Optimal current frequency for the detection of changes in extracellular water in patients on hemodialysis by measurement of total body electrical resistance.

BACKGROUND & AIMS: Measurement of total body electrical resistance (TBER) to an alternating current is useful to monitor extracellular water (ECW) in patients on hemodialysis (HD). Which current frequency is preferable is subject of ongoing debate. The aim of this study was to quantify the implications of TBER measurements at current frequencies ranging from 0 to 1000 kHz for ECW monitoring in patients on HD. METHODS: Bioimpedance spectroscopy measurements were performed in 39 patients on HD using the Body Composition Monitor (BCM, Fresenius Medical Care). TBER data at 5, 50, 200, 500, and 1000 kHz were compared with the extrapolated TBER at 0 kHz (TBER0) assessed by Cole-Cole analysis. Sensitivity of each TBER configuration was evaluated at individual level, by assessment of the smallest ultrafiltration (UF) volume that induced a significant change in TBER, i.e. a change in TBER ≥ 2.7%. RESULTS: TBER precision was very high for all frequencies, with coefficients of variation of 0.25%-0.28%. Baseline TBER decreased with increasing current frequency. TBER was 2.9% lower at 5 kHz (P < 0.001), 11.6% lower at 50 kHz, and up to 22.0% lower at 1000 kHz. This pattern is attributed to a progressive increase in intracellular current conduction at higher frequencies. Sensitivity to volume changes induced by UF also decreased with increasing current frequency. At 0 and 5 kHz, an UF volume ≤ 0.5 L was sufficient to induce a significant increase in TBER in 87% of patients. This decreased to 69% at higher frequencies. CONCLUSION: ECW monitoring by TBER requires measurement at 5 kHz or less to ensure optimal performance.

Towards personalized hydration assessment in patients, based on measurement of total body electrical resistance: Back to basics.

BACKGROUND & AIMS: Assessment of tissue hydration by conventional bioelectrical impedance analysis (BIA) has produced conflicting results because of flaws in the algorithms that are used to translate measurements of total body electrical resistance (TBER) into liters of body water. This type of error can be eliminated by a return to the TBER measurement itself, without attempting to convert Ohms into liters of body water. Aims of this study were to quantify tissue hydration based on TBER, to establish TBER normal values (TBERnorm), to improve the prediction of TBERnorm values in individual patients, and to evaluate this approach in patients on hemodialysis (HD). METHODS: TBERnorm values were obtained in 213 healthy controls and corrected for body height (H-TBERnorm). Inter-individual H-TBERnorm variability was reduced by correction for arm muscle cross-sectional area (AMA). Performance of this approach was evaluated in 94 patients on HD. RESULTS: H-TBERnorm was inversely related to AMA. Correction for AMA reduced the H-TBERnorm standard deviation by 31% in men and 23% in women. When applied to patients on HD, H-TBER changes within subjects were inversely related to ultrafiltration volumes, with a mean R2 of 0.95 ± 0.04 in men and 0.93 ± 0.07 in women. Clinically significant H-TBER increments occurred after volume reductions of 0.39 ± 0.25 L in men and 0.37 ± 0.18 L in women. CONCLUSIONS: TBER measurements, corrected for height and AMA, have the potential to become an objective and sensitive method to assess hydration in patients. Its clinical value remains to be shown in intervention studies.

Metformin associated lactic acidosis: incidence and clinical correlation with metformin serum concentration measurements.

WHAT IS KNOWN AND OBJECTIVE: The reported incidence of metformin associated lactic acidosis (MALA) in type 2 diabetes mellitus (DM) is 3-9 cases per 100,000 patient-years. In clinical practice, 22-94% of patients using metformin have contraindications to metformin, so the incidence of MALA may be higher than reported. AIM OF THE STUDY: To estimate the incidence of MALA in type 2 DM patients by means of metformin serum concentration measurements and investigate the correlation of metformin serum concentration with the clinical outcome of MALA. METHODS: MALA cases were identified by reviewing the medical records of patients with metformin serum concentrations measured between January 2000 and October 2008. MALA was defined as arterial pH <7·35 and lactate concentration >5·0 mmol/L in patients using metformin. The incidence of MALA was calculated from the number of cases and the at risk population. The correlation coefficient between the metformin and lactate concentration was calculated by linear regression. The relationship between metformin serum concentration, lactate concentration and outcome was examined by calculating the mean metformin and lactate concentration in patients who survived and those who died. The Student's t-test was used to compare groups. RESULTS AND DISCUSSION: In 29 patients metformin serum concentration was measured, 16 had MALA. Eleven of the 16 MALA cases (69%) had risk factors for lactic acidosis in their medical history, 13 cases (81%) had renal failure on admission. The incidence of MALA was estimated at 47 per 100,000 patient-years, this is 5-16 times higher than previously reported. This may be explained by the use of metformin in the presence of risk factors for lactic acidosis. Survivors had a higher metformin serum concentration (18·9 mg/L) than non-survivors (2·9 mg/L, P = 0·006) which can be explained by less severe underlying disease in patients who survived MALA, rather than an effect of metformin itself. WHAT IS NEW AND CONCLUSION: The incidence of MALA estimated from metformin serum concentration measurements in type 2 DM patients is 5-16 times higher than reported in literature. MALA is probably caused by the frequent use of metformin in the presence of risk factors for lactic acidosis. Metformin serum concentration measurements may aid in the timely diagnosis and therapy of MALA. The outcome of MALA is determined by the severity of the underlying disease, rather than by metformin itself.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

Successful treatment with recombinant factor VIIa of therapy-resistant severe bleeding in a patient with acquired von Willebrand disease.

We describe an elderly man who presented with life-threatening hematuria and gastrointestinal bleeding caused by acquired von Willebrand disease associated with monoclonal gammopathy of undetermined significance (MGUS). Standard therapy with desmopressin, von Willebrand factor-containing factor VIII concentrate, tranexamic acid, and immunoglobulin failed to achieve adequate hemostasis. However, treatment with recombinant activated factor VII (rFVIIa) arrested the bleeding completely. Since acquired von Willebrand disease can lead to life-threatening hemorrhage, clinicians should consider rFVIIa as an effective treatment option if standard therapy fails.

[Nosocomial transmission of hepatitis C virus in a Dutch dialysis center]. / Nosocomiale transmissie van het hepatitis-C-virus in een Nederlands dialysecentrum.

OBJECTIVE: To describe the transmission of hepatitis C virus (HCV) in a dialysis centre in the Netherlands, to analyse risk factors and to redefine additional preventive measures. DESIGN: Descriptive. METHODS: The data of patients attending the dialysis centre of the Deventer Hospital, the Netherlands, who had participated in a national prospective survey on the epidemiology of HCV among Dutch dialysis patients, were examined. In addition, patients who developed signs of hepatic failure in the ensuing year were included in this study. To diagnose an HCV-infection serology as well as polymerase chain reaction were used. Genotyping and sequence analysis were used to assess phylogenetic relations. Infection control practices were audited. RESULTS: In the dialysis centre a cluster of four almost identical HCV isolates genotype 2a was found. Within a period of one year another cluster of four HCV-infected dialysis patients was detected in the same centre. These four isolates were almost identical to a fifth isolate, genotype 2b, found in the earlier study from another patient dialysing in the same unit. It was observed that possibly contaminating procedures were not strictly separated. Some of the shared medical equipment was not sterilised but only cleaned. Also blood-contaminated gloves might have played a role in the transmission of HCV. CONCLUSION: Nosocomial transmission plays an important role in the epidemiology of HCV in dialysis patients. Shared medical equipment and blood-contaminated gloves may constitute a potential route of transmission. There is a need for stringent implementation and regular auditing of infection control measures.

[Hyperthyroidism due to contamination of the alternative drug Ader-Rein (Vascu-Vitaal)]. / Hyperthyreoïdie door verontreiniging van het alternatieve geneesmiddel Ader-Rein (Vascu-Vitaal).

A 52-year-old woman developed hyperthyroidism due to the alternative Vascu-Vitaal pills. She was suffering from nephrotic syndrome due to membranoproliferative glomerulonephritis and subclinical hypothyroidism, possibly due to renal loss of thyroid hormone. For peripheral vascular disease she took the non-registered Vascu-Vitaal pills on her own initiative. According to the product information, these pills contain multiple vitamins, minerals, amino acids and tissue extracts of bovine adrenals, hypophysis and thymus. The patient developed hyperthyroidism after starting on a new batch of the preparation; it subsided after stopping the treatment. A technetium thyroid scan showed decreased uptake and subsequently the Vascu-Vitaal pills were found to contain both thyroxine and triiodothyronine. The thyroid hormone contamination was probably caused by bovine thyroid tissue. It is suggested to require a health warning statement on the package of alternative therapeutics stating that production and contents are not subject to governmental supervision.

Enalapril-induced anemia in two kidney transplant recipients.

Two renal transplant patients developed anemia during treatment of hypertension with enalapril medication. Hemoglobin levels normalized after administration of enalapril was stopped. In one patient, it was demonstrated that the discontinuation of enalapril was followed by a decrease in renal blood flow and a significant increase in the plasma erythropoietin levels that preceded the rise in hemoglobin. These observations are consistent with the hypothesis that angiotensin-converting enzyme inhibition may cause anemia by increasing renal blood flow and consequently decreasing erythropoietin levels.

Atrial natriuretic peptide.

In the past several years great progress has been made in the understanding of the (patho) physiology of ANP. Because an inhibitor of ANP is not available for human use, there is still discussion about the physiological role of ANP. Nevertheless, from the studies described above the evidence is accumulating that ANP has a role in protecting against fluid overload and hypertension by means of inducing natriuresis, inhibition of the renin-angiotensin-aldosterone system and vasopressin and by vasodilation. The therapeutic potential of modulation of the ANP system seems promising, but must await further research.

The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors.

The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade.

Arterial and venous effects of atrial natriuretic peptide in the human forearm.

Atrial natriuretic peptide (ANP) has direct vasodilating properties in addition to its diuretic and natriuretic effects. Furthermore, vascular permeability may be influenced. Because relatively little is known about the venous and capillary actions of ANP in humans, we investigated the spectrum of vascular actions of ANP in the human forearm. In seven healthy subjects, ANP was infused intraarterially in consecutive doses of 0, 10, 50, and 250 ng/100 mL tissue/min together with vehicle or norepinephrine 1 ng/kg/min. In seven other subjects, 0.5 ng/kg/min angiotensin II and 10 ng/kg/min serotonin were used as a constrictor. Venous occlusion plethysmography was used to measure forearm blood flow, venous compliance, capillary filtration rate, and maximum venous outflow. Intraarterial infusion of ANP induced a dose-dependent increase of forearm blood flow but the relative increases were not influenced by concomitant vasoconstriction. Venous compliance was not affected by the infusions, but serotonin and angiotensin II decreased the changes of both forearm volume and venous pressure. ANP antagonized these effects of angiotensin II. Capillary filtration rate was not affected by ANP infusion. ANP alone had no effect on the maximum venous outflow, but it attenuated the decrease induced by norepinephrine and angiotensin II. These results indicate that in the human forearm ANP has predominantly arterial effects, whereas the venous actions become manifest only in the presence of vasoconstriction. The venous effect of ANP may therefore gain importance in disease states with elevated levels of vasoconstrictors, for instance, in congestive heart failure.

The effects of dietary excesses in animal protein and in sodium on the composition and the crystallization kinetics of calcium oxalate monohydrate in urines of healthy men.

Dietary excesses in animal protein and/or salt have been implicated as risk factors in calcium oxalate urolithiasis. The underlying physicochemical mechanism is, however, not known. Eight healthy men were given four different diets varying in animal protein and in sodium content for 1 week each. On a high protein intake (2 g/kg.day) significant changes in urinary calcium, uric acid, and citrate excretion rates were found. Similar changes in calcium and citrate were induced by a high sodium intake (310 mmol/day). The changes were more pronounced when a high protein was combined with a high sodium diet. Urinary calcium increased from 3.79 +/- 0.31 to 6.42 +/- 0.61 mmol/24 h and urinary uric acid from 4.69 +/- 0.26 to 8.0 +/- 0.47, whereas urinary citrate decreased from 3.93 +/- 0.53 to 2.79 +/- 0.34 mmol/24 h. All three dietary regimens induced a significant decrease in the ability of urines to inhibit calcium oxalate monohydrate crystal agglomeration, which was most marked during the combined diet (from 345 +/- 39 to 205 +/- 28 min). The ability of urines to inhibit crystal agglomeration was related to their citrate content (r = 0.69, P less than 0.0001). These results show that high animal protein and/or sodium intake decrease the ability of urines to inhibit the agglomeration of calcium oxalate crystals and provide a possible physicochemical explanation for the adverse effects of dietary aberrations on renal stone formation.

Atrial natriuretic peptide and chronic renal effects of changes in dietary protein and sodium intake in man.

1. Plasma levels of atrial natriuretic peptide and several other hormones were measured and related to the renal responses to chronic changes in the dietary intake of protein and sodium, alone and in combination. Eight healthy subjects consumed four diets for 1 week: a basal diet containing 140 mmol of sodium/day and 1 g of protein day-1 kg-1, the same diet with isocaloric addition of 1 g of meat protein day-1 kg-1, the basal diet with addition of 170 mmol of sodium chloride/day and the basal diet with both additions. 2. Creatinine clearance was increased significantly both by protein and, to a smaller extent, by sodium. Plasma atrial natriuretic peptide and the urinary excretion of guanosine 3':5'-cyclic monophosphate were increased significantly by sodium but were not affected by protein. Protein induced a significant rise in plasma glucagon levels, whereas the rise in somatomedin C (insulin-like growth factor I) just failed to reach statistical significance. 3. These findings demonstrate that atrial natriuretic peptide does not mediate chronic protein-induced hyperfiltration, although it may contribute to the renal effects of sodium. Glucagon and somatomedin C (insulin-like growth factor I) may have contributed to chronic protein-induced hyperfiltration.