HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis. / La infección por VHB es un factor de riesgo de enfermedad renal crónica: revisión sistemática y metaanálisis.

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.

Is there an association between severity of illness and psychiatric symptoms in patients with chronic renal failure?

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.

Pregnancies in women receiving renal transplant for lupus nephritis: description of nine pregnancies and review of the literature.

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.

Predictors of renal survival in ANCA-associated vasculitis. Validation of a histopatological classification schema and review of the literature.

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.

A randomized study evaluating cinacalcet to treat hypercalcemia in renal transplant recipients with persistent hyperparathyroidism.

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.

Antiviral therapy (pegylated interferon and ribavirin) of hepatitis C in dialysis patients: meta-analysis of clinical studies.

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.

Meta-analysis of observational studies: hepatitis C and survival after renal transplant.

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.

Hepatitis C virus infection and glomerular disease.

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.

Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years.

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.

Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality?

Recent evidence has been accumulated showing that anti-HCV-positive serologic status is significantly associated with lower survival in dialysis populations, but the mechanisms underlying this negative relationship are still unclear. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus (HCV) infection on all-cause and disease-specific mortality of patients on regular dialysis. The relative risk of all-cause, cardiovascular and liver disease-related mortality 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 with HCV across the published studies. We identified fourteen observational studies involving 145 608 unique patients on long-term dialysis. Pooling of study results demonstrated that anti-HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all-cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25-1.47. Stratified analysis showed that the adjusted RR for liver disease-related death was 3.82 (95% CI, 1.92; 7.61); heterogeneity statistics, R(i) = 0.58 (P-value by Q-test = 0.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10; 1.45); no heterogeneity was found (NS). This meta-analysis of observational studies indicates that anti-HCV-positive patients on dialysis have an increased risk of either liver or cardiovascular disease-related mortality compared with anti-HCV-negative patients. Further studies are in progress to understand better the link between HCV and cardiovascular risk among patients on maintenance dialysis.

Interferon therapy of acute hepatitis C in dialysis patients: meta-analysis.

The efficacy and safety of antiviral therapy in patients with acute hepatitis C on long-term dialysis remains unclear, although a number of small clinical studies have been published addressing this issue. We evaluated the efficacy and safety of interferon therapy in chronic dialysis patients with acute 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 eight clinical studies (173 unique patients), three (37.5%) being controlled clinical trials (CCTs). Among CCTs, the viral response was much more common in study (patients on antiviral therapy) than control (patients who did not receive therapy) groups; the pooled odds ratio of SVR being 27.06, 95% Confidence Intervals (95% CI), 9.26; 79.1 (P = 0.00001). No difference in the dropout rate between study and control patients was shown, odds ratio = 0.920 (95% CI, 0.367; 1.92), NS. Pooling all study results (n = 8 studies) demonstrated that the summary estimate for SVR and dropout rate was 58% (95% CI, 38; 77) and 9% (95% CI, 4; 14), respectively. The most frequent side-effects requiring interruption of the treatment were flu-like symptoms (n = 4, 18%), followed by haematological changes and loss to follow-up. A strong relationship between increasing age and reported dropout rate was recognized (P = 0.001). The studies were heterogeneous with regard to SVR but not to dropout rate. Our meta-analysis of CCTs showed that the viral response after antiviral therapy was more common than the spontaneous viral clearance in dialysis patients with acute hepatitis C. Pooled analysis demonstrated that IFN-based therapy of acute hepatitis C in dialysis populations gives SVR in around one half of patients. These results support IFN-based therapy for acute hepatitis C in patients on maintenance dialysis.

A novel model of in vitro osteocytogenesis induced by retinoic acid treatment.

Despite recent research which more and more stresses the importance of osteocytes in regulating bone and systemic mineral metabolism, current molecular and functional knowledge of osteocyte properties are still incomplete, mostly due to limited availability of in vitro models. Osteocytes are terminally differentiated dendritic cells, and therefore are not easy to obtain and maintain in primary cultures. As an alternative, osteocyte differentiation can be induced by progressive osteoblast embedding in mineralised extracellular matrix. In this model, which is suitable for reproduction of bone development, the presence of calcified matrix prevents several cell biological methods from being used. Therefore, the osteocyte-like MLO-Y4 cell line continues to be the most widely used cellular system. Here we show that treatment of primary osteoblasts or MC3T3-E1 cells with retinoic acid generates a homogeneous population of ramified cells with osteocyte features, as confirmed by morphological and molecular analyses. The first morphological changes are detectable in primary cells after 2 days of treatment, and in the cell line after 4 days of treatment. Differentiation is complete in 5 and 10 days, respectively, with progressive development of dendrites, loss of the ability to produce extracellular matrix, down-regulation of osteoblast markers, and up-regulation of osteocyte-specific molecules, most notably among them sclerostin. Compared to other published protocols, our method has a number of advantages. It is easy to perform and does not require special instrumentation, it is highly reproducible, and rapidly generates a mature osteocyte population in the complete absence of extracellular matrix, allowing the use of these cells for unlimited biological applications.

Intradermal vs intramuscular vaccine against hepatitis B infection in dialysis patients: a meta-analysis of randomized trials.

Chronic dialysis patients are at risk of contracting hepatitis B virus infection and have a diminished immune response to hepatitis B virus vaccine. Recent reports support intradermal administration of hepatitis B virus vaccine in patients on regular dialysis but the efficacy and safety of this approach remain unclear. We conducted a meta-analysis of randomized, controlled clinical trials to compare seroprotection achieved by intradermal vs intramuscular hepatitis B vaccine, in patients on maintenance dialysis. Meta-analysis of data from 718 adults (14 trials) on long-term dialysis demonstrated that intramuscular hepatitis B vaccination was less likely to achieve seroprotection than intradermal vaccination, the pooled odds ratio was 0.454 (95% CI, 0.3; 0.67), P = 0.001. The test of study heterogeneity was not significant. This difference did not persist during follow-up (6-60 months after completing vaccine schedule), the pooled odds ratio being 0.718 (95% CI, 0.36; 1.47), NS. Some evidence of significant heterogeneity including publication bias was present but stratified analysis in various subgroups showed that this issue did not meaningfully change our results. Intradermal hepatitis B vaccine was safe and well tolerated. We conclude that intradermal hepatitis B vaccine induces a superior response rate compared to intramuscular route at completion of vaccine cycle, despite a lower vaccine dose. No significant advantage was found over longer follow-up. It remains unclear whether the higher seroprotection rate achieved with intradermal route translates into a lower frequency of de novo hepatitis B among patients on maintenance dialysis.

Hepatitis C virus and the immunological response to hepatitis B virus vaccine in dialysis patients: meta-analysis of clinical studies.

It is well known that the seroconversion rate of patients following hepatitis B virus (HBV) vaccination is lower in uraemic than healthy subjects. A variety of inherited or acquired factors have been implicated in this diminished response, and the high prevalence of hepatitis C virus (HCV) infection among patients on maintenance dialysis has been suggested to play a role. However, the impact of HCV on the immune response to HB vaccine in patients receiving long-term dialysis is not entirely understood. Here, we evaluate the influence of HCV infection on the immunological response to HBV vaccine in dialysis population by performing a systematic review of the literature with a meta-analysis of clinical studies.We used the random-effects model of DerSimonian and Laird with heterogeneity and sensitivity analyses. The end-point of interest was the rate of patients showing seroprotective anti-hepatitis B titres at completion of HBV vaccine schedule among HCV-positive versus HCV-negative patients on chronic dialysis. We identified eight studies involving 520 unique patients on long-term dialysis. Aggregation of study results did not show a significant decrease in response rates among HCV-infected versus noninfected patients [pooled odds ratio = 0.621 (95% CI, 0.285; 1.353)]. The P-value was 0.007 for our test of study heterogeneity. Stratified analysis in various subgroups of interest did not meaningfully change our results. Our meta-analysis showed no association between immunological response to hepatitis B vaccine and HCV infection in individuals on long-term dialysis. These results support the use of recombinant vaccine against hepatitis B in patients on regular dialysis with HCV infection.

Combined antiviral therapy of hepatitis C virus in dialysis patients: meta-analysis of clinical trials.

The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long-term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with heterogeneity and sensitivity analyses. We identified 10 clinical studies (151 unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long-term haemodialysis. The summary estimate for SVR and drop-out rate was 56% [95% Confidence Intervals (95% CI) 28-84] and 25% (95% CI, 10-40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg-IFN, peg-IFNalfa-2a or alfa-2b), trial design (controlled or cohort study), or clinical characteristics of patients (naïve, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop-out rate. Combination antiviral therapy (interferon plus ribavirin) gives encouraging results in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta-analysis hampers definitive conclusions.

Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium levels in patients with secondary hyperparathyroidism irrespective of its severity.

AIMS: To evaluate the relationship between the severity of secondary hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet. MATERIALS AND METHODS: In this post hoc analysis, data were pooled from three randomized, placebo-controlled trials in which dialysis patients with iPTH ≥ 300 pg/ml were dose-titrated with cinacalcet or placebo in addition to conventional treatment to achieve iPTH ≤ 250 pg/ml. In 953 patients analyzed (cinacalcet, 545; placebo, 408), baseline iPTH levels were categorized in 100 pg/ml intervals (300 - ≥ 1,000 pg/ml), and the impact of baseline iPTH on changes in iPTH, phosphate (P), calcium (Ca) and calcium- phosphate product (Ca × P) was evaluated. RESULTS: Cinacalcet reduced iPTH (47% reduction), P (9%), Ca (7%), and Ca × P (15%) across all subgroups. For patients receiving cinacalcet, the mean percentage reduction from baseline in iPTH varied from 35 to 55%, being consistently decreased across the severity subgroups. The mean absolute change in iPTH was more pronounced in patients with higher baseline iPTH levels, particularly in the ≥ 1,000 pg/ml subgroup vs. the other subgroups. However, as baseline iPTH levels increased, iPTH ≤ 250 pg/ml was achieved in fewer patients. A trend towards greater absolute change from baseline was observed for P in patients with more severe disease (iPTH ≥ 800 pg/ml) treated with cinacalcet compared with patients with less severe disease (iPTH 300 - < 800 pg/ml). CONCLUSIONS: Cinacalcet lowers plasma iPTH and serum P, Ca and Ca × P levels in dialysis patients with SHPT, regardless of disease severity. Patients with more severe disease experienced greater reductions in PTH and P, but fewer achieved iPTH ≤ 250 pg/ml by the efficacy assessment phase. Use of cinacalcet when baseline PTH is lower may result in more stable control of SHPT and help to control bone and mineral alterations.

HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis.

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.

Oxidative stress and homocysteine metabolism in patients with lupus nephritis.

The objective of this study was to compare oxidative status and homocysteinemia in patients with lupus nephritis (LN) and in controls. Total antioxidant capacity (TAC), reactive oxygen species (ROS), homocysteine and related vitamins were measured in 68 patients with LN and in 50 controls. LN patients had lower TAC (p = 0.05) and higher ROS and homocysteinemia (p = 0.01) than controls. TAC, significantly lower in active than in quiescent LN (p = 0.01), was correlated with albuminemia (p = 0.02), inversely with proteinuria (p = 0.01) and anti-DNA antibodies (p = 0.004). ROS values, higher both in active and in inactive LN, correlated with age (p = 0.02), C-reactive protein (CRP) (p = 0.0005) and inversely with prednisone dosage (p = 0.05). At multivariate analysis, CRP (p = 0.04) and age (p = 0.005) were independent ROS predictors. Homocysteine, higher in active than in quiescent LN (p = 0.016) and in patients with antiphospholipid antibodies (p=0.05), correlated with serum creatinine (p = 0.00001) and proteinuria (p = 0.015). At multivariate analysis serum creatinine (p = 0.006) and active nephritis (p = 0.003) were independent predictors of hyperhomocysteinemia. Patients with LN showed impaired oxidative status, even without clinical signs of renal activity. ROS production may be counterbalanced by adequate antioxidant capacity in some patients with quiescent LN. The association of hyperhomocysteinemia and antiphospholipid antibodies positivity may increase the risk of cardiovascular and/or thrombotic events in LN patients.

Vitamin D and subclinical cardiac damage in a cohort of kidney transplanted patients: a retrospective observational study.

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.

Are laboratory tests useful for monitoring the activity of lupus nephritis? A 6-year prospective study in a cohort of 228 patients with lupus nephritis.

OBJECTIVES: To evaluate the role of immunological tests for monitoring lupus nephritis (LN) activity. METHODS: C3, C4, anti-dsDNA and anti-C1q antibodies were prospectively performed over 6 years in 228 patients with LN. RESULTS: In membranous LN only anti-C1q antibodies differentiated proteinuric flares from quiescent disease (p = 0.02). However, in this group 46% of flares occurred with a normal value of anti-C1q antibodies versus 20% in proliferative LN (p = 0.02). In patients with antiphospholipid antibodies (APL), 33% of flares occurred with normal levels of anti-C1q antibodies versus 14.5% in patients that were APL-negative (p = 0.02). In proliferative LN, anti-C1q antibodies showed a slightly better sensitivity and specificity (80.5 and 71% respectively) than other tests for the diagnosis of renal flares. All four tests had good negative predictive value (NPV). At univariate analysis anti-C1q was the best renal flare predictor (p<0.0005). At multivariate analysis, the association of anti-C1q with C3 and C4 provided the best performance (p<0.0005, p<0.005, p<0.005 respectively). CONCLUSIONS: Anti-C1q is slightly better than the other tests to confirm the clinical activity of LN, particularly in patients with proliferative LN and in the absence of APL. All four "specific" tests had a good NPV, suggesting that, in the presence of normal values of each, active LN is unlikely.