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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2000  |  Volume : 11  |  Issue : 3  |  Page : 381-395
Management of Lupus Nephritis

Medical Clinic I, Cologne City Hospital, Cologne-Merheim, Germany

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Summary : Renal disease is common in systemic lupus erythematosus (SLE) and significantly influences patient prognosis. Immunosuppressive therapy has markedly improved outcome, however, it increases the risk of infection and cancer induction. Although several therapeutic regimens have proved to be effective in controlling lupus nephritis (LN), optimal therapy is still a matter of discussion. The following review summarizes our current knowledge in treating LN and discusses new aspects in pathogenesis. Hopefully, continuing progress in uncovering details about the pathogenesis of SLE might lead to more disease­specific approaches to treat the underlying immunological disorder.

Keywords: Systemic lupus erythematosus, Autoimmunity, Immunosuppressive therapy, Lupus nephritis, Glomerulonephritis.

How to cite this article:
Merkel F, Gross O, Weber M. Management of Lupus Nephritis. Saudi J Kidney Dis Transpl 2000;11:381-95

How to cite this URL:
Merkel F, Gross O, Weber M. Management of Lupus Nephritis. Saudi J Kidney Dis Transpl [serial online] 2000 [cited 2021 Apr 10];11:381-95. Available from: https://www.sjkdt.org/text.asp?2000/11/3/381/36660

   Introduction Top

Systemic lupus erythematosus (SLE) is an autoimmune disease with a broad range of manifestations and a great polymorphism in clinical expression. [1] The course of the disease is marked by episodes of active inflammation and clinically silent remission.

All organ tissues may be involved, but it is the skin, the joints, the heart, the nervous system and the kidney that are most commonly affected. Clinical evidence of renal disease occurs in 35 to 75% of patients with SLE. [2] Probably, the total prevalence of renal involvement may exceed 90% because of changes of diffuse lupus nephritis (LN) seen in kidney biopsies from SLE patients without clinical evidence of renal involve­ment. [3] In most cases, renal involvement is mild with, for instance, proteinuria seen in 42%, [4] while life threatening renal disease is relatively rare. Rapidly declining renal function remains a subject of special attention which demands early diagnosis, optimal clinical monitoring, and aggressive immunosuppressive therapy. The survival of patients with SLE is influenced both by the severity of renal involvement and by the serious toxic side effects of the immuno­suppressive agents used.

The pathogenesis of nephritis in SLE

Research in SLE has increased our understanding of the various mechanisms that are important for the induction of the disease. Genetic, hormonal, and environ­mental factors contribute to the patho­genesis, although the etiology of SLE still remains unknown. One of the common features of systemic lupus is the presence of auto-antibodies to various cellular antigens. Whether these auto-antibodies are able to cause disease is still a matter of discussion, but there is evidence that they may play a causal role in the induction of clinical features. [5] One of the mechanisms for tissue injury appears to be the in-situ formation of immune deposits. [6],[7] The deposits are then able to activate the complement cascade and attract the Fc- and complement-receptor bearing leucocytes. The localisation of immune deposits subsequently determines the kind of inflammation in the glomeruli. In membranous nephritis, sub-epithelial deposits of immunoglobulins can be demonstrated histologically with little cellular infiltration. In proliferative glomerulonephritis, deposits can be found in the mesangium and the sub-endothelial space. The activation of complement and the access to the vascular space results in the influx of neutrophils and mononuclear cells. Apart from these humoral and neutrophil­mediated mechanisms, there is an important role for mononuclear cells in the development of glomerular hypercellularity and crescent formation. [8] Such infiltrating inflammatory cells are a major source of pro-inflammatory cytokines in LN. [9] More­over, local resident glomerular cells like endothelial cells, mesangial cells, and epithelial cells are by themselves able to secrete cytokines. [10] Apart from glomerular inflammation, the presence of tubulo­interstitial disease is important for subsequent kidney failure. Here, T lympho­cytes and mononuclear cells may mediate inflammation independent of immuno­globulin and complement deposition. [11]

Auto-antibodies are an important diagnostic feature in SLE, but their role in causing the disease is still a matter of debate. Some of the auto-antibodies are strongly associated with the presence of nephritis such as antibodies to dsDNA, C1q, Sm, and phospholipids. [12] How these antibodies localize to tissue cannot be definitely explained. A trapping of circulating antigen-antibody complexes to glomerular structures seems to be unlikely since pre­formed anti-DNA/DNA complexes are not able to fix to the glomerular basement membrane as shown experimentally. [13] In contrast, nucleosomes have a high affinity for anionic structures within glomeruli and in turn may bind anti-DNA and anti-histone antibodies. This is supported by the fact that the presence of anti-nucleosome antibodies correlated better with the occurrence of nephritis than did the presence of anti­dsDNA antibodies. [14] There is evidence that positively charged histone-DNA complexes act as a bridge between the negative charge of the glomerular basement membrane and DNA at the outer layer of the sandwich. [13],[15] The generation of large amounts of nucleosomes may be due to impaired phagocytosis of apoptotic cells by macro­phages.

Various immune abnormalities have been described in SLE, including a polyclonal activation of B cells in the early phase of the disease, a defect in B cell tolerance, [16],[17] an increase in CD4+ T-cells, [18] and an imbalance in Th1 versus Th2 cytokine production. [16],[17] More recent studies have identified aberrations in antigen receptor mediated signalling events in lymphocytes from SLE patients. [19] They include a decrease in CD2 signalling, an increase in the expression of surface molecules such as CD40L, and an increased production of intracellular calcium and phosphotyrosine. The intrinsic abnormalities in lupus lymphocytes might explain some of the immunoregulatory defects in human lupus.

Genetic predisposition has been described for the development of SLE. The propensity to develop SLE has been linked with markers for the chromosomal region 1q41­q42. [20] Patients with SLE also have a higher frequency of specific genetic markers than the general population such as HLA-B8, HLA-DR2, HLA-DR3, HLA-DQW1, C2 deficiency (C2D), and C4 (especially C4A) deficiency (C4D). [12]

Hormonal factors also seem to play a role in SLE since increased estrogen stimulates CD4+ and CD8+ T-cells, B-cells, and macrophages. The release of certain cytokines (e.g. interleukin-1) is enhanced, and both HLA and endothelial cell adhesion molecules are more frequently expressed. [21] So, as insight from murine models predicts, any one disease-predisposing factor might be unable to produce the full clinical feature of systemic lupus, but it is the addition of a second or third factor that substantially increases the likelihood of disease expression.

The clinical features of lupus nephritis

Nephritis is a common visceral manifes­tation of SLE. An abnormal urinalysis is present in almost half of the patients at the beginning of the disease and in up to 75% in the later course. [4] The total incidence of renal involvement might probably exceed 90% since renal biopsy in patients without any clinical evidence has revealed focal or diffuse proliferative glomerulonephritis. [3] However, severe life threatening renal disease is relatively rare.

Lupus nephritis demonstrates a wide spectrum of glomerular alterations reaching from mesangial through focal proliferative to diffuse proliferative glomerulonephritis with crescent formation. Tubulointerstitial nephritis may also be an additional feature. In order to describe the various lesions in the kidney the WHO standard classification is commonly used. In this classification, type I represents an entirely normal kidney biopsy at light microscopy, on immunofluo­rescence, and electron microscopy. [22] Mesangial and sub-endothelial deposits are characteristics of focal or diffuse proliferative immune-complex glomerulonephritis (type II-IV, [Table - 1]). Diffuse thickening of the basement membrane with normal glomerular cellularity and electron-dense deposits in the sub-epithelial space of the basement membrane are found in type V LN. Appro­ximately 75% of renal biopsy specimens reported in several studies have been classified as focal proliferative, diffuse proliferative, or membranous glomerulo­nephritis. [23] In some patients with slowly progressive renal dysfunction and a relatively normal urinary sediment, only sclerosing glomerulonephritis can be found histologically (type VI). This form may represent healing from a prior inflammatory injury. In an individual patient, multiple histopathological findings belonging to more than one WHO class in parallel may be apparent on biopsy. [24],[25],[26]

Since the clinical course in LN is extremely variable, an individual prognosis is difficult to predict. In recent years, a substantial improvement in the survival of patients with SLE has been documented. [27] Five-year survival rates of 90% and 10-year survival rates of more than 80% have now been demonstrated, [25] compared with 5-year survival rates of 25 to 40% in the decade 1960 to 1970. [28] The improvement has been due to advances in therapeutic options and in general medical care. Survival is still low in SLE patients with severe multi-system disease. Infection is the most common cause of death. [29] Other leading causes are related to acute vascular neurologic events, renal failure, [30] and coronary artery disease. [31] The presence of severe renal disease and systolic hypertension seems to be associated with a decreased survival in SLE. [32]

The prognosis of SLE with renal involve­ment depends on the activity of the underlying renal disease, and the degree of already existing renal functional impairment. Whether or not renal pathological findings may be of prognostic help still remains controversial. Some studies found that active (hypercellularity, fibrinoid necrosis, cellular crescents) or chronic (glomerulo­sclerosis, fibrous crescents, interstitial fibrosis, tubular atrophy) lesions on kidney biopsy were helpful to discriminate between favorable and worse renal outcome. [33],[34],[35] Especially, the demonstration of chronic lesions have been reported to increase the risk of later development of renal insuf­ficiency. [36],[37],[38] However, others were not able to find a correlation between the chronicity index and renal outcome. [39],[40] In fact, these lesions might only reflect post-inflam­matory scarring without implication for future renal damage. Not surprisingly, histologically documented irreversible nephron damage is unresponsive to therapy. [41] Information from kidney biopsy is further limited by the fact that transformation of one morphological pattern to another occurs in 15 to 40% of rebiopsied patients. [42] By contrast, patients with severe active disease indicated by diffuse proliferative lupus glomerulonephritis with endocapillary proliferation or necrosis in more than 50% of the glomeruli (WHO class IV) have a worse prognosis compared to all other groups. [43] The reported 10-year survival in this group is about 60%. Prognostic approaches including clinical and histologic parameters such as nephrotic range protei­nuria, evidence of systemic disease activity, and histologic evidence of extensive crescents and fibrinoid necrosis seem to indicate a greater likelihood of renal disease progres­sion. [25],[44] Moreover, hypertension and/or initial serum creatinine have been identified as predictors of outcome. [45] The former is a well known prognostic factor in all kidney diseases. The latter represents a pre-existing decline in glomerular filtration rate and an already reduced renal function prior to diagnosis. In general, kidney survival has considerably improved during the last decade as shown in a multicenter study of 536 patients with lupus nephropathy. About 80% of patients still retained adequate renal function 10 years after diagnosis. [46] Memb­ranous glomerulonephritis in SLE has an unpredictable course and outcome. [47] This variability is related to the extent and degree of glomerulonephritis seen on renal biopsy. While the course in membranous glomerulonephritis in SLE is reported to be similar to that of the idiopathic variety, [48] the prognosis is poor in patients with superimposed focal or diffuse proliferative glomerulonephritis. [49]

   Treatment Top

Treatment of patients with LN is a balance between the risk of progressive disease with deterioration of renal function and a potentially harmful medication. No clear cut evidence­based medicine has been established although a broad range of possibilities is available.


Glucocorticoids are the cornerstone in the treatment of SLE. Their positive effects on extrarenal manifestations have been well documented. [43],[50] This was then extended to LN, though it's effectiveness is less well established. In one of the first studies, a group of patients were treated with high doses of corticosteroids and compared retrospectively with a group of patients formerly treated with low doses of corticosteroids. Although this was not a randomized trial, the high-dose treatment in this study was more effective in treating nephritis in SLE. [51] Since then, most of the patients with renal manifestations of SLE are treated with steroids at doses of at least 1 mg/kg body weight per day. For patients with mesangial or mild focal proliferative glomerulonephritis, low to intermediate doses of glucocorticoids (0.2-0.5 mg/kg body weight per day) are usually sufficient. [7][52] On the other hand, most investigators believe that low-dose steroid therapy is inadequate to treat diffuse proliferative and severe focal proliferative glomerulo­nephritis although no well-controlled clinical trials exist. Since the 1970s, pulse intravenous corticosteroid therapy has been introduced to treat diffuse LN. Methyl­prednisolone is usually given at doses of 1g/day intravenously for three consecutive days, followed by oral prednisone at doses of 0.5 mg/kg/day for four weeks, reduced to alternate day therapy by week eight. [53] In small controlled and uncontrolled studies this kind of therapy proved to be beneficial particularly when renal deterioration has been of short duration. [54],[55],[56] For example, in a study of 34 patients with diffuse proliferative LN treated with pulse steroid therapy, only 12 experienced at least a 20% decrease in plasma creatinine within the first two months of treatment. [54] Neverthe­less, the long-term effect of steroid therapy on patient survival and renal function is still questionable. [57] Some patients may do well with initial therapy consisting of high doses of oral or intravenous glucocorticoids, and therefore, most clinicians believe that a trial of glucocorticoid therapy should be attempted before other cytotoxic agents are introduced.

Cytotoxic drugs

Several cytotoxic drugs which interfere with the autoimmune inflammatory process have been tested in patients with renal manifestations of SLE. These cytotoxic drugs were usually tested in combination with low-dose steroids (5 to 30 mg/day oral prednisone). Because of small numbers of patients involved in those studies, the results were conflicting. Both azathioprine and cyclophosphamide proved to be effective in the treatment of SLE. [58],[59] In a meta-analysis of eight randomized trials conducted between 1972 and 1982, the superiority of cytotoxic drugs in combination with oral steroids compared to high-dose steroid therapy alone could be demon­strated. [60] Patients who received either cyclophosphamide or azathioprine had less deterioration of renal function and were less likely to develop renal failure; mortality was similar in both groups.

In a study from the NIH in the mid-1980s, active LN was treated in 107 patients by using five different treatment protocols: a) high-dose steroids (prednisone 1 mg/kg body weight per day), b) azathioprine (up to 4 mg/kg body weight per day), c) oral cyclophosphamide (up to 4 mg/kg body weight per day), d) combined oral azathioprine and cyclophosphamide up to 1 mg of each per kg body weight per day, and e) intravenous (i.v.) cyclophosphamide every three months at initial doses of 0.75g/m 2 . [61] Superior results were observed in patients receiving one of the cytotoxic drug regimes. A significant difference in the risk of developing end-stage renal disease (ESRD) could only be demonstrated when comparing i.v. pulse cyclophosphamide with the sole application of prednisone. This difference was maintained beyond five years of follow-up. The majority of patients who were included in this study had diffuse proliferative glomerulonephritis (class IV), but a few patients with membranous or severe focal proliferative glomerulo­nephritis (class III and V) were also included. In a subsequent report, the follow­up in the same group of patients was extended by 40 months. [62] The probability of developing ESRD was less in the groups treated with either i.v. or oral cyclophos­phamide and combined oral administration of azathioprine and cyclophosphamide. From the 107 patients at the beginning of the study, only few patients could be monitored for more than five years. Therefore, changes in the survival curves were based on relatively small numbers of cases. Remarkably, the effect of therapy on patient survival did not differ among any of the five treatment groups. Similar results were obtained in a trial of 50 patients who were treated for a 6-month period with either a) oral prednisone (40 mg/d), b) low doses of oral prednisone (25 mg/d) or c) oral cyclophosphamide (1-2 mg/kg body weight per day). [63] After four years of observation, the incidence of progressive nephritis was less in the patients who were initially treated with a combination of cyclophosphamide and prednisone compared to those given prednisone alone. However, in the five-year follow-up, no difference in the patient survival or in the frequency of ESRD could be observed. [64] In another small uncontrolled trial, monthly i.v. administration of cyclophosphamide proved to be beneficial after six months in nine patients with LN. [65] Unfortunately, the follow-up was too short to draw any conclusions about the long-term benefit. In a subsequent trial from the NIH, patients with severe LN have been treated either with monthly pulses of methylprednisolone, monthly pulses of i.v. cyclophosphamide for six months (short course), or monthly pulses of i.v. cyclophosphamide for six months followed by an additional dose every three months for two years (long course). [66] After a minimum follow-up of five years, pulse steroids have been found to be less effective than i.v. cyclophos­phamide. Moreover, flare-ups of active renal or extra-renal disease were more likely to occur in patients who received an intensive 6-month course of pulse cyclo­phosphamide than in those who received a 30-month course. Doubling of the serum creatinine level occurred in 50% of the pulse methylprednisolone group, 25% developed ESRD. Short course of i.v. cyclophosphamide resulted in a doubling of the serum creatinine level in 33% and ESRD in 25%. Long-term therapy reduced the frequency of doubling of serum creatinine level to 15%, and the occurrence of ESRD to 10%. On the basis of this data, it has been recommended that patients should receive quarterly pulse cyclophos­phamide as maintainance therapy for approximately one year. [7]

In patients with SLE and rapidly declining renal function, therapy remains unsatisfactory. In a recently published prospective five­year study, patients with severe active LN were treated with six-monthly i.v. pulses of cyclophosphamide together with high-dose corticosteroids. Five out of twenty patients failed to respond to treatment. This is defined as a doubling of serum creatinine over the baseline. [67] Three patients developed ESRD. Those who did not respond to therapy were more likely to have diffuse proliferative LN (WHO class IV) lesions on initial biopsy.

Treatment of membranous lupus nephritis

The appropriate treatment of membranous LN is even more controversial. There is some agreement that patients without severe proteinuria and stable renal function should only be treated symptomatically. On the other hand, most reported patients with membranous LN are treated with steroids because of extrarenal disease manifestation(s). Thus, the natural history is difficult to predict. The renal prognosis is usually good [68] and many patients do well when they are treated primarily with prednisone. [49] There is little evidence about the use of cytotoxic drugs in severe nephrotic syndrome. As in idiopathic membranous nephropathy, a combination of chlorambucil and methylprednisolone may be used. In a retrospective study involving 19 patients, the combination seems to induce a more stable remission and may better protect renal function in the long-term than corticosteroids alone. [69] In another small study of 22 patients with membranous nephropathy, patients were treated either with prednisone alone, pulse cyclophos­phamide or cyclosporine for one year. [70] Each therapy seemed to be effective with cyclophosphamide perhaps being most beneficial.

Long-term complications of therapy

Complications of LN and its treatment are frequent in the long-term. In a study of 110 patients, serious complications occurred in 49%, with sepsis in 32%, ischemic heart disease in 20%, thrombosis in 1% and avascular necrosis of bone in 8%. [71]

Toxicity from immunosuppressive drugs is one of the major problems in long-term therapy. The most common toxic effect is depression of normal hematopoesis predisposing first to infection or second to the induction of a malignant tumor. [72] Infection has replaced renal failure as the most common cause of death in SLE. The total number of infections did not differ when patients were treated with either corticosteroids alone or with a combination of steroids and cyclophosphamide. [66] But, as shown in a recent study, the risk of serious infection was increased when cyclophos­phamide was included in the treatment regimen. [73] One hundred SLE patients who were treated with cyclophosphamide were observed for occurrence of serious infections during therapy and the subsequent three months after therapy. Infection occurred in 45 patients with a WBC nadir < 3,000/cu mm. No difference between oral and i.v. cyclophosphamide therapy could be observed.

In a study of 1,634 patients who were treated with immunosuppressive drugs (68% with azathioprine, 28% with cyclophosphamide), an excess of non­Hodgkin's lymphoma, squamous cell skin cancer and bladder cancer was observed. [74] The relative risks were 10.9, 5.0, and 3.7 respectively. Cyclophospamide therapy is specifically associated with serious side effects. Long-term oral administration of this drug is associated with an important risk of urotoxicity, including hemorrhagic cystitis and invasive bladder cancer (average dose of cyclophosphamide 101gm). [75] The risk might be reduced by adequate hydration and the administration of 2-mercaptoethane sulfonate (mesna). Alkylating agents have a dose-related toxic effect on reproductive tissue. The cumulative threshold dose above which oligospermia may be expected is between 150 and 250 mg per kg body weight. [76] While hemorrhagic cystitis and bladder cancer have been observed mainly in patients treated with oral cyclophos­phamide, i.v. pulse therapy increases the risk for gonadal failure. [66] Amenorrhoea occurred in many female patients who were treated with i.v. cyclophosphamide. [77]

Treatment of resistant lupus nephritis

Failure of conventional therapy with steroids, cyclophosphamide or azathioprine is defined as resistant LN, usually of the diffuse proliferative type. In such cases, other therapeutic options have been tried, including plasmapheresis, cyclosporine, i.v. immunoglobulins, and mycophenolate mofetil.


In small uncontrolled studies, plasma­pheresis in combination with low-dose steroids and cytotoxic agents was claimed to have a beneficial effect especially in those patients with diffuse proliferative nephritis. In a prospective study, the expected additive beneficial effect of plasmapheresis in combination with low-dose steroids and cytotoxic agents could not be demonstrated compared to the effectiveness of prednisone and daily oral cyclophosphamide alone. [78] Other investigators have proposed that the benefit might be increased by synchronized plasmapheresis and i.v. pulse cyclophos­ phamide therapy. [79],[80] However, definitive results have not been reported since then, probably indicating failure of that hypothesis. Although treatment-free clinical remission might be achieved in some patients with severe SLE, the number of patients who were treated is much too small (4 and 12 patients, respectively) to draw any general conclusions. A significant number of adverse effects, including serious infections and death in association with plasmapheresis and pulse cyclophos­phamide therapy have been reported. [81] Thus, up till now, there is no proven role for plasmapheresis in LN given the limited evidence of efficacy and the possibility of increased toxicity.


Cyclosporine is not generally accepted in the treatment of SLE. Although there are some encouraging results, [82] some inves­tigators found that the nephrotoxic side effects of cyclosporine can outweigh the immunosuppressive benefit. [83] There are however, single reports of patients who responded to cyclosporine better than to other treatment regimes such as steroid therapy, cyclophosphamide, or plasma­pheresis. [84] A further role for cyclosporine may be lupus membranous nephropathy. [85] In pediatric LN with heavy proteinuria (type III-V), cyclosporine A was used to treat those with steroid resistance or with severe corticosteroid toxicity. [86] Therapy proved to be effective in suppressing proteinuria. That cyclosporine A is effective and can be used in long-term treatment, has been shown in two small studies with nine and 17 patients respectively. [87],[88] We also treated six patients, who were defined as treatment failures under conventional therapy, successfully into clinical remission. In summary, the combination of cyclosporine and prednisone was effective and safe, although with the risk of nephrotoxicity.

Mycophenolate mofetil (MMF)

Another drug which is effectively used as immunosuppressive therapy in renal transplant patients is mycophenolate mofetil (MMF). Therapeutic effect of MMF was first tested in SLE-prone MRLlpr/lpr mice. [89],[90] Survival of MMF treated lupus mice was signifi­cantly improved compared to untreated animals. MMF reduced the severity of glomerulonephritis and proved to be as efficacious as treatment with cyclosporine A. These results warrant clinical trials of MMF in SLE patients with glomerulo­nephritis. Unfortunately up to now, there are only few uncontrolled studies with small numbers of patients. Two patients with diffuse proliferative glomerulonephritis who failed to respond to i.v. cyclophos­phamide therapy were treated with MMF and responded favorably. [91] In a second study, 12 patients with relapsing or resistent nephritis were treated with MMF (0.5 to 2g/d) and prednisone. [92] Mean duration of therapy was 12.9 months (range 3 to 24 months). MMF was well tolerated and seemed to be effective in decreasing proteinuria and improving renal function as expressed in a decline in serum creatinine values. Nevertheless, controlled clinical trials are needed to define the role of MMF in the treatment of LN.


Methotrexate has been used successfully in the treatment of rheumatoid arthritis and might also be effective and well tolerated in patients with SLE. [93] Five patients including three with renal disease, were treated with methotrexate because of high disease activity under immunosuppression with prednisone or azathioprine, or because of allergic reactions to azathioprine. No renal biopsies were performed. After three to six weeks of methotrexate therapy, renal function improved and remained stable for the following 12 months. Patients with symptomatic SLE and renal disease may also be treated with i.v. immunoglobulins. [94] Intravenous immunoglobulin therapy seemed to have a temporary beneficial effect in mild to moderately active SLE. [95] In the 12 patients treated in this study, the mean disease activity score declined from 7.33 to 5.25. In three out of the 12 patients, the improvement lasted between five and 12 months. Moreover, there may be some benefit even in those patients with active SLE and progressive renal failure, although only few reports exist and further clinical studies are needed. [96] Novel approaches in the treatment of LN may include the use of extracorporeal immunoadsorption using DNA or anti-DNA-immunoadsorbents, [97],[98] treatment with a blocking monoclonal antibody specific for complement component C5, [99] drugs that deplete specific B cell clones involved in the synthesis of nephritogenic auto-antibodies and blocking of signal transduction pathways required for antigen-dependent antibody synthesis. [100],[101] Especially, the CD40 mediated B-cell activation might be a target for immune modulation and treatment of glomerulo­-nephritis in SLE patients. [102]

End-stage renal disease due to lupus nephritis

Only a small number of patients with LN progress to ESRD (10-30%) and require dialysis or renal transplantation. After the institution of dialysis, extra-renal and serologic manifestations of lupus gradually resolve in most patients and the disease typically remains inactive. [103],[104] Patient survival on hemodialysis or CAPD is similar to the population of patients with ESRD due to other causes. However, there seems to be an increased risk of death during the first three months of dialysis. [104] This might be due to sepsis and other complications of immunosuppressive therapy. Graft survival at five or ten years in patients with SLE is similar to those patients with other diseases indicating that renal transplantation is a safe procedure for lupus patients with ESRD. The rate of recurrent renal disease in the renal allograft varies between 2.0 and 9.0 percent, [104],[105] but is not always associated with allograft loss. Recurrent LN is sometimes found without clinical or serological evidence of active SLE. [106]

   Conclusion and outlook Top

Although immunosuppressive therapy has markedly improved survival in patients with glomerulonephritis due to SLE, physicians have to decide between the benefit and potential side effects of the cytotoxic agents used. Especially in the treatment of resistant LN, further controlled studies are necessary to define the role of alternative treatment options. Furthermore, the risk and benefit between an intensive but short-term treatment of relapsing LN and a long-term, low-intensity maintenance immunosuppressive therapy should be addressed in future clinical trials. Hopefully, continuing progress in uncovering details about the pathogenesis of SLE might lead to additional, more disease-specific approaches to treat the underlying immunological disorder.

   References Top

1.Appel GB, Valeri A. The course and treatment of lupus nephritis. Annu Rev Med 1994;45:525-37.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Estes D, Christian CL. The natural history of system lupus erythematosus by prospective analysis. Medicine Baltimore 1971;50:85-95.  Back to cited text no. 2  [PUBMED]  
3.Leehey DJ, Katz AI, Azaran AH, et al. Silent diffuse lupus nephritis: Long-term follow-up. Am J Kidney Dis 1983;2(Suppl 1):188-96.  Back to cited text no. 3    
4.Wallace DJ. The clinical presentation of SLE. In: Wallace DJ, Hahn BH, eds. Dubois's systemic lupus erythematosus. 4th ed. Philadelphia: Lea & Febiger 1992;317­-21.  Back to cited text no. 4    
5.Walport MJ. The pathogenesis of systemic lupus erythematosus. In: Davinson AM, Cameron JS, Grunfeld JP, Kerr DNS, Ritz E, Winearls CG, eds. Oxford Textbook of Clinical Nephrology. 2nd ed. Oxford University Press 1997.  Back to cited text no. 5    
6.Schwartz MM: Lupus nephritis. Curr Opin Nephrol Hypertens 1995;4:162-8.  Back to cited text no. 6    
7.Boumpas DT, Fessler BJ, Austin HA 3rd, Balow JE, Klippel JH, Lockshin MD. Systemic lupus erythematosus: emerging concepts. Part 1: Renal neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med 1995;122:940-50.  Back to cited text no. 7    
8.Cole EH, Schulman J, Urowitz M, Keystone E, Williams C, Levy GA. Monocyte procoagulant activity in glomerulo-nephritis associated with systemic lupus erythematosus. J Clin Invest 1985;75:861-8.  Back to cited text no. 8    
9.Takemura T, Yoshioka K, Murakami K, et al. Cellular localization of inflammatory cytokines in human glomerulonephritis. Virchows Arch 1994;424:459-64.  Back to cited text no. 9    
10.Couser WG. Pathogenesis of glomerulo­nephritis. Kidney Int Suppl 1993;42:S19-26.  Back to cited text no. 10    
11.Alexopoulos E, Seron D, Hartley RB, Cameron JS. Lupus nephritis: correlation of interstitial cells with glomerular function. Kidney Int 1990;37:100-9.  Back to cited text no. 11    
12.Walport MJ. The pathogenesis of systemic lupus erythematosus. In: Camron S, Davison AM, Grunfeld JP, Kerr D, Ritz E, eds. Oxford Textbook of Nephrology. OTCN on CD-ROM, Oxford University Press, Oxford Chapter 1997;4.7.1.  Back to cited text no. 12    
13.Schmiedeke TM, Stockl FW, Weber R, Sugisaki Y, Batsford SR, Vogt A. Histones have high affinity for the glomerular basement membrane. Relevance for immune complex formation in lupus nephritis. J Exp Med 1989;169:1879-94.  Back to cited text no. 13    
14.Burlingame RW, Boey ML, Starkebaum G, Rubin RL. The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. J Clin Invest 1994;94:184-92.  Back to cited text no. 14    
15.Bernstein KA, Valerio RD, Lefkowith JB. Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex. J Immunol 1995;154:2424-33.  Back to cited text no. 15    
16.Klinmann DM, Steinberg AD. Inquiry into murine and human lupus. Immunol Rev 1995;144:157-93.  Back to cited text no. 16    
17.Mohan C, Datta SK. Lupus: key pathogenic mechanisms and contributing factors. Clin Immunol Immunopathol 1995;77:209-20.  Back to cited text no. 17    
18.Tsokos GC. Lymphocytes, cytokines, inflammation, and immune trafficking. Curr Opin Rheumatol 1995;7:376-83.  Back to cited text no. 18    
19.Tsokos GC, Liossis SN. Immune cell signaling defects in lupus: activation, energy and death. Immunol Today 1999;20:119-24.  Back to cited text no. 19    
20.Tsao BP, Cantor RM, Kalunian KC, et al. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. J Clin Invest 1997;99:725-31.  Back to cited text no. 20    
21.Cutolo M, Sulli A, Seriolo B, et al. Estrogens, the immune response and auto­immunity. Clin Exp Rheumatol 1995;13: 217-26.  Back to cited text no. 21    
22.Churg J, Sobin LN. Renal nephritis. In: Churg J, Sobin LH, eds. Renal disease. Classification and atlas of glomerular disease. New York: Igaku-Schoin 1982; 127-49.  Back to cited text no. 22    
23.Golbus J, McCune WJ. Lupus nephritis. Classification, prognosis, immunopatho­genesis, and treatment. Rheum Dis Clin North Am 1994;20:213-42.  Back to cited text no. 23    
24.Baldwin DS, Gluck MC, Lowenstein J, Gallo GR. Lupus nephritis. Clinical course as related to morphologic forms and their transitions. Am J Med 1977;62:12-30.  Back to cited text no. 24    
25.Appel GB, Cohen DJ, Pirani CL, Meltzer JI, Estes D. Long-term follow-up of patients with lupus nephritis. Study based on the classification of the World Health Organization. Am J Med 1987;83:877-85.  Back to cited text no. 25    
26.Kashgarian M. Lupus nephritis: lessons from the path lab. Kidney Int 1994; 45:928­-38.  Back to cited text no. 26    
27.Pistiner M, Wallace DJ, Nessim S, Metzger AL, Klinenberg JR. Lupus erythematosus in the 1980s: a survey of 570 patients. Semin Arthritis Rheum 1991;21:55-64.  Back to cited text no. 27    
28.Baldwin DS, Lowenstein J, Rothfield NF, Gallo G, McClusky RT. The clinical course of the proliferative and membranous forms of lupus nephritis. Ann Intern Med 1970;73:929-42.  Back to cited text no. 28    
29.Hellmann DB, Petri M, Whiting-O'Keefe Q. Fatal infections in systemic lupus erythe­matosus: the role of opportunistic organisms. Medicine Baltimore 1987;66:341-8.  Back to cited text no. 29    
30.Hochberg MC. Epidemiology of systemic lupus erythematosus. In: Wallace DJ, Hahn BH, eds. Dubois's systemic lupus erythematosus. 4th ed. Philadelphia: Lea & Febiger 1992;49-57.  Back to cited text no. 30    
31.Sturfelt G, Eskilsson J, Nived O, Truedsson L, Valind S. Cardiovascular disease in systemic lupus erythematosus. A study of 75 patients from a defined population. Medicine Baltimore 1992;71:216-23.  Back to cited text no. 31    
32.Seleznick MJ, Fries JF. Variables associated with decreased survival in systemic lupus erythematosus. Semin Arthritis Rheum 1991;21:73-80.  Back to cited text no. 32    
33.Austin HA 3d, Muenz LR, Joyce KM, Antonovych TT, Balow JE. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int 1984;25:689-95.  Back to cited text no. 33    
34.Esdaile JM, Joseph L, MacKenzie T, Kashgarian M, Hayslett JP. The patho­genesis and prognosis of lupus nephritis: information from repeat renal biopsy. Semin Arthritis Rheum 1993;23:135-48.  Back to cited text no. 34    
35.Balow JE, Austin HA 3d, Muenz LR, et al. Effect of treatment on the evolution of renal abnormalities in lupus nephritis. N Engl J Med 1984;311:491-5.  Back to cited text no. 35    
36.Austin HA 3d, Boumpas DT, Vaughan EM, Below JE. Predicting renal outcomes in severe lupus nephritis: contributions of clinical and histological data. Kidney Int 1994;45:544-50.  Back to cited text no. 36    
37.Austin HA 3d, Muenz LR, Joyce KM. Prognostic factors in lupus nephritis: Contribution of renal histologic data. Am J Med 1983;75:382-91.  Back to cited text no. 37    
38.Leaker B, Fairley KF, Dowling J, Kincaid­Smith P. Lupus nephritis: clinical and pathological correlation. Q J Med 1987;62:163-79.  Back to cited text no. 38    
39.Schwartz MM, Lan SP, Bernstein J, Hill GS, Holley K, Lewis EJ. Irreproducibility of the activity and chronicity indices limits their utility in the management of lupus nephritis. Am J Kidney Dis 1993;21:374-7.  Back to cited text no. 39    
40.Schwartz MM, Bernstein J, Hill GS, Holley K, Phillips EA. Predictive value of renal pathology in diffuse proliferative lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group. Kidney Int 1989;36:891-6.  Back to cited text no. 40    
41.McLaughlin JR, Bombardier C, Farewell VT, Gladman DD, Urowitz MB. Kidney biopsy in systemic lupus erythematosus III. Survival analysis controlling for clinical and laboratory variables. Arthritis Rheum 1994;37:559-67.  Back to cited text no. 41    
42.Lee HS, Mujais SK, Kasinath BS, Spargo BH, Katz AL. Course of renal pathology in patients with systemic lupus erythe­matosus. Am J Med 1984;77:612-21.  Back to cited text no. 42    
43.Glassock RJ, Cohen AH, Adler SG. Secondary glomerular diseases. In: Brenner BM (ed). The Kidney, 5th ed. WB Saunders, Philadelphia 1996;1489-1516.  Back to cited text no. 43    
44.Schwartz MM, Kawala KS, Corwin HL, Lewis EJ. The prognosis of segmental glomerulonephritis in systemic lupus erytehmatosus. Kidney Int 1987;32:274-9.  Back to cited text no. 44    
45.Magil AB, Puterman ML, Ballon HS, et al. Prognostic factors in diffuse proliferative lupus glomerulonephritis. Kidney Int 1988;34:511-7.  Back to cited text no. 45    
46.Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 10 years after diagnosis. (Gisnel) Am J Kidney Dis 1992;19:473-9.  Back to cited text no. 46    
47.Sloan RP, Schwartz MM, Korbet SM, Borok RZ. Long-term outcome in systemic lupus erythematosus membranous glome­rulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol 1996;7:299-305.  Back to cited text no. 47    
48.Pasquali S, Banfi G, Zucchelli A, Moroni G, Ponticelli C, Zucchelli P. Lupus memb­ranous nephropathy: long term outcome. Clin Nephrol 1993;39:175-82.  Back to cited text no. 48    
49.Radhakrishnan J, Szabolcs S, d'Agati V. Lupus membranous nephropathy: course and prognosis in 50 patients. J Am Soc Nephrol 1993;4:284.  Back to cited text no. 49    
50.Boumpas DT, Fessler BJ, Austin HA 3rd, Fessler BJ, Balow JE, Klippel JH, Lockshin MD. Systemic lupus erythe-matosus: emerging concepts. Part 2: Dermatologic and joint disease, the anti-phospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis. Ann Intern Med 1995;123:42-53.  Back to cited text no. 50    
51.Pollak VE, Pirani CL, Kark RM. Effect of large dose of prednisone on the renal lesions and life span of patients with lupus glomerulonephritis. J Lab Clin Med 1961;57:495-511.  Back to cited text no. 51    
52.Ponticelli C, Banfi G. Systemic lupus erythematosus. In: Cameron S, Davison AM, Grunfeld JP, Kerr D, Ritz E, eds. Oxford Textbook of Clinical Nephrology, Oxford University Press, Oxford 1992;646-67.  Back to cited text no. 52    
53.Kimberly RP. Treatment: Corticosteroids and anti-inflammatory drugs. Rheum Dis Clin North Am 1988;14:203-21.  Back to cited text no. 53    
54.Cathcart ES, Idelson BA, Scheinberg MA, Couser WG. Beneficial effects of methyl­prednisolone "pulse" therapy in diffuse proliferative lupus nephritis. Lancet 1976; 1:163-6.  Back to cited text no. 54    
55.Kimberly RP. Pulse methylprednisolone in SLE. Clin Rheum Dis 1982;8:261-78.  Back to cited text no. 55    
56.Ponticelli C, Zucchelli P, Banfi G. Treatment of diffuse proliferative lupus nephritis by intravenous high dose methylprednisolone. Q J Med 1982;51:16-24.  Back to cited text no. 56    
57.Albert DA, Hadler NN, Ropes MW. Does corticosteroid therapy affect the survival of patients with systemic lupus erythematosus? Arthritis Rheum 1979;22:945-53.  Back to cited text no. 57    
58.Sztejnbok M, Stewart A, Diamond H, Kaplan D. Azathioprine in the treatment of systemic lupus erythematosus. A controlled study. Arthritis Rheum 1971;14:639-45.  Back to cited text no. 58    
59.McCune WJ. Immunosuppressive drug therapy. Curr Opin Rheumatol 1996;8:183-7.  Back to cited text no. 59    
60.Felson DT, Anderson J. Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis. N Engl J Med 1984;311:1528-33.  Back to cited text no. 60    
61.Austin HA 3d, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisolone and cytotoxic drugs. N Engl J Med 1986;314:614-9.  Back to cited text no. 61    
62.Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 1991;34:945-50.  Back to cited text no. 62    
63.Donadio JV Jr, Holley KE, Ferguson RH, Ilstrup DM. Treatment of diffuse prolife­rative lupus nephritis with prednisone and combined prednisone and cyclophos­phamide. N Engl J Med 1978;299:1151-5.  Back to cited text no. 63    
64.Donadio JV Jr, Holley KE, Ilstrup DM. Cytotoxic drug treatment of lupus nephritis. Am J Kidney Dis 1982;2:178-81.  Back to cited text no. 64    
65.McCune WJ, Golbus J, Zeldes W, Bohlke P, Dunne R, Fox DA. Clinical and immuno­logic effects of monthly administration of intravenous cyclophosphamide in severe systemic lupus erythematosus. N Engl J Med 1988;318:1423-31.  Back to cited text no. 65    
66.Boumpas DT, Austin HA 3d, Vaughn EM, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741-5.  Back to cited text no. 66    
67.Valeri A, Radhakrishnan J, Estes D, et al. Intravenous pulse cyclophosphamide treatment of severe lupus nephritis: a prospective five-year study. Clin Nephrol 1994;42:71-8.  Back to cited text no. 67    
68.Donadio JV Jr. Treatment of membranous nephropathy in systemic lupus erythematosus. Nephrol Dial Transpl 1992; 7(Suppl 1):97-104.  Back to cited text no. 68    
69.Moroni G, Maccario M, Banfi G, Quaglini S, Ponticelli C. Treatment of membranous lupus nephritis. Am J Kidney Dis 1998; 31:681-6.  Back to cited text no. 69    
70.Austin HA, Vaugham EM, Boumpas DT. - controlled trial of prednisone, pulse cyclophosphamide, and cyclosporine A (abstract). J Am Soc Nephrol 1996;7:1328.  Back to cited text no. 70    
71.Bono L, Cameron JS, Hicks JA. The very long-term prognosis and complications of lupus nephritis and its treatment. Q J M 1999;92:211-8.  Back to cited text no. 71    
72.Donadio JV Jr, Glassock RJ. Immuno­suppressive drug therapy in lupus nephritis. Am J Kidney Dis 1993;21:239-50.  Back to cited text no. 72    
73.Kinlen LJ. Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med 1985;78(1A):44-9.  Back to cited text no. 73    
74.Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med 1992; 116:488-98.  Back to cited text no. 74    
75.Trompeter RS, Evans PR, Barratt TM. Gonadal function in boys with steroid­responsive nephrotic syndrome treated with cyclophosphamide for short periods. Lancet 1981;1:1177-9.  Back to cited text no. 75    
76.Boumpas DT, Austin HA 3d, Vaugham EM, Yarboro CH, Klippel JH, Balow JE. Risk of sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann Intern Med 1993;119:366-9.  Back to cited text no. 76    
77.Pryor BD, Bologna SG, Kahl LE. Risk factors for serious infection during treatment with cyclophosphamide and high-dose corticosteroids for systemic lupus erythe­matosus. Arthritis Rheum 1996;39:1475-82.  Back to cited text no. 77    
78.Lewis EJ, Hunsicker LG, Lan SP, Rhode RD, Lachin JM. A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collabo­rative Study Group. N Engl J Med 1992;326:1373-9.  Back to cited text no. 78    
79.Hanly JG, Hong C, Zayed E, Jones JV, Jones E. Immunomodulating effects of synchronized plasmapheresis and intrave­nous bolus cyclophosphamide in systemic lupus erythematosus. Lupus 1995;4:457-63.  Back to cited text no. 79    
80.Euler HH, Schroeder JO, Harten P, Zeuner RA, Gutschmidt HJ. Treatment-free remission in severe systemic lupus erythe­matosus following synchronization of plasmapheresis with subsequent pulse cyclophosphamide. Arthritis Rheum 1994; 37:1784-94.  Back to cited text no. 80    
81.Arainger M, Smolen JS, Graninger WB. Severe infections in plasmapheresis-treated systemic lupus erythematosus. Arthritis Rheum 1994;37:1784-8.  Back to cited text no. 81    
82.Miescher PA, Miescher A. Combined cyclosporine-steroid treatment of systemic­lupus erythematosus. In: Schindler, ed: Cyclosporin in Autoimmune Disease. Springer Verlag, Berlin 1985;334-48.  Back to cited text no. 82    
83.Fathman CG, Myers BD. Cyclosporine therapy for autoimmune disease. N Engl J Med 1992;326:1693-5.  Back to cited text no. 83    
84.Hernandez Perez J, Fernandez-Fernandez J, Sanz Moreno C, Garrancho JM, Botella J. Primary ascites as the presenting feature of systemic lupus erythematosus: response to cyclosporin therapy. Nephrol Dial Transplant 1995;10:1451-3.  Back to cited text no. 84    
85.Radhakrishnan J, Kunis CL, D'Agati V, Appel GB. Cyclosporine treatment of lupus membranous nephropathy. Clin Nephrol 1994;42:147-51.  Back to cited text no. 85    
86.Fu LW, Yang LY, Chen WP, Lin CY. Clinical efficacy of cyclosporin a neoral in the treatment of paediatric lupus nephritis with heavy proteinuria. Br J Rheumatol 1998;37:217-21.  Back to cited text no. 86    
87.Lukac J, Rovensky J, Rauova L, Cebecauer L, Malis F. Long-term cyclosporin a treatment in systemic lupus erythematosus. Int J Immunother 1998;14:33-40.  Back to cited text no. 87    
88.Tam LS, Li EK, Leung CB, et al. Long­term treatment of lupus nephritis with cyclosporin A. Q J M 1998;91:573-80.  Back to cited text no. 88    
89.Jonsson CA, Svensson L, Carlsten H. Beneficial effect of the inosine mono­phosphate dehydrogenase inhibitor myco­phenolate mofetil on survival and severity of glomerulonephritis in systemic lupus erythematosus (SLE)-prone MRLlpr/lpr mice. Clin Exp Immunol 1999;116:534-41.  Back to cited text no. 89    
90.Corna D, Morigi M, Facchinetti D, Bertani T, Zoja C, Remuzzi G. Mycophenolate mofetil limits renal demage and prolongs life in murine lupus autoimmune disease. Kidney Int 1997;51:1583-9.  Back to cited text no. 90    
91.Glicklich D, Acharya A. Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am J Kidney Dis 1998;32:318-22.  Back to cited text no. 91    
92.Dooley MA, Cosio FG, Nachman PH, et al. Mycophenolate mofetil therapy in lupus nephritis: clinical observations. J Am Soc Nephrol 1999;10:833-9.  Back to cited text no. 92    
93.Walz LeBlanc BA, Dagenais P, Urowitz MB, Gladman DD. Methotrexate in systemic lupus erythematosus. J Rheumatol 1994;21:836-8.  Back to cited text no. 93    
94.Sany J. Intravenous immunoglobulin therapy for rheumatic disease. Curr Opin Rheum 1994;6:305-10.  Back to cited text no. 94    
95.Schroeder JO, Zeuner RA, Euler HH, Loffler H. High dose intravenous immuno­globulins in systemic lupus erythematosus: clinical and serological results of a pilot study. J Rheumatol 1996;23:71-5.  Back to cited text no. 95    
96.Becker BN, Fuchs H, Hakim R. Intra­venous immune globulin in the treatment of patients with systemic lupus erythe-matosus and end-stage renal disease. J Am Soc Nephrol 1995;5:1746-50.  Back to cited text no. 96    
97.Gao CL, Li BA, Chen CZ, Yu YT, Yuan P, Song JC. Clinical trials of immuno­adsorbent in systemic lupus erythematosus therapy. Artif Organs 1995;19:468-9.  Back to cited text no. 97    
98.Matsuki Y, Suzuki K, Kawakami M, et al. High-avidity anti-DNA antibody removal from the serum of systemic lupus erythematosus patients by adsorption using dextran sulfate cellulose columns. J Clin Apheresis 1996;11:30-5.  Back to cited text no. 98    
99.Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA. Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5. Proc Natl Acad Sci USA 1996;93:8563-8.  Back to cited text no. 99    
100.Tumlin JA. Lupus nephritis: novel immunosuppressive modalities and future directions. Semin Nephrol 1999;19:67-76.  Back to cited text no. 100    
101.Illei GG, Klippel JH. Novel approaches in the treatment of lupus nephritis. Lupus 1998;7:644-8.  Back to cited text no. 101    
102.Jayne DR. Immunotherapy for auto­immune and inflammatory renal diseases. Curr Opin Nephrol Hypertens 1998;7:311-5.  Back to cited text no. 102    
103.Mojcik CF, Klippel JH. End-stage renal disease and systemic lupus erythematosus. Am J Med 1996;101:100-4.  Back to cited text no. 103    
104.Cheigh JS, Stenzel KH. End-stage renal disease in systemic lupus erythematosus. Am J Kidney Dis 1993;21:2-7.  Back to cited text no. 104    
105.Stone JH, Amend WJ, Criswell LA. Outcome of renal transplantation in systemic lupus erythematosus. Semin Arthritis Rheum 1997;27:17-26.  Back to cited text no. 105    
106.Stone JH, Millward CL, Olson JL, Amend WJ, Criswell LA. Frequency of recurrent lupus nephritis among ninety­seven renal transplant patients during the cyclosporine era. Arthritis Rheum 1998;41:678-86.  Back to cited text no. 106    

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