Changes in macrophage infiltration and podocyte injury in lupus nephritis patients with repeated renal biopsy: Report of three cases

BACKGROUND In this study,we retrospectively analysed macrophage infiltration and podocyte injury in three patients with diffuse proliferative lupus nephritis(LN)who un-derwent repeated renal biopsy.CASE SUMMARY Clinical data of three diffuse proliferative LN patients with different pathological characteristics(case 1 was LN IV-G(A),case 2 was LN IV-G(A)+V,and case 3 was LN IV-G(A)+thrombotic microangiopathy)were reviewed.All patients underwent repeated renal biopsies 6 mo later,and renal biopsy specimens were studied.Macrophage infiltration was assessed by CD68 expression detected by immunohistochemical staining,and an immunofluorescence assay was used to detect podocin expression to assess podocyte damage.After treatment,Case 1 changed to LN III-(A),Case 2 remained as type V LN lesions,and Case 3,which changed to LN IV-S(A),had the worst prognosis.We observed reduced macro-phage infiltration after therapy.However,two of the patients with active lesions after treatment still showed macrophage infiltration in the renal interstitium.Before treatment,the three patients showed discontinuous expression of podocin.Notably,the integrity of podocin was restored after treatment in Case 1.CONCLUSION It may be possible to reverse podocyte damage and decrease the infiltrating ma-crophages in LN patients through effective treatment.

Severe acute kidney injury due to oxalate crystal induced severe interstitial nephritis:A case report

BACKGROUND Acute kidney injury(AKI)due to interstitial nephritis is a known condition primarily attributed to various medications.While medication-induced interstitial nephritis is common,occurrences due to non-pharmacological factors are rare.This report presents a case of severe AKI triggered by intratubular oxalate crystal deposition,leading to interstitial nephritis.The aim is to outline the case and its management,emphasizing the significance of recognizing uncommon causes of interstitial nephritis.CASE SUMMARY A 71-year-old female presented with stroke-like symptoms,including weakness,speech difficulties,and cognitive impairment.Chronic hypertension had been managed with hydrochlorothiazide(HCTZ)for over two decades.Upon admis-sion,severe hypokalemia and AKI were noted,prompting discontinuation of HCTZ and initiation of prednisolone for acute interstitial nephritis.Further investigations,including kidney biopsy,confirmed severe acute interstitial nephritis with oxalate crystal deposits as the underlying cause.Despite treatment,initial renal function showed minimal improvement.However,with prednisolone therapy and supportive measures,her condition gradually improved,high-lighting the importance of comprehensive management.CONCLUSION This case underscores the importance of a thorough diagnostic approach in identifying and addressing uncommon causes of interstitial nephritis.The occurrence of interstitial nephritis due to oxalate crystal deposition,especially without typical risk factors,emphasizes the need for vigilance in clinical practice.

Focus on laboratory tests related to the pathological types of lupus nephritis to implement renal biopsy as early as possible:clinical and pathological analysis of 217 cases of single center lupus nephritis

Objective:To analyze the clinical and laboratory indices of patients with lupus nephritis(LN)of different pathological types and explore the related factors of LN pathological classification,it is helpful to grasp the timing of renal biopsy.Methods:The clinical manifestations,laboratory parameters and renal pathological types of LN patients in recent 20 years were analyzed retrospectively by SPSS 26.0 software.Results:In this study,the first three pathological types were V,IV,V+IV;latent nephritis was common in type II and V;nephritic syndrome was common in type V;nephrotic syndrome was common in type V+IV;chronic renal insufficiency group was mostly type IV;pathological types were correlated with serum creatinine,C3,albumin and erythrocyte sedimentation rate(r=0.315,P<0.001),and serum creatinine was moderately correlated(r=0.315,P<0.001);AI,CI and SLEDAI scores were significantly different among LN patients of different pathological types.Conclusion:LN is closely related to clinical pathology,clinical manifestations,comprehensive analysis of laboratory indicators and SLEDAI score to make a preliminary prediction of LN pathological type,help to initially assess the severity of pathology,improve the timing of renal biopsy implementation,optimize the timing of treatment.

Reversible Chronic Interstitial Nephritis Induced by Tacrolimus —Tacrolimus Chronic Interstitial Nephritis

Calcineurin inhibitors (CNI) are potent immunosuppressive agents in prophylaxis against graft rejection and autoimmune diseases including primary glomerulopathies. Previous research showed reversible;acute afferent arteriolar vasculopathy and irreversible chronic interstitial fibrosis associated with CNI nephrotoxicity. In this case report we describe a patient, with minimal change disease, that had developed chronic and progressive renal disease while receiving therapeutic dose of Tacrolimus. His serum creatinine had reached 537 umol/L and his nephrotic state worsened. Kidney biopsy showed chronic interstitial nephritis. Tacrolimus was discontinued and he was treated with 1 mg/kg prednisone in addition to Mycophenolate mofetil (MMF) 1 g twice daily. By the 2nd month;serum creatinine returned to normal and by the 3rd month serum albumin too. After 1 month of therapy;the dose of Prednisone was tapered down gradually till 5 mg daily by the end of 3rd month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3rd month. After 2 years of follow up;he remained stable and without relapse of NS or renal failure. In conclusion, reversible renal disease, due to chronic interstitial nephritis can be induced by CNI which is amenable to treatment with Prednisone and MMF.

Association of C-reactive protein and complement factor H gene polymorphisms with risk of lupus nephritis in Chinese population

BACKGROUND Complement overactivation is a major driver of lupus nephritis(LN).Impaired interactions of C-reactive protein(CRP)with complement factor H(CFH)have been shown as a pathogenic mechanism that contributes to the overactivation of complement in LN.However,genetic variations of neither CRP nor CFH show consistent influences on the risk of LN.AIM To examine whether genetic variations of CRP and CFH in combination can improve the risk stratification in Chinese population.METHODS We genotyped six CRP single nucleotide polymorphisms(SNPs)(rs1205,rs3093062,rs2794521,rs1800947,rs3093077,and rs1130864)and three CFH SNPs(rs482934,rs1061170,and rs1061147)in 270 LN patients and 303 healthy subjects.RESULTS No linkage was found among CRP and CFH SNPs,indicating lack of genetic interactions between the two genes.Moreover,CRP and CFH SNPs,neither individually nor in combination,are associated with the risk or clinical manifestations of LN.Given the unambiguous pathogenic roles of the two genes.CONCLUSION These findings suggest that the biological effects of most genetic variations of CRP and CFH on their expressions or activities are not sufficient to influence the disease course of LN.

Network pharmacology and data analysis method to explore the traditional Chinese medicine regulates ferroptosis key genes in the occurrence and prognosis of lupus nephritis

Purpose:To explore the traditional Chinese medicine(TCM)regulates ferroptosis key genes in the occurrence and development of lupus nephritis(LN)based on biological information database.Patients and methods:Ferroptosis related genes were identified based on FerrDb database and literature retrieval.Used the OMIM,Gene Cards,Drug Bank to obtain the targets of LN.Cytoscapes 3.8.2 software and STRING database were used to analyze protein-protein interaction(PPI)network.Metacape software and Weishengxin were used to analyze the gene ontology(GO)classification and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.UniProt Database and Traditional Chinese Systems Pharmacology Database and Analysis Platform analysis platform were used to obtain the data table of key TCM and related targets.Cytoscapes 3.8.2 software was used to analyze the PPI network.Results:A total of 401 ferroptosis-related genes,361 LN related genes and 21“Ferroptosis-LN”intersection genes were obtained.Ferroptosis in the occurrence and prognosis of LN mainly involved the inflammatory response,cell activation,positive regulation of chemokine production and it was mainly involved in necroptosis,inflammatory bowel disease,ferroptosis and other pathways.A total of 412 TCMs containing key genes of“Ferroptosis-LN”were acquired.The most key genes were contained in Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua.15 key genes of“TCM-LN”were obtained.5 ferroptosis-related key genes in LN regulated by TCM were obtained,which were IL1β,TLR4,IFNG,STAT3 and HMOX1.Conclusion:TCM,such as Mahuang,Gehua,Baiguo,Chuanniuxi,Jinyinhua,may affect the occurrence and development of LN through the key ferroptosis genes,such as IL1B,TLR4,IFNG,STAT3 and HMOX1.

Advances in Diagnosis and Treatment of Lupus Nephritis(Class V)

Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.

Immunoglobulin A vasculitis nephritis:Current understanding of pathogenesis and treatment

The clinical spectrum of immunoglobulin A vasculitis nephritis(IgAVN)ranges from the relatively common transitory microscopic hematuria and/or low-grade proteinuria to nephritic or nephrotic syndrome,rapidly progressive glomerulonephritis,or even renal failure.Clinical and experimental studies have shown a multifactor pathogenesis:Infection triggers,impaired glycosylation of IgA1,complement activation,Toll-like-receptor activation and B cell proliferation.This knowledge can identify IgAVN patients at a greater risk for adverse outcome and increase the evidence for treatment recommendations.

Effect of Rituximab Versus Mycophenolate Mofetil or Cyclophosphamide as Control in Lupus Nephritis:A Meta-Analysis

Objective:To evaluate the effects of rituximab versus mycophenolate mofetil or cyclophosphamide as control in lupus nephritis by meta-analysis.Methods:A systematic search was carried out up to January 2022,obtaining 7 studies involving 645 participants with lupus nephritis at the commencement of the investigation;198 of them were treated with rituximab,while 447 were treated with mycophenolate mofetil or cyclophosphamide.We determined the odds ratio(OR)and mean difference(MD)with 95%confidence index(CI)to compare rituximab’s efficacy to that of mycophenolate mofetil or cyclophosphamide as control in lupus nephritis using random-or fixed-effects model by dichotomous or continuous techniques.Results:The rituximab group showed significantly higher complete renal remission rate(OR=2.52;95%CI 1.30-4.91,P=0.006)and total renal remission rates(OR=2.22;95%CI 1.36-3.63,P=0.001)than the control group.However,there was no significant difference in terms of end Systemic Lupus Erythematosus Disease Activity Index(SLEDAI)score(MD-1.16;95%CI-2.88-0.57,P=0.19),proteinuria(MD-0.31;95%CI-0.70-0.09,P=0.013),and serum creatinine(MD 0.01;95%CI-0.04-0.07,P=0.64)between the rituximab group and the control.Conclusion:Rituximab exhibited significantly greater complete renal remission rate and total renal remission rates,with no significant difference in terms of shorter-end SLEDAI,proteinuria,and serum creatinine,compared with the control in individuals with lupus nephritis.

Experimental Study on Prevention and Treatment of Rat Passive Hermann Nephritis (PHN) with Ligustrazine

Objective: To explore the effects of ligustrazine on proteinuria, serumcreati-nine, urinary thromboxane A_2(TxA_2), metabolism of prostacyclinI_2(PGI_2)―6-keto-PGF_(1α), and renal pathological changes of SD rats with passive Hermannnephritis (PHN). Methods: The PHN model was induced by intravenous injection of rabbit anti-ratrenal tubular epithelial antigen (Tub―Ag) an-tiserum to SD rats. I. P. administration ofligustrazine to rats was given every 2 d for 1 to 5 weeks. The proteinuria, creatinine, TxA_2 and6-keto-PGF_(1α) were measured by sulfosaticylic acid, picric acid, and direct radioimmunoassayrespectively. The renal pathological changes were observed under light microscope, electronicmicroscope and by direct immunofluorescence staining rabbit and rat IgG. Results: The PHN ratstreated with ligustrazine had significantly less proteinuria, serum creatinine, urinary TxA_2 andpathological changes of kidney, and more urinary 6-keto-PGF_(1α) than those without administrationof ligustrazine. Conclusion: Ligustrazine decreases proteinuria, urinary TxA_2, and renal tissueinjury and increases urinary 6-keto-PGF_(1α). These data indicate that ligustrazine may modulatethe balance of TxA_2 and PG I_2 in rat PHN model and can be used for preventing and treatingmembranous glomerulonephritis.

Detection of the Level of Urinary FPA in Chronic Nephritis with Renal Failure and Its Clinical Implication

The level of urinary FPA was assayed by high per formance liquid chromatography (HPLC ) in 42 normal controls, 57 cases of chronic glomeru-lonephritis, including 24 with normal renal function, 12 with renal insufficiency and 21 with uremia. Their levels were 24. 40± 10. 30 μg/L, 26. 99±5.77 μg/L,38. 81±6. 28 μg/L, 79. 74± 18. 76 μg/L, respectively. The level of urinary FPA in renal insufficiency function group was significantly higher than those of the con-trol group and normal renal function group (P<0.01). The patients with uremia presented dramatically higher level of urinary FPA than those in the renal insufficiency group (P<0.01). A positive correlation was found between the level of urinary FPA and the blood creatine (r= 0. 9120, P<0. 01 ). It was suggested that a hypercoagulable state existed in the patients with chronic nephritis with renal failure, in which the severity was closely related with the occurrence and development of the disease. The urinary FPA could serve as a good indicator for renal function.

Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism in Children with Henoch-Schonlein Purpua Nephritis

This study investigated the relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism and the occurrence, severity, prognosis of HSPN. The polymorphism of ACE gene in 103 HSPN cases and 100 healthy children was studied by using the polymerase chain reactions (PCR). Its relation to the clinical manifestation, pathological classification and prognosis of HSPN was analyzed accordingly. The results showed that: (1) there was a significantly higher frequency for DD genotype in HSPN children (P<0.01); (2) DD genotype was more frequently seen in HSPN children with gross hematuria and massive proteinuria (P<0.05), while DI genotype was more common in HSPN children group with renal insufficiency (P<0.05); (3) although mesangial proliferative lesion was most frequently observed in 21 biopsied HSPN children, and DD genotype frequency was still higher in children with severe pathology (Class Ⅲ Ⅳ); (4)II genotype was significantly frequent in HSPN children with complete remission in the follow-up of 32 HSPN children. It was concluded that the deletion allele of ACE gene might play a role, at least to some extent, in the occurrence, deterioration and progression in juvenile HSPN.

Relationship Between Serum DNA Replication, Clinicopathological Characteristics and Prognosis of Hepatitis B Virus-associated Glomerulonephritis with Severe Proteinuria by Lamivudine Plus Adefovir Dipivoxil Combination Therapy

Objective To explore the relationship between HBV DNA and the clinical manifestations, pathological types, injury severity, and prognosis with HBV-GN. Methods 102 patients with HBV-GN were divided into 3 groups, according to the serum titer of the HBV DNA. 24-h urine protein excretion, and other parameters were measured. Renal biopsy were performed. The association between HBV DNA and the pathological stage of membranous nephropathy was analyzed in 78 patients with HBV-MN. 24-h urine protein excretion was used for the evaluation of the prognosis, and the relationship between HBV DNA and prognosis were analyzed. Results Several findings were demonstrated with the increase of serum HBV DNA： 24-h urine protein excretion, plasma cholesterol, and triglycerides increased significantly（P〈0.05）, while the plasma level of albumin decreased significantly（P〈0.05）; The changes of serum creatinine, C3 and C4 were found but no statistical significance. Glomerular deposition of HBVAg increased, and the pathological injury was more severe. The clinical remission rate was lower in the high replication group after treatment as compared with the low replication group（P〈0.01）. Conclusion With the increase of serum HBV DNA, the urine protein excretion and the kidney injury were more severe, and the clinical remission rate was decreased.

Successful treatment of tubulointerstitial nephritis in immunoglobulin G4-related disease with rituximab: A case report

BACKGROUND Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition that consisted of disorders that share particular clinical,serologic and pathologic properties.The common presentation of disease includes tumor-like swelling of involved organs and the histopathological findings are a lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells,and a variable degree of fibrosis that has a characteristic "storiform" pattern in biopsy specimens of tumorlike masses.Major presentations of this disease,which often affects more than one organ,include autoimmune pancreatitis,salivary gland disease (sialadenitis),orbital disease and retroperitoneal fibrosis.The steroid treatment is essential for the treatment of the disease however,other immunosuppressive drugs including cyclophosphamide or rituximab could be an option in resistant cases.CASE SUMMARY Herein,we reported a 34-year-old woman whom previously had diagnosed with asthma,rheumatoid arthritis and Sj?gren’s syndrome (SS) referred our nephrology department due to acute kidney failure development at the last rheumatology visit.After kidney biopsy she has been diagnosed with IgG4-RD and tubuluointerstitial nephritis.She had been accepted resistant to steroid,mycophenolate mofetil,methotrexate and azathioprine therapies due to receiving in last two years.She refused to receive cyclophosphamide due to potential gonadotoxicity of the drug.Thus,rituximab therapy was considered.She received 1000 mg infusion,15 d apart and 6 mo later it has been administered same protocol.After one year from the last rituximab dose serum creatinine decreased from 4.4 mg/dL to 1.6 mg/dL,erythrocyte sedimentation rate decreased from 109 mm/h to 13 mm/h [reference range (RR) 0-20],and Creactive protein decreased from 55.6 mg/L to 5 mg/L (RR 0–6).All pathologic lymph nodes and masses were also disappeared.CONCLUSION Patients with IgG4-RD usually misdiagnosed with rheumatologic diseases including systemic lupus erythematous or SS and also they were screened for the presence of malignancy.Rituximab could be an important treatment option in cases with steroid resistant tubulointerstitial nephritis in IgG4-RD.

Childhood Henoch-Schnlein Purpura Nephritis and IgA Nephropathy: One Disease Entity?——A Clinico-pathologically Comparative Study

Summary： In order to characterize their relationship through clinicopathological comparison between IgA nephropathy and Henoch-Schoenlein purpura nephritis （HSPN）, 31 children with IgA nephrop- athy aged between 3 to 15 years and 120 children with HSPN aged between 4 to 15 years were compared with each other in clinical manifestation, blood biochemistry, serum immunology and followup study. Renal pathological findings under light microscope, immunofluorescence and electronic microscope were analyzed and also compared between 31 children with IgA nephropathy and 32 biopsied children with HSPN. The results showed that the onset age was over 12 years in 25.8 % children with IgA nephropathy, but only 10 % in HSPN （P〈0.05）. The clinical patterns of IgA nephropathy and HSPN were similar, but extra-renal manifestations were more often in HSPN, all of them had skin purpura, 59 % had gastrointestinal symptoms and 47 % suffered from arthralgia, compared with only abdominal pain in 3.2 % children with IgA nephropathy. The renal pathological investigation showed global sclerosis in 35.5 % of IgA nephropathy and 3.1% of HSPN, mesangial sclerosis in 41.9 % of IgA nephropathy and 6.3 % of HSPN, but endothelial proliferation in 65.6 % of HSPN and 29 % of IgA nephropathy （all P〈0.01）. Thin basement membrane nephropathy was only found in 6. 5 % children with IgA nephropathy, no in HSPN. The electronic dense deposits in HSPN were sparse, lodse and wildly spread in glomerular mesangium, subendothelial area and even intra basement membrane, but it was dense, lumpy and mostly limited in mesangium and paramesangium in IgA nephropathy. Predominant IgA deposits were found in 81.2% of HSPN, and overwhelming IgG deposits in 12.5 % of HSPN with relatively weak IgA deposits, moreover 6.3 % of HSPN showed linear IgG deposits in glomerular capillary. Totally 71. 9 G of HSPN had IgG deposits in glomeruli and only 19.4% of IgA nephropathy showed glomerular IgG deposits （P〈0. 01）. No IgG deposit was observed in 81. 6 % of IgA nephropathy, among them most showed IgA and IgM and/or C3 deposits, moreover overwhelming IgG deposits and linear IgG deposits couldn＇t be found in IgA nephropathy. Mean 20 months follow-up showed complete remission in 72.5% of HSPN, but only 19.4% in IgA nephropathy after 34 months follow-up. Moreover, 64.5 % of IgA nephropathy had consistent hematuria and proteinuria and 16. 1% had active nephritides （P〈0.05）. It was concluded that significant clinico-pathological difference was found between HSPN and IgA nephropathy, which didn＇t support the one disease entity hypothesis. HSPN and IgA nephropathy are probably two diseases with similar immune abnormalities.

TSP-1 promotes glomerular mesangial cell proliferation and extracellular matrix secretion in Thy-1 nephritis rats

The proliferation of glomerular mesangial cells （GMC） and secretion of the extracellular matrix （ECM） in rat with Thy-1 nephritis （Thy-lN） resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 （TSP-1） gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. 111 the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-lN rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation （P 〈 0.01） and ECM secretion （P 〈 0.01） as well as urinary protein secretion （P 〈 0.05） in Thy-lN rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-lN rats.

Cytomegalovirus enteritis mimicking Crohn's disease in a lupus nephritis patient:A case report

Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.

Effect of Lipo-prostaglandin E_1 on Mesangial Proliferative Glomerulonephritis in Rats

Summary： The antinephritic effect of lipo-prostaglandin E1. prostaglandin E1 incorporated in lipid mierospheres was investigated using an experimental model of mesangial proliferative glomerulonephritis （MsPGN）. Twenty-two female rats were randomly divided into nephritic group （N, n=6）, lipo-prostaglandin E1 treated group （NL, n=8） and control group （C, n=6）. Lipo-prostaglandin E1 was given intravenously at 40 μg·kg^-1·d^-1 from the 6th week to the 8th week. Twenty-four h urinary protein contents and blood ereatinine （Cr） were determined and the pathological changes were observed in the experiment. The expression of proliferating cell nuclear antigen （PCNA）, extraeellular matrix （fibroneetin, FN; collagen type Ⅳ , Col Ⅳ ） and transforming growth factor β1 （TGFβ1） was detected by using immunohistoehemistry. The results showed that lipo-prostaglandin E1 significantly inhibited the glomerular histopathologieal changes as well as the elevation of plasma Cr （P〈0.05）. The overexpression of PCNA, FN, Col Ⅳ and TGFβ1 were also obviously inhibited in group NL as compared with the group N （P〈0.01）. It was suggested that lipo-prostaglandin E1 could improve renal function, inhibit the proliferation of glomerular cells and reduce the deposition of extraeellular matrix, which may be related to the down-regulation of the TGFβ1 expression.

Acute lobar nephritis in children: Not so easy to recognize and manage

Acute lobar nephritis(ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.

Treatment of young patients with lupus nephritis using calcineurin inhibitors

Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis