Urea as a marker of adequacy in hemodialysis: lesson from in vivo urea dynamics monitoring.

BACKGROUND: "Dialysis dose," a concept developed by Sargent and Gotch based on urea kinetic modeling, is a useful and recognized tool that is used to quantitate and optimize a dialysis-efficacy program. However, it has been shown that oversimplification of the "dialysis adequacy" concept to the Kt/V index might lead to dramatic underdialysis and subsequent deleterious consequences on morbidity and mortality of dialysis patients. With this perspective, the determination of Kt/V must be very cautious and rely on accurate measurement of postdialysis urea concentration and its use integrated as a tool in a quality-assurance process. METHODS: In this study, we analyzed urea dynamics by means of a blood side (ultrafiltrate) continuous online urea monitoring system interfaced with a two-pool model hosted in a microcomputer. The study was designed to provide instantaneous dialysis performances (body and dialyzer clearances, dialyzer mass transfer coefficient) and to determine the in vivo functional permeability characteristics of the patient [intercompartment urea mass transfer coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16 years; 12 male and 1 female) were studied during nine consecutive dialysis sessions (3 weeks). RESULTS: Urea kinetics obtained from the urea monitoring system fitted closely the urea kinetic modeling prediction, confirming the validity of the double-pool model structure. Effective in vivo urea mass transfer coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported with more invasive methods. Large variations ranging from 363 to 1249 mL/min were observed among patients, confirming very large interindividual patient permeability differences. Interestingly, the urea mass transfer coefficient was inversely correlated with the postdialysis rebound values. Intraindividual variations were also noted as a function of time denoting functional changes in urea mass transfer coefficient values. The urea distribution volume was 38.1 +/- 7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2 to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/- 6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume ratio was 0.31 (approximately one third) and was not as usually defined by the paradigm 1/2 ratio. CONCLUSION: Online double-pool urea kinetic modeling gave a new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a double-compartment model structure. Accessible extracellular volume to hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient must be considered as an individual and variable characteristic of ESRD patients that should be taken into consideration when prescribing the hemodialysis schedule.

Assessment of efficiency using on-line urea kinetic modeling in hemodiafiltration.

Urea kinetics has recently been re-evaluated using an on-line urea monitoring system applied to hemodiafiltration. This system allows evaluation of different components possibly responsible for the gap between prescribed and delivered dose of dialysis, such as access and cardiopulmonary recirculation, and altered dialysis parameters, such as blood flow and dialysate flow rates. Furthermore, the system allows prediction of postdialysis rebound urea concentrations. The aim of the present study was to apply the on-line urea monitoring system to assess the dialytic efficiency of double chamber hemodiafiltration in different conditions of blood-dialysate flow rates, reinfusion volumes, and dialyzer configurations (high + low flux membranes or high + high flux membranes) in 10 patients (age, 60 +/- 9 years; dry weight, 65 +/- 5 kg). There was a significantly lower Kt/V (K, dialyzer clearance; t, dialysis time; V, urea distribution volume) at equilibrium with the high + high vs high + low flux configuration, possibly because of a higher tendency toward urea compartmentalization. This difference was evident when reinfusion was performed post dilution. These studies support the concept that small molecular weight uremic toxins may be more efficiently removed using low flux membranes in a modified form of hemodiafiltration.

[Pharmacoeconomics in hemodialysis. Role of iron in the treatment with erythropoietin]. / Farmacoeconomia in emodialisi. Il ruolo del ferro nel trattamento con eritropoietina.

BACKGROUND: Although its efficacy is well known, the high economic cost of erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal Hb level with the lowest dosage of EPO seams to be correlated to the way of administration and an adequate iron supplementation. METHODS: The study evaluates the influence of iron supplementation on the control of EPO-related expenses. RESULTS: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our data show that this value, as far as pharmacoeconomic is concerned, is highly underestimated. CONCLUSIONS: A higher i.v. iron supplementation correlates with a significant raise of serum ferritin level and saves on EPO-related expenses up to 1 million/per patient/per year.

[24 Hour arterial pressure in insulin-dependent diabetics and non-insulin-dependent diabetics with preserved renal function]. / Pressione arteriosa/24 h in diabetici insulino-dipendenti e non insulino-dipendenti con conservata funzione renale.

BACKGROUND: The aim of the study was to value the behaviour of systolic (S) and diastolic (D) arterial pressure (AP)/24 hrs in a group of diabetic patients insulin-dependent (IDDM) and non insulin-dependent (NIDDM) with preserved renal function. METHODS: We examined 65 diabetic patients (aged 39.1 +/- 23.3), 33 IDDM (aged 18.2 +/- 7.5; years of diabetes: 5.8 +/- 4.9) and 32 NIDDM (aged 60.7 +/- 11.4; years of diabetes: 7.2 +/- 7.5). In all of them we computed BMI and determined creatinine clearance, glycosylated haemoglobin A, total and HDL-associated cholesterol, triglyceridemia, middle glycemia and microalbuminuria. AP measurement was performed by 24 hrs monitoring (periodicity 15') using a Takeda 2420 measurer. Chronobiological characteristics of AP were analysed by statistical method of cosinor according to Halberg, examining if there was or not a blood pressure circadian rhythm (PCR) (p < 0.05) and its characteristics represented by the mesor, the amplitude and the acrophase. Moreover the patients were subjected to a diet with fixed contents of sodium (130 mEq/day) and afterwards we drew (every 4 hours) renin (R), aldosterone (A1) and atrial natriuretic factor (ANF) which were analysed with cosinor's method. The purpose was not to compare the two populations, not homogeneous between them and not different only for the years of diabetes, but to study their blood pressure behaviour, the rhythm, the order of the indicated hormones for possible pathogenetic connections. RESULTS: NIDDM presented higher blood pressure values (PAS 134.2 +/- 3.5 and PAD 80.9 +/- 2 mmHg) than IDDM (PAS 116.6 +/- 1 and PAD 66.4 +/- 1.7 mmHg), still in limits of substantial normality. The acrophase was in the midday for NIDDM (PAS 11:25', PAD 12:06') and in the early afternoon for IDDM (PAS 14:15', PAD 14:06'). Analysing the trend of the AP in the single cases, PCR was present in 70% and absent in 30% of IDDM while it was persistent in 56% and disappeared in 44% of NIDDM. IDDM without PCR differed from those with it in years of diabetes (p < 0.001), body weight (p < 0.02), BMI (p < 0.01), triglyceridemia (p < 0.05), all more elevated, as well as in higher PAS and PAD (p < 0.001) and in higher concentration of ANF (p < 0.05). The same comparison was done in NIDDM. Patients without PCR were older (p < 0.025), had higher PAS (p < 0.025) and PAD (p < 0.001) and also a more activated ANF (p < 0.001). CONCLUSIONS: This hormonal anomaly may be ascribed to a lower excretion of sodium with consequent expansion of extracellular volume due to antinatriuretic action of insulin often found at high plasmatic levels particularly in NIDDM.

[The lipid model in hemodialyzed patients]. / Il modello lipidico negli emodializzati.

In the context of metabolic alteration in dialysis patients the Authors have studied the characteristics, incidence, pathogenesis, effect of dialysis, atherogenic risk and therapeutic approach to hyperlipemia in hemodialysis patients. Hypertriglyceridemia secondary to reduced lipolytic activity is the most frequent alteration observed in hemodialytic patients (36.7% of cases). In addition, hemodialysis reduces the levels of lipoprotein in the blood whereas the atherogenic role of hyperlipemia does not appear to be as important as that of arterial hypertension and smoking. Simvastatin breaks down the lipidic fractions which are involved in atherogenesis and coronary cardiopathy, thus acting as a valuable prevention against cardiovascular involvement in dialysis.

[The intradialytic kinetics of uremic toxins in the diffusion-convection hemodialysis method]. / La cinetica intradialitica delle tossine uremiche nell'emodialisi a meccanismo diffusivo-convettivo.

A kinetic evaluation of dialytic methods using a diffusive-convective mechanism in comparison to the standard bicarbonate dialysis was performed in order to verify the possible therapeutic uses. The "kinetic" comparison of PFD and HDF to HBD, using equal quantities of dialysate, showed no significant change in the mention of uremic toxins of small molecular weight and a more efficient capacity to extract beta 2M by the diffusive-convective methods. The biophysical evaluation of dialysis still appears to represent the best means of defining the clearance possibilities and of identifying the most suitable technique for achieving a dialytic adequacy.

[Immunological determination of various blood proteins in clinical nephrology]. / Dosaggio immunologico di alcune proteine sieriche nella clinica nefrologica.

The serum levels of certain proteins were determined in 130 nephropathics collected into 8 different diagnostic groups, and in 20 normal subjects considered as a control group. The purpose was mainly to assess the clinico-diagnostic interest of such a measurement in nephrological practice. The results point to its clinical usefulness, particularly in differential diagnosis. It is possible to formulate interesting physiopathological interpretations notwithstanding the limitations of the eminently clinical features of the research.

[Polyomavirus infection in an immunocompetent patient and literature overview]. / Infezione da Polymavirus in paziente immunocompetente e revisione della letteratura.

BACKGROUND: Polyoma virus (PV) is a double-stranded DNA virus, member of the Papovaviridae family. BKV and JCV are the most studied in human pathology, whereas simian virus 40 (SV40) is pathogenic in the monkey and has been implicated in human carcinogenesis. PV is associated with renal and urinary tract pathology. The initial infection by PV occurs in childhood, probably by airways, and is usually asymptomatic. Subsequently, it remains latent in kidneys, tonsils and CNS and may reactivate in concomitance with significant T-cell dysfunction. Infection in immunocompromised patients can be clinically relevant. However, asymptomatic viruria may be detected in 0.3 % of individuals without a known history of immunodeficiency. CASE REPORT: We describe the case of a male patient, aged 31, admitted to our Unit for arterial hypertension and urinary abnormalities. He had a history of hemorrhagic cystitis in 1996 and persistent microscopic hematuria thereafter. Renal function was normal, arterial pressure well controlled with an ACE-inhibitor; urine culture was negative and most of the immunologic and rheumatologic tests were normal, with the exception of slightly reduced levels of C3 and an inverted CD4/CD8 ratio. Serology for HCV, HBV, HIV and screening for tumor markers were negative. Renal ultrasonography displayed an increased reflectivity, as seen in medical nephropathies; no nephrolithiasis was found. Urinary cytology showed "decoy cells", as typically found in PV infection, whose presence was confirmed by n-PCR. Diagnosis at discharge from the hospital was primary arterial hypertension and urinary JCV infection. Currently, no treatment of proven efficacy against PV is available. CONCLUSIONS: We think that there is an increasing amount of evidence to include screening for PV in the diagnosis of urinary tract abnormalities of unknown origin, even in apparently immunocompetent patients. Urinary cytology, in experienced hands, may be a useful and relatively inexpensive first step diagnostic tool.