Unraveling the relationship between mortality, hyponatremia, inflammation and malnutrition in hemodialysis patients: results from the international MONDO initiative.

BACKGROUND/OBJECTIVES: Hyponatremia is a risk factor for mortality in hemodialysis (HD) patients. It is not well known to which extent the comorbidities, malnutrition, fluid status imbalance and inflammation are related to hyponatremia and affect outcomes. SUBJECTS/METHODS: We studied 8883 patients from the European subset of the international MONitoring Dialysis Outcomes initiative. Nutritional and fluid statuses were assessed by bioimpedance spectroscopy. Fluid depletion was defined as overhydration⩽-1.1 l and fluid overload as overhydration>+1.1 l, respectively. Malnutrition was defined as a lean tissue index below the 10th percentile of age- and gender-matched healthy controls. Hyponatremia and inflammation were defined as serum sodium levels <135 mEq/l and C-reactive protein levels>6.0 mg/l, respectively. We used logistic regression to test for predictors of hyponatremia and Cox proportional hazards analysis to assess the association with all-cause mortality. RESULTS: Hyponatremia was predicted by the presence of malnutrition (odds ratio (OR)=1.49 (95% confidence interval (CI)=1.30-1.70), inflammation (OR=1.44 (95% CI=1.26-1.64)) and fluid overload ((>+1.1 l to +2.5 l) OR=0.73 (95% CI=0.62-0.85)) but not by fluid depletion (OR=1.34 (95% CI=0.92-1.96)). Malnutrition, inflammation, fluid overload, fluid depletion and hyponatremia (hazard ratio=1.70 (95% CI=1.46-1.99)) were independent predictors for all-cause mortality. CONCLUSIONS: In HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.

Peritoneal dialysis in patients with heart failure.

Both in dialysis patients and non-uremic patients heart failure is associated with an adverse prognosis. In a state of abrupt worsening of cardiac function, acute cardiogenic shock or decompensated congestive heart failure, acute kidney injury may occur, whereas in a more chronic worsening of cardiac function chronic kidney injury may occur. Recently, the term cardiorenal syndrome was adopted and defined as "a pathophysiological disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ". Despite better treatment techniques and the continuous development of new medications volume overload in patients with cardiorenal syndrome is difficult to treat. Especially treatment of cardiorenal syndrome type I and II is notoriously difficult. Peritoneal dialysis might be, because of the gradual fluid removal, a therapeutic option in these patients. However, data on the effect of peritoneal dialysis in patients with heart failure with fluid overload and/or renal impairment are scarce. In this review, the role of peritoneal dialysis in the treatment cardiorenal syndrome type I, II and IV will be discussed.

Peritoneal dialysis in patients with primary cardiac failure complicated by renal failure.

BACKGROUND/AIMS: Clinical outcome in cardiorenal syndrome type II and treated with peritoneal dialysis (PD). METHODS: Retrospective analysis over a period of 10 years. RESULTS: Twenty-four patients with mean age at start of dialysis of 67 ± 10 years had mean survival on dialysis of 1.03 ± 0.84 years (median survival 1.0 year). The number of hospitalizations for cardiovascular causes were reduced (13.7 ± 26.5 predialysis vs. 3.5 ± 8.8 days/patient/month postdialysis, p = 0.001). Patients who survived longer than the median survival time (n = 12) also had a reduced number of hospitalizations for all causes (3.7 ± 3.8 predialysis vs. 1.4 ± 2.1 days/patient/month postdialysis, p = 0.041), a lower age (62 ± 10 vs. 71 ± 8 years, p = 0.013) and fewer had diabetes (2 vs. 7 patients, p = 0.039), but left ventricular ejection fraction was not different. CONCLUSION: After starting PD for cardiorenal syndrome, hospitalizations for cardiovascular causes were reduced for all patients. Survival after starting PD is highly variable. Age and diabetes seem to be significant prognostic factors, but not left ventricular ejection fraction.

Measurement of hemodialysis vascular access flow using extracorporeal temperature gradients.

A reduction in vascular access flow poses a risk for thrombosis. We present a new technique to measure vascular access flow during dialysis based on extracorporeal temperature gradients, and their changes, on reversing the extracorporeal bloodlines without having to inject an indicator. Fistula temperatures were measured by the blood temperature monitor with normal line position and after manual switching of the bloodlines using the same extracorporeal blood flow. The access flow by our temperature gradient method (TGM) was compared to access flow derived by saline dilution with measurements in the same patients repeated in subsequent weeks. In 70 pairs of TGM and saline dilution measurements in 35 patients, the repeatability of the TGM measurements was not significantly different from that of saline dilution. There was a highly significant correlation between the two techniques with an acceptable confidence level for limits of agreement for the difference between them. It took about 9 min to complete the TGM method and about 5 min for saline dilution. Our studies show that the novel TGM method showed excellent agreement and reproducibility with the saline dilution method without the need for indicator dilution.

Association of serum fetuin-A levels with mortality in dialysis patients.

Calcifying atherosclerosis is an active process, which is controlled by calcification inhibitors and inducers. Fetuin-A, an acute phase glycoprotein, is one of the more powerful circulating inhibitors of hydroxyapatite formation. A prospective multicenter cohort study was initiated to include both hemodialysis (HD) and peritoneal dialysis (PD) patients in an evaluation of the association of serum fetuin-A levels with both cardiovascular (CV) and non-CV mortality. An increase in the serum fetuin-A concentration of 0.1 g/l was associated with a significant reduction in all-cause mortality of 13%. There was a significant 17% reduction in non-CV mortality and a near significant reduction in CV mortality. This association of fetuin-A and mortality rates was comparable in both HD and PD patients even when corrected for factors, including but not limited to age, gender, primary kidney disease, C-reactive protein levels, and nutritional status. We conclude that serum fetuin-A concentrations may be a general predictor of mortality in dialysis patients.

Wall shear stress assessment in the common carotid artery of end-stage renal failure patients.

Under physiological circumstances in the common carotid artery (CCA), mean wall shear stress (WSS), defined as mean wall shear rate (WSR) times local whole blood viscosity (WBV), is maintained at approximately 1.5 Pa. In patients with end-stage renal failure (ESRF) whole blood viscosity is low and it is not unlikely that mean WSS is lower in these patients than in control subjects. Moreover, hemodialysis causes an acute increase in blood viscosity with possible effects on WSS. In this study WSS in the CCA was determined with the Shear Rate Estimating System, an apparatus based on ultrasound, in ESRF patients (n = 13) and in presumed healthy age- and sex-matched control subjects (n = 13). Prior to hemodialysis, mean WSS (0.67 +/- 0.23 Pa) was significantly lower (p < 0.05) in patients with ESRF, due to both a lower WBV (2.80 +/- 0.52 mPa.s) and mean WSR (271 +/- 109 s(-1)), than in the control subjects (mean WSS: 1.24 +/- 0.20 Pa; WBV: 3.20 +/- 0.29 mPa.s; WSR: 387 +/- 51 s(-1)). Hemodialysis induced an increase in WBV (up to 3.71 +/- 1.54 mPa.s, p < 0.01), but mean WSS did not change significantly due to a reciprocal decrease in mean wall shear rate. These findings demonstrate that WSS is lower in hemodialysis patients than in control subjects, and that mean WSS is maintained at this low level despite an acute change in blood viscosity.

Optimizing dialysis dose by increasing blood flow rate in patients with reduced vascular-access flow rate.

Dialysis efficacy indexed by Kt/V can generally be augmented by increasing the dialyzer blood flow rate. However, increasing the dialyzer blood flow rate may lead to vascular-access recirculation (AR) in patients with a compromised vascular-access flow rate. This can have an attenuating effect on dialysis efficacy. The aim of the present study is to investigate the effect of dialyzer blood flow rates of 200, 300, and 400 mL/min on AR and Kt/V in 8 patients with low (<600 mL/min) and 13 patients with normal (>600 mL/min) vascular-access flow rates. AR and vascular-access flow rate were determined using an ultrasound saline dilution technique, and session-delivered Kt/V was computed using an on-line dialysate urea monitor. AR was minor and only observed in 4 patients in the low vascular-access flow rate group (0.9% +/- 0.6%) at dialyzer blood flow rates of 200 mL/min (1 patient), 300 mL/min (2 patients), and 400 mL/min (3 patients) and 4 patients in the normal vascular-access flow rate group (1.2% +/- 1.1%) at dialyzer blood flow rates of 200 mL/min (3 patients) and 300 mL/min (1 patient). Kt/V increased with increasing dialyzer blood flow rates in both groups, and in individual cases, there was no decrease in Kt/V at greater dialyzer blood flow rates in either group. Also in those patients with minor AR, Kt/V increased at greater dialyzer blood flow rates, except in 1 patient in the low-flow group, in whom Kt/V remained unchanged at a change in dialyzer blood flow rate from 300 to 400 mL/min, whereas AR increased. From this study, it is concluded that even in patients with low access flow, increasing dialyzer blood flow rate in general leads to an increase in delivered Kt/V regardless of vascular access flow rate.

Role of bioimpedance spectroscopy in assessment of body water compartments in hemodialysis patients.

Bioimpedance spectroscopy (BIS) has been advocated as a tool to assess fluid status in hemodialysis (HD) patients. However, uncertainty remains about the reliability of BIS in patients with abnormalities in fluid status. Aims of the study are to assess the agreement between total-body water (TBW) and extracellular volume (ECW) measured by BIS and tracer dilution (deuterium oxide [D(2)O] and sodium bromide [NaBr]), the influence of the relative magnitude of water compartments (expressed as TBW(D(2)O) and ECW(NaBr):body weight) on the agreement between BIS and tracer dilution, and the ability of BIS to predict acute changes in fluid status. BIS and tracer dilution techniques were performed in 17 HD patients before a dialysis session. Moreover, the relation between BIS and gravimetric weight changes was assessed during both isolated ultrafiltration and HD. Correlation coefficients between TBW and ECW measured by BIS and tracer dilution were r = 0.71 and r = 0.71, respectively. Mean differences (tracer-BIS) were 6.9 L (limits of agreement, -1.5 to 21.6 L) for TBW and 2.3 L (limits of agreement, -1.7 to 9.7 L) for ECW. There was a significant relationship between the relative magnitude of TBW and ECW compartments and disagreement between BIS and tracer dilution (r = 0.65 and r = 0.77; P < 0.05). During both isolated ultrafiltration and HD, there was a significant relation between gravimetric changes and change in ECW(BIS) (r = 0.83 and r = 0.76; P < 0.05), but not with change in TBW(BIS). In conclusion, agreement between BIS and tracer dilution techniques in the assessment of TBW and ECW in HD patients is unsatisfactory. The discrepancy between BIS and dilution techniques is related to the relative magnitude of body water compartments. Nevertheless, BIS adequately predicted acute changes in ECW during isolated ultrafiltration and HD, in contrast to changes in TBW.

A comparison between office and ambulatory blood pressure measurements in renal transplant patients with chronic transplant nephropathy.

Hypertension is an important risk factor for chronic transplant nephropathy. Therapy is usually based on casual office blood pressure (BP) measurements. However, it is not well known how casual BP predicts 24-hour BP in this population. The main focus of this study is to compare casual office BP with 24-hour ambulatory BP monitoring in renal transplant recipients with signs of chronic transplant nephropathy. Moreover, in this group, the day-night BP profile was assessed. In 36 renal transplant recipients with incipient or progressive proteinuria or an increase in serum creatinine level greater than 20%, 24-hour ambulatory BP was performed. Patients were defined as a nondipper if the mean BP decreased by less than 10% during the nighttime period. The correlation between single office and 24-hour ambulatory BPs was 0.61 for systolic BP and 0.55 for diastolic BP (P < 0.001). The mean difference between 24-hour ambulatory and single office BPs was -4.2 +/- 18.6 mm Hg (range, -44 to 36 mm Hg) for systolic BP and -1.1 +/- 10.7 mm Hg (range, -34 to 27 mm Hg) for diastolic BP; 94.5% of patients were classified as nondippers. There was a significant relation between the nightly decline in mean arterial pressure and calculated creatinine clearance (r = 0.34; P < 0.05). In conclusion, in renal transplant recipients with chronic transplant nephropathy, a large difference between office and ambulatory BPs is present, with both overestimation and underestimation of 24-hour BP by office BP measurements. Moreover, a severely disturbed day-night BP rhythm was observed. In transplant recipients with compromised graft function, office BP may not reflect 24-hour BP adequately, and ambulatory BP measurements should be considered.

The influence of increasing dialysis treatment time and reducing dry weight on blood pressure control in hemodialysis patients: a prospective study.

A good blood pressure control can be achieved with long hemodialysis sessions (dialysis center of Tassin, France). However, it is not well known whether a higher dialysis dose or a lower dry weight is responsible for this phenomenon. In a preliminary study, 21 hypertensive dialysis patients, dialyzed three times a week for 3-5 h, were randomized into three groups during a 3-month study period. In 6 patients, the dialysis treatment time was increased by 2 h, and the dry weight was gradually decreased (group 1). In 7 patients the dialysis treatment time was increased by 2 h without a change in dry weight (group 2). In 8 patients the dry weight was gradually lowered without changing the dialysis treatment time (group 3). Before and after the study, cardiac index and left ventricular mass index (echocardiography) and forearm vascular resistance (strain gauge plethysmography) were determined on a middialytic day. The blood pressure was assessed by 48-hour ambulatory monitoring. The antihypertensive medication was reduced when the postdialytic blood pressure became <130/80 mm Hg. The dry weight was reduced by 2.6 +/- 1.4 kg in group 1 and by 2.3 +/- 0.8 kg in group 3 (p < 0.05). The number of classes of antihypertensive medication was reduced from 3.3 to 1.8 in group 1 (NS), from 2.4 to 1.7 in group 2 (NS), and from 3.1 to 1.3 in group 3 (p < 0.05). The dose of the remaining antihypertensive drugs was reduced by 50% in group 1 (p < 0.05), by 32% in group 2 (NS), and by 72.2% in group 3 (p < 0.05). The interdialytic systolic blood pressure decreased significantly after increasing the dialysis time without changing the dry weight (group 2: 7 +/- 5 mm Hg; p < 0.05). The systolic blood pressure was also lower in the other patients groups: group 1: 13 +/- 26 mm Hg, group 3 : 7 +/- 16 mm Hg (NS). The pulse pressure decreased significantly in group 2 (7 +/- 5 mm Hg; p < 0.05) and in group 3 (6 +/- 7 mm Hg; p < 0.05) and tended to decrease in group 1 (11 +/- 12 mm Hg; p = 0.08). The diastolic blood pressure and the day-night blood pressure difference did not change significantly, nor did cardiac index and left ventricular mass index. The forearm vascular resistance tended to decrease in the patients on long dialysis sessions. This preliminary study suggests that the dialysis treatment time might have an independent beneficial effect on blood pressure control.

[Acute renal replacement therapy in the intensive care unit]. / Acute nierfunctievervangende therapie op de intensive-careafdeling.

On the intensive care department the most frequently used acute renal replacement techniques are intermittent haemodialysis and continuous haemofiltration. Although continuous techniques appear to have distinct advantages in the treatment of critically ill patients, no consistent differences in mortality have been found between continuous and intermittent treatment modalities. Due to uncertainty in this area, the use of unmodified cellulose membranes is probably best avoided. No good randomised studies are available with regard to the starting time of renal replacement techniques in critically ill patients. However, generally speaking a 'late' start should be avoided. With continuous techniques, the filtration volume should not be below 35 ml/kg/h. Although continuous (high-volume) filtration techniques may contribute to an improvement in the haemodynamics, the mechanisms behind this phenomenon remain unclear. At present, no randomised studies are available which have shown a beneficial effect of continuous techniques on the survival of critically ill patients without manifest renal insufficiency being demonstrated.

Effects of a venous cuff at the venous anastomosis of polytetrafluoroethylene grafts for hemodialysis vascular access.

INTRODUCTION AND METHODS: The most frequent complication of polytetrafluoroethylene (PTFE) arteriovenous grafts for hemodialysis is thrombotic occlusion due to stenosis caused by intimal hyperplasia. This complication is also known for peripheral bypass grafts. Because the use of a venous cuff at the distal anastomosis improves the patency of peripheral bypass grafts, we considered that it might also improve the patency of PTFE arteriovenous grafts. Therefore, a randomized multicenter trial was carried out to study the effect of a venous cuff at the venous anastomosis of PTFE arteriovenous grafts on the development of stenoses and the patency rates. RESULTS: Of the 120 included patients, 59 were randomized for a venous cuff. The incidence of thrombotic occlusion was lower in the cuff group (0.68 per patient-year) than in the no-cuff group (0. 88 per patient-year; P =.0007). However, the primary and secondary patency rates were comparable. The cuff group tended to have fewer stenoses at the venous and arterial anastomoses when examined with duplex scan. Graft failure was higher in patients with an initial anastomosing vein diameter smaller than 4 mm (7 of 18 [39%]) than in those with a vein diameter of 4 mm or larger (16 of 88 [18%]; P =. 052). Local edema, skin atrophy, and obesity yielded a higher risk on graft failure (23% vs 11%). CONCLUSION: A venous cuff at the venous anastomosis of PTFE arteriovenous grafts for hemodialysis reduced the incidence of thrombotic occlusions; stenosis at the venous anastomosis was reduced. However, this did not result in a better patency rate. Therefore, the venous cuff should not be used routinely. Initial vein diameter and local problems (edema, obesity, or skin atrophy) appear to be the most important risk factors for graft failure.