BACKGROUND: Prevalence and pathogenicity of hepatitis G virus infection in long-term renal transplant recipients, are not fully known. AIM: To evaluate long-term impact of HGV infection on liver disease of renal transplanted patients. PATIENTS AND METHODS: A total of 155 hepatitis B surface antigen negative kidney transplant recipients, followed for a mean of 11 years after renal transplantation, were studied. Of these 48 (31%) patients had persistently elevated serum aminotransferase values. Frozen serum samples were tested for HGV-RNA and HCV-RNA by nested reverse transcribed polymerase chain reaction, and for anti-hepatitis G virus and anti-hepatitis C virus by enzyme-linked immunosorbent assay Hepatitis C virus-RNA was typed by a line probe assay and quantified by a branched DNA signal amplification assay RESULTS: Hepatitis G virus-RNA was detected in 37 (24%) patients and anti-hepatitis G virus in another 26 (17%). Seventy (45%) patients had serum anti-hepatitis C virus and 63 of these (90%) had serum hepatitis C virus-RNA. Hepatitis G virus-RNA positive and negative patients were similar in terms of age, sex, duration of dialysis, rate of transfusion, chronic liver disease, rate of hepatitis C virus infection and immunosuppressive therapy. Fifteen (41%) hepatitis G virus-RNA seropositive patients were hepatitis C virus co-infected. Hepatitis C virus-RNA levels were significantly lower in the 15 hepatitis C virus/hepatitis G virus co-infected patients than in the 48 patients with hepatitis C virus infection only (2.2 vs 10.8 MEq/ml, p = 0.02). Only 3 hepatitis G virus carriers had persistently elevated alanine aminotransferase compared to 29 hepatitis C virus carriers (14% vs 60%, p < 0.001), 10 patients co-infected with both hepatitis G virus and hepatitis C virus, and in 6 patients with neither infection (67% vs 8%, p < 0.001). CONCLUSIONS: Hepatitis G virus infection is common among kidney transplant patients, it carries a low risk of chronic liver disease even in long-term follow-up. Low levels of hepatitis C virus-RNA found in hepatitis G virus carriers suggest an interaction between these two viruses in immunosuppressed patients.

Adult↗

PubMedDate not supplied

Role of proteinuria reduction in the progression of IgA nephropathy.

UNLABELLED: Proteinuria has been shown to play a causal role in the progression towards ESRD of IgA nephropathy (IgAN). We demonstrated that steroids are effective in reducing proteinuria and preserving renal function. AIM: to evaluate the long-term effect of steroids in IgAN patients (6th year evaluation) and better clarify the role of proteinuria reduction in slowing down the progression. METHODS: multicenter randomized controlled trial of 86 adult IgAN patients with serum creatinine < or = 1.5 mg/ dL and moderate proteinuria. They received either supportive therapy or methylprednisolone 1-g i.v. for three days at months 1, 3, and 5, plus oral prednisone (0.5 mg/kg every other day for six months). RESULTS: Proteinuria significantly decreased in the treated patients (from 2.0+/-0.60 g/24 h at baseline to 1.0+/-0.68 g/24 h at six months) and remained stable till the 6th year (0.67+/-0.5 g/24 h), it slightly decreased in the control group. Six-year renal survival was significantly better in the steroid than in the control group: 9 patient (20.9%) in the steroid group and 15 (34.8%) in the control group reached the primary end-point of a 50% increase in serum creatinine from baseline. Five controls and none of the steroid-treated patients started dialysis. Steroid-treated patients did not experience any major side effects during follow-up. CONCLUSIONS: Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN patients. Early reduction of proteinuria could also be marker of a persistent reduction in its levels over time and of a better outcome in the long term.

Adult↗

PubMedDate not supplied

Combined treatment with steroids and azathioprine in IgA nephropathy: design of a prospective randomised multicentre trial.

Corticosteroids have had variable success in IgA nephropathy (IgAN). Our previous trial with a six-month course of steroids in IgAN patients showed they were effective in reducing the risk of renal function deterioration and proteinuria, but this effect seemed to decrease in the long term. This new randomised trial was designed to prospectively evaluate whether adding low-dose azathioprine to steroids improves long-term renal survival in adult biopsy-proven IgAN patients with proteinuria > or = 1 g/24 h and plasma creatinine < or = 2.0 mg/dl. The patients will be treated with steroids (methylprednisolone 1 g i.v. for three consecutive days at months 1, 3 and 5, plus oral prednisone 0.5 mg/kg every other day for six months) plus azathioprine 1.5 mg/kg/day for six months or steroids alone with the same schedule. Altogether a minimum of 346 patients should be enrolled within a four-year recruitment period. The planned duration of follow-up is five years.

Adolescent↗

PubMedDate not supplied

Renal transplantation, past, present and future.

In the absence of immunosuppression, renal transplantation was sporadically and unsuccessfully performed during the first half of this century. Over the past 40 years, immunosuppressive drug regimens have evolved greatly and transformed solid-organ transplantation into a routine clinical procedure with a 1-year graft survival between 80% and 90%. The original immunosuppressive scheme was based on the administration of glucocorticoids and azathioprine. However, many patients developed acute rejection which required very high dose of prednisone. As a consequence, a high mortality rate due to opportunistic infections was frequently observed, since this immunosuppressive regimen nonselectively inhibited elements of host resistance such as monocytes, granulocytes, and macrophages. In the early Eighties, the introduction of monoclonal antibodies directed against the CD3 molecule and of cyclosporine, a lymphokine synthesis inhibitor, allowed a more effective control of acute allograft rejection and a more specific target with maintenance immunosuppression. Furtherly, with the knowledge of molecular immunology the better understanding of the cellular and molecular mechanisms that underlie the immunological response to transplanted organs, led to the discovery of new immunosuppressive agents, such as tacrolimus, rapamycin, interleukin-2 monoclonal antibodies, and mycophenolate mofetil. All these drugs showed a more selective mechanism for T- and B-cell alloimmune responses. The results of recent clinical trials based on the combination of these drugs with steroids and cyclosporine reduced the incidence of acute rejection episodes to less than 10% and permitted a steroid-sparing policy in kidney transplantation. Today, the main problem is related to the side-effects of vigorous and prolonged immunosuppression, mainly infections and malignancies. If it were possible to obtain permanent immunological tolerance, immunosuppressive therapy could be minimized. In this respect, the new generation of drugs, FTY 20, antisense oligonucleotides and agents capable of blocking the costimulatory pathway of allorecognition, might have the potential of favoring tolerance in the host against alloantigens.

Acute Disease↗

PubMedDate not supplied

Preliminary evaluation of incremental peritoneal dialysis in 25 patients.

BACKGROUND: Incremental dialysis has been suggested for patients with some residual renal function. However, very little published clinical data exist on the feasibility of this schedule. OBJECTIVES: To assess feasibility of incremental dialysis, with regard to its effect, complications, and impact on quality of life. DESIGN: Pilot prospective study, not controlled. SETTING: Nephrology division, public clinical research hospital. PATIENTS: Twenty-five patients (19 men, mean age 61+/-13 years, body weight 63+/-11 kg) began peritoneal dialysis (the first treatment of uremia) with a single nightly exchange lasting 10 hours or 2 daily exchanges over 12 hours according to creatinine clearance and Kt/N. Patients gave informed consent and reported their work activity, degree of rehabilitation, and their quality of life by answering a questionnaire prepared for this purpose. OUTCOME MEASURES: Survival rate, complications related to peritoneal dialysis, and residual renal and peritoneal clearances. RESULTS: During the study period no patient died. Complications related to dialysis were peritonitis (0.41 episodes/year) and exit-site infection (0.32 episodes/year). All patients continued to work with full rehabilitation and considered 1 or 2 exchanges per day less troublesome than 3 or 4. CONCLUSIONS: Incremental dialysis is well accepted by patients and staff. This technique does not involve a high risk of complications and is economical. Therefore incremental dialysis is feasible.

Adult↗

PubMedDate not supplied

Lupus nephritis.

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Adrenal Cortex Hormones↗

PubMedDate not supplied

Renal transplantation strengths and shortcomings.

Although renal transplantation remains the treatment of choice for many uremic patients there are still problems not completely solved. The risk of acute rejection can be minimized by the modern immunosuppression but many grafts fail in the long-term because of the so-called chronic allograft nephropathy, which can be caused both by alloantigen dependent and independent mechanisms. Recurrent renal disease is another important cause of failure in the long-term. Death represents the second cause of failure. Cardiovascular complications, infections, and cancer are the most frequent causes of death. Careful selection of the candidate tailored immunosuppression, aggressive diagnostic and therapeutic approaches are needed to minimized mortality in transplant recipients. However, the main limit for the success of transplantation is the shortage of donors. Use of marginal donors, non-heart-beating donors, and living unrelated donors has been recommended by many authorities to overcome the shortage of organs.

Acute Disease↗

PubMedDate not supplied

[Living-donor kidney transplantation in the cyclosporine era].

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.

Adolescent↗

PubMedDate not supplied

[Natural history of hepatitis B virus infection in dialysis patients: prospective study by quantitative analysis of HBV viremia].

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.

DNA, Viral↗

PubMedDate not supplied

[Hepatopathy and hepatitis B virus infection in dialysis patients: cross-sectional study].

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.

Aged↗

PubMedDate not supplied

[The Lorenzo syndrome (Lorenzo de' Medici)].

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Art↗

PubMedDate not supplied

[Natural history of hepatitis C virus infection in dialysis].

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.

Acute Disease↗

PubMedDate not supplied

[Natural history of HBV in 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.

Antiviral Agents↗

PubMedDate not supplied

[HCV-related liver disease in hemodialysis population: clinical and biochemical characteristic].

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.

Hepatitis C, Chronic↗