15, 5.91), 3.44 (2.14, 5.51), and 3.51 (2.21, 5.51) compared to normal kidney function (>90 mL/min/1.73 m²).

Conclusions:

In individuals with T1D, risk of hospitalization for heart failure was over 2 times greater at eGFR 45-60 ml/min/1.73 m² and more than 3 times greater at eGFR <30 ml/min/1.73 m² when compared to normal eGFR.     

Kidney Disease among Patients with Sickle Cell Disease,Hemoglobin SS and SC

Background and objectives

Sickle cell disease (SCD) is an inherited anemia that afflicts millions worldwide. Kidney disease is a major contributor to its morbidity and mortality. We examined contemporary and historical SCD populations to understand how renal disease behaved in hemoglobin SS (HbSS) compared with HbSC.

Design, setting, participants, & measurements

Kidney function was examined in the multicentered Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) Trial (HbSS=463; HbSC=127; years 2007–2009) and historical comparator populations from the Cooperative Study of Sickle Cell Disease (CSSCD; HbSS=708) and the Multicenter Study of Hydroxyurea in Sickle Cell Disease (MSH; HbSS=299).

Results

In adults with SCD, eGFR was lower among older individuals: −1.78 ml/min per 1.73 m² per year of age (95% confidence interval [95% CI], −2.06 to −1.50; Walk-PHaSST Trial), −1.75 ml/min per 1.73 m² per year of age (95% CI, −2.05 to −1.44; MSH), and −1.69 ml/min per 1.73 m² per year of age (95% CI, −2.00 to −1.38; CSSCD) in HbSS compared with −1.09 ml/min per 1.73 m² per year of age (95% CI, −1.39 to −0.75) in HbSC (Walk-PHaSST Trial). Macroalbuminuria was seen in 20% of participants with SCD (HbSS or HbSC; P=0.45; Walk-PHaSST Trial), but microalbuminuria was more prevalent in HbSS (44% versus 23% in HbSC; P<0.002). In the Walk-PHaSST Trial, albuminuria was associated with hemolysis (higher lactate dehydrogenase, P<0.001; higher absolute reticulocyte count, P<0.02; and lower Hb, P=0.07) and elevated systolic BP (P<0.001) in HbSS. One half of all participants with HbSS (20 of 39) versus one fifth without (41 of 228) elevated tricuspid regurgitant jet velocity (≥3 m/s; adverse prognostic indicator in SCD) had macroalbuminuria (P<0.001). In the CSSCD, overt proteinuria, detected (less sensitively) by urine dipstick, associated with higher 3-year mortality (odds ratio, 2.48; 95% CI, 1.07 to 5.77). Serum bicarbonate was lower in HbSS (23.8 versus 24.8 mEq/dl in HbSC; P<0.05) and associated with reticulocytopenic anemia and decreased renal function.

Conclusions

In SCD, albuminuria or proteinuria was highly prevalent, in HbSS more than in HbSC. Proteinuria associated with mortality in HbSS. Older individuals had a lower than expected eGFR, and this was more prominent in HbSS. Current management does not routinely address renal complications in SCD, which could plausibly reduce morbidity and mortality.     

Age-Specific Association of Reduced Estimated Glomerular Filtration Rate and Albuminuria with All-Cause Mortality

Summary

Background and objectives

It has been suggested that reduced estimated GFR (eGFR) among older adults does not necessarily reflect a pathologic phenomenon.

Design, setting, participants, & measurements

We examined the association between eGFR and albumin-to-creatinine ratio (ACR) and all-cause mortality stratified by age (45 to 59.9, 60 to 69.9, 70 to 79.9, and ≥80 years) among 24,350 U.S. adults in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study. A spot urine sample was used to calculate ACR, and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. All-cause mortality was assessed over a median follow-up of 4.5 years.

Results

Among participants ≥80 years of age (n = 1669), the age, race, gender, and geographic region of residence adjusted hazard ratios (95% confidence intervals) for mortality associated with eGFR levels of 45 to 59.9 and <45 ml/min per 1.73 m², versus ≥60 ml/min per 1.73 m², were 1.6 (1.3 – 2.1) and 2.2 (1.7 – 2.9), respectively. Also, among participants ≥80 years of age, the hazard ratios for mortality associated with ACR levels of 10 to 29.9, 30 to 299.9, and ≥300 mg/g, versus <10 mg/g, were 1.7 (1.3 – 2.1), 2.5 (1.9 – 3.3), and 5.1 (3.6 – 7.4), respectively. These associations were present after further multivariable adjustment and within the younger age groupings studied.

Conclusions

These data suggest that reduced eGFR and albuminuria confer an increased risk for mortality in all age groups, including adults ≥80 years of age.     

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.     

A study on the status of normoalbuminuric renal insufficiency among type 2 diabetes mellitus patients: A multicenter study based on a Chinese population

BackgroundPatients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population.MethodsWe included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin‐to‐creatinine ratio (UACR), participants were stratified into four groups—normal albuminuria, albuminuria, normoalbuminuria with eGFR < 60 mL/min/1.73 m², and albuminuria with eGFR < 60 mL/min/1.73 m². Clinical parameters and characteristics of patients with normoalbuminuria and eGFR < 60 mL/min/1.73 m² were retrospectively analyzed.ResultsA total of 1060 out of 8131 individuals with diabetes had decreased eGFR (<60 mL/min/1.73 m²). Normoalbuminuria accounted for 63.3% of participants with eGFR < 60 mL/min/1.73 m², and microalbuminuria and macroalbuminuria accounted for 30.1% and 6.3%, respectively. Patients with normoalbuminuria and reduced eGFR were more frequently male, older, and had higher levels of triglycerides than patients with normal albuminuria and eGFR. We also detected a correlation between lower extremity arterial disease, newly diagnosed diabetes, and normoalbuminuria‐reduced eGFR. Compared with participants with both albuminuria and eGFR decline, those with normoalbuminuria had better metabolic indicators, including systolic blood pressure and glycosylated hemoglobin, and shorter diabetes duration. Even in the normal range, UACR has a significant correlation with the risk of eGFR insufficiency.ConclusionsNormoalbuminuric renal insufficiency, characterized by male sex, older age, a higher level of triglyceride levels, and a higher risk of lower extremity arterial disease, accounted for a dominant proportion of diabetic patients with eGFR decline.     

Urinary Kidney Injury Molecule-1 and the Risk of Cardiovascular Mortality in Elderly Men

Background and objectives

Kidney injury molecule-1 (KIM-1) has been suggested as a clinically relevant highly specific biomarker of acute kidney tubular damage. However, community-based data on the association between urinary levels of KIM-1 and the risk for cardiovascular mortality are lacking. This study aimed to investigate the association between urinary KIM-1 and cardiovascular mortality.

Design, setting, participants, & measurements

This was a prospective study, using the community-based Uppsala Longitudinal Study of Adult Men (N=590; mean age 77 years; baseline period, 1997–2001; median follow-up 8.1 years; end of follow-up, 2008).

Results

During follow-up, 89 participants died of cardiovascular causes (incidence rate, 2.07 per 100 person-years at risk). Models were adjusted for cardiovascular risk factors (age, systolic BP, diabetes, smoking, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering treatment, aspirin treatment, and history of cardiovascular disease) and for markers of kidney dysfunction and damage (cystatin C–based eGFR and urinary albumin/creatinine ratio). Higher urinary KIM-1/creatinine (from 24-hour urine collections) was associated with a higher risk for cardiovascular mortality (hazard ratio per SD increase, 1.27; 95% confidence interval [95% CI], 1.05 to 1.54; P=0.01). Participants with a combination of high KIM-1/creatinine (upper quintile, ≥175 ng/mmol), low eGFR (≤60 ml/min per 1.73 m²), and microalbuminuria/macroalbuminuria (albumin/creatinine ratio≥3 g/mol) had a >8-fold increased risk compared with participants with low KIM-1/creatinine (<175 ng/mmol), normal eGFR (>60 ml/min per 1.73 m²), and normoalbuminuria (albumin/creatinine ratio<3 g/mol) (hazard ratio, 8.56; 95% CI, 4.17 to 17.56; P<0.001).

Conclusions

These findings suggest that higher urinary KIM-1 may predispose to a higher risk of cardiovascular mortality independently of established cardiovascular risk factors, eGFR, and albuminuria. Additional studies are needed to further assess the utility of measuring KIM-1 in the clinical setting.     

Fibroblast Growth Factor 23 and Incident CKD in Type 2 Diabetes

Background and objectives

High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.

Design, setting, participants, & measurements

A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR<60 ml/min per 1.73 m² that represented a ≥25% decrease from baseline in an individual with eGFR≥60 ml/min per 1.73 m² and no microalbuminuria (<30 mg/g creatinine) at baseline, was tested.

Results

The mean baseline eGFR in the random subcohort was 90.9±22.7 ml/min per 1.73 m². During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.7–55.1 versus 39.8, interquartile range=31.9–49.5 pg/ml; P<0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope.

Conclusions

Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes.     

Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry

Aims/IntroductionThe evidence regarding the effects of coffee consumption on incident chronic kidney disease is inconclusive, and no studies have investigated the relationship in patients with diabetes. We aimed to prospectively investigate the relationship between coffee consumption and the decline in estimated glomerular function rate (eGFR) in patients with type 2 diabetes.Materials and MethodsA total of 3,805 patients (2,112 men, 1,693 women) with type 2 diabetes (mean age 64.2 years) and eGFR ≥60 mL/min/1.73 m² were followed (completion of follow up, 97.6%; median 5.3 years). Coffee consumption was assessed at baseline. The end‐point was a decline in eGFR to <60 mL/min/1.73 m² during the follow‐up period.ResultsDuring follow up, 840 participants experienced a decline in eGFR to <60 mL/min/1.73 m². Higher coffee consumption reduced the risk of decline in eGFR. Compared with no coffee consumption, the multivariate‐adjusted hazard ratios (95% confidence intervals) were 0.77 (0.63–0.93) for less than one cup per day, 0.77 (0.62–0.95) for one cup per day and 0.75 (0.62–0.91) for two or more cups per day (P for trend 0.01). This trend was unaffected by further adjustment for baseline eGFR and albuminuria. The mean eGFR change per year was −2.16 mL/min/1.73 m² with no coffee consumption, −1.89 mL/min/1.73 m² with less than one cup per day, −1.80 mL/min/1.73 m² with one cup per day and −1.78 mL/min/1.73 m² with two or more cups per day (P for trend 0.03).ConclusionsCoffee consumption is significantly associated with a lower risk of decline in eGFR in patients with type 2 diabetes.     

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Background and objectives

Patients with CKD are more likely than others to have abnormalities in serum potassium (K⁺). Aside from severe hyperkalemia, the clinical significance of K⁺ abnormalities is not known. We sought to examine the association of serum K⁺ with mortality and hospitalization rates within narrow eGFR strata to understand how the burden of hyperkalemia varies by CKD severity. Associations were examined between serum K⁺ and discontinuation of medications that block the renin-angiotensin-aldosterone system (RAAS), which are known to increase serum K⁺.

Design, setting, participants, & measurements

A cohort of patients with CKD (eGFR<60 ml/min per 1.73 m²) with serum K⁺ data were studied (n=55,266) between January 1, 2009, and June 30, 2013 (study end). Serum K⁺, eGFR, and covariates were considered on a time-updated basis. Mortality, major adverse cardiovascular events (MACE), hospitalization, and discontinuation of RAAS blockers were considered per time at risk.

Results

During the study, serum K⁺ levels of 5.5–5.9 and ≥6.0 mEq/L were most prevalent at lower eGFR: they were present, respectively, in 1.7% and 0.2% of patient-time for eGFR of 50–59 ml/min per 1.73 m² versus 7.6% and 1.8% of patient-time for eGFR<30 ml/min per 1.73 m². Serum K⁺ level <3.5 mEq/L was present in 1.2%–1.4% of patient-time across eGFR strata. The median follow-up time was 2.76 years. There was a U-shaped association between serum K⁺ and mortality; pooled adjusted incidence rate ratios were 3.05 (95% confidence interval, 2.53 to 3.68) and 3.31 (95% confidence interval, 2.52 to 4.34) for K⁺ levels <3.5 mEq/L and ≥6.0 mEq/L, respectively. Within eGFR strata, there were U-shaped associations of serum K⁺ with rates of MACE, hospitalization, and discontinuation of RAAS blockers.

Conclusions

Both hyperkalemia and hypokalemia were independently associated with higher rates of death, MACE, hospitalization, and discontinuation of RAAS blockers in patients with CKD who were not undergoing dialysis. Future studies are needed to determine whether interventions targeted at maintaining normal serum K⁺ improve outcomes in this population.     

Plasma Vitamin D Level and Change in Albuminuria and eGFR According to Sodium Intake

Background and objectives

Low circulating 25-hydroxyvitamin D [25(OH)D] and high sodium intake are both associated with progressive albuminuria and renal function loss in CKD. Both vitamin D and sodium intake interact with the renin-angiotensin-aldosterone system. We investigated whether plasma 25(OH)D or 1,25-dihydroxyvitamin D [1,25(OH)₂D] is associated with developing increased albuminuria or reduced renal function and whether these associations depend on sodium intake.

Design, setting, participants, & measurements

Baseline plasma 25(OH)D and 1,25(OH)₂D were measured by liquid chromatography tandem mass spectrometry, and sodium intake was assessed by 24-hour urine collections in the general population–based Prevention of Renal and Vascular End-Stage Disease cohort (n=5051). Two primary outcomes were development of urinary albumin excretion >30 mg/24 h and eGFR (creatinine/cystatin C–based CKD Epidemiology Collaboration) <60 ml/min per 1.73 m². Participants with CKD at baseline were excluded. In Cox regression analyses, we assessed associations of vitamin D with developing increased albuminuria or reduced eGFR and potential interaction with sodium intake.

Results

During a median follow-up of 10.4 (6.2–11.4) years, 641 (13%) participants developed increased albuminuria, and 268 (5%) participants developed reduced eGFR. Plasma 25(OH)D was inversely associated with increased albuminuria (fully adjusted hazard ratio [HR] per SD higher, 0.86; 95% confidence interval [95% CI], 0.78 to 0.95; P=0.003) but not reduced eGFR (HR, 0.99; 95% CI, 0.87 to 1.12; P=0.85). There was interaction between 25(OH)D and sodium intake for risk of developing increased albuminuria (P interaction =0.03). In participants with high sodium intake, risk of developing increased albuminuria was inversely associated with 25(OH)D (lowest versus highest quartile: adjusted HR, 1.81; 95% CI, 1.20 to 2.73, P<0.01), whereas this association was nonsignificant in participants with low sodium intake (HR, 1.29; 95% CI, 0.94 to 1.77; P=0.12). Plasma 1,25(OH)₂D was not significantly associated with increased albuminuria or reduced eGFR.

Conclusions

Low plasma 25(OH)D is associated with higher risk of developing increased albuminuria, particularly in individuals with high sodium intake, but not of developing reduced eGFR. Plasma 1,25(OH)2D is not associated with risk of developing increased albuminuria or reduced eGFR.