Forms Of Lupus Nephritis Research Articles

Lupus Cystitis, From Myth to Reality: A Narrative Review.

Systemic lupus erythematosus is a multisystemic disease that usually involves the urinary tract, often in the form of lupus nephritis. However, another form of compromise of this system is lupus cystitis, which, despite being an unusual condition, turns out to be a challenging diagnosis due to the spectrum of nonspecific abdominal and urinary symptoms. Although the exact pathophysiological mechanism of bladder inflammation remains to be established, the role of small vessel vasculitis measured by immune complexes continues to be supported as a central axis for considering possible therapeutic targets. Additionally, there are no clinical studies that dictate a guideline regarding its treatment, however, the evidence from most cases described in the literature suggests the initiation of pulses of methylprednisolone and cyclophosphamide in treatment regimens similar to those of lupus nephritis. Despite its low prevalence, obstructive complications and kidney damage can lead to increased morbidity and mortality.

P0266PREDICTIVE FACTORS OF COMPLETE RENAL RESPONSE IN PROLIFERATIVE LUPUS NEPHRITIS: A COLLABORATIVE STUDY

Abstract Background and Aims Proliferative lupus nephritis (class III and IV) is the most severe form of lupus nephritis and requires prompt diagnosis and treatment with immunosuppressive therapy. Since it represents the most serious entity and has the greatest functional consequences there is a need to determine which factors in proliferative lupus nephritis are most predictive of good long-term renal function. Method Methods We analysed the data of 49 biopsy-proven proliferative lupus nephritis (18,4% class III and 81,6% class IV) of three different Spanish hospitals to find prognostic factors for complete renal response (CRR), defined as loss of <25% of eGFR and the absence of proteinuria and microhematuria at the end of the follow up. Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. We performed univariate analysis and logistic regression to identify independent risk factors. Results The median follow-up was 8 years (IQR: 3-12,5), during which time 18 patients (36,7 %) achieved CRR. In the univariate analysis complete renal response was related to: (1) at the diagnosis to: age [40,52 (11,29) years vs 29,92 (11,93) p=0,004]; (2) in kidney biopsy to less leukocyte infiltration (42,3% p=0,05); (3) during the follow up to: less comorbities (27,8% vs 64,3% p=0,02), less infections (27,8% vs 58,6% p=0,04) and less hospitalizations due to infections (0% vs 33,3% p=0,010), less prevalence of high BP (22,2% vs 60,7% p=0,01), (4) at the end of follow up to : serum albumin [3,97 (0,59) vs 4,31(0,19) mg/dL p=0,03]. In the logistic regression comorbidies (HR : 5,71 95%IC: 1,56-20,93 p=0,008) and age at the moment of diagnosis (HR : 1,046 95%IC:1,001-1,071 p=0,04) were related to complete renal response. We didn´t find any differences concerning treatments. Conclusion Proliferative lupus nephritis is one of the most severe manifestations of lupus nephritis, resulting in increased morbidity and mortality. Traditionally it has been thought that older patients have a worst prognosis, however we demonstrated that they achieved more frequently CRR. In the management of the patients traditional reno protective measures like strict control of BP must be considered since it is a predictive factor of CRR. We shouldn´t forget about the implications of an aggressive immunosuppressive treatment such as hospitalizations due to infections and comorbities.

Lupus nephritis

Lupus nephritis (LN) is the most frequent and one of the most severe organ manifestations of systemic lupus erythematosus. The central pathogenetic mechanism is characterized by the loss of immune tolerance against autoantigens of the cell nucleus, which can lead to renal inflammation via the formation of nuclear autoantibodies. The clinical manifestations of LN encompass nephritic syndrome with the special form of rapidly progressive glomerulonephritis, nephrotic syndrome and thrombotic microangiopathy. The diagnostic procedures consist of renal function and urine analysis as well as the determination of serum autoantibody profiles and complement components. An early renal biopsy enables a differentiation between the prognostically different forms of LN. In addition to supportive measures, a differentiated immunosuppressive treatment is the main approach for prognostically unfavorable forms. Important components are corticosteroids, cyclophosphamide and mycophenolate mofetil for induction treatment. Currently investigated treatment principles include next generation calcineurin inhibitors and anti-B cell treatment.

Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.

Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease, most commonly in the form of lupus nephritis. Bladder involvement in the disease course takes a subclinical form and may affect both children and adults. Lupus cystitis can precede SLE diagnosis and may present with very unspecific urinary and digestive tract symptoms or no symptoms at all. The exact mechanism of bladder inflammation in lupus is not fully understood; however, histopathological studies suggest a possible role of immune complex-mediated small vessel vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for physicians, due to its complex diagnostics and treatment.

Study of the agreement between clinical opinion of rheumatologists regarding the need for immunosuppression and the result of renal biopsy in adult patients with lupus nephritis

Abstract Introduction In patients with lupus nephritis it is necessary to define the need for immunosuppressive therapy according to histological class observed in renal biopsy. Objective To evaluate the agreement between the opinions of six independent clinical rheumatologists regarding the need for immunosuppression and the result of renal biopsy in patients with lupus nephritis. Materials and methods A cross-sectional study on the agreement between a diagnostic test in adult patients with systemic lupus erythematosus. Each rheumatologist predicted the outcome of the biopsy. In order to evaluate the agreement, a dichotomous qualitative outcome was defined and was considered zero if it was not necessary to add a cytotoxic (classes I, II and VI), and otherwise was (classes III, IV, V or combinations). The percentage agreement and kappa statistics with a confidence interval of 95% was measured. Results Information was collected on 34 patients, with a total of 204 predictions made by 6 rheumatology interns. Rheumatologists were correct in their clinical impression in 180 cases (88.2% concordance rate, overall kappa of 0.62 (95% CI = 0.48–0.76)). Of the 204 scenarios generated, 162 corresponded to proliferative forms of lupus nephritis, for which the rheumatologists anticipated the need for immunosuppression in 153 and failed to treat in 9 cases (5.5%, or about 1 in 18). Conclusions The clinical opinion of rheumatologist is quite successful in defining the need for immunosuppression. In general, expert opinion could eventually be offered as an alternative choice to renal biopsy for the patient.

The role of rituximab in the therapy of secondary glomerulonephritis

Rituximab (RTX), a B-lymphocytes depleting monoclonal antibody, deeply changed the therapeutic landscape of secondary glomerulonephritis in the past decade.RTX has proved to be as effective as cyclophosphamide in inducing remission in ANCA-associated vasculitis and better than azathioprine as maintenance therapy in three different RCT. Treatment's duration and modality, however, remain debated.RTX has been widely used in resistant or relapsing proliferative lupus nephritis (LN), with positive results reported by retrospective studies; however, when employed as an “add-on” induction therapy in a RCT, it did not show a definite additive effect to standard therapy with mycophenolate mofetil and steroid in moderate forms of LN. In prospect, it remains a promising tool both as second-line therapy for resistant forms and as a “steroid-sparing” agent to strengthen induction and to allow reduced or minimal maintenance therapy.RTX is effective in the treatment of HCV-related cryoglobulinemic vasculitis, including ...

Update on the management of lupus nephritis

Abstract The treatment of lupus nephritis still represents a therapeutic challenge for the clinician. Besides early recognition, appropriate guiding by the histologic classification at presentation as well as at relapsing disease, is essential. The most severe proliferative and mixed forms require aggressive induction therapy. Nevertheless, recent but established by RCTs advances, as low dose iv cyclophosphamide, lower doses of cor-ticosteroids and mychophenolate acid (MPA) allow us to achieve remission induction with lower toxicity without any cost in terms of efficacy. For maintenance, azathioprine and mycophenolate acid with concomitant low dose steroids have shown both good results with a slight superiority of mycophenolate acid. Emerging therapies as B cell targeting-either by depleting agents as the anti-CD 20 mAb Rituximab, or by modulating agents as the anti-Bliss Belimumab, further contribute to the effort to minimize toxicity. This review mainly focuses on the recent efforts to treat the most aggressive form of lupus nephritis effectively with the minimal possible toxicity.

FRI0400 Prognostic Role of Allelic Variations of Genes Affecting Haemostasis in the Development of Antiphospholipid Syndrome and Renal Damage in Patients with Systemic Lupus Erythematosus

BackgroundSecondary Antiphospholipid Syndrome (APS) can develop in 20-30% of patients with Systemic Lupus Erythematosus (SLE). Renal damage in the form of Lupus nephritis (LN) develops in 50-70% of SLE patients....

Rare transformation in repeat renal biopsies suggests a different pathogenesis of segmental and global lesions in proliferative lupus nephritis

Heterogeneous histological findings in the renal biopsies of patients with systemic lupus erythematosus were distinguished early into different types of lupus nephritis with different outcomes. The effort to unify the terminology resulted in six classes of the World Health Organization (WHO) classification published in 1982 [1]. Having apart biopsies with normal histology (Class I) and advanced sclerotic lesions (Class VI), it became apparent that there are two main types of lupus nephritis: membranous (Class V) and proliferative (Classes III and IV), although there were also patients with a combination of both membranous and proliferative lesions. Membranous lupus nephritis was shown early to have better outcome than proliferative lupus nephritis, but the relation between focal (Class III) and diffuse (Class IV) lesions remained uncertain. Segmental lesions typical for Class III lupus nephritis resemble the lesions present in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and are very different from global lesions typical for Class IV which, on the other hand, may resemble the immune complex-mediated lesions present, e.g. in idiopathic membranoproliferative glomerulonephritis. According to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) histological classification [1] segmental lesions may be present both in Class III (focal lupus nephritis) if affecting 50% of glomeruli. The ISN/RPS Class IV category thus mixes together segmental lesions in >50% of glomeruli (Class IV-S) and diffuse proliferative lesions (Class IV-G) affecting >50% of glomeruli [2]. Although some authors argued that focal segmental lesions may evolve into diffuse global lesions and both of them may regress (after treatment) into mesangial (Class II) lupus nephritis, other authors referred that there are significant differences between WHO Classes III and IV (and ISN/RPS Class IV-S and IV-G) lupus nephritis both concerning the histological characteristics, clinical presentation and outcome, and that the pathogenesis of segmental and global proliferative lesions may be different [3]. In this issue of NDT Pagni et al. evaluated 142 patients with lupus nephritis and repeat biopsies. Although their original main aim was to look at the role of repeat renal biopsies in routine clinical practice, their paper also adds an important contribution to our understanding of the putatively different pathogenesis of different histological classes of (proliferative) lupus nephritis. Patients with IV-G class of lupus nephritis had, at presentation compared with segmental forms of lupus nephritis (Classes III and IV-S), higher proteinuria, serum creatinine and blood pressure and more mesangial proliferation, wire loops and tuft necrosis in the biopsy. The disease was more severe in both first and repeat biopsy in Class IV-G compared with Class III and IV-S patients and repeat renal biopsy predicted better trend of serum creatinine and proteinuria than the first biopsy. Most importantly, although the transitions between different histological classes were quite frequent (40.8%), the transition between segmental (III/IV-S) and mesangial (II/IV-G) forms was extremely rare, strongly suggesting that really both forms may have not only different clinical and histological features, but also different pathogenesis. Important differences in the histology between IV-G and IV-S patients were repeatedly (and relatively consistently) described. Patients with IV-S class had, compared with IV-G class, e.g. fewer glomeruli with wire loops [3, 4] and hyalin thrombi [3], more frequent fibrinoid necrosis [4–7], lower endocapillary proliferation [6], significant trend to the higher proportion of crescents [4], less frequent infiltration of glomeruli with monocyte/macrophages, lower interstitial inflammation [6] and less IgG (or even complete absence of IgG) on immunofluorescence [3]. Histologic differences may be translated into some differences in the clinical presentation. Class IV-G lupus nephritis was shown to present, compared with Class IV-S, with higher serum creatinine, worse proteinuria [4–6] and higher diastolic blood pressure [4, 7] and also lower C3 [5, 6] and lower proportion of patients with the positivity of anticardiolipin antibodies [6]. Patients with Class III were also shown to have a lower prevalence of the positivity of anti-C1q compared with Class IV patients [8] and patients with segmental lesions (Classes III and IV-S) have the lowest levels of complement factor H in SLE and lupus nephritis patients [9]. IN F O C U S

An Update on Treatment and Outcome of Lupus Nephritis in Children

Lupus nephritis (LN) is the most common manifestation of systemic lupus erythematosus (SLE) in children to determine the course and outcome of the disease. Although its prognosis has improved in recent decades, varying degrees of chronic renal impairment, including end-stage renal disease (ESRD), can still develop. Early and adequate treatment in LN protects the kidneys from developing chronic damage. Treatment should be based on the clinical severity of the disease and renal histology. Although there are still many controversies on the best treatment of pediatric LN, corticosteroids (CS) are still the first-line drugs used for induction therapy. Less severe forms of LN do not require specific therapy, apart from the treatment of underlying SLE itself, but focal or diffuse proliferative glomerulonephritis requires more aggressive therapy with different combinations of other immunosuppressive drugs. Induction pro tocols in most centers mainly included intravenous cyclophosphamide (CYC) pulse therapies with promising initial results, although more recent studies have been less encouraging. Oral mycophenolate mofetil (MMF) was shown to be at least equally effective as CYC for induction and maintenance therapies and has now become more commonly utilized in pediatric patients. There have also been increasing reports about successful B-lymphocyte depletion therapy with rituximab (RTX) in recent years. Mizoribine, azathioprine, cyclosporine A, and hydroxychloroquine are other therapeutic agents that are used in many centers for induction and maintenance therapies. Plasma exchange and stem cell transplantation can be used in very severe and refractory cases of SLE. New treatment approaches are still under investigation.

Recent advances in the treatment of lupus nephritis

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) which is associated with significant morbidity and mortality. The concept of two phases of therapy for lupus nephritis, such as an induction phase and a maintenance phase, is widely accepted. Since the renal involvement in SLE is heterogeneous, the treatment of lupus nephritis is governed by its pathological type and ranges from nonspecific measures, such as maintenance of adequate blood pressure control and blockade of the renin-angiotensin-aldosterone system, to the use of immunosuppressive agents. Cyclophosphamide (CYC) in combination with prednisone has been the standard method of treatment of the proliferative forms of lupus nephritis. However, the high rates of progression to end-stage renal disease coupled with the adverse effects of CYC and prednisone have led to an intensive search for more effective and less toxic therapies for lupus nephritis. We review the options available for the treatment of proliferative and membranous lupus nephritis and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.

Clearing the complexity: immune complexes and their treatment in lupus nephritis

Systemic lupus erythematosus (SLE) is a classic antibody-mediated systemic autoimmune disease characterised by the development of autoantibodies to ubiquitous self-antigens (such as antinuclear antibodies and antidouble-stranded DNA antibodies) and widespread deposition of immune complexes in affected tissues. Deposition of immune complexes in the kidney results in glomerular damage and occurs in all forms of lupus nephritis. The development of nephritis carries a poor prognosis and high risk of developing end-stage renal failure despite recent therapeutic advances. Here we review the role of DNA-anti-DNA immune complexes in the pathogenesis of lupus nephritis and possible new treatment strategies aimed at their control.

Treatment of proliferative lupus nephritis: a slowly changing landscape

Proliferative lupus nephritis is the most severe form of lupus nephritis. Outcomes of this disease are affected by ethnicity, clinical characteristics, irreversible damage on renal biopsy, initial response to treatment and future disease course (for example, the occurrence of renal flares). Initial intensive (induction) treatment of proliferative lupus nephritis is aimed at achieving remission, but optimal duration and intensity are not well defined. A combination of intravenous cyclophosphamide and corticosteroids have been shown to decrease the risk of end-stage renal disease, but are associated with substantial acute toxic effects (such as infections) and chronic toxic effects (such as ovarian failure). In white populations, low-dose cyclophosphamide is a reasonable alternative to high-dose cyclophosphamide as it is similarly effective and associated with less toxicity. Mycophenolate mofetil is as effective as high-dose intravenous cyclophosphamide in terms of inducing remission and similar in terms of safety. Although most patients respond to induction treatment, remission is often only achieved after patients are switched to maintenance treatment. As maintenance treatment, mycophenolate mofetil is superior to azathioprine and azathioprine is similarly effective to ciclosporin in terms of prevention or reducing the risk of relapse. Rituximab should be reserved for patients with refractory disease. Treatment of lupus nephritis should be individually tailored to patients, with more aggressive therapy reserved for patients at high risk of renal dysfunction and progression of renal disease.

Long-Term Outcome of Patients with Lupus Nephritis: A Single Center Experience

Lupus nephritis (LN) is an immune inflammation of kidneys caused by systemic lupus erythematosus (SLE), a chronic inflammatory disease that affects the body's immune system. Aim of this study was to analyze clinical manifestation and treatment results of patients with LN. Forty one patients with clinical signs of LN were included in the study. Mean age of patients was 31.9+/-12.1 years in the moment of first diagnosis of LN, with female-male ratio 8:1. Renal disease was pathohistologically (PTH) verified in 53.7% of patients (4 pts with class III, 17 pts with class IV, one pt with class V of lupus nephrites). Patients with high nephrotic proteinuria were treated with pulse dose of methylprednisolone and pulse doses of cyclophosphamide (CYC) in induction therapy. Corticosteroid and CYC were continued according to treatment protocol. The other group of LN patients with lower nephrotic proteinuria was treated with mycophenolate mofetil (MMF) in induction therapy at a dose of 2x1 g/day for six months, and than in maintenance 2x0.5 g/day. The patients with non-nephrotic proteinuria and normal renal function were treated with oral prednisolone 0.75-1 mg/kg/day in a single morning dose, and then gradually reduced to the dose of maintenance. The mean time of patient's follow-up was 10.9+/-4.1 years. Partial renal remission was accomplished in 29.2% pts, and complete remission in 60.9% pts for period of 17.2+/-13.3 months from the beginning of the treatment. Duration of complete renal remission was 30.1+/-19.1 months. During the period of follow-up, 29.3% pts developed at least one nephritic flare and were treated again. These results confirmed that the aggressive form of lupus nephritis should be treated associating cyclophosphamide with corticosteroids therapeutical regiment. MMF is a new promising immunosuppressive drug for a treatment of this serious disease.

Chemoattractant mechanism of Th1 cells in class III and IV lupus nephritis

Proliferative lupus nephritis (PLN) is the common, severe, and important form of lupus nephritis. Recent report showed that T cells producing Interferon (IFN)γ (Th1 cells) increased in patients with World Health Organization class IV. However, the relation between the increase of Th1 cells and the pathogenesis has been made unclear. The aim of this study was to examine the chemoattractant mechanism of Th1-producing cells and whether in vitro IFNγ secretion from Th1-producing cells in PLN. The Th1:Th2 ratio in peripheral blood was measured by flow cytometry. The serum levels of IL-2, IFNγ, IL-13, monocyte chemoattractant protein-1 (MCP-1) and IP-10 were determined by using enzyme-linked immunosorbent assay. In in vitro IFNγ production assay, CD4+T cells co-cultured with IL-12 and/or IL-18. Th1:Th2 ratio in PLN was high and not correlated with the serum Th1 cytokine level. This Th1-producing cell tended to go toward the inflammatory lesion by low CD62L expression and chemokines. The level of MCP-1 and IP-10 in patients with PLN significantly increased. Lastly, in vitro IFNγ production assay, patients with PLN CD4+T cells produced IFNγ by the addition of IL-12 and IL-18, while CD4+T cells in normal controls did not produce. These findings suggest that combination of Th1 inducers and chemokine inhibition might be powerful threrapeutic approach in PLN.

Immunohistochemical Expression of Activated Caspase-3 as a Marker of Apoptosis in Glomeruli of Human Lupus Nephritis

The role of apoptosis in lupus nephritis (LN) is still controversial. One of the key events in the process of apoptosis is activation of caspase-3. Studies of experimental models suggested that activated caspase-3 is a reliable indicator of apoptotic rate, with a favorable comparison against terminal transferase-mediated DNA nick-end labeling (TUNEL) assay. Our aim is to study apoptosis in various forms of LN and its relationship to histomorphological changes and selected laboratory findings by using activated caspase-3 as a novel marker of apoptosis. We investigated glomerular cell apoptosis in 51 biopsy specimens from patients with LN classified according to the International Society of Nephrology/Renal Pathology Society classification by using the TUNEL method and immunohistochemistry against activated caspase-3. In addition, activity and chronicity indices were calculated and anti-Ki-67 antibody was used to estimate proliferative activity. Activated caspase-3-positive cells were present in glomeruli of 88.2% of cases, observed in the glomerular tuft and cellular and fibrocellular crescents. In the glomerular tuft, they were found mainly in segments with active inflammatory lesions. There was good correlation between apoptotic index assessed by using activated caspase-3 immunolabeling and the TUNEL method (r = 0.72; P < 0.01). We observed a significant positive correlation between apoptotic index and LN class (P < 0.001). Apoptotic index correlated significantly with activity index, proliferation index, and daily protein excretion (P < 0.001), but not chronicity index, creatinine concentration, or anti-DNA antibody-binding activity in serum. Apoptotic rate is greater in severe active glomerular lesions in human LN, suggesting that apoptosis may be involved in augmenting inflammation in human LN.

Defining the Role of Mycophenolate Mofetil in the Treatment of Proliferative Lupus Nephritis

Systemic lupus erythematosus, which predominantly affects young women, is frequently complicated by renal involvement. The presence of acute glomerulonephritis significantly adds to morbidity and mortality. Cyclophosphamide has become the mainstay of treatment in patients with proliferative forms of lupus nephritis. However, adverse events such as severe infections and infertility have spurred the search for novel treatment regimens and agents. Sequential therapy has significantly reduced adverse events. In several pilot studies, mycophenolate mofetil (MMF) has emerged as a promising therapeutic approach for both the induction and maintenance phase in patients with lupus nephritis, delivering equal efficacy and a better adverse effect profile; however, these studies had a limited power, and a large, multicentre and probably multinational clinical trial will be needed to discern the optimal therapeutic approach. On the basis of the currently available literature, sequential therapy with cyclophosphamide induction followed by azathioprine or MMF maintenance can be recommended for most patients. In selected populations, induction with MMF is a reasonable option to reduce adverse events.

The classification of glomerulonephritis in systemic lupus erythematosus revisited

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

Renal disease in the inner city

For various ethnic and socioeconomic reasons the pattern of renal disease in the inner city displays distinctive features. Hypertension is frequent, often intractable, and generally conditioned by salt sensitivity and a high sodium intake. Chronic hypertensive nephrosclerosis, found predominantly in African Americans, comprises marked cardiomegaly, renal shrinkage, and hypertensive retinopathy. It has been overdiagnosed in the past, but actually accounts for less than 20% of end-stage renal disease (ESRD) in African Americans. Malignant hypertension, less frequent nowadays, may cause renal shutdown, which is reversible in a few cases; the heart and kidneys are often of normal size. Idiopathic focal segmental glomerulosclerosis is the most common cause of the primary nephrotic syndrome in blacks, but its incidence has also been rising in whites and Hispanics; it does not respond well to treatment, and almost one half of the patients develop ESRD within 10 years. Systemic lupus erythematosus is also more common in African Americans, in whom the severe proliferative forms of lupus nephritis pursue a more virulent course: one half of such patients develop ESRD in 5 years. Cocaine, the use of which has assumed epidemic proportions, may cause accelerated hypertension, acute renal failure from rhabdomyolysis, and progression of preexisting renal disease. Heroin nephropathy has all but disappeared and has been replaced by human immunodeficiency virus (HIV) nephropathy. The prognosis of HIV-infected patients maintained by dialysis has greatly improved. Sickle glomerulopathy, consisting of mesangial expansion, basement membrane duplication, and the absence of immune deposits, may cause the nephrotic syndrome in 4% of patients with severe sickle cell anemia, heralding death within 2 years in one half of patients and ESRD in two thirds; survival has not improved with dialysis. Diabetes is now the most common cause of ESRD. Familial aggregation of ESRD is frequently encountered. Interventions useful in the general population, such as vascular bypass procedures, should be undertaken with great caution and restraint in dialysis patients.

Renal vascular lesions in lupus nephritis.

We retrospectively studied the prevalence, histologic features, clinical correlations, and long-term outcome of the intrarenal vascular lesions of lupus nephritis (LN) in a series of 169 renal biopsies performed between 1980 and 1994 in 132 patients with systemic lupus erythematosus. The most common vascular lesions were nonspecific sclerotic changes, found in 37% of the biopsies (24% if only the cases with moderate to severe changes are considered). The other common vascular lesions were "immunoglobulin microvascular casts," found in 24% of the biopsies. Vasculitis and thrombotic microangiopathy were rare lesions and were seen in only 4 (2.4%) and 1 (0.6%) cases, respectively. Isolated sclerotic vascular changes were present in biopsies from older patients with a longer duration of LN, compared with the group with no vascular lesions, and were associated with a significantly higher prevalence of hypertension. Overall, however, the long-term renal and patient survival of this group did not differ significantly from that of the patients without vascular changes. Immunoglobulin microvascular casts (IMCs) ("lupus vasculopathy") were characterized by the presence of immunoglobulin deposition within the glomerular capillaries and small arterioles. In the present study we extensively investigated the morphologic and immunologic features of this lesion. The lesions were notable for the absence of endothelial or parietal vascular lesions and of fibrin, platelets, and leukocytes, which indicates that thrombosis is not involved in the vascular obstruction. According to our data immunoglobulin precipitation in the microvasculature seems to play a central role in the pathogenesis of this lesion, which is why we propose the term "immunoglobulin microvascular casts." In general, IMCs were associated with the most severe and active forms of diffuse proliferative lupus nephritis (World Health Organization [WHO] class IV). However our data show that, in contrast to previous studies, the long-term outcome of patients with IMCs is not worse than that of other patients with class IV LN. It may even be somewhat better, suggesting that this type of lesion may reverse with immunosuppressive therapy. In addition, we did not find any association between the presence of IMCs and the lupus anticoagulant, IgG anticardiolipin antibodies, or extrarenal vascular manifestations. Concerning vasculitis and thrombotic microangiopathy, our results confirm that their occurrence is quite rare in-lupus nephritis. The outcome of our 4 patients with vasculitis was not particularly poor, which could be related to early and/or aggressive treatment. Taken as a whole, our data confirm that the presence of active and severe forms of diffuse proliferative LN (WHO class IV) carries a worse prognosis compared with the other forms of LN. In our study, and in agreement with previous reports (23), the long-term renal survival of patients with class IV LN was significantly worse than that of patients with other forms of LN, with a 10-year renal survival of 70% compared with 85%, respectively. However our data do not support the conclusions of some previous studies that the presence of intrarenal vascular lesions is a marker of poor renal prognosis in lupus nephritis. More precisely, our data show that the somewhat poorer renal outcome observed in patients with IMCs is related to the fact that in most cases these lesions are associated with class IV lupus nephritis, and not related to the presence of the vascular lesion per se.