Immunosuppressive treatment has changed the prognosis of Lupus nephritis over time, but improvement in prognosis is difficult to analyze in different historical periods, and should be better demonstrated in comparison with life expectancy of sex-and age-matched people. Long-term patient and renal survival of 90 patients diagnosed with Lupus nephritis at our center from 1968 to 2001 with a follow-up time of 14±8 years was retrospectively evaluated. Patient and kidney survival significantly increased over time. Multivariate analyses show that risks of patient and renal death decreased by 8% at each year of follow-up, and increased by more than 5 time in patients aged > 30 years at diagnosis. As only 14 patients were men, relative survival as compared to that of the sex- and age-matched general population of the Piedmont Region was calculated for the 76 women. Improvement in the survival of the cohort of women was seen at any time of follow-up: in particular, it was sharply lower in the first period (relative survival at 5,10 and 15 years = 0.784, 0.665, and 0.620, respectively) and increased in the second (relative survival at 5,10 and 15 years = 0.939, 0.921, and 0.850, respectively) nearly approaching that expected for the general population, i.e. 0.993, 0.983 and 0.967, respectively. Taken together, our data allow us to draw the conclusion that life expectancy in women with Lupus nephritis has improved over time, paralleling an improved awareness of the disease and a significant increase in steroid pulse therapy as induction/remission phase. Improvement in survival is for the first time demonstrated to cover the gap with life expectancy of the general population for women with Lupus nephritis.

To the Editor: The Nephrology Forum discussed by Professor Savage reminded us of two items about ANCA-associated renal vasculitis (AARV): (1) the complex pathogenesis, where ANCA are much but not enough; and (2) the role of cytokines1.Savage C.O.S. “ANCA-associated renal vasculitis”.Kidney Int. 2001; 60: 1614-1627Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar. Two years ago, we conducted an observational study on 14 first diagnosed, previously untreated, biopsy-proved AARV patients referred to our Renal Unit, testing a set of markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocyte count, fibrinogen, ferritin, C3 and C4 factors, IgG, ANCA title and antigens] for sensitivity, specifity, and prognostic value. The control group included 14 cases with “vasculitis look-alike” diseases (mainly primary glomerulonephritides) with similar age and renal impairment. As expected, ANCA title and antigens and all other data did not show any relation with histology, severity of renal failure, lung involvement, or outcome. Interestingly, however, no cases with high serum IgG needed dialysis (five out of five patients), but six of nine with normal IgG did so (P = 0.01, Fisher's Exact Test). We thought that these five had a more recent stage of vasculitis, when therapy can be more effective. Professor Savage's hypothesis of a shift from humoral (antibody-dependent) to cellular (T-cell-dependent) damage in vasculitis course is in agreement with our findings. Apart of ANCA, only CRP and ferritin had diagnostic value. The former was more sensitive (100% vs. 71%), the latter more specific (93% vs. 43%). Ferritin specificity was a surprise. Was it related to a bias or to some mechanism of disease (oxidative injury, tumor necrosis factor (TNF) action)? Professor Savage's lesson on the role of TNF in AARV could be the answer to our doubt.

Despite many studies on the subject, the causal relationships between viruses and presentation/exacerbation of autoimmune diseases are still elusive. The possibility of false positive IgM antibody tests for human cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE) has been pointed out. Here we report a case of a patient who developed lupus nephritis, with biochemical and clinical markers of CMV infection with intestinal involvement. At first, the antibodies to CMV were regarded as spurious aspecific signs of autoimmune disease. The patient had had serious flare-ups of the disease, hemolytic-uremic syndrome with thrombotic microangiopathy superimposed on SLE nephritis, and life-threatening infections for three years until CMV infection was confirmed by the persistence of anti-CMV IgM-antibodies coupled with positive results of tests for viral replication. After therapy with ganciclovir, his clinical and biochemical condition improved and remained stable for three years, with only very low maintenance steroid coupled with hydroxychloroquine. IgM anti-CMV were no longer detectable in spite of the persistence of other autoantibodies such as anti-DNA and ANA. Keeping in mind that CMV-IgM has been reported in only 5% of patients with SLE nephritis, the history of our patient indicates that CMV infection must be carefully excluded before IgM antibodies against CMV can be simply classified as an aspecific sign of cross-reacting autoantibodies formed in SLE patients.

Background. Hepatitis C virus (HCN) infection may be associated with various extrahepatic immunological disorders. Uremic patients on chronic regular dialytic treatment (RDT) frequently develop immunological abnormalities. The aim of this study was to evaluate the probability that HCV infection creates an increased risk for extrahepatic immunological abnormalities in chronic RDT patients.Subjects and Methods. In a series of one hundred sixteen chronic RDT patients, HCV status was determined by anti-HCV antibodies, polymerase chain reaction (PCR) RNA and viral genotyping. After excluding four anti-HCV negative/PCR-RNA positive patients, a comparison was made between 51 anti-HCV negative/PCR-RNA negative and 61 anti-HCV positive patients, this latter group including seventeen PCR-RNA negative, fifteen genotype 1, thirteen genotype 2, three genotype 3, four genotype 4, four undeterminable genotype and five mixed genotypes. The following investigations were performed: cryoglobulinemia (presence, titer and, when possible, identification), monoclonal gammopathy, antineutrophil cytoplasm antibodies, antidouble stranded DNA antibodies, circulating immunocomplexes and immunoglobulin levels.Results. Cryoglobulinemia was found in 77% of anti-HICV positive versus 29% of anti-HCV negative patients, and cryocrit > 1% in 50% versus 9.8% respectively, p =< 0.01. Also cryoglobulin concentration was higher (logarithmic transformation: 4.38+/-0.94 vs 3.11+/-1.06, p =< 0.001) in anti-HCV positive versus negative patients. Multivariate logistic regression analysis showed a significantly increased odds ratio (12.0, confidence interval 3.0 to 48.3) for having high levels of cryoglobulins (cryocrit >1%) after adjusting for age and dialytic age. The prevalence of this abnormality did not differ significantly among patients infected with different genotypes, but a tendency towards a lower frequency was observed in the anti-HCV positive/PCR negative subgroup. Cryoglobulins were identified as type I (2 anti-HCV positive case), type II (2 anti-HCN positive and I anti-HCN negative case) and type 3 (1 anti-HCV negative case). The frequency of monoclonal gammopathy was not significantly different between anti-HCV positive and anti-HCV negative patients (6,5% versus 2%) as well as that of the other parameters evaluated except for Ige concentration which was higher in the anti-HCV positive group (1685+/-605 versus 1349+/-352 mg/dl, p 0.006). Five events, potentially linked to HCN infection, occurred in our anti-HCN positive patients: 2 cases of porphyria cutanea, 1 case of unexplained peripheral neuropathy, 1 cutaneous leukocytoclastic vasculitis, 1 death for non-Hodgkin's lymphoma. In one anti-HCN positive patient treated with interferon-cr, the presence of cryoglobulins, monoclonal gammopathy and high IgG levels strictly paralleled that of viremia, disappearing during the recovery phase under treatment and reappearing shortly after stopping treatment.Conclusions. HCV infection provides a significantly increased risk for developing extrahepatic immunological abnormalities also in chronic RDT patients. It is possible that the clinical relevance of this event might be scant because of the low level of these abnormalities, but an awareness of its possibility should to be taken into account.

Background: In an attempt to find new parameters able to evaluate the actual iron availability by bone marrow cells, zinc protoporphyrin (ZnPP), a metabolic intermediate generated in the red blood cell by the incorporation of zinc instead of iron, has been proposed. ZnPP is a good marker of iron-deficiency anemia in non-uremic people, as red blood cell ZnPP concentration rises specifically (except for lead intoxication) in this condition. Existing data on ZnPP as a marker of iron deficiency in uremic patients comes mainly from cross sectional studies on chronic hemodialysis and has produced conflicting results. Subjects and methods: Therefore, we prospectively studied 42 HID patients, 28 - 88 years old, 13 - 346 months of dialysis age, beginning from a period of maximal iron deficiency, due to the lack of parenteral iron compounds (TO) up to the end of more than one year of follow-up with continuous parenteral iron supplementation (T4). ZnPP, hemoglobin, transferrin saturation and ferritin were serially determined before and after six weeks (T1), four months (T2), seven months (T3) and 14 months (T4) of parenteral iron supplementation at a maintenance dose of 0.5 - 1 mg/kg/week. Results: In comparison with baseline values (95 +/- 37 mu mol/mol heme) there were no significant changes in ZnPP levels at T1 and T2 despite a continuous increase in both transferrin saturation and ferritin values, while ZnPP significantly decreased at T4 (63 +/- 37 mu mol/mol heme, p < 0.001). There was no correlation between ZnPP and both transferrin saturation and ferritin at any time during the study, the same was true for ZnPP and zinc and lead serum concentration, fibrinogen and reactive C protein levels at T1 and T4, respectively. At T4, only 2/10 patients who still showed ZnPP levels > 80 mu mol/mol heme had absolute or functional iron deficiency, when the percentage of hypochromic red cells were measured. Conclusion: We conclude that ZnPP untimely parallels a change in iron balance in only a proportion of uremic people, in as much as confounding factors, such as chronic inflammation and uremia in itself may obscure its relationship with iron status. Therefore, ZnPP cannot be assumed to be a first-line diagnostic marker of iron balance in uremic patients.

The objective of this study was to look for the occurrence of catastrophic antiphospholipid syndromes (APS) and to try to detect discriminating factors for predicting a worse prognosis, related to Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL), in systemic lupus erythematosus (SLE) with main renal involvement. Regression, recursive partition and logistic regression analyses were applied to our 80 SLE patients prospectively followed up since 1980. Immunologic and other laboratory parameters including beta 2-glycoprotein 1 dependence, resistance to activated protein C caused by a substitution on the coagulation factor V gene, induction of monocyte procoagulant activity. Regression studies demonstrated an overall worse prognosis in term of both thrombosis and death for the group of LA/aPL positive patients (33/80). However, recursive partition analysis was able to isolate a small high risk-subgroup (8/33) characterized by persistent LA/aPL antibodies positive result, widespread signs of noninflammatory vasculopathy (skin, brain, kidney) and renal pathology mimicking that of thrombotic microangiopathy or arteriolosclerosis, also in the absence of classic SLE-nephritis. Only in this subset, three catastrophic APS were recorded, while, in traditional SLE nephritis, even persistent LA/aPL positive results (sometimes after one previous thrombosis) did not seem to imply a particularly severe prognosis. All serologic criteria employed are unable to identify high-risk patients. We conclude that catastrophic APS is a rare event in renal SLE. Before more predictive serologic markers become available, a simple algorithm, dealing with clinical data and renal histologic patterns, may help physicians to identify putatively high risk-LA/aPL antibodies in SLE patients with main renal involvement. This ominous subset does not belong to the group of classic SLE-nephritis.

Letters| February 26 1999 How to Save Money for Erythropoietin Therapy by Changing from ‘Roller Coaster’ to Continuous Iron Supplementation Subject Area: Nephrology Caterina Canavese; Caterina Canavese Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Anna Grill; Anna Grill Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Ester De Costanzi; Ester De Costanzi Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Guido Martina; Guido Martina Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Enrica Buglione; Enrica Buglione Occupational and Health Diseases, University of Torino, Search for other works by this author on: This Site PubMed Google Scholar Daniela Valente; Daniela Valente Occupational and Health Diseases, University of Torino, Search for other works by this author on: This Site PubMed Google Scholar Onorata David; Onorata David Biochemical Laboratory of Regina Margherita Hospital and Search for other works by this author on: This Site PubMed Google Scholar Maddalena Saitta; Maddalena Saitta Biochemical Laboratory of Regina Margherita Hospital and Search for other works by this author on: This Site PubMed Google Scholar Emanuela Maddalena; Emanuela Maddalena Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Sara Barbieri; Sara Barbieri Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Fabrizio Fop; Fabrizio Fop Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Mario Salomone; Mario Salomone Valletta Hospital, Torino, Italy Search for other works by this author on: This Site PubMed Google Scholar Giuseppe Piccoli Giuseppe Piccoli Departments of Medical and Surgical Sciences, Section Nephrourology, and Search for other works by this author on: This Site PubMed Google Scholar Nephron (1999) 81 (3): 362–363. https://doi.org/10.1159/000045312 Article history Published Online: February 26 1999 Content Tools Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Caterina Canavese, Anna Grill, Ester De Costanzi, Guido Martina, Enrica Buglione, Daniela Valente, Onorata David, Maddalena Saitta, Emanuela Maddalena, Sara Barbieri, Fabrizio Fop, Mario Salomone, Giuseppe Piccoli; How to Save Money for Erythropoietin Therapy by Changing from ‘Roller Coaster’ to Continuous Iron Supplementation. 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However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or... 1999Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. 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High-dose intravenous (i.v.) immunoglobulin (Ig) has been shown to be effective in the treatment of several disorders, including bacterial and viral infections in primary and secondary immunodeficiency states, as well as in autoimmune diseases. Recently, successful results obtained by treatment with i.v. Ig in patients with recurrent abortions and antiphospholipid antibody syndrome (APS) have been summarized (Orvieto et al, 1991). As far as autoimmune disorders are concerned, the suggested mode of action of i.v. Ig includes competitive binding to macrophage receptors, increasing the number of T-suppressor cells, masking the recognition of class II major histocompatibility complex and immuno-manipulation consequent to favourable changes in the network of idiotypic interactions (Berkman et al, 1990). In the context of APS-related pregnancy loss, a pathogenic role of antiphospholipid antibodies, recognized as antiphospholipid (aPL) or anticardiolipin (aCL) on the basis of different antigens employed in commercial kits, might be supported by experimental studies, showing that passive transfer of aPL/aCL may have direct effects on the fecundity and outcome of pregnancy (Blank et al, 1991). As i.v. Ig is beneficial, a decrease in aPL/aCL levels following Ig infusion might be expected. However, this is not the case, in that the treatment may transiently suppress the lupus anticoagulant activity, but aPL/aCL levels decrease only slightly or remain elevated (Orvieto et al, 1991). As natural antibodies against phospholipids are recognized in humans (Alving, 1984) and commercial i.v. Ig are prepared from large pools of normal donors, we tested five commercial preparations licensed in Italy for the presence of IgG (GPL) and IgM (MPL) isotypes of aPL or anticardiolipin (aCL) antibodies detected by two ELISA commercial kits (Diagnostica Stago and Byk Gulden respectively). We also looked for antineutrophil cytoplasm antibodies (ANCA: antiMPO 1⁄4 C-ANCA, ANTI-PR3 1⁄4 P-ANCA) by ELISA (MEDIC) following suggestions that the presence of some amount of ANCA in i.v. Ig might explain the early increase in ANCA levels following i.v. Ig administration in vasculitis ( Jayne et al, 1991). Although ANCA levels were always undetectable, aPL and/or aCL were found in all the five samples of commercial preparations of Ig tested (Table I). These results may stimulate speculation on the reasons for the success of i.v. Ig in APS-related pregnancy loss. Previous reports supported the hypothesis that one mechanism of aPL/aCL production might be an immune response to myocardial injury, thus allowing the suggestion that ‘it is not beyond the realms of possibility that administration of exogenous aPL/aCL in the immediate postinfarct period, in a fashion analogous to the administration of anti-D to rhesus negative mothers, could prevent such sensitization’ (Morton et al, 1986). Might the beneficial effects of i.v. Ig in the context of APS-related pregnancy loss be dealing with the aPL/aCL entailed in i.v. Ig, as these antibodies could prevent (or overwhelm) some ongoing sensitization process? Obviously, many other potential mechanisms have to be investigated. A recent hypothesis suggests that aPL/aCL, as many other autoantibodies putatively related to pregnancy loss, are nothing more than an epiphenomenon due to some primary abnormality of T lymphocyte in recognizing self antibodies (Gleicher, 1994). In this sense, i.v. Ig could possibly correct these abnormalities of T lymphocytes, as well as providing anti-idiotypic antibodies. British Journal of Haematology, 1997, 96, 872–882

Lupus anticoagulant (LA), anticardiolipin (aCL), and/or antiphospholipid (aPL) antibodies are the hallmarks of the antiphospholipid syndrome, characterized by widespread thrombosis. The syndrome has been described as primary or secondary when aCL/aPL are the only classes of detectable autoantibodies or occur in the context of systemic lupus erythematosus (SLE) or SLE-like disease. However, since LA/aCL/aPL have been extensively looked for, it has become evident that they may also be detected in the absence of any clinical correlation with thrombosis. In particular, among SLE patients, these antibodies mean a high risk of thrombosis only in a small subset, sharing clinical features with primary antiphospholipid syndrome. As laboratory examination is still unable to distinguish between high-risk and non-high-risk antiphospholipid antibodies, it is crucial to have some reasonable criteria able to guide the day-to-day clinical practice. We attempt to trace: the following guidelines: (1) distinguish between transient and persistent LA/aCL/aPL results; (2) do not forget the LA phenomenon in the era of aCL/aPL; (3) maintain a strict communication with the laboratory; (4) exclude other causes of primary coagulation abnormalities; (5) look at the time of appearance of LA/aCL/aPL with respect to thrombosis; (6) analyze any possible laboratory clue putatively useful to distinguish between 'rouge' and 'non-rouge' LA/aCL/aPL; (7) look for signs of widespread noninflammatory vasculopathy; (8) do not engage a war to the knife against LA/aCL/aPL by immunosuppressive therapies.

The actual disappearance of pregnancy-related acute renal failure (PR-ARF) is a common ''feeling'' for nephrologists. The aim of this study was to exactly quantify this event by evaluating epidemiology and the extent of renal damage in PR-ARF: From 1958 to 1994, 84 cases of PR-ARF were observed (5.8% of total number of ARF needing dialysis). In four successive periods (1956-67, 1968-77, 1978-87, 1988-94), the incidence of PR-ARF fell from 43% to 0.5% with respect to the total number of ARF, and from 1/3000 to 1/18,000 with respect to the total number of pregnancies. Maternal mortality in the past was high (31%), but no cases of death in the last period were seen. Irreversible renal damage was recorded in 11.1% of PR-ARF: and, in particular in 18.7% of cases of preeclampsia-eclampsia (PE-E). The worst maternal and renal prognosis occurred in PE-E that was complicated by abruptio placentae (AP). Neither disseminated intravascular coagulation (DIC), microangiopathic hemolytic anemia, nor prostacyclin imbalance were significantly related to the severity of renal damage. Heparin therapy did not modify DIC evolution and renal outcome and was aggravated by severe hemorragic complications. Support therapy with plasma infusion, antithrombin III, and antiplatelet agents seems to be helpful. In conclusion, PR-ARF has become a rare occurrence and, in our experience, no cases of death or irreversible renal damage were observed in the last 7 years. The most important reasons for this favorable evolution seem to be an improved medical care and more effective measures of careful prevention, mainly regarding tempestive delivery.