Renal biopsy in patients over 75: 131 cases.

INTRODUCTION: Demographic analysis shows the ageing of the global population and the consequent increase in the age of hospitalized subjects and of patients starting dialysis. Hence, interest in the feasibility, safety, and usefulness of renal biopsy in elderly patients is growing. We examined the data of 131 patients over the age of 75 who underwent renal biopsy. We analyzed the safety of the procedure, treatment, and outcomes. RESULTS: Histological diagnoses included: membranous glomerulonephritis (GN) 20.6%, crescentic GN 12.9%, IgAGN 10.6%, focal segmental glomerulosclerosis 9.1%, acute GN 4.5%, amyloidosis 9.1%, and acute tubular necrosis 3.8%. Mean glomerular obsolescence was 28.9 Â ± 27.9%. Mean age of the patients was 78.7 Â ± 5.73 years. At the time of biopsy, serum creatinine (SCr) was 4.47 Â ± 2.56 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day. Targeted treatment was given to 51.9% of patients, 52.9% of whom had a good clinical response. Eight patients had clinically non-relevant side effects (11.7%). A positive response (defined as a more than 50% reduction of SCr, or by partial or complete remission of proteinuria) was observed in 36 patients (52.9%). 76 patients were monitored for 57 Â ± 9.89 months: 18 patients were on dialysis (follow-up 2.56 Â ± 3.61 months), 15 died (follow-up 58.5 Â ± 13.43 months), and 52 remained under nephrologic observation for 36 Â ± 31 months (SCr was 2.56 Â ± 0.75 mg/dL and proteinuria was 4.82 Â ± 6.78 g/day). CONCLUSION: In our experience, renal biopsy is safe even in very elderly patients; it allowed targeted treatment in 51.9% of patients, 52.9% of whom had a good clinical response, possibly contributing to prolonged patient survival and improved quality of life.

Non invasive evaluation of cardiac hemodynamics in end stage renal disease (ESRD).

OBJECTIVE: Volume overload is typical of haemodialysis patients; correct volume status evaluation is crucial in achieving blood pressure homeostasis, hypertension management and good treatment planning. This study evaluates the effect of acute volume depletion on ultrasonographic parameters and suggests two of them as able to predict patients volume overload. PATIENTS AND INTERVENTION: 27 patients with end stage renal disease treated with haemodialysis underwent a complete echocardiographic exam before, after 90 min and at the end of the dialysis. MAIN OUTCOME AND RESULTS: Blood pressure levels significantly drop during the first 90 min of dialysis (139 ± 20 vs 126 ± 18; p < 0.0001), reaching a steady state with significantly lower values compared to baseline (130 ± 28; p = 0.02). LV and left atrial volume significantly decreased (baseline vs end dialysis 98 ± 32 vs 82 ± 31 p = 0.003 and 28 ± 10 vs. 21 ± 9 cc/m(2) p < 0.001). A significant reduction of systolic function (EF 61.6 % ± 9 vs 58.7 % ± 9 p = 0.04), of diastolic flow velocities (E/A 1.13 ± 0.37 vs. 0.87 ± 0.38 p < 0.001) and mitral annulus TDI tissue velocity (i.e. E' lat 10.6 ± 3 vs. 9.4 ± 3 cm/s; p 0.0001) were observed. Stroke work (SW) and LV end-diastolic diameter (LVEDd) indexed to height 2.7(LVEDdi) were able to predict volume overload: cut off values of respectively 13.5 mm/m(2.7) for LVEDdi and 173 cJ for SW were able to predict with a specificity of 100 % the presence of a volemic overload of at least 4 %. CONCLUSIONS: Blood pressure, cardiac morphology and function are significantly modified by acute volume depletion and such variations are strictly interrelated. SW and LVEDd/height(2.7) may identify ESRD patients carrying an higher volume load.

[Acute kidney injury and septic shock: experiences in treatment]. / Insufficienza renale acuta e shock settico: esperienze terapeutiche.

Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

[Pyelonephritis]. / Le pielonefriti.

Acute pyelonephritis (APN) is a frequent pathological condition. Its etiology is prevalently due to E. coli and risk factors include sexual activity, genetic predisposition, old age and urinary instrumentation. No correlation between APN and vesicoureteral reflux has been established in adults. The diagnosis of APN is usually clinical, but computed tomography (CT) and magnetic resonance imaging (MRI) allow a more precise definition and can document evidence of abscesses. Severe cases should be treated with a fluoroquinolone or an extended-spectrum cephalosporin. Treatment should last 10-14 days. The long-term evolution of APN is prevalently favorable in adults, even though formation of cortical scars and development of macroalbuminuria and renal failure have been described. The formation of renal abscesses is underestimated and must be evaluated by CT or MRI. Abscesses need to be drained only when they are large, and medical treatment is successful in the majority of cases.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

[Home hemodialysis and peritoneal dialysis compared]. / Dialisi domiciliare sì, ma quale? Emodialisi domiciliare e dialisi peritoneale a confronto: una controversia non controversa.

The evolution of home dialysis marked the main steps in the progress of renal replacement therapy. From the origins when home hemodialysis was often the only alternative to death, to the advent and widespread use of peritoneal dialysis, the dream of kidney transplant as a solution to all problems (at least in the young), and ultimately the profound social and organizational changes that have led to a drastic reduction of home hemodialysis, we arrive at the present with the rediscovery of the clinical, rehabilitative and economic advantages of home dialysis. Seven experts from five different centers with different expertise in home dialysis report their opinions on the future of home dialysis in a ''noncontroversial controversy''. Beyond the sterile competition between peritoneal dialysis and home hemodialysis, the shared opinion is that the two methods may complement each other, allowing a tailored treatment for each patient and a tailored organization in each setting. The organizational solutions are many; the authors underline the importance of longer survival and better rehabilitation, and the ethical need of offering each patient a choice among all available treatments. Add to this the importance of dedicated educational programs targeted to physicians, nurses and patients alike and focused on self-care and patient empowerment. A new generation of dialysis machines, easier technical solutions, and financial incentives may strengthen motivations and simplify problems; all these elements may in the near future be combined in a joint effort to increase peritoneal dialysis and revive home hemodialysis in Italy.

Acute pyelonephritis in adults: a case series of 223 patients.

BACKGROUND: Acute pyelonephritis (APN) is a common disease which rarely evolves into abscesses. METHODS: We prospectively collected clinical, biochemical and radiological data of patients hospitalized with a diagnosis of APN from 2000 to 2008. RESULTS: Urinary culture was positive in 64/208 patients (30.7%) and blood cultures in 39/182 cases (21.4%). Two hundred and thirteen patients were submitted to computed tomography (CT) or nuclear magnetic resonance (NMR): confirmation of APN was obtained in 196 patients (92%). Among these, 46 (23.5%) had positive urine culture, 31 (15.8%) had positive blood culture and 15 (7.6%) had positive cultures of both urine and blood. In 98 patients, either urine or blood cultures were negative, but CT/NMR were positive for APN. Fifty of the 213 patients submitted to CT/NMR (23.5%) had intrarenal abscesses: only 2 were evidenced by ultrasound examination. No differences were found between patients with positive or negative CT with regards to fever, leucocytosis, C-reactive protein, pyuria, urine cultures and duration of symptoms before hospitalization. No differences were found between patients with or without abscesses with regards to these parameters and risk factors. Patients with abscesses had a longer duration of treatment and hospitalization. CONCLUSIONS: Our data suggest that in APN it is not always possible to routinely document urinary infection in a clinical setting. This finding could be explained by previous antibiotic treatment, low bacterial growth or atypical pathogens. Systematic CT or NMR is necessary to exclude evolution into abscesses, which cannot be suspected on clinical grounds or by ultrasound examination and may also develop in the absence of risk factors.

[Vesicoureteral reflux in adults]. / Il reflusso vescico-ureterale nell'adulto.

Vesicoureteral reflux (VUR) may be congenital or acquired. The most frequent form of congenital VUR is primary VUR. Its prevalence in adults is not exactly known, but it is higher in women, whose greater propensity for urinary tract infections increases the likelihood of an instrumental examination leading to the diagnosis of less severe cases. In men, even severe VUR may go undiagnosed for a long time. Primary VUR is due to a defect in the valve mechanism of the ureterovesical junction. In physiological conditions, the terminal ureter enters the bladder wall obliquely and bladder contraction leads to compression of this intravesical portion. Abnormal length of the intravesical portion of the ureter due to a genetic mutation (whose location is yet to be established) leads to VUR. In its less severe forms VUR may be asymptomatic, but in 50-70% of cases it manifests with recurrent cystitis or pyelonephritis. The manifestations leading to a diagnosis of VUR in adults, besides urinary tract infections, are proteinuria, renal failure and hypertension. The gold-standard diagnostic examination is a micturating cystourethrogram. Reflux nephropathy develops as a result of a pathogenetic mechanism unrelated to high cavity pressure or urinary tract infections but due to reduced formation of the normal renal parenchyma (hypoplasia or dysplasia). Abnormal renal parenchyma development is attributable to the same genes that control the development of the ureters and ureterovesical junction. VUR is considered only a marker of this abnormal development, playing no role in scar formation. There is no conclusive evidence regarding the indications for VUR correction. However, the risk that VUR leads to recurrent pyelonephritis and reflux nephropathy must be kept in mind. VUR certainly has to be corrected in women who contemplate pregnancy.

[Activity in a nephrology ward in 2009, Piemonte, Italy]. / Fotografia dell'attivita' in un anno di una corsia nefrologica in Piemonte.

The characteristics of patients hospitalized in nephrology wards in Italy have changed in recent years due to the aging Italian population and the increased immigration. We analyzed the demographic and clinical characteristics of patients hospitalized in our nephrology ward (17 beds) from 15 November 2008 to 15 November 2009. In this period there were 507 hospitalizations including 448 patients. The mean age was 64.4+/-18 years (range 16-96 years). Foreigners accounted for 10% of the total; their mean age was significantly lower than that of Italian patients (38.2+/-13.4 vs 67.4+/-15.9 years, p<0.01). 36.3% of patients were on dialysis, 10% were transplant recipients: the reasons for admission in these cases were internal medicine related; 18.15% were hospitalized because of emergency unit crowding without indications for admission to a nephrology ward. Hospitalization lasted a mean of 13+/-13 days. The most frequent diagnosis at discharge was acute renal failure (ARF) (28.9%) (prerenal 42.1%, obstructive 12.2%, drug induced 6.8%, other causes of ARF 38.7%). Patients with ARF were older than patients with other kidney conditions (67.05+/-16.98 vs 56.03+/-18.65 years, p<0.01). ARF resolved or improved in 86 patients (63.7%). Other diagnoses were cardiovascular disease 25.1%, glomerular disease 18.7%, acute pyelonephritis 10.6%, other 16.7%. Foreign patients presented infectionrelated diseases more often than Italian patients (39.2% vs 20.4%, p=0.02). 392 patients were discharged to their homes, 40 (7.9%) found a place in a long-term care facility or home for the elderly, 25 (4.9%) in other hospital units, and 50 patients died (9.8%). In conclusion, patients hospitalized in nephrology wards in 2009 were mostly elderly with a high frequency of cardiovascular disease and diabetes. The most frequent diagnosis was prerenal ARF. These data suggest the necessity of improving the prevention of this type of kidney disease. Moreover, the length of hospitalization, which is increasing because of difficult clinical and social situations, could be shortened if more nursing homes, convalescent homes and homes for the elderly were available in Italy.

[Immigrants and dialysis: a survey in Piedmont]. / Immigrazione e uremia: indagine nei centri dialisi del Piemonte.

The number of immigrants has been rapidly increasing in Italy in the last decade, with potentially profound effects on the national health care system. Yet, few data are available on the clinical and demographic features of these subjects, or on their need for nephrological care and dialysis treatment. A survey was conducted in 19 dialysis facilities of Piedmont (a northwestern Italian region) about immigrants on chronic dialysis treatment. Data on native country, administrative position, clinical and dialysis aspects were anonymously collected. Overall, 93 immigrant dialysis patients coming from 24 foreign countries were registered. Most of them were young (mean age 46∓14 years) and on extracorporeal treatment (87%); late referral (38%) or starting dialysis in emergency (17%) were common modalities of presentation. Glomerular (33%) or unknown (31%) nephropathies were the most representative causes of end stage renal disease. No difference in incidence of HCV, HBV and HIV compared with native Italian patients was observed. Notably, more than 50% of the immigrant patients had low-level knowledge of Italian. As regards administrative position, 69% were regular foreign citizens, 19% were temporary foreign workers, and 9% had a residence permit. Our survey confirms the existence of a young immigrant population on dialysis in Piedmont, whose social and relational problems are more challenging than clinical aspects and call for new organizational models to manage this growing population on dialysis.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

[Indications from the first audit on peritoneal dialysis in Piedmont and Aosta valley]. / Indicazioni dal primo audit sulla dialisi peritoneale in Piemonte e in Valle D'Aosta.

In March 2009 a clinical audit was held in Turin on peritoneal dialysis in order to analyze the problems that still hinder the effective deployment of the technique in Piedmont-Aosta Valley. Various data about epidemiological and clinical management were collected by means of a questionnaire that all 26 nephrology centers of the two regions responded to. The two major critical issues highlighted were the role of the outpatient facility dedicated to uremic patients and why the peritoneal technique was not chosen for new dialysis patients. With regard to the first issue, the presence of a well structured outpatient facility dedicated to chronic renal failure seems to direct more uremic patients to peritoneal dialysis, at the same time decreasing the rate of late referrals. Regarding the second issue, patient choice was the leading cause followed by problems related to the partner, while traditional clinical contraindications interfered to a lesser extent with the choice of dialysis technique. We therefore believe that it will be possible to increase the use of peritoneal dialysis by improving organizational aspects of the dialysis center and trying to remedy the lack of social support. Accurate information and early care of uremic patients by dedicated outpatient facilities are in fact able to lead more patients to choose peritoneal dialysis. The implementation of measures of support, such as financial incentives to dialysis patients following a recent decision of the Piedmont region, could help to overcome problems related to the lack or unhelpfulness of a partner.

[Cancer treatment-induced nephrotoxicity: BCR-Abl and VEGF inhibitors]. / ''Terapie oncologiche e danno renale: cisplatino, metotrexate, interferone, radioterapia...''

The nephrotoxicity of some cancer drugs is well known. Given the rapid development of cancer research, careful assessment of patients treated with new drugs, which may have new toxicity profiles, is mandatory. The nephrotoxicity of cisplatin is likely due to inhibition of autophagy priming, while that of methotrexate is related to direct tubular toxicity and intratubular precipitation. Both can be prevented by adequate hydration. The mechanism of radiation nephropathy development is unclear, but chronic oxidative stress and inflammation seem to play a key role. Mesangiolysis is a characteristic feature, followed by vascular alterations, atrophy, fibrosis, and necrosis. Inhibitors of vascular endothelial growth factor (VEGF), such as bevacizumab, sunitinib, and sorafenib, interfere with angiogenesis. Bevacizumab is a humanized monoclonal antibody which binds to circulating VEGF. Sunitinib and sorafenib are small molecules inhibiting tyrosine kinase of the intracellular domain of the VEGF receptor. Treatment with anti-VEGF drugs is frequently complicated by proteinuria, acute renal failure, and hypertension. The most frequent histological lesion is thrombotic microangiopathy. Inhibitors of the BCR-Abl tyrosine kinase domain on the Philadelphia chromosome (imatinib, nilotinib and dasatinib) may cause acute renal failure.

[Isolated microhematuria: biopsy, yes or no?]. / La microematuria isolata: biopsia si', biopsia no?

Isolated asymptomatic hematuria is frequently encountered in clinical practice but there are no established recommendations for its evaluation and management. There is controversy regarding which tests are necessary and whether renal biopsy is indicated. In the pediatric population, renal biopsy should be considered if there is evidence of progressive renal disease or when parents are worried about their child's diagnosis or prognosis. In adults, examinations for isolated microhematuria should include exclusion of pharmacological causes, journeys to endemic areas for S. haematobium or tuberculosis, sickle-cell disease, endometriosis and, in patients older than 40 years, kidney, ureteral or bladder cancer. Examination of urinary sediment may help in identifying the origin of microhematuria. If it is decided to perform a renal biopsy, the patient should be carefully informed of the possible complications of renal biopsy, including the possibility of finding normal renal tissue.

Retroperitoneal fibrosis and schistosomiasis: a causal relationship?

Retroperitoneal fibrosis (RPF) is characterized by replacement of the normal tissue of the retroperitoneum with fibrosis and/or chronic inflammation. About two-thirds of cases of RPF are idiopathic and one-third is secondary to drugs, infections (tuberculosis, syphilis, actinomycosis, fungal infections), retroperitoneal hemorrhage, or malignancy. We report the case of a patient who was diagnosed as having RPF and schistosomiasis caused by Schistosoma haematobium with histological documentation. He was treated with praziquantel and afterwards with corticosteroids with remission of RPF. To our knowledge, the association between schistosomiasis and RPF has not been described in the literature. We postulate that there is a causal relationship between these two conditions.

Do central venous catheters have advantages over arteriovenous fistulas or grafts?

Central venous accesses have become an integral component of vascular access procedures for hemodialysis. Although the DOQI guidelines recommend that less than 10% of chronic hemodialysis patients should be maintained on catheters, in some countries higher prevalences are reported, as in the United States and the United Kingdom (18% and 24%, respectively, according to the DOPPS). The native arteriovenous fistulas are still the best suited accesses for hemodialysis. However, this option is impractical in many situations, so that several justifiable reasons exist for protracted dialysis catheter use; these include the catheter as a bridge angioaccess device, while the patient is awaiting living-related kidney donor transplantation or maturation of an autologous fistula or graft or, increasingly, as the permanent vascular access for patients with unsuitable vascular anatomy who have exhausted all other options. Moreover, the surgical creation of an AVF is felt to be impossible or at least seems to entail significant risks in situations of high output cardiac failure, myocardial ischaemic events and steal syndrome. In these cases, the dialysis access catheter brings considerable advantages, but it also carries tremendous drawbacks. In addition to the increased risk of luminal thrombosis, infection, unreliable blood flows, central venous stenosis, shorter use life and patient cosmetic concern, tunneled catheters are associated with an increased risk of death. Tunnellization, exit site protection, antibiotic-coated or antiseptic-impregnated hemodialysis catheters, antibiotic lock solutions could be helpful in preventing and treating catheter-related bacteremias. Moreover, the development of a subcutaneous port, that is durable, offers a high blood flow and is fully implantable subcutaneously, may become an alternative for chronic use. In our 10-year experience we implanted in our center over 450 central venous catheters with a satisfactory survival (86% at 1 year and 79% at 2 years for the subcutaneous port). In a matched comparison between Tesio twin catheters and Dialock ports (37 vs. 35, respectively), followed for a 2 year period, no significant differences emerged as regards bacteremia incidence, 0.58/1,000 catheter-days in the Tesio catheter group vs. 0.9/1000 catheter-days in the subcutaneous port group, p=0.12; thrombolytic agents needed, 4.5% vs 4.3% of dialysis sessions; or access failure with removal of the device, 8.1% vs 14.2%, p=0.4. The longer duration of antibiotic therapy in the Tesio group (24.6 vs 14.3 days, p=0.006) was due to the higher incidence of cutaneous infectious episodes (3.8 vs 0.16/1,000 catheter-days). In conclusion, although central venous catheter is the vascular access of last choice, in particular cases it can be a useful alternative, provided that strict protocols for nursing care and proper catheter management are implemented in every center.

The Diamant Alpin Dialysis cohort study: clinico-biological characteristics and cardiovascular genetic risk profile of incident patients.

BACKGROUND: Clinical and therapeutic characteristics of chronic dialysis patients vary widely at national and/or regional levels. Their increased cardiovascular (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk factors only. Therefore, this study aimed to investigate and compare the characteristics of patients starting dialysis in a homogeneous Alpin region and possibly to identify new biological parameters (phenotypes or genotypes), which eould be responsible for the increased CVD seen in end-stage renal disease (ESRD) patients. METHODS: A cohort of 279 non-selected consecutive patients entering a dialysis program was prospectively investigated in eight centers of three adjacent regions in France, Italy and Switzerland. In addition to the usual demographic, clinical and biological data, we analyzed at study entry the blood levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism. RESULTS: At entry, 90.3% of patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were current smokers; 42% of patients had already experienced at least one CV event: peripheral artery disease (26% of the cohort), coronary artery disease (22%) or ischemic cerebro-vascular disease (16%). Forty-two patients had had > or =2 CV events or documented atherosclerotic localizations. Anemia was not optimally treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients received erythropoietin (EPO) prior to dialysis, large national differences were observed. Compared to the reference population, ESRD patients exhibited increased homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent to that of the reference population. In addition, none of the analyzed phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype, could be associated with the existence of a previous adverse CV event. CONCLUSIONS: (1) The clinical characteristics of the ESRD patients entering dialysis in our region were comparable to the currently observed dialysis populations in most European countries with the deleterious role of advancing age, diabetes, previous CVD, smoking and hypertension evident (2). Except for anemia therapy, there were no regional or national differences observed at dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors demonstrated differences with the reference population only for hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable differences among the participating centers.

Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other thrombotic process?

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.