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In this paper, we investigated whether cholecalciferol supplementation may increase the risk of stone recurrence in patients with calcium nephrolithiasis and Vitamin D deficiency. Thirty-three stone formers (56 ± 17 years old, 12 males) with 25(OH)D 1 mean supersaturation. Cholecalciferol was prescribed as oral bolus of 100,000–200,000 IU, followed by weekly (5000–10,000 IU) or monthly (25,000–50,000 IU) doses. Calcium intake varied between 800 and 1000 mg/day. In urine, total nitrogen (TNE) was taken as an index of protein intake, sodium as a marker of dietary intake, and net acid excretion (NAE) as an index of acid–base balance. TNE, sodium, and NAE did not change during the study (p = ns). Compared to baseline values, after cholecalciferol, both serum calcium and phosphate did not vary (p = ns); 25(OH)D increased from 11.8 ± 5.5 to 40.2 ± 12.2 ng/mL (p

Dalbavancin (DBV) is an intravenous long-acting second-generation glycolipopeptide antibiotic with high efficacy and excellent tolerability, approved for use in the treatment of Gram-positive skin and skin structure infections (ABSSSI). Nevertheless, little is known about its pharmacokinetic/pharmacodynamic (PK/PD) properties in real life, which is also due to technical challenges in its quantification in human plasma, preventing an effective application of therapeutic drug monitoring (TDM). In fact, DBV has a high affinity to plasma proteins, possibly resulting in poor recovery after extraction procedure. The aim of this study was to validate a simple, cheap and reliable HPLC-MS method for use in TDM, in accordance with FDA and EMA guidelines. The optimized protein precipitation protocol required 50 μL of plasma, while chromatographic analysis could be performed in 12 min/sample. This method fulfilled the guidelines requirements and then, it was applied for routine DBV TDM in patients receiving off-label high doses (two 1500 + 1500 mg weekly infusions instead of 1000 + 500 mg), with normal renal function or undergoing hemodialysis: continuous hemodiafiltration caused a relevant reduction in DBV exposure, while intermittent dialysis showed comparable DBV concentrations with those of patients with normal renal function. This confirmed the eligibility of the presented method for use in TDM and its usefulness in clinical practice.

Nephrolithiasis is one of the most frequent causes of hospitalization in nephrology and urology units in our country and is an important source of discomfort in affected patients. Despite the availability of modern, minimally invasive endourological procedures to remove stones from the urinary tract, prevention of stone recurrences remains an essential strategy. Chemical analysis of stones, whether passed spontaneously or removed surgically, is a crucial step in etiological diagnostics aimed at devising adequate prevention strategies. Modern endoscopic lithotripsy techniques provide complete fragmentation of stones and, compared to extracorporeal shock wave lithotripsy, have the advantage of avoiding painful elimination of fragments through the urinary tract. This means, however, that stone fragments are often unavailable for analysis, thereby depriving the nephrologist of an important tool for diagnosis. As a consequence, metabolic evaluation tends to be the only means of establishing the etiology of sto...

In this paper we investigated whether cholecalciferol supplementation, prescribed to treat vitamin D deficiency in patients with nephrolithiasis, increased the risk of stone recurrence.Calcium excretion and urine supersaturation with calcium oxalate (βCaOx) and brushite (βbsh) were evaluated in 33 kidney stone formers (aged 56±17; 12 males), both before and after therapy with cholecalciferol, prescribed as oral bolus of 100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000-10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a dietary regimen which included a daily calcium intake of about 800-1000 mg.Urinary nitrogen, sodium and ash-acid excretion did not significantly change during the study. After cholecalciferol supplementation, the main results were as follows: both serum calcium and phosphate did not vary significantly; 25(OH)VitD₃ increased from 11,8±5,5 to 40,2±12,2 ng/mL (p0,01); 1,25(OH) ₂ VitD₃ increased from 41,6±17,6 to 54,0±16,0 pg/mL (p0,01); PTH decreased from 75,0±27,2 to 56,7±21,1 pg/mL (p0,01); daily urinary calcium increased from 2,7±1,5 to 3,6±1,6 mg/Kg b.w. (p0,01), whereas fasting urinary calcium did not change significantly. After therapy, βbsh increased from 0,9±0,7 to 1,3±1,3 (p=0,02) and βCaOx did not vary significantly. Before cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric, whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation (pX²=0,03).Cholecalciferol supplementation for vitamin D deficiency may increase both urinary calcium and urine supersaturation in stone formers. If vitamin D supplements are needed in these patients, a careful monitoring of urine metabolic profile is warranted, in order to customize the metaphylaxis accordingly (hydration, potassium citrate, thiazides).

Many recent papers analyze the association between renal stone disease and other diseases that are typical of industrialized countries. Epidemiology studies from large series indicate that the prevalence of nephrolithiasis is higher among patients with metabolic syndrome, diabetes, and hypertension. Patients with nephrolithiasis also have an increased risk of myocardial infarction and stroke. It has been hypothesized that the common underlying defect could be insulin resistance. This, in turn, alters the urine biochemistry (i.e. more acidic pH and less urine citrate) thereby increasing the propensity of stone forming. In the diabetic rat renal steatosis has been implicated in the reduced production of ammonia, which has been shown to be reversible after PPARγ administration. Furthermore, pioglitazone was shown to be effective in reducing ethylene glycol-induced renal injury. Another significant association concerns gout. Two recent papers report that both calcium and uric acid stone disease are more prevalent among patients with gout. The metabolic derangements found in gouty and non-gouty patients were quite similar. CT imaging in patients with gout indicates that the incidence of nephrolithiasis is underestimated if only based on stone history. Finally, stone episodes may occur many years before the first gouty attack. Another interesting issue is that of a potential adverse effect of calcium and vitamin D supplementation on the risk of stone formation. It has been shown that treated post-menopausal women have a slight but significantly higher risk of forming stones, independently of other interfering variables. From this the recommendation to evaluate the actual benefit of supplementation, even more in the face of its ineffectiveness to prevent fractures in older women. Bariatric surgery is increasingly proposed for managing severe obesity, and in the last few years it has shown a widespread use in the US. Previous procedures of digestive diversion were often complicated by hyperoxaluria and renal oxalosis. More recent techniques, including Roux-en-Y gastric bypass and gastric bending, seem to give better outcomes. Hyperoxaluria and hypocitraturia following these procedures induce only minor increases in the risk of forming stones, but some recent reports of renal oxalosis after gastric bypass deserve attention.

Oxalate (Ox) is an end-product of metabolism, important for poor solubility of its calcium salt in biological fluids. Ox can therefore be found in about 70% of urinary calculi. Hyperoxaluria (HOx) defined as Ox exceeding 0.5 mmol)/day, may cause nephrolithiasis/nephrocalcinosis and may be classified as dietary (DH), enteric (EH) or primary (PH). Fractional intestinal absorption of Ox is less than 10%, but increases to over 20% at calcium intakes below 200 mg/day. DH is often related to low-calcium diets. EH is caused by non-absorbed fatty acids which bind to calcium and lower its concentration in the intestinal lumen. Ox forms more soluble complexes with other cations and results in HOx. Similar mechanisms may cause HOx following bariatric surgery. PHs are the most severe causes of HOx. Three types have so far been described, all being autosomic recessive. PH1 is due to mutations of AGXT gene encoding liver alanine-glyoxylate aminotransferase, PH2 is caused by mutations of GR-HPR gene encoding glyoxylate reductase and PH3 by mutations of HOGA1 encoding for hydroxyl-oxoglutarate aldolase. HOx results from deficient detoxification from glyoxylate, which is oxidized to Ox. The three PHs have different severity, though not always clinically distinguishable. They are identified through genetics and, in PH1, good genotype/phenotype correlations have been established. Thanks to early biochemical and genetic diagnosis, which are crucial to either prevent progression to ESRF or choose adequate transplantation strategies, the outlook of PH patients has dramatically improved in the last decades and will furtherly do in view of new therapeutic strategies.

Many recent papers analyze the association between renal stone disease and other diseases that are typical of industrialized countries. Epidemiology studies from large series indicate that the prevalence of nephrolithiasis is higher among patients with metabolic syndrome, diabetes, and hypertension. Patients with nephrolithiasis also have an increased risk of myocardial infarction and stroke. It has been hypothesized that the common underlying defect could be insulin resistance. This, in turn, alters the urine biochemistry (i.e. more acidic pH and less urine citrate) thereby increasing the propensity of stone forming. In the diabetic rat renal steatosis has been implicated in the reduced production of ammonia, which has been shown to be reversible after PPARγ administration. Furthermore, pioglitazone was shown to be effective in reducing ethylene glycol-induced renal injury.Another significant association concerns gout. Two recent papers report that both calcium and uric acid stone disease are more preval...

This is the second part of an article on the metabolic diagnosis of nephrolithiasis, the first part of which was published in the previous issue of this journal. Here we report on three clinical cases representative of a rational diagnostic workup of nephrolithiasis in specific clinical contexts: secondary hyperuricemia, cystinuria, and primary hyperoxaluria. Nephrolithiasis is one of the most frequent causes of hospitalization in nephrology and urology units in our country and is an important source of discomfort in affected patients. Despite the availability of modern, minimally invasive endourological procedures to remove stones from the urinary tract, prevention of stone recurrences remains an essential strategy. Chemical analysis of stones, whether passed spontaneously or removed surgically, is a crucial step in etiological diagnostics aimed at devising adequate prevention strategies. Modern endoscopic lithotripsy techniques provide complete fragmentation of stones and, compared to extracorporeal shock wave lithotripsy, have the advantage of avoiding painful elimination of fragments through the urinary tract. This means, however, that stone fragments are often unavailable for analysis, thereby depriving the nephrologist of an important tool for diagnosis. As a consequence, metabolic evaluation tends to be the only means of establishing the etiology of stones and preventing their recurrence. We conclude that close collaboration between nephrologists and urologists is a prerequisite for optimizing the diagnosis and treatment of stone disease.

Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet. PTX compared to baseline reduced PTH (4617 vs 15786 pg/mL, p0.01), calcemia (9.40.5 vs 11.30.9 mg/dL, p0.01), calciuria (3.62.3 vs 9.24.5 mmol/24h, p0.01), phosphaturia (18.47.1 vs 21.99.9 mmol/24h, p0.05), CaOx (4.73.9 vs 9.86.8, p0.01) and bsh (1.10.9 vs 3.22.2, p0.01). Cinacalcet decreased both PTH (13379 vs 17187 pg/mL, p0.05) and calcemia (9.70.6 vs 11.20.8 mg/dL, p0.001), whereas no change was seen in calciuria (7.42.2 vs 7.42.4 mmol/24h, p=ns), phosphaturia (21.97.3 vs 23.06.5 mmol/24h, p=ns), CaOx (6.92.7 vs 5.42.5, p=ns) and bsh (1.71.1 vs 1.31.3, p=ns). We conclude that in patients with PHPT, PTX is able to decrease the risk for crystallization of calcium salts, whereas calcimimetic Cinacalcet did not. Therefore, in patients with PHPT complicated with nephrolithiasis only PTX can improve urine biochemistries thereby reducing the risk for recurrent calcium stone disease.

Background: Cholesterol crystal embolism syndrome (CCE) is an increasing end-stage renal disease cause. Few cases have been described on dialysis, despite the high prevalence of the predisposing factors. Methods: The diagnostic criteria of the present study were: skin lesions, myalgia, fatigue, fever and acute inflammatory serologic signs, in the presence of severe vasculopathy. The precipitating factors were: anticoagulation, endovascular intervention and ulcerated atherosclerotic plaque. Results: Between October 2003 and September 2005, CCE was diagnosed in 6 dialysis patients (of 200–210 on chronic treatment): 5 males, 1 female, median age 59.5 years (47–70) and end-stage renal disease follow-up 11.5 years (3–25). All had severe vasculopathy, 5 cardiopathy, and 4 were failed graft recipients. The treatment included: peritoneal dialysis, daily dialysis, ‘conventional’ hemodialysis (2 cases) and hemodiafiltration. The diagnosis was based on the clinical-laboratory picture in 1 patient. In the 5 others clues were present (dicumarol therapy, angioplasty, femoral artery thrombosis, CCE predialysis and ulcerated aortic plaque). The therapeutic approach consisted of corticosteroids (5 cases), statins (4 cases) and prostaglandin analogues (4 cases). Conclusion: The differential diagnosis of CCE should also be considered in dialysis patients (necrotic lesions, limb pain and vasculitis-like signs).

Background. Concerns about vascular access failure may have limited the widespread use of daily haemodialysis (DHD). We assessed the incidence and type of vascular access complications during DHD and other schedules, both at home and on limited care haemodialysis. Methods. All patients were treated in a limited care and home haemodialysis unit with a stable caregiver team (November 1998–November 2002). Vascular access failure, surgical treatment, angioplasty and declotting were studied alone or in combination by univariate and multivariate models. We analysed the effects of age, sex, comorbidity, previous vascular events, schedule, setting of treatment (home, limited care), dialysis follow-up, vascular access (native vs prosthetic, first vs subsequent) and setting of vascular access creation. ‘Intention to treat’ and ‘per protocol’ analyses were performed. Results. In 2160 patient-months (home dialysis: DHD 400 months, non-DHD 655 months; limited care: DHD 208 months; non-DHD 897 months), 57 adverse events occurred (27 failures), in which 30 were at home (nine DHD) and 27 were in limited care (five DHD). The probability of remaining free from adverse events at 6 and 12 months was 89% and 80% on DHD and 79% and 76% on other schedules (‘intention to treat’). Univariate analyses revealed a significant difference for the setting of the vascular access creation (lower risk of vascular access complications in our centre) and sex (male sex was protective). Logistic regression and Cox analyses confirmed the role for the setting of the vascular access creation. Conclusions. Although DHD did not appear as a risk factor for vascular access morbidity or failure at home or in a limited care centre setting, the setting of vascular access creation may influence its success.

Non-compliance is crucial in chronic diseases and increases with complexity of therapies. Objective and methods: to build and validate, in a pilot study involving home and self-limited hemodialysis (HD) patients, a questionnaire assessing dialysis related discomfort (12 items, 4 fields: support therapies, time requirements, relationship with hospital-machine, dialysis related discomfort) and the advantages of flexible schedules and simplified therapies (6 items). A 0–10 visual analogue scale was employed. Results. The study was completed by 50/52 (96%) patients on home or self-limited care HD in a satellite Unit: median age 50 yrs (24–80), follow-up 40 mths (2–360); therapy: 10 pills/day (2–24), 2 subcutaneous injections/week (2–30). The highest scores, describing discomfort, were recorded for: time requirements (median score 8/10), dependence upon the machine (7/10), needle punctures (6/10), drug therapy, vascular access and dependence upon others (5/10). The option of flexible schedules and simplified support therapies obtained maximal scores (median 10/10). No relationship among single scores, clinical data, dialysis or support therapy was found. According to the pattern of the answers, patients were grouped into three main profiles (attitude towards dialysis related problems): stoic (20 cases), suffering (11) and selective (19). No correlation with clinical data and profile was found. Conclusion. Support therapies and organizational aspects cause important discomfort to our dialysis patients. Further studies in different cohorts are needed to define them, to optimize treatment acceptance and compliance.

One of the most feared problems in DHD is the risk of vascular access failure, so that it often limits the diffusion of this technique. Available data are limited; moreover, in most cases data regard home hemodialysis (HHD) patients, with the problem of the risk of a selection bias. The aim of the study was to evaluate the number of fistula complications (occlusion, infections, necessity of surgical treatment, angioplasty or urokinasi) in two groups of patients either on a DHD or on other dialysis schedules, in patients at home or in Limited Care Center. In the period considered (total period about 1500 patient-months; HHD: non DHD 463, DHD 278 months; Limited Care Center: non DHD 613, DHD 140 months) we registered 37 events (12 with vascular access occlusion, 11 with necessity of surgical treatment, 14 with necessity of other intervention, angioplasty or urokinasi). In particular, we registered 23 events in HHD (18 non DHD, 6 with vascular access occlusion and 5 DHD, 3 with vascular access occlusion, respectively 4/100 and 2/100 patient-months), 14 events in Limited Care Center (8 non DHD, none with vascular access failure and 6 DHD, 3 with vascular access failure, respectively 1/100 and 4/100 patient-months). Survival curves according to Kaplan-Meier didn’t show significant differences for DHD group; a worse survival was shown for HHD patients. In a Cox-proportional hazard model history of previous vascular episodes and HHD were independent risk factors (RR 2.01, 95% CI 1.06–3.83 and RR 1.98, 95% CI 1.15–3.39 respectively; overall score 0.04), while a protective role for male sex was present (RR 0.54, 95% CI 0.30–0.96). In conclusion: The increased number of punctures in DHD didn’t cause, in our study, an increase in the risk of vascular access occlusion. The surprise was the disadvantage of HHD compared to dialysis in Limited Care Center, contrary to all expectations. Results from this observational study will be study in depth (relationship with previous vascular problems, hypotension, body weight loss, biochemical risk factors, dialysis efficiency) and for a more prolonged period.

The Evidence Based Medicine is a new approach looking for implementation in the academic teaching of Internal Medicine. Objective: to include this subject in our post-graduate medical school, in the curriculum and as a research project. Methods: since 2000, each year one of the post-graduate nephrology fellows starts a Cochrane revision with the tutorial help of Nephrologists and Methodologists. Results: two titles were accepted for inclusion within the Cochrane Library (“Haemodialysis frequency for end stage renal disease” and “Home versus in-centre haemodialysis for end stage renal disease”) and one protocol will be published in the 4th issue 2002. The main methodological and clinical point of the accepted protocol are: – explanation, in the background section, of the state of the art and of the reasons why to perform a systematic review in this field; – explicitation of criteria for including studies (study design, type of participants, type of interventions, outcome measures) and for assessing methodological quality of the studies; – elaboration of a sensible and reproducible search strategy aimed to identified any relevant article (even not published) seeking electronic bibliographic databanks (MEDLINE, EMBASE, CIHNAL), patients’ websites and ESRD registries (www.renalnet.com, www.kidney.org); – identification of any sources of heterogeneity between studies; – elaboration of statistical analysis using a specific and validated program (Rev.Man) tailored for testing for heterogeneity and for combining data related to the identified studies in a metanalysis when appropriate. Conclusion: the direct involvement of the post-graduate Nephrology school in the systematic reviews is a precious didactic tool.

Background: Home hemodialysis is usually considered a superior therapy, whose decline is related to demographic, social, psychological and financial factors as well as to competition with renal transplantation and PD. Methods: A home hemodialysis program was started in November 1998 in the University of Torino, Italy (200–210 patients on dialysis). Its main features are the tailoring of dialysis schedules and the acceptance of patients with comorbidity. Nurses assist home sessions in case of short-term problems, while the training center ensures follow-up for long-term clinical and logistic problems. Results: The program started in November 1998 on a previous one (active from 1970 to 1998; 6 patients on treatment in November 1998). Since then, 25 more patients joined the program. Out of 31 patients followed since November 1998, 4 were grafted, 2 died, and 2 dropped out from training. In June 2001, 15 patients were on home hemodialysis, 8 on training. Dialysis schedules and controls are flexible and tailored; in June 2001, range of dialysis time was 1.20–5 h; sessions: 2–6; 8 patients were on thrice-weekly dialysis, 7 on daily dialysis; all patients reached target EKRc >10 ml/min (median 15, range 11–24 ml/min). Conclusion: Tailored, flexible schedules allowed home hemodialysis in over 10% of our patients, confirming that there is still room for this treatment in our setting.

Background Informed consent is crucial in therapeutic choices; however, the forms presented to patients are often locally developed and information may not be homogeneous. Objective To prepare an evidence-based model for informed consent, applied in the case of erythropoietin therapy (EPO) as a teaching tool for medical students. Methods Methodological tools of Evidence-Based Medicine (EBM) were developed within the EBM Course in the Medical School of Torino, Italy, as problem solving and patient information tools (5th year students work in small groups under the supervision of statisticians, epidemiologists and experts of internal medicine - nephrology in this case). Results Methodological and ethical problems were identified: in the pre-dialysis field, evidence from randomized clinical trials (RCT) is scant; how to use evidence gathered in dialysis? How to deal with implementation? How with the mass media? Do we need to discuss the drug choice with the patients? How to deal with rare and severe side effects?). The “evidence” was searched for on Medline/Embase, by using key-words and free terms. About 680 papers were retrieved and screened. Forms available on the Internet were retrieved and a general scheme was drawn: it included 5 areas: title, aim and targets (patients and family physicians); search strategies and updating; pros and cons of therapy; alternative options; open questions. Conclusions EBM may offer valuable tools for systematically approaching patient information; the inclusion of this kind of exercise in the Medical School EBM courses may help enhance the awareness of future physicians of the correct communication with patients.

There are good epidemiological (increased numbers of dialysis patients), economical (renal replacement therapy (RRT) costs) and clinical reasons (new highly efficient schedules) to reconsider the choice of home hemodialysis (HD).Analysis of the results and costs of a flexible, tailormade home dialysis program (1998-2003).Home HD facility of the University of Turin-Italy.Results were analyzed in terms of feasibility (enrolment rate, logistical problems--the two usual caregivers performed a retrospective analysis of the clinical records; production costs, assessed with a logic bottom-up technique). Since the main program feature was the tailoring of dialysis to the patient, kinetic data were analyzed to control the efficiency of the chosen schedules.In 1998-2003 (54 months), 31 patients joined the home HD program (six patients were already being treated), while another 12 patients were treated in the training area and trained for an ongoing self-care program; mean age was 47.1 +/- 12.8 yrs; 35/49 patients had clinical comorbidities. During the study, four patients died, 10 were grafted, and six patients dropped out or were transferred. In March 2003, 23 patients were at home/in training and six were being treated in the training area: 11 patients were on a conventional schedule, four on daily dialysis, 12 on other schedules (two patients non-resident in the Piedmont region were not considered). Dialysis efficiency reached the target (EKRc11 mL/min) in all but four patients (schedules with more frequent sessions were planned for these patients). Costs were comparable to limited care HD (daily: 96.5 euros/session at home, 98.76 euros/session in the center; conventional: 133.48 euros/session at home, 131.25 euros/session in the center).A tailored, flexible policy can help to revive a home HD program.

Maintenance of residual renal clearance is a clinical advantage, protecting against the long-term effects of uremia: although demonstrated in peritoneal dialysis, the strategies in hemodialysis are less clear. This case suggests that dialysis schedules individualized on the basis of renal clearances may help preserve residual function. SB is a 58 year-old male who started dialysis in emergency (creatinine 30.7 mg/dL) in 1993. He had a history of gout, small shrunken kidneys and moderate hypertension. The clinical diagnosis was vasculointerstitial nephropathy. Eighteen months after starting hemodialysis on a conventional thrice weekly schedule, the patient was switched to 2 sessions/week (creatinine clearance increased to 6 ml/min). Thereafter, clearances were checked in alternate months and treatment was tailored to an equivalent renal clearance 12 ml/min (1–2 sessions, 2-3.30 hours/week). Ten years after beginning dialysis, he is on a twice weekly schedule (3.30 hours), is normotensive, works full-time and does not want to go on a transplant waiting list.

Organ shortage for transplantation has focused attention on educational interventions. Italy is a nonhomogenous country whose cultural and economic differences are reflected in the health-care system: dialysis is mainly public in the north versus private in the south; and transplantation rates display a wide range from 3.4 to 37.8 per million people in 2002. The aim of the present study was to analyze the opinions of population of high school students (last two years) in two large cities: northern (Torino) and southern (Napoli) Italy, as a knowledge base for a randomized controlled trial on the efficacy of educational interventions on renal replacement therapy and organ donation, targeted to high school students. Methods This preliminary study included eight public high schools that completed a first and anonymous semistructured questionnaire. Five hundred and eighty nine questionnaires were retrieved in Torino and 539 in Napoli. In both cities most students answered that they would give a kidney to a brother, sister, or partner needing dialysis (Torino: yes 80.6%; no 2.2%, uncertain—blank 17.2%; Napoli: yes 86.1%, no 1.1%; uncertain—blank 12.8%). Only 36.3% of the students in Torino and 37.7% in Napoli answered that they would consent to organ donation, if they had to choose for a strict relative with brain death. Opposition was 28% in Torino and 23.7% in Napoli; 35.7% in Torino and 38.6% in Napoli were blank—uncertain. These data underline the need for detailed information on the opinions of the overall population as basis for tailored educational campaigns.

Background. The renin–angiotensin system (RAS) and nitric oxide synthase (NOS) play a key role in the progression of primary glomerulonephritis (GN). Although previous studies have examined genetic risk associated with single gene variations, experiments assessing risk conferred by multiple gene variations are still scanty. Methods. The effect of combination of variant alleles of four genes encoding for three components of the RAS [angiotensin converting enzyme insertion/ deletion (ACE I/D), angiotensin II receptor 1 (AT1R 1166A/C), angiotensinogen (AGT M235T)] and for NOS (ecNOS4b/a) on the development and progression of membranous GN (MGN) were evaluated in a longitudinal study comparing 117 patients with serum creatinine (s-Cr)

Recently increased attention for chronic renal failurehas stimulated new interest in renal function assess-ment by direct measurement as well as by algorithmsor formulas [1–3]. In the failing renal graft, a situationin which pharmacological therapy may interfere withthe complex adaptation mechanisms of renal failure,the assessment of renal function may be particularlydifficult [4]. Studies of patients with liver or hearttransplantation and advanced kidney disease suggestthat creatinine-based indexes may be poor indicatorsof residual renal function under calcineurin inhibitors[5,6]. The following two cases, displaying a discrepancybetween creatinine and urea clearances, draw attentionto this rather neglected, yet clinically relevant, aspectof renal function assessment.

Background In this era of globalization, in which different cultural and economic barriers are progressively abated, in the context of the development of rapid information networks such as the Internet, physicians are increasingly challenged by clinical and ethical questions. Kidney vending, banned in some countries, legal or tolerated in others, may be the prototype of the ethical aspects of health-care globalization. Methods To test the interest and the opinions of medical school students, a simulated case was proposed to students attending a seminar within the nephrology course fourth year of the Medical School of Torino, san Luigi): an Italian patient comes to the nephrologist's office asking for advice on the possibility to legally buy a kidney in a foreign country. The 43 students attending the lesson answered a semistructured questionnaire (15 boys, 28 girls, of median age 23 years). Attendance was within the usual standards (50 students inscribed per year). From the clinical point of view, 11.6% were favorable to kidney vending, 51.2% were contrary, 37.2% were uncertain. From the ethical point of view, no student was pro, 81.4% were contrary, and 18.6% were uncertain. The open comments underline the importance of patient self-determination and of informed consent. Similar opinions were recorded in a nonstructured question: “What should physician's attitude be, in the face of a choice he/she doesn't share?” Conclusion Students' uncertainties and doubts underline the need to discuss ethical scenarios in the clinical teachings of the medical school.

The prognosis of diabetic patients on renal replacement therapy (RRT) is usually poor. We report on the type 1 diabetic woman with the longest RRT follow-up in our area: over 20 years, half on dialysis, half with a renal graft. CS started RRT at age 27 on peritoneal dialysis (3 years), continued until an underdialysis syndrome developed, was switched to acetate dialysis and, because of poor tolerance, to hemofiltration which with good clinical results, allowing her to become the first Italian patient on home hemofiltration, which continued for 5 years. A cadaver graft lasted for the subsequent decade, despite several complications; afterwards she resumed bicarbonate dialysis, choosing a frequent home hemodialysis schedule. Despite several vascular access problems, her clinical conditions were good enough to candidate her for a second renal transplant, performed 3 years ago. This history of active self-care may draw attention to the advantages of a multiple choice dialysis network.

Keywords: aortic aneurism; atherosclerosis; endo-prothesis; daily haemodialysis; long-term RRTThe impressive calcifications seen in the computedtomography (CT) reconstruction of an aortic aneur-ysm of the abdominal aorta in Figure 1 belong to a 48-year-old male, on renal replacement therapy (RRT)from the age of 22. His end-stage renal diseasewas membrano-proliferative glomerulonephritis withsevere and prolonged nephrotic syndrome. In 1981,3 years after diagnosis, he started RRT on peritonealdialysis; he was switched to haemodialysis in 1985 dueto functional exhaustion of the peritoneum, and acadaveric graft was performed in 1993. Haemodialysiswas resumed in 1996 after graft failure due to recurrentmembranous and proliferative glomerulonephritis,again with severe nephrotic syndrome. He hadhypertension, usually well controlled by multipledrug therapy, parathyroidectomy because of severehyperparathyroidism unresponsive to conservativetreatment (1993) and a coronary by-pass (1997). Theaortic aneurysm shown in Figure 1 was first diagnosedin 1991: at that time, the maximum diameter was4.2cm. The diameter was stable until March 2000,when it increased to 4.6cm and further to 4.8cmin November 2000, despite a daily haemodialysisschedule (started in 1999), minimizing weight lossper dialysis and with a good blood pressure controlwithout need for drug therapy.Balancing the young age of the patient and thesurgical risks due to the diffuse arterial calcificationstypical of uraemic patients (Figure 2), a percutaneousendoluminal approach was chosen and successfullyperformed in January 2001, employing a modular

Background Nephrotic syndrome due to diabetic nephropathy is presently considered an indication for pancreas-kidney transplantation even in the absence of severe renal failure. Reversal of the nephrotic syndrome has been reported, but the mechanisms of this effect are unclear. Aim To describe the renal morphofunctional pattern and the pattern of proteinuria before and after preemptive pancreas-kidney transplantation. Methods Methods included quantitative and qualitative assessment of proteinuria as well as renal ultrasound and scintiscan. Case report A 42-year-old woman with type 1 diabetes since age 24 had widespread end-organ damage. Renal biopsy (2001) showed a mainly nodular pattern of diabetic nephropathy. Following referral (1999), her serum creatinine ranged from 1.6 to 2.2 mg/dL, with nephrotic range proteinuria (glomerular nonselective, tubular complete). Renal scintiscan revealed bilateral, symmetric, well-perfused kidneys. The functional data before pancreas-kidney graft (February 2003) were: serum creatinine 1.6 mg/dL, creatinine clearance 58 mL/min, serum albumin 2.6 g/dL, proteinuria 9.1 g/d. At hospital discharge (March 2003), the creatinine was 1.2 mg/dL, the creatinine clearance 97 mL/min, the proteinuria 0.676 g/d. Two months later, the creatinine was 1.2 mg/dL and proteinuria 0.421 g/d. A renal scintiscan demonstrated the functional prevalence of the grafted kidney (77% of total function), with vital, almost completely excluded native kidneys (functional contribution, 11.5% each). Proteinuria, ranging from 0.3 to 0.6 g/d, showed a physiological pattern. Conclusions Functional exclusion of the native kidneys by renal scintiscan gives morphological support to reversal of the nephrotic syndrome.

To the Editor: The interesting paper by Chertow et al1 brings up five interesting points. First, their study does not discuss previous studies with electron beam tomography (EBT) in dialysis patients2,3, which demonstrate different progression rates associated with lipid status3, like that in the general population Figure 1, and show a lack of any relationship between serum calcium and EBT score in the general population4.