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This article collects the personal stories of the young doctors who in the early sixties contributed to the birth and development of the Croff pavilion at the Policlinico Hospital in Milan. Inaugurated on October 19, 1964, this has been the first institute in Italy entirely devoted to patients with kidney diseases. Since its inception, it has significantly contributed to the progress of nephrology thanks to important and pioneering investigations in the main fields of our specialty, which still continue nowadays. The different stories reported here follow the chronological order in which the young doctors arrived at Croff, each story representing a personal narrative that interweaves and integrates that of others. This gives rise to a vivid many-voiced account, from which emerge not only the figures of these young doctors, but also those of patients, nurses, and laboratory technicians., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Innate immunity is the first barrier against pathogen infection and has also the important function of activating the adaptive immunity. The receptors of innate immunity, such as toll-like receptors and other receptors, recognize as danger signals the molecular patterns of pathogens as well as those of endogenous molecules released by dying cells. The information is transmitted to adapter proteins that, through a chain of kinases that translate the signal to transcription factors regulating inflammatory genes. In the inflammatory milieu dendritic cells become mature, intercept the antigen and migrate to lymphoid organs where they present the antigen to naïve T cells. Complement also exerts an important role of bridge between innate and adaptive immunity. In donor-deceased kidney transplantation, the innate immunity is triggered in the donor by brain death and is aggravated by the cold ischemia and even more by reperfusion. Once activated, innate immunity produces a local inflammatory environment leading to dendritic cell maturation and complement activation. Dendritic cells present the alloantigen to T cells and induce their differentiation towards effector Th1 and Th17 while inhibiting Th2 and T regulatory cells. A main goal of the current research in transplantation is to obtain an immunological tolerance. Experimental studies showed the possibility of inducing operative tolerance in murine models and even in primates with the infusion of regulatory dendritic cells. However, there are no data with this technique in clinical transplantation.

Hepatitis C virus (HCV) infection remains frequent among patients on maintenance dialysis. It has been claimed that infrequent and slight abnormalities in serum aminotransferase activity could occur in dialysis patients with HCV. We describe a 61-year-old male patient on maintenance dialysis who acquired HCV by a nosocomial route. The natural history of HCV in this patient over 8 yrs featured frequent and high increases in serum aminotransferase and gamma-glutamyl transpeptidase (gamma-GT) levels. In December 2001, serum GOT and GPT were, respectively, 965 and 1294 UI/L; gamma-GT activity was 241 UI/L. HCV genotype was 2a/2c; median HCV RNA values in serum were 2.3 x 10⁵ UI/mL (range, 1.14 x 10⁴ to 4.6 x 10⁵ UI/mL). Total bilirubin, serum albumin, and colinesterase levels remained normal over the entire follow-up. Liver biopsy was not performed and interferon (IFN) therapy was not given. Currently, biochemical liver tests (GOT/GPT/gamma-GT) are in the upper range of normal values and the patient remains viremic. Efficacy and tolerability of initial monotherapy with IFN for chronic hepatitis C among dialysis patients are briefly discussed. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in the dialysis population.

Dialysis patients remain at risk of acquiring hepatitis B virus (HBV) infection. The issue of the natural history of HBV among patients undergoing long-term dialysis remains unclear. Assessing the natural history of hepatitis B in patients on maintenance dialysis is problematic because of the unique characteristics of this population: serum aminotransferase activity is lower in dialysis patients compared with patients without renal disease; also, chronic hepatitis B has an insidious and prolonged natural history, and the competing mortality from complications of end-stage renal disease may obscure the long-term consequences of hepatitis B. HBV-related liver disease frequently runs an asymptomatic course in dialysis patients and the liver-related mortality in this population is very low; thus, the prognosis for chronic HBV infection in dialysis patients has been reported as benign. However, the frequency of liver cancer in dialysis patients appears higher than that observed in the general population, this has been related to a greater exposure to HBV/HCV. Cirrhosis is not a frequent comorbid condition in the dialysis population of industrialised countries, but the death rate for dialysis patients with cirrhosis is 35% higher than for those without it. In addition, it has been observed that liver disease remains a significant cause of mortality among HbsAg-positive carriers on dialysis in developing countries. The low viral load measured in dialysis patients with persistent HBsAg carriage could be accounted for by the relatively benign course of HBV-related liver disease in this population. Prospective clinical trials are under way to better define the virological features of HBV in the dialysis population.

Dialysis patients remain at risk for acquiring hepatitis C virus (HCV) infection. The issue of the natural history of HCV infection among patients undergoing long-term dialysis is surrounded by great controversy. An accurate assessment of the clinical outcomes of HCV in end-stage renal disease (ESRD) is hampered by numerous items, namely the primary features of the disease: its onset is rarely recognized and its course is prolonged exceedingly. Viral, host, and/or environmental factors may influence the outcome of chronic HCV infection but their precise role in promoting disease progression are yet to be defined in dialysis patients. It is well known that HCV-related liver disease usually runs an asymptomatic course and the liver-related mortality in the dialysis population is very low. In addition, it has been suggested that the HD procedure may exert a protective effect on the course of HCV and several mechanisms have been advocated to this purpose. However, the rate of persistence of HCV after acute hepatitis C is probably extremely high among dialysis patients. Recently a strong and independent relationship between HCV status and survival in the dialysis population has been observed. The frequency of liver cancer in dialysis patients appears higher than that seen in the general population. These findings have been obtained by several prospective studies with adequate size and long follow-ups. The natural history of HCV in patients on long-term dialysis will be better defined as more data are generated from ongoing studies. Dialysis patients desperately need effective and safe antiviral agents for the treatment of HCV-related liver disease.

Background: The natural history of hepatitis B virus (HBV) infection in patients undergoing maintenance dialysis is still unclear. The aim of this study was to measure the HBV viral load (HBV DNA) in a cohort (n=20) of HBsAg positive chronic dialysis patients over a 12-month observation period. METHODS; HBV DNA was measured by the Amplicor HBV MonitorTM Test Kit, an in vitro test that utilizes Polymerase Chain Reaction (PCR) nucleic acid amplification and DNA hybridisation for the quantitative measurement of hepatitis B viral DNA in human serum. Amplicor HBV MonitorTM Test Kit amplifies a sequence in the pre-Core/Core region of the HBV genome with biotinylated and non-biotinylated oligonucleotide primers., Results: There was no significant difference between the median HBV load at the start and the end of the study, 1.85 x 104 HBV copies/ml (percentile 16.84; 6.35 x 102 - 3.5 x 106 HBV copies/ ml) and 8.5 x 103 HBV copies/ml (percentile 16.84; 5.5 x 102 - 6.38 x 105 HBV copies/ml), respectively. These serum HBV DNA levels were lower than those measured by the same test in patients with chronic hepatitis B and normal renal function (Hepatology 2000; 32: 116-23). In the group of HBsAg positive carriers on dialysis, we identified three patterns of HBV viremia over time: 1) patients (n=6) with persistent HBV DNA, 2) those (n=2) with undetectable HBV DNA and 3) those (n=12) with intermittent HBV DNA. Patients with persistent HBV DNA (median, 3.3 x 104 HBV copies/ml; percentile 16.84; 3.5 x 103 - 2.3 x 106 HBV copies/ml) had higher viral HBV load than those with intermittent HBV viremia (median, 1.2 x 103 HBV copies/ml; percentile 16.84; 3.5 x 102 - 2.3 x 104 HBV copies/ml) (p=0.0001). Patients with persistent HBV DNA had higher frequency of serum hepatitis B e antigen (HBeAg) positivity than those showing intermittent and negative HBV DNA, 50% (3/6) vs. 0% (p=0.04). The frequency of serum IgM antibody against hepatitis B core antigen (IgM anti-HBc) was higher in patients with persistent HBV DNA than those having intermittent or negative HBV DNA, 100% (6/6) vs. 33% (4/12), p=0.03. We detected no difference in aminotransferase activity between patients with persistent HBV DNA and those showing intermittent or negative HBV DNA. In the group with persistent HBV DNA, the mean difference between maximum and minimum values of HBV DNA observed in each individual patient was 6.13+/-1.25 decimal logarithm (Log10) and in patients with intermittent HBV DNA 3.87+/-1.49 Log10 (p=0.006). In the entire group, the fluctuations in HBV DNA values over time between and within individuals were not significant., Conclusions: The viremic HBV load was low and relatively stable over a 12-month follow-up period; three patterns of HBV viremia over time were observed; 30% of the viremic patients had persistent HBV viremia, and those patients had larger viral load and higher frequency of HBeAg and anti-HBc IgM than did patients with intermittent or negative HBV DNA. Prospective studies with longer observation periods are in progress to fully understand the natural history of HBV in these immunosuppressed patients.

Background: Control of spread of HBV infection in dialysis units in developed countries has been one of the major advances in managing end-stage renal disease (ESRD). Patients with chronic HBV, however, continue to enter the population pool of dialysis patients and transplant candidates. The clinical significance related to the presence of HBsAg in serum of dialysis patients has not been completely understood., Aim and Methods: We collected demographic, biochemical and virological data from a large (n=464) population of patients on maintenance dialysis. This was done to assess the influence of virological and host factors on hepatocellular damage, as shown by serum aminotransferase activity., Results: The frequency of HBsAg positivity in our dialysis population was 8.2 % (38/464); the rate of HBsAg positive patients showing HBe antigen was 20.6% (7/34). Twenty-two (84.6%) of 26 HBsAg positive patients showed detectable HBV DNA in serum by Amplicor HBV MonitorTM Test. HBsAg positive patients had serum aminotransferase activity significantly higher than HBsAg negative individuals; GOT (AST) 25.1+/-29.9 vs. 16+/-21.5 UI/L (p=0.001), and GPT (ALT) 31.3+/-52.5 vs. 17.7+/-21.9 UIL (p=0.034). In the subset of HBsAg positive dialysis patients, those in the replicative phase HBeAg positive) had aminotransferase activity higher than HBeAg negative individuals, AST, 42.3+/-43.6 vs. 22.4+/-27.3 UI/L (p=0.097) and ALT, 49.41+/-54.7 vs. 29.17+/-55.76 UI/L (NS) respectively. We did a multivariate analysis by standard least square model on the entire patient group and we found independent and significant association between detectable HBsAg in serum and AST (p=0.0089)and ALT (p=0.0159) values. There was an independent and significant relationship between age and ALT (p=0.01)., Conclusions: In our study group, HBsAg positive patients on dialysis had serum aminotransferase activity significantly higher than that measured in HBsAg negative individuals. However, mean transaminase levels in HBsAg positive patients on dialysis were below the upper limit of normal for the reference range of healthy controls. HBsAg positive dialysis patients with active viral replication showed the greatest liver damage. Studies are in progress to understand further HBV-related liver disease in dialysis population.

Background: Renal transplantation is the best possibile form of treatment for chronic renal failure. It offers the patient a longer life expectancy when compared to dialysis. Aim of the study was to evaluate our results with live donor transplantation and the variables that influenced the long-term patient and graft survival., Methods: 190 patients received a live donor kidney transplantation in our Hospital between 1984 and 2000. Thirty-eight of them received a graft from an HLA identical donor, 130 from an HLA haploidentical donor, 22 from a living unrelated donor (spouse). Fourteen patients underwent a pre-emptive transplantation. Aim of the study was to evaluate which variables could influence the long-term patient and graft survival., Results: The median follow-up of recipients was 69.5 months. The 10-year patient and graft survival were 94.7% and 73.4% respectively. Graft half-life was 29.6 years. Six patients died. Twelve patients lost their graft because of vascular thrombosis and five patients because of rejection within the first six months. After the first year, 11 patients lost their graft because of chronic rejection and 4 after recurrence of the original disease. One hundred and forty-four patients are still under observation, and at the last examination their mean plasma creatinine was 2.0+/-1.1 mg/dl. At univariate statistical analysis the absence of locus DR incompatibility was associated with a trend toward a better long-term survival of both patient and graft (P=0.05), while less than one year of dialysis showed a significantly better survival rate (P < 0.01)., Conclusions: Living-donor transplantation offers an excellent long-term patient and graft survival.

The Kallmann's syndrome is a rare nosological phenomenon characterized by hypogonadotropic hypogonadism and anosmia. In 1944, Kallmann first studied the genetic aspects of this syndrome in three different families in which 11 subjects suffered of deafness, syncinesis, brain disorders or skeletal anomalies along with olfactory dysfunction. In these patients histological studies revealed either a degeneration in the olfactory bulb tract or a generalized hypoplasia of the olfactory system. In the light of the presence of brain lesions and the possible association with several other endocrine pathologies, hypogonadism should be related to a diminished increase of releasing factors from the hypothalamus. At present the Kallmann's syndrome is considered a genetic syndrome linked to the X-chromosome. The hypothalamus is a genetic disorder target gland and its eventual close connection to the olfactory system could explain endocrine as well as olfactory pathology. Several recent studies carried out on mice by M. Schwanzel-Fukuda and D. Pfaff showed that neurons expressing Luteinizing hormone-releasing hormone (LH-RH) are located in the nervus terminalis, a cranial nerve that is a part of the accessory olfactory system and which projects directly from the nose to the septal-preoptic nuclei in the brain. Clinically, these data could explain the gonadotropin deficiency in association with olfactory dysfunction in the Kallmann's syndrome. In this paper the Authors report two cases of Kallmann's syndrome: a 41-year-old male with eunuchoidism and anosmia, and a 7-year-old child with hypospadia and anosmia.

We report our experience of 202 cadaveric renal transplant performed over a 9 year period. Actuarial patient survival rate was 87.5% at 1 year and 81% at 9 years; graft survival rate was 58.5% at 1 year and 43% at 9 years. In order to improve patient and graft survival, from September 1977 renal transplantation was performed only in patients with a previous careful clinical selection and who had received at least three blood transfusions. Out of 18 patient, actuarial patient and graft survival rate at 1 year were 100% and 76% respectively.

32 graft rejection episodes requiring dialysis within four days appeared in the first month after transplantation in 224 renal transplants. Our report shows that oliguric renal failure is not related to the severity of rejection but probably to the appearance of an acute tubular necrosis. Therefore graft renal failure requiring dialysis is not necessarily related to a bad prognosis.