Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin ß2-Microglobulin in Spent Dialysate.

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of ß2-microglobulin (ß2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of ß2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated ß2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of ß2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin ß2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.

Assessment of removal and adsorption enhancement of high-flux hemodialyzers in convective therapies by a novel in vitro uremic matrix.

Adsorption properties of hemodialyzers are traditionally retrieved from diffusive treatments and mainly focused on inflammatory markers and plasma proteins. The possible depurative enhancement of middle and high molecular weight solutes, as well as protein-bound uremic toxins by adsorption in convective treatments, is not yet reported. We used discarded plasma exchanges from uremic patients and out-of-date erythrocytes as a novel in vitro uremic precursor matrix to assess removal and adsorption patterns of distinct material and structure but similar surface hemodialyzers in hemodialysis and on-line hemodiafiltration treatments. We further related the obtained results to the possible underlying membrane pore blocking mechanisms. Convection improved removal but slightly enhanced adsorption in the cellulosic and synthetic dialyzers tested. The polymethylmethacrylate hemodialyzer obtained the highest extracted ([Formula: see text]) and adsorbed ([Formula: see text]) mass values when submitted to hemodiafiltration for all molecules analyzed including albumin ([Formula: see text] g, [Formula: see text] mg), whereas the polyamide membrane obtained substantial lower results even for this molecule ([Formula: see text] g, [Formula: see text] mg) under the same treatment parameters. Hemodiafiltration in symmetric and enlarged pore hemodialyzers enhances removal and adsorption by internal pore deposition (intermediate pore-blocking) for middle and high molecular weight toxins but leads to substantial and deleterious albumin depuration.

Epidemiology, impact, and treatment options of restless legs syndrome in end-stage renal disease patients: an evidence-based review.

Restless legs syndrome (RLS) (or Willis-Ekbom disease) is a neurological disorder with high prevalence among the end-stage renal disease population. This is one of the most predominant types of secondary RLS, and it is called uremic RLS. Despite the fact that uremic RLS has been less studied compared to idiopathic RLS, recent studies now shed light in many aspects of the syndrome including clinical characteristics, impact, epidemiology, and treatment options. The current review discusses the above topics with special emphasis given on the management of uremic RLS, including the management of symptoms that often appear during a hemodialysis session. Uremic RLS symptoms may be ameliorated by using pharmacological and nonpharmacological treatments. Evidence so far shows that both approaches may be effective in terms of reducing the RLS symptom's severity; nevertheless, more research is needed on the efficiency of treatments for uremic RLS.

In vivo assessment of bacteriotherapy on acetaminophen-induced uremic rats.

OBJECTIVES: Acetaminophen is a commonly used antipyretic agent which, at high doses, causes renal tubular damage and uremia. Bacteriotherapy affords a promising approach to mitigating uremic intoxication by ingestion of live microbes able to catabolize uremic solutes in the gut. The present study evaluates the nonpathogenic soil-borne urease-positive bacterium Sporosarcina pasteurii (Sp) as a potential urea-targeted component for such an "enteric dialysis" formulation. METHODS: Twenty-four albino male rats were randomly divided into 4 groups: The control group (group NC) received distilled water intraperitoneally for 7 days. The positive control group (group U) received 500 mg/kg acetaminophen intraperitoneally for 7 days. The tested group (group UP) was administered Sp at a dosage of 10(9) cells/day for 5 weeks, after receiving 500 mg/kg per day of acetaminophen intraperitoneally for 7 days. Vehicle control (group VC) received only Sp at a dosage of 10(9) cells/day for 5 weeks without acetaminophen treatment. Blood, kidney, liver and stool samples were collected after scarification, for biochemical (urea, creatinine, malondialdehyde, superoxide dismutase, catalase, glutamate oxaloacetate transaminase [GOT] and glutamate pyruvate transaminase [GPT] of blood, kidney and liver) tests. Limited fecal analysis was performed. RESULTS: Blood urea nitrogen (urea, creatinine) and toxicity indicators (GOT, GPT) were increased, and antioxidant enzymes were decreased in group U. Blood urea nitrogen and toxicity indicators were reduced, and antioxidant enzymes were increased significantly in the group UP (p<0.05) compared with group U. The number of Sp was increased in Sp-treated groups compared with groups NC and U. CONCLUSIONS: The study demonstrated that the bacteria tested reduced blood urea nitrogen levels significantly.

Uremic pruritus.

Uremic pruritus remains one of the most frustrating and potentially disabling symptoms in patients with end-stage renal disease. It affects up to 90% of patients on dialysis. Several hypotheses have been postulated for the possible underlying etiology, but none is conclusive. Aside from kidney transplantation, which is the only definitive treatment, therapeutic approaches have largely been empirical, and no firm evidence-based treatments are available. The main goal of therapy remains to minimize the severity of pruritus and improve the quality of life especially among those who are not transplantation candidates or are waiting for surgery.

Hemodiafiltration with endogenous reinfusion with and without acetate-free dialysis solutions: effect on ESA requirement.

BACKGROUND: Hemofiltrate reinfusion (HFR) is a form of hemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine hemodialysis and HDF contain small quantities of acetate (3-5 mM) as a stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. The impact of AF DS during HFR on Hb levels and erythropoietic-stimulating agent (ESA) requirement in chronic dialysis patients was assessed. PATIENTS AND METHODS: After obtaining informed consent, 30 uremic patients treated by standard bicarbonate dialysis (BHD, DS with acetate) were randomized to treatment in 3-month cycles: first AF HFR, followed by HFR with acetate, and again AF HFR. At the beginning and end of each period, Hb and ESA requirements were evaluated. RESULTS: A significant increase in the Hb level was observed throughout all periods of HFR versus BHD (from 11.1 to 11.86 g/dl; p = 0.04), with a significant decrease of ESA requirements from 29,500 to 25,033 IU/month (p = 0.04). CONCLUSION: Regardless of the presence or absence of acetate in DS, HFR per se allows a significant lowering of ESA dosage versus BHD, while at the same time increasing Hb levels. Taking for granted the clinical impact produced, HFR seems to provide a relevant decrease in end-stage renal disease patient costs.

Automated monitoring of hemodialysis adequacy by dialysis machines: potential benefits to patients and cost savings.

Hemodialysis adequacy can be quantified using ultraviolet absorbance of the spent dialysate, or by analysis of dialysate conductivity at the dialyzer inlet and outlet in response to changes in dialysate electrolyte concentration. These measurements can be made at every dialysis, including initial and acute treatments and can help detect access recirculation. No disposables or reagents are required. Cost may be reduced by reducing the need for blood sampling and laboratory analysis.

Stressful ethical issues in uremia therapy.

The objectives of this review are to introduce and explore the following representative ethical problems generated by modern renal replacement therapy: (1) reviewing the historical origin of medical ethics with specific reference to nephrology; (2) recognizing the complex stresses surrounding assignment of a deceased donor renal transplant to a geriatric patient while young patients continue waiting for a donor kidney; and (3) appreciating the concept of futility and support for a uremic patient opting for death rather than further uremia therapy as the best in choice in coping with renal failure.

A longitudinal study of uremic pruritus in hemodialysis patients.

BACKGROUND AND OBJECTIVES: Although uremic pruritus (UP) is a highly prevalent complication of chronic kidney disease, it remains poorly characterized. There have been no longitudinal studies of natural history, and no health-related quality of life (HR-QOL) instruments have been developed for UP. The objectives of this study were to describe the natural history of UP, to compare rating scales of itching intensity, and to assess usefulness and validity of HR-QOL instruments for UP. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The intensity, severity, and effects of pathologic itching on HR-QOL were assessed prospectively in 103 patients with UP on chronic hemodialysis. Outcome measures were obtained at scheduled intervals over 3.5 months. RESULTS: Itching daily or nearly daily was reported by 84% of patients and had been ongoing for >1 year in 59%. In 83%, pruritus involved large, nondermatomal areas with striking bilateral symmetry. Two thirds of the patients were using medications such as antihistamines, steroids, and various emollients without satisfactory relief of itching. Statistically significant associations were found among itching intensity, severity, and HR-QOL measures in domains such as mood, social relations, and sleep. Among patients with moderate-to-severe UP, changes in itching intensity of 20% or greater were associated with significant reductions in HR-QOL measures. CONCLUSIONS: This first longitudinal study of UP describes key features of UP and its effect on HR-QOL. The assessment instruments we have developed are easily used, are responsive to changes in UP intensity, and should facilitate clinical evaluation and research to meet the needs of afflicted patients.

Substitute treatment and replacement in chronic kidney disease: peritoneal dialysis, hemodialysis and transplant.

Chronic dialysis replacement treatments or renal transplants are instituted when the patient's glomerular filtration rate, measured by 24-h urine endogenous creatinine clearance, is <10-15 ml/mm and, as the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI), European and Canadian guidelines point out, when one or two of the following complications occur: "uremic toxicity" symptoms, significant fluid retention that does not respond to loop diuretics, hyperkalemia, chronic anemia (hemoglobin <8 g), metabolic acidosis or acute pulmonary edema. In all patients for whom transplant is indicated, a selected live donor must be sought or, in the absence of contraindications, the patient should be registered with the national cadaver donation waiting list. While waiting for the transplant, patients will be on a chronic dialysis program. There is no national registry of patients undergoing chronic dialysis; only indirect data from the Mexican Kidney Foundation and the dialysis industry are available. However, it is estimated that 40,000-50,000 people are under this treatment and the numbers grow by 11% every year. Overall, it is thought that for every patient receiving chronic dialysis, there is one more patient who dies without access to therapy. Hemodialysis units must comply with the Official Hemodialysis Standard and the General Health Council Hemodialysis Unit Quality Assessment Form.

More of the same: improving outcomes through intensive hemodialysis.

The typical dialysis patient faces both a poor quality of life and a significantly shortened survival. This is often blamed on "uremia." However, defining the clinical entity of uremia is surprisingly difficult. It represents the clinical sequelae of the effects of retention products, other effects of renal disease, and the effects of other comorbid conditions. The list of retention products that could act as uremic toxins is lengthy, but it would appear that urea itself does not contribute significantly to the uremic state. Larger molecular weight substances are likely the major contributors to the uremic milieu. Regardless of the causes, the uremic state persists in many patients who are reaching their dialysis adequacy targets as defined by urea clearance. This raises the possibility that more intensive hemodialysis could improve patient outcomes. Hemodialysis can be intensified by increasing dialysis efficiency without changing duration or frequency. Alternatively, hemodialysis duration, frequency, or both can be increased. All intensification methods increase small solute removal, but the removal of larger molecular weight retention products depends more upon treatment time. Modalities such as short daily hemodialysis, long intermittent hemodialysis, and quotidian nocturnal hemodialysis have been associated with a variety of clinical improvements, as well as improvements in quality of life and a lower standardized mortality ratio. However, the HEMO study approach of intensifying small solute clearance without significant modifications of the dialysis schedule does not appear to be effective. Future research will help to define the optimal treatment duration and frequency in hemodialysis patients.

Tratamientos sustitutivos en enfermedad renal: diálisis peritoneal, hemodiálisis y trasplante renal / Substitute treatment and replacement in chronic kidney disease: peritoneal dialysis, hemodialysis and transplant

Los tratamientos sustitutivos de diálisis crónica o trasplante renal se inician cuando la filtración glomerular del paciente medida por la depuración de creatinina endógena en la orina de 24 horas es inferior a 15 o 10 ml/mm y cuando se presentan complicaciones. A los enfermos con indicaciones de trasplante se les debe buscar un donador vivo seleccionado o inscribirlos en la lista de espera nacional de donación cadavérica si no existen contraindicaciones. Aun cuando no hay un registro nacional mexicano de pacientes en diálisis crónica, solo datos indirectos de la Fundación Mexicana del Riñón y de la industria de diálisis, se estima que de 40 mil a 50 mil son sujetos a este tratamiento y que anualmente la cifra se incrementa 11 %. En términos generales se considera que por cada enfermo en diálisis crónica hay otro que fallece sin acceso al tratamiento. Las unidades de hemodiálisis deben cumplir con la norma oficialmexicana de hemodiálisis y la cédula de evaluación de la calidad de las unidades de hemodiálisis del Consejo de Salubridad General. Es aconsejable que los pacientes sean incorporados a diálisis crónica después de ser presentados al comité de diálisis, y que el tratamiento se aplique con la aceptación del enfermo o sus familiares y se registre en el censo nominal.

Chronic dialysis replacement treatments or renal transplants are instituted when the patient's glomerular filtration rate, measured by 24-h urine endogenous creatinine clearance, is <10-15 ml/mm and, as the The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI), European and Canadian guidelines point out, when one or two of the following complications occur: "uremic toxicity" symptoms, significant fluid retention that does not respond to loop diuretics, hyperkalemia, chronic anemia (hemoglobin <8 g), metabolic acidosis or acute pulmonary edema. In all patients for whom transplant is indicated, a selected live donor must be sought or, in the absence of contraindications, the patient should be registered with the national cadaver donation waiting list. While waiting for the transplant, patients will be on a chronic dialysis program. There is no national registry of patients undergoing chronic dialysis; only indirect data from the Mexican Kidney Foundation and the dialysis industry are available. However, it is estimated that 40,000-50,000 people are under this treatment and the numbers grow by 11% every year. Overall, it is thought that for every patient receiving chronic dialysis, there is one more patient who dies without access to therapy. Hemodialysis units must comply with the Official Hemodialysis Standard and the General Health Council Hemodialysis Unit Quality Assessment Form.

Uremic syndrome and end-stage renal disease: physical manifestations and beyond.

PURPOSE: This review summarizes data concerning the incidence, definition, pathophysiology, and physical manifestations of patients with uremic syndrome. DATA SOURCES: Data sources utilized in writing this article included the National Kidney Foundation Guidelines, the United States Renal Data System, textbooks of medicine and pathophysiology, and medical care and nursing journals. CONCLUSIONS: Early identification of kidney disease in the early stages is essential to preserving kidney function for as long as possible. The progression of chronic kidney disease (CKD) and the manifestations of uremic syndrome leading to end-stage renal failure (ESRF) are often not addressed in the literature for nurse practitioners. IMPLICATIONS FOR PRACTICE: Patients with progressing CKD and ESRF often present in the primary care setting for treatment of acute and chronic conditions not pertaining to their renal status (e.g., viral upper respiratory infections, diabetes, hypertension). Nurse practitioners need to be knowledgeable about the subtle early presentation of uremic syndrome and ESRF, risk factors for kidney disease, assessment tools to make the diagnosis and stage the disease, treatment of this disease, as well as psychological, economic, and the social impact that ESRF imposes on individuals, families, communities, and the healthcare system as a whole when the chronic disease has progressed to end stage.

A critical assessment of uremia research.

There are considerably fewer randomized controlled trials investigating hemodialysis (HD) than other fields of internal medicine, and no significant improvements have been observed over time. Only the National Cooperative Dialysis Study and the HEMO trial were based on hard endpoints such as morbidity and mortality, but neither considered on-line hemodiafiltration or super-flux membranes, which are thought to provide a number of advantages in terms of the cardiovascular condition of uremic patients. However, results of well-designed clinical trials showing that increasing convection may improve the clinical outcome of HD patients are still lacking. The need for maximizing removal of uremic toxins calls for more frequent HD sessions, but this may be affected by many organizational problems. Therefore, well-designed, long-term clinical trials are urgently needed to investigate which currently available therapeutic instruments can improve the clinical outcome of uremic patients.

[Health related quality of life (HRQoL) assessment in uremic patients: a qualitative review of concepts, methods, available instruments and results]. / Misurare la Qualità della Vita correlata alla Salute (QdV-S) nel paziente uremico: una review dei concetti, dei metodi, degli strumenti disponibili e dei risultati.

The health related quality of life (HRQoL) assessment is a complex and multidimensional concept usually defined as the perception by individuals of the impact of diseases and medical treatments on physical, psychological and social aspects of health and life. HRQoL has become more popular in the last 20 yrs as an important indicator of the effectiveness of the medical care in clinical research protocols, and as part of so-called patient-reported outcomes (PRO), which are concepts concerning aspects of health perceived, reported and rated by study subjects or patients. Generic and disease specific questionnaires are usually used to assess the individual's perceptions about health and life, and more valid and reliable instruments are now available to use in research settings. Instruments that can be useful in daily clinical practice, in the management of the single patient, are not yet available. A large portion of the scientific literature dealing with HRQoL is actually focused on many aspects of uremic syndrome, renal transplantation and dialysis therapies, probably because several reasons make this clinical setting particularly favorable for HRQoL assessment. Early referral to a nephrologist, anemia treatment with epoetin, daily and nocturnal dialysis, kidney transplantation, a program of physical exercise and the treatment of some co-existent conditions and symptoms (i.e. depression, pain, erectile dysfunction and restless leg symptoms) are the most effective ways to ameliorate HRQoL in renal patients. Moreover, HRQoL is a reliable prognostic factor for morbidity and mortality in uremic patients.

Hypertension and cardiovascular risk assessment in dialysis patients.

INTRODUCTION: Cardiovascular (CV) disease is the main cause of morbidity and mortality in dialysis patients. Hypertension in patients affected by chronic renal insufficiency (CRI) has been recognized as one of the major classical CV risk factors in CRI from the very beginning of the dialysis era. However, its treatment is still unsatisfactory. METHODS: A discussion is employed to achieve a consensus on key points relating to the epidemiological, pathophysiological and clinical characteristics of hypertension in renal patients, in the light of global CV risk assessment. RESULTS: CV disease is accelerated by CRI, in particular by uraemia-specific risk factors. This is reflected by the fact that general population-based equations for calculating CV risk underestimate the real CV risk in CRI and dialysis patients. Hypertension in dialysis patients is clearly a major CV risk factor. Isolated systolic hypertension with increased pulse pressure is the most prevalent blood pressure (BP) anomaly in dialysis patients, due to stiffening of the arterial tree. BP should be assessed by clinical measurements on a routine basis, leaving 24 h monitoring for selected cases. The targets of BP control should be those recommended by the present guidelines, i.e. <140/90 mmHg, or the lowest possible values that are well tolerated. The pathophysiological cornerstone of hypertension in dialysis patients is extra-cellular volume expansion, which is typically sodium-sensitive, given the loss of renal function. Therefore, the principles of hypertension treatment in dialysis are an achievement of dry body weight, proper dialysis prescription with respect to dialysis time and intra-dialytic sodium balance, and dietary sodium and water restriction. Pharmacological treatment should only be the second option, after the adequate and complete application of all other means. No comparative pharmacological trials have specifically addressed the issue of hypertension control in dialysis patients. Therefore, this workshop group had to rely largely on data obtained in the general population. Drugs interfering with the renin-angiotensin system were felt to be the first choice, as they have widely been shown to interfere significantly with CV remodelling. Despite long-standing concerns, beta-blockers are being used increasingly even in patients with congestive heart failure and ischaemic cardiomyopathy. Other drug classes may be used in association or as first-line agents according to clinical requirements. CONCLUSIONS: Hypertension in renal patients has to be given particular and continued attention, and it should be adequately treated in light of the increased CV risk of this patient population. Research into the mechanisms of uraemic cardiomyopathy and cardiovascular remodelling should provide a precious new insight and lead to more precisely targeted and more effective therapies than in the past.

The extent of uremic malnutrition at the time of initiation of maintenance hemodialysis is associated with subsequent hospitalization.

OBJECTIVE: End-stage renal disease (ESRD) patients with signs of uremic malnutrition at the time of initiation of maintenance hemodialysis (MHD) are likely to remain malnourished over the subsequent year. Because poor nutritional status is associated with worse clinical outcomes in MHD patients, we hypothesized that ESRD patients with evidence of uremic malnutrition at the time of initiation of MHD would have more hospitalization events compared with patients initiating MHD without signs of malnutrition during the first year of therapy. DESIGN/INTERVENTION: This was an observational cohort of incident MHD patients, with no specific nutritional intervention. SETTING: Vanderbilt University Outpatient Dialysis Unit. PATIENTS: All newly initiated MHD patients at Vanderbilt University Outpatient Dialysis Unit were recruited for study purposes. A total of 149 patients were included in the study. MAIN OUTCOME MEASURE: The following parameters were recorded at the time of initiation of MHD: age; race; gender; serum concentrations of albumin, creatinine, cholesterol, and transferrin; and whether the patient had insulin-dependent diabetes mellitus. The number of hospital admissions and length of stay in the hospital were recorded for all study patients during the first year of MHD. Associated hospital charges were obtained for a subgroup of 52 patients. RESULTS: Study variables were associated with hospitalization in the subsequent year, the number of hospital admissions, and the length of stay in the hospital. Patients who initiated MHD in the lowest quartile of serum albumin had a significantly greater average of admissions compared with patients who initiated in the highest quartile (1.77 +/- 1.82 versus 0.72 +/- 0.96 admissions, P =.002). The length of stay in the hospital was also higher in the lowest quartile of serum albumin (8.96 +/- 9.96 versus 3.83 +/- 5.68 days, P =.006). Serum creatinine was also inversely associated with greater average number of admissions (2.27 +/- 2.41 versus 0.83 +/- 1.68 admissions, P =.004) and longer length of stay (12.43 +/- 15.15 versus 4.72 +/- 11.57 days, P =.017) in lowest compared with the highest quartile. In addition, the costs associated with hospitalizations were higher in the group of patients initiating MHD with lower concentrations of serum albumin and serum creatinine. CONCLUSIONS: In this study of incident MHD patients, the concentrations of 2 nutritional parameters, serum albumin and serum creatinine at the time of initiation of MHD, were significantly and negatively associated with hospitalization events. There was also a trend for greater hospital charges in patients with lower concentrations of serum albumin and creatinine.

[Uremic patients--late referral, early death]. / Urämische Patienten--späte Uberweisung, früher Tod.

BACKGROUND AND OBJECTIVE: A number of reports from various countries document that patients with renal failure who are referred late to renal units, have more complications e. g. lack of vascular access when dialysis has to be started as well as longer hospitalisation and have also a higher risk of early death. No data on these points are available from Germany. PATIENTS AND METHODS: In a retrospective analysis the timing of referral to the nephrologists was studied in two Departments of Medicine, e. g. Heidelberg and Vienna, for all patients who started renal replacement therapy. For patients in Heidelberg the relation between timing of referral and survival on dialysis was analysed using the Kaplan-Maier-technique. RESULTS: In Heidelberg 280 patients were analysed, 174 men, 106 women, age 61.8 +/- 14.5 years; 136 diabetic patients (9 type 1). They had been referred from GPs (n = 131), specialists (diabetologists, cardiologists; n = 20), emergency departments (n = 33), other hospitals (n = 90) or other institutions (n = 16). The measured median creatinine clearance at the time of referral was 14 ml/min (5-34). The median interval between referral and start of dialysis was 17 weeks. 137 patients had been referred < 17 weeks and 143 patients > or = 17 weeks prior to the start of dialysis. 97 of the 111 patients referred < or = 4 weeks prior to dialysis and 59 of the 169 patients referred > 4 weeks had to be dialysed with a central catheter. There were clear differences in patient survival. In patients referred < 17 weeks before the start of dialysis, the actuarial risk of death during the first 12 month was 34.2 % compared to 5.5 % (p < 0.0001) in patients referred > or = 17 weeks. Even the mortality in the interval between 12 and 24 months after the start of dialysis was clearly higher (15.3 %) in patients with late compared to early referral (11.4 %). CONCLUSION: Late referral of patients with impaired renal function to renal units causes more frequent problems of vascular access, longer hospitalisation, more medical complications, higher costs and higher mortality. Early referral of patients with renal failure is indispensable to improve dialysis outcomes.