The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based eGFR values and between eGFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.

Fluid overload and cardiac dysfunction is well established in hemodialysis patients. But in predialysis chronic kidney disease, the association of fluid overload and cardiac dysfunction is relatively unknown. In this study, we aimed to investigate the relationship between fluid overload and cardiac dysfunction in predialysis chronic kidney disease patients.

We enrolled 107 consecutive patients in our study. Fluid overload was assessed via body composition monitor. Patients were dichotomized according to the fluid overload status. The patients with FO < 1.1L were determined as normovolemic and those with FO ≥ 1.1L as hypervolemic according to the previously reported physiologic model. Left atrial volume index (LAVI), left ventricular end-diastolic-end-systolic index (LVEDVI, LVESVI), E/e', LVMI and global longitudinal left ventricular left ventricular strain (GLS-%) were evaluated in each patient as markers of cardiac dysfunction. Arterial stiffness was also assessed by Mobil-O-Graph(®) 24h pulse wave analysis monitor and pWV values were recorded.

Fifty-five patients were normovolemic and 52 patients were hypervolemic. LAVI, LVMI, LDEDVI, LVEDSVI, E/e' were increased in hypervolemic patients. Also in hypervolemic patients pulse wave velocity was increased and GLS was decreased. Multivariate analysis showed that FO was independently associated with GLS which is the most specific echo-parameter for left ventricular dysfunction.

FO was independently associated with cardiac dysfunction in patients with chronic kidney disease not ongoing dialysis. Effective treatment of hypervolemia may be important in these patients to avoid further cardiac damage.

The kidneys and the interstitial compartment play a vital role in body fluid regulation. The latter may be significantly altered in renal dysfunction, but experimental studies are lacking. To help define this we measured the subcutaneous interstitial pressure, bioimpedance volumes, and edema characteristics in 10 healthy subjects and 21 patients with obvious edema and chronic kidney disease (CKD). Interstitial edema was quantified by the time taken for a medial malleolar thumb pit to refill and termed the edema refill time. Interstitial pressure was significantly raised in CKD compared to healthy subjects. Total body water (TBW), extracellular fluid volume (ECFV), interstitial fluid volume, the ratio of the ECFV to the TBW, and segmental extracellular fluid volume were raised in CKD. The ratio of the ECFV to the TBW and the interstitial fluid volume were the best predictors of interstitial pressure. Significantly higher interstitial pressures were noted in edema of 2 weeks or less duration. A significant nonlinear relationship defined interstitial pressure and interstitial fluid volume. Edema refill time was significantly inversely related to interstitial pressure, interstitial compartment volumes, and edema vintage. Elevated interstitial pressure in CKD with obvious edema is a combined function of accumulated interstitial compartment fluid volumes, edema vintage, and tissue mechanical properties. The edema refill time may represent an important parameter in the clinical assessment of edema, providing additional information about interstitial pathophysiology in patients with CKD and fluid retention.

In healthy, normotensive individuals, age-related changes in carotid augmentation index (AI) are more prominent in younger individuals (< 50 years), whereas changes in aortic pulse wave velocity (PWV) are more marked in older individuals (> 50 years). We investigated whether the differential effects of age on AI and PWV also existed in end-stage renal disease (ESRD) patients.

Two hundred and fifty-seven patients (50% male; mean age, 53.9 +/- 15.0 years) with ESRD and 260 normal controls (52% male; mean age, 51.4 +/- 17.8 years) received a comprehensive evaluation of cardiovascular structure and function.

The percent differences in PWV between the younger and older subjects were similar in both ESRD patients (+46.2%) and normal controls (+52.5%). The percent differences in PWV between normal controls and ESRD patients were also similar in both younger (+28.2%) and older (+22.9%) subjects. In contrast, the differences in AI between the younger and older subjects were small in ESRD patients (7.3%) but large in normal controls (19.7%). Furthermore, there was a large difference in AI between normal controls and ESRD patients in the younger (+13.3%) subjects, but no difference in the older subjects (+0.8%) (interaction between study groups and age: p < 0.001).

Markedly differential effects of age on AI and PWV were observed in ESRD patients. PWV increased with age similarly in both ESRD patients and normal controls, whereas AI increased markedly in the younger but only slightly in the older ESRD patients.

The study aimed to assess whether the mitral peak Doppler E-wave to peak mitral annulus velocity ratio (E/Ea) estimates left ventricular (LV) filling pressure (LVFP) and predicts mortality in end-stage renal disease.

In all, 125 candidates for renal transplant were prospectively studied. LV end-diastolic pressure of 15 mm Hg or greater at cardiac catheterization was defined as elevated LVFP.

Severe coronary artery disease, N- terminal pro-B-type natriuretic peptide level, left atrial size, flow propagation velocity, mitral E/Ea ratio, pulmonary atrial reversal velocity, and pulmonary-mitral atrial wave duration predicted an increased LVFP. However, the mitral E/Ea ratio (odds ratio 8.1, 95% confidence interval 5.1-9.6, P = .003) was the only independent predictor. An E/Ea of 15 or more, seen in 31 (25%) patients, predicted increased LVFP with sensitivity of 82% and specificity of 88%, and was associated with increased mortality (P = .005).

In end-stage renal disease, mitral E/Ea ratio 15 or higher accurately predicts increased LVFP and mortality.

Pulmonary venous flow patterns have been well described in the literature to assess severity of mitral regurgitation (MR) and the degree of diastolic dysfunction. We report a case of posterior mitral leaflet perforation due to bacterial endocarditis causing an alteration of pulmonary venous flow, not previously described in the literature. This pulmonary venous flow pattern is unique in that it reflects dynamic changes in left atrial pressure in the background of severe MR.

A total of 32 patients without regional wall motion abnormality of the left ventricle underwent sequential tissue Doppler echocardiography and cardiac catheterization. Peak velocities of systolic (Sa), early diastolic (Ea), and late diastolic (Aa) motion of the mitral annulus were measured. Normal references for Sa, Ea and Aa were obtained from 138 volunteers. Indices of left ventricular (LV) systolic and diastolic function were evaluated using high-fidelity LV pressure and volume signals. By multivariate analysis, Sa, Ea and As were significantly and independently related to the maximum of the first derivative of pressure over time (dP/dt(max)), LV relaxation time constant (tau), and LV ejection fraction (EF), respectively. Using the fifth percentiles of the age-stratified normal references as cut-offs, low Sa, low Ea and low Aa identified declined dP/dt(max), prolonged tau and reduced EF, respectively, with good sensitivities and specificities. In conclusion, mitral annulus velocities by tissue Doppler echocardiography can be used to identify patients with declined dP/dt(max), prolonged tau and reduced EF.