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1.
Clin Nephrol ; 75(4): 362-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21426891

ABSTRACT

The majority of patients with non-HIV-related collapsing focal segmental glomerular sclerosis (FSGS) have idiopathic disease. Only a few genetic forms associated with rare syndromes have been described in families. Here we report two families with multiple members who have collapsing FSGS with no clear associated secondary etiology. Genetic analysis revealed a defect in the TRPC6 gene in one family, but excluded all known common inherited podocyte defects in the other family. The course and response to treatment differed dramatically among members of the same family.


Subject(s)
Glomerulosclerosis, Focal Segmental/genetics , Adult , Biopsy , Disease Progression , Female , Glomerulosclerosis, Focal Segmental/diagnosis , Glomerulosclerosis, Focal Segmental/drug therapy , Humans , Male , Pedigree
2.
Clin Nephrol ; 74(3): 173-81, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20860901

ABSTRACT

FSGS is an important cause of ESRD and tends to recur in allografts (rFSGS). Older series suggest recurrence rates of 30-60%. In the modern era of transplant immunosuppression, recurrence rates are unknown. There are also few data regarding prevalence of known genetic mutations in adult FSGS patients who undergo transplantation. Recently, FSGS has been subdivided into histological variants, which may predict renal outcomes; there is little information on patterns of recurrence and outcomes in these variants. Finally, treatment for rFSGS relies upon up-titrating calcineurin inhibitors and plasmapheresis. Insufficient information exists on the use of these regimens for rFSGS in the era of modern immunosuppression. We conducted a retrospective chart review involving all renal transplant recipients at Columbia University Medical Center from December 1999 to March 2007. Those with biopsy confirmed primary FSGS were included and information regarding baseline characteristics, histologic variants, genetics, treatment, and clinical outcomes were collected. FSGS recurred in 23% of patients. Those with collapsing histology on native kidney biopsy, tended to recur with the same histology. No known genetic mutations were identified among those with recurrence. Plasmapheresis resulted in complete or partial remission in 75% of those with recurrence. Recurrent FSGS resulted in a trend toward the combined outcome of ESRD or death compared to those without recurrence (27% vs. 12%). Modern immunosuppression does not reduce the rate of rFSGS, known genetic mutations are uncommon in such adult patients, collapsing FSGS tends to recur with the same histology, and plasmapheresis may be helpful in the treatment of recurrence.


Subject(s)
Glomerulosclerosis, Focal Segmental/pathology , Immunosuppression Therapy/methods , Kidney Transplantation , Adolescent , Adult , Biopsy , Child , Child, Preschool , Female , Humans , Logistic Models , Male , Middle Aged , Plasmapheresis , Recurrence , Retrospective Studies , Risk Factors , Statistics, Nonparametric
3.
Kidney Int ; 73(8): 905-7, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18379525

ABSTRACT

Acute interstitial nephritis (AIN) is an uncommon form of acute renal failure that is usually medication related. Although the clinical features and renal histopathology are well recognized, therapy beyond discontinuing the offending drug has been a challenge. The use of corticosteroids, although supported by numerous small retrospective studies and anecdotal case reports, has been controversial. The study by González et al., although it has limitations, provides solid support for the early use of corticosteroids in the treatment of drug-related AIN.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Nephritis, Interstitial/drug therapy , Humans , Nephritis, Interstitial/chemically induced
4.
Lupus ; 16(12): 972-80, 2007.
Article in English | MEDLINE | ID: mdl-18042591

ABSTRACT

The Phase III Aspreva Lupus Management Study (ALMS) will investigate mycophenolate mofetil (MMF) therapy for lupus nephritis (LN). Eligibility criteria include: 12-75 years of age; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria; and biopsy-demonstrated LN (Class III-V). Randomized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks. The primary efficacy endpoint is treatment response [decreased proteinuria and stabilized (within 25% of baseline) or improved serum creatinine level]. Patients achieving response or complete remission (normalization of all parameters) will be rerandomized to double-blind, placebo-controlled maintenance treatment with MMF or azathioprine, both plus corticosteroids. The maintenance phase primary endpoint is time to treatment failure. To detect a 15% rate improvement in the MMF group compared with cyclophosphamide, and to provide 90% power, a total of 358 patients will be required for the induction phase. On the basis of a projected 278 rerandomized patients, the maintenance phase will have 90% power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5% and 40.7%, respectively. Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Lupus Nephritis/drug therapy , Mycophenolic Acid/analogs & derivatives , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Child , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Mycophenolic Acid/therapeutic use , Remission Induction/methods
5.
Kidney Int ; 70(8): 1403-12, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16929249

ABSTRACT

Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. Although the use of aggressive immunosuppression has improved both patient and renal survival over the past several decades, the optimal treatment of LN remains challenging. Improved outcomes have come at the expense of significant adverse effects owing to therapy. Moreover with long-term survival, the chronic adverse effects of effective therapies including risk of malignancy, atherosclerosis, infertility, and bone disease all become more important. Finally, some patients fail to achieve remission with standard cytotoxic therapy and others relapse when therapy is reduced. For these reasons, recent clinical trials have attempted to define alternate treatment protocols that appear to be efficacious in achieving and maintaining remission, but with less toxicity than standard regimens. This paper discusses established and newer treatment options for patients with proliferative and membranous LN, with an emphasis on the results of these recent clinical trials. We also review the experimental and human data regarding some of the novel targeted forms of therapy that are under investigation and in different phases of clinical trials.


Subject(s)
Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Lupus Nephritis/drug therapy , Chemotherapy, Adjuvant , Humans , Immunologic Factors/physiology , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/etiology , Lupus Nephritis/immunology , Randomized Controlled Trials as Topic
6.
Kidney Int ; 69(11): 1939-44, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16641925

ABSTRACT

Although IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, our understanding of the pathogenesis of this complex disease remains limited. IgA nephropathy may appear with a variety of clinical presentations, a number of different clinical and histopathologic risk factors for progressive renal disease, and a very variable course over time. Thus, it is not surprising that a single therapeutic treatment plan has not been established. Many of the studies dealing with IgAN are retrospective, lack statistical significance, or have confounding designs, which hinder their general acceptance. Nevertheless, a number of well-designed studies have been performed. This paper reviews currently available therapeutic options for IgAN. It attempts to address several important questions: Why do we treat patients with IgAN? How do we decide which patients should be treated? What are the general treatment guidelines for all IgAN patients? What is the role of specific therapy such as fish oils, tonsillectomy, and immunosuppression in the treatment of patient with IgAN? It also addresses several on-going trials and goals for future therapeutic studies for IgAN patients.


Subject(s)
Glomerulonephritis, IGA/therapy , Humans
8.
Clin Nephrol ; 62(4): 245-59, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15524054

ABSTRACT

The nephrotic syndrome occurs in association with a diverse array of primary and secondary glomerular disorders. Despite the different etiologies, many of the clinical effects are similar. This review focuses on the pathogenesis and treatment of edema formation, hyperlipidemia, and the hypercoagulable state. Major abnormalities of the endocrine system and evidence of erythropoietin deficiency will be reviewed. Finally, non-specific treatments aimed at reducing proteinuria will also be discussed.


Subject(s)
Edema/therapy , Endocrine System Diseases/therapy , Hyperlipidemias/therapy , Nephrotic Syndrome/complications , Proteinuria/therapy , Thrombophilia/therapy , Edema/etiology , Endocrine System Diseases/etiology , Humans , Hyperlipidemias/etiology , Proteinuria/etiology , Thrombophilia/etiology
9.
Clin Nephrol ; 62(6): 405-11, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15630898

ABSTRACT

AIMS: Primary focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease in both children and adults. Our current treatments are suboptimal, and a significant percentage of cases are resistant to current therapy. PATIENTS AND METHODS: We performed an open-label, 6-month trial of the new immunosuppressive agent mycophenolate mofetil (MMF) in 18 biopsy-proven patients resistant to a course of corticosteroids therapy. Seventy-five percent had also failed to respond to a cytotoxic agent and/or a calcineurin inhibitor. RESULTS: A substantial improvement in proteinuria was seen in 44% (8/18) of the patients by 6 months. This was sustained for up to 1 year post treatment in 50% (4/8) of this group. No patient had a complete remission. No deterioration in renal function was observed in any patient over the treatment period, but 3 progressed to chronic kidney failure during follow-up. Adverse effects were mild. Only 1 patient required a dose reduction due to an intercurrent infection. CONCLUSIONS: MMF appears safe to use in this group of patients and did lower proteinuria in 44% of this cohort resistant to other forms of treatment. Relapses were common, suggesting more prolonged or combination therapy may be required. More rigorous trials utilizing this medication should be considered to further assess the risk-benefit ratio of treatment with MMF in patients with FSGS.


Subject(s)
Glomerulosclerosis, Focal Segmental/drug therapy , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Adult , Aged , Female , Glomerulosclerosis, Focal Segmental/complications , Humans , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/etiology , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Treatment Outcome
10.
Clin Nephrol ; 59(2): 137-42, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12608557

ABSTRACT

Both membranous glomerulopathy and acute interstitial nephritis have been reported to occur following treatment with non-steroidal anti-inflammatory drugs. We report the first cases of membranous glomerulopathy and acute interstitial nephritis following treatment with celecoxib (Celebrex), a selective COX-2 inhibitor. The rapid and complete resolution of both conditions following discontinuation of Celebrex strongly implicates this agent in disease pathogenesis. These cases enlarge the spectrum of potential renal toxicities of the COX-2-specific non-steroidal anti-inflammatory drugs.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Glomerulonephritis, Membranous/chemically induced , Kidney/pathology , Nephritis, Interstitial/chemically induced , Sulfonamides/adverse effects , Acute Disease , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Celecoxib , Female , Follow-Up Studies , Glomerulonephritis, Membranous/drug therapy , Glucocorticoids/therapeutic use , Humans , Male , Nephritis, Interstitial/drug therapy , Osteoarthritis/drug therapy , Prednisone/therapeutic use , Pyrazoles , Sulfonamides/therapeutic use
11.
Clin Nephrol ; 57(2): 120-6, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11863121

ABSTRACT

We report the clinical and pathologic findings in 7 patients with systemic lupus erythematosus and minimal change disease. All 7 patients presented with full nephrotic syndrome including peripheral edema, nephrotic range proteinuria (mean 9.6 g/day), and hypoalbuminemia (mean 1.8 g/dl). In all cases, renal biopsy revealed diffuse foot process effacement in the absence of significant peripheral capillary wall immune deposits, findings consistent with minimal-change disease. In addition, 5 cases displayed mesangial electron-dense deposits, with or without associated mesangial proliferation, consistent with underlying lupus nephritis class II. In all cases, steroid therapy induced a rapid remission of nephrotic syndrome. Minimal change disease is an underrecognized and readily reversible form of nephrotic syndrome in systemic lupus erythematosus. Because it may occur superimposed on mild mesangial proliferative lupus nephritis, this entity may be misinterpreted as an atypical presentation of lupus nephritis class II. Proper recognition of this entity requires careful integration of the renal biopsy immunofluorescence and electron microscopic findings.


Subject(s)
Kidney/pathology , Lupus Erythematosus, Systemic/complications , Nephrosis, Lipoid/pathology , Adolescent , Adult , Female , Humans , Male , Middle Aged , Nephrosis, Lipoid/complications , Nephrotic Syndrome/complications , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/pathology
12.
Clin Exp Rheumatol ; 19(6 Suppl 25): S37-40, 2001.
Article in English | MEDLINE | ID: mdl-11695250

ABSTRACT

Cyclooxygenase-2 (COX-2) selective inhibitors are now extensively used for their anti-inflammatory and analgesic efficacy. Several large controlled trials provide evidence to support the proposition that they cause fewer major gastro-intestinal side effects and less toxicity than routine nonsteroidal anti-inflammatory drugs (NSAIDs). In view of the documented different localizations of the cyclooxygenase-1 and COX-2 enzymes in the kidney, it was initially hoped that COX-2 inhibitors would be associated with fewer renal side effects than other NSAIDs. This has not been borne out by subsequent studies. Like other NSAIDs, COX-2 inhibitors can cause salt and water retention, leading to edema and worsening hypertension. They can also cause acute declines in renal function and glomerular filtration rate. These events are, however, uncommon in large rheumatology populations and infrequently lead to discontinuation of the medications. Judicious use of COX-2 inhibitors in high-risk patients (such as those with chronic renal insufficiency, diabetes or congestive heart failure) will lead to a decreased incidence of adverse renal events.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cyclooxygenase Inhibitors/adverse effects , Kidney Diseases/chemically induced , Kidney/drug effects , Contraindications , Cyclooxygenase 1 , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Diabetes Complications , Humans , Isoenzymes/metabolism , Kidney/enzymology , Kidney Diseases/enzymology , Membrane Proteins , Prostaglandin-Endoperoxide Synthases/metabolism , Randomized Controlled Trials as Topic
13.
Clin Nephrol ; 56(4): 271-8, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11680656

ABSTRACT

Plasmapheresis (PP) is often employed in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the renal allograft, where it appears to be effective in the pediatric population. The efficacy of PP in adults and predictors of response are not well documented. We analyzed the records of 13 adult patients from three transplant centers who underwent PP for recurrent FSGS between 1993 and 1999. One patient (8%) had a complete response, one (8%) had a partial response, and 3 (23%) partially responded but remain PP-dependent. All 5 responders were started on PP within 30 days of recurrence, while 7 of the 8 non-responders initiated PP after a delay of at least 42 days (p = 0.0047). FSGS recurred within 30 days of transplantation in all 5 responders, while 4 of 8 non-responders had no evidence of recurrence until 42-150 days after transplantation (p = 0.098). Post-transplant biopsies were examined in 10 patients and revealed either cellular (6) or collapsing (4) variants of FSGS. We conclude PP is less effective in adults than in children as a treatment for recurrent FSGS in the renal allograft. Predictors of response to PP include early initiation of treatment after recurrence and possibly an early recurrence of disease.


Subject(s)
Glomerulosclerosis, Focal Segmental/etiology , Glomerulosclerosis, Focal Segmental/therapy , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Plasmapheresis , Adult , Female , Glomerulosclerosis, Focal Segmental/pathology , Humans , Kidney/pathology , Kidney/surgery , Kidney Failure, Chronic/pathology , Kidney Transplantation/pathology , Male , Middle Aged , Recurrence , Remission Induction , Retrospective Studies , Time Factors , Treatment Outcome
14.
Am J Nephrol ; 21(5): 351-6, 2001.
Article in English | MEDLINE | ID: mdl-11684793

ABSTRACT

We report two cases of nephrotic syndrome presenting 18 and 20 months after allogeneic stem cell transplantation (alloSCT) with chronic myelogenous leukemia. Both patients had acute and chronic graft-versus-host disease (GVHD) and renal biopsy findings of membranous glomerulopathy (MG). A review of the literature revealed 10 additional cases of immune-complex-mediated glomerular disease following alloSCT, 8 of which were diagnostic of MG. All patients showed evidence of acute or chronic GVHD. Patients typically presented with preserved renal function (mean creatinine 1.2 mg/dl) and full nephrotic syndrome including heavy proteinuria (mean 9.2 g/24 h), edema, hypoalbuminemia (mean 2.1 g/dl) and hypercholesterolemia (mean 472 mg/dl). Most patients showed stabilization of renal function and significant decreases in proteinuria when treated with steroids and/or cyclosporine. The close temporal association as well as evidence from murine models of GVHD support a pathogenetic association between GVHD and the development of MG.


Subject(s)
Glomerulonephritis, Membranous/etiology , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Acute Disease , Adult , Chronic Disease , Female , Humans , Immunosuppressive Agents/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Male , Middle Aged , Syndrome , Transplantation, Homologous
15.
J Cardiovasc Pharmacol Ther ; 6(2): 111-9, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11509917

ABSTRACT

A major concern associated with the use of antiarrhythmic drugs (AAD) is the occurrence of ventricular proarrhythmia, especially torsade de pointes (TdP). The AADs associated with TdP most commonly include quinidine, procainamide, disopyramide, sotalol, and the newer class III agents, such as ibutilide and dofetilide. It is not simply the administration and nature of an AAD but also several additional factors such as heart rate, ventricular hypertrophy, congestive heart failure, gender, age, concomitant drugs, and impaired drug clearance that influence TdP development. Dosing of these agents should be adjusted to take such factors into account to minimize the incidence of proarrhythmia.


Subject(s)
Anti-Arrhythmia Agents/adverse effects , Long QT Syndrome/chemically induced , Torsades de Pointes/chemically induced , Age Factors , Anti-Arrhythmia Agents/therapeutic use , Creatine/metabolism , Dose-Response Relationship, Drug , Heart Diseases/etiology , Humans , Kidney Function Tests , Metabolic Clearance Rate , Renal Insufficiency/etiology
16.
Semin Nephrol ; 21(4): 403-10, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11455529

ABSTRACT

The influence of racial and socioeconomic factors on the incidence, prognosis, and response to therapy of many diseases has long been noted. Although glomerular diseases comprise 10% to over 16% of the dialysis and renal transplant populations, respectively, only recently have racial and socioeconomic factors been evaluated. Several glomerular diseases are associated with a striking African-American predominance. These include idiopathic focal sclerosis, and especially its collapsing variant, human immunodeficiency virus (HIV)-associated nephropathy, and severe lupus nephritis. In many of these entities the renal disease is also more aggressive and rapidly progressive than in other populations. Recent data points to genetic-biologic as well as social and economic factors that may be responsible for these findings. Studies dealing with the therapy of glomerular lesions must be stratified for racial and social background differences to avoid bias in outcome. Whether racial and socioeconomic data should be used in treating individual patients, and how, remains an area of controversy.


Subject(s)
AIDS-Associated Nephropathy/ethnology , Glomerulosclerosis, Focal Segmental/ethnology , Lupus Nephritis/ethnology , Socioeconomic Factors , AIDS-Associated Nephropathy/diagnosis , Black People , Female , Glomerulosclerosis, Focal Segmental/diagnosis , Homosexuality/statistics & numerical data , Humans , Incidence , Lupus Nephritis/diagnosis , Male , Risk Factors , United States/epidemiology , White People
17.
Clin Nephrol ; 55(2): 101-8, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11269672

ABSTRACT

End-stage renal disease (ESRD) is associated with an overall one-year mortality of 23.5% in the US, of which cardiac causes constitute 50% of all deaths. Data on incident ESRD patients were obtained from the Health Care Financing Administration's 2728 and 2746 forms by special request from the ESRD Network of New York. 4,948 ESRD patients, who started dialysis in New York State from April 1, 1995, through April 1, 1996, were assessed to identify risk factors present at the initiation of dialysis that predict cardiac death. 899 deaths were registered during the 19-month-follow-up period, 50% of which were from cardiac causes. Using the Cox-proportional hazards model, the increasing age category, white race, the presence of one or more vascular co-morbid conditions, and the presence of diabetes and one or more cardiac co-morbid conditions significantly predicted cardiac death (p < 0.05). Diabetes increased the risk for cardiac death by 48% for those patients without any cardiac co-morbidities (RR = 1.48, p < 0.0082). In contrast with results observed in the general population, gender, serum albumin and body mass index were not significant predictors of cardiac death. In identifying risk factors present at the initiation ofdialysis that predict cardiac death, this study highlights factors that may be modified prior to dialysis initiation in order to improve life expectancy and mortality rates and decrease health care costs for the ESRD population.


Subject(s)
Cardiovascular Diseases/mortality , Kidney Failure, Chronic/complications , Adolescent , Adult , Aged , Cardiovascular Diseases/etiology , Child , Child, Preschool , Comorbidity , Demography , Female , Humans , Infant , Infant, Newborn , Kidney Failure, Chronic/therapy , Male , Middle Aged , New York/epidemiology , Proportional Hazards Models , Renal Dialysis/adverse effects , Risk Factors , Survival Analysis
18.
Kidney Int ; 59(4): 1484-90, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11260412

ABSTRACT

BACKGROUND: A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy (MGN) was conducted. Although MGN remains the most common cause of adult-onset nephrotic syndrome, its management is still controversial. Cyclosporine has been shown to be effective in cases of progressive MGN, but it has not been used in controlled studies at an early stage of the disease. METHODS: We conducted a randomized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone. All patients were followed for an average of 78 weeks, and the short- and long-term effects on renal function were assessed. RESULTS: Seventy-five percent of the treatment group versus 22% of the control group (P < 0.001) had a partial or complete remission of their proteinuria by 26 weeks. Relapse occurred in 43% (N = 9) of the cyclosporine remission group and 40% (N = 2) of the placebo group by week 52. The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study (cyclosporine 39%, placebo 13%, P = 0.007). Renal function was unchanged and equal in the two groups over the test medication period. In the subsequent follow-up, renal insufficiency, defined as doubling of baseline creatinine, was seen in two patients in each group, but remained equal and stable in all of the other patients. CONCLUSION: This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN. Although a high relapse does occur, 39% of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment, with no adverse effect on filtration function.


Subject(s)
Cyclosporine/therapeutic use , Glomerulonephritis, Membranous/drug therapy , Immunosuppressive Agents/therapeutic use , Steroids/therapeutic use , Adult , Cyclosporine/adverse effects , Dose-Response Relationship, Drug , Drug Resistance , Drug Therapy, Combination , Female , Glomerulonephritis, Membranous/urine , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Prednisone/administration & dosage , Prednisone/therapeutic use , Prospective Studies , Proteinuria/etiology , Recurrence , Retreatment , Single-Blind Method , Treatment Outcome
19.
Annu Rev Med ; 52: 63-78, 2001.
Article in English | MEDLINE | ID: mdl-11160768

ABSTRACT

Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic for the disease. Different forms of glomerulonephritis can occur in patients with SLE and can contribute significantly to the associated morbidity and, ultimately, mortality from the disease. Over the past two decades, there have been significant strides in our understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal damage and end-stage renal disease. In this chapter, we review the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discuss the experimental and human data regarding some of the potential newer forms of therapy. We discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD40 ligand, and CTLA4Ig.


Subject(s)
Immunoconjugates , Lupus Nephritis/therapy , Mycophenolic Acid/analogs & derivatives , Abatacept , Antigens, CD , Antigens, Differentiation/immunology , Antigens, Differentiation/therapeutic use , CTLA-4 Antigen , Cyclosporins/immunology , Cyclosporins/therapeutic use , Humans , Immunoglobulins, Intravenous/immunology , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/immunology , Immunosuppressive Agents/therapeutic use , Indazoles/immunology , Indazoles/therapeutic use , Linseed Oil/therapeutic use , Lupus Nephritis/epidemiology , Lupus Nephritis/etiology , Lupus Nephritis/immunology , Morbidity , Mycophenolic Acid/immunology , Mycophenolic Acid/therapeutic use , Oligonucleotides/immunology , Oligonucleotides/therapeutic use , Plasmapheresis , Propionates/immunology , Propionates/therapeutic use , Treatment Outcome
20.
Curr Opin Nephrol Hypertens ; 10(2): 175-81, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11224691

ABSTRACT

The antiphospholipid syndrome is a disorder of hypercoagulability in association with circulating antiphospholipid antibodies directed against epitopes on oxidized phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Disorders associated with antiphospholipid antibodies but not the antiphospholipid syndrome, such as HIV and hepatitis C infection, appear to lack antibodies to beta 2-glycoprotein I. Patients with systemic lupus erythematosus have a high incidence of antiphospholipid antibodies with a high risk of thrombosis, often associated with anticardiolipin antibodies, beta 2-glyocoprotein I antibodies, and the presence of the lupus anticoagulant. Antiphospholipid antibodies are a significant cause of morbidity and mortality in renal patients with and without systemic lupus erythematosus. Renal manifestations include thrombotic microangiopathy and large vessel thrombosis. In patients with end-stage renal disease, antiphospholipid antibodies are prevalent and may increase in frequency with time on dialysis, possibly as a result of oxidative stress incurred during dialysis. The presence of anticardiolipin antibodies have been associated with a high incidence of hemodialysis access clotting. In renal transplant recipients, the incidence of antiphospholipid antibodies is also elevated and may be associated with a higher incidence of primary graft non-function. Although patients with systemic lupus erythematosus have similar renal allograft survival rates to the general population, survival is worse for those patients who are also antiphospholipid antibody positive. Additionally, in hepatitis C positive renal transplant recipients, the presence of anticardiolipin antibodies confers an increased risk of thrombotic complications and the development of thrombotic microangiopathy. Treatment of antiphospholipid antibody syndrome remains centered around anticoagulation with warfarin. The use of immunosuppressive agents has had no dramatic effect on antiphospholipid antibody titers and little clinical effect on thrombotic events.


Subject(s)
Antiphospholipid Syndrome/complications , Kidney Diseases/complications , Antibodies, Antiphospholipid/blood , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Antiphospholipid Syndrome/immunology , Humans , Kidney Diseases/immunology , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Kidney Transplantation/immunology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/immunology
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