Gerjan Navis

Increased Central Venous Pressure Is Associated With Impaired Renal Function and Mortality in a Broad Spectrum of Patients With Cardiovascular Disease

OBJECTIVES We sought to investigate the relationship between increased central venous pressure (CVP), renal function, and mortality in a broad spectrum of cardiovascular patients. BACKGROUND The pathophysiology of impaired renal function in cardiovascular disease is multifactorial. The relative importance of increased CVP has not been addressed previously. METHODS A total of 2,557 patients who underwent right heart catheterization in the University Medical Center Groningen, the Netherlands, between January 1, 1989, and December 31, 2006, were identified, and their data were extracted from electronic databases. Estimated glomerular filtration rate (eGFR) was assessed with the simplified modification of diet in renal disease formula. RESULTS Mean age was 59 +/- 15 years, and 57% were men. Mean eGFR was 65 +/- 24 ml/min/1.73 m(2), with a cardiac index of 2.9 +/- 0.8 l/min/m(2) and CVP of 5.9 +/- 4.3 mm Hg. We found that CVP was associated with cardiac index (r = -0.259, p < 0.0001) and eGFR (r = -0.147, p < 0.0001). Also, cardiac index was associated with eGFR (r = 0.123, p < 0.0001). In multivariate analysis CVP remained associated with eGFR (r = -0.108, p < 0.0001). In a median follow-up time of 10.7 years, 741 (29%) patients died. We found that CVP was an independent predictor of reduced survival (hazard ratio: 1.03 per mm Hg increase, 95% confidence interval: 1.01 to 1.05, p = 0.0032). CONCLUSIONS Increased CVP is associated with impaired renal function and independently related to all-cause mortality in a broad spectrum of patients with cardiovascular disease.

Comparative Performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study Equations for Estimating GFR Levels Above 60 mL/min/1.73 m2

BACKGROUND The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels>60 mL/min/1.73 m2, with variable accuracy among subgroups; consequently, estimated GFR (eGFR)>or=60 mL/min/1.73 m2 is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics. STUDY DESIGN Test of diagnostic accuracy. SETTING & PARTICIPANTS Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index. INDEX TESTS eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine. REFERENCE TEST Measured GFR using urinary or plasma clearance of exogenous filtration markers. RESULTS Mean measured GFR was 68+/-36 (SD) mL/min/1.73 m2. For eGFR<30 mL/min/1.73 m2, both equations have similar bias (median difference compared with measured GFR). For eGFR of 30-59 mL/min/1.73 m2, bias was decreased from 4.9 to 2.1 mL/min/1.73 m2 (57% improvement). For eGFR of 60-89 mL/min/1.73 m2, bias was decreased from 11.9 to 4.2 mL/min/1.73 m2 (61% improvement). For eGFR of 90-119 mL/min/1.73 m2, bias was decreased from 10.0 to 1.9 mL/min/1.73 m2 (75% improvement). Similar or improved performance was noted for most subgroups with eGFR<90 mL/min/1.73 m2, other than body mass index<20 kg/m2, with greater variation noted for some subgroups with eGFR>or=90 mL/min/1.73 m2. LIMITATIONS Limited number of elderly people and racial and ethnic minorities with measured GFR. CONCLUSIONS The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR>or=60 mL/min/1.73 m2 can be reported using the CKD-EPI equation.

Immediate Postoperative Renal Function Deterioration in Cardiac Surgical Patients Predicts In-Hospital Mortality and Long-Term Survival

Postoperative renal function deterioration is a serious complication after cardiac surgery with cardiopulmonary bypass and is associated with increased in-hospital mortality. However, the long-term prognosis of patients with postoperative renal deterioration is not fully determined yet. Therefore, both in-hospital mortality and long-term survival were studied in patients with postoperative renal function deterioration. Included were 843 patients who underwent cardiac surgery with cardiopulmonary bypass in 1991. Postoperative renal function deterioration (increase in serum creatinine in the first postoperative week of at least 25%) occurred in 145 (17.2%) patients. In these patients, in-hospital mortality was 14.5%, versus 1.1% in patients without renal function deterioration (P < 0.001). Multivariate analysis significantly associated in-hospital mortality with postoperative renal function deterioration, re-exploration, postoperative cerebral stroke, duration of operation, age, and diabetes. In patients who were discharged alive, during long-term follow-up (100 mo), mortality was significantly increased in the patients with renal function deterioration (n = 124) as compared with those without renal function deterioration (hazard ratio 1.83; 95% confidence interval 1.38 to 3.20). Also after adjustment for other independently associated factors, the risk for mortality in patients with postoperative renal function deterioration remained elevated (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32). The elevated risk for long-term mortality was independent of whether renal function had recovered at discharge from hospital. It is concluded that postoperative renal function deterioration in cardiac surgical patients not only results in increased in-hospital mortality but also adversely affects long-term survival.

Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction

Renal failure in heart failure is related to decreased cardiac output. However, little is known about its association with venous congestion.

Drawbacks and Prognostic Value of Formulas Estimating Renal Function in Patients With Chronic Heart Failure and Systolic Dysfunction

Background— Renal function is an important risk marker for morbidity and mortality in chronic heart failure (CHF) and is often estimated with the use of creatinine-based formulas. However, these formulas have never been validated in a wide range of CHF patients. We validated 3 commonly used formulas estimating glomerular filtration rate (GFR) with true GFR in CHF patients. Furthermore, we compared the prognostic value of these formulas for cardiovascular outcome with that of true GFR during 12 months of follow-up. Methods and Results— In 110 CHF patients (age, 57±11.7 years; left ventricular ejection fraction, 0.27±0.09; NYHA class, 2.5±0.9), we measured 125I-iothalamate clearance. Cockcroft-Gault (GFRcg), Modification of Diet in Renal Disease (MDRD), and simplified MDRD (sMDRD) equations were used as creatinine-based renal function estimations. Furthermore, 24-hour creatinine clearance (CrCl) was determined. CrCl and GFRcg were the most accurate. MDRD was most precise formula, although it was also highly biased. All formulas overestimated in the lower ranges and underestimated in the upper ranges of the GFR corrected for body surface area. The predictive performance of the formulas was best in severe CHF (NYHA classes III and IV). The prognostic value of CrCl and MDRD for cardiovascular outcome was comparable to that of GFR, the sMDRD was slightly less, and the GFRcg had a significantly worse prognostic value. Conclusions— In the more severe ranges of CHF, creatinine-based formulas and CrCl corrected for body surface area appeared to be more precise and accurate in estimating true GFR corrected for body surface area. The MDRD formula is the most precise and has a good prognostic value, whereas the sMDRD is slightly less accurate but uses fewer parameters, which makes this formula a practical alternative in clinical practice.

Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Predicts Mortality in Hemodialysis Patients

Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.

Effects of Dietary Sodium and Hydrochlorothiazide on the Antiproteinuric Efficacy of Losartan

There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these interventions is unknown. Therefore, this randomized, double-blind, placebo-controlled trial to determine the separate and combined effects of a low-sodium diet and hydrochlorothiazide (HCT) on proteinuria and BP was performed. In 34 proteinuric patients without diabetes, mean baseline proteinuria was 3.8 g/d, and this was reduced by 22% by a low-sodium diet alone. Losartan monotherapy reduced proteinuria by 30%, and the addition of a low-sodium diet led to a total reduction by 55% and the addition of HCT to 56%. The combined addition of HCT and a low-sodium diet reduced proteinuria by 70% from baseline (all P < 0.05). Reductions in mean arterial pressure showed a similar pattern (all P < 0.05). In addition, individuals who did not demonstrate an antiproteinuric response to losartan monotherapy did respond when a low-sodium diet or a diuretic was added. In conclusion, a low-sodium diet and HCT are equally efficacious in reducing proteinuria and BP when added to a regimen containing losartan and especially seem to benefit individuals who are resistant to RAAS blockade. Combining these interventions in sodium status is an effective method to maximize the antiproteinuric efficacy of RAAS blockade.

A central body fat distribution is related to renal function impairment, even in lean subjects

BACKGROUND Overweight and obesity are believed to be associated with renal damage. Whether this depends on fat distribution is not known. We hypothesize that in addition to overweight, fat distribution may be associated with renal function abnormalities. METHODS We studied the relation between body weight and fat distribution and microalbuminuria and elevated or diminished filtration in 7,676 subjects without diabetes. Microalbuminuria is defined as urinary albumin excretion (UAE) of 30 to 300 mg/24 h. Elevated and diminished filtration are defined as filtration plus or minus 2 SDs of a nondiabetic lean group with a peripheral fat distribution and UAE of 0 to 15 mg/24 h, corrected for age and sex. The total population was divided into six groups according to body weight (overweight is defined as body mass index [BMI] > 25 and < or = 30 kg/m2; obesity, as BMI > 30 kg/m2) and fat distribution. RESULTS In logistic regression analysis, obese subjects with central fat distribution had a greater risk for microalbuminuria (relative risk, 1.7; 95% confidence interval, 1.19 to 2.35). Obese subjects with either peripheral or central fat distribution had a greater risk for elevated filtration (relative risk, 3.2; 95% confidence interval, 1.19 to 8.47; relative risk, 2.6; 95% confidence interval, 1.59 to 4.28, respectively). Furthermore, subjects with central fat distribution, either lean, overweight, or obese, had a greater risk for diminished filtration (relative risk, 1.9; 95% confidence interval, 1.19 to 3.12; relative risk, 2.0; 95% confidence interval, 1.19 to 3.19; and relative risk, 2.7; 95% confidence interval, 1.46 to 4.85, respectively). Finally, by dividing waist-hip ratio (WHR) into quartiles, greater WHR was associated with a greater risk for diminished filtration, even when corrected for BMI. CONCLUSION Not only overweight and obese subjects, but also lean subjects with central fat distribution are at risk for diminished filtration. Therefore, a central pattern of fat distribution, not overweight or obesity by itself, seems to be important for renal impairment.

Common variants near TERC are associated with mean telomere length

We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 × 10−14) at a locus that includes TERC, which encodes the telomerase RNA component. Each copy of the minor allele of rs12696304 was associated with an ∼75-base-pair reduction in mean telomere length, equivalent to ∼3.6 years of age-related telomere-length attrition.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12–p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10−10 to 10−15). Of these, rs10206899 (near NAT8, 2p12–p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10−5 and P = 3.6 × 10−4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease.