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1.
Phys Rev Lett ; 118(14): 141803, 2017 Apr 07.
Article in English | MEDLINE | ID: mdl-28430473

ABSTRACT

We present direct detection constraints on the absorption of hidden-photon dark matter with particle masses in the range 1.2-30 eV c^{-2} with the DAMIC experiment at SNOLAB. Under the assumption that the local dark matter is entirely constituted of hidden photons, the sensitivity to the kinetic mixing parameter κ is competitive with constraints from solar emission, reaching a minimum value of 2.2×10^{-14} at 17 eV c^{-2}. These results are the most stringent direct detection constraints on hidden-photon dark matter in the galactic halo with masses 3-12 eV c^{-2} and the first demonstration of direct experimental sensitivity to ionization signals <12 eV from dark matter interactions.

2.
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
3.
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
4.
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
5.
Lupus ; 19(1): 65-72, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19933721

ABSTRACT

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.


Subject(s)
Homocysteine/metabolism , Lupus Nephritis/metabolism , Oxidative Stress , Adult , Antioxidants/metabolism , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Reactive Oxygen Species/metabolism
6.
Exp Cell Res ; 315(5): 849-62, 2009 Mar 10.
Article in English | MEDLINE | ID: mdl-19167380

ABSTRACT

Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.


Subject(s)
Cell Transformation, Viral , Endogenous Retroviruses/physiology , Melanoma/virology , Virus Activation/physiology , Caco-2 Cells , Cell Proliferation , Cell Transformation, Viral/genetics , Cells, Cultured , Clone Cells/virology , Disease Progression , Endogenous Retroviruses/genetics , Humans , Jurkat Cells , K562 Cells , Melanocytes/pathology , Melanocytes/ultrastructure , Melanocytes/virology , Melanoma/etiology , Melanoma/genetics , Melanoma/pathology , Models, Biological , RNA, Viral/isolation & purification , Virion/growth & development , Virus Activation/genetics
7.
Ann Rheum Dis ; 68(2): 234-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18718989

ABSTRACT

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.


Subject(s)
Lupus Nephritis/diagnosis , Adult , Antibodies, Antinuclear/blood , Autoantibodies/blood , Biomarkers/blood , Complement C1q/immunology , Complement C3/metabolism , Complement C4/metabolism , DNA/immunology , Epidemiologic Methods , Female , Humans , Male , Middle Aged , Severity of Illness Index , Young Adult
8.
J Nephrol ; 32(1): 139-150, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30628019

ABSTRACT

Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21-18% and 25%, moderate in 22-30% and 26% and severe in 30-18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD-. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.


Subject(s)
Cell Adhesion Molecules/metabolism , Kidney Diseases/etiology , Kidney Transplantation/adverse effects , Kidney/metabolism , Leukocyte Common Antigens/metabolism , Vimentin/metabolism , Adult , Biomarkers/metabolism , Biopsy , Epithelial-Mesenchymal Transition , Female , Fibrosis , Graft Survival , Humans , Immunohistochemistry , Kidney/pathology , Kidney/physiopathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Kidney Diseases/physiopathology , Male , Middle Aged , Time Factors , Treatment Outcome
9.
G Ital Nefrol ; 25 Suppl 44: S68-S75, 2008.
Article in Italian | MEDLINE | ID: mdl-19048589

ABSTRACT

Approximately 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). In some cases with a rapidly progressive course, treatment may result in partial recovery of renal function. The choice of aggressive treatment should be balanced against the risk of enhanced morbidity due to side effects in patients with renal insufficiency; one should therefore desist from preventing ESRD at any cost. Renal replacement therapy (both hemodialysis and peritoneal dialysis) may offer lupus patients with ESRD good chances of survival. The indications for renal replacement therapy are similar to those in other uremic patients. Systemic lupus erythematosus activity may be quenched by renal replacement therapy but it may also persist, especially during the first year. Immunosuppression and corticosteroids should be stopped when possible, as lupus patients on dialysis are liable to increased morbidity consisting of infections and cardiovascular events due to side effects of therapy. The presence of antiphospholipid antibodies may favor thrombotic events. Renal transplant offers the best rehabillitation for most lupus patients with ESRD. Many studies have reported similar patient and graft survival rates in lupus and nonlupus transplant recipients. The results are better for living-donor transplants. Patients with antiphospholipid antibodies have a higher graft failure risk. Active lupus and iatrogenic side effects are risk factors for enhanced morbidity after transplant; a 6-12 washout period before transplant is advisable for these candidates. Recurrence of lupus nephritis is a rare event which usually does not compromise the outcome of the graft.


Subject(s)
Kidney Failure, Chronic/therapy , Kidney Transplantation , Lupus Nephritis/therapy , Renal Dialysis , Humans , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/rehabilitation , Kidney Failure, Chronic/surgery , Lupus Nephritis/complications , Lupus Nephritis/rehabilitation , Peritoneal Dialysis , Recovery of Function , Survival Analysis , Treatment Outcome
10.
J Nephrol ; 31(2): 271-278, 2018 04.
Article in English | MEDLINE | ID: mdl-29081027

ABSTRACT

Autoantibody against phospholipase A2 receptor (anti-PLA2R) is a sensitive and specific biomarker of idiopathic membranous nephropathy (iMN), being found in approximately 70% of iMN patients and only occasionally in other glomerular diseases. However, whereas its diagnostic specificity vs. normal controls and other glomerulonephritides (GN) has been firmly established, its specificity vs. membranous nephropathy associated with various diseases (sMN) has given inconsistent results. The aim of our study was to evaluate the prevalence of anti-PLA2R antibodies in iMN in comparison with various control groups, including sMN. A total of 252 consecutive iMN patients, 184 pathological and 43 healthy controls were tested for anti-PLA2R antibody using indirect immunofluorescence (PLA2R IIFT, Euroimmun). Anti-PLA2R autoantibodies were detectable in 178/252 iMN patients, 1/80 primary GN, 0/72 secondary GN, 9/32 sMN and 0/43 healthy controls, with a diagnostic sensitivity of 70.6%. The diagnostic specificity of anti-PLA2R antibody vs. normal and pathological controls was 100 and 94.6% respectively. However, when the diagnostic specificity was calculated only vs. secondary forms of MN, it decreased considerably to 71.9%. Interestingly enough, 9 out of 10 anti-PLA2R positive patients in the disease control groups had membranous nephropathy associated with various diseases (7 cancer, 1 Crohn's disease, 1 scleroderma). In conclusion, anti-PLA2R positivity in a patient with MN, should not be considered sufficient to abstain from seeking a secondary cause, especially in patients with risk factors for neoplasia. The causal relationship between tumors and anti-PLA2R-induced MN remains to be established, as well as the possible mechanisms through which malignancies provoke autoimmunity.


Subject(s)
Autoantibodies/blood , Glomerulonephritis/blood , Glomerulonephritis/diagnosis , Neoplasms/complications , Receptors, Phospholipase A2/immunology , Aged , Crohn Disease/complications , Diagnosis, Differential , Female , Glomerulonephritis/etiology , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, Membranoproliferative/blood , Glomerulonephritis, Membranoproliferative/diagnosis , Glomerulonephritis, Membranous/blood , Glomerulonephritis, Membranous/diagnosis , Glomerulonephritis, Membranous/pathology , Glomerulosclerosis, Focal Segmental/blood , Glomerulosclerosis, Focal Segmental/diagnosis , Humans , Lupus Nephritis/blood , Lupus Nephritis/diagnosis , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
11.
Expert Opin Pharmacother ; 18(2): 175-186, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28042710

ABSTRACT

INTRODUCTION: Lupus nephritis is a frequent complication and a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Area covered: The main characteristics and mechanisms of action of the synthetic drugs more frequently used in lupus nephritis are described. Possible strategies aimed to reduce the potential adverse events without affecting efficacy are reported. Expert opinion: Many synthetic immunosuppressive drugs used in lupus nephritis have a low therapeutic index. Good knowledge of their pharmacologic characteristics, mechanisms of action, and drug-to-drug interactions, coupled with a strategy aimed to increase immunosuppression in the active phases of SLE while reducing the dosage in quiescent periods can reduce the iatrogenic morbidity while maintaining efficacy. Biologic agent may allow to reduce the use or the dosage of synthetic immunosuppressive drugs.


Subject(s)
Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/drug therapy , Humans , Immunosuppression Therapy/methods
12.
Expert Opin Drug Saf ; 16(3): 411-419, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27927040

ABSTRACT

INTRODUCTION: Hydroxychloroquine (HCQ) is an alkalinizing lysosomatropic drug that accumulates in lysosomes where it inhibits some important functions by increasing the pH. HCQ has proved to be effective in a number of autoimmune diseases including systemic lupus erythematosus (SLE). Areas covered: In this review the mechanisms of action, the efficacy, and the safety of HCQ in the management of patients with SLE have been reviewed. HCQ may reduce the risk of flares, allow the reduction of the dosage of steroids, reduce organ damage, and prevent the thrombotic effects of anti-phospholipid antibodies. The drug is generally safe and may be prescribed to pregnant women. However, some cautions are needed to prevent retinopathy, a rare but serious complication of the prolonged use of HCQ. Expert opinion: HCQ may offer several advantages not only in patients with mild SLE but can also exert important beneficial effects in lupus patients with organ involvement and in pregnant women. The drug has a low cost and few side effects. These characteristics should encourage a larger use of HCQ, also in lupus patients with organ involvement.


Subject(s)
Antirheumatic Agents/therapeutic use , Hydroxychloroquine/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Animals , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/physiopathology , Pregnancy , Retinal Diseases/chemically induced , Retinal Diseases/prevention & control
13.
G Ital Nefrol ; 22 Suppl 33: S3-10, 2005.
Article in Italian | MEDLINE | ID: mdl-16419003

ABSTRACT

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory autoimmune disease affecting multiple organ systems, skin and joints the most involved. Lupus Nephritis occurs in Approximately 50% of patients, sometimes it may be the first manifestation of SLE. Clinical features range from asymptomatic urinary abnormalities to full-blown nephrotic syndrome or rapidly progressive renal failure. Because of the heterogeneity of clinical renal manifestations, renal biopsy plays an important role in the management of patients with SLE: it provides information about the class, severity, activity and chronicity of the renal disease that cannot be accurately predicted on the basis of clinical parameters. The complexity of protean renal manifestation of SLE can be approached using the original WHO classification (1982), recently revised (2004).


Subject(s)
Lupus Erythematosus, Systemic/complications , Lupus Nephritis/etiology , Humans , Lupus Nephritis/pathology , Prognosis , Time Factors
14.
Am J Kidney Dis ; 31(4): 681-6, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9531186

ABSTRACT

In this study, we retrospectively analyzed the effects of treatment in 19 patients with membranous lupus nephritis (MLN) and nephrotic syndrome. Eight patients were treated with corticosteroids alone, and the other 11 patients received methylprednisolone and chlorambucil alternated every other month for 6 months. At presentation, sex, age, duration of renal disease before renal biopsy, plasma creatinine, and arterial hypertension were similar in the two study groups. Of the eight patients treated with corticosteroids alone, three showed complete remission and one partial remission of the nephrotic syndrome. During the follow-up (mean, 114+/-63 months), seven of these eight patients developed one or more renal flare-ups. Of the 11 patients treated with methylprednisolone and chlorambucil, seven had complete remission, and the other four had partial remission of the nephrotic syndrome. During the follow-up (mean, 83+/-59 months), only one patient had renal flare-up. At the end of the follow-up, all patients were alive, but three patients in the group treated with corticosteroids alone had developed a doubling of plasma creatinine, and another patient had persistent nephrotic syndrome. Two other patients were in complete remission, one patient was in partial remission, and the last patient had nonnephrotic proteinuria. In the group of patients treated with methylprednisolone and chlorambucil, one patient developed extracapillary glomerulonephritis and eventually entered end-stage renal failure 24 years after the clinical onset of renal disease. Seven patients were in complete remission, and three patients were in partial remission at the last follow-up visit. This retrospective study suggests that methylprednisolone and chlorambucil may induce a more stable remission of nephrotic syndrome and may better protect renal function in the long term in comparison with corticosteroids alone. However, these results must be confirmed by a prospective controlled trial.


Subject(s)
Lupus Nephritis/drug therapy , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Chlorambucil/administration & dosage , Drug Evaluation , Drug Therapy, Combination , Female , Glucocorticoids/administration & dosage , Humans , Methylprednisolone/administration & dosage , Middle Aged , Nephrotic Syndrome/drug therapy , Proteinuria/drug therapy , Retrospective Studies , Time Factors , Treatment Outcome
15.
Am J Kidney Dis ; 34(3): 530-9, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10469865

ABSTRACT

Little information is available about the role of repeated renal biopsies in lupus nephritis. We analyzed retrospectively the prognostic significance of serial renal biopsies in patients with lupus nephritis. Thirty-one patients with lupus nephritis underwent two or more renal biopsies during follow-up. The indications for repeated biopsy were as follows: improvement of renal disease but persistence of nonnephrotic proteinuria (group A, 7 patients); persistent or relapsing nephrotic syndrome (group B, 12 patients); and worsening of renal function (group C, 19 patients). After a median follow-up of 10.5 years, 17 patients reached the end point (persistent doubling of plasma creatinine level). At repeated renal biopsy, there was a correlation between improved clinical and histological features for group A. In these patients, treatment was reduced or stopped successfully. Histological features remained almost unchanged in group B. All patients showed an improvement of proteinuria after reinforcement of therapy. In group C, the worsening of renal function was associated with a variable and clinically unpredictable combination of active and chronic lesions. Only the few patients with an elevated activity index and moderate chronicity index showed a favorable and persistent improvement of renal disease after reinforcement of therapy. At multivariate analysis of clinical and histological data at presentation, only male sex was predictive of an adverse outcome (P = 0.015). At repeated renal biopsy, crescents in more than 30% of glomeruli (P = 0.0009) and chronicity index of 5 or greater (P = 0.00006) were associated with the probability of reaching the end point at multivariate analysis. Repeated renal biopsy may be helpful for establishing the prognosis in patients with lupus nephritis, particularly in the presence of worsening of renal function.


Subject(s)
Kidney Function Tests , Lupus Nephritis/pathology , Adolescent , Adult , Azathioprine/administration & dosage , Biopsy , Creatinine/blood , Cyclophosphamide/administration & dosage , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/administration & dosage , Kidney/pathology , Lupus Nephritis/diagnosis , Lupus Nephritis/drug therapy , Male , Methylprednisolone/administration & dosage , Prednisolone/administration & dosage , Treatment Outcome
16.
Am J Kidney Dis ; 37(3): 490-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11228172

ABSTRACT

It is still uncertain which, if any, immunologic parameters may help diagnose a renal flare of lupus nephritis. Anti-C1q antibody (Ab) titers have been elevated in patients with lupus with renal involvement, but little information is available on whether the titers are different in quiescent and active phases of lupus nephritis. In this study, we compared anti-C1q Ab titers with other serological test results in 48 patients with biopsy-proven lupus nephritis to assess which parameter could offer the best reliability for differentiating between quiescent and active phases of lupus nephritis. Serum C3 and C4 levels, as well as anti-double-stranded DNA, antiendothelial cell, anti-C1q, and antiphospholipid Ab titers, were evaluated in patients with quiescent renal disease (38 samples) and those with clinical evidence of renal activity (23 samples). Only anti-C1q Ab titers correlated with active renal disease in both univariate (P < 0.0001) and multivariate analysis (P < 0.0001), with a sensitivity of 87% and a specificity of 92%. In six patients, immunologic parameters were measured serially. In all patients, the high anti-C1q Ab titers returned to normal values after treatment-induced remission. The other serological parameters did not show a significant association with renal disease activity. In patients with biopsy-proven lupus nephritis, anti-C1q Ab titers appear to be strongly related to renal disease activity. Their measurement may be useful for confirming the diagnosis of renal flares of lupus nephritis.


Subject(s)
Complement C1q/analysis , Lupus Nephritis/diagnosis , Adult , Analysis of Variance , Antibodies/immunology , Antibodies, Antiphospholipid/blood , Complement C1q/immunology , Complement C3/analysis , Complement C4/analysis , DNA/blood , Disease Progression , Endothelium/cytology , Endothelium/immunology , Female , Humans , Lupus Nephritis/immunology , Male , Regression Analysis , Sensitivity and Specificity
17.
Chest ; 99(6): 1433-7, 1991 Jun.
Article in English | MEDLINE | ID: mdl-2036827

ABSTRACT

Circulating levels of the soluble interleukin 2 receptor (sIL-2R) could provide an in vivo measure of the immunologic response to human tumors. We performed a total of 326 sIL-2R serum assays in 126 patients with lung cancer (67 at diagnosis, 59 during and after treatment), 112 patients with pulmonary benign diseases, and 63 voluntary healthy subjects. Patients with lung cancer had a median value of sIL-2R of 791 U/ml, which was superior to that of both controls (398 U/ml, p less than 0.001) and patients with noninflammatory benign diseases (583 U/ml, p less than 0.02). However, infectious pulmonary disorders, such as tuberculosis and pneumonia, were associated with the highest values of the substance (median, 1150 U/ml; p less than 0.001). At the diagnosis of lung cancer, sIL-2R correlated neither with the stage of disease nor with the cell type. On the contrary, posttreatment levels of the receptor were significantly related to disease status (RO = .41, p less than 0.002), particularly in the subgroup of nonsurgical patients (RO = .48, p less than 0.001). Patients with abnormal sIL-2R levels had a nearly significant reduction in survival as compared with patients with normal values (p less than 0.1). Measurements of sIL-2R could be useful in monitoring patients under treatment for bronchogenic carcinoma, as well as in prognostication. In this setting, sIL-2R might open a new class of biologic markers, providing information that is complementary to those of the more classic tumor-derived markers.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Bronchogenic/diagnosis , Lung Neoplasms/diagnosis , Receptors, Interleukin-2/blood , Adult , Aged , Aged, 80 and over , Carcinoma, Bronchogenic/blood , Carcinoma, Bronchogenic/therapy , Female , Humans , Lung Diseases/blood , Lung Neoplasms/blood , Lung Neoplasms/therapy , Male , Middle Aged , Solubility
18.
Arch Virol Suppl ; 4: 205-9, 1992.
Article in English | MEDLINE | ID: mdl-1333323

ABSTRACT

We investigated the prevalence of anti-HCV in 160 consecutive patients with primary biliary cirrhosis. By ELISA, 19 (12%) were positive, as compared to a 68% prevalence in 135 patients with chronic non-A, non-B hepatitis. Serum IgG levels were significantly higher in the anti-HCV positive group. By RIBA, seropositivity was confirmed for 4 patients, whereas 7 were indeterminate. A slight, non-significant reduction of life expectancy was found in anti-HCV positive patients. Until reliable and independent confirmatory tests become available, definitive conclusions on the importance of anti-HCV positivity in primary biliary cirrhosis are improper.


Subject(s)
Hepacivirus/immunology , Hepatitis Antibodies/blood , Liver Cirrhosis, Biliary/immunology , Adult , Aged , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Survival Analysis
19.
Clin Nephrol ; 28(6): 263-71, 1987 Dec.
Article in English | MEDLINE | ID: mdl-3327639

ABSTRACT

The follow-up of 43 patients with diffuse proliferative lupus nephritis is reported. After histological diagnosis, all patients were treated with 3 intravenous high-dose methylprednisolone pulses and then with low-dose oral steroids and 31 with cytotoxic drugs. Renal and extra-renal exacerbations were also treated with intravenous high-dose steroids. Patients were followed for 1 to 13 years. At 10 years the patient survival rate was 87% and the kidney survival rate was 79%. If 3 extra-renal deaths are excluded, the actuarial 10-year kidney survival rate is 91%. At present, 21 patients do not show any renal abnormalities, 13 patients have normal plasma creatinine but proteinuria, 3 patients have stable renal function impairment, 2 patients have worsening of their renal function, 1 is on regular dialysis. The other 3 patients died (from cardiac failure, cerebral hemorrhage and a car accident). The incidence of flare-ups was low (0.1 episodes per year). Severe side effects were rare in this series. It is concluded that the long-term prognosis of diffuse lupus nephritis is becoming considerably better. Therapy based on a short course of intravenous high-dose methylprednisolone and on a maintenance regimen with low doses of steroid and cytotoxic agents can contribute to preserving renal function while avoiding severe side effects.


Subject(s)
Lupus Nephritis/drug therapy , Methylprednisolone/therapeutic use , Prednisone/therapeutic use , Administration, Oral , Adolescent , Adult , Creatinine/blood , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Kidney/pathology , Kidney Function Tests , Lupus Nephritis/blood , Lupus Nephritis/mortality , Lupus Nephritis/pathology , Male , Methylprednisolone/administration & dosage , Methylprednisolone/adverse effects , Middle Aged , Prednisone/administration & dosage , Prognosis , Proteinuria/etiology
20.
Clin Nephrol ; 39(4): 175-82, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8491046

ABSTRACT

The follow-up of 42 patients affected by lupus membranous nephropathy (LMN) is reported and compared with that of 43 patients affected by diffuse proliferative lupus glomerulonephritis (DPGN), who were the object of a previous study. According to the WHO classification, the patients were subdivided into two groups: pure LMN (Va + Vb class) and LMN with superimposed proliferative lesions (Vc + Vd class). Antiphospholipid antibodies (APA) and lupus anticoagulant were tested in 23 subjects. All the patients were treated with corticosteroids, which were associated to cytotoxic drugs in 28 cases. Although a higher number of complete remissions was obtained in patients with pure LMN, the difference between the 2 groups was not significant (7/26 vs 1/16). At 10 years kidney survival was 93% in all LMN patients with no significant differences between the 2 groups. This 10-year kidney survival rate is very similar to that previously observed by us for DPGN (91%). The WHO histological classification and the chronicity index did not identify the patients who reach end-stage renal failure. Eight patients suffered from thrombotic manifestations which were the cause of death in two cases. Fourteen of the 20 patients studied presented echocardiographic abnormalities. A statistically significant association was found between the occurrence of cardiovascular complications and APA levels. The effectiveness of treatment in LMN remains controversial. We suggest, however, that adequate therapy may significantly improve the prognosis of lupus nephritis thus reducing the differences in the outcome of SLE patients having different histological WHO classes. Cardiovascular illness represents a frequent and severe late complication.


Subject(s)
Glomerulonephritis, Membranous/epidemiology , Lupus Nephritis/epidemiology , Adult , Antibodies, Antiphospholipid/analysis , Cardiovascular Diseases/epidemiology , Echocardiography , Female , Follow-Up Studies , Humans , Kidney Failure, Chronic/epidemiology , Lupus Coagulation Inhibitor/analysis , Male , Prognosis , Retrospective Studies , Thrombosis/epidemiology , Time Factors
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