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1.
Rev. clín. esp. (Ed. impr.) ; 221(10): 600-611, dic. 2021. tab, graf
Article in Spanish | IBECS | ID: ibc-227042

ABSTRACT

Antecedentes El papel del virus de la hepatitis B (VHB) como factor de riesgo en la incidencia y progresión de la enfermedad renal crónica (ERC) no ha sido clarificado. Objetivo Evaluamos el impacto producido por la infección con el VHB sobre el riesgo de la ERC en la población general. Material y métodos Llevamos a cabo una revisión sistemática de la literatura médica publicada a fin de evaluar si existe, en la población adulta general, una relación entre la infección por el VHB y un aumento del riesgo de ERC. Adoptamos el modelo de efectos aleatorios de DerSimonian y Laird para proporcionar una estimación resumida del riesgo de ERC (definida por una tasa de filtración glomerular reducida y/o una proteinuria detectable) por infección con el VHB en los estudios publicados. También se realizaron metarregresiones y análisis estratificados. Resultados Recogimos 33 estudios (n=7.849.849 pacientes) publicados en 26 artículos y se realizó un metaanálisis por separado conforme a los resultados. La agrupación de los resultados de los estudios de cohortes (11 estudios, n=1.056.645 pacientes) demostró una relación entre un estatus serológico VHB positivo y el aumento de la incidencia de la ERC, con una estimación resumida para la HR ajustada con VHB en todas las encuestas del 1,40 (IC 95% 1,16-1,69; p<0,001). Se observó heterogeneidad entre estudios (valor Q: 49,5; p<0,0001). En el subconjunto de estudios transversales no se detectó relación entre el VHB y la prevalencia de la ERC (10 estudios; n=3.222.545 pacientes; OR ajustada 1,04; IC 95% 0,90-1,218; p=0,5). Los análisis de metarregresión informaron de una relación entre el estatus HBcAg positivo y la incidencia de ERC en la población general (p<0,015). Conclusiones Parece que la exposición a la infección por VHB está asociada con un aumento en el riesgo de desarrollar ERC en la población adulta general. Se están realizando estudios destinados a comprender los mecanismos responsables de dicha asociación (AU)


Background The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. Aim We evaluated the impact of infection with HBV on the risk of CKD in the general population. Material and methods We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. Results We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). Conclusions It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way (AU)


Subject(s)
Humans , Renal Insufficiency, Chronic/virology , Hepatitis B, Chronic/complications , Glomerular Filtration Rate , Risk Factors
2.
Rev Clin Esp (Barc) ; 221(10): 600-611, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34183297

ABSTRACT

BACKGROUND: The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM: We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS: We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS: We retrieved 33 studies (n = 7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n = 1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P < .001). Between-study heterogeneity was noted (Q value, 49.5, P < .0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n = 3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P = .5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P < .015). CONCLUSIONS: It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.


Subject(s)
Hepatitis B , Renal Insufficiency, Chronic , Adult , Cross-Sectional Studies , Hepatitis B/complications , Hepatitis B/epidemiology , Hepatitis B virus , Humans , Renal Insufficiency, Chronic/epidemiology , Risk Factors
3.
Sci Rep ; 10(1): 19160, 2020 11 05.
Article in English | MEDLINE | ID: mdl-33154468

ABSTRACT

In 178-kidney transplanted patients (KTxp), the prevalence of hypovitaminosis-D, the presence and novel development of left ventricular hypertrophy(LVH) and the correlations between native Vitamin-D (25OHD) and LVH were evaluated during the 1st year of transplantation (KTx). Clinical and instrumental data were recorded at pre-KTx and at one (T1) and 12 (T12) months after KTx. 25OHD levels were considered sufficient (s25OHD, ≥ 30 ng/dL) or insufficient (i25OHD, < 30 ng/dL). 25OHD correlated at T1 with parathormone(PTH), and at T12 with 25OHD-T1 and PTH-(T1,T12). At T12, s25OHD (15%) had higher 25OH and alkaline phosphatase (ALP), lower Ca, at T1, and lower PTH-(T1, T12) than i25OH-T12. At T1, KTxp with LVH (LVH-T1pos, 42%) were older and with longer dialysis vintage than LVH-T1neg. At T12, KTxp with LVH (LVH-T12pos, 53%) were older, with higher systolic blood pressure (SBP) at T12 than LVH-T12neg. No relation between 25OHD and LVH were found. Novel LVH was found in 14% of KTxp. They were older, had higher SBP-T12 and lower serum albumin-T12 than the others. LVH-modifications and 25OHD were not correlated. Hypovitaminosis-D is highly prevalent in KTxp. LVH correlates with different risk factors according to the time elapsed from KTx. However, during the 1st year of KTx, no relationship between LVH and 25OHD was observed.


Subject(s)
Hypertrophy, Left Ventricular/epidemiology , Kidney Transplantation , Transplant Recipients , Vitamin D Deficiency/epidemiology , Vitamin D/blood , Adult , Age Factors , Alkaline Phosphatase/blood , Calcium/blood , Female , Humans , Hypertrophy, Left Ventricular/blood , Male , Middle Aged , Parathyroid Hormone/blood , Prevalence , Retrospective Studies , Serum Albumin , Vitamin D Deficiency/blood
4.
Rev Clin Esp ; 2020 Feb 06.
Article in English, Spanish | MEDLINE | ID: mdl-32037008

ABSTRACT

BACKGROUND: The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. AIM: We evaluated the impact of infection with HBV on the risk of CKD in the general population. MATERIAL AND METHODS: We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. RESULTS: We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). CONCLUSIONS: It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way.

5.
Sci Rep ; 9(1): 6869, 2019 05 03.
Article in English | MEDLINE | ID: mdl-31053792

ABSTRACT

Coronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0-233]. At T5 AS was 119 [1-413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs.


Subject(s)
Coronary Artery Disease/epidemiology , Kidney Transplantation/statistics & numerical data , Vascular Calcification/epidemiology , Adult , Cohort Studies , Coronary Artery Disease/mortality , Coronary Artery Disease/pathology , Disease Progression , Female , Follow-Up Studies , Humans , Male , Middle Aged , Vascular Calcification/mortality , Vascular Calcification/pathology
6.
Transplant Proc ; 51(3): 707-714, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30979454

ABSTRACT

Single-antigen bead (SAB) platform permits the identification of antibodies not detectable by complement-dependent lymphocytotoxicity test, but their clinical significance is not completely understood. The aim of this study was to evaluate whether the presence of pretransplant SAB-detected antibodies is associated with the development of allograft failure. This is a single-center cohort study with 10-year follow-up in which 573 kidney recipients with negative pretransplant complement-dependent lymphocytotoxicity crossmatch who received transplants at the Kidney Transplant Center of Policlinico, Milan, from deceased donors between 1996 and 2005 were evaluated. Pretransplant plasma samples were retrospectively analyzed by SAB assay. Survival analyses were performed to assess the risk of allograft failures by SAB-detected antibodies. Pretransplant antibodies were found in 160 (28.0%) recipients, of whom 42 subsequently developed an allograft failure for a survival rate of 70.9% (95% confidence interval [CI), 63.5-78.4). Among those without antibodies, 58 (14.0%) returned to dialysis with a survival rate of 84.7% (95% CI, 81.0-88.4). In Cox regression analyses, patients with SAB-positivity had 2-fold higher risk of allograft failure than those who were SAB-negative (hazard ratio, 2.07; 95% CI, 1.39-2.79). Results did not change after adjustment for putative confounders. In conclusion, in this single-center cohort, 10-year allograft survival rate was significantly influenced by the presence of SAB-detected antibodies.


Subject(s)
Graft Survival/immunology , HLA Antigens/immunology , Histocompatibility Testing/methods , Isoantibodies/immunology , Kidney Transplantation/methods , Adult , Cohort Studies , Female , Graft Rejection/immunology , Humans , Isoantibodies/analysis , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies
7.
Psychol Health Med ; 23(8): 970-979, 2018 09.
Article in English | MEDLINE | ID: mdl-29334234

ABSTRACT

Chronic renal failure (CRF) is a frequent condition in elderly subjects, and it is associated with psychiatric comorbidity, especially depressive symptoms. Purpose of the present research was to compare patients with different severity of chronic kidney disease (CKD) in terms of psychiatric symptoms. One hundred CKD subjects were randomly selected among those attending the Department of Nephrology, University of Milan. The patients were evaluated through the following rating scales: Mini-Mental State Examination (MMSE), Beck Depression Inventory (BDI), Symptom Checklist (SCL-90), Kidney Disease Quality of Life- Short Form (KDQOL-SF) and Cumulative Illness Rating Scale (CIRS). A multivariable linear regression analysis was performed considering eGFR as continuous-dependent variable and rating scale scores as independent variables. A worse eGFR significantly correlated with the score about the effects of kidney disease on daily life (r = 0.25, p = 0.01) and the burden of kidney disease (r = 0.18, p = 0.05). Statistical significance of kidney disease on daily life persisted also in the final multivariate model (t = 2.04, p = 0.04). Severity of renal dysfunction seems to influence few psychiatric outcomes, particularly those related to quality of life and daily functioning. This result might depend on the over-worrying derived from the necessity to start a renal replacement therapy in the near future.


Subject(s)
Cognitive Dysfunction/psychology , Depression/psychology , Quality of Life/psychology , Renal Insufficiency, Chronic/psychology , Aged , Aged, 80 and over , Anxiety/psychology , Comorbidity , Cross-Sectional Studies , Female , Glomerular Filtration Rate , Humans , Kidney Failure, Chronic/physiopathology , Kidney Failure, Chronic/psychology , Linear Models , Male , Multivariate Analysis , Psychiatric Status Rating Scales , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index
10.
Bone ; 83: 35-47, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26476373

ABSTRACT

INTRODUCTION: AHSG, a serum glycoprotein with recognized anti-calcification activity, has also been suggested to modulate both bone formation and resorption. Though the bulk of AHSG is mostly synthesized in the liver, it has been claimed that also bone cells might produce it. However, the extent of the bone AHSG production and the potential controlling factors remain to be definitively proven. A relevant number of studies support the notion that FGF23, a bone-derived hormone, not only regulates the most important mineral metabolism (MM) related factors (phosphate, parathyroid hormone, vitamin D, etc.), but might be also involved in cardiovascular (CV) outcome, both in chronic kidney disease (CKD) patients and in the general population. Furthermore, in addition to some direct autocrine and paracrine effects in bone, FGF23 has been suggested to interact with AHSG. In this study we investigated if AHSG is really produced by bone cells, and if its bone production is related and/or controlled by FGF23, using cultured bone cells, according to a new method recently published by our group. RESULTS: Our data show that AHSG is consistently produced in osteocytes and to a far lesser extent in osteoblasts. Both FGF23 addition to the culture medium and its over-expression in osteocytes were associated with a consistent increase of both AHSG mRNA and protein, while FGF23 silencing was followed by opposite effects. Though most of these results were largely affected by the blockage of FGF23 receptors, the role of these receptors in the different experimental sets is still not completely clarified. In addition, we found that FGF23 and AHSG proteins co-localized both in cytoplasm and nucleus, which suggests a possible reciprocal interactivity. CONCLUSIONS: Our data not only confirm that AHSG is produced in bone, mainly in osteocytes, but show for the first time that its production is modulated by FGF23. Since both proteins play important roles in the bone and cardiovascular pathology, these results add new pieces to the puzzling relationship between bone and vascular pathology, in particular in CKD patients, prompting future investigations in this field.


Subject(s)
Fibroblast Growth Factors/metabolism , Osteocytes/metabolism , alpha-2-HS-Glycoprotein/biosynthesis , Animals , Cattle , Cells, Cultured , Culture Media , Fibroblast Growth Factor-23 , Fibroblast Growth Factors/genetics , Fluorescent Antibody Technique , Gene Expression Regulation/drug effects , Gene Silencing/drug effects , Humans , Male , Mice, Inbred BALB C , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteocytes/drug effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Receptors, Fibroblast Growth Factor/antagonists & inhibitors , Receptors, Fibroblast Growth Factor/metabolism , Recombinant Proteins/pharmacology , Tibia/drug effects , Tibia/metabolism , Time Factors , alpha-2-HS-Glycoprotein/genetics
11.
Clin Exp Rheumatol ; 33(2 Suppl 89): S-56-63, 2015.
Article in English | MEDLINE | ID: mdl-26016751

ABSTRACT

OBJECTIVES: In 2010 a histopathological classification of ANCA-associated glomerulonephritis was proposed to predict the outcomes at diagnosis. Our aim was to validate the proposed classification in our cohort of patients and to compare the studies already published. METHODS: The data of 93 patients who underwent kidney biopsy in a single Italian centre within 15 years were retrospectively collected. RESULTS: The 10-year renal and patients' survival were 60% and 81%, respectively. Biopsies were classified as 21% focal, 30% crescentic, 39% mixed and 10% sclerotic. Survival without ESRD at 5 years was 82% in focal, 37% in crescentic, 81% in mixed and 51% in sclerotic group. The Kaplan-Meier analysis highlights that renal survival was not different between sclerotic and crescentic groups (p=0.9) but both had a significantly worse prognosis than focal (p=0.04 and 0.015 respectively) and mixed groups (p=0.05 and 0.03 respectively). Focal and mixed groups had the same renal survival (p=0.7). At multivariate analysis the independent predictors of end-stage renal disease were less than 20% of normal glomeruli at kidney biopsy (p=0.022), high serum creatinine (p=0.009) and arterial hypertension at presentation (p= 0.006). CONCLUSIONS: In our cohort, the proposed histological classification was not predictive of renal prognosis. The focal and the mixed classes had the same prognosis and a significantly better renal outcome than both the crescentic and the sclerotic classes. At multivariate analysis among the histological features only less than 20% of normal glomeruli defines the renal prognosis together with renal function and arterial hypertension at baseline.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/pathology , Glomerulosclerosis, Focal Segmental/pathology , Hypertension/etiology , Kidney Failure, Chronic/pathology , Kidney Glomerulus/pathology , Adult , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Cohort Studies , Creatinine/blood , Disease Progression , Female , Glomerulosclerosis, Focal Segmental/etiology , Humans , Kaplan-Meier Estimate , Kidney/pathology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/etiology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors
12.
Lupus ; 24(11): 1210-3, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25908479

ABSTRACT

BACKGROUND: Few data are available on pregnancy in renal transplanted women for lupus nephritis (LN). METHODS: Among 38 women with LN who received a renal transplant in our Unit, three had nine pregnancies. During the pregnancies, patients were followed by a multidisciplinary team including gynecologists and nephrologists. RESULTS: Two patients received a living related and one a deceased kidney transplant. The immunosuppressive therapy consisted of steroids calcinurin inhibithors and mycophenolate mofetil. The last drug was substituted with azathioprine in prevision of pregnancy. All patients had normal renal function and urinalysis. In two patients some signs of immunological activity persisted after transplantation. Five pregnancies ended in miscarriage and four in live births. Two pregnancies were uneventful. Pre-eclampsia occurred in a hypertensive patient in two pregnancies that ended in preterm delivery in one case and in a small for gestation age in both cases. And finally, follow-up graft function and urinalysis continued to be normal in all patients. CONCLUSIONS: After renal transplantation our LN women continue to have frequent miscarriages. The other pregnancies ended in live births and, with the exception of pre-eclampsia in a hypertensive patient, no renal or extra-renal complications occurred during or after pregnancy, even in cases with active immunological tests.


Subject(s)
Kidney Failure, Chronic/physiopathology , Kidney Transplantation , Lupus Nephritis/physiopathology , Lupus Nephritis/surgery , Pregnancy Complications/etiology , Abortion, Spontaneous/etiology , Adult , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Antibodies, Antinuclear/analysis , Antihypertensive Agents/therapeutic use , Azathioprine/therapeutic use , Female , Humans , Immunosuppression Therapy/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/etiology , Lupus Nephritis/drug therapy , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Pre-Eclampsia/physiopathology , Prednisone/administration & dosage , Prednisone/therapeutic use , Pregnancy , Pregnancy Complications/drug therapy , Pregnancy Outcome
14.
Am J Transplant ; 14(11): 2545-55, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25225081

ABSTRACT

Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels (≤11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value<10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcet- versus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p<0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p=0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p<0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.


Subject(s)
Hypercalcemia/drug therapy , Hyperparathyroidism/complications , Kidney Transplantation , Naphthalenes/therapeutic use , Adult , Bone Density , Bone Remodeling , Calcium/blood , Cinacalcet , Double-Blind Method , Female , Humans , Hypercalcemia/complications , Male , Middle Aged , Naphthalenes/adverse effects , Phosphorus/blood , Placebos
15.
J Viral Hepat ; 21(10): 681-9, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25040244

ABSTRACT

Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Renal Dialysis , Ribavirin/therapeutic use , Adult , Aged , Antiviral Agents/adverse effects , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/methods , Drug Therapy, Combination/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Interferon-alpha/adverse effects , Male , Middle Aged , Ribavirin/adverse effects , Treatment Outcome , Viral Load
16.
Minerva Urol Nefrol ; 66(2): 139-49, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24988205

ABSTRACT

The association between hepatitis C virus (HCV) infection and chronic kidney disease (CKD) is well established and remains an area of intense research. HCV infection is associated with a large spectrum of histo-pathological lesions in both native and transplanted kidneys. The frequency of kidney damage in HCV-infected patients appears low even if is not fully detailed. The most frequent HCV-associated renal lesion is type I membrano-proliferative glomerulonephritis, usually in the context of type II mixed cryoglobulinemia. Various approaches have been tried for the treatment of HCV-related glomerulonephritis, including immunosuppressive therapy (corticosteroids and cytotoxic agents), plasma exchange and antiviral agents. Antiviral treatment of HCV-associated glomerulonephritis has shown encouraging results. Immunosuppressive therapy is particularly recommended for cryoglobulinemic kidney disease. Two distinct approaches should be considered for the treatment of HCV-associated cryoglobulinemic glomerulonephritis according to the level of proteinuria and kidney failure. Some evidence on rituximab therapy for HCV-related cryoglobulinemic glomerulonephritis exists but several questions related to its use need to be addressed.


Subject(s)
Hepatitis C, Chronic/complications , Renal Insufficiency, Chronic/etiology , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antiviral Agents/therapeutic use , Clinical Trials as Topic , Cryoglobulinemia/drug therapy , Cryoglobulinemia/etiology , Cryoglobulinemia/virology , Glomerular Filtration Rate , Glomerulonephritis, Membranoproliferative/etiology , Hematuria/etiology , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C, Chronic/drug therapy , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Interferons/therapeutic use , Kidney Transplantation , Nephritis, Interstitial/etiology , Postoperative Complications/virology , Proteinuria/etiology , RNA, Viral/blood , Rituximab , Viremia/complications
17.
J Thromb Haemost ; 12(9): 1440-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24853860

ABSTRACT

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy characterized by hemolysis, platelet consumption, and renal injury. Eculizumab, a mAb that blocks complement activity, has been successfully used in aHUS. OBJECTIVES: To optimize eculizumab therapy in aHUS patients by monitoring complement functional tests and markers of disease activity. PATIENTS/METHODS: We studied 18 patients with aHUS (10 males; eight females; age range, 2-40 years) treated with eculizumab to induce and/or maintain disease remission. Patients were followed up for a cumulative observation period of 160 months, during which blood samples were obtained at various time intervals to measure complement activity (Wieslab for the classical, alternative and mannose-binding lectin complement pathways) and the parameters of disease activity (haptoglobin and lactate dehydrogenase serum levels, and platelet count). The intravenous eculizumab doses of 12-33 mg kg(-1) were initially administered every week, with the interval between doses being gradually extended to 2 weeks, 3 weeks and 4 weeks on the basis of strict laboratory and clinical control. RESULTS: Complement activity was normal before eculizumab treatment, regardless of the state of the disease (activity or remission). It was completely suppressed 1 week, 2 weeks and 3 weeks after the last eculizumab infusion (mean values ± standard deviation: 1% ± 1% to 3% ± 5% for both the classical and alternative pathways; P = 0.0001 vs. baseline), and partially suppressed after 4 weeks (22% ± 26% and 16% ± 27%; P = 0.0001 vs. baseline). The increase in the time interval between eculizumab infusions did not change disease activity markers. CONCLUSIONS: Monitoring complement tests can allow a safe reduction in the frequency of eculizumab administration in aHUS while keeping the disease in remission.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/drug therapy , Complement C3/antagonists & inhibitors , Complement C5/antagonists & inhibitors , Adolescent , Adult , Atypical Hemolytic Uremic Syndrome/genetics , Blood Platelets/metabolism , Child , Child, Preschool , Complement C3/chemistry , Complement C5/chemistry , Complement Factor H/chemistry , Female , Hemolysis , Humans , Kidney Transplantation , Male , Mutation , Platelet Count , Remission Induction , Thrombotic Microangiopathies/drug therapy , Time Factors , Young Adult
18.
J Viral Hepat ; 21(5): 314-24, 2014 May.
Article in English | MEDLINE | ID: mdl-24716634

ABSTRACT

Recent evidence has shown that anti-HCV-positive serologic status is significantly linked to lower patient and graft survival after renal transplant, but conflicting results have been given on this point. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of HCV infection on all-cause mortality and graft loss after RT. The relative risk of all-cause mortality and graft loss was regarded as the most reliable outcome end-point. Study-specific relative risks were weighted by the inverse of their variance to obtain fixed- and random-effect pooled estimates for mortality and graft loss with HCV across the published studies. We identified eighteen observational studies involving 133 530 unique renal transplant recipients. The summary estimate for adjusted relative risk (aRR) of all-cause mortality was 1.85 with a 95% confidence interval (CI) of 1.49; 2.31 (P < 0.0001); heterogeneity statistics, Ri = 0.87 (P-value by Q-test = 0.001). The overall estimate for adjusted RR of all-cause graft loss was 1.76 (95% CI, 1.46; 2.11) (P < 0.0001), heterogeneity statistics, Ri = 0.65 (P-value by Q-test = 0.001). Stratified analysis did not change meaningfully these results. Meta-regression showed that living donor rate had a favourable influence on patient (P = 0.031) and graft survival (P = 0.01), whilst diabetes mellitus having a detrimental role on patient survival (P = 0.001). This meta-analysis of observational studies supports the notion that HCV-positive patients after RT have an increased risk of mortality and graft loss. Further studies are in progress to understand better the mechanisms underlying the relationship between HCV and mortality or graft dysfunction after renal transplant.


Subject(s)
Graft Survival , Hepatitis C/mortality , Kidney Transplantation/adverse effects , Transplant Recipients , Adult , Aged , Female , Humans , Male , Middle Aged , Survival Analysis , Young Adult
19.
Transplant Proc ; 45(7): 2715-7, 2013 Sep.
Article in English | MEDLINE | ID: mdl-24034030

ABSTRACT

Hyperbilirubinemia often accompanies liver failure; therefore, artificial liver support devices are currently used as a bridge to more definitive treatments to eliminate water-soluble and albumin-bound toxins. We report 2 patients, of which, after liver transplantation, the first experienced early allograft dysfunction and the other hyperbilirubinemia linked to chronic rejection. After 3 cycles of coupled plasma filtration adsorption (CPFA), the bilirubin promptly decreased in both cases. CPFA is an extracorporeal therapy that uses plasma filtration associated with an adsorbent cartridge and hemofiltration to remove cytokines and inflammatory mediators associated with septic shock, severe sepsis, and multiple organ dysfunction syndrome. Each cycle of treatment lowered the bilirubin of our patients by ∼40%. CPFA deserves attention as a potential inexpensive short-lasting device to treat hyperbilirubinemia after liver surgery or transplantation. Moreover, the effects of CPFA should be further studied to address inflammatory mediators in chronic rejection after liver transplantation or other immunologic disorders.


Subject(s)
Hyperbilirubinemia/etiology , Liver Transplantation/adverse effects , Adsorption , Female , Humans , Male , Middle Aged , Plasmapheresis/methods
20.
Lupus ; 22(8): 810-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23764764

ABSTRACT

Whether the long-term patient and renal survival of those diagnosed with lupus nephritis (LN) has improved over the decades is still debated. Eighty-nine patients diagnosed between 1968 and 1990 entered this study and their outcome was evaluated after 20 years. At presentation 54% of patients had class IV LN, 39.3% had renal insufficiency and 59.5% had nephrotic syndrome. Patients were divided into two groups: Group 1 consisted of 30 patients diagnosed between 1968 and 1980; Group 2 consisted of 59 patients diagnosed between 1981 and 1990. In Group 1 patient survival at 20 years was 84% versus 95% in Group 2 (p=0.05). Survivals without end-stage renal failure were respectively 75% and 84% at 20 years (p=0.05). Survivals without severe infection at 20 years were 44% in Group 1 and 66.5% in Group 2 (p=0.02). Survivals without cardiovascular events at 20 years were: 53% in Group 1 and 90% in Group 2 (p=0.005). At presentation, patients in Group 1 had higher serum creatinine (1.96 vs 1.15 mg/dl, p=0.01), higher activity index (8 vs 5.5, p=0.01), lower hematocrit (31% v s6%, p=0.008) and lower serum C4 levels (p=0.04) than Group 2 patients. Patients in Group 1 also received less frequent methylprednisolone pulses (43% vs 81%, p=0.0006). In Italian patients with LN, long-term life expectancy and renal survival progressively improved over the decades, while morbidity progressively declined. An earlier referral and refinement of therapy achieved this goal.


Subject(s)
Kidney Failure, Chronic/epidemiology , Lupus Nephritis/physiopathology , Nephrotic Syndrome/epidemiology , Renal Insufficiency/epidemiology , Adolescent , Adult , Creatinine/blood , Female , Follow-Up Studies , Glucocorticoids/administration & dosage , Hematocrit , Humans , Italy , Kidney Failure, Chronic/etiology , Life Expectancy , Male , Methylprednisolone/administration & dosage , Nephrotic Syndrome/etiology , Outcome Assessment, Health Care , Renal Insufficiency/etiology , Survival Rate , Time Factors , Young Adult
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