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Background: No specific treatment for IgA nephropathy (IgAN) after kidney transplantation is currently available., Methods: We conducted a retrospective single-center study on 29 patients with biopsy-proven de novo and recurrent IgAN after kidney transplantation, divided into two groups. Group 1 (n = 16) received intravenous methylprednisolone 500 mg per day for three consecutive days at the beginning of months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for 6 months. The control group (n = 13, Group 2) received supportive therapies., Results: The two groups were comparable for serum creatinine (sCr) and proteinuria at the time of renal biopsy, but differed significantly at the end of follow-up. sCr was 1.8 ± 0.4 mg/dl in Group 1 vs. 2.7 ± 0.9 in Group 2 (p = 0.002), and proteinuria was 0.9 g/day in Group 1 vs. 1.9 in Group 2 (p = 0.04). The composite outcome of death-censored graft loss or doubling of sCr displayed 2 events in Group 1 (12.5 % of the entire group) and 5 events in Group 2 (38.5 % of the entire group), p = 0.19, odds ratio (OR) 4.4 [95 % confidence interval (CI) 0.7-27.8]., Conclusions: In the absence of therapeutic guidelines for de novo or recurrent IgAN after kidney transplantation, our study reports that therapy with pulse and oral steroids for 6 months is associated with an improved renal function. Nevertheless, further randomized controlled studies in larger patient cohorts are necessary to establish the gold standard treatment.

Background: Encapsulating peritoneal sclerosis (EPS) is a serious complication in patients on peritoneal dialysis (PD) causing intestinal obstruction. Two different forms of EPS are reported: the classical one observed in patients on PD, and post-transplantation EPS (PostTx-EPS). The first-line therapy of classical and PostTx-EPS remains surgical treatment, but for both the complication rate and mortality are high. Recently, a few cases of EPS were successfully treated with inhibitors of mammalian target of rapamycin (mTORi). The aim of this study was to evaluate PostTx-EPS outcome in our patients, focusing on the potential benefit of mTORi treatment., Methods: We performed a retrospective analysis on 1,048 kidney transplanted patients at our center between 11/2001 and 12/2011., Results: In the 226 patients treated with PD at any time before grafting, we found 10 cases of PostTx-EPS (prevalence 4.4%). The mean age was 54.9 years (26-69), with a mean time on PD of 83.1 months (33-156). The interval between kidney transplant and EPS diagnosis was 10.5 months (4-18.9). Five of the ten patients were treated after the diagnosis with mTORi, with a favorable outcome in 4/5 cases. This result was substantially independent of surgical and steroid therapy, performed in 9/10 and 10/10 patients respectively., Conclusion: EPS is a serious complication but susceptible to improvement if early diagnosed. mTORi represent a useful option for EPS treatment. We too suggest adopting an immunosuppressive protocol based on mTORi, mycophenolate mofetil and steroids in order to prevent PostTx-EPS in transplanted patients at high risk.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT.

Microscopic sediment analysis of urine from a 56-year-old woman who underwent renal transplantation showed many uncommon clusters of rounded and translucent cells containing globular mucous cytoplasmic inclusions (HPF, x400). These cells were bigger than leukocytes and, compared with uroepithelial cells, showed a smaller nucleus to cytoplasm ratio and appeared eosinophilic, being pink rather than azurophilic with Sternheimer-Malbin stain. They were also unlikely to be tubular cells, which are usually smaller, singly distributed and associated with dysmorphic erythrocytes and/or casts and/or a worsening in renal function. A review of the patient's history showed that a pretransplantation urologic surgical treatment, including ileal bladder reconstruction, had been performed. Intestinal epithelial cells should be remembered when examining urinary sediment.

Rejection prevention and control have been pivotal aims of medical research since the time that renal transplant was first developed. While acute rejection rates have generally fallen to 10%-15% at 1 year, chronic rejection and chronic allograft nephropathy (CAN) still erode long-term transplant potential. Furthermore, drug tolerability and their 'secondary' effects other than immunosuppression have become as important as their effectiveness in a recipient population that is increasingly old and burdened by cardiovascular morbidity. We review the state of the art of new immunosuppressive drugs: some of them have already entered clinical practice (e.g., mycophenolate mofetil, anti-CD25 monoclonal antibodies and sirolimus [SRL]); others are at different stages of the pre-registration phase (everolimus, mycophenolic acid, FTY 720, leflunomide-FK 778 and Campath-1H), and many others show promising potential for the future (rituximab, monoclonal antibodies against costimulatory molecules). Especially, new drugs with antiproliferative and antifibrogenic effects (SRL, everolimus, leflunomide and mycophenolic acid) could to be decisive in still challenging areas such as CAN and cardiovascular and neoplastic transplant complications. The key to solving these open issues probably lies in the possibility of relying on a wide repertoire of drugs with different profiles, to be exploited in several associations, and in our capacity to integrate new and old immunosuppressive drugs.

Background: Predialysis care is vital for the patient and is crucial for dialysis choice: empowered, early referred patients tend to prefer out-of-hospital and self-care treatment; despite these claims, early referral remains too often a program more than a reality. Aim of the study was to evaluate the pattern and reasons for RRT choice in patients treated in a long-standing outpatient network, presently following 850 chronic patients (about 80% diabetics), working with an early referral policy and offering a wide set of dialysis options (home hemo and PD; self care and limited care hemodialysis; hospital hemodialysis)., Methods: Prospective historical study. All patients who started RRT in January 2001-December 2003 were considered. Correlations between demographical (sex, age, educational level) or clinical variables (pre-RRT follow-up, comorbidity, SGA and Karnofsky) and treatment choice have been tested by univariate (chi-square, Kruskal-Wallis) and multivariate models (logistic regression), both considering all choices and dichotomising choice into "hospital" versus "out of hospital dialysis"., Results: Hospital dialysis was chosen by 32.6% of patients; out of hospital in 67.4% (PD 26.5%, limited-care 18.4%, home hemodialysis 4.1%, self-care 18.4%). Hospital dialysis and PD were chosen by elderly patients (median age: 67.5 and 70 years respectively) with multiple comorbidities (75% and 92.3%); no difference for age, comorbidity, Karnofsky, SGA and educational level. 6/13 PD patients needed the help of a partner. Self-care/home hemodialysis patients were younger (median age 52), had higher educational level (p = 0.014) and lower prevalence of comorbidity (63.6% vs 94.7% in the other dialysis patients, p = 0.006). In the context of a long follow-up period (3.9 years) a statistically significant difference was found comparing hospital dialysis (3.3 years) vs out of hospital dialysis (4.9 years) (p = 0.035). In a logistic regression model, only pre-RRT follow-up was correlated with dialysis "hospital vs "out of hospital" choice (p = 0.014)., Conclusion: Early nephrological follow-up may enhance self and home-based dialysis care.

Unlabelled: Living kidney donation is an important clinical option, encountering different fortunes in the world., Aim: To analyse the opinions of a large subset of older teenagers attending high school (7999 students, median age 18) on different aspects of living kidney transplantation., Methods: Analysis of semistructured questionnaires submitted within an educational campaign on dialysis and transplantation in the high schools of Torino and its county (about 2,000,000 inhabitants)., Results: Over 90% of the students had already heard of transplantation, mainly via television (88.4% county, 84.5% city). 80% would donate a kidney to a family member (3.5% wouldn't, 16.5% uncertain); answers were correlated with sex (females more than males p<0.0001), school type (istituti tecnici versus licei p=0.007), interest (yes versus other p<0.0001). A lower percent of individuals would receive a kidney (58.4% county, 59.4% city), only 10% would ask for donation. Over 40% of students consider legally buying a kidney a patient's right, only 26.6% would discourage this choice. The answers were correlated with the reverse pattern as for non-mercenary donation with type of school (licei more than istituti tecnici: p<0.0001), sex (males versus females p<0.0001), interest (not versus yes: p=0.002)., Conclusions: Teenagers are favourable towards all forms of living kidney donation. The lower prevalence of positive answers on acceptance versus donation suggests that fears of endangering the donor's health may be one of the causes for a low living donation rate in our setting. The mixed answers on mercenary donation suggest discussing this complex issue in future educational programs.

Background: Type 1 diabetic patients are a small but challenging subset of chronic kidney disease. The new frontiers of pancreas-kidney transplantation may enhance the need for early referral., Objective: To analyze the referral pattern of type 1 diabetics to a specialized Nephrology Unit, and to quantify the indications for pancreas or pre-emptive pancreas-kidney transplantation at referral in this population., Patients and Methods: Setting of study was a Nephrology Outpatient Unit, dedicated to diabetics, active since 1986; period of study 1991--2002. The main biochemical and clinical parameters were analyzed at referral. Indications for transplantation were put at: serum creatinine (sCr)> or =2 mg/dL or > or =3 mg/dL and/or nephrotic syndrome. Pancreas: lesser degrees of functional impairment without worsening after FK-506 challenge., Results: 90 type 1 diabetics were referred: 48 males, 42 females; median age: 38 (18-65) years; median diabetological follow-up 20 (3-37) years; sCr 1.2 (0.6-7) mg/dL, proteinuria 0.9 (0-12.3) g/day; creatinine clearance: 58 (6-234) ml/min; Hbalc: 8.8% (5.9-14), diastolic blood pressure: 80 (55-100) mmHg, systolic blood pressure: 137.5 (70-180) mmHg. 85.6% had signs of end-organ damage due to diabetes. 67% of the patients had diabetic nephropathy, 20.7% hypertensive with or without diabetic nephropathy. According to the chosen criteria, 30.6% had indications for pancreas-kidney graft (sCr > or = 2 mg/dL), 25.9% considering sCr > or = 3 mg/dL; 28.2% further patients could be considered for isolated pancreas graft., Conclusions: At referral to the nephrologist, over 50% of type 1 diabetics may have indications for pancreas-kidney or pancreas graft; an earlier multidisciplinary work-up is needed to optimize an early pre-emptive transplant approach.

Background: 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)., Study Aim: Analysis of the results and costs of a flexible, tailormade home dialysis program (1998-2003)., Setting: Home HD facility of the University of Turin-Italy., Methods: 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., Results: 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 (EKRc > 11 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)., Conclusion: A tailored, flexible policy can help to revive a home HD program.

Background: Daily hemodialysis (DHD) is an interesting dialysis option, experienced worldwide by only a few hundred patients, because of clinical and logistic limitations. This study describes the main clinical and implementation results of a flexible policy applied in starting a DHD program., Methods: The setting is the University Nephrology Center of Turin, Italy (approximately 150 hemodialysis and 50 peritoneal dialysis (PD) patients) where in November 1998 a short daily DHD program was started. Outcome measures were logistical (enrollment rate, indications and drop-outs) and clinical (dialysis efficiency, metabolic control, hypertension and anemia control)., Results: 25 patients experienced DHD, 16 (11% of the hemodialysis pool) were on DHD in November 2001; overall the DHD follow-up was 409.1 months (median 18, range 0.7-36 months). Flexibility was applied to schedules (patients modulated dialysis time and could switch to 3-4 sessions/wk); treatment setting (home: 11 patients, limited care center: 13; alternate settings: one); clinical selection (23/25 patients with comorbidity). Main reasons for choice were poor tolerance of previous schedule and the search for "best" treatment. Five patients dropped out (work reasons), one died on DHD and three were grafted. As compared to baseline, dialysis efficiency increased (EKRc pre-DHD 14.5 +/- 2.1 mL/min; 17.4 +/- 2.8 mL/min and 17.7 +/- 3.5 mL/min at 1-6 months; p<0.000). Despite the potentially confusing effect of comorbidity, the main clinical data improved., Conclusions: A flexible approach allowed development of DHD in approximately 11% of hemodialysis patients, with promising clinical results, despite frequent comorbidity.

Background: In the last few years advances in surgical techniques and immunosuppression have improved not only survival, but also quality of life in organ transplanted patients. Hence, the number of women of child-bearing age who decide to have a child--which means resuming a normal life--has increased. This multicenter retrospective study describes pregnancies after kidney transplantation and is the first such survey in Italy., Methods: We analyzed the outcomes from 56 pregnancies in 42 kidney transplant recipients from data collected in questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA), azathioprine (AZA), corticosteroids or tacrolimus (FK506) before and during pregnancy., Results: The average time from transplantation to childbirth was 62 months (range 12 to 180). Complications arose during pregnancy in 16 out of 36 term pregnancies (44.4%). Four transplant rejections (11.8%) were documented, two of them irreversible. Thirty-six infants were born, and 20 abortions reported (35.7%). Of these 36 babies, 16 (44.4%) were born at term, and 20 (55.6%) before term. Thirty-three Cesarean sections were performed (91.7%). Among the 20 pre-term babies, 11 can be grouped as follows: 5 low-birth-weight (LBW) (13.9%), 4 very low-birthweight (VLBW) (8.3%) and 2 extremely very low-birth-weight (EVLBW) (5.6%). The children were followed up for periods ranging from 2 months to 13 years., Conclusions: In kidney transplant recipients who became pregnant the incidence of spontaneous abortion and preterm delivery was increased. Newborns delivered to these patients had low birth weight, but no congenital defects were noted and their development was normal.

Background: Urinalysis is a fundamental test in internal medicine and nephrology. Figures for costs are available in the general laboratory, where biochemical and microscopic urinalysis are commonly performed as semiautomated screening tests. Information on costs is lacking in the nephrology laboratory, where a time-consuming morphological analysis is usually preferred. This study analyses the costs of urinalysis in a nephrology laboratory., Methods: In the nephrology laboratory at the University of Turin - Italy, biochemical urinalysis consists of multi-property strip and proteinuria/creatininuria, done by laboratory technicians. Phase-contrast microscopy is done by a nephrologist or biologist. Time dedicated to the tests was recorded by the same operator over 20 working days, during which 350 urine samples were processed (median 19/day, range 842). The production costs were calculated with the logic bottom-up technique., Results: Overall time needed was 11.9 minutes/sample. Biochemical urinalysis required 6.6 minutes/sample; time required and samples processed were inversely related (< or =19 samples: 7.95 minutes/sample; >19 samples: 5.6 minutes/sample, p=0.01). Microscopic urinalysis took 5.3 minutes/slide; the best time-to-samples ratio was at 18-22 samples per day (with peak efficiency at 21 samples: 4.6 minutes). Cost of reagents and disposables was Euro1.06/sample. Time accounted for euro 5.32/sample (technicians, nephrologist-biologist), with total direct cost of euro 6.38/sample., Conclusion: In a nephrology laboratory, microscopic urinalysis is a time-consuming, expensive test. Analysis of cost and modalities may be useful, in a time of budget constrains, to maintain a role for this precious semeiotic art.

Acquired cystic kidney disease (ACKD) is a complication of end-stage renal disease, the prevalence of which is related to dialysis duration; incidence of ACKD and associated conditions (neoplasia, hemorrhage) have decreased with improvements in renal transplantation and with the ageing of the dialysis population. This report regards spontaneous kidney rupture in a 57-year old patient, on home hemodialysis for 11 years, with ACKD for 5 years. At the end of a dialysis session, the patient reported sudden onset of colicky flank pain, followed by macrohematuria. Pain remitted with low doses of pain relievers, leaving dull flank discomfort. The patient self diagnosed a renal colic, and called the hospital two days later. At referral, two large hemorrhagic renal masses (7 and 2.8 cm) were found at ultrasound and CT scan. At surgery, kidney rupture was diagnosed. This case highlights the life threatening complications associated with ACKD, and underlines that massive renal hemorrhage may occur with relatively minor symptoms.

We report the case of a 48-year-old male, whose musculoskeletal manifestations, previously related to long-term renal replacement therapy (RRT), were diagnosed as ankylosing spondylitis when symptoms changed their pattern on daily hemodialysis (DHD). The patient started RRT in 1981; in 1985 he received a cadaver graft, which failed in 1987. Secondary hyperparathyroidism, amyloid geoids, bilateral carpal tunnel syndrome and high aluminium levels were present. Musculoskeletal pain, reported since 1986, involved feet, heels, hips, shoulders, hands, spine. Symptoms impairing daily life did not improve after parathyroidectomy. He developed chronic hypotension and recurrent atrial fibrillation. In 1994 and 1998, because of thoracic pain, coronarography was performed (normal on both occasions). In June 2000, DHD was started. Equivalent renal clearance increased from 9-12 to 15-17 mL/min. Well-being remarkably improved. In September 2000, musculoskeletal pain worsened and bilateral Achilles tendinitis occurred. The worsening of musculoskeletal symptoms despite the improvements in well-being and other dialysis related symptoms prompted a re-evaluation of the case. The diagnosis of ankylosing spondylitis was based on: history of plantar fasciitis, bilateral Achilles tendinitis, inflammatory spinal pain with limitation of lumbar spine mobility (positive Schober test), radiological evidence of grade 2 bilateral sacroiliitis, presence of HLA-B27. This diagnosis cast light on the episodes of chest pain, explained by enthesopathy at the costosternal and manubriosternal joints and atrial fibrillation, due to HLA-B27 associated impairment in heart conduction. This case exemplifies the difficulty of differential diagnosis of multisystem illness in patients with long RRT follow-up.

While the clinical impact of the impaired immune response, commonly described in chronic dialysis patients, is still a matter of discussion, it is usually considered that immunological diseases tend to become progressively less active after the start of regular renal replacement therapy (RRT). We reported a case of Henoch-Schonlein Purpura in a 51-year-old male, on RRT for 20 years, 8 on dialysis and 12 with renal graft, because of ESRD of unknown origin (chronic glomerulonephritis?). The acute onset of the syndrome, presenting purpuric rash, abdominal discomfort and asymmetric joint pain with edema and local signs of acute inflammation, was followed by several relapses over a 2 years period. This biopsy proven diagnosis offered an explanation for his chronic renal failure; furthermore, we conclude that, possibly because of the usually good correction of uremic immunodepression by efficient dialysis (this patient's Kt/V ranged from 1.1 to 1.3 according to Lowrie's formula), the possibility of immune diseases should be carefully considered even in long long-term RRT patients.

Limited care dialysis is an interesting option, which has gained attention in several settings because of the aging of the uremic cohort. The aim of this study was to assess its potential in the Piedmont region in northern Italy, evaluating patients' and care-givers' preferences and testing them in a mathematical model of organisation. The study was conducted in the satellite unit of a university hospital (200-210 dialysis patients), following 35 patients (15 at home, 20 in the center, 10 on daily dialysis). Opinions were collected with a questionnaire and features identified were empirically tested through a simulation model. Most patients (34/35) preferred a small unit, with a stable caring team. Further options were flexibility of dialysis schedule, multiple treatment options, integrated center/home care. These needs could be met by a flexible organization including conventional dialysis (3/week) and daily dialysis (6/week). We employed a simulation model (ARENA software) to calculate the nurses required for each shift and the opening hours and best schedule for the unit. Addition of daily dialysis (2-3 hours) to two conventional 4-5 hour sessions to increased the number of patients followed or "spared" beds, ensuring flexibility. According to patients' best choice (7 dialysis stations), and to the recorded calls, the needs are for two nurses per shift, two shifts per day and six nurses for up to 30 patients in limited care. In conclusion, small centers with flexible schedules can tailor dialysis to patients' needs. A managerial approach is valuable for testing cost/benefit ratios in specific contexts.