Synthesis and photophysical properties of a bichromophoric system hosting a disaccharide spacer.

The synthesis of an efficient energy donor-acceptor system is reported, together with its photophysical properties. The bichromophoric species has been conceived to show potentialities for biological applications since a biocompatible disaccharide spacer, constituted of d-galactose and d-glucose derivatives, was used in compound 12 to connect two BODIPY units with different absorption/emission properties. The luminescence spectrum in acetonitrile of 12 shows an intense fluorescence band with a maximum at about 770 nm that is almost identical to that of the lowest-energy BODIPY, regardless of the excitation wavelength used. The quantum yield is 0.2 with an excited state lifetime of 2.5 ns. Excitation and ultrafast transient absorption spectroscopy demonstrates that a very efficient energy transfer takes place in 12 from the highest-energy lying BODIPY subunit to the lowest-energy emissive BODIPY moiety, with a time constant of about 31 ps. Noteworthily, the emission of 12 falls in the near infrared window, suitable for potential biological applications.

Early cytomegalovirus-specific T-cell response and estimated glomerular filtration rate identify patients at high risk of infection after renal transplantation.

BACKGROUND: Assessing the risk of cytomegalovirus (CMV) viremia in kidney transplant recipients (KTR) may be helpful to indicate in which patient it is worth starting antiviral treatment during preemptive strategy. METHODS: In 40 CMV-seropositive KTR preemptively treated with ganciclovir, we used interferon (IFN)-γ ELISpot test to evaluate whether monitoring T cells directed against phosphoprotein (pp) 65 and immediate early (IE)-1 antigens could predict the onset of viremia. RESULTS: CMV viremia occurred in 24 patients (60%) within 120 days after transplantation. Non-viremic patients had higher anti-pp65, anti-IE-1 T cells, and estimated glomerular filtration rate (eGFR) in the first 90 days after transplantation. At logistic regression, anti-pp65, anti-IE-1 T cells, and eGFR measured at day 30 were significantly associated with CMV infection. Cutoff values of 15 spot-forming cells (SFCs)/200,000 peripheral blood mononuclear cells (PBMCs) for anti-IE, 40 SFCs/200,000 PBMCs for anti-pp65, and 46.6 mL/min/1.73 m(2) for eGFR, respectively, predicted the risk of CMV infection with high sensitivity and specificity (area under the receiver operating characteristic curve >0.75). Using a classification tree model, we identified as high-risk patients those showing anti-pp65 <42 SFCs/200,000 PBMCs and eGFR <62 mL/min/1.73 m(2) , as well as anti-pp65 ≥42 and anti-IE-1 <6.5 SFCs/200,000 PBMCs. CONCLUSION: Monitoring CMV-specific T-cell responses and eGFR in the first month post transplant can identify patients at high risk of CMV infection, for whom preemptive antiviral therapy is recommended.

A Bodipy as a luminescent probe for detection of the G protein estrogen receptor (GPER).

We report the rational design, based on docking simulations, and synthesis of the first fluorescent and selective probe of GPER for bioimaging purposes and functional dissecting studies. It has been conceived as a Bodipy derivative and obtained by accessible and direct synthesis. Its optical properties have been measured in different solvents, showing insensitivity to their polarity. Its binding to GPER was achieved by competition assays with [3H]E2 and [5,6-3H] nicotinic acid in ER-negative and GPER-positive SkBr3 breast cancer cells. SkBr3 cells, transfected with a GPER expression vector containing a FLAG tag, were used to confirm that the fluorophore binds to GPER in a specific manner.

High nerve growth factor blood concentration in renal transplantation: a new prognostic marker?

BACKGROUND: Nerve growth factor (NGF) belongs to the family of neurotropic proteins NGF is markedly expressed in proteinuric renal diseases and in end-stage renal disease; it might be involved in kidney physiopathology. To date, little is known about NGF concentrations in kidney transplant recipients (KTRs). Because NGF exerts its action on cell survival and differentiation, tissue repair, and inflammatory responses, it may also be implicated in the pathogenesis of chronic allograft nephropathy. The aim of this study was to determine circulating NGF concentrations in KTRs and to ascertain their use as a prognostic marker for kidney transplant outcomes. METHODS: Using enzyme-linked immunosorbent assay, we performed quantification of NGF in the serum of 40 prevalent KTRs at baseline and at 6 months. RESULTS: NGF concentrations in KTRs averaged 1.16 ± 0.67 ng/mL. They negative-linearly correlated with recipient age. Logistic multivariate regression analysis showed NGF to be independently associated with increased proteinuria over the 6-month follow-up. CONCLUSIONS: Our data demonstrated that serum concentrations of NGF in KTRs were elevated and that they could be considered to be a prognostic marker in kidney transplantation.

Increasing levels of hemoglobin improve renal transplantation outcomes.

INTRODUCTION: Several studies have reported various data on prevalence of posttransplant anemia (PTA). We have little information about its impact on long-term graft outcomes and few studies of the optimal hemoglobin (Hb) target in kidney transplantation. METHODS: We examined retrospectively 144 kidney transplant recipients of mean age 44.4 ± 12.3 years and follow-up of 40.5 ± 4.6 months. Exclusion criteria were age below 18 years, multiorgan transplantation, and graft failure in the first year. Using simple and multiple linear regression models, we evaluated the potential prediction of a serum concentration of Hb at 1 year after renal transplantation on allograft outcome as measured by Δ% estimated glomerular filtration rate (eGFR), the difference between eGFR, measured with the Modification of Diet in Renal Disease (MDRD) formula, at the end of follow-up, and at 1 year. Multiple models were adjusted for recipient sex, recipient age, donor age, ESA therapy, acute rejection episodes (ARE), days of delayed graft function, human leukocyte antigen mismatches and cold ischemia time. RESULTS: At 1 year after transplantation, the mean Hb level was 13.77 ± 1.87 g/dL in males and 12.52 ± 1.53 g/dL in females. The average eGFR at 1 year was 63.07 ± 25.88 mL/min. At the end of follow-up, the mean Δ% eGFR was -5.73% ± 27.30%. Blood concentration of Hb correlated with donor, recipient sex, ARE, and eGFR at 1 year. There was a close correlation between the Δ% Hb and eGFR upon univariate analysis and the multiple linear regression model. Hb was the only predictor of transplant outcome. CONCLUSIONS: Many factors are involved in kidney allograft function. Among these, Hb is important. In this work we demonstrated that increasing levels of Hb at 1 year after transplantation seemed to predict better preservation of graft function, representing a marker of a good quality graft.

Thyroid status and kidney transplantation outcomes.

INTRODUCTION: It is known that end-stage renal disease patients can display abnormal thyroid gland function, which may cause autoimmune hypothyroidism or subclinical alterations. The impact of thyroid function on graft outcomes is not completely clear among renal transplant patients. The aim of this study was to evaluate thyroid function among a cohort of 136 consecutive renal recipients in correlation with clinical parameters of graft function. MATERIALS AND METHODS: We performed a cross-sectional study on 136 subjects including 84 males and 52 females of overall mean age of 49.71 ± 10.98 years who underwent renal transplantations between 2005 and 2009 and had a mean follow-up of 28.3 ± 15.7 months. All patients were treated with a calcineurin inhibitor, steroids, and mycophenolate mofetil. The exclusion criteria were age below 18 years, multiorgan transplantation, graft failure in the first 6 months, or presence of a thyroid neoplasm. We evaluated levels of serum FT3, FT4, and thyroid-stimulating hormone (TSH) in relation to the following parameters: body mass index (BMI), serum creatinine, estimated glomerular filtration rate estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) formula, proteinuria/24 hours, serum sodium, potassium, calcium, phosphorus, cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, and hemoglobin (Hb). RESULTS: Only 6.4% of our transplant recipients were treated with levothyroxine sodium. The patients showed an average FT3 of 3.24 ± 0.5 mg/dL; average FT4 of 0.84 ± 0.1 mg/dL, and mean TSH of 1.29 ± 0.8 mg/dL. The study showed no relationship between thyroid hormones and age of the transplant, while there was a significant difference in FT3 levels between men and women. We also observed a significant correlation between FT3 and serum creatinine, eGFR, serum sodium, BMI, and Hb; whereas there was no correlation with other variables. The correlations between FT4 and TSH and all examined variables were not significant. CONCLUSIONS: The interactions between the thyroid and the kidney have been incompletely studied among patients with renal transplants. Our data showed that the presence of low serum FT3 levels correlated with worse graft function, anemia, BMI, and serum sodium. Thus low FT3 levels could be predictive of graft function, especially in the 5 years posttransplantation.

Proteinuria is a predictor of posttransplant anemia.

INTRODUCTION: Posttransplant anemia (PTA) involves many factors. Although the link between the hemoglobin (Hb) levels and renal function is known, the relationship between proteinuria and PTA hemoglobin has not been widely explored. The aim of this study was to evaluate whether proteinuria was a predictor of anemia and whether erythropoietin-stimulating agent therapy was a protective factor for kidney damage among transplantation patients. METHODS: We retrospectively examined 144 kidney transplant recipients of mean age 44.4 ± 12.3 years and a mean follow-up period of 40.5 ± 4.6 months. Exclusion criteria were age under 18 years, multiorgan transplantation, proteinuria at 6 months over 1.5 g/d, and transplant failure within the first year. Using regression models, we evaluated the potential predictive power of proteinuria at 6 months after renal transplantation for anemia as expressed by Hb levels at 1 year. RESULTS: The frequency of patients with PTA was 38.89% at 1 year, 35.21% at 2 years, and 31.43% at 3 years. Variables with significant correlations with anemia upon univariate analysis were: proteinuria, donor age, acute rejection, estimated glomerular filtration rate, s-creatinine, and salbumin. Upon multivariate regression analysis 24-hour proteinuria and s-albumin remained independent predictors of 1-year PTA. Univariate analysis among the entire cohort showed a significant correlation between 1-year Hb and proteinuria/24 hours at 6 months (P=.007), an observation that was confirmed in the adjusted model along with recipient sex. Patients were then divided into two groups regarding treatment with erythropoiesis stimulating agents (ESA). Multivariate analysis showed that proteinuria (P=.005) was a predictor of Hb only among the group of patients who did no receive erythropoietin, whereas this relationship disappeared among the group treated with ESA. CONCLUSIONS: These results showed that proteinuria at 6 months was a predictor of Hb levels at 1 year. Treatment of transplant patients with ESA may be a protective factor for renal endothelial damage expressed as proteinuria.

Impact of continuous value of body mass index on graft loss in overweight patients.

INTRODUCTION: High body mass index (BMI) is associated with increased cardiovascular mortality and risk of progression to end-stage renal disease both among the general population and among renal transplant patients. However, in the latter condition no unequivocal studies have been reported in the literature. The aim of our study was to investigate continuous versus categorical values of BMI (World Health Organization classification) as an independent risk factor in renal transplantation. PATIENTS AND METHODS: We retrospectively studied 194 renal transplant patients (128 males and 66 females) whose mean age at transplant was 43.9 years. They had 5 years follow-up. To investigate the association between BMI and graft survival, we performed univariate and multivariate analyses using the Cox regression model. This model was adjusted both for classical covariates (age, gender, time on dialysis, HLA mismatches, donor status) and other covariates as delayed graft function (DGF), acute rejection episodes (AR), and chronic allograft nephropathy (CAN), which are universally recognized to be predictors of graft loss as evidenced by a need for dialysis treatments. RESULTS: At the time of transplantation, the BMI averaged 24.4 +/- 2.65 kg/m(2). Upon univariate analysis, age (P = .049), BMI (P = .005), DGF (P = .009), ARE (P < .0001), and CAN (P = .001) were significantly related to poor transplant outcomes. Upon multivariate analysis, only the BMI value, considered as continuous value (P = .013), DGF (P = .030), and ARE (P < .0001) were significantly related to graft loss. CONCLUSIONS: BMI as a continuous value represented an independent risk factor for renal transplant loss at 5 years. Correction of pretransplant body weight both in overweight (25

Prediction of chronic allograft nephropathy using classification trees.

INTRODUCTION: For its intrinsic potential to mine causal relations, machine learning techniques are useful to identify new risk indicators. In this work, we have shown two classification trees to predict chronic allograft nephropathy (CAN), through an evaluation of routine blood and urine tests. METHODS: We retrospectively analyzed 80 renal transplant patients with 60-month follow-up (mean = 55.20 +/- 12.74) including 52 males and 28 females of overall average age of 41.65 +/- 12.52 years. The primary endpoint was biopsy-proven CAN within 5 years from transplantation (n = 16). Exclusion criteria were multiorgan transplantations, patients aged less than 18 years, graft failure, or patient death in the first 6 months posttransplantation. Classification trees based on the C 4.8 algorithm were used to predict CAN development starting from patient features at transplantation and biochemical test at 6-month follow-up. Model performance was showed as sensitivity (S), false-positive rate (FPR), and area under the receiver operating characteristic curve (AUC). RESULTS: The two class of patients (no CAN versus CAN) showed significant differences in serum creatinine, estimated Glomerular Filtration Rate with Modification of Diet in Renal Disease study formula (MDRD), serum hemoglobin, hematocrit, blood urea nitrogen, and 24-hour urine protein excretion. Among the 23 evaluated variables, the first model selected six predictors of CAN, showing S = 62.5%, TFP = 7.2%, and AUC = 0.847 (confidence interval [CI] 0.749-0.945). The second model selected four variables, showing S = 81.3%, TFP = 25%, and AUC = 0.824 (CI 0.713-0.934). CONCLUSIONS: Identification models have predicted the onset of multifactorial, complex pathology, like CAN. The use of classification trees represent a valid alternative to traditional statistical models, especially for the evaluation of interactions of risk factors.

Decisional trees in renal transplant follow-up.

INTRODUCTION: The predictive potentialities of application of data mining algorithms to medical research are well known. In this article, we have applied to a transplant population classification trees to build predictive models of graft failure, evaluating the interactions between body mass index (BMI) and other risk factors. The decision trees have been widely used to represent classification rules in a population by a hierarchical sequential structure. PATIENTS AND METHODS: We retrospectively studied 194 renal transplant patients with 5 years of follow-up (128 males, 66 females, mean age at time of transplant of 43.9 +/- 12.5 years). Exclusion criteria were: age < 18 years, multiorgan transplant, and retransplant. The BMI was calculated at the time of transplantation. In the classification algorithm, we considered the following parameters: age, sex, time on dialysis, donor type, donor age, HLA mismatches, delayed graft function (DGF), acute rejection episode (ARE), and chronic allograft nephropathy (CAN). The primary endpoint was graft loss within 5-years follow-up. RESULTS: The classification algorithm produced a decision tree that allowed us to evaluate the interactions between ARE, DGF, CAN, and BMI on graft outcomes, producing a validation set with 88.2% sensitivity and 73.8% specificity. Our model was able to highlight that subjects at risk of graft loss experienced one or more events of ARE, developed DGF and CAN, or has a BMI > 24.8 kg/m(2) and CAN. CONCLUSIONS: The use of decision trees in clinical practice may be a suitable alternative to the traditional statistical methods, since it may allow one to analyze interactions between various risk factors beyond the previous knowledge.

Kidney transplantation at Annunziata Hospital of Cosenza: report of 10 years experience.

OBJECTIVE: Kidney transplantation represents the gold standard for treatment of patients with end-stage renal disease. Herein we sought to report our 10-year experience with cadaveric kidney transplantations. PATIENTS AND METHODS: From February 1995 to September 2008, we performed 115 kidney transplantations. Patients were followed for an average of 4.9 years (range, 2.2-10.6 years). The cold ischemia time (CIT) averaged 13 +/- 3 hours, while the mean warm ischemic time was 25 +/- 10 minutes. The ureteral-bladder anastomosis was performed using Bracci catheters in the first series of 72 transplants, and double-J stents in the other 41 cases. The average waiting time was 122 +/- 21 months. The immunological regimens were prescribed according to the American Society of Nephrology (K/DOQI) with reference to comorbidity and concomitant risk factors and reported drug toxicity events. We transplanted kidneys with anatomic variations, ie, multiple arteries and double veins, and one double transplant of marginal organs. RESULTS: Our overall complication rate was 9.18%. The 10-year patient and graft survival rates were 89% and 84%, respectively. The percentage of biopsy-proven acute rejection episodes was 22.16%, while chronic allograft nephropathy (CAN) accounted for 15.3% at 5 years. The incidence of delayed graft function (DGF) was 14.05%. Finally, we noted 3 cases of cardiovascular death. CONCLUSION: Our experience showed excellent patient outcomes compared with other Italian and European data.

[Acute renal failure in granulomatous interstitial nephritis]. / Insufficienza renale acuta secondaria a nefrite granulomatosa interstiziale.

Sarcoidosis is a granulomatous disorder with multiorgan involvement which may appear in an isolated form but more often as a systemic disease. We report the case of a 53-year-old woman presenting with acute renal failure, hypercalcemia, elevated 1.25 dihydroxycholecalciferol, and a history of fatigue, weight loss and arthralgia of several months. Kidney biopsy had revealed interstitial noncaseating granulomas, so sarcoidosis was considered as a potential diagnosis after exclusion of other granulomatous disorders. Granulomatous tubulo-interstitial nephritis (GIN) is an uncommon disease with a low, but perhaps underestimated incidence: only about 100 cases have been described in the literature. In these cases it was found that the disease may lead to deterioration of renal function and irreversible progress to end-stage renal disease. The treatment of choice is the administration of steroids.

[Myoglobinuric acute renal failure secondary to convulsion]. / Insufficienza renale acuta mioglobinurica secondaria a convulsioni.

Myoglobinuric acute renal failure secondary to convulsion.

[Polyomavirus BK nephropathy in renal transplant: 2 cases with different clinical expressions and review of the literature]. / Nefropatia da Poliomavirus BK nel trapianto renale: 2 casi con espressione clinica diversa e revisione della letteratura.

INTRODUCTION: Polyomavirus BK nephropathy is emerging as a significant cause of interstitial nephritis and allograft dysfunction (1-2). CASE REPORT: Two patients with renal transplants from cadaveric kidneys were treated with Tacrolimus plus Mycophenolate Mofetil (MMF) and Cyclosporine plus MMF, respectively. Their renal function gradually deteriorated eight to twelve months after the transplant. The renal biopsy of the first patient showed signs of significant interstitial tubulite, which necessitated the anti-rejection therapy with intravenous steroid pulses. After the pulses there was an additional dramatic increase in plasmatic creatinine, which suggested a revaluation of the kidney biopsy because of suspected Polyomavirus BK (BKV) nephropathy. In fact, after a more careful review, the suspicion of BKV infection was confirmed by the presence of intranuclear inclusions of tubular epithelium cells and marked denudation of the tubular basal membrane. The subsequent screening in both cases confirmed the presence of decoy cells in the urine, while the immunohistochemical analysis of the renal biopsy was strongly positive for the SV40 antigen. Our diagnosis was that of interstitial nephritis due to Polyomavirus BK that, in the first patient, was expressed by more aggressive clinical progress, probably due to enhanced immunosuppression from incorrect diagnosis of the interstitial rejection. The pre-transplant clinical outcome of the first patient was characterised by proteinuric nephropathy without any histological confirmation. Furthermore, we observed abundant pre-transplant residual diuresis and glucose intolerance. All these elements led us to hypothesise that native kidneys could have a fundamental role as viral reservoirs. CONCLUSION: Even though we reconfirm the decisive role of the immunosuppressive therapy and of the donor s kidney as the fundamental causes of Polyomavirus reactivation, we believe that it cannot be the result of a possible active role by the native kidney. In fact, as already noted, the SV40 genome is important in the pathogenesis of focal gomerulosclerosis. Furthermore, reports of polyoma nephropathy in not-yet-transplanted patients could accredit the role of the native kidneys as important viral reservoirs capable of inducing nephropathy in renal transplant patients.

Renal tubular function by lithium clearance in liver cirrhosis.

Increased tubule sodium reabsorption has been largely suspected in liver cirrhosis (LC), however studies in humans have produced contrasting results. Therefore to ascertain the entity of renal sodium handling in LC this study was devised. A total of 13 patients with child A LC were studied along with 26 age-sex matched healthy controls (HC). Patients and controls were kept on daily Na-intake of 100 mmol for at last 1 week, by measuring glomerular filtration rate (GFR; inulin) and lithium clearance. We have calculated (1) C(Li); (2) the absolute reabsorption of isotonic fluid in the proximal tubule (APR) as GFR - C(LI); (3) the fractional proximal sodium reabsorption (FPRNa) as 1 - (C(Li)/GFR); (4) the absolute distal reabsorption of sodium (ADRNa) as (C(LI) - C(Na)) x P(Na;) and (5) the fractional distal sodium reabsorption (FDRNa) as (C(LI) - C(Na))/C(Li). GFR was significantly lower in LC (P<.001), C(Li) was significantly higher in LC than in HC (P<.001). APRNa and FPRNa were reduced in LC (P<.0001). ADRNa was higher in LC than in HC (P<.001). No difference was found for FDRNa. In conclusion, lithium clearance discloses an increase sodium reabsorption in distal tubule in humans with LC.

Berengario da Carpi.

Berengario da Carpi was magister of anatomy and surgery at the University of Bologna from 1502 to 1527. Eustachio and Falloppia defined him as 'the restaurator of anatomy'. He was a great surgeon, anatomist and physician of illustrious patients including Lorenzo II dei Medici, Giovanni dalle Bande Nere, Galeazzo Pallavicini, Cardinal Colonna, and Alessandro Soderini. He had strong links to the intellectuals of his time (Forni, Bonamici, Manuzio, Pomponazzi) as well as with the Medici family. He was respected by the Popes Julius II, Leo X and Clement VII. His main contributions are the Isogogae Breves, De Fractura calvae sive cranei, and the illustrated Commentaria on the Anatomy of Mondino de Liucci, a textbook utilized for more than 200 years, which Berengario aimed to restore to its initial text. The Commentaria constitutes the material for the last part of this paper which concludes with a personal translation of some passages on 'The kidney', where the author gives poignant examples of experimental ingenuity.

A contribution to the history of common salt.

Salt has influenced human nutrition, health, politics, taxation, economy, freight, transport, and commerce throughout the ages. All human activities have been influenced by salt including economy, religious beliefs and practices, art, literature, psychoanalysis, superstitions, and exorcism. Salt is recognized as a symbol for friendship, hospitality, chastity, alliance, table fellowship, fidelity, fertility, blessing, curse and endurance, etc. The Bible is the first book of salt and contains no fewer than 24 references to this substance. In the Gospels the parable of salt is a central one. Many many church fathers have written on salt a substance, which up to 1969 was a relevant element in the rite of Baptism. This paper reviews the importance of common salt for human life, and by drawing from various scientific and literary sources makes a special discussion of its various symbolisms.