A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience.

BACKGROUND: Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. METHODS: We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. RESULTS: Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). CONCLUSIONS: The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients.

Endothelial progenitor cell-derived microvesicles improve neovascularization in a murine model of hindlimb ischemia.

Paracrine mediators released from endothelial progenitor cells (EPCs) have been implicated in neoangiogenesis following ischemia. Recently, we demonstrated that microvesicles (MVs) derived from EPCs are able to activate an angiogenic program in quiescent endothelial cells by a horizontal transfer of RNA. In this study we aim to investigate whether EPC-derived MVs are able to induce neoangiogenesis and to enhance recovery in a murine model of hindlimb ischemia. Hindlimb ischemia was induced in severe combined immunodeficient (SCID) mice by ligation and resection of the left femoral artery and mice were treated with EPC-derived MVs (MVs), RNase-inactivated MVs (RnaseMVs), fibroblast-derived MVs or vehicle alone as control (CTL). Since MVs contained the angiogenic miR-126 and miR-296, we evaluated whether microRNAs may account for the angiogenic activities by treating mice with MVs obtained from DICER-knock-down EPC (DICER-MVs). The limb perfusion evaluated by laserdoppler analysis demonstrated that MVs significantly enhanced perfusion in respect to CTL (0.50±0.08 vs 0.39±0.03, p<0.05). After 7 days, immunohistochemical analyses on the gastrocnemius muscle of the ischemic hindlimb showed that MVs but not fibroblast-MVs significantly increased the capillary density in respect to CTL (MVs vs CTL: 24.7±10.3 vs 13.5±6, p<0.0001) and (fibroblast-MVs vs CTL: 10.2±3.4 vs 13.5±6, ns); RNaseMVs and DICER-MVs significantly reduced the effect of MVs (RNaseMVs vs CTL: 15.7±4.1 vs 13.5±6, ns) (MVs vs DICER-MVs 24.7±10.3 vs 18.1±5.8, p <0.05), suggesting a role of RNAs shuttled by MVs. Morphometric analysis confirmed that MVs enhanced limb perfusion and reduced injury. The results of the present study indicate that treatment with EPC-derived MVs improves neovascularization and favors regeneration in severe hindlimb ischemia induced in SCID mice. This suggests a possible use of EPCs-derived MVs for treatment of peripheral arterial disease.

Loss of nephrin expression in glomeruli of kidney-transplanted patients under m-TOR inhibitor therapy.

The development of proteinuria has been observed in kidney-transplanted patients on m-TOR inhibitor (m-TORi) treatment. Recent studies suggest that m-TORi(s) may alter the behavior and integrity of glomerular podocytes. We analyzed renal biopsies from kidney-transplanted patients and evaluated the expression of nephrin, a critical component of the glomerular slit-diaphragm. In a group of patients on 'de novo' m-TORi-treatment, the expression of nephrin within glomeruli was significantly reduced in all cases compared to pretransplant donor biopsies. Biopsies from control transplant patients not treated with m-TORi(s) failed to present a loss of nephrin. In a group of patients subsequently converted to m-TORi-treatment, a protocol biopsy performed before introduction of m-TORi was also available. The expression of nephrin in the pre-m-TORi biopsies was similar to that observed in the pretransplant donor biopsies but was significantly reduced after introduction of m-TORi(s). Proteinuria increased after the m-TORi inititiation in this group. However, in some cases proteinuria remained normal despite reduction of nephrin. In vitro, sirolimus downregulated nephrin expression by human podocytes. Our results suggest that m-TORi(s) may affect nephrin expression in kidney-transplanted patients, consistently with the observation in vitro on cultured podocytes.

Extubation score in the operating room after liver transplantation.

BACKGROUND: Early extubation after liver transplantation (LT) is an increasingly applied safe practice. The aim of the present study was to provide a simple extubation rule for accelerated weaning in the operating room (OR). METHODS: Data of 597 patients transplanted at the LT center of Turin (Italy) were retrospectively analyzed. Fifty-two nonextubated patients (excluding those with a scheduled early reoperation) were compared with 545 successfully extubated patients (not in need of reintubation within the first 48 h). Significant variables at univariate analysis were entered into a logistic regression model and the regression coefficients of independent predictors were used to yield a prognostic score called the safe operating room extubation after liver transplantation (SORELT) score. RESULTS: Two major and three minor criteria were found. The major ones were blood transfusions (higher than/or equal to 7 U of packed red blood cells) and end of surgery lactate (higher than/or equal to 3.4 mmol/l). The minor ones were status before LT (home vs. hospitalized patient), duration of surgery (longer than/or equal to 5 h), vasoactive drugs at the end of surgery (dopamine higher than 5 microg/kg/min or norepinephrine higher than 0.05 microg/kg/min). Patients who fulfill the SORELT score-derived criteria (fewer than two major/one major plus two minor/three minor criteria) can be considered for OR extubation. CONCLUSION: Early extubation after LT requires a very careful assessment of the pre-operative, intraoperative, graft and post-operative care data available. The SORELT score helps as a simple and objective aid in considering such a decision.

Assessment of cardiovascular risk in waiting-listed renal transplant patients: a single center experience in 558 cases.

Cardiac screening is recommended to prevent cardiovascular death after renal transplantation. This retrospective observational study illustrates the results of application of a cardiac assessment algorithm in a series of 558 renal transplant candidates at a single center in Turin, Italy. A dipyridamole-stress sestamibi myocardial scintiscan (DMS) performed in 302/558 (54.1%) cases was positive in 52 (17.2%), negative in 200 (66.2%), borderline in 16 (5.3%), and with signs of previous necrosis in 34 (11.4%). Coronary lesions detected by angiography in 48.1% of the 52 positives were treated medically (13.5%) or by percutaneous/surgical procedure (34.6%). Coronary lesions were detected in 14.1% of asymptomatic population subgroup. The minor and major cardiovascular event rates and the cardiovascular death rate were 1.9%, 0%, and 0%, respectively, in positive DMS group (high-cardiological risk) vs. 10%, 4.5%, and 3.5% in the negatives (p > 0.5; n.s.). It is suggested that not increased cardiovascular event or deaths rates in the high-risk group reflect early coronary lesion detection and correction. Since 55.9% of cardiovascular events or deaths occurred in the negative group more than 24 months after the DMS, its mandatory repetition every two yr after a negative finding is recommended.

Life expectancy of women with lupus nephritis now approaches that of the general population.

Immunosuppressive treatment has changed the prognosis of Lupus nephritis over time, but improvement in prognosis is difficult to analyze in different historical periods, and should be better demonstrated in comparison with life expectancy of sex-and age-matched people. Long-term patient and renal survival of 90 patients diagnosed with Lupus nephritis at our center from 1968 to 2001 with a follow-up time of 14+/-8 years was retrospectively evaluated. Patient and kidney survival significantly increased over time. Multivariate analyses show that risks of patient and renal death decreased by 8% at each year of follow-up, and increased by more than 5 time in patients aged > 30 years at diagnosis. As only 14 patients were men, relative survival as compared to that of the sex- and age-matched general population of the Piedmont Region was calculated for the 76 women. Improvement in the survival of the cohort of women was seen at any time of follow-up: in particular, it was sharply lower in the first period (relative survival at 5, 10 and 15 years = 0.784, 0.665, and 0.620, respectively) and increased in the second (relative survival at 5, 10 and 15 years = 0.939, 0.921, and 0.850, respectively) nearly approaching that expected for the general population, i.e. 0.993, 0.983 and 0.967, respectively. Taken together, our data allow us to draw the conclusion that life expectancy in women with Lupus nephritis has improved over time, paralleling an improved awareness of the disease and a significant increase in steroid pulse therapy as induction/remission phase. Improvement in survival is for the first time demonstrated to cover the gap with life expectancy of the general population for women with Lupus nephritis.

[Kidney retransplantation: indications and limits]. / Il ritrapianto renale: indicazioni e limiti.

Whether or not to consider a uremic patient for retransplantation remains a matter of debate. Donor shortage and putative poor outcomes are the main cons, improved results in the last decade and a better survival (HR 0.50) with retransplantation than dialysis stand as pros. The percentage of patients waitlisted for retransplantation or already having been retransplanted is increasing (up to 20-30%) and the absolute contraindications are limited to rare conditions (loss of previous transplant due to anti-glomerular basement antibodies in Alport's syndrome, early recurrence of GNF or hemolytic uremic syndrome). When retransplantation is considered, however, careful screening for risk factors is mandatory, whether they are related to the previous graft or to the recipient's clinical features or the donor's demographics and immunological status. In the last decade the clinical outcomes of retransplantation have significantly improved. No difference in patient survival at the fifth year has been reported between first, second and third grafts. The kidney survival at the same interval is above 70% for the second graft and 65% for the third graft. Nephrectomy of a previous graft is not necessary if not for clinical reasons. As far as the maximum number of retransplants is concerned, most transplant centers (69%) set no clear-cut limit. In conclusion, also taking into account that many patients after graft failure ask for readmission to the waiting list (75% in our experience), we think the retransplantation option should always be evaluated.

Preoperative oral immunonutrition versus standard preoperative oral diet in well nourished patients undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomy is still associated to high morbility, especially due to pancreatic surgery related and infectious complications: many risk factors have already been advocated. Aim of this study is to evaluate the role of preoperative oral immunonutrition in well nourished patients scheduled for pancreaticoduodenectomy. METHODS: From February 2014 to June 2015, 54 well nourished patients undergoing pancreaticoduodenectomy were enrolled for 5 days preoperative oral immunonutrition. A series of consecutive patients submitted to the same intervention in the same department, with preoperative standard oral diet, was matched 1:1. For analysis demographic, pathological and surgical variables were considered. Mortality rate, overall postoperative morbility, pancreatic fistula, post pancreatectomy haemorrhage, delayed gastric emptying, infectious complications and length of hospital stay were described for each groups. Chi squared test, Fisher's Exact test and Student's T test were used for comparison. Differences were considered statistically significant at p < 0.05. Statistics was performed using a freeware Microsoft Excel (®) based program and SPSS v 10.00. RESULTS: No statistical differences in term of mortality (2.1% in each groups) and overall morbility rate (41.6% vs 47.9%) occurred between the groups as well as for pancreatic surgery related complications. Conversely, statistical differences were found for infectious complications (22.9% vs 43.7%, p = 0.034) and length of hospital stay (18.3 ± 6.8 days vs 21.7 ± 8.3, p = 0.035) in immunonutrition group. CONCLUSION: Preoperative oral immunonutrition is effective for well nourished patients scheduled for pancreaticoduodenectomy; it helps to reduce the risk of postoperative infectious complications and length of hospital stays.

Clinical impact of bacterial contamination of perfusion fluid in kidney transplantation.

Contamination of perfusion fluid (PF) could lead to serious infections in kidney transplant recipients. Preemptive therapy (PE-T) in case of yeast contamination of PF is mandatory. The usefulness of PE-T in presence of bacteria remains unclear. In this study we evaluated the incidence of PF bacterial contamination and the impact of PE-T on clinical outcome. Microbiological data of 290 PF and clinical data of the corresponding recipients collected in our hospital from January 2010 and December 2012 were analyzed. Recipients with bacterial contaminated PF (101) were divided in 3 groups: group 1 (n = 52) PE-T treated bacteria resistant to perioperative antibiotic prophylaxis (PAP), group 2 (n = 28) bacteria sensitive to PAP, group 3 (n = 21) PE-T-untreated bacteria resistant to PAP. Incidence of positive PF was 34.8 %, 50.4 % staphylococci, 9.9 % C. albicans. No significant differences in the rate of PF-related infections between the three groups were found. In conclusion, although PF contamination is frequent, the incidence of PF-related infections is very low. In addition, in this study PE-T did not help to reduce the rate of PF-related infection suggesting that a resonable reduction in the use of antibiotic terapy could be made. However, waiting for largest and prospective clinical trials to confirm our findings, a closely clinical and microbiologic monitoring of the recipient is highly recommended in case of PF contamination.

Renal transplantation in patients over 65 years of age: no more a contraindication but a growing indication.

INTRODUCTION: Worldwide organ shortage and the increasing age of end-stage renal disease patients demanding a graft have prompted extensive use of marginal donors. The "old-for-old" allocation has been proposed for the elderly. The aim of this study was to evaluate the results of a policy of free acceptance into the waiting list of recipients older than 65 years. METHODS: From 1987 to 2004 70 patients whose mean age was 67.4 +/- 2.8 years, underwent an extensive pretransplant evaluation including cardiac studies. Immunosuppression was based upon low-dose steroids, and cyclosporine (50%) or tacrolimus (44%). RESULTS: Patient and graft survival at 1, 3, 5, and 10 years were 85%, 78.5%, 75%, 50%, and 80%, 74%, 70%, 36%, respectively. Death occurred in 17/70 (24%), 14 of whom had a functioning graft. The causes of death were 30% cancer, 23% cardiovascular, 23% sepsis, 12% cerebrovascular hemorrhage, 12% meningitis. The acute rejection (AR) rate was 18.6%. The causes of graft loss were: 71% patient death, 4% irreversible AR, 4% vascular thrombosis, and 21% chronic allograft dysfunction. The main complications were: 52% prostatic hypertrophy, 40% urinary tract infections, 8.6% diabetes, 11% pneumonia, 10% cardiovascular diseases, 7% urological complications, 8% abdominal pathology, 6% acute pyelonephritis, 8% non-skin cancer. CONCLUSIONS: Despite the increased vulnerability of the elderly, they should not be excluded a priori from renal transplantation. Extensive pretransplant screening, mainly cardiovascular, and a tailored immunosuppression are two crucial issues. The moderate rate of AR suggests that these patients do not have an impaired immunocompetence as far as acute rejection is concerned.

Angiotensin I-converting enzyme genotype significantly affects progression of IgA glomerulonephritis in an italian population.

To evaluate the role of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the progression of immunoglobulin A glomerulonephritis (IgA-GN), genotype distribution in 81 biopsy-proven cases of IgA-GN was studied. A logistic regression model showed that the risk for homozygous DD was not significantly elevated in patients with IgA-GN compared with healthy subjects (odds ratio = 1.16; confidence interval [CI], 0.4 to 3.3). However, the 5-year (78% v 90%) and 10-year (52% v 82%) renal survival rates for 47 patients with serum creatine (Cr) levels of 1.5 mg/dL or less at biopsy was significantly less in DD patients (n = 18; chi2 = 5.41; P = 0.02). The hazard ratio (HR) for DD (multivariate analysis from Cox proportional model after adjustment for known factors of progression, such as hypertension [HPT] and proteinuria [PTO]) was 3.07 (CI, 1.1 to 9.4). The HR for heavy PTO was 6.1 (CI, 1.9 to 19). The association of DD genotype with progression was even more striking when patients with other risk factors (heavy proteinuria) were excluded, as shown by DD-related risk in the absence (HR = 3.6; CI, 1.1 to 12) and presence (HR = 2; CI, 0.4 to 10) of PTO. The risk ratio was further increased by the coexistence of DD + PTO (HR = 9.16; CI, 1.8 to 15.7). Furthermore, in a cross-sectional study among patients with IgA-GN, a logistic regression model showed that the risk for homozygous DD was greater, although not at a statistically significant level in the end-stage renal failure subgroup compared with the normal renal function subgroup (odds ratio = 3.16; CI, 0.7 to 13.7) after adjustment by sex, age at biopsy, HPT, PTO, and therapy. Last, DD was significantly more frequent in those patients who started hemodialysis at an earlier age (chi2 for trend = 6.81; P = 0.009). Our study further supports that ACE genotype is a risk factor not for the development, but for the worsening of IgA-GN clinical course. However, on the basis of current knowledge, we cannot exclude that I/D polymorphism may simply serve as a prognostic marker, eventually linked with other discrete loci involved in the progression of renal damage.

Use of arterial conduit as an alternative technique in arterial revascularization during orthotopic liver transplantation.

BACKGROUND: The risk of hepatic artery thrombosis after orthotopic liver transplantation is higher in cases of poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, unsafe native hepatic arteries. AIMS: To assess the use of arterial conduits as alternative technique for graft revascularization. PATIENTS: At the Liver Transplant Center of the "S. Giovanni Battista" Hospital in Torino, a review has been made of 600 consecutive orthotopic liver transplantations in 545 adult patients from 1990 to 1999. METHODS: In 95 orthotopic liver transplantations (15.8%) in 88 patients, the graft was supplied by infrarenal conduit, while in 505 orthotopic liver transplantations (84.2%) in 457 patients, a direct anastomosis was used. RESULTS AND CONCLUSIONS: The overall incidence of hepatic artery thrombosis in our series was 3.5% (21/600): 5.3% (5/91) for conduits and 3.2% (16/505) for standard technique (p=ns, chi2 test). The actuarial 5-year graft survival was 67.7% for conduits and 68.6% for the standard technique; p (log rank): ns. The iliac prosthesis torsion was the only complication related to the use of infrarenal iliac conduit. The arterial conduit, performed with donor iliac artery, is an effective and safe revascularization technique in patients at high risk of arterial thrombosis.

Rubidium deficiency in dialysis patients.

BACKGROUND: Since dialysis has brought long-term survival to uremic patients, we can now speculate on more subtle problems derived from imbalance or sub-optimal regulation of some elements such as trace metals. We focused on the rubidium (Rb) status in dialysis patients (HD), as concerns about its possible deficiency have been raised. METHODS: Rb in uremic patients was evaluated by: A) serum concentration (graphite furnace atomic absorption spectroscopy) from blood samples of 70 patients on chronic hemodialysis (HD) in comparison with 75 controls; B) tissue concentration (neutron activation analysis) from autopsy or biopsy samples (20) of HD patients in comparison with 21 controls; C) in vivo intradialytic mass balance during standard bicarbonate dialysis in 8 HD patients. RESULTS: A) Serum Rb concentrations in HD patients significantly were lower than in normal controls (304 +/- 81 micrograms/L versus 350 +/- 74 micrograms/L p < 0.001, log-transformed 5.68 +/- 0.28 versus 5.84 +/- 0.20, p < 0.001). Univariate logistic regression analysis found a significantly higher risk of serum Rb < 250-300 and 350 micrograms/L in uremic patients than in controls (Odd ratios or 12.6, 95% CI 2.77-57.04; 4.0, 95% CI 1.92-8.4; 2.08, 95% CI 1.02-4.25, respectively). B) Rb was significantly lower in tissues of HD patients, including brain (2250 +/- 1520 ng/g versus 5490 +/- 1250 ng/g, p = 0.0002) than normal controls. C) Rb was transferred from the patients' blood to the dialysis bath during a standard bicarbonate dialysis session, giving mean intradialytic Rb removal of 4.0 +/- 1.1 mg/session. CONCLUSIONS: These results confirm that Rb deficiency may arise in uremic patients, and indicate that diffusive dialysis treatments allow Rb removal which, however, with a standard bicarbonate schedule does not seem to be any greater than that expected with normal urine output (20 mg/week). Further studies are needed to clarify the roles of many factors in this Rb deficiency, including the effects of uremia by itself, pre-dialysis factors (diet, impaired renal function and drugs), dialysis procedures (frequency, hours, diffusive/convective components) or other biochemical/clinical parameters (hemoglobin, body mass index, age). The finding of a Rb deficiency in uremia is important as it has a role in neurobehavioural functions, mainly as an antidepressant. As Rb deficiency may be implicated in central nervous system alterations which strongly influence the quality of life, we believe that monitoring serum Rb in uremic patients and clarifying the causal mechanisms of deficiency will facilitate future therapeutic approaches.

Extrahepatic immunological manifestations of hepatitis C virus in dialysis patients.

BACKGROUND: Hepatitis C virus (HCV) infection may be associated with various extrahepatic immunological disorders. Uremic patients on chronic regular dialytic treatment (RDT) frequently develop immunological abnormalities. The aim of this study was to evaluate the probability that HCV infection creates an increased risk for extrahepatic immunological abnormalities in chronic RDT patients. SUBJECTS AND METHODS: In a series of one hundred sixteen chronic RDT patients, HCV status was determined by anti-HCV antibodies, polymerase chain reaction (PCR) RNA and viral genotyping. After excluding four anti-HCV negative/PCRRNA positive patients, a comparison was made between 51 anti-HCV negative/PCR-RNA negative and 61 anti-HCV positive patients, this latter group including seventeen PCR-RNA negative, fifteen genotype 1, thirteen genotype 2, three genotype 3, four genotype 4, four undeterminable genotype and five mixed genotypes. The following investigations were performed: cryoglobulinemia (presence, titer and, when possible, identification), monoclonal gammopathy, antineutrophil cytoplasm antibodies, antidouble stranded DNA antibodies, circulating immunocomplexes and immunoglobulin levels. RESULTS: Cryoglobulinemia was found in 77% of anti-HCV positive versus 29% of anti-HCV negative patients, and cryocrit > 1% in 50% versus 9.8% respectively, p=<0.01. Also cryoglobulin concentration was higher (logarithmic transformation: 4.38 +/- 0.94 vs 3.11 +/- 1.06, p =< 0.001) in anti-HCV positive versus negative patients. Multivariate logistic regression analysis showed a significantly increased odds ratio (12.0, confidence interval 3.0 to 48.3) for having high levels of cryoglobulins (cryocrit >1%) after adjusting for age and dialytic age. The prevalence of this abnormality did not differ significantly among patients infected with different genotypes, but a tendency towards a lower frequency was observed in the anti-HCV positive/PCR negative subgroup. Cryoglobulins were identified as type I (2 anti-HCV positive case), type II (2 anti-HCV positive and 1 anti-HCV negative case) and type 3 (1 anti-HCV negative case). The frequency of monoclonal gammopathy was not significantly different between anti-HCV positive and anti-HCV negative patients (6.5% versus 2%) as well as that of the other parameters evaluated except for IgG concentration which was higher in the anti-HCV positive group (1,685 +/-605 versus 1349 +/- 352 mg/dl, p 0.006). Five events, potentially linked to HCV infection, occurred in our anti-HCV positive patients: 2 cases of porphyria cutanea, 1 case of unexplained peripheral neuropathy, 1 cutaneous leukocytoclastic vasculitis, 1 death for non-Hodgkin's lymphoma. In one anti-HCV positive patient treated with interferon-alpha, the presence of cryoglobulins, monoclonal gammopathy and high IgG levels strictly paralleled that of viremia, disappearing during the recovery phase under treatment and reappearing shortly after stopping treatment. CONCLUSIONS: HCV infection provides a significantly increased risk for developing extrahepatic immunological abnormalities also in chronic RDT patients. It is possible that the clinical relevance of this event might be scant because of the low level of these abnormalities, but an awareness of its possibility should to be taken into account.

Limited value of zinc protoporphyrin as a marker of iron status in chronic hemodialysis patients.

BACKGROUND: In an attempt to find new parameters able to evaluate the actual iron availability by bone marrow cells, zinc protoporphyrin (ZnPP), a metabolic intermediate generated in the red blood cell by the incorporation of zinc instead of iron, has been proposed. ZnPP is a good marker of iron-deficiency anemia in non-uremic people, as red blood cell ZnPP concentration rises specifically (except for lead intoxication) in this condition. Existing data on ZnPP as a marker of iron deficiency in uremic patients comes mainly from cross sectional studies on chronic hemodialysis and has produced conflicting results. SUBJECTS AND METHODS: Therefore, we prospectively studied 42 HID patients, 28-88 years old, 13-346 months of dialysis age, beginning from a period of maximal iron deficiency, due to the lack of parenteral iron compounds (T0) up to the end of more than one year of follow-up with continuous parenteral iron supplementation (T4). ZnPP, hemoglobin, transferrin saturation and ferritin were serially determined before and after six weeks (T1), four months (T2), seven months (T3) and 14 months (T4) of parenteral iron supplementation at a maintenance dose of 0.5-1 mg/kg/week. RESULTS: In comparison with baseline values (95+/-37 micromol/mol heme) there were no significant changes in ZnPP levels at T1 and T2 despite a continuous increase in both transferrin saturation and ferritin values, while ZnPP significantly decreased at T4 (63+/-37 micromol/mol heme, p<0.001). There was no correlation between ZnPP and both transferrin saturation and ferritin at any time during the study, the same was true for ZnPP and zinc and lead serum concentration, fibrinogen and reactive C protein levels at T1 and T4, respectively. At T4, only 2/10 patients who still showed ZnPP levels >80 micromol/mol heme had absolute or functional iron deficiency, when the percentage of hypochromic red cells were measured. CONCLUSION: We conclude that ZnPP untimely parallels a change in iron balance in only a proportion of uremic people, in as much as confounding factors, such as chronic inflammation and uremia in itself may obscure its relationship with iron status. Therefore, ZnPP cannot be assumed to be a first-line diagnostic marker of iron balance in uremic patients.

Minimization of anti-hepatitis B surface antigen immunoglobulins for prophylaxis of hepatitis B viral recurrence in the first month after liver transplantation: the meaning of HBsAg quantitative level at the time of transplant.

BACKGROUND: Hepatitis B virus recurrence after liver transplantation (LT) has practically disappeared with a prophylaxis combining anti-hepatitis B surface antigen Immunoglobulins (HBIg) and antiviral drugs. Recently, cost-saving requirements pushed us to move from a fixed schedule of 50,000 IU intravenous HBIg in the first month after LT to an "on demand" administration guided by close monitoring of HBV surface antigen (HBsAg) and anti-HBV surface Antigen antibody (HBsAb) with a serological target of HBsAg negative and HBsAb>300 mIU/mL. In this context, we investigated the meaning of HBsAg quantitative determination at LT in predicting the need of HBIg in the first month after LT. METHODS: From February 2012 to July 2013, we performed 35 LTs in HBsAg-positive patients, 18 of whom had hepatitis Delta virus coinfection (Delta-positive). Anti-HBV prophylaxis was based on nucleos(t)ide analogues from day 1 post-LT and intravenous HBIg (10,000 IU intraoperatively and, in the following days, 5,000 IU and 2,500 IU pulses to reach and maintain the serological target). RESULTS: The HBsAg quantitative level at LT was significantly higher in Delta-positive recipients. Complete negativization of HBsAg and HBsAb serum level>300 mIU/mL was achieved on day 3 in Delta-positive and on day 2 in Delta-negative. A positive linear correlation between HBsAg quantitative level at LT and HBIg administered in the first month after LT was observed (RHO=.788), with a total of 32,500 IU HBIg used in HDV-positive and 22,000 IU in HDV-negative recipients (P=.0016). Compared to the old schedule, we saved a median of 14,750 IU in HDV-positive and 28,000 IU in Delta-negative. No HBV recurrence was observed in a median follow-up of 10.5 months. CONCLUSIONS: Delta-positive patients need higher doses of HBIg to reach the serological target after LT because they have greater HBsAg quantitative levels at LT. In future studies, pre-LT HBsAg quantitative determination will be helpful to predict the actual need of HBIg early after LT.

Assessment of platelet function analyzer (PFA-100) in kidney transplant patients before renal allograft biopsy: a retrospective single-center analysis.

BACKGROUND: Kidney biopsy (KB) represents the criterion standard to obtain information on diagnosis and prognosis of renal allograft dysfunctions. However, it can be associated with bleeding complications (BCs). Bleeding time test (BTT), the best predictive indicator of post-biopsy BCs, is not a very reproducible test and is invasive. Therefore, the aim of this study was to evaluate whether the platelet function analyzer (PFA-100), a very reliable test to investigate primary hemostasis, could be useful in predicting the risk of bleeding complications in transplant patients undergoing KB. METHODS: We carried out a retrospective analysis of PFA-100 collagen-epinephrine (C-EPI) and collagen-adenosine diphosphate (C-ADP) closure times in 119 patients undergoing KB in our center. Data regarding BTT, age, sex, blood pressure, number of renal allograft punctures for each biopsy procedure, thromboplastin time, prothrombin time, complete blood count, and prophylactic therapy with desmopressin were also collected. Major (need for blood transfusion) or minor (no need for any intervention) BCs (hematoma and hematuria) were recorded. RESULTS: Indications for KB were: delayed graft function (n=23), allograft dysfunction (n=40), proteinuria (n=27), allograft dysfunction plus proteinuria (n=19), and protocol biopsy (n=10). Nine of the 119 patients (7.5%) developed minor BCs (6 macrohematuria, 3 hematoma), major BCs did not develop. No significant differences were found in any of the clinical and laboratory data, including BTT and PFA-100 (C-EPI and C-ADP) between patients who developed BCs compared with those who did not. In addition, there was no correlation between PFA-100 test (C-EPI and C-ADP) values and BTT data [R2=0.002; P=.6]. CONCLUSIONS: The PFA-100 test was not useful in predicting the risk of BCs in kidney transplant patients undergoing renal allograft biopsy.

Analysis of four scoring systems and monocentric experience to optimize criteria for marginal kidney transplantation.

There is a strong need among the transplantation community to identify common criteria to utilize the pool of expanded criteria donors (ECD), considering the disparity between organ demand and supply as well as the benefits of transplantation on long-term mortality compared with survival on dialysis, also in patients transplanted with these organs. The purpose of this article was to analyze scoring systems proposed in literature by Nyberg, Anglicheau, Rao (Kidney Donor Risk Index), and Schold, seeking to verify whether our clinical and histological allocation strategy matched the Nyberg score. Herein we have reported the results of a preliminary retrospective study on the 5-year outcomes of organs from 60 marginal donors, who were older than 50 years and histologically evaluated before implantation. The donors matched Nyberg class C and D, that is, marginal donors. We noted a tendency toward an association between global and vascular scores with class D (odds ratio 2.2 and 4.3, respectively). Kaplan-Meier graft survival curves were similar to Nyberg data: 83% for class C versus 73% for class D at 5 years. Without any comparison to the Nyberg score, the only feature that was predictive of renal function at 5 years in our population was hypertension in the donor. Further studies are required to identify which of the scoring systems--clinical and/or histological--is more suitable to allocate ECD kidneys and to predict recipient outcomes.