"Real-World" use of cinacalcet for managing SHPT in different European countries: analysis of data from the ECHO observational study.

AIMS: The pan-European ECHO observational study evaluated cinacalcet in adult dialysis patients with secondary hyperparathyroidism (SHPT) in "real-world" clinical practice. A sub-analysis compared data for 7 European countries/country clusters: Austria, CEE (Czech Republic and Slovakia), France, Italy, Netherlands, Nordics (Denmark, Finland, Norway, and Sweden), and the UK/Ireland. METHODS: Data on serum intact parathyroid hormone (iPTH), phosphorous, calcium, as well as the usage of cinacalcet, active vitamin D analogues and phosphate binders were compared. RESULTS: 1,865 patients (mean age 58 years) were enrolled: median baseline iPTH levels ranged from 605 pg/ml in Austria to 954 pg/ml in the UK/Ireland. After ~1 year of cinacalcet, median iPTH reductions from baseline ranged from 38% in the UK/Ireland to 58% in the Netherlands. The proportion of patients achieving NKF/K-DOQITM iPTH targets (150 - 300 pg/ml) at Month 12 ranged from 14% in the UK/Ireland to 40% in CEE. In general, use of sevelamer decreased, while use of calcium-based phosphate binders increased, during cinacalcet treatment. Vitamin D changes were more variable. CONCLUSION: The iPTH level at which cinacalcet is initiated in clinical practice differs considerably among different countries: where cinacalcet was started at a lower iPTH level this resulted in better achievement of serum iPTH targets.

Urotensin II is an inverse predictor of death and fatal cardiovascular events in chronic kidney disease.

Urotensin II (UTN), a cyclic vasoactive peptide expressed in multiple organs, had higher plasma levels that was previously shown to predict longer survival in dialysis patients. We sought to determine if this association exists in earlier stages of chronic kidney disease (CKD) by studying a cohort of 122 incident clinically stable pre-dialysis patients. Linear models were used to determine associations of UTN with baseline characteristics such as renal function and traditional and nontraditional cardiovascular risk factors. We used Cox regression analysis to model time-to-death as a function of UTN and the same variables for adjustment including a time-varying covariate that indicated progression to end-stage renal disease. No correlation was found between baseline glomerular filtration rate and plasma UTN. In adjusted analysis, UTN correlated directly with serum albumin and, inversely, with history of previous coronary events. During a mean follow-up of 41 months, 43 patients died - 29 from cardiovascular events. After adjusting for potential confounding factors, increased UTN predicted lower risk of death from all-cause and cardiovascular causes. In patients with moderate-to-severe CKD, plasma UTN was found to be an inverse predictor of overall and cardiovascular mortality.

[Confounding and interaction in multiple regression]. / Confondimento e interazione nella regressione multipla.

In multiple regression the effect of an input (independent) variable on a continuous output (dependent or response) variable can be adjusted for the effect of confounding and modifying variables. This adjustment is useful to obtain either an unbiased estimate of the true association between an exposure and an outcome or to predict the outcome for given inputs after removing the influence of other factors. These factors are defined as confounders if they are associated with the exposure and are independent risk factors for the outcome, without being intermediates on the biological pathway between exposure and outcome. An interaction between exposure and another independent variable is present when the exposure-disease relationship varies across different values of this variable. Multivariable regression modeling removes the association between the confounder and the outcome eliminating the necessary condition for confounding. An interaction term can be also incorporated into the model to quantify any potential modifying effect.

[Statistical models and multivariable analysis]. / Concetti di modello statistico e analisi multi-variabile.

Most clinical research can be simplified as an investigation of an input/output relationship. The inputs are called explanatory (independent) variables or predictors and are thought to be related to the outcome, or response (independent) variable. This relationship is usually complicated by other factors related to both the input and the output (presence of confounding) and can vary according to the levels of the other variables (presence of interaction). This input/output relationship is usually described by statistical models that include a fit part and a residual component or difference between the data and the fit. The most popular models are the general linear models, which can be considered the paradigm of all models used in multi-variable analyzes.

[Introduction of the general linear models]. / Introduzione ai modelli lineari generali.

General linear models can be considered the paradigm of all models used in clinical epidemiology. In these models, the independent variables combine in linear fashion to predict the values of the variable response. Since no model predicts the variable response perfectly, an error term is incorporated into the model to acknowledge what remains to be explained after getting a fit to the data. When this error term is normally distributed with constant variance, the linear models are reasonably appropriate to describe the input/output relationship of interest.

Atherosclerotic renovascular disease: medical therapy versus medical therapy plus renal artery stenting in preventing renal failure progression: the rationale and study design of a prospective, multicenter and randomized trial (NITER).

BACKGROUND: Many studies suggest a major prevalence of atherosclerotic renovascular disease (ARVD), caused by mono or bilateral renal artery stenosis (RAS). Unfortunately, there is no definite therapy to cure this disease to date; therefore, ARVD is burdened by important clinical complications with high social and economic costs. The last few years have seen important advancements in both medical therapy and in interventional radiology (for example, percutaneous transluminal renal artery stenting (PTRS)). All of them could affect, in some way, the natural history of ARVD, but to date the optimal strategy has not been established. METHODS: The protocol of a prospective, multicenter, randomized trial "Nephropathy Ischemic Therapy (NITER)" is presented. It enrolls patients with stable renal failure (glomerular filtration rate (GFR) >or=30 ml/min) and hypertension, and hemodynamically significant atherosclerotic ostial RAS (>or=70%) diagnosed by duplex Doppler (DD) ultrasonography and confirmed by magnetic resonance angiography (MRA). This study aims to evaluate whether medical therapy plus interventional PTRS is superior to medical therapy alone according to the following combined primary endpoint: death or dialysis initiation or reduction by >20% in estimated GFR after 0.5, 1, and 2 yrs of follow-up and an extended follow-up until the 4th year. Medical therapy means drugs to control hypertension, improve dyslipidemia and optimize platelet anti-aggregant therapy. The sample size is estimated in 50 patients per group to achieve a statistical significance of 0.05 in case of a reduction by 50% in the combined endpoints.

[Epidemiology and demography of uremia: data from the Lombardy Dialysis and Transplantation Registry (RLDT)]. / Epidemiologia e demografia dell'uremia: dati dal Registro Lombardo Dialisi e Trapianto (RLDT).

The Lombardy Registry of Dialysis and Transplantation (RLDT) since 1983 has collected data concerning patients affected by end-stage renal disease (ESRD) on renal replacement therapy (RRT) in Lombardy, a region of Northern Italy with 9 million inhabitants. This report illustrates the main features of ESRD patients on RRT: there were 6589 patients undergoing treatment at 31 December 2003, with a prevalence rate of 727 pmp. Patient numbers regularly increased by 4.5%/yr for the last 5 yrs. This phenomenon is probably due to the high incidence rate (172 pmp) of ESRD patients in Lombardy during these years related to a relatively stable mortality rate (15.2%). The increasing incidence is probably correlated to the population's characteristics: higher rates (189-223 pmp) were observed in certain provinces (Cremona, Lodi and Pavia) with a larger elderly population (people >65 yrs = >20%, people <65 yrs = <16%). Of dialysis modalities, 85% of prevalent patients were on hemodialysis (HD), 55% in hospital, and 30% in limited care units. The number of patients treated by peritoneal dialysis (PD) was stable during the last years, but showed a slow percentage decline (15% during 2003) since 1999. However, PD remains the first dialysis modality for 21.4% of new patients, with a wide variability among renal units. Regarding HD, highly efficient techniques (on-line hemodiafiltration (HDF)) represented 19.2%, with a significant increase (1.8%) compared to 2002. During 2003, the number of dialysis units in Lombardy was stable; there was only an increase in facility beds in limited care units in order to treat the increasing numbers of uremic patients.

[Control of calcium and phosphate metabolism and prevention of vascular calcifications in uremic patients]. / Controllo del metabolismo calcio-fosforico e prevenzione delle calcificazioni vascolari nel paziente uremico.

Vascular calcifications are more frequent in dialysis patients than in the general population or in patients with cardiovascular disease (CVD) and normal renal function. The reasons for this high incidence are multiple; they include traditional factors such as hypertension, diabetes, dyslipidemia, and specific factors such as sodium overload, hyperomocysteinemia, chronic inflammation and oxidative stress, as well as mineral metabolism disturbances. Specifically, hyperphosphatemia and the elevated calcium (Ca) x phosphate product have been associated with an increased risk for the development of vascular calcification and death. Treatment with Ca salts can induce hypercalcemia, increased Ca x phosphate product and Ca overload. Sevelamer substitution for Ca salts has been documented to attenuate the progression of coronary artery and aortic calcification. A possible mechanism explaining this observation could be ongoing Ca loading related to oral Ca ingestion. Treatment with Ca salts could induce Ca overload, particularly in patients dialyzed against a high dialysate Ca (>1.5 mmol/L) solution, which is known to determine a positive dialysis balance. Conversely, an overall negative Ca balance can result from low Ca dialysate use (1.25 mmol/L) when the patients do not receive Ca supplements or vitamin D metabolites. Maintaining normal Ca and phosphate balances remains a primary goal in the management of dialysis patients. Control of hyperphopshataemia should be achieved either using Ca and aluminum-free phosphate binders, such as sevelamer, or Ca salts, alone or in combination, provided that a daily oral elemental Ca intake of 1.5 g is not exceeded.

The short- and long-term impact of multi-disciplinary clinics in addition to standard nephrology care on patient outcomes.

BACKGROUND: This two country case control study of incident dialysis patients evaluates the outcomes of patients exposed to formalized multi-disciplinary clinic (MDC) programmes vs standard nephrologist care. METHODS: Patients commencing dialysis in two centres (Vancouver, Canada and Cremona, Italy) were evaluated at and after dialysis start, as a function of MDC exposure vs nephrologist care alone. Only chronic kidney disease patients, with longer than 3 months of exposure to nephrology care, who had not previously received kidney replacement therapy were included. Study outcomes included laboratory parameters and survival. The MDC was similar in both countries and average exposure was 6-8 h per patient-year, as compared to 2-4 h for standard care. All patients had equal access to resources prior to dialysis and with respect to dialysis start, as all had been referred to the same local nephrology practices. RESULTS: During the evaluation period 288 patients commenced dialysis after receiving more than 3 months nephrology care prior to dialysis. There were no major demographic differences between the cohorts. Mean duration of nephrology care prior to dialysis was 42 months, and dialysis was initiated at similar low glomerular filtration rate (GFR), though statistically significantly different (7.0 and 8.4 ml/min/m2, P = 0.001). The MDC patients had higher haemoglobin (102 vs 90 g/l, P<0.0001), albumin (37.0 vs 34.8 g/l, P = 0.002) and calcium levels (2.29 vs 2.16 mmol/l, P<0.0001) at dialysis start. Survival was significantly better in the MDC group demonstrated by Kaplan-Meier analysis (P = 0.01). Cox proportional hazards analysis demonstrated standard nephrology clinic vs MDC attendance was a statistically significant independent predictor of death (hazards ratio = 2.17, 95% confidence interval 1.11-4.28) after adjusting for other variables known to impact outcomes. CONCLUSIONS: This analysis of outcomes in two different countries suggests that despite equal and long exposure to nephrology care prior to dialysis, there appears to be an association of survival advantage for those patients exposed to formalized clinic care in addition to standard nephrologist follow-up. While other known predictors of survival such as adequacy of dialysis and severity of illness measures were not included in the model, those parameters require time on dialysis to be accumulated. Thus, the data do suggest that knowledge of patient status at the time of dialysis start is important. Further research is needed to determine which specific components of care both prior to dialysis and after its commencement are most important with respect to outcomes.

[Italian study on the treatment of anaemia in chronic dialysis patients switched over to less frequent doses of darbepoetin from human recombinant erythropoietin (rHuEPO)]. / Studio italiano sul trattamento dell'anemia in pazienti in terapia dialitica sostitutiva con darbepoetina alfa con una minore frequenza di somministrazione della dose rispetto all'eritropoietina ricombinante umana (rHuEPO).

BACKGROUND: Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin (rHuEPO), including a three-fold longer elimination half-life that allows for less frequent dosing. This study was aimed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO. METHODS: Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha. Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha. Patients received darbepoetin alpha by the same route of administration (SC or IV) as the one used for rHuEPO. The unit doses of darbepoetin alpha (10-150 microg) were titrated to maintain haemoglobin concentration within -1.0 and +1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks. RESULTS: The mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was statistically but not clinically significant [-0.10 g/dL (95% CI: -0.18, -0.02]. In general, the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [(from 26.10 micro g/wk to 25.90 microg/wk; percentage change -0.40% (95% CI: -3.78, 3.10)]. Overall, darbepoetin alpha was well tolerated. CONCLUSIONS: The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency.

[Disturbances of mineral metabolism and vascular calcifications in dialysis patients (review)]. / Alterazioni del metabolismo calcio-fosforico e calcificazioni vascolari nei pazienti in dialisi.

Vascular calcifications are more frequent in dialysis patients than in the general population or in patients with cardiovascular disease and normal renal function. The reasons for this high incidence are multiple. They include traditional factors such as hypertension, diabetes, dyslipidaemia, and specific factors such as sodium overload, hyperomocysteinaemia, chronic inflammation, oxidative stress as well as disturbance of mineral metabolism. Specifically, hyperphosphataemia and the elevated calcium (Ca) x phosphate product have been associated with an increased risk for development of vascular calcification and death. Even though a causal relationship between the use of Ca- containing phosphate binders and the development of vascular calcifications has not been documented, treatment with Ca salts can induce hypercalcaemia, increased Ca x phosphate product, and Ca overload. A net intestinal Ca absorption of 180-500 mg has been documented in uraemic patients after a meal containing 1200 mg of Ca. Thus, treatment with Ca salts may induce Ca overload when a patient is dialyszed against a high dialysate Ca (> 1.5 mmol/L) solution, which is known to determine a positive dialysis balance. On the contrary, an overall negative Ca balance can result from the use of a low Ca dialysate (1.25 mmol/L) when the patients do not receive Ca supplements or vitamin D metabolites. Maintaining a normal Ca and phosphate balance remains one of the primary goals in the management of dialysis patients. Control of hyperphopshataemia should be obtained using either Ca and aluminium- free phosphate binders, such as sevelamer, or Ca salts, while avoiding a daily oral elemental Ca intake > 1.5 g.

Von Willebrand factor and autoantibodies against oxidized LDL in hemodialysis patients treated with vitamin E-modified dialyzers.

Oxidant stress is a well known cause of damage in the atherosclerotic process. Vitamin E is one of the most promising natural antioxidants. In this study we investigated if a vitamin E-coated dialyzer was able to reduce the plasma levels of auto-antibodies against oxidized-LDL, von Willebrand factor (vWf) and thrombomodulin (TM) as markers of endothelial damage. In this controlled 6-month prospective study, we investigated these markers in two matched groups (n=16 each) of patients on regular hemodialysis not yet diagnosed for atherosclerosis cardiovascular disease (ACVD) (mean age=58.3+/-7.0 yrs, mean dialysis age=30.1+/-10.0 months), in which cellulosic (CLS) and vitamin E-modified dialyzers (CLE) were compared. At inclusion all the patients were treated with CLS. Then, the study group was shifted to CLE for 6 months. At baseline the patients showed normal levels of vitamin E and high levels of oxLDL-Ab, vWf and TM compared to healthy subjects. In the CLE group oxLDL-Ab and vWf, but not TM levels, decreased progressively (from 472+/-287 to 264+/-199 mU/mL, p<0.0001 and from 101.1+/-7.5% to 76.7+/-18.5%; p<0.001, respectively), and vitamin E increased from 4.40+/-0.81 to 7.81+/-1.16 microg/mg of cholesterol. At the end of the study, 8 of the patients treated with CLE were randomly selected and went back to the membrane without Vitamin E for six months. They showed an significant increase in OxLDL-Ab and vWf levels and a significant reduction in tocoferol levels. In conclusion, CLE compared to cellulosic dialyzers can lower some indices of damage to LDL and endothelial cells.

[Effect of an ambulatory program devoted to chronic renal insufficiency on the reduction of mobidity and hospitalization among patients at the beginning of dialysis treatment]. / Effetto dell'ambulatorio dedicato all'insufficienza renale cronica sulla riduzione della morbilità e dell'ospedalizzazione nei pazienti che iniziano il trattamento dialitico.

BACKGROUND: Late nephrological referral of end-stage renal disease (ESRD) patients is associated with increased risk of emergent dialysis start and poor complications control. However, the relative contribution of pre-dialysis care organization is unknown. METHODS: All 175 consecutive patients who started chronic dialysis for ESRD at our Institution from 1.1.99 to 30.6.02 were grouped as follows: referred ? 3 months before dialysis, (A, n=50); followed by non-dedicated specialists (B, n=74) or by pre-dialysis educational program personnel (PEP, n=51). We examined the first six months of hospitalization, uraemic complications control, type of dialysis initiation, and first dialysis modality. RESULTS: There was no difference in baseline characteristics and comorbidities among groups. PEP patients had higher creatinine clearance, haemoglobin, calcemia and BMI at initiation. They also made greater use of ACE-inhibitors and were more likely to have a planned start and choose peritoneal dialysis. Emergent starts were 50% (A 100%, B 45%, PEP 4%, p<0.001). Mean pre-dialysis hospitalization (due to in-patient emergency dialysis onset for unplanned starts and planned for access insertion for elective out-patient starts) was shorter among PEP patients (7days-PEP, 17days-B, 30days-A). Logistic regression confirmed the predictive role of PEP for emergent start (AOR 0.03, 0.001 to 0.101, p<0.001) even excluding late referrals (AOR 0.1, 0.033 to 0.306, p<0.001), independently of baseline characteristics and comorbidities. CONCLUSIONS: Pre-dialysis follow-up by dedicated personnel was more effective than traditional specialist care in reducing morbidity and health care resources utilization in patients starting dialysis.

Impact of blood and dialysate flow and surface on performance of new polysulfone hemodialysis dialyzers.

Optimization of hemodialysis treatment parameters and the characteristics of the dialyzer are crucial for short- and long-term outcome of end stage renal disease patients. The new high-flux membrane Helixone in the dialyzer of the FX series (Fresenius Medical Care, Germany) has interesting features, such as the relationship of membrane thickness and capillary diameter which increases middle molecule elimination by convection, as well as higher capillary packing and microondulation to improve the dialysate flow and distribution. Blood flow, dialysate flow and surface area are the main determinants of the performance of a dialyzer, however the impact of each parameter on small and middle molecule clearance in high flux dialysis has not been well explored. In order to find the best treatment condition for the new dialyzer series, we evaluated urea, creatinine, phosphate clearances and reduction rate of beta2-microglobulin in ten stable patients treated with different blood flows (effective Qb 280 and 360 ml/min), dialysate flow (Qd 300 or 500 ml/min) and dialyzer surfaces (1.4 and 2.2 m2, FX60 or FX100). KoA and Kt/V were also calculated. Blood flow, dialysate flow and surface area demonstrated a significant and independent effect on clearance of urea, creatinine and phosphate, as well as on Kt/V. Small solute clearance was stable over the treatment. In contrast to small solutes, reduction rate of beta2-microglobulin was related to increasing dialyzer surface only. The new dialyzer design of the FX series proves highly effective due to improved dialysate distribution and reduced diffusive resistance as shown by the small solute clearance. A high reduction rate of beta2-microglobulin is favored by improved fiber geometry and pore size distribution. These findings have potential long-term benefits for the patient.

Early failure rates of arterovenous fistulas for hemodialysis: evaluation of six-year activity.

Maintenance and complications of vascular access (VA) for hemodialysis (HD) represent the leading cause of morbidity and health care cost among end stage renal disease population. To define the reasons for the use of a particular VA at the beginning of replacement treatment, we prospectively evaluated the early failure rate and survival of arterovenous fistula (AVF) in 183 patients. These patients had high prevalence of cardiovascular risk factors and co-morbid conditions, and began HD in our renal unit from the 1st of January 1995. As a part of this study the present analysis focuses on potential predictors of early failure of the first AVF (within the first 7 days after the operation). Overall, 279 AVF were prepared: 193 at the wrist and 86 at the upper arm, including 11 prosthetic grafts; 150 patients (82%) were given a distal AVF in the first operation. Our conservative policy resulted in a relatively high prevalence of native AVF in use among our prevalent HD patients (84.3%). Early failure of the first VA was 10.4%. Multivariate analysis showed that this event was neither significantly associated with all traditional risk factors and co-morbids tested, nor with the operating surgeon. We conclude that in this prospectively studied cohort, the high rate of native AVF created in order to preserve the vascular bed, though associated with a high early failure rate unaffected by traditional cardiovascular risk factors, resulted in a low proportion of permanent catheters and arterovenous grafts in use among prevalent HD patients. (The Journal of Vascular Access 2001; 2: 154-160).

The PTH-calcium curve and the set point of calcium in primary and secondary hyperparathyroidism.

BACKGROUND: The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism (HPT). A similar abnormality may occur in secondary HPT, but comparisons of PTH secretion in normal subjects and those with secondary HPT have given contrasting results. Differences in baseline serum ionized calcium (ICa) may partly account for these conflicting results. The aim of the present study was to evaluate whether the regulation of PTH secretion by calcium differs from normal in patients with primary and secondary HPT and to determine whether serum calcium concentration per se can affect the set point of calcium and the PTH-calcium relationship. METHODS: The PTH-ICa relationship and the set point of ICa were evaluated in 19 patients with primary HPT (1-HPT), 16 normocalcaemic patients with secondary HPT (2-HPT; PTH 344+/-191 pg/ml), 19 hypercalcaemic patients with secondary HPT (3-HPT; PTH 806+/-254 pg/ml) and 14 healthy volunteers, by inducing hypocalcaemia and hypercalcaemia in order to maximally stimulate or inhibit PTH secretion. In five 1-HPT patients the PTH-ICa curve was restudied after normalization of serum ICa by pamidronate. Parathyroid gland volume was determined by measuring gland size at parathyroidectomy or by means of high-resolution color Doppler ultrasonography. RESULTS: In 1-HPT patients the PTH-ICa curve, constructed using maximal PTH secretion induced by hypocalcaemia as 100%, was shifted to the right, the set point of ICa was increased, and the slope of the curve was reduced when compared to normal subjects. After normalization of baseline serum ICa by pamidronate, a shift of the PTH-ICa curve towards normal and a reduction in the set point of ICa was observed. However, basal PTH and maximal PTH secretion induced by hypocalcaemia increased, minimal PTH secretion induced by hypercalcaemia remained increased and the slope of the curve did not change significantly. The alterations in the PTH-ICa relationship in hypercalcaemic patients with secondary HPT were similar to those found in 1-HPT patients. In normocalcaemic patients with secondary HPT baseline PTH, maximal and minimal PTH secretion and parathyroid gland size were reduced compared to 3-HPT patients. Compared to normal subjects, 2-HPT patients showed greater calcium-induced minimal PTH secretion. The increase in non-suppressible PTH secretion resulted in a rightward shift of the PTH-ICa curve and an increase in the set point of ICa. A strong correlation was found, in both primary and secondary HPT, between the set point of ICa and baseline serum ICa, and between parathyroid gland size and baseline PTH, maximal PTH and minimal PTH. Multivariate regression analysis showed that baseline serum ICa was the main determinant of the set point of ICa in both primary and secondary HPT. CONCLUSIONS: (i) The regulation of PTH secretion by calcium is abnormal in secondary as well as in primary HPT. (ii) Parathyroid gland enlargement in secondary HPT is associated with reduced sensitivity to serum ICa and resistance of parathyroid gland to calcium-mediated PTH suppression, resulting ultimately in PTH hypersecretion, despite hypercalcaemia. (iii) The set point of calcium is strongly dependent on baseline serum calcium, and the PTH-ICa relationship can be affected by variations in serum ICa concentrations. Thus, when the set point of calcium and the PTH-ICa relationship are evaluated, possible differences in baseline serum ICa concentration among the patients should be taken into account.

Comparison of mortality in ESRD patients on convective and diffusive extracorporeal treatments. The Registro Lombardo Dialisi E Trapianto.

BACKGROUND: The aim of this study was to evaluate the effect of convective [hemodiafiltration (HDF) or hemofiltration (HF)] versus diffusive treatments [hemodialysis (HD)] on end-stage renal disease (ESRD) patient mortality and dialysis-related amyloidosis (DRA) using data from the Lombardy Registry. METHODS: For this purpose, 6, 444 patients (aged 56.4 +/- 15.6 years, females 39.5%, diabetics 10. 6%) who started renal replacement therapy (RRT) on HD, HDF, or HF between 1983 and 1995 were considered. A total of 1,082 patients were treated with HDF or HF (first choice in the case of 188), with a median follow-up of 29.7 months. The median follow-up of the 6,298 patients on HD (first choice in the case of 6256) was 22.4 months. The time of survival on dialysis to carpal tunnel syndrome (CTS) surgery was evaluated as a hard marker of DRA morbidity. Survival was compared by means of the Cox proportional regression hazards model, using CTS surgery and all deaths as events for morbidity and mortality, respectively. Explanatory covariates were age, gender, and comorbidities; dialysis modality was tested as a time-dependent covariate. RESULTS: The relative risk (RR) for CTS surgery was significantly higher in older patients [RR = 1.04 per year of age on admission to RRT, 95% confidence interval (CI) 1.02 to 1.06; P = 0. 0001], in diabetics (RR = 2.63, 95% CI 1.30 to 5.31; P = 0.0007), and in patients with heart disease (RR = 5.36, 95% CI 2.27 to 12.68 P = 0.0001). Adjusting for age and diabetic status, the RR for CTS surgery was 42% lower in the patients treated with HDF or HF (RR = 0. 58, 95% CI 0.35 to 0.95, P = 0.03). The RR for mortality, adjusted for age, gender, and comorbidities, was 10% lower in patients treated with HDF or HF (RR = 0.90, 95% CI 0.76 to 1.06; P = NS). CONCLUSION: These results support the hypothesis that convective treatments are associated with a nonsignificant trend toward better survival and significantly delay the need for CTS surgery. An older age and the presence of diabetes and heart disease are other important risk factors for CTS surgery. These results could have an important clinical impact given the relevance of DRA in dialysis patient morbidity.