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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 19 recordsLinked to original sources
PubMed2006

Earthquakes and crush syndrome casualties: lessons learned from the Kashmir disaster.

Major earthquakes may provoke a substantial number of crush casualties complicated by acute kidney injury (AKI). After the 1988 Armenian earthquake, the International Society of Nephrology (ISN) established the Renal Disaster Relief Task Force (RDRTF) to organize renal care in large disasters; this approach proved to be useful in several recent disasters. This paper depicts the organizational aspects of the rescue intervention during the Kashmir earthquake, in 2005. Specific problems were fierce geographic circumstances, lack of pre-registered local keymen, transportation problems, and inexperience of local teams to cope with problems related to mass disasters. Once treatment was installed, global outcomes were favorable. It is concluded that well-organized international help in renal disasters can be effective in saving many lives, but still necessitates conceptual adaptations owing to specific local circumstances.

Acute Disease↗
PubMed2006

Biochemical validation of a rat model for polycystic kidney disease: comparison of guanidino compound profile with the human condition.

Polycystic kidney disease (PKD) accounts for 7-10% of all dialyzed renal insufficient patients. Accumulation of specific guanidino compounds (GCs) has been related to neurological, cardiovascular, hematological, and immunological complications of renal failure. In this study, we investigate whether the PKD/Mhm rat model can be used as a biochemical model for human PKD. For the validation of the rat model, we performed the first detailed evaluation of the concentrations of GCs in serum and urine of patients with PKD in addition to the GC patterns in the plasma, urine, and tissues of the PKD/Mhm rat model. The GCs were determined after separation on a cation exchange resin and fluorescence detection. The GC levels and changes observed in blood and urine of patients with PKD are comparable with those found in patients with renal insufficiency due to different etiologies. The PKD/Mhm rat model can be used as a biochemical model for human PKD as the obvious increases of urea, guanidinosuccinic acid, creatinine, guanidine, methylguanidine, and N(G)N(G)-dimethylarginine (symmetrical dimethylarginine) seen in blood of oldest heterozygous and younger homozygous PKD rats were largely within the same range as those found in the studied human PKD population, especially in patients with a glomerular filtration rate below 60 ml/min/1.73 m(2). The decreased levels of plasma guanidinoacetic acid seen at end-stage renal disease in homozygous and oldest heterozygous rats were also observed in serum of patients with a glomerular filtration rate below 20 ml/min/1.73 m(2). The PKD/Mhm rat model has, besides similar disease characteristics with human PKD, comparable GC alterations.

Animals↗
PubMed2006

What is uremia? Retention versus oxidation.

The uremic syndrome is characterized by the retention of a host of compounds which in healthy subjects are secreted into the urine by the healthy kidneys. These compounds disturb many physiologic functions, resulting in toxicity. However, many of the retained compounds as well as many of the pathophysiologic actions of the known retention solutes remain unknown. In this publication, we review recent information on uremic toxicity. Especially the difficulty to remove compounds, such as protein-bound compounds and larger molecules, seems to play a crucial role. New strategies enhancing their removal might be highly useful. Part of the retained compounds are the result of oxidative processes due to the inflammatory status of uremic patients; however, other compounds are not, and even the concentration of oxidative compounds will be further increased by disturbances of urinary clearance.

Hemodialysis Solutions↗
PubMed2006

The impact of the pre-transplant renal replacement modality on outcome after cadaveric kidney transplantation: the ghent experience.

For suitable patients, renal transplantation is still the most preferable renal replacement modality, offering the best outcome in terms of survival and quality of life [Meier-Kriesche, H.U. et al: Semin Dial 2005;18:499-504]. The shorter the period on dialysis, the better the outcome after transplantation seems to be [Meier-Kriesche, H.U. et al: Transplantation 2002;74: 1377-1381]. However, for most patients, a pre-emptive transplantation is not an option by lack of a suitable organ. Therefore, most people have to undergo hemodialysis or peritoneal dialysis (PD) while awaiting a donor kidney. There is evidence that PD positively impacts on the outcome after transplantation [Van Loo, A.A. et al: J Am Soc Nephrol 1998;9:473-481], an effect that could be attributed to a more stable fluid homeostasis, but also to an independent effect of biocompatibility of the dialysis membrane [Van Biesen, W. et al: Transplantation 2000;69:508-514], which is by definition better in PD. Based on these findings, since 1999, all hemodialysis patients at the university of Ghent are dialyzed on a low complement activating dialyzer, and dialysis and especially ultrafiltration in the 24 h preceding the transplantation are avoided as much as possible. A recent re-analysis of the data of the outcome of our transplant program showed that this approach resulted in a reduction of delayed graft function in the hemodialysis patients, allowing to reach an outcome level comparable to that of the PD patients. However, the long-term patient survival still is slightly superior in the PD patients.

Cadaver↗
PubMed2005

Isolation and quantification of dinucleoside polyphosphates by using monolithic reversed phase chromatography columns.

In former studies, dinucleoside polyphosphates were quantified using ion-pair reversed-phase perfusion chromatography columns, which allows a detection limit in the micromolar range. The aim of this study was both to describe a chromatographic assay with an increased efficiency of the dinucleoside separation, which enables the reduction of analytical run times, and to establish a chromatographic assay using conditions, which allow MALDI-mass spectrometric analysis of the resulting fractions. We compared the performance of conventional silica reversed phase chromatography columns, a perfusion chromatography column and a monolithic reversed-phase C18 chromatography column. The effects of different ion-pair reagents, flow-rates and gradients on the separation of synthetic diadenosine polyphosphates as well as of diadenosine polyphosphates isolated from human platelets were analysed. Sensitivity and resolution of the monolithic reversed-phase chromatography column were both higher than that of the perfusion chromatography and the conventional reversed phase chromatography columns. Using a monolithic reversed-phase C18 chromatography column, diadenosine polyphosphates were separable baseline not only in the presence of tetrabutylammonium hydrogensulfate (TBA) but also in the presence of triethylammonium acetate (TEAA) as ion-pair reagent. The later reagent is useful because, in contrast to TBA, it is compatible with MALDI mass-spectrometric methods. This makes TEAA particularly suitable for identification of unknown nucleoside polyphosphates. Furthermore, because of the lower backpressure of monolithic reversed-phase chromatography columns, we were able to significantly increase the flow rate, decreasing the amount of time for the analysis close to 50%, especially using TBA as ion-pair reagent. In summary, monolithic reversed phase C18 columns markedly increase the sensitivity and resolution of dinucleoside polyphosphate analysis in a time-efficient manner compared to reversed-phase perfusion chromatography columns or conventional reversed-phase columns. Therefore, further dinucleoside polyphosphate analytic assays should be based on monolithic silica C18 columns instead of perfusion chromatography or conventional silica reversed phase chromatography columns. In conclusion, the use of monolithic silica C18 columns will lead to isolation and quantification of up to now unknown dinucleoside polyphosphates. These chromatography columns may facilitate further research on the biological roles of dinucleoside polyphosphates.

Blood Platelets↗
PubMed2005

Chronic kidney disease as cause of cardiovascular morbidity and mortality.

To make an evidence-based evaluation of the relationship between kidney failure and cardiovascular risk, we reviewed the literature obtained from a PubMed search using pre-defined keywords related to both conditions and covering 18 years (1986 until end 2003). Eighty-five publications, covering 552 258 subjects, are summarized. All but three studies support a link between kidney dysfunction and cardiovascular risk. More importantly, the association is observed very early during the evolution of renal failure: an accelerated cardiovascular risk appears at varying glomerular filtration rate (GFR) cut-off values, which were >/=60 ml/min in at least 20 studies. Many studies lacked a clear definition of cardiovascular disease and/or used a single determination of serum creatinine or GFR as an index of kidney function, which is not necessarily corresponding to well-defined chronic kidney disease. In six studies, however, chronic kidney dysfunction and cardiovascular disease were well defined and the results of these confirm the impact of kidney dysfunction. It is concluded that there is an undeniable link between kidney dysfunction and cardiovascular risk and that the presence of even subtle kidney dysfunction should be considered as one of the conditions necessitating intensive prevention of this cardiovascular risk.

Cardiovascular Diseases↗
PubMed2005

Right atrial thrombus in an asymptomatic hemodialysis patient with malfunctioning catheter and patent foramen ovale.

The creation of an accurate functioning arteriovenous fistula has been a long-lasting problem in the hemodialysis setting. In spite of recent guidelines and largely because of the old age of the current dialysis population and a high incidence of diabetes mellitus, atherosclerosis, and related vascular problems, it is not always possible to create an adequate fistula. In that case, long-term tunneled indwelling central vein catheters are a frequently used alternative. Of the many possible complications related to venous access in hemodialysis patients, catheter dysfunction is the most prevalent. We report a 23-year-old female hemodialysis patient in whom such malfunctioning was followed by echocardiography that revealed a large right atrial thrombus (RAT) in close contact to the tip of a long-term indwelling catheter in the presence of a patent foramen ovale. Although RAT is a rare complication in hemodialysis patients, it has very specific therapeutic implications. The present patient underwent a successful surgical atrial thrombectomy. Our experience underscores that in cases of malfunctioning catheter, echocardiographic screening is mandatory.

Adult↗
PubMed2005

New insights in uremic toxicity.

The uremic syndrome is characterised by the retention of a host of compounds that in healthy subjects are secreted by the kidneys into normal urine. These compounds disturb many physiologic functions, resulting in toxicity. Many of the responsible compounds remain unknown, however, as well as many patho-physiologic actions of the known retention solutes. In this publication, we review recent new information regarding uremic toxicity. Especially difficult to remove compounds, such as protein bound and larger molecules, seem to play a role. New strategies enhancing their removal might be highly useful.

Dinucleoside Phosphates↗
PubMed2004

Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.

Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and guanidinosuccinic acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.

Animals↗
PubMed2004

Lessons learned from the catastrophic Marmara earthquake: factors influencing the final outcome of renal victims.

BACKGROUND: During catastrophic earthquakes, crush syndrome is the second most frequent cause of death after the direct impact of trauma. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 639 crush syndrome victims with acute renal problems. The factors influencing their final outcome have been the subject of this study. PATIENTS/METHODS: Within the first week of the disaster questionnaires asking about 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information obtained by means of these questionnaires, including the factors with a potential influence on outcome, was submitted to analysis. RESULTS: Overall mortality rate was 15.2%. In univariate analysis, nonsurvivors were older (p = 0.048); the highest mortality rates were observed among the victims coming from the closest cities to the reference hospitals. Admission within the first 3 days of the disaster (p = 0.016), with oliguria (p = 0.042), lower figures for blood pressure (p < 0.001), platelets (p = 0.004) and serum albumin (p = 0.005) were associated with mortality. Also, higher body temperature (p = 0.013) and serum potassium (p < 0.001) as well as suffering from thoracic or abdominal traumas, extremity amputations and medical complications other than renal failure (for all 4: p < 0.0001) in addition to need of dialysis support (p = 0.015) and mechanical ventilation (p < 0.0001) indicated higher risk of death. In the multivariate analysis, age (p = 0.030, OR = 1.02), presence of disseminated intravascular coagulation (p = 0.001, OR = 4.49), abdominal trauma (p = 0.012, OR = 4.05) and amputations (p = 0.010, OR = 2.81) were predictors of mortality. Dialyzed patients were characterized by higher mortality rates than nondialyzed victims (17.2% versus 9.3%, p = 0.015). CONCLUSION: Outcome of the renal victims of catastrophic earthquakes is influenced by the type of trauma, comorbid events and complications observed during the clinical course as well as epidemiological features such as age, distance to reference hospitals and time lapse between disaster and admission to reference hospitals.

Acute Kidney Injury↗
PubMed2003

The low nanomolar levels of N G-monomethylarginine in serum and urine of patients with chronic renal insufficiency are not significantly different from control levels.

There are no reliable mean values of N(G)-monomethylarginine (NMMA) in blood and urine of patients with renal insufficiency available in the literature. Therefore we investigate whether the NMMA levels are changed in blood and urinary excretion of nondialysed and dialysed patients with chronic renal insufficiency to evaluate whether NMMA may reach sufficiently increased concentrations in blood of the patients to exert toxic biological activity. In nondialysed as well as in dialysed patients we find no significant difference in serum concentration of NMMA between patients and controls. In nondialysed patients (all with a residual creatinine clearance lower than 15 ml/min), we find 94.5 +/- 26.1 nM (mean +/- SD) versus 94.6 +/- 19.5 nM in controls. Similar levels are found in serum of haemodialysed patients (each with serum creatinine levels >700 micro M): 83.0 +/- 20.2 nM. The urinary excretion of NMMA in nondialysed patients is also not significantly different from the excretion of controls: 123 +/- 110 in patients versus 157 +/- 117 nmol/24 hrs in controls. Furthermore, the clearance of NMMA is much lower compared to the clearance of the dimethylarginine derivatives. Based on the literature, the low nanomolar levels of NMMA found in blood of patients with renal insufficiency do not support the statement that NMMA proper may act as a uremic toxin.

Adult↗
PubMed2003

Nitric oxide in uremia: effects of several potentially toxic guanidino compounds.

Vascular and neurologic impairment remain an important source of morbidity in patients with chronic renal failure (CRF). A portion of CRF patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in CRF patients, even in those with otherwise adequate dialysis treatment [1]. Premature vascular disease, including myocardial infarction, stroke, and peripheral vascular disorder, are the leading causes of death in this population. Although several traditional risk factors for vascular disease and endothelial dysfunction, including smoking, diabetes, dyslipidemia, and hypertension, are often increased in CRF, these factors can only partly explain the high vasculopathy-related morbidity and mortality. Several authors have postulated that CRF-associated atherosclerosis and endothelial dysfunction result from accumulation of certain 'uremic factors,' the identities of which are still a matter of debate. These factors include a variety of guanidino compounds (GCs), which have been shown to be nitric oxide synthase (NOS) modulators both in vitro and in vivo. However, other effects of accumulated uremic GCs have been identified.

Guanidines↗
PubMed2003

Survival of hemodialysis patients and uremic toxin removal.

Uremic toxin removal based on diffusion and/or convection allows eliminating solutes with negative metabolic impact. Uremic solutes can be classified as small and water-soluble compounds, larger "middle" molecules, or protein bound solutes. The question arises whether more removal of each of these solute classes affects patient survival. Kt/V of urea is currently used as a surrogate for small water-soluble solute removal. There is ample evidence that Kt/V and survival are correlated, but the threshold Kt/V remains a matter of debate. Probably, the actually proposed threshold of 1.2 is too low. This impact of Kt/V is in contradiction with the low toxicity of urea and points to a role for other water-soluble solutes, e.g., potassium. More removal of middle molecules results in a lower morbidity and also in a lower mortality. In addition, a relationship has been demonstrated between the use of membranes with large pore size and a decrease of inflammatory status, by itself an important factor related to mortality. One of the problems is that large pore membranes are at the same time more biocompatible and reflect more dialysate impurities, compared to many small pore membranes, whereas they also reflect more dialysate impurities. It remains uncertain which one of these factors, if any, has a predominant effect. Recent studies point to a separate effect of pore size but await confirmation. Protein bound toxins inhibit several biochemical functions. Their removal pattern is totally different from that of classical markers such as urea. In analogy with drugs, it is essentially the free unbound fraction that exerts biological action; this free fraction is inversely related to serum albumin, another inflammatory marker related to survival. In a final section of this presentation, attention will be drawn to the relationship in uremic patients between inflammation, malnutrition, cardiovascular disease, and mortality, and some of the potential culprits are discussed. Virtually all of these molecules have a high molecular weight or are protein bound. It is concluded that both small and middle molecule removal have an impact on survival, so that more than urea removal alone should be pursued.

Humans↗
PubMed2003

Dialysis strategies in critically ill acute renal failure patients.

PURPOSE OF REVIEW: Acute renal failure requiring dialysis is a frequent complication in critically ill patients, with a high morbidity and mortality. Until now, no evidence-based guidelines on the optimal treatment of acute renal failure on the ICU are available. This article reviews recent publications that shed light on several specific topics, like optimal treatment modality, dose of dialysis, type of dialysis membrane, and new developments such as slow extended daily dialysis. RECENT FINDINGS: For a long time, it has been claimed that continuous renal replacement therapies were superior to intermittent hemodialysis. Several recent articles addressed this topic, but none of them could demonstrate superiority of one of the two modalities. A meta-analysis confirmed this lack of differences in outcome. A landmark study underscored the importance of dose of dialysis in continuous renal replacement therapy. Although a comparable study in intermittent hemodialysis is still lacking, it was shown that daily dialysis is an absolute prerequisite for adequate intermittent hemodialysis. A meta-analysis further demonstrated that the use of biocompatible membranes can influence patient survival positively, without effect on recovery of renal function. Slow extended daily dialysis emerged as a hybrid renal replacement therapeutic modality and has promising features because it combines the advantages of both continuous renal replacement therapy and intermittent hemodialysis. SUMMARY: Adequate dialysis is needed to reduce mortality related to acute renal failure in ICU patients. This necessitates an approach that is completely different from that in chronic renal failure.

Acute Kidney Injury↗