Categories Of Kidney Function Research Articles

Efficacy and Safety of Anti-Osteoporotic Agents across CKD Stages: A Meta-Analysis of Randomized Clinical Trials.

Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5. We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic. We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials. Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

Risk factors for hip and vertebral fractures in chronic kidney disease: the CRIC study.

Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the chronic renal insufficiency cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11.1 (4.8) years (2.4 events per 1000 person-years [95% CI: 2.0, 2.9]). Measured at baseline, diabetes, lower body mass index (BMI), steroid use, proteinuria, and elevated parathyroid hormone (PTH) were each associated with fracture risk after adjusting for covariates. Lower time-updated estimated glomerular filtration rate (eGFR) was associated with fractures (HR 1.20 per 10mL/min/1.73m2 lower eGFR; 95% CI: 1.04, 1.38) as were lower time-updated serum calcium and bicarbonate concentrations. Among time-updated categories of kidney function, hazard ratios (95% CI) for incident fracture were 4.53 (1.77, 11.60) for kidney failure treated with dialysis and 2.48 (0.86, 7.14) for post-kidney transplantation, compared with eGFR ≥60. Proton pump inhibitor use, dietary calcium intake, measures of vitamin D status, serum phosphate, urine calcium and phosphate, and plasma fibroblast growth factor-23 were not associated with fracture risk. In conclusion, lower eGFR in CKD is associated with higher fracture risk, which was highest in kidney failure. Diabetes, lower BMI, steroid use, proteinuria, higher serum concentrations of PTH, and lower calcium and bicarbonate concentrations were associated with fractures and may be modifiable risk factors.

Comparing five equations to estimate glomerular filtration rate or creatinine clearance and assign individuals to KDIGO categories across the full age spectrum using real world data

AbstractFive equations are commonly used by biopharma companies to estimate glomerular filtration rate (GFR) or creatinine clearance (CrCl) based on regulatory and stakeholder recommendations. Changes observed in GFR and/or CrCl can be challenging to interpret as participants transition between age strata, prompting changes in equations. This manuscript explores how GFR, CrCl, and the resulting Kidney Disease Improving Global Outcomes (KDIGO) categories of kidney function can change when different equations are used. We analyzed descriptively real‐world data (RWD) from 48 health care organizations in the United States to identify patients with data (age, sex, height, weight, serum biomarkers such as creatinine [Scr] and/or cystatin C [Scys]) sufficient to estimate GFR and/or CrCl. Five equations (Bedside Schwartz, Modified Schwartz, Cockcroft‐Gault, 2021 Chronic Kidney Disease‐Epidemiology Collaboration [CKD‐EPI] Scr, and 2021 CKD‐EPI Scr/Scys) were used to estimate GFR and/or CrCl and assign individuals to KDIGO categories (G1–G5). We identified 32,728 patients, including 378 infants (<2 years), 1191 younger children (2 to <6 years), 1891 older children (6 to <12 years), 3174 adolescents (12 to <18 years), 16,367 younger adults (18 to <65 years), and 9727 older adults (65+ years) with sufficient information to estimate kidney function. For patients greater than or equal to 2 years, estimated GFR and/or CrCl and KDIGO categories based on the 2021 CKD‐EPI Scr/Scys equation appeared similar to those based on currently recommended equations. RWD suggests the 2021 CKD‐EPI Scr/Scys equation could potentially be used to estimate GFR in individuals aged 2 years and older; more research is needed to confirm these findings.

Evaluation of kidney function among people living with HIV initiating antiretroviral therapy in Zambia.

As the response to the HIV epidemic in sub-Saharan Africa continues to mature, a growing number of people living with HIV (PLHIV) are aging and risk for non-communicable diseases increases. Routine laboratory tests of serum creatinine have been conducted to assess HIV treatment (ART) suitability. Here we utilize those measures to assess kidney function impairment among those initiating ART. Identification of non-communicable disease (NCD) risks among those in HIV care creates opportunity to improve public health through care referral and/or NCD/HIV care integration. We estimated glomerular filtration rates (eGFR) using routinely collected serum creatinine measures among a cohort of PLHIV with an HIV care visit at one of 113 Centre for Infectious Disease Research Zambia (CIDRZ) supported sites between January 1, 2011 and December 31, 2017, across seven of the ten provinces in Zambia. We used mixed-effect Poisson regression to assess predictors of eGFR <60ml/min/1.73m2 allowing random effects at the individual and facility level. Additionally, we assessed agreement between four eGFR formulae with unadjusted CKD-EPI as a standard using Scott/Fleiss method across five categories of kidney function. A total of 72,933 observations among 68,534 individuals met the inclusion criteria for analysis. Of the 68,534, the majority were female 41,042 (59.8%), the median age was 34 (interquartile range [IQR]: 28-40), and median CD4 cell count was 292 (IQR: 162-435). The proportion of individuals with an eGFR <60ml/min/1.73m2 was 6.9% (95% CI: 6.7-7.1%) according to the unadjusted CKD-EPI equation. There was variation in agreement across eGFR formulas considered compared to unadjusted CKD-EPI (χ2 p-value <0.001). Estimated GFR less than 60ml/min/1.73m2, per the unadjusted CKD-EPI equation, was significantly associated with age, sex, body mass index, and blood pressure. Using routine serum creatinine measures, we identified a significant proportion of individuals with eGFR indicating moderate or great kidney function impairment among PLHIV initiating ART in Zambia. It is possible that differentiated service delivery models could be developed to address this subset of those in HIV care with increased risk of chronic kidney disease.

Anticoagulation control in atrial fibrillation patients with chronic kidney disease receiving warfarin for stroke prevention: The west Birmingham AF project

The effectiveness and safety of warfarin is optimised in atrial fibrillation (AF) patients when the International Normalised Ratio (INR) is 2.0–3.0. Anticoagulation control comparing different categories of kidney function has not been well-assessed, although poorer INR control may be more likely in AF patients with chronic kidney disease.

Apixaban or Vitamin K Antagonists and Aspirin or Placebo According to Kidney Function in Patients With Atrial Fibrillation After Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From the AUGUSTUS Trial.

In the AUGUSTUS trial (An Open-Label, 2×2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban Versus Vitamin K Antagonist and Aspirin Versus Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention), apixaban resulted in less bleeding and fewer hospitalizations than vitamin K antagonists, and aspirin caused more bleeding than placebo in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention treated with a P2Y12 inhibitor. We evaluated the risk-benefit balance of antithrombotic therapy according to kidney function. In 4456 patients, the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was used to calculate baseline estimated glomerular filtration rate (eGFR). The effect of apixaban versus vitamin K antagonists and aspirin versus placebo was assessed across kidney function categories by using Cox models. The primary outcome was International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and ischemic events (death, stroke, myocardial infarction, stent thrombosis [definite or probable], or urgent revascularization). Creatinine clearance <30 mL/min was an exclusion criterion in the AUGUSTUS trial. Overall, 30%, 52%, and 19% had an eGFR of >80, >50 to 80, and 30 to 50 mL·min-1·1.73 m-2, respectively. At the 6-month follow-up, a total of 543 primary outcomes of bleeding, 1125 death or hospitalizations, and 282 ischemic events occurred. Compared with vitamin K antagonists, patients assigned apixaban had lower rates for all 3 outcomes across most eGFR categories without significant interaction. The absolute risk reduction with apixaban was most pronounced in those with an eGFR of 30 to 50 mL·min-1·1.73 m-2 for bleeding events with rates of 13.1% versus 21.3% (hazard ratio, 0.59; 95% CI, 0.41-0.84). Patients assigned aspirin had a higher risk of bleeding in all eGFR categories with an even greater increase among those with eGFR >80 mL·min-1·1.73 m-2: 16.6% versus 5.6% (hazard ratio, 3.22; 95% CI, 2.19-4.74; P for interaction=0.007). The risk of death or hospitalization and ischemic events were comparable to aspirin and placebo across eGFR categories with hazard ratios ranging from 0.97 (95% CI, 0.76-1.23) to 1.28 (95% CI, 1.02-1.59) and from 0.75 (95% CI, 0.48-1.17) to 1.34 (95% CI, 0.81-2.22), respectively. The safety and efficacy of apixaban was consistent irrespective of kidney function, compared with warfarin, and in accordance with the overall trial results. The risk of bleeding with aspirin was consistently higher across all kidney function categories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

Associations between urinary cadmium levels, blood pressure, and hypertension: the ESTEBAN survey.

Cadmium is inconsistently associated with blood pressure (BP) and hypertension. Our study focuses to understand the association between urinary cadmium levels, blood pressure, and hypertension in a French representative sample. Our study included 2015 subjects from the ESTEBAN survey (2014-2015) with measured urinary cadmium. Associations between natural logarithm-transformed cadmium levels and BP (systolic (SBP) and diastolic blood pressure (DBP)) were performed by adjusted linear regression models. Associations between cadmium and hypertension were performed by adjusted logistic regression models. Models were stratified by gender, smoking habits, body mass index (BMI), and kidney function categories. Men present higher SBP (131.7 vs. 121.5mmHg, p < 0.0001) and DBP (78.9 vs. 74.7mmHg, p < 0.0001) in comparison to women. Creatinine-adjusted urinary cadmium levels (0.48 vs. 0.39μg/L, p < 0.0001) were higher in hypertensive subjects. Nevertheless, no difference was observed after adjustment for age, gender, and smoking habits. No correlation between urinary cadmium, BP, and hypertension was observed in overall population. Stratified models showed inverse correlations between urinary cadmium and hypertension among obese (OR = 0.39, 95% CI [0.21-0.57], p = 0.0009), chronic kidney function (OR = 0.68 95%CI [0.75-0.97], p = 0.003), and current smokers (OR = 0.78, 95% CI [0.64-0.92], p = 0.04). A correlation between urinary cadmium levels, BP, and hypertension is observed in subpopulations. Nevertheless, directions and significance of these associations differs by gender, BMI, smoking, and kidney function categories.

Association of High-Density Lipoprotein Particles and High-Density Lipoprotein Apolipoprotein C-III Content With Cardiovascular Disease Risk According to Kidney Function: The Multi-Ethnic Study of Atherosclerosis.

BackgroundChronic kidney disease is associated with structural and compositional abnormalities in high‐density lipoprotein particles (HDLp). We examined associations of HDLp size, particle subfractions, and apolipoprotein C‐III content with incident cardiovascular disease (CVD) events across categories of estimated glomerular filtration rate (eGFR).Methods and ResultsAnalyses included 6699 participants in MESA (Multi‐Ethnic Study of Atherosclerosis) with measurements of HDLp and 5723 participants with measurements of HDL apolipoprotein C‐III. Cox‐regression methods were used to evaluate associations between HDLp and apolipoproteins with CVD events. Larger HDLp size was associated with lower CVD risk in participants with lower eGFR: hazard ratio (95% CI) per SD higher mean HDL size was 1.00 (0.90–1.11) in eGFR ≥60 mL/min per 1.73 m2, 0.65 (0.48–0.86) in eGFR 45 to 59 mL/min per 1.73 m2, and 0.48 (0.25–0.93) in eGFR <45 mL/min per 1.73 m2 (P for interaction=0.05). Associations of HDLp subfractions with CVD varied significantly by eGFR (P for interaction=0.04), with significant inverse associations between higher concentrations of large HDLp and CVD events across categories of kidney function, but nonsignificant results for small HDLp. Only HDLp without apolipoprotein C‐III was associated with lower risk of CVD events, with seemingly (albeit not statistically significant) stronger associations among participants with lower eGFR (P for interaction=0.19).Conclusions HDL particles of larger size and higher concentrations of large HDL and of HDL without apolipoprotein C‐III were associated with lower CVD risk, with risk estimates seemingly stronger among participants with lower eGFR. Future larger studies are needed to corroborate these findings.

Concordance between modification of diet in renal disease, chronic kidney disease epidemiology collaboration and Cockcroft-Gault equations in patients with chronic kidney disease at St. Paul\u2019s hospital millennium medical college, Addis Ababa, Ethiopia

BackgroundThe most commonly used glomerular filtration rate estimating equations for drug dosing are Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. However there is still a concern about whether to use MDRD and CKD-EPI interchangeably with CG for drug dosage adjustment.MethodsThe study was initiated to determine the concordance between MDRD, CKD-EPI and CG equations and associated factors in patients with chronic kidney disease at Saint Paul’s Hospital Millennium Medical College (SPHMMC). This was a cross sectional study which involved patient chart review and physicians self-administered questionnaire. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The correctness of the drug dose prescribed for the level of renal function were compared to the drug database (Lexi-Comp) available through Up-to-date version 21.2.ResultsAmong the total of 422 patients, 249 (59%) were males. Mean age of patients was 46.09 years. The use of MDRD equation for drug dose adjustment by physicians working in the renal clinic of SPHMMC was six out of nine physicians. The Pearson correlation coefficient between the CG with MDRD and CKD-EPI equations was r = 0.94, P < 0.001 and r = 0.95, P < 0.001, respectively. The concordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories was 73.7%, Kappa = 0.644 and 74.9%, Kappa = 0.659, respectively. Concordance between the CG with MDRD and CKD-EPI equations for the drug dosing recommendation was 89.6%, kappa = 0.782 and 92%, kappa = 0.834, respectively. Age > 70 years was associated with discordance between CG and MDRD equations for drug dosing recommendation whereas serum creatinine 1.2–3.5 mg/dL, weight < 61 Kg and age > 70 years were associated with discordance between the CG with MDRD and CKD-EPI equations for FDA assigned kidney function categories. However, none of the factors associated with discordance between CG and CKD-EPI for drug dosing.ConclusionMDRD equation can be used interchangeably with CG equation for drug dosing recommended in all adult patients between the age of 18 and 70 years. CKD-EPI can be used interchangeably with CG in all adult Ethiopian patients with CKD.

Kidney function, albuminuria and life expectancy.

BackgroundLower estimated glomerular filtration rate is associated with reduced life expectancy. Whether this association is modified by the presence or absence of albuminuria, another cardinal finding of chronic kidney disease, is unknown.ObjectiveOur objective was to estimate the life expectancy of middle-aged men and women with varying levels of eGFR and concomitant albuminuria.DesignA retrospective cohort study.SettingA large population-based cohort identified from the provincial laboratory registry in Alberta, Canada.ParticipantsAdults aged ≥30 years who had outpatient measures of serum creatinine and albuminuria between May 1, 2002 and March 31, 2008.MeasurementsPredictor: Baseline levels of kidney function identified from serum creatinine and albuminuria measurements. Outcomes: all cause mortality during the follow-up.MethodsPatients were categorized based on their estimated glomerular filtration rate (eGFR) (≥60, 45–59, 30–44, and 15–29 mL/min/1 · 73 m2) as well as albuminuria (normal, mild, and heavy) measured by albumin-to-creatinine ratio or urine dipstick. The abridged life table method was applied to calculate the life expectancies of men and women from age 40 to 80 years across combined eGFR and albuminuria categories. We also categorized participants by severity of kidney disease (low risk, moderately increased risk, high risk, and very high risk) using the combination of eGFR and albuminuria levels.ResultsAmong men aged 50 years and with eGFR ≥60 mL/min/1.73 m2, estimated life expectancy was 24.8 (95% CI: 24.6-25.0), 17.5 (95% CI: 17.1-17.9), and 13.5 (95% CI: 12.6-14.3) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for men with mild and heavy albuminuria was 7.3 (95% CI: 6.9-7.8) and 11.3 (95% CI: 10.5-12.2) years shorter than men with normal proteinuria, respectively. A reduction in life expectancy was associated with an increasing severity of kidney disease; 24.8 years for low risk (95% CI: 24.6-25.0), 19.1 years for moderately increased risk (95% CI: 18.7-19.5), 14.2 years for high risk (95% CI: 13.5-15.0), and 9.6 years for very high risk (95% CI: 8.4-10.8). Among women of similar age and kidney function, estimated life expectancy was 28.9 (95% CI: 28.7-29.1), 19.8 (95% CI: 19.2-20.3), and 14.8 (95% CI: 13.5-16.0) years for participants with normal, mild and heavy albuminuria respectively. Life expectancy for women with mild and heavy albuminuria was 9.1 (95% CI: 8.5-9.7) and 14.2 (95% CI: 12.9-15.4) years shorter than the women with normal proteinuria, respectively. For women also a graded reduction in life expectancy was observed across the increasing severity of kidney disease; 28.9 years for low risk (95% CI: 28.7-29.1), 22.5 years for moderately increased risk (95% CI: 22.0-22.9), 16.5 years for high risk (95% CI: 15.4-17.5), and 9.2 years for very high risk (95% CI: 7.8-10.7).LimitationsPossible misclassification of long-term kidney function categories cannot be eliminated. Possibility of confounding due to concomitant comorbidities cannot be ruled out.ConclusionThe presence and degree of albuminuria was associated with lower estimated life expectancy for both gender and was especially notable in those with eGFR ≥30 mL/min/1.73 m2. Life expectancy associated with a given level of eGFR differs substantially based on the presence and severity of albuminuria.Electronic supplementary materialThe online version of this article (doi:10.1186/s40697-014-0033-6) contains supplementary material, which is available to authorized users.

Chronic Kidney Disease, Plasma Lipoproteins, and Coronary Artery Calcium Incidence

To determine the association of chronic kidney disease and coronary artery calcium (CAC) incidence, and the distribution of lipoproteins across categories of kidney function and their association with CAC risk. We analyzed data from 2795 participants in the Multi-Ethnic Study of Atherosclerosis with no CAC (calcium score=0) at baseline enrolled at the first Multi-Ethnic Study of Atherosclerosis visit between the years 2000 and 2002. During a median follow-up of 2.4 years, incident calcium (calcium score>0 at follow-up) developed in 12%, 19%, and 27% of participants with a cystatin-c estimated glomerular filtration rate (mL/min per 1.73 m)(2) of ≥90, 60 to 89, and 30 to 59 (P for difference <0.001), respectively. Compared with those with normal kidney function (estimated glomerular filtration rate≥90), adjusted CAC incidence risk ratios, and 95% confidence intervals (CIs) were as follows: 1.26 (95% CI, 1.04-1.52), and 1.56 (95% CI, 1.11-2.20; P(trend)=0.014) in those with estimated glomerular filtration rate of 60 to 89 and 30 to 59, respectively. These associations were attenuated after adjusting for a characteristic and strongly interrelated lipid phenotype (principal component 1), which was more common in those with chronic kidney disease and characterized by a predominance of triglyceride-rich lipoproteins: CAC incidence risk ratios=1.21 (95% CI, 1.00-1.46) and 1.44 (95% CI, 1.02-2.04; P(trend)=0.06) in those with estimated glomerular filtration rate 60 to 89 and 30 to 59, respectively, after adjusting for principal component 1. Chronic kidney disease is strongly associated with CAC incidence. Part of this association is mediated through a characteristic lipid phenotype comprising elevations in triglyceride-rich lipoproteins.

Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients

Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the US Food and Drug Administration (FDA) Guidance for industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared with recommended dosages based on the level of estimated kidney function, 3-19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing-related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.

Comparison of Drug Dosing Recommendations Based on Measured GFR and Kidney Function Estimating Equations

Kidney disease alters the pharmacokinetic disposition of many medications, requiring dosage adjustment to maintain therapeutic serum concentrations. The Cockcroft-Gault (CG) equation is used for pharmacokinetic studies and drug dosage adjustments, but the Modification of Diet in Renal Disease (MDRD) Study equation is more accurate and more often reported by clinical laboratories than the CG equation. Diagnostic test study. Pooled data set for 5,504 participants from 6 research studies and 4 clinical populations with measured glomerular filtration rate (GFR). Estimated kidney function using the MDRD Study and CG equations incorporating actual (CG) or ideal body weight (CG(IBW)) and standardized serum creatinine concentrations. Measured GFR assessed by using iodine-125-iothalamate urinary clearance. Concordance of assigned kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies and recommended dosages of 15 medications cleared by the kidneys. Concordance of kidney function estimates with measured GFR for FDA-assigned kidney function categories was 78% for the MDRD Study equation compared with 73% for the CG equation (P < 0.001) and 66% for the CG(IBW) equation (P < 0.001). Concordance between the MDRD Study equation and CG and CG(IBW) equations was 78% and 75%, respectively (P < 0.001). Concordance of kidney function estimates with measured GFR for recommended drug dosages was 88% for MDRD Study equation compared with 85% for the CG equation (P < 0.001) and 82% for the CG(IBW) equation (P < 0.001), with lower concordance when dosing recommendations for drugs included narrow GFR ranges. Concordance rates between the CG and CG(IBW) equations and MDRD Study equation were 89% and 88%, respectively (P < 0.05). Results based on simulation rather than pharmacokinetic studies. Outcome was drug dosage recommendations, rather than observed drug efficacy and safety. The MDRD Study equation can also be used for pharmacokinetic studies and drug dosage adjustments. As more accurate GFR-estimating equations are developed, they should be used for these purposes.

Cystatin C Levels in U.S. Adults, 1988–1994 Versus 1999–2002

Creatinine-based estimates of GFR suggest an evolving epidemic of chronic kidney disease (CKD) in U.S. adults that is inadequately explained by conventional, modifiable risk factors. Cystatin C has recently emerged as a promising measure of GFR. To enable further insights into the evolution of CKD in the U.S. population, this study aimed to examine cystatin C levels in U.S. adults. Stored serum samples, measured in 2006, were used to compare cystatin C levels among adult participants in the National Health and Nutrition Examination Survey (NHANES) in two time periods, 1988-1994 (n = 6877) and 1999-2002 (n = 4563). Mean cystatin C levels (0.9 versus 0.9 mg/L, P = 0.65) and urinary albumin-creatinine ratios were similar (5.8 versus 5.9 mg/g, P = 0.19) in the 2 study eras. In contrast, standardized serum creatinine (0.8 versus 0.9 mg/dl, P < 0.0001) was higher and estimated GFR (93.2 versus 87.6 ml/min/1.73 m(2), P < 0.001) was lower in 1999-2002. Similar discrepancies in population trends (when cystatin C and creatinine-based methods were used to define GFR) were present when categories of kidney function were considered, and when adjustment was made for demography and comorbid illness. The disparity between temporal trends when kidney function is assessed with different measurements suggests that estimating trends in disease burden remains an open question.

High Prevalence of Nephrogenic Systemic Fibrosis in Chronic Renal Failure Patients Exposed to Gadodiamide, a Gadolinium-Containing Magnetic Resonance Contrast Agent

Nephrogenic systemic fibrosis (NSF) is a serious disease affecting renal failure patients. It may be caused by some gadolinium (Gd)-containing contrast agents, including gadodiamide. The study aimed at estimating the prevalence of NSF after gadodiamide exposure for patients with chronic kidney disease (CKD). Retrospective cohort study of 190 consecutive nephrological patients in different categories of kidney function referred for gadodiamide-enhanced magnetic resonance imaging in the period January 1, 2004 to March 21, 2006. Eighteen patients (18/190; 10%, 95% CI: 6%-15%) were diagnosed with NSF within a mean follow-up period of 29 months (range 16-43 months). All 18 cases had stage 5 CKD (ie, estimated glomerular filtration rate less than 15 mL/min/1.73 m2 or in dialysis therapy) at the time of their gadodiamide exposure. The prevalence of NSF among patients with stage 5 CKD at exposure (n = 102) was 18% (95% CI: 11%-27%). No cases were seen among 88 gadodiamide-exposed patients who had milder degrees of renal insufficiency (prevalence 0%, 95% CI: 0%-4%). The risk of NSF is unacceptably high among stage 5 CKD patients exposed to gadodiamide.

Statin therapy is associated with improved outcomes in vascular surgery patients with renal impairment

Little is known about the association between baseline kidney function, statin therapy, and outcome after vascular surgery in patients with and without chronic kidney disease. A total of 2126 patients underwent elective major vascular surgery and were divided into 2 categories based on baseline creatinine clearance (CrCl), calculated using the Cockcroft-Gault equation: CrCl > or = 60 mL/min (n = 1358, reference) and CrCl < 60 mL/min (n = 768). Outcome measures were 30-day and long-term all-cause, cardiac, and cerebrocardiovascular mortality. Mean follow-up was 6.0 +/- 3.7 years. Multivariate Cox regression analysis, including potential confounders and propensity score for statin use, was applied. Data are presented as hazard ratios (HRs) with 95% CI. Thirty-day all-cause, cardiac, and cerebrocardiovascular mortality rates were 3.8% versus 10.2%, 1.3% versus 4.2%, and 2.7% versus 7.8%, respectively, according to the 2 categories of kidney function. In addition, long-term all-cause, cardiac, and cerebrocardiovascular mortality rates were 46.6% versus 72.5%, 14.6% versus 26.4%, and 23.0% versus 40.6%, respectively. Statin therapy was associated with an overall significant improved 30-day and long-term all-cause mortality, independent of other important confounders. However, in patients with a CrCl > or = 60 mL/min, the long-term cardiac and cerebrocardiovascular beneficial effects did not reach statistical significance (HR 0.93, 95% CI 0.61-1.41 and HR 0.89, 95% CI 0.63-1.24, respectively) when compared with patients with a CrCl of < 60 mL/min (HR 0.63, 95% CI 0.41-0.96 and HR 0.67, 95% CI 0.48-0.94, respectively). The level of kidney function is an independent predictor of short- and long-term outcome after major noncardiac surgery. In addition, perioperative statin use in patients with kidney disease is associated with a reduction in the short- and long-term all-cause, cardiac, and cerebrocardiovascular mortality.

Survival after coronary revascularization among patients with kidney disease.

The optimal approach to revascularization in patients with kidney disease has not been determined. We studied survival by treatment group (CABG, percutaneous coronary intervention [PCI], or no revascularization) for patients with 3 categories of kidney function: dialysis-dependent kidney disease, non-dialysis-dependent kidney disease, and a reference group (serum creatinine <2.3 mg/dL). Data were derived from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), which captures information on all patients undergoing cardiac catheterization in Alberta, Canada. Characteristics and patient survival in 662 dialysis patients (1.6%) and 750 non-dialysis-dependent kidney disease patients (1.8%) were compared with the remainder of the 40,374 patients (96.6%). For the reference group, the adjusted 8-year survival rates for CABG, PCI, and no revascularization (NR) were 85.5%, 80.4%, and 72.3%, respectively (P<0.001 for CABG versus NR; P<0.001 for PCI versus NR). Adjusted survival rates were 45.9% for CABG, 32.7% for PCI, and 29.7% for NR in the nondialysis kidney disease group (P<0.001 for CABG versus NR; P=0.48 for PCI versus NR) and 44.8% for CABG, 41.2% for PCI, and 30.4% for NR in the dialysis group (P=0.003 for CABG versus NR; P=0.03 for PCI versus NR). Compared with no revascularization, CABG was associated with better survival in all categories of kidney function. PCI was also associated with a lower risk of death than no revascularization in reference patients and dialysis-dependent kidney disease patients but not in patients with non-dialysis-dependent kidney disease. The presence of kidney disease or dependence on dialysis should not be a deterrent to revascularization, particularly with CABG.