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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2003  |  Volume : 14  |  Issue : 1  |  Page : 43-56
Lupus Nephritis in Childhood

Department of Pediatrics, College of Medicine & KKUH, King Saud University, Riyadh, Saudi Arabia

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The manifestations of lupus nephritis (LN) range from minor abnormalities detected on urinalysis to severe renal insufficiency requiring renal replacement therapy. In children, LN is often more severe than in adults. The female to male predominance is not as marked as in adults. The risk of progression to end-stage renal disease in children is 18 to 50%. The majority of children with LN have proteinuria, while the nephrotic syndrome is seen in approximately 50% of affected patients. Children with LN have higher frequency of hypertension which is considered as the most important prognostic clinical finding. The current practice of estimation of complement components, C 3 and C 4 does not adequately reflect disease activity. There are racial differences in renal survival and response to treatment. Arab patients with LN do not exhibit a distinctive serological profile. Lupus nephritis is classified into six groups depending on the severity of the histological lesion. Transformation between the histological classes occurs frequently. Histological outcome predictions have been significantly enhanced by the addition of activity and chronicity indices. Treatment of the LN may be guided by the severity of the renal biopsy appearances. Controversy persists as to the most effective cytotoxic treatment in LN and oral or intravenous (i.v.) cyclophosphamide, azathioprine, cyclosporin, i.v. immunoglobulin, plasma exchange and recently mycophenolate mofetil have been used in different units. Today, children with LN much less commonly go into renal failure. Outcome after renal transplantation of children with end-stage renal disease caused by LN is similar to non-lupus patients. Morbidity of the disease and the treatment remain a major problem.

Keywords: Childhood, Lupus nephritis, Methyl prednisolone, Cytotoxic drugs.

How to cite this article:
Al Salloum AA. Lupus Nephritis in Childhood. Saudi J Kidney Dis Transpl 2003;14:43-56

How to cite this URL:
Al Salloum AA. Lupus Nephritis in Childhood. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2022 Aug 7];14:43-56. Available from: https://www.sjkdt.org/text.asp?2003/14/1/43/33087

   Introduction Top

Systemic lupus erythematosis (SLE) is a disease that is infrequent in childhood. Its importance is derived from the fact that it is a life-threating illness associated with significant complications. [1] It is a disease of immunological origin with autoantibodies, polyclonal B-cell activation and T-cell dysfunction. Ensuing immune complexes are deposited or formed in situ in many organs, and affect commonly the kidney as lupus nephritis (LN). [2] Although SLE has been reported in children in the first 1-2 years of life, it is rare in those under five years of age. The peak presentation of childhood SLE occurs around puberty. [3] As in adults, a female to male predominance is seen in pre-pubertal SLE, although this is not as marked as in adult-onset disease. The female-male ratio is in fact about 4.5:1 throughout childhood and adolescence, lower than 8-13:1 reported in a series of adult-onset patients. [4] Lupus nephritis is extremely common in the pediatric presen­tation of SLE. It has been reported that 40-75% of SLE patients develop clinically apparent nephritis within five years of disease onset, and almost all patients exhibit some degree of glomerular abnormality. [5] Both nephritis and the consequences of its treatment cause signifi­cant morbidity. The risk of progression to end­stage renal disease in children with renal involvement is 18-50%. [4],[6] There is no doubt that the use of high-dose corticosteroids has improved the prognosis of severe lupus nephritis. During the past 20 years, new therapeutic approaches, including the use of cytotoxic agents, have further improved renal survival rates, which have reached 80% at 10 years. [7] However, there is still some controversy regarding the best treatment, mainly due to lack of well-designed prospective therapeutic studies with adequate numbers of patients. Most publications report uncontrolled trials and retrospective analyses, which do not allow definitive conclusions to be drawn.

   Clinical Presentation of Lupus Nephritis in Childhood Top

Renal involvement in children with SLE is extremely variable, with some patients showing minimal urinary abnormalities while others have rapidly progressive renal failure with the nephrotic syndrome. Hematuria and proteinuria are the most commonly identified abnormalities. [3] The majority of children with LN have proteinuria, while the nephrotic syndrome is seen in approximately 50% of affected children at diagnosis. Hematuria is nearly universal, being reported in 67-100% of affected children in different series. Hyper­tension and decreased renal function are also commonly seen at the time of diagnosis of LN, occurring in approximately 50% of affected children. [4] The clinical picture is related to the severity of histological abnorm­alities on renal biopsy. [7] In one study of age­related differences in the clinical manife­stations of SLE, children were found to have higher rates of hypertension (14% vs 3.4%), proteinuria (71% vs 44%), hematuria (69% vs 25%), cellular casts (39% vs 15%) and elevated serum creatinine concentration (25% vs 7%). [1]


The laboratory findings in SLE include a positive anti-nuclear antibodies (ANA) in high titers with circulating anti-desoxyribose nuclear acid (DNA) antibodies. The positive ANA may demonstrate a specked, homo­genous, mixed or other patterns, and they can be directed against double-stranded native DNA or other antigens including Ro, La, Sm and RNP. [8] Anti-Sm antibodies are almost entirely specific for lupus, but are found only in about 30% of patients and thus, have a very low sensitivity. [4] Antibodies to ribosomal P protein are more prevalent in childhood SLE than in adults and the presence of anti-P antibodies is strongly associated with severe nephritis. [9] Usually, both adult and childhood "lupus like" patients with negative ANA show little or no renal disease [10] although there are exceptions. [11],[12] Immune complexes can be detected in the serum of the majority of children with LN and the titer in general rises and falls with clinical activity. However, their utility in diagnosis is minimal. [13] Hypocomplementemia is present in more than 75% of untreated children with LN. Concentrations of C 4 and C 1q tend to be more depressed than C 3 , suggesting complement activation via the classical pathway. Also, low levels of properdin and factor B level are present suggesting alternate pathway activation. [4] Injuries induced by the formation of immune complexes involving glomerular or non-glomerular antigens are largely complement-dependent and can be greatly ameliorated, or prevented entirely, by manouvers that inhibit complement activation. [14]

The current practice of estimation of complement components C 3 and C4 does not adequately reflect disease activity, as their serum levels merely express the balance between synthesis and catabolism. Urinary complement degradation products C3d and C4d reflect complement activation more accurately than C3 and C4 levels and have been found to correlate better with disease activity of LN. [15] Serum levels of IgG anti- C1q were significantly increased in patients with active proliferative nephritis. [16]

Although there are differences in renal survival rate and response to treatment in LN among different races, [17],[18],[19],[20] Arab patients and Africans with LN do not exhibit a distinctive serological profile. [21],[22]

The reported prevalence of anti-phospholipid antibodies in LN in children vary from 38 to 87%. [23] The presence of anti-phospholipid antibodies is thought to represent a risk factor for thrombotic episodes. [1] Nevertheless, in a recent study limited to 36 children with LN, an increased risk of thrombotic episodes could not be demonstrated. [24]

Tubular Dysfunctions

Renal tubular dysfunction is a well­recognized complication of LN in adults and includes distal renal tubular acidosis (dRTA), impaired tubular potassium excretion, hyporeninemic hypo-aldosteronism, and decresed urinary concentrating ability. According to Kozeny et al, [25] up to 60% of adult patients with LN have either overt or latent dRTA. However, tubular dysfunction in childhood and adolescence is rare. [26]

Renal Biopsy

Patients with hematuria, proteinuria with or without the nephrotic syndrome, and a normal or subnormal glomerular filtrations rate may have any class of glomerular lesions (focal or diffuse proliferative glomerulo­nephritis with varying degrees of severity or membranous glomerulonephritis). The prognosis is different and knowledge of the underlying histological lesion is most important to decide the best therapy. [27] The clinical picture is not related in some cases to the severity of histological abnormalities on renal biopsy; [7] some patients with the so called silent LN may reveal severe histological lesions. [28]

Multiple renal biopsies may be needed during the course of treatment of LN. Transformation between LN classes occurs frequently, more than two-thirds of follow­up biopsies were different than the first biopsy, and less than half of patients remained in the original LN class on their last biopsy. [5],[29]

Some of the transformation may have occurred in response to immuno-suppressive therapy. Lehman et al [30] reported seven children whose initial biopsies were class IV, and had class II on follow-up after three years of therapy. Sequential renal biopsy is indicated on the basis of one of these clinical situations: a) improvement of renal disease but persistent of non-nephrotic proteinuria to determine whether to continue therapy, b) persistent or relapsing nephrotic syndrome to determine whether to increase immunosuppression, and c) worsening of renal functions to determine whether to administer aggressive immuno­suppression to rescue renal function. [29]

Histopathological classification of lupus nephritis

The World Health Organization (WHO) classification for LN was developed in 1973 to help the clinician distinguish the different histologic presentations and with the hope that it may help in guiding treatment. This classification uses light microscopy, immuno­fluorescence, and electron microscopy, and is now widely accepted. [7],[31] This classification has been modified into six histological groups and constitutes the first step before deciding on any therapy. [7]

The (WHO) has classified LN as follows [32]

Class I: Normal glomeruli; (a) nil (by all techniques), (b) normal by light microscopy but deposits by electron or immunofluorescence microscopy.

Class II: Pure mesangial alterations (mesangiopathy); (a) mesangial widening and / or mild hypercellularity; (b) moderate hypercellularity.

Class III: Focal segmental glomerulonephritis (associated) with mild or moderate mesangial alterations); (a) "active" necrotizing lesions; (b) "active" and sclerosing lesions; (c) sclerosing lesions.

Class IV: Diffuse glomerulonephritis (severe mesangial, endocapillary or mesangio-capillary proliferation and/or extensive subendothelial deposits); (a) without segmental lesions; (b) with "active" necrotizing lesions; (c) with active and sclerosing lesions; (d) with sclerosing lesions. Class V: Diffuse membranous glomerulo­nephritis; (a) pure membranous glomerulo­nephritis; (b) associated with lesions of category IIa or IIb; (c) associated with lesions of category III(a-c); (d) associated with lesions of category IV(a-d). Alternatively, cases in these latter two sub-categories are sometimes classified under class III or IV.

Class VI: Chronic, sclerosing glomerulopathy.

In an analysis of nine investigations of the patterns of glomerular damage seen in renal biopsies in pediatric LN, comprising 365 children and adolescents, 25% had WHO Class I-II histology while 65% had Class III or IV, indicating a high frequency of severe renal involvement, Class V was seen in only 9% of affected pediatric patients. [1] However, Sorof et al [5] noticed a recent increase in the incidence of childhood Class V LN; 28% (17/60) of their patients had Class V LN on the first renal biopsy.

Outcome predictions based on the WHO classification, were significantly enhanced by the addition of activity and chronicity indices. [33] A close correlation was observed between a poor renal outcome and the presence of chronic lesions on renal biopsy. [34] The combination of cellular crescents and interstitial fibrosis was particularly ominous. [33] Active histological lesions include fibrous crescents, endocapillary proliferation, fibrinoid necrosis, karyorrhexis, thrombi, wire loops with subendothelial immune deposits, glomerular leukocyte infiltration, and intersti­tial mononuclear cell infiltration. These active lesions are each graded 0-3 (with both necrosis and cellular crescents graded 0-6) to give an activity index graded 0-24. Active lesions are potentially reversible with treatment. Chronicity index includes glomerular sclerosis, fibrous crescents, tubular fibrosis and interstitial fibrosis. These lesions are irreversible and do not respond to treat­ment. [7] The chronicity index score is the most powerful prognostic factor. [35] The National Institute of Health (NIH) group found that an activity index > 12/24 or chronicity index > 4 were indicative of a poor renal prognosis. [33]

   The Treatment of Lupus Nephritis Top

Despite more than 30 years of study, the optimal treatment of LN remains unclear. [36] This is because it is not clear whether we are dealing with a primary B-cell overactivity, a defect in T-suppressor cell regulation of B­cell, or an excess of T help. [37]

However, the outcome for pediatric patients with SLE has improved dramatically over the past three decades. Ten year survival rates of 30% or less were reported in the 1960's; this improved to a 75% 10 year survival in the 1970's while in the 1980's and early 1990's, 10 years survival in excess of 80% has been reported. [38] These figures allow us to approach the treatment of this chronic illness much more optimistically. The effect of extra-renal lupus may have a major role in the mortality. Thus, infections have now replaced renal failure as the most common cause of death in childhood SLE. [39]

The treatment of LN in the pediatric age­group requires a balance between aggressive early therapy directed toward controlling the disease and effective long-term maintenance therapy minimizing the side effects of the drugs. Long delay between the onset of LN disease and the start of appropriate therapy correlates with a poor clinical outcome. [40]

Therapy of Class I, II LN (mild renal lesions)

Class I is a rare situation and patients have no renal symptoms. [7]

Class II patients may have mild proteinuria and microscopic hematuria but the glomerular filtration rate is usually normal. Renal disease in these patients does not need specific therapy. Evidence that corticosteroid therapy is beneficial from the standpoint of long­term renal prognosis is lacking and treatment is determined by the extra-renal manifestations of the disease. [1] Nevertheless, careful follow-up of the patient is necessary, as progression to a more severe renal disease is possible. [5]

Therapy of Class III LN (moderate renal lesion)

The natural course of the disease depends upon the extent of renal lesion. When less than 20% of the glomeruli are affected by small segmental lesions, the long-term prognosis is favorable with probably less than 5% risk of progression to end-stage renal failure after five years. [41] Patients usually have mild renal symptoms, with low grade proteinuria without nephrotic syndrome, and a normal glomerular filtration rate. In this setting, there is no indication for specific therapy, which may however be required for extra-renal symptoms. [7] The situation is different when cellular proliferation, necrosis and large sub-endothelial deposits involve more than 40% of the glomeruli present in the biopsy sample and clinical symptoms are more severe with an active urine sediment, the nephrotic syndrome, hypertension and in some patients, moderate renal insufficiency. The course of the disease will be similar to that of diffuse proliferative glomerulonephritis (Class IV), and the same aggressive therapy is needed. [7]

Therapy of Class IV LN (severe renal lesions)

Class IV corresponds to diffuse proliferative glomerulonephritis (DPG). It is widely recognized that patients with DPG are at risk for hypertension, the nephrotic syndrome, and progressive renal insufficiency. [17] Prompt and aggressive therapy directed toward controlling the renal manifestations of the disease is indicated in these patients.


Patient and renal survival rates in SLE have dramatically improved with the intro­duction of corticosteroid therapy.

Four decades ago, Pollak et al [42] showed that high-dose of oral corticosteroids could improve the course of DPG whereas low doses were ineffective. For two decades this report was incorporated into all textbooks on the subject. [43] Subsequent studies suggest that high doses of oral corticosteroids are no better than low doses in the treatment of DPG in children. High doses of oral predni­solone alone not only give poor results in the long-term but also are often associated with serious side effects. Tejani A et al [44] showed that 25% of their patients had died of renal causes and another 25% were undergoing dialysis, received transplants, or in chronic renal failure. These patients were treated with prednisone in a dose of 60 mg/m 2 /day. Steinberg et al [45] assessed long­term preservation of renal function in 111 patients in a randomized treatment trial; four different drug treatment programs were used. Each allowed the use of low-dose oral prednisolone in addition to cytotoxic drugs and were compared with regimen consisting solely of high-dose oral prednisone. Patients randomized to receive intravenous cyclophos­phamide or oral cyclophosphamide had significantly better preservation of renal functions than did patients who were randomized to receive prednisone alone. With similar conclusion Austin et al, [46] showed that addition of the cytotoxic drugs resulted in better preservation of renal function than treatment with oral prednisone alone.

Since 1975, many authors have proposed initiation of therapy with intravenous methyl­prednisolone pulses for the acute phase of the disease, mimicking the successful use of similar treatment in transplant rejection. The justifi­cation for this treatment, was the resemblance between the interstitial infiltrate of lupus nephritis and of allograft rejection. [47],[48]

Intravenously administered pulse methyl­prednisolone 20-30 mg/kg, up to 1 gm daily, for three days often leads to striking impro­vement in renal function in LN, especially in the subset of patients with recent antecedent function deterioration. [49] However, the long­term effect of methylprednisolone pulses alone in preserving renal function was similar to oral prednisone. [48],[49] Side effects included cardiac arrhythmias or even cardiac arrest if given through central venous lines, unpleasant flushing sensations, acute hypertension, and occasionally acute psychosis. [4]


Cyclophosphamide is metabolized, primarily in the liver to active metabolites that alkylate and phosphorylate macromolecules. [43],[50] Selective effects of cyclophosphamide on different components of the lymphoid system have been described. [32] Several studies have shown that renal survival is significantly better when cyclophosphamide is added to corticosteroids. [30],[36],[40],[48],[51],[52] Although initially used predominantly in oral regimens in a dose of 1-3 mg/kg/day for 8-12 weeks, intermittent intravenous cyclophosphamide bolus therapy, 500-1000 mg/m 2 , on monthly basis and subsequently bi-monthly or every three months, has now become a frequently utilized treatment modality for severe LN. [1],[30],[45],[48]

Cyclophosphamide given as monthly boluses at a starting dose of 750 mg/m 2 may be less toxic than given orally everyday at a dose of 2 mg/kg. [53] The dose of cyclophos­phamide given in bolus form is increased to 1000 mg/m 2 if the white blood cell count remains above 3000/mm 3 . [54] The duration of therapy following initial control of LN is not well defined. Lehman et al [54] treated 16 children with cyclophosphamide monthly for six months and then every three months until three years elapsed. They reported a significant improvement at one year in urine protein excretion, hemoglobin levels, C 3, C4, and creatinine clearance despite a significant reduction in prednisone dosage. Short courses of pulse cyclophosphamide may be effective in reducing the risk of renal progression within the first few years and may be more tolerable and less toxic than extended therapy, but may not be optimal for preventing exacerbation of the disease or progression to more renal insufficiency. [48] Valeri et al [55] used a treatment regimen of six-monthly intravenous pulses of cyclophosphamide (0.5 to 1 g/m 2 ) together with high-dose corticosteroid therapy which was rapidly tapered. Over the first six months of treatment, this regimen resulted in improvement of clinical activity, lupus serology, stabilization of renal function and decreased proteinuria in 19/20 patients. Over five years of follow-up, there were five patients with doubling of serum creatinine over baseline and three patients required renal replacement therapy.

Patients with severe LN and normal serum creatinine may have an excellent outcome with short course (six months duration) of cyclophosphamide pulses. Patients with more severe clinical presentation may benefit from more expanded regimen.

Therapy with cyclophosphamide, carries considerable risk of toxicity, including alopecia, bone marrow suppression, hemorr­hagic cystitis, gonadal failure and develop­ment of malignancy. [36] The incidence of hemorrhagic cystitis is very low provided adequate intravenous hydration for 24h is ensured. As mentioned earlier, tubular dysfunction has been reported in LN and periodic electrolyte assessment is needed during hydration to avoid hyponatremia and seizures. [54] In order to minimize the risk of hemorrhagic cystitis, administration of mesna, which binds to cyclophosphamide metabolites in the urine, is recommended. No cases of hemorrhagic cystitis or bladder cancer have yet been reported in the various treatment studies. [50] Nausea and vomiting were common during the first 24 hours after i.v. cyclophos­phamide administration. [54] This may be in part prevented by the concomitant use of antiemetic agents such as Ondansetron (Zofren). [7] Hair thinning of variable severity developed in all children during the first six months of therapy in one study, [54] but most regained a normal appearance by one year. Cyclophos­phamide pulses often result in neutropenia, with a serious risk of infection. Herpes Zoster infections are frequent in these patients. [56] The risk of amenorrhea depend on the age of the patient at the start of the treatment and the total number of pulses. When treatment is given for six months, the risk of amenorrhea is very low if the patient is less than 25 years of age. When the total number of pulses exceeds 15, the likelihood of developing amenorrhea is 17%. The gonadal toxicity of pulse cyclophosphamide in males with LN has not been studied. [7]


Azathioprine has been the anti-metabolic used most frequently to treat patients with LN. It interferes with protein synthesis by competing for, and blocking specific receptors. [50] Azathio­prine in doses of 2 to 2.5 mg/kg per 24 hrs has proved remarkably safe in the long-term, although higher doses will induce leuco­penia. [37] Azathioprine may be used in combi­nation with prednisone in the early treatment of severe LN, [57] or it may be substituted for cyclophosphamide following 8-12 weeks of initial therapy with oral cyclophosphamide and prednisolone, [1] or as a substitute to i.v. cyclophosphamide after six months, if the disease is under control. [7] Azathioprine has steroid sparing effect, [34],[43],[50] and as such withdrawal of the drug without change in steroid dosage may lead to relapse. [37] Azathioprine can cause bone marrow suppression after 7 to 14 days of admini­stration, the hematopoietic suppression being dose dependent and reversible on dis­continuation of treatment. [50] Rare reports have mentioned cases of intrahepatic cholestasis, pancreatitis, cancer of the skin and uterine cervix and central nervous system lymphoma after long period of azathioprine administration. [43]

Cyclosporin A

Cyclosporin A (CsA) was introduced in recent years for the treatment of LN in patients with steroid resistance or in those with severe corticosteroid toxicity. [58] The basis for its use relates to its interference with the production of lymphokines produced by activated T-lymphocytes. By inhibiting the production of interleukin-2, the recruitment of cytotoxic T cells is arrested, decreasing the inflammatory response to precipitating and depositing immune complexes in the kidney.In individuals with severe LN, CsA use in conjunction with corticosteroids has been shown to decrease proteinuria and stabilize renal function. There was a significant increase in growth rate, compared to the prednisolone plus cyclophosphamide patients. However, it seems that CsA alone is not effective in controlling serological activity. [58],[59]

Toxicity is minimal, with hypertension, transient elevations of serum creatinine concentration, hypertrichosis, gingival hyperplasia and paresthesia. [1]

Mycophenolate mofetil

Mycophenolate mofetil (MMF) is a novel immunosuppressant that now forms part of routine prophylaxis and treatment of acute renal allograft rejection. MMF is a morpholino­ethyl ester of mycophenolic acid (MPA), which inhibits de novo purine synthesis. Because lymphocytes rely on de novo purine synthesis, whereas other cells do not, MMF is more selective for lymphocytes than other cells. [60]

Anecdotal reports of the successful use of MMF in LN have recently been published. [60],[61]

Of the 20 cases published, the majority received MMF after failure of frequent cycles of i.v. cyclophosphamide. MMF was used in a dose of 20-25 mg/kg/24h for 10-12 months. There was dramatic response to MMF in this group of patients, with rapid achievement of clinical and laboratory remission of nephritis. Corticosteroid-sparing effects were noted in each case. [61] MMF was well-tolerated, the only adverse effects noted being mild gastro­intestinal symptoms. Numerous unanswered questions remain. As yet, no randomized controlled trials of MMF in LN have been conducted to define the indications or compare the efficiency of MMF with standard therapies. Also, the cost of MMF is considerable in comparison to traditional immunosuppressive agents. Over all, MMF might be a promising drug for cyclophosphamide-resistant LN.

Intravenous Immunoglobulins (i.v. Ig)

Currently i.v. Ig is used for the treatment of immunodeficiency states, and various auto­immune and inflammatory conditions that include idiopathic thrombocytopenic purpura, Guillian-Barre syndrome and Kawasaki disease. Additionally, i.v. Ig is used empirically in other autoimmune diseases, in which its role remains controversial. [62]

In a recent pilot randomized trial, [63] the safety and efficacy of maintenance therapy with monthly i.v. Ig in proliferative LN was compared with cyclophosphamide. The i.v. Ig was given in a dose of 400 mg/kg for 18 months, while, cyclophosphamide was given i.v. in a dose of 1 g/m 2 once a month for six months and then every three months for one year. Both groups received oral prednisolone in addition. At the end of the follow-up period (24 months) neither groups showed deterio­ration of renal functions and none of the patients developed nephrotic range proteinuria.

Similar observation by Lin et al [60] showed that high-dose i.v. Ig therapy is effective in about half of the cases in steroid and immuno­suppressive drug-resistant Class IV lupus nephritis.

The few reports of i.v. Ig use in LN are case reports in adults. [62],[63],[64] The toxicity of high-dose i.v. Ig was minimal. It included chills, fever, hypotension, acute urticuria, twitching and skin rash. [64] The occurance of transient and reversible renal failure after i.v. Ig therapy has been reported in one patient with borderline renal function. [65] The most likely explanation for the renal damage induced by i.v. Ig is sucrose nephropathy; sucrose is used as a stabilizer in i.v. Ig preparations and can cause severe proximal tubular vacualization with cellular swelling as evident in humans and animals given intravenous infusion of hypertonic sucrose. [62] However, acute renal failure also has been reported after treatment with i.v. Ig preparations not containing sucrose and may be related to dehydration or rapid infusion of the drug. [62],[65]

Plasma exchange

There is an obvious rational for plasma exchange in lupus, since in the active disease, the plasma contains antibodies and immunecomplexes that are believed to play a role in tissue injury. Most workers have assumed that concomitant immuno­suppression should be given to avoid "rebound" antibody synthesis when exchange ceases. [37] However, treatment with plasma exchange plus standard regimen of prednisolone and oral cyclophosphamide therapy does not seem to improve the clinical outcome in patients with severe LN as compared with the standard regimen alone. [66]

Treatment of patients with Class V LN

A greater frequency of Class V LN has been recently noted in childhood than has been reported earlier. [57] In some patients, the membranous lesions are associated with mesangial proliferation. This category resembles diffuse proliferative glomerulonephritis. [17] The nephrotic syndrome often develops. Moderate renal failure and hypertension are observed in 25% of patients. [7] Patients with pure membranous nephro­pathy, mild proteinuria, and normal renal functions have a good prognosis with a 5­year-renal survival close to 85%. [5] The management of the patient having Class V with proliferative lesions must be aggressive treatment with cytotoxic agents including i.v. cyclophosphamide. [5]

Patients with Class V pure membranous nephropathy should receive oral prednisolone either alone or in conjunction with i.v. methyl­ prednisolone. [5],[7]

Infantile Lupus Nephritis

Infantile LN is extremely rare, and only a few cases have been reported. [67],[68] The presentation of the disease tends to be severe, [67] the pathology mainly shows proliferative lesions. Intravenous cyclophos­phamide seems to be beneficial in these patients. [67]

Prognosis of LN in Children

Diffuse proliferative glomerulonephritis (Class IV LN) is associated with a poor prognosis. [69],[70] A positive correlation was observed between the presence of chronic lesions (high chronicity index) on renal biopsy and a poor renal outcome. [34],[35] The presence of high degree of interstitial fibrosis in the first renal biopsy is associated with a poorer renal prognosis. [36]

The combination of cellular cresent and interstitial fibrosis is particularly ominous. [33] Renal survival is significantly worse in some races like American blacks inspite of more aggressive treatment. [44]

Patients with normal initial serum creatinine levels have low risk of renal failure. [36],[71] The presence of hypertension at the time of diagnosis and persistent hypertension lasting greater than four months is considered the most important poor prognostic clinical finding in LN in children. [69],[70],[72] Also, severe nephrotic syndrome and anemia are considered as predictors of poor renal outcome. [32] Age, gender, degree of hypo-complementemia and ANA positivity are not associated with progression to renal failure. [4],[69],[70]

The occurance of renal flares characte­rized by rapid increase in plasma creatinine after cessation of treatment is a strong predictor of development of irreversible deterioration of renal functions. It is recommended that all patients with LN, particularly hyper­tensive patients, continue to be closely monitored in order to catch and treat early and vigorously any possible deterioration of renal function caused by LN flares. [29]

End-stage renal disease (ESRD) in LN children

The risk of progression to ESRD in children with LN is 18 to 50%. [6] This compli­cation developed after a mean period of five years. [7] However, the progression of LN severe enough to require dialysis does not necessarily indicate that it is "end-stage". Ten to 28% of patients with LN who develop renal failure requiring dialysis will recover enough function to come off dialysis. [73],[74]

Dialysis and Transplantation

Dialysis, either hemo or peritoneal, can be started, and these patients do as well as non­lupus patients with end-stage renal disease. Clinical and biological symptoms of the disease most often improve in patients on chronic dialysis, thus allowing discontinuation of corticosteroids and immuno-suppressive therapy. [7],[74] However, clinical manifestations can persist or even get exaggerated at this stage secondary to stress factors. [7]

Renal transplantation is the treatment of choice for those who progress to renal failure.

Patients with ESRD secondary to LN are excellent candidates for renal trans­plantation and recurrence of LN is rare. [75] Graft and patient survival after the first cadaveric and first living-related renal transplantations are similar in patients with ESRD caused by LN and patients with ESRD from other causes. [76] The results of 100 renal transplantations in children with LN reported recently by Batrosh, [6] were comparable to those seen in an age, race, and gender-matched control group. This is despite the fact that SLE patients have an underlying disease with multi-organ involve­ment and have received immunosuppression for prolonged periods before transplantation.

   Conclusion Top

The treatment of LN has been one of the success stories of nephrology during the past three decades. However, this condition continues to cause significant mortality and morbidity. Improvement in survival has come at the expense of long-term complications of therapy, which in the pediatric age group have profound consequences.

The treatment of diffuse proliferative glomerulonephritis should be vigorous. There are still some questions on the duration of treatment, the physician should bear in mind that inadequate treatment of severe nephritis exposes the patient to the risk of progression to renal failure. Lupus nephritis requires long-term and careful follow-up of affected patients and meticulous attention is required to optimize patient outcome.

   References Top

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Correspondence Address:
Abdullah A Al Salloum
Department of Pediatrics (39), College of Medicine & KKUH, King Saud University, P.O. Box 2925, Riyadh 11461
Saudi Arabia
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