More infiltration in less mature fistulae?
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Age Factors↗
Biomedical subjects
Fabio Malberti
Publications and source records attributed to Fabio Malberti.
Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach.
High plasma asymmetrical dimethylarginine (ADMA) signals endothelial dysfunction and atherosclerosis in the general population and predicts mortality in ESRD. The relationship among plasma levels of ADMA, renal function, and the risk for progression to ESRD (halving GFR or dialysis start) and death in an incident cohort of 131 patients with chronic kidney disease was investigated. Cox's competing risk regression was used to model double-failure times (progression to ESRD and death) as a function of ADMA. Covariates that were considered for adjustment included clinical characteristics, baseline GFR (Modification of Diet in Renal Disease equation 7 formula), proteinuria, traditional cardiovascular risk factors, serum C-reactive protein, homocysteine, and concomitant therapies. Mean age at enrollment was 71 +/- 11 yr, and 24% of patients had diabetes. Baseline GFR ranged from 8 to 77 ml/min per 1.73 m2 (average 31 +/- 15 ml/min per 1.73 m2). ADMA was inversely related to GFR, ranking as the third predicting factor (partial r = -0.22, P = 0.01), after hemoglobin and urinary protein, in a general linear model that included multiple correlates of GFR. After a mean follow-up of 27 mo (range 3.4 to 36), 29 patients progressed to ESRD and 31 died. ADMA (hazard ratio per 0.1 muM/L 1.203; 95% confidence interval 1.071 to 1.350) predicted event occurrence independent of other potential confounders, including GFR, proteinuria, hemoglobin, and homocysteine. In patients with mild to advanced chronic kidney disease, plasma ADMA is inversely related to GFR and represents a strong and independent risk marker for progression to ESRD and mortality. These novel findings further expand the implications of previous observations in ESRD patients and generate hypotheses on the role of ADMA in progressive chronic nephropathies.
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Fistula maturation: doesn't time matter at all?
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Arteriovenous Shunt, Surgical↗
Cardiovascular comorbidity and late referral impact arteriovenous fistula survival: a prospective multicenter study.
Autologous arteriovenous fistulas (AVF) have the best 5-yr patency and the lowest complication rate among hemodialysis vascular accesses. However, maturation requirements to optimize survival are unknown. A longitudinal cohort study was conducted to ascertain risk factors for failure, maturation time, and survival of the first AVF. All patients who initiated hemodialysis between January 1, 1997, and December 31, 2002, in three centers were included in this study. Analysis was restricted to patients who received an AVF. Cox regression was used to estimate the association between predictors of interest and primary and secondary AVF survival. Of the 535 patients enrolled (mean age, 66.5 yr; 57.8% male; 26.7% diabetic), 513 (96%) received an AVF. Patients who initiated with catheters (47%) cannulated their AVF earlier (median maturation period, 0.78 versus 1.80 mo; P < 0.001). Median primary and secondary survivals were longer than 50 and 72 mo, respectively. After adjustment for confounding factors, cardiovascular disease (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.26 to 2.67), utilization earlier than 1 mo after placement (HR, 1.94; 95% CI, 1.34 to 2.82), and referral within 3 mo of dialysis start (HR, 1.55; 95% CI, 1.04 to 2.32) were associated with a reduction in primary AVF survival. Presence of cardiovascular disease (HR, 2.21; 95% CI, 1.38 to 3.55), maturation time <15 d (HR, 2.12; 95% CI, 1.20 to 3.73), and presence of catheters at hemodialysis initiation (HR, 1.79; 95% CI, 1.13 to 2.84) were associated with lower secondary AVF survival. It is concluded that cardiovascular disease, late referral, temporary catheters, and early cannulation are associated with impaired AVF survival. It is recommended that AVF be allowed to mature at least 1 mo before cannulation.
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The choice of the dialysate calcium concentration in the management of patients on haemodialysis and haemodiafiltration.
The choice of an appropriate dialysate calcium (Ca) concentration is crucial in the management of dialysis patients: an excessive Ca load has been associated with vascular calcifications, whereas Ca depletion can worsen secondary hyperparathyroidism (HPT) and decrease bone mass. In haemodialysis (HD), Ca transfer by diffusion depends on the concentration gradient between dialysate and blood, and a gain of Ca is expected when the dialysate Ca is >1.5 mmol/l. However, Ca losses by convective transport (ultrafiltration rate) can even exceed the amount of Ca gained by diffusion. Dialysis Ca balances, in normocalcaemic patients with a mean weight loss of 2-4 kg per session, have been shown to be positive, moderately negative or clearly negative using a dialysate Ca of 1.75, 1.50 or 1.25 mmol/l, respectively. Serum ionized Ca increases during sessions with a dialysate Ca of 1.5 and 1.75mmol/l, and decreases to the lower limits of normal after HD with 1.25 mmol/l. In haemodiafiltration (HDF), Ca mass transfer is strongly affected by the Ca content in the replacement solutions. Bicarbonate-containing bags are Ca free so that dialysate Ca needs to be increased above 1.75 mmol/l to overcome the convective losses and avoid markedly negative balances. Ca mass transfer in HDF is also affected by the infusion mode. Ca balance in post-dilution HDF, for a given concentration gradient between blood and dialysate, does not differ from HD. Conversely, in pre-dilution HDF, dialysate Ca concentration should be increased by approximately 0.25 mmol/l to maintain comparable balances. A given dialysate Ca concentration should be prescribed considering the dialysis Ca mass balance, other concomitant therapies (Ca salts, vitamin D metabolites) and the type of bone disease. The current strategy of maintaining normal Ca levels by ensuring an adequate intestinal Ca absorption with large doses of Ca-containing phosphate binders and concomitantly avoiding positive Ca balances from dialysis by using a low Ca dialysate has been questioned recently because of the risk of either worsening HPT or accelerating the progression of vascular calcifications. A dialysate Ca of 1.5 mmol/l seems to be suitable for the majority of patients on HD or post-dilution on-line HDF because the moderately negative dialysis balances can be easily counterbalanced by the administration of mild doses of Ca-containing phosphate binders in order to ensure a neutral total body Ca balance. If necessary, aluminium-free and Ca-free binders can be added to achieve a satisfactory control of hyperphosphataemia, while avoiding an excessive Ca load.
Calcium↗
Predictors of renal and patient outcomes in atheroembolic renal disease: a prospective study.
Atheroembolic renal disease (AERD) is part of a multisystemic disease accompanied by high cardiovascular comorbidity and mortality. Interrelationships between traditional risk factors for atherosclerosis, vascular comorbidities, precipitating factors, and markers of clinical severity of the disease in determining outcome remain poorly understood. Patients with AERD presenting to a single center between 1996 and 2002 were followed-up with prospective collection of clinical and biochemical data. The major outcomes included end-stage renal disease (ESRD) and death. Ninety-five patients were identified (81 male). AERD was iatrogenic in 87%. Mean age was 71.4 yr. Twenty-three patients (24%) developed ESRD; 36 patients (37.9%) died. Cox regression analysis showed that significant independent predictors of ESRD were long-standing hypertension (hazard ratio [HR] = 1.1; P < 0.001) and preexisting chronic renal impairment (HR = 2.12; P = 0.02); use of statins was independently associated with decreased risk of ESRD (HR = 0.02; P = 0.003). Age (HR = 1.09; P = 0.009), diabetes (HR = 2.55; P = 0.034), and ESRD (HR = 2.21; P = 0.029) were independent risk factors for patient mortality; male gender was independently associated with decreased risk of death (HR = 0.27; P = 0.007). Cardiovascular comorbidities, precipitating factors, and clinical severity of AERD had no prognostic impact on renal and patient survival. It is concluded that AERD has a strong clinical impact on patient and renal survival. The study clearly shows the importance of preexisting chronic renal impairment in determining both renal and patient outcome, this latter being mediated by the development of ESRD. The protective effect of statins on the development of ESRD should be evaluated in a prospective study.
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Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.
The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.
Alkalosis↗
Vascular access surgery managed by renal physicians: the choice of native arteriovenous fistulas for hemodialysis.
BACKGROUND: After decades of success in dialysis research and treatment, prompt availability of a well-functioning vascular access for dialysis remains a disturbing problem. On the basis of a single-center experience in which nephrologists are responsible for access surgery, we sought to identify predictors of catheter use at the start of hemodialysis (HD) therapy and risk factors affecting first permanent access survival. METHODS: Demographics, comorbid conditions, predialysis follow-up, and access-related procedures of the 197 consecutive patients beginning extracorporeal treatment between 1995 and 2001 were prospectively entered into our database. RESULTS: Despite the high prevalence of comorbidities (diabetes, 22%; cardiovascular disease, 50%; neoplasm, 15%), all subjects received a native fistula as a first permanent access, but almost 60% initiated HD therapy using a catheter. The latter showed more comorbidities and were referred later. According to the Kaplan-Meier method, median primary and secondary survivals of the first fistula were 38.1 months and more than 70 months, respectively. The Cox model indicated that diabetes and previous catheter use were independently associated with 85% and 63% greater relative risks for first failure, but only diabetes led to a greater risk for final failure (relative risk, 2.38; P = 0.05). CONCLUSION: Both the absence of predialysis care and presence of comorbidity influence access type at HD therapy initiation and fistula survival. Earlier intervention strategies can increase the use and durability of a native fistula for HD. Direct involvement of nephrologists in the management of access surgery can be helpful in this respect.
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Survival and development of cardiovascular disease by modality of treatment in patients with end-stage renal disease.
Patients undergoing dialysis are at high risk for cardiovascular disease (CVD). The aim of this study was to evaluate the influence of hemodialysis (HD) versus peritoneal dialysis (PD) on survival and the risk of developing de novo CVD. Of the 4191 patients with end-stage renal disease (ESRD) who started renal replacement treatment (RRT) in Lombardy between 1994 and 1997, 4064 (who were on dialysis 30 d after the start of RRT) were considered for survival analysis: 2772 were on HD (mean age 60.9 yr; 21.2% diabetic) and 1292 on PD (mean age 63.6 yr; 16% diabetic). The 3120 patients who were free of CVD at the start of RRT were included in the analysis of the risk of developing de novo CVD. HD and PD were compared by use of a Cox-regression proportional hazard model, stratified by diabetic status; the explanatory covariates were age and gender. The death rate was 13.3 per 100 patient-years (13.0 on HD and 13.9 on PD); 197 (6.3%) of the 3120 patients included in the CVD analysis developed de novo CVD (128 on HD and 69 on PD). After adjustment for age, gender, and established CVD and stratification by diabetic status, there was no significant between-treatment difference in 4-yr survival (relative risk [RR], 0.91; 95% confidence interval [CI], 0.79 to 1.06). The risk of de novo CVD did not differ significantly by treatment modality (RR, 1.06; 95% CI, 0.79 to 1.43). The risk of mortality and de novo CVD for new patients with ESRD assigned to HD or PD was similar in Lombardy in the period 1994 through 1997.
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Parathyroidectomy in patients on renal replacement therapy: an epidemiologic study.
Secondary hyperparathyroidism is a frequent complication of long-term dialysis treatment, and despite recent advances in medical therapy, surgical parathyroidectomy (PTx) is necessary in a considerable number of uremic patients. A prevalence of PTx of 22% was reported in Europe in 1988 in patients on dialysis from 10 to 15 yr, but no large-scale epidemiologic study has been published since then. The aim of the study was to evaluate the prevalence, incidence, and risk factors for PTx in patients on renal replacement therapy (RRT) in Lombardy and to determine whether the incidence has changed over time. The study involved 14,180 patients included in the Lombardy Registry of Dialysis and Transplantation who received RRT for end-stage renal disease (ESRD) between 1983 and 1996. Cox-proportional hazards regression models were used to evaluate the risk factors of PTx, the explanatory covariates being age on admission to RRT, gender, underlying renal disease (nondiabetic or diabetic nephropathy), and dialysis modality (peritoneal dialysis or hemodialysis). The prevalence of PTx in the 7371 ERSD patients who were alive on December 31, 1996, was 5.5% and increased with the duration of RRT (9.2% after 10 to 15 yr, 20.8% after 16 to 20 yr). Similarly, the incidence of PTx increased from 3.3 per 1000 patient-years in patients who had been on RRT for <5 yr to 30 per 1000 patient-years in those receiving RRT for >10 yr. The Cox regression models showed that the relative risk for PTx was significantly higher in women and lower in elderly and diabetic patients. The relative risk for PTx (adjusted for gender, age, and nephropathy) was higher in the patients on peritoneal dialysis than in those on hemodialysis and decreased after transplantation. During the course of a follow-up of 7 yr, the incidence of PTx in patients who started RRT between 1990 and 1992 was no different from that observed in patients who started RRT between 1983 and 1985. In conclusion, the prevalence and incidence of PTx in patients receiving RRT in Lombardy is lower than that in Europe and Italy as a whole, as reported by the 1988 European Dialysis and Transplantation Association Registry; its frequency has not changed significantly during the past few years. The need for PTx decreases markedly after successful transplantation. The epidemiologic finding that the rate of PTx is greater in women, young patients, and individuals who do not have diabetes suggests the need for a more aggressive medical treatment of secondary hyperparathyroidism particularly in such patients.
Adult↗
Structured pre-dialysis programs: more than just timely referral?
BACKGROUND: Patients who begin chronic dialysis within 3 months of seeing a nephrologist (late referral)have increased morbidity and mortality. However, it is not known whether formal pre-dialysis education programs (PEPs) are more advantageous, regarding early dialysis outcomes and resource use, than unstructured specialist follow-up. METHODS: We prospectively collected information on specialist care, unstructured or PEP, modality choice and hospitalizations in the 1st 3 months of dialysis for all consecutive patients who started dialysis between 1st January 1999 and 30th June 2002 in two Italian centers. RESULTS: The 229 patients who participated in this study (62% male, median age 70 yrs) had a high prevalence of diabetes (27.5%) and cardiovascular disease (60%). Of these, 22.7% received unstructured follow-up and 40.6% received PEP care. Peritoneal dialysis (PD) was the first choice modality for 41.5% of patients and 55% had a planned start. Excluding late referrals (36.7%), the likelihood of PD selection was similar between PEP and unstructured care (52.7% vs. 40.4%, p = NS), while that of a planned start was greater among PEP patients (91.4% vs. 38.5%, p < 0.001). Multivariate analysis showed that only PEP (but not unstructured care) vs. late referral had a significant association with reduced odds of hemodialysis (HD) selection (OR: 0.301, [95%CI 0.153, 0.594]), emergency start (0.031 [0.013, 0.075]), 1st hospitalization > 5 days (0.165 [0.081, 0.333]), and further hospitalizations (0.346 [0.174, 0.685]). Late referrals independently predicted the lack of modality selection (1.847 [1.007, 3.388]). CONCLUSIONS: A structured PEP seemed to improve early dialysis outcomes and resource usage beyond that gained by a timely referral, except for the opportunity to select modality.
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Multidisciplinary chronic kidney disease management improves survival on dialysis.
BACKGROUND: Delayed nephrology referral is associated with increased morbidity and mortality after patients begin dialysis. However, whether a pre-dialysis educational program (PEP) confers any survival advantage in comparison to unstructured specialist care is not established. METHODS: Cox's regression analysis was used to estimate the association between the type of pre-dialysis follow-up and mortality in all consecutive end-stage renal disease (ESRD) adults starting dialysis therapy in two centers, between 1 January 1999 and 30 June 2002, and followed until 30 June 2003. RESULTS: 229 patients participated in the study. The patients tended to be male (62%), elderly (median age 70 yrs) and to have cardiovascular diseases (60%). Median follow-up on dialysis was 37.8 months, with 624 patient-yrs at risk and a 0.15 yr(-1) mortality rate. Patients receiving regular unstructured care (22.7%) appeared to have similar risk for death as late referrals (36.7%), while PEP patients (40.6%) showed longer survival (hazard ratio 0.48 (95% CI 0.27, 0.87)), allowing for demographics, comorbidities, duration of the pre-dialysis follow-up and dialysis modality. Planned dialysis commencement, a better metabolic status at dialysis initiation and the previous use of angiotensin converting enzyme inhibitors were the main factors associated with improved outcomes. The survival advantage associated with PEP was still present after late referrals or observation for < or = 1 yr were excluded, as well as when survival analysis was limited to the 1st year after dialysis initiation. CONCLUSION: A multidisciplinary approach to chronic kidney diseases seems more effective than just timely referral to nephrologists in improving patient survival on dialysis.
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Factors associated with unsuccessful utilization and early failure of the arterio-venous fistula for hemodialysis.
BACKGROUND: Arteriovenous fistulae survive longer than grafts and catheters. However, their short term outcomes may not be as good. We sought to determine whether fistulae created in patients referred to a nephrologist less than 3 months before dialysis start show higher risk of unsuccessful use and early failure. METHODS: All patients receiving a new vascular access over a six-year period at three centres were enrolled. Logistic and Cox's regression techniques were used to model late referral on successful utilization for <6 consecutive HD-sessions and time to failure within the first month from access creation, adjusting for demographics, comorbidities and surgical strategies. RESULTS: Among the 535 subjects enrolled, 513 received a fistula. Without considering revisions, 119 fistulae (23.2%) were not successfully used and 61 (11.9%) failed early. Independent predictors of unsuccessful utilization were late referral (Odds Ratio 2.15 [95% Confidence Interval 1.23, 3.75]), vascular diseases (1.86 [1.16, 2.97]), absence of treated hypertension (2.07 [1.17, 3.68]), and heart failure limited to late referrals (10.74 [4, 28.82]). Late referral (Hazard Ratio 1.72 [1.05, 2.81]), absence of treated hypertension (1.80 [1.02, 3.18]) and heart failure (2.34 [1.34, 4.08]) also predicted primary early failure. CONCLUSIONS: Late patient referral and presence of cardiovascular diseases, particularly heart failure, are potentially modifiable risk factors for short-term outcomes improvement of hemodialysis fistulae.
Aged↗