[Quantifying dialysis efficiency for middle molecules in haemodialysis and in convective and mixed techniques]. / La quantificazione pratica dell'efficienza dialitica per le medie molecole in dialisi e nelle tecniche convettive e miste.

In contrast to the negative results of the primary analysis, secondary analyses of the HEMO study do support the clinical importance of middle molecule removal. This is in agreement with the findings of large observational studies showing an improvement in mortality and morbidity in dialysis patients treated with high-flux hemodialysis or convective techniques as compared to low-flux hemodialysis. For practical assessment of middle molecule removal, we suggest using the Kt/V of beta2-microglobulin (Kt/Vbeta2-m) with a reference (adequate) value of >or=0.66, which was the average value for the high-flux arm in the HEMO study. For patients on low-flux hemodialysis, where Kt/Vbeta2-m cannot reliably be assessed, we suggest using the Kt/V of vitamin B12 (Kt/VB12), with a reference (adequate) value of >or=0.74, adapted from the findings of the Case Mix Adequacy Study (AJKD 1999). To simplify the routine assessment of these indices, two nomograms are introduced: the first allows to estimate Kt/Vbeta2-m from the post- to pre-dialysis beta2-microglobulin concentration ratio, the second allows to estimate the diffusion dialysis clearance of vitamin B12 from the in vitro dialyzer KoAB12 and actual plasma water flow rate. While waiting for specific trials addressing the issue of dialysis adequacy related to middle molecule removal, clinical experience with the middle molecule indices could provide further quantitative tools for dialysis prescription and favor an increase in dialysis time (or frequency) and/or the use of high-flux hemodialysis and convective techniques.

[Regional clinical audit, guideline targets, and local and regional benchmarks]. / L'Audit clinico a livello regionale, Target delle Linee Guida e Benchmarks locali e regionali.

Regional clinical Audit, guideline Targets and local and regional Benchmarks In order to improve the quality of dialysis treatment, we have devised some routines, particularly suitable for electronic data management systems. First, we suggest a systematic monthly analysis of 10 common clinical performance measures (CPM), with the following guideline based targets: predialysis systolic blood pressure (SBP) < 140 mmHg; session length >/= 240 min; dialysis dose (spKt/V) >/=1.3; normalized protein catabolic rate (NPCR) >/=1.2 g/kg/d; hemoglobin (Hb) >/=11 g/dL; serum calcium (Ca) 8.4-9.5 mg/dL; serum phosphorus (P) 3.5-5.5 mg/dL; Ca x P /=20 mmol/L; serum potassium (K) 3.5-6.0 mmol/L. The Hb target should be reached in at least 85% of all maintenance hemodialysis (HD) patients in the unit; for all other targets, an arbitrary >/=80% is proposed. Since the above percentages are quite difficult to reach on a short-term basis, an intermediate local or regional standard (benchmark) could be devised as an average of the percentage of patients who actually reach the targets for each CPM at any dialysis unit in a given regional area; and therefore, from truly comparable patients. As an example, we simulated a regional audit by using the above targets with available data from 398 patients from southern Italy. A further step in this process was to find the cause(s) of failure in each patient who did not reach the targets. To this end, we suggest a systematic search of the well-known factors that could affect each CPM, for each failed patient. As an example, we screened all patients with Hb < 11 g/dL at a single unit, to establish the presence/absence of any common cause associated with inadequate response to epoetin treatment. Moreover, by using criteria for prescribing iron therapy or increasing epoetin dose, we found that some patients did not receive the appropriate therapy after blood sampling results. To avoid this possible common problem, we suggest the need for a monthly report of failure cases for any particular CPM and a check that the appropriate treatment has been delivered to all patients at the dialysis unit. This should also favor guideline implementation.

[Vitamin B12 clearance (Kd-B12) in hemodialysis (HD) and hemodiafiltration (HDF)]. / La clearance della vitamina B12 (Kd-B12) in emodialisi (HD) e in emodiafiltrazione (HDF).

PURPOSE: The dialysis dose is usually assessed by Kt/V urea; however, it is possible that middle molecule (MM) removal could play a role in optimal treatment. Vitamin B12 is a classical MM marker and Kd-B12 is used to compute a MM-based dialysis index, requiring a weekly total clearance (Kd-B12 + renal creatinine clearance (CrCl) > or =30 L, corresponding to IDB12> or =1 (Babb et al, Kidney Int, 1975). Recently, it was demonstrated that by increasing the total Kd-B12 per session (TCV) from 10 to 16 and to 26 L, the relative risk (RR) of death was reduced from 1 to 0.79 and to 0.62, respectively (Leypoldt et al, Am J Kidney Dis 1999). This implies that a minimum TCV of 16 L, but preferably of 26 L per session, should be delivered, for anuric HD patients on a 3x/wk schedule. To extend these results to the whole hemodialysis (HD) population, we suggest transforming TCV into the corresponding IDB12 values: i.e. a TCV=10 L on 3x/wk corresponds to IDB12=1, a TCV=16 and 26 L corresponds to IDB12=1.6 and 2.6, respectively. METHODS: This study aimed to assess Kd-B12 and IDB12 for all stable patients in our unit. There were 62 patients (33 males, 29 females): five patients were being dialyzed once per week (1x), nine patients twice (2x), 46 patients three (3x) and two patients four times (4x) per week (wk); the session length was 232+/-18 min. Most dialyzers had a large surface area (mean 1.9+/-0.3 m2), with KoA-B12=211+/-92 mL/min. Eleven patients, 3x/wk, were on hemodiafiltration (HDF): the reinfusion rate was 33+/-3 mL/min in five patients (sHDF) and 76+/-12 mL/min in six patients (HDF on-line (OL). Kd-B12 was computed as a function of KoA-B12, effective plasma flow, Qd and ultrafiltrate (UF). IDB12 was computed from Kd-B12, ses-sion length and schedule, CrCl and body surface area. RESULTS: The main results are given below: [table: see text] On average, Kd-B12 was 105 +/- 13 mL/min on HD and 152+/-34 mL/min on HDF. A significant difference was found only for HDF-OL and was essentially due to the higher UF. Of note, the presence of renal function allowed good IDB12 values for 1x/wk and 2x/wk patients, even better than for the standard 3x/wk patients. CONCLUSIONS: We have demonstrated that most available dialyzers provide high Kd-B12 values (but HDF-OL performs significantly better) and that IDB12, by quantifying the impact of UF, session length, schedule and renal function, allows the assessment of dialysis adequacy beyond Kt/V urea, for all HD or HDF patients, on a routine basis and at no added cost.

[Regional epidemiology of chronic nephropathies: referral to nephrologist and initiation of dialysis]. / Epidemiologia regionale/locale delle nefropatie croniche: profili di "referral" ambulatoriale e inizio dialisi.

BACKGROUND: The epidemiology of pre-dialysis chronic nephropathies (CN) in well-defined contexts is essential to prevent delays in delivering appropriate care. METHODS: The registration of consecutive patients in seven out-patient and four in-patient dialysis centers of Basilicata (2001) formed a retrospective study on clinical charts and dialysis registers integrated with ad hoc data. RESULTS: Newly observed outpatients (I) numbered 328; prevalent patients (P) numbered 343. The age and gender of both I and P patients was similar (males: 60%, age media: 67 yr). In 316 I patients with creatinine (mean Cr: 2.3 mg/dL), the mean filtration rate (GFR) was 40.9 mL/min/1.73 m2: 13.6% were in advanced stage (S5) of GFR (<15 mL/min), 23.4% in S4/severe (15-29), 45.6% in S3/moderate (30-59), 10.8% in S2/mild (60-89), and 6.6% in S1 (>90). When compared to I patients, P patients had a mean GFR of 35.0 mL/min; S4+S5 was 48% (vs. 37%); hypertension 68% (vs. 58%); vasculopathies 15% (vs. 10%); coronary disease 10% (vs. 4%); erythropoietin 13% (vs. 7%); and low-protein diet 34% (vs. 20%) (p<0.01). Of 316 I patients, 117 in S5+S4 ('late referral' 37%) had a (mean) GFR of 18.4 mL/min, Cr 3.7 mg/dL, and were aged 70 yrs (vs. 64 yrs for 'early referral'). Of 53 new patients on dialysis, 26 (49%) were seen for the first time <6 months prior to starting (mean age: 71 yr vs. 62; female 58% vs. 26%; complications 50% vs. 17%). CONCLUSIONS: In this population, age-related factors are associated with late referral. Although sociodemographic variables depend on local contexts, these results are consistent with similar international studies. Social and cultural factors may influence physicians to postpone referring patients to a nephrologist, independently of clinical conditions.

[The need for integrated care of patients with chronic nephropathies: the epidemiology of 'late referral']. / Epidemiologia dei bisogni di gestione integrata: il "late referral" in Nefrologia.

BACKGROUND: The recent need for information has prompted this collaboration between health system epidemiologists (Basilicata) and clinicians to compare models of 'local' epidemiology in the management of diseases. The referral of patients to a nephrologist represents a working hypothesis of research- intervention. METHODS: Analysis of renal registry (RR) and administrative databases (hospital discharge abstracts/HDA, ambulatory);ad hoc surveys. RESULTS: Patients on dialysis between 1994 and 1998 are 594, cumulative deaths are 190 (32%). Males and the elderly (age = 65 years) are associated with more than 50% and threefold increase in relative risk of death, and with a diabetic nephropathy of 60% vs other renal diseases. Of 570 patients alive in 1996, 442 are linked with 2,628 HAD. Comorbid conditions are underreported in the RR (the Charlson index has been computed using HDA). Of 66 new dialysis cases, 31 are referred to a nephrologist only 6 months before the start of dialysis (47%) (22% diabetics). Patients discharged with chronic nephropathies (CN) and diabetes are 21% of CN patients (5% of diabetics). Of 100 patients with pre-end stage renal disease and diabetes, only 11-14 are discharged from the nephrology ward. At the local level, 3 out of 4 patients with serum creatinine higher than 1.5 mg/dl are not referred to a nephrologist. The prevalence of CN may vary from 0.4% to more than 1%. CONCLUSIONS: While an improvement in health databases in the regions is underway, collaboration studies are essential for planning specific interventions for prevention and management of diabetic nephropathy to improve the use of resources in nephrology.

Jugular vein catheterization for hemodialysis: correct positioning control using real-time ultrasound guidance.

The jugular vein catheterism (JVC) is adopted for blood access in patients with acute renal failure, in chronic renal failure and when patients show failure of traditional vascular access. The technique of catheter insertion in the jugular vein is quick and easy. Usually correct catheter positioning, before starting the dialytic procedure, is controlled by chest X-ray or by intra-cavitary electrocardiogram. The aim of this work is to evaluate the feasibility of the real-time ultrasound guidance to control the correct positioning of the catheter instead of the usual chest X-ray control. We have studied 158 patients with JVC insertion before the hemodialytic procedure; 54 patients have undergone both ultrasound and a chest X-ray control while 104 were only submitted to ultrasound control. The ultrasound procedure includes an under xifoid scanning, with a convex 3.5 Mhz drill to evaluate the four heart cavities. When the right atrium is identified a second operator rapidly infuses in the venous catheter 15 ml of physiological solution thus creating a blood turbolence easily observed in real time as a light jet inside the atrium. This turbolence appears to be the main evidence for good catheter positioning and we were able to show the light jet in 156 (98%) patients. All light jet positive patients were submitted to the hemodialytic procedure without any complications during and after dialysis. We concluded that the intraoperative ultrasound control technique is an alternative to the chest X-ray evaluation because it offers the possibility for safe intraoperative immediate control thus reducing the total costs of the procedure.

The equivalent renal urea clearance: a new parameter to assess dialysis dose.

BACKGROUND: Currently the total (dialytic plus renal) urea clearance (KT) is computed as Kt/V plus the equivalent Kt/V (KT/VKR) provided by the renal urea clearance (KR). However, KT/VKR is computed with two different formulae, by Gotch and Keshaviah respectively. Moreover Teschan suggested a weekly KT, that is a multiple of Keshaviah's KT. We suggest the equivalent renal urea clearance (EKR), that kinetically quantifies the "time-averaged KT' and is independent of treatment type and schedule. METHODS: Computer simulation has been used to analyse the relationship between EKR, as corrected for urea volume (EKRc), and Kt/V. Data from 66 HD patients, of whom eight were on once-weekly and 11 on twice-weekly HD, had been used to compare EKR with current KTs. RESULTS: For each individual schedule, the relationship between EKRc and Kt/V is linear and each ml/min of KR increases EKR by the same amount. For instance, for thrice-weekly HD patients, EKRc = 1 + 10 x Kt/V: so that, the critical Kt/V values of 0.8 and 1.0 correspond to EKRc values of 9.0 and 11 ml/min respectively, independently from treatment type and schedule. As to the clinical data, all once- and twice-weekly patients had a significant KR and excellent clinical status, but most of them had 9 < or = EKRc < 11 ml/min. After appropriate reconciliation of units, it has been found that kinetic KT was overestimated by about 10-12% (range, 2-23%) by Keshaviah and Teschan's KT, and by about 2-7% (range, 0.3-15%) by Gotch's KT. CONCLUSIONS: EKRc can account for KR and provide guidelines for all types of dialysis treatments: as far as urea is concerned, dialysis adequacy should require EKRc > or = 11 ml/min. However, it is likely that EKRc > or = 9 ml/min could suffice for patients with a substantial residual renal function.

Prescription and surveillance of the acetate-free biofiltration sessions: the bicarbonate cycle.

A computerized system, structured by 4 different models concerning urea depuration, and bicarbonate and sodium handling in acetate-free hemodiafiltration has been conceived for integrated use covering each step of the therapeutic cycle, from a) the prescription of the session to b) its delivery, up to c) the dose-response analysis: the system, now fully developed for the bicarbonate cycle, covers both working areas; the medical one, with a program implemented on a Personal Computer, called Skipper which deals with steps a) and c), and the nursing area, with a program built into the dialytic equipment software. The Skipper program supports the prescription step (a) testing the session schedule by bicarbonate, sodium and urea kinetics. The dialytic equipment, (step(b)) using a different program, on the basis of the scheduled parameters memorizes the end-session plasma bicarbonate level and reacts to any modifications of the parameters regarding blood flow and fluid reinfusion flow suggesting opposite changes in order to reach the scheduled results. Finally (step (c)), the Skipper system statistically evaluates the observed end session bicarbonate plasma level with an expected value with upper and lower confidence bounds obtained by a multiple regression analysis performed on a large population of patients.

A modified Two-BUN method for routine urea modeling: clinical validation in 120 patients on a free diet.

Recently, a modified algorithm of the Two-BUN method (MA2p), avoiding dialyzer clearance measurement, was presented for routine assessment of Kt/V and NPCR. To validate MA2p in patients on a free diet (FDP), we studied 120 stable dialysis FDP by measuring Kt/V and NPCR with both MA2p and a modified version of the standard Three-BUN method (MA3p), for the 3 weekly sessions. The NPCR values (g/kg/day), calculated by MA3p for the 3 interdialyses were: 1.286 +/- 0.274, 1.256 +/- 0.276, and 1.116 +/- 0.230, respectively. The correlation coefficient (r) for averaged Kt/V values obtained by the two methods was 0.999 and the percent error (Error%) for MA2p vs. MA3p results ranged from -1.5 to +0.78%. The respective results for NPCR were: r = 0.967, Error% range from -11.7 to +13.9%. In conclusion, MA2p can be safely used in patients on a free diet. The lowest NPCR values were observed during the long interdialysis.

Reconciliation between urea kinetics and direct dialysis quantification.

Previous studies comparing urea kinetic model (UKM) and direct dialysate quantification technique (DDQ) found statistically different results as far as the urea distribution volume (V) and protein catabolic rate (PCR) are concerned. In these studies, however, the true values for both the dialyser urea clearance (K) and urea concentration (C) were not used. The aim of this study was to compare UKM and DDQ using for both methods a variable-volume single-pool (VVSP) model as well as plasma water C and effective K. The study was performed during paired filtration dialysis (PFD) sessions because this technique allows bloodless measuring of K. Twenty dialysis patients were studied during a single PFD session. Dialysate and ultrafiltrate C and urea mass transfer rate were measured every 15 min to compute averaged K and total urea removal. Blood samples were obtained as for a three-point UKM, and an iterative technique was used for both methods. The results (means +/- SD) obtained with UKM were as follows: K = 176 +/- 23 ml/min; V = 29986 +/- 7620 ml, PCR = 65 +/- 15 g/day, Kt/V = 1.04 +/- 0.17. These results were not statistically different from those obtained using DDQ. In conclusion, when methodological errors are avoided, DDQ and UKM provide very similar results. This study shows also that PFD is very useful for studying solute kinetics during dialysis.

A modified algorithm of the single pool urea kinetic model.

Urea Kt/V, calculated according to the variable volume single pool urea kinetic model (UKM), has been accepted as the yardstick reflecting the adequacy of haemodialysis therapy. However, the classical algorithm of UKM requires great care in dialyser urea clearance (K) measurement in order to avoid major inaccuracies in estimating the urea distribution volume (V). Thus, we suggest a modified algorithm of UKM which avoids the measurement of K. It assumes an arbitrary V value and then calculates kinetically K as a function of the assumed V value. The rationale of the modified algorithm can be derived from the knowledge that the classical algorithm imposes a proportionality ration between K and V: given a particular set of data, a change in the attributed value of K leads to a proportional change in the calculated V value, so that the ratio K/V remains nearly constant. Aims of the study were (1) to validate the modified algorithm by comparing the resulting Kt/V and normalised protein catabolic rate (NPCR) values with the homologous ones obtained using the classical algorithm in a group of 33 patients on thrice-weekly haemodialysis; plasma water urea concentrations were used with the classical algorithm (CApw) and the modified algorithm (MApw); and (2) to verify the possibility of using plasma urea concentrations with the modified algorithm (MAp) instead of the more rigorous plasma water concentrations. NPCR (g/kg per day) was 1.33 +/- 0.05 in CApw, 1.29 +/- 0.05 in MApw and 1.28 +/- 0.04 in MAp. Kt/V was 1.27 +/- 0.03 in CApw, 1.25 +/- 0.03 in MApw and 1.26 +/- 0.03 in MAp.(ABSTRACT TRUNCATED AT 250 WORDS)