[Palliative and Supportive Dialysis: Current Practices and Recommendations for Best Clinical Practice].

"Palliative dialysis" is defined as the renal replacement therapy directed to patients living the most critical phases of illness and the end-of-life stage. Offering targeted dialysis prescriptions becomes imperative when health conditions, along with comorbidities, unfavorable prognosis and complications, do not allow standard dialysis to be started or continued. Management should also integrate adequate supportive care measures in both incident and prevalent patients. This document summarizes nephrological recommendations and scientifical evidence regarding the palliative approach to dialysis, and proposes operative tools for a good clinical practice. After planning and sharing the route of care ("shared-decision-making"), which includes multidimensional evaluation of the patient, a pathway of treatment should be started, focusing on combining the therapeutical available options, adequacy and proportionality of care and patients' preferences. We propose a framework of indications that could help the nephrologist in practicing appropriate measures of treatment in patients' frailest conditions, with the aim of reducing the burden of dialysis, improving quality of life, providing a better control of symptoms, decreasing the hospitalization rates in the end-of-life stage and promoting a home-centered form of care. Such a decisional pathway is nowadays increasingly needed in nephrology practice, but not standardized yet.

The Role of Uremic Retention Solutes in the MIA Syndrome in Hemodialysis Subjects.

INTRODUCTION: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome." METHODS: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients. RESULTS: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01). CONCLUSION: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors.

Variáveis socioeconômicas e demográficas associadas a autorrelato de violência doméstica durante o "Fique em casa!": estudo transversal com amostra de uma comunidade universitária / Socioeconomic and Demographic Variables Associated with Self-Reported Domestic Violence During the "Stay At Home!" Mandate: a Cross-Sectional Study with a Sample of a University Community

Este estudo teve como objetivo estimar a frequência e identificar variáveis socioeconômicas e demográficas associadas ao autorrelato de violência doméstica durante as medidas de distanciamento social decorrentes da pandemia da COVID-19 em uma comunidade universitária. Trata-se de estudo transversal com amostra de conveniência online. Estudantes, técnicos administrativos e professores eram elegíveis ao estudo. A participação consistiu em responder a um questionário autoaplicável com questões sociodemográficas e da vivência da pandemia. Foram calculadas frequências absolutas e relativas e comparadas as proporções nas variáveis categóricas pelo teste Qui-Quadrado. Estimaram-se razões de chances via regressão logística para identificar os fatores associados ao autorrelato de violência doméstica durante o distanciamento social. De julho a agosto de 2020, 2.629 participantes responderam ao questionário. A maioria era do sexo feminino (57%), solteira (67%), branca (55%) e com até 29 anos de idade (62%). O autorrelato de violência doméstica esteve associado ao nível fundamental/médio (RCaj.: 2,80; IC95%: 1,60 ­ 5,50), ao nível de graduação (RCaj.: 2,20; IC95%: 1,20 ­ 4,40), ao sexo feminino (RCaj.: 1,60; IC95%: 1,20 ­ 2,20) e a ser solteiro (RCaj.: 1,60; IC95%: 1,10 ­ 2,40). O enfrentamento da violência, especialmente contra as mulheres, pessoas solteiras e com baixa escolaridade, deve ser construído a partir de uma base intersetorial e em rede, envolvendo ações emancipatórias, cuidado, proteção, assistência psicossocial e capacitação profissional.

This study aimed to estimate the frequency and identify socioeconomic and demographic variables associated with self-reporting of domestic violence during social distancing measures resulting from the COVID-19 pandemic in a university community. This is a cross-sectional study with an online convenience sample. Students, administrative assistants, and professors were eligible for the study. Participation consisted of answering a self-administered questionnaire with sociodemographic questions and experiences of the pandemic. Absolute and relative frequencies were calculated, and the proportions of categorical variables were compared using the chi-square test. Odds ratios were estimated via logistic regression to identify factors associated with self-reporting of domestic violence during social distancing. From July to August 2020, 2,629 participants responded to the questionnaire. Most were female (57%), single (67%), white (55%), and were up to 29 years of age (62%). Self-reported domestic violence was associated with elementary/high school education (AOR.: 2.80; 95% CI: 1.60 ­ 5.50), undergraduate level (AOR.: 2.20; 95% CI: 1.20 ­ 4 .40), female sex (AOR.: 1.60; 95% CI: 1.20 ­ 2.20), and single status (AOR.: 1.60; 95% CI: 1.10 ­ 2.40). Combating violence, especially against women, single and low educated people, must be constructed from intersectoral and networked basis, involving liberating actions, care, protection, psychosocial assistance, and professional training.

Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR &lt; 30 (n = 23), 30 &lt; eGFR &lt; 60 (n = 33), eGFR &gt; 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.

Efficacy and Safety of COVID-19 Vaccine in Patients on Renal Replacement Therapy.

Patients with CKD on RRT are at high risk for severe disease and mortality in COVID-19 disease. We decided to conduct an observational prospective study to evaluate antibody response after vaccination for COVID-19 in a cohort of 210 adult patients on RRT (148 on HD; 20 on PD; and 42 kidney transplant recipients). Blood samples were taken before and 4 weeks after vaccination. Antibody levels were evaluated with CLIA immunoassay testing for IgG anti-trimeric spike protein of SARS-CoV-2. A positive antibody titer was present in 89.9% of HD patients, 90% of PD patients, and 52.4% of kidney transplant recipients. Non-responders were more frequent among patients on immunosuppressive therapy. Mycophenolate use in kidney transplant patients was associated with lower antibody response. The median antibody titer was 626 (228-1480) BAU/mL; higher in younger patients and those previously exposed to the virus and lower in HD patients with neoplasms and/or on immunosuppressive therapy. Only two patients developed COVID-19 in the observation period: they both had mild disease and antibody titers lower than 1000 BAU/mL. Our data show a valid response to COVID-19 mRNA vaccination in HD and PD patients and a reduced response in kidney transplant recipients. Mycophenolate was the most relevant factor associated with low response.

Forced diuresis oriented by point-of-care ultrasound in cardiorenal syndrome type 5 due to light chain myeloma-The role of hepatic venogram: A case report.

Monitoring venous congestion by ultrasound assessment of hepatic venogram allowed individualized fluid management in severe cardiorenal syndrome type 5 due to light chain myeloma, preserving residual renal function and avoiding heart failure.

Effects of a medium cut-off (Theranova®) dialyser on haemodialysis patients: a prospective, cross-over study.

BACKGROUND: Despite significant advances in haemodialysis (HD) in recent decades, current dialysis techniques are limited by inadequate removal of uraemic solutes such as middle molecules and protein-bound uraemic toxins. Novel medium cut-off (MCO) membrane or 'expanded haemodialysis' (HDx) provides diffusive removal of conventional and large middle molecular weight uraemic toxins, with marginal albumin leak. METHODS: This prospective, open-label, controlled, cross-over pilot study compared HDx (novel MCO membrane Theranova® 400) and conventional HD in 20 prevalent HD patients. Biochemical, dialysis adequacy and safety measures (adverse events, infections and hospitalization frequency) were recorded. Ten patients underwent conventional HD high-flux dialyser and 10 patients underwent HDx for 3 months, and the patients then switched and received the other treatment for a further 3 months. RESULTS: Treatment with HDx was associated with a significant reduction in serum albumin concentration [median (interquartile range) reduction -0.45 g/dL (-0.575 to -0.05); P = 0.025]. However, median albumin levels were ≥3.5 g/dL and no patients had clinical symptoms of hypoalbuminaemia or needed intravenous albumin administration. The number of infections was lower in patients treated with HDx (n = 7/19) compared with patients treated with HD (n = 14/20; P = 0.03). Patients treated with HDx had reduced levels of interleukin (IL)-1ß (from 0.06 ± 0.02 pg/mL versus 0.28 ± 0.18 pg/mL with HD) and IL-6 (6.45 ± 1.57 pg/mL versus 9.48 ± 2.15 pg/mL), while tumour necrosis factor-α levels remain unchanged. CONCLUSIONS: This study demonstrates that the chronic use of the novel MCO dialyser Theranova® appears to be safe and well-tolerated, without serious side effects or hypoalbuminaemia, as well as fewer infections. These results need to be confirmed in larger randomized clinical trials.

Percutaneous microwave ablation of renal angiomyolipomas in tuberous sclerosis complex to improve the quality of life: preliminary experience in an Italian center.

AIM: To evaluate efficacy, safety and quality of life of the patients with renal angiomyolipomas (AMLs) associated with tuberous sclerosis complex (TSC) treated with percutaneous microwave ablation (MWA). MATERIALS AND METHODS: Nine patients (7 females and 2 males; mean age 27.6 years, range 23-34), with 10 renal AMLs with a mean size of 6.3 cm (range 4.5-8.5) were treated with image-guided percutaneous MWA. Indications for treatment were the risk of rupture/hemorrhage due to size greater than 4 cm and symptomatology; in one case, a previous hemorrhage was the indication for treatment. During follow-up, the volume of the ablated AMLs and its relationship with the relief of symptoms were registered. Technical and clinical success, safety, and quality of life (QOL) were evaluated in a mean follow-up of 9 months (range 3-12). RESULTS: Technical success was obtained in all cases. Clinical success was obtained in all cases; the volume of the ablated AMLs was not related with symptoms relief; all patients referred a significant improvement in their QOL, with a regularization of daily activities. There were no major procedural complications or delayed adverse events. A small self-limited post-procedural subcapsular hematoma was registered. Post-ablation syndrome was registered in 5 cases and was self-limited in all cases. CONCLUSIONS: Symptoms relief, lower risk of hemorrhage and a normalized QOL were obtained in all patients with a safe and mini-invasive procedure.

Osteoporosis, bone mineral density and CKD-MBD: treatment considerations.

Osteoporosis and chronic kidney disease (CKD) have both independently important potential impact on bone health. A significant number of patients with CKD stages 3a-5D have been shown to have low bone mineral density (BMD), leading to a strikingly elevated risk of fractures (mainly hip fractures) and higher associated morbidity and mortality. Mechanical properties of bone beyond age and menopausal status are additionally affected by intrinsic uremic factors. Therefore, we review in this article not only general concepts of osteoporosis and related consequences, but also the diagnostic and therapeutic implications of low BMD and bone fractures in CKD, beyond increased vascular calcification. Antiresorptive agents (mainly bisphosphonates) were not previously recommended when the estimated glomerular filtration rate (GFR) was lower than 30 ml/min/1.73 m2. However, post-hoc analysis of large randomized clinical trials found that these drugs (i.e. alendronate, ribandronate, denosumab) had comparable efficacy in improving BMD and reducing fracture risk in individuals (mainly women) with moderate reductions of GFR (mostly CKD stages 3-4). Therefore, at least in the absence of clear abnormalities of CKD-related mineral metabolism disturbances, bone antiresorptive agents (and maybe anabolic agents) that are or will be approved for general osteoporosis may be appropriate for CKD. Nephrologists should probably not ignore any longer fracture risk assessment, especially in patients with additional risk factors for osteoporosis if results will impact treatment decisions. However, although different therapeutic agents have been shown to reduce the risk of fracture in CKD patients with low BMD, specific prospective studies, with or without bone biopsies, in CKD are urgently needed.

Laparoscopic Left Hemicolectomy for Colon Cancer in Peritoneal Dialysis Patients: A Valid and Safe Surgical Technique to Ensure Peritoneal Dialysis Survival.

A laparoscopic approach represents an effective alternative to open surgery in patients undergoing peritoneal dialysis (PD). In these patients, conventional thinking provides for removal of the peritoneal catheter during left colon resections because of higher risk of patient contamination and peritonitis. The present paper describes 3 cases of laparoscopic left hemicolectomy for colon cancer performed in PD patients without complications and without peritoneal catheter removal, leading to subsequent early PD resumption.Three normotype PD patients affected by early-stage sigmoid colon adenocarcinoma (T1-T2, M0, N0) underwent integrated surgical and nephrological management to reduce peritoneum stress, infective risk and postoperative complications. The day before surgery, patients were shifted to isovolumetric hemodialysis through tunneled central venous catheter. All patients underwent laparoscopic left hemicolectomy without Tenckhoff catheter removal. The postoperative period was uneventful, with concomitant antibiotic prophylaxis until the fifth day after surgery. Flushing of the PD catheter was performed twice a week postoperatively. Peritoneal dialysis was recovered 4 weeks after surgery in 2 cases with a well-maintained dialytic adequacy. One patient did not proceed to PD due to improvement of renal function after surgery.In selected PD patients, a minimally invasive surgical approach combined with careful nephrological management may represent a valid and safe strategy to treat early-stage colon cancer, avoiding PD drop-out.

[Phosphate binders in renal patients: a point estimate from rationale, through evidences to the real world setting]. / Quali risultati abbiamo ottenuto sino a oggi con i chelanti del fosforo? Razionali, evidenze e mondo reale.

Phosphate binders represent a common intervention in renal patients affected by chronic kidney disease and mineral bone disorder (CKD-MBD). Although counteracting P overload through binders adoption is argued by a physiology-driven approach, the efficacy of this intervention on hard endpoints remains poorly evident. The inconsistencies between rationale and methodological weakness, concerning the clinical relevance of P binding in chronic kidney disease, will be herein discussed with special focus on the need of a multi-factorial treatment against CKD-MBD, which is currently more achievable due to the variety of P binders and the rapid evolution of nutritional therapy, dialysis techniques and nursing science.

[Iron-based Phosphate Binders for ESRD Patients]. / Chelanti del fosforo a base di ferro: quali nuovi vantaggi?

Several factors influence the choice of phosphate binder for patients, including older age, male gender, post-menopause, diabetes, low bone turnover, vascular/valvular calcification and inflammation. Unlike calcium-based phosphate binders, non-calcium-based phosphate binders, such as sevelamer and lanthanum carbonate, have been able to reduce the progression of bone disease to adynamic bone among patients with CKD. New iron-based phosphate binders are now available. With multiple options available for the reduction of phosphate, the focus has been on agents that do not contain calcium. This is because it is thought that calcium itself functions as a substrate for calcification.

[Quality end of life in uremic patients: theory and practice]. / Qualità del fine vita nel paziente uremico: dalla teoria alla pratica.

The rate of fragile elderly patients affected by chronic kidney disease stage 5-5D is rapidly increasing. The decision making process regarding the start and the withdrawal of dialysis is often difficult for all those involved: patients, relatives, nephrologists and renal nurses. Therefore nephrologists and renal nurses are called to rapidly improve their theoretical and practical competence about the end-of-life care. The quality of clinical intervention and management requires a sound expertise in the ethical, legal, organizational and therapeutic aspects, not trivial nor even deductible from purely private and individual opinions nor from traditional medical practice. The present paper discusses the ethical and legal implications related to the start rather than to withdrawn from dialysis, preferring a non-dialysis medical treatment and / or palliative care. Operational aspects regarding the regional network of palliative care, the path of shared decision making process and a systematic approach to optimize medical and nursing interventions through the Liverpool Care Pathway program are discussed thereafter.

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region.

BACKGROUND: The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy. MATERIALS AND METHODS: A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (ß) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics. RESULTS: Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11-100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [ß =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [ß = 6.7 (-2.32; 18.30), p = 0.199] or for all-confounding factors [ß = 5.6 (-5.50; 17.08), p = 0.337]. CONCLUSIONS: This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.

[World Kidney Day 2013 and the Italian experience since 2006]. / Giornata Mondiale del Rene 2013 e l'esperienza Italiana dal 2006 a oggi.

Renal disease is common, insidious and treatable. The prevalence of chronic kidney disease and its cumulative global costs are rapidly increasing. Since 2006 the World Kidney Day (WKD) has worked to raise awareness of the disease and the importance of its prevention within communities and institutions. Italian Nephrology, through the joint action of the Italian Society of Nephrology (SIN) and the Italian Kidney Foundation (FIR) has worked to convey the message during WKD celebrations,meeting the community directly in Italian town squares and high schools, where informative material was provided together with blood pressure and urine dip-stick testing. This year, the WKD was held on March 14th, and was preceded by an extensive program of information broadcast on TV and radio and published in newspapers and magazines. More than 100 nephrology units in 118 cities were either involved in at least one of the programs organized in Italian town squares, high schools and renal clinics, or provided other spontaneous initiatives. This paper describes the history of the Italian experience in the WKD from its beginning in 2006 until the present day.

Cardiac valve calcification: an immutable pathologic finding in chronic kidney disease?

Although less frequent than vascular calcification, cardiac valve calcification (CVC) is a relevant clinical problem affecting about 2%-10% of adults from the general population aged 75 years and older, and is 5- to 10-fold more prevalent in individuals with impaired kidney function. An expanding body of evidence suggests that mineral metabolism abnormalities aside from traditional cardiovascular risk factors are involved in CVC pathogenesis. Nonetheless, very few studies have investigated whether mineral metabolism manipulation impacts CVC. In this issue of the Journal of Nephrology, it is reported that a combination of low-phosphate diet and sevelamer may reduce CVC. Though the observational nature of that study and the lack of a control group significantly limit the generalizability of these results, they fit in with the ongoing debate on the role of chronic kidney disease mineral bone metabolism (CKD-MBD) in the pathogenesis of vascular disease and suggest the importance of mineral metabolism control in patients with CKD.

Vascular calcification and cardiovascular outcome in dialysis patients: the role of gene polymorphisms.

Vascular calcification and accelerated atherosclerosis are major causes of death in hemodialysis (HD) patients. Epigenetic mechanisms of gene regulation may be crucial determinants of cellular behavior in uremic conditions, determining an increased risk of cardiovascular morbidity and mortality. The common polymorphisms on different gene promoters have been related to increased coronary artery calcification and associated with cardiovascular outcome in HD population. In this review, we reported the gene polymorphisms of different proteins as negative prognostic risk factors for all-cause mortality in HD patients, independent of traditional risk factors. These data may have important implications for better understanding the pathogenesis of the increased mortality in this population.

Arterial accelerated aging in dialysis patients: the clinical impact of vascular calcification.

Chronic Kidney Disease Mineral and Bone Disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism that occurs in Chronic Kidney Disease (CKD). In addition to abnormalities in serum calcium (Ca) and phosphate (P) profile, CKD-MBD is characterized by abnormalities of bone turnover, mineralization, volume and growth as well as vascular calcification (VC). Indeed, the co-localization of bone markers such as Osteopontin, Alkaline Phosphatase and Osteocalcin along with osteoblast-like cells in the contest of the arterial wall of uremic patients, indicate that VC is an active biological process with peculiar analogies with bone mineralization. Thus, VC represents a plausible link between Ca and P derangements and the increased mortality associated with CKD-MBD. The process of VC starts in early stages of CKD and patients with CKD-3, -4 and -5 not undergoing haemodialysis may present a significant burden of calcification in the coronaries. Considering that presence and extent of VC in CKD portend poor prognosis, many efforts have been made to shed light on this complicated phenomenon to prevent VC deposition and progression. Indeed, careful control of calcium load, serum P and parathyroid hormone along with the use of calcium-free P binders and vitamin D analogs represent our current armamentarium to improve quality of life and reduce mortality in CKD. We herein summarize the current understanding and evidence supporting strategies available for VC treatment.

Awareness of hypertension and proteinuria in randomly selected patients in 11 Italian cities. A 2005 report of the National Kidney Foundation of Italy.

Arterial hypertension and proteinuria are risk factors for chronic kidney disease. A mobile clinic was parked in a central plaza of 11 Italian cities to check blood pressure (BP), prescribe antihypertensive drugs, assess for proteinuria, and provide awareness about hypertension. Among 3757 patients, 56% were hypertensive, 37% were not diabetic nor proteinuric with BP >or=140/90 mm Hg, 17% were diabetic or proteinuric with BP >or=130/80 mm Hg, and 11% were on treatment with BP at target. Among 1204 treated patients, 400 (33%) had controlled BP. Among all 2114 hypertensive patients, only 1344 (64%) were aware of their hypertension. Awareness was greater among treated patients at target (99%). As many as 523 (14%) patients had proteinuria >or=30 mg/dL. The authors conclude that awareness of people walking in the street about their BP and proteinuria is insufficient. Mobile screening clinics may increase public awareness and detection of hypertension and proteinuria in the general community and detect patients at risk for chronic kidney disease.

Matrix metalloproteinase-1 and matrix metalloproteinase-3 gene promoter polymorphisms are associated with mortality in haemodialysis patients.

BACKGROUND: Vascular calcification and accelerated atherosclerosis are major causes of death in haemodialysis (HD) patients. Matrix metalloproteinases (MMPs) are a family of enzymes, involved in the biology of extracellular matrix and in atherogenesis. MMP1 and MMP3 contribute to the enlargement and instability of atherosclerotic plaque, respectively. The common polymorphisms on MMP1 (2G/2G) and MMP3 (6A/6A) gene promoters have been related to increased coronary artery calcification and to carotid artery stenosis. The aim of this study was to evaluate the association of MMP1 and MMP3 polymorphisms with end-stage renal failure (ESRD) and all-cause mortality risk in HD. METHODS: Ninety-nine HD patients, followed-up for 36 months, and 133 matched controls were genotyped for the two polymorphisms. HD patients' characteristics were age 64 +/- 13 years, males 64%, diabetic 24%, hypertensive 62%, smokers 38%, dyslipidaemic 28%, all undergoing standard HD thrice weekly. RESULTS: ESRD was strongly associated with the combination of 2G/2G and 6A/6A homozygosity: OR 2.57 (0.95-7.4), P = 0.037, but not with isolated 2G/2G and 6A/6A homozygosity (P = 0.09 and P = 0.11, respectively). Isolated 2G/2G was associated with all-cause mortality risk independently from age, gender, diabetes, hypertension, smoking, dyslipidaemia, C-reactive protein, albumin, dialysis vintage and history of cardio-vascular disease: HR 2.96 (1.29-6.80), P = 0.01. A trend for the association of mortality and isolated 6A/6A homozygosity was also observed: HR 3.01 (0.88-10.26), P = 0.078. Combination of 2G/2G and 6A/6A homozygosity significantly increased the mortality risk in the same Cox regression model: HR 4.69 (1.72-12.81), P = 0.003. CONCLUSIONS: In this study, we demonstrated for the first time that MMP-1 and MMP-3 gene polymorphisms are negative prognostic risk factors for all-cause mortality in HD patients, independently from traditional risk factors. These data may have important implications for better understanding the pathogenesis of the increased mortality in HD patients.