Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dysl...Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dyslipidemia,particularly secondary hyperlipemia,in patients with diabetic kidney disease.Methods We conducted a two-sample Mendelian randomization study using genome-wide association study(GWAS)summary data.Genetic variants associated with MR levels were selected as exposures,with TIN and lipid profiles[including low-density lipoprotein cholesterol(LDL-C),triglyceride,and high-density lipoprotein cholesterol]as outcomes.A two-step Mendelian randomization approach was used to assess TIN as a mediator,employing inverse variance weighted regression as the primary analysis,supplemented by Mendelian randomization-Egger,weighted median,and sensitivity analyses.Results Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN(OR=0.8598,95%CI[0.7775-0.9508],P<0.001).Although no significant causal relationship was identified between MR level and secondary hyperlipemia,a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed(OR=0.9901,95%CI[0.9821-0.9983],P=0.018).Additionally,TIN exhibited causal links with secondary hyperlipemia(OR=1.0016,95%CI[1.0002-1.0029],P=0.020)and elevated LDL-C(OR=1.0111,95%CI[1.0024-1.0199],P=0.012),particularly LDL-C in European males(OR=1.0230,95%CI[1.0103-1.0358],P<0.001).Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride(OR=0.7027,95%CI[0.6189-0.7978],P<0.001),high-density lipoprotein cholesterol(OR=1.1247,95%CI[1.0019-1.2626],P=0.046),and LDL-C(OR=0.8423,95%CI[0.7220-0.9827],P=0.029).Notably,TIN mediated 16.7%of the causal association between MR and LDL-C levels.Conclusions MR plays a critical role in the development of TIN and lipid metabolism,highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.展开更多
Staphylococcus associated glomerulonephritis (SAGN) is an uncommon infection-related glomerulonephritis. Although infection is typically ongoing when patients present with SAGN, in the case of deep-seated infections, ...Staphylococcus associated glomerulonephritis (SAGN) is an uncommon infection-related glomerulonephritis. Although infection is typically ongoing when patients present with SAGN, in the case of deep-seated infections, the presence of infection may not be apparent. The aim of this study is to highlight the importance of renal biopsy when the diagnosis is not obvious. We present a case of staphylococcus associated glomerulonephritis in a patient treated with beta-lactam antibiotics for staphylococcus bacteraemia. A renal biopsy helped differentiate between interstitial nephritis and staphylococcus associated glomerulonephritis.展开更多
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 ...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.展开更多
Calcineurin inhibitors (CNI) are potent immunosuppressive agents in prophylaxis against graft rejection and autoimmune diseases including primary glomerulopathies. Previous research showed reversible;acute afferent ar...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 2<sup>nd</sup> month;serum creatinine returned to normal and by the 3<sup>rd</sup> 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 3<sup>rd</sup> month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3<sup>rd</sup> 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.展开更多
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-pharma...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.展开更多
We report a case of IgG4-related disease presenting both tubulointerstitial nephritis and retroperitoneal fibrosis causing acute renal failure in a 63-year-old male. He was admitted to our hospital because of acute re...We report a case of IgG4-related disease presenting both tubulointerstitial nephritis and retroperitoneal fibrosis causing acute renal failure in a 63-year-old male. He was admitted to our hospital because of acute renal failure requiring emergent hemodialysis. Computed tomography showed a soft-tissue density mass with an irregular border in the retroperitoneum. The mass involved bilateral ureters and had caused acute renal failure by bilateral hydronephrosis. Because of a history of uveitis and high IgG4 levels, we considered a diagnosis of retroperitoneal fibrosis, IgG4-related disease. Kidney biopsy revealed IgG4-related kidney disease with interstitial nephritis. After relief of urinary obstruction by inserting ureteral catheters into the bilateral ureters, renal function recovered.展开更多
Objective:To explore the clinical and pathological features of Fabry disease complication of acute interstitial nephritis.Methods:A retrospective analysis of a patient with Fabry disease and acute interstitial nephrit...Objective:To explore the clinical and pathological features of Fabry disease complication of acute interstitial nephritis.Methods:A retrospective analysis of a patient with Fabry disease and acute interstitial nephritis diagnosed and in the Department of Nephrology,Children’s Hospital Affiliated to Capital Institute of Pediatrics in January 2017 was performed.A literature search was performed with“Fabry disease,acute interstitial nephritis”as the keywords in Wanfang database and PubMeds database.Result:The patient was 10-years-old with acute renal dysfunction.Electron microscopy showed stratified myelin-like bodies,zebra bodies and fused foot segment.The patient was finally diagnosed with the combination of Fabry disease and acute interstitial nephritis.By now,such cases have been reported.Conclusion:Whether Fabry's disease and acute interstitial nephritis shared the common pathogenic mechanism is unclear.Early renal biopsy is important for the diagnosis of this disease.展开更多
920149 The relationship between renal tis-sue subsets of lymphocytes and clinicalfeatures in IgA nephropathy.LIU Zhihong （刘志红）,et al.Dept Nephrol,Jinling Hosp,Nanjing（210002）.Chin J Nephrol 1991; 7 （4）: 230.A...920149 The relationship between renal tis-sue subsets of lymphocytes and clinicalfeatures in IgA nephropathy.LIU Zhihong （刘志红）,et al.Dept Nephrol,Jinling Hosp,Nanjing（210002）.Chin J Nephrol 1991; 7 （4）: 230.Amount of CD<sub>4</sub><sup>+</sup>,CD<sub>8</sub><sup>+</sup> and B cells in展开更多
970370 The expression of AT1A receptor and itsmodulation by benazepril in the renal tubulointerstitiallesions induced by ureteral obstruction. CHEN Xi-angmei(陈香美), et al. Nephrol Div, General Hosp,PLA, Beijing, 100...970370 The expression of AT1A receptor and itsmodulation by benazepril in the renal tubulointerstitiallesions induced by ureteral obstruction. CHEN Xi-angmei(陈香美), et al. Nephrol Div, General Hosp,PLA, Beijing, 100853. Natl Med J China 1997; 77(4):245-248.展开更多
930568 The production and significance of IL4in patients with idiopathic nephroctic syndrome.YAO Zhi(姚智),et al.Dept Immunol,BeijingMed Univ,Beijing,100083,Natl Med J China1993;73(5):261—263.Samples of serum and PBM...930568 The production and significance of IL4in patients with idiopathic nephroctic syndrome.YAO Zhi(姚智),et al.Dept Immunol,BeijingMed Univ,Beijing,100083,Natl Med J China1993;73(5):261—263.Samples of serum and PBMC were collected atthe same time from 42 pediatric patients with id-iopathic nephrotic syndrome(INS)and 28 age—matched healthy individuals.The level os IgE inserum was detected and IL4 in supernatant ofPHA-activated PBMC assayed by sandwichELISA.The levels of IL4 and IgE in healthy in-dividuals were 400～500 pg/ml and 50～100 U/ml respectively,and those of IL and IgE in theINS patients were on the average 1080～4000Pg/ml and 380～1000 U/ml.Positive correla-展开更多
950358 Detection of glucocorticoid receptor (GCR)of lymphocyte in childnephrotic syndrome (NS).TANG Jieru(汤洁如),et al.Dept Pediatr,1st AffiliHosp,Sun Yat-sen Meal Univ,Guangzhou.Chin JNephrol 1994;10(6):342-343.Asse...950358 Detection of glucocorticoid receptor (GCR)of lymphocyte in childnephrotic syndrome (NS).TANG Jieru(汤洁如),et al.Dept Pediatr,1st AffiliHosp,Sun Yat-sen Meal Univ,Guangzhou.Chin JNephrol 1994;10(6):342-343.Assesment of steroid receptor content in humanneoplastic cells or mammary tumor cells has been pre-viously used to prearct steriod sensitivity in variouscancers.In the present study,we evaluated the rela-tionship between GCR content and the prednisone sen-展开更多
930331 Significance of determination of urinealbumin for early diagnosis of diabeticnephropathy.ZHOU Zhongyuan (周中源),Shanghai 4th People’s Hosp.Shanghai Med J1993;16(2):74—76.The results of urine albumin determin...930331 Significance of determination of urinealbumin for early diagnosis of diabeticnephropathy.ZHOU Zhongyuan (周中源),Shanghai 4th People’s Hosp.Shanghai Med J1993;16(2):74—76.The results of urine albumin determination in208 patients with non-insulin dependent dia-betes mellitus but tested negative for urinaryprotein on routine examination and in 177 nor-mal controls were reported.The results showedthat the excretion of urine albumin in 131 pa-tients was obviously higher than that in normalcontrols (p【0.001).In the diabetic patientstested negative for urinary protein on routineexamination the excretion of urine albumin展开更多
Tubulointerstitial nephritis complicated by primary Sj?gren’s syndrome in a patient under treatment for type 2 diabetes mellitus was diagnosed in the early stage of the disease by renal biopsy. The symptoms of primar...Tubulointerstitial nephritis complicated by primary Sj?gren’s syndrome in a patient under treatment for type 2 diabetes mellitus was diagnosed in the early stage of the disease by renal biopsy. The symptoms of primary Sj?gren’s syndrome, such as thirst and polydipsia, were masked by the characteristic symptoms of type 2 diabetes mellitus. An association between sicca symptoms and diabetes mellitus (types 1 and 2) has been previously reported. Hence, it is possible that there are common underlying immunological mechanisms between primary Sj?gren’s syndrome and diabetes mellitus of both types. Intervention with steroids in a timely manner appears to have prevented or slowed the progression of re- nal impairment.展开更多
930154 Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in diabetic nephropathyWANG Yao（王尧）,et al,Dept Endocrinol,1stAffil Hosp,Nanjihng Railway Med Coll.210009.Chin J Nephrol 1992;8（5）:275-277.The plasma...930154 Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in diabetic nephropathyWANG Yao（王尧）,et al,Dept Endocrinol,1stAffil Hosp,Nanjihng Railway Med Coll.210009.Chin J Nephrol 1992;8（5）:275-277.The plasma levels of TXB<sub>2</sub> and 6-keto-PGF<sub>1</sub>were measured by RIA in 14 diabetics with and49 diabetics without nephropathy and 35 normalsubjects.The results showed that the levels ofplasma TXB<sub>2</sub> and the ratio of TXB<sub>2</sub>/6-keto-PGF<sub>.</sub>were increased both in diabetics with展开更多
BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological ...BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological characteristics and long-term outcomes in terms of remission,requirement of kidney replacement therapy(KRT),and patient survival.METHODS A retrospective analysis was conducted on biopsy-proven focal or diffuse PLN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation and followed up at the renal clinic for a minimum of 5 years.All patients were induced with a combination of intravenous cyclophosphamide and corticosteroids for 6 months,followed by maintenance treatment with azathioprine(AZA)or mycophenolate mofetil(MMF).Data were analyzed using Statistical Package for the Social Sciences,version 22.0.P≤0.05 was considered statistically significant.RESULTS The mean age at the onset of systemic lupus erythematosus was 24.12 years±8.89 years,and at LN onset,26.63 years±8.61 years.There was a female predominance of 184(88.9%)cases.Among baseline characteristics,reduced estimated glomerular filtration rate,presence of hypertension,requirement of KRT,and underlying renal histology(International Society of Nephrology/Renal Pathology Society class IV than class III)were significantly associated with end-stage kidney disease(ESKD)and mortality.The renal outcomes were negatively correlated with age,duration of symptoms,and 24-hour urinary protein excretion.The overall remission rate was 89.8%at the end of induction therapy.At 5 years,141(68.11%)patients were in complete and partial remission(94[45.4%]and 47[22.7%],respectively).In total,19(9.2%)patients required KRT on presentation,and at 5 years,38(18.4%)patients developed ESKD,and 28(13.5%)patients died.Thirty-four(16.4%)patients had a renal relapse,more with AZA than MMF(30[88.2%]vs 4[11.76%],respectively;P=0.04).Renal survival at 6 months was 89.8%,while at 5 years,it was 68.11%,showing a significant improvement in patients who did not need KRT at the time of presentation(P<0.0001).CONCLUSION Baseline renal functions,requirement of KRT,and diffuse proliferative disease were the most relevant prognostic factors for kidney survival among this cohort.Short-term renal outcomes were good.Long-term outcomes were poorer with AZA-based maintenance therapy than with MMF,with more ESKD and mortality.展开更多
Objective To review and synthesize preclinical and clinical evidence regarding traditional Chinese medicine(TCM)formulations and bioactive herbal compounds in lupus nephritis(LN),and to identify direction and research...Objective To review and synthesize preclinical and clinical evidence regarding traditional Chinese medicine(TCM)formulations and bioactive herbal compounds in lupus nephritis(LN),and to identify direction and research priorities for integrating TCM with professional care.Methods A narrative literature review was conducted by searching Scopus,PubMed,Web of Science,and Google Scholar for articles published between January 1,2011 and March 31,2024.Search terms combined controlled vocabulary[e.g.,medical subject headings(MeSH)]and free-text words including lupus nephritis,traditional Chinese medicine,Chinese herbal medicine,formulation,and names of specific herbs[Leigongteng(Tripterygii Wilfordii Radix et Rhizoma),Baishao(Paeoniae Radix Alba),and Yinghao(Artemisiae Annuae Herba)].Both randomized controlled trials and observational studies were included,along with mechanistic preclinical studies and pharmacologic investigations.Inclusion criteria were studies that reported renal outcomes(proteinuria and estimated glomerular filtration rate),immunemodulatory mechanisms,or safety and herb-drug interaction data.Studies without primary data,case reports,or those lacking relevance to LN were excluded.References of key articles were manually screened to identify additional eligible studies.Results TCM formulas[e.g.,Liuwei Dihuang Pills(六味地黄丸),Zhibai Dihuang Pills(知柏地黄丸),and Huanglian Jiedu Decoction(黄连解毒汤)]and herbal medicines[e.g.,extracts from Leigongteng(Tripterygii Wilfordii Radix et Rhizoma),Baishao(Paeoniae Radix Alba),and Yinghao(Artemisiae Annuae Herba)]were commonly used in the above studies.TCM formulations and their constituent compounds showed multi-modal mechanisms relevant to LN pathogenesis,encompassing immunomodulation(reduction of autoreactive B/T cell activity,regulatory T cell enhancement),inhibition of pro-inflammatory signaling pathways nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),mitogen-activated protein kinase(MAPK),nucleotide-binding oligomerization domain(NOD),leucine-rich repeat(LRR)and pyrin domain-containing protein 3(NLRP3 inflammasome),anti-fibrotic and antioxidant effects,and direct renal-protective properties.In many studies,these indicators can reduce proteinuria and improve renal function.Clinical data,while promising,are heterogeneous in design,sample size,endpoints,and TCM formulation standardization.Safety concerns(notably with Tripterygium preparations)and potential herb-drug interactions with immunosuppressants remained important considerations.Conclusion TCM offers biologically plausible and multi-targeted adjuvant strategies for LN that may enhance therapeutic efficacy and reduce toxicity when combined with modern therapies.To translate these promises into clinical practice,future work should prioritize the standardization of TCM preparations,randomized controlled trials with clinically meaningful renal endpoints,elucidation of molecular mechanisms,and systematic evaluation of pharmacokinetic and safety interactions.Such integrative research will be essential to define the TCM’s role in evidence-based,patient-centered LN management.展开更多
Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis(LN),and targeting plasma cell aggregation offers a promising therapeutic strategy.Ginsenoside com-pound K(i.e.,20-O-...Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis(LN),and targeting plasma cell aggregation offers a promising therapeutic strategy.Ginsenoside com-pound K(i.e.,20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol)(CK),a derivative of ginsenoside,has indicated significant potential in alleviating renal damage in lupus-prone mice,potentially by modu-lating B cell dynamics in response to endoplasmic reticulum(ER)stress.In this study,CK(20 or 40 mg/kg)was orally administered to female MRL/lpr mice for 10 weeks.The effects of CK on B cell sub-populations,renal function,and histopathological changes were evaluated.Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury.Additionally,in vitro B cell assays were conducted to explore the role of the sirtuin-1(SIRT1)-X-box binding protein 1(XBP1)axis in ER stress.Our findings demonstrated that CK effectively reduced anti-double stranded DNA(dsDNA)antibody levels,alleviated systemic inflamma-tion,improved renal function,and facilitated the clearance of deposited immune complexes.CK likely suppressed the unfolded protein response(UPR),delaying the differentiation of renal-activated B cells into plasma cells.It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form,XBP1s.CK also restored ER morphology by interacting with calmodulin(CALM)to maintain ER calcium storage,reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation,thereby limiting plasma cell differentiation.In conclusion,CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing,offering a potential therapeutic approach for LN.展开更多
Pediatric lupus nephritis(LN)is a challenging and severe condition in pediatrics.Traditional Chinese medicine(TCM)has shown significant advantages in improving immune disorders,reducing recurrence rates,and mitigating...Pediatric lupus nephritis(LN)is a challenging and severe condition in pediatrics.Traditional Chinese medicine(TCM)has shown significant advantages in improving immune disorders,reducing recurrence rates,and mitigating the toxic side effects of Western medications.However,it faces challenges such as the lack of a unified TCM syndrome differentiation system,insufficient standardization of dynamic syndrome differentiation,an incomplete efficacy evaluation system,and a lack of precise intervention methods.This study focuses on the clinical advantages of TCM.On 1 September 2024,the 35th Clinical Advantage Disease Series Salon was held in Zhengzhou,discussing the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.Experts in TCM and integrated Chinese-Western medicine,along with interdisciplinary researchers,conducted extensive and in-depth discussions.They proposed specific recommendations for TCM and integrated Chinese-Western medicine in treating pediatric LN and reached a consensus.Based on this,the study analyzes the challenges in treating pediatric LN from the perspective of its development patterns,and summarizes three key areas and six research directions to highlight the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.It focuses on three key areas:The construction of a TCM system for pediatric LN,the prevention and treatment of complications,and chronic disease management.And it proposes six research directions:(1)Constructing a syndrome differentiation system for pediatric LN;(2)Formulating TCM and integrated Chinese-Western medicine guidelines for pediatric LN;(3)Researching the mechanisms of enhancing efficacy and reducing toxicity in integrated Chinese-Western medicine for pediatric LN;(4)Preventing and treating complications in pediatric LN;(5)Developing and researching TCM regimens for preventing and treating the recurrence of pediatric LN;(6)Strategies for the full-cycle chronic disease management of pediatric LN.Finally,the study summarizes and generalizes the technological layout and research directions for pediatric LN.Therefore,based on the series of salons on traditional Chinese medicine advantages for children LN diseases,this paper puts forward a research paradigm of scientific and technological breakthroughs for children LN,in order to provide reference for the construction and research direction of children LN diagnosis and treatment system with traditional Chinese medicine characteristics.展开更多
Objective To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephrit...Objective To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed.Methods Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05).Conclusions The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.展开更多
文摘Objective To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor(MR)and the development of tubulointerstitial nephritis(TIN),and to evaluate the impact of MR on dyslipidemia,particularly secondary hyperlipemia,in patients with diabetic kidney disease.Methods We conducted a two-sample Mendelian randomization study using genome-wide association study(GWAS)summary data.Genetic variants associated with MR levels were selected as exposures,with TIN and lipid profiles[including low-density lipoprotein cholesterol(LDL-C),triglyceride,and high-density lipoprotein cholesterol]as outcomes.A two-step Mendelian randomization approach was used to assess TIN as a mediator,employing inverse variance weighted regression as the primary analysis,supplemented by Mendelian randomization-Egger,weighted median,and sensitivity analyses.Results Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN(OR=0.8598,95%CI[0.7775-0.9508],P<0.001).Although no significant causal relationship was identified between MR level and secondary hyperlipemia,a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed(OR=0.9901,95%CI[0.9821-0.9983],P=0.018).Additionally,TIN exhibited causal links with secondary hyperlipemia(OR=1.0016,95%CI[1.0002-1.0029],P=0.020)and elevated LDL-C(OR=1.0111,95%CI[1.0024-1.0199],P=0.012),particularly LDL-C in European males(OR=1.0230,95%CI[1.0103-1.0358],P<0.001).Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride(OR=0.7027,95%CI[0.6189-0.7978],P<0.001),high-density lipoprotein cholesterol(OR=1.1247,95%CI[1.0019-1.2626],P=0.046),and LDL-C(OR=0.8423,95%CI[0.7220-0.9827],P=0.029).Notably,TIN mediated 16.7%of the causal association between MR and LDL-C levels.Conclusions MR plays a critical role in the development of TIN and lipid metabolism,highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.
文摘Staphylococcus associated glomerulonephritis (SAGN) is an uncommon infection-related glomerulonephritis. Although infection is typically ongoing when patients present with SAGN, in the case of deep-seated infections, the presence of infection may not be apparent. The aim of this study is to highlight the importance of renal biopsy when the diagnosis is not obvious. We present a case of staphylococcus associated glomerulonephritis in a patient treated with beta-lactam antibiotics for staphylococcus bacteraemia. A renal biopsy helped differentiate between interstitial nephritis and staphylococcus associated glomerulonephritis.
文摘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.
文摘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 2<sup>nd</sup> month;serum creatinine returned to normal and by the 3<sup>rd</sup> 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 3<sup>rd</sup> month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3<sup>rd</sup> 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.
文摘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.
文摘We report a case of IgG4-related disease presenting both tubulointerstitial nephritis and retroperitoneal fibrosis causing acute renal failure in a 63-year-old male. He was admitted to our hospital because of acute renal failure requiring emergent hemodialysis. Computed tomography showed a soft-tissue density mass with an irregular border in the retroperitoneum. The mass involved bilateral ureters and had caused acute renal failure by bilateral hydronephrosis. Because of a history of uveitis and high IgG4 levels, we considered a diagnosis of retroperitoneal fibrosis, IgG4-related disease. Kidney biopsy revealed IgG4-related kidney disease with interstitial nephritis. After relief of urinary obstruction by inserting ureteral catheters into the bilateral ureters, renal function recovered.
文摘Objective:To explore the clinical and pathological features of Fabry disease complication of acute interstitial nephritis.Methods:A retrospective analysis of a patient with Fabry disease and acute interstitial nephritis diagnosed and in the Department of Nephrology,Children’s Hospital Affiliated to Capital Institute of Pediatrics in January 2017 was performed.A literature search was performed with“Fabry disease,acute interstitial nephritis”as the keywords in Wanfang database and PubMeds database.Result:The patient was 10-years-old with acute renal dysfunction.Electron microscopy showed stratified myelin-like bodies,zebra bodies and fused foot segment.The patient was finally diagnosed with the combination of Fabry disease and acute interstitial nephritis.By now,such cases have been reported.Conclusion:Whether Fabry's disease and acute interstitial nephritis shared the common pathogenic mechanism is unclear.Early renal biopsy is important for the diagnosis of this disease.
文摘920149 The relationship between renal tis-sue subsets of lymphocytes and clinicalfeatures in IgA nephropathy.LIU Zhihong （刘志红）,et al.Dept Nephrol,Jinling Hosp,Nanjing（210002）.Chin J Nephrol 1991; 7 （4）: 230.Amount of CD<sub>4</sub><sup>+</sup>,CD<sub>8</sub><sup>+</sup> and B cells in
文摘970370 The expression of AT1A receptor and itsmodulation by benazepril in the renal tubulointerstitiallesions induced by ureteral obstruction. CHEN Xi-angmei(陈香美), et al. Nephrol Div, General Hosp,PLA, Beijing, 100853. Natl Med J China 1997; 77(4):245-248.
文摘930568 The production and significance of IL4in patients with idiopathic nephroctic syndrome.YAO Zhi(姚智),et al.Dept Immunol,BeijingMed Univ,Beijing,100083,Natl Med J China1993;73(5):261—263.Samples of serum and PBMC were collected atthe same time from 42 pediatric patients with id-iopathic nephrotic syndrome(INS)and 28 age—matched healthy individuals.The level os IgE inserum was detected and IL4 in supernatant ofPHA-activated PBMC assayed by sandwichELISA.The levels of IL4 and IgE in healthy in-dividuals were 400～500 pg/ml and 50～100 U/ml respectively,and those of IL and IgE in theINS patients were on the average 1080～4000Pg/ml and 380～1000 U/ml.Positive correla-
文摘950358 Detection of glucocorticoid receptor (GCR)of lymphocyte in childnephrotic syndrome (NS).TANG Jieru(汤洁如),et al.Dept Pediatr,1st AffiliHosp,Sun Yat-sen Meal Univ,Guangzhou.Chin JNephrol 1994;10(6):342-343.Assesment of steroid receptor content in humanneoplastic cells or mammary tumor cells has been pre-viously used to prearct steriod sensitivity in variouscancers.In the present study,we evaluated the rela-tionship between GCR content and the prednisone sen-
文摘930331 Significance of determination of urinealbumin for early diagnosis of diabeticnephropathy.ZHOU Zhongyuan (周中源),Shanghai 4th People’s Hosp.Shanghai Med J1993;16(2):74—76.The results of urine albumin determination in208 patients with non-insulin dependent dia-betes mellitus but tested negative for urinaryprotein on routine examination and in 177 nor-mal controls were reported.The results showedthat the excretion of urine albumin in 131 pa-tients was obviously higher than that in normalcontrols (p【0.001).In the diabetic patientstested negative for urinary protein on routineexamination the excretion of urine albumin
文摘Tubulointerstitial nephritis complicated by primary Sj?gren’s syndrome in a patient under treatment for type 2 diabetes mellitus was diagnosed in the early stage of the disease by renal biopsy. The symptoms of primary Sj?gren’s syndrome, such as thirst and polydipsia, were masked by the characteristic symptoms of type 2 diabetes mellitus. An association between sicca symptoms and diabetes mellitus (types 1 and 2) has been previously reported. Hence, it is possible that there are common underlying immunological mechanisms between primary Sj?gren’s syndrome and diabetes mellitus of both types. Intervention with steroids in a timely manner appears to have prevented or slowed the progression of re- nal impairment.
文摘930154 Plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha in diabetic nephropathyWANG Yao（王尧）,et al,Dept Endocrinol,1stAffil Hosp,Nanjihng Railway Med Coll.210009.Chin J Nephrol 1992;8（5）:275-277.The plasma levels of TXB<sub>2</sub> and 6-keto-PGF<sub>1</sub>were measured by RIA in 14 diabetics with and49 diabetics without nephropathy and 35 normalsubjects.The results showed that the levels ofplasma TXB<sub>2</sub> and the ratio of TXB<sub>2</sub>/6-keto-PGF<sub>.</sub>were increased both in diabetics with
文摘BACKGROUND Proliferative lupus nephritis(PLN)is the most severe form of lupus nephritis(LN).There are limited data available on renal outcomes of PLN from developing countries.AIM To determine the clinicopathological characteristics and long-term outcomes in terms of remission,requirement of kidney replacement therapy(KRT),and patient survival.METHODS A retrospective analysis was conducted on biopsy-proven focal or diffuse PLN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation and followed up at the renal clinic for a minimum of 5 years.All patients were induced with a combination of intravenous cyclophosphamide and corticosteroids for 6 months,followed by maintenance treatment with azathioprine(AZA)or mycophenolate mofetil(MMF).Data were analyzed using Statistical Package for the Social Sciences,version 22.0.P≤0.05 was considered statistically significant.RESULTS The mean age at the onset of systemic lupus erythematosus was 24.12 years±8.89 years,and at LN onset,26.63 years±8.61 years.There was a female predominance of 184(88.9%)cases.Among baseline characteristics,reduced estimated glomerular filtration rate,presence of hypertension,requirement of KRT,and underlying renal histology(International Society of Nephrology/Renal Pathology Society class IV than class III)were significantly associated with end-stage kidney disease(ESKD)and mortality.The renal outcomes were negatively correlated with age,duration of symptoms,and 24-hour urinary protein excretion.The overall remission rate was 89.8%at the end of induction therapy.At 5 years,141(68.11%)patients were in complete and partial remission(94[45.4%]and 47[22.7%],respectively).In total,19(9.2%)patients required KRT on presentation,and at 5 years,38(18.4%)patients developed ESKD,and 28(13.5%)patients died.Thirty-four(16.4%)patients had a renal relapse,more with AZA than MMF(30[88.2%]vs 4[11.76%],respectively;P=0.04).Renal survival at 6 months was 89.8%,while at 5 years,it was 68.11%,showing a significant improvement in patients who did not need KRT at the time of presentation(P<0.0001).CONCLUSION Baseline renal functions,requirement of KRT,and diffuse proliferative disease were the most relevant prognostic factors for kidney survival among this cohort.Short-term renal outcomes were good.Long-term outcomes were poorer with AZA-based maintenance therapy than with MMF,with more ESKD and mortality.
文摘Objective To review and synthesize preclinical and clinical evidence regarding traditional Chinese medicine(TCM)formulations and bioactive herbal compounds in lupus nephritis(LN),and to identify direction and research priorities for integrating TCM with professional care.Methods A narrative literature review was conducted by searching Scopus,PubMed,Web of Science,and Google Scholar for articles published between January 1,2011 and March 31,2024.Search terms combined controlled vocabulary[e.g.,medical subject headings(MeSH)]and free-text words including lupus nephritis,traditional Chinese medicine,Chinese herbal medicine,formulation,and names of specific herbs[Leigongteng(Tripterygii Wilfordii Radix et Rhizoma),Baishao(Paeoniae Radix Alba),and Yinghao(Artemisiae Annuae Herba)].Both randomized controlled trials and observational studies were included,along with mechanistic preclinical studies and pharmacologic investigations.Inclusion criteria were studies that reported renal outcomes(proteinuria and estimated glomerular filtration rate),immunemodulatory mechanisms,or safety and herb-drug interaction data.Studies without primary data,case reports,or those lacking relevance to LN were excluded.References of key articles were manually screened to identify additional eligible studies.Results TCM formulas[e.g.,Liuwei Dihuang Pills(六味地黄丸),Zhibai Dihuang Pills(知柏地黄丸),and Huanglian Jiedu Decoction(黄连解毒汤)]and herbal medicines[e.g.,extracts from Leigongteng(Tripterygii Wilfordii Radix et Rhizoma),Baishao(Paeoniae Radix Alba),and Yinghao(Artemisiae Annuae Herba)]were commonly used in the above studies.TCM formulations and their constituent compounds showed multi-modal mechanisms relevant to LN pathogenesis,encompassing immunomodulation(reduction of autoreactive B/T cell activity,regulatory T cell enhancement),inhibition of pro-inflammatory signaling pathways nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB),mitogen-activated protein kinase(MAPK),nucleotide-binding oligomerization domain(NOD),leucine-rich repeat(LRR)and pyrin domain-containing protein 3(NLRP3 inflammasome),anti-fibrotic and antioxidant effects,and direct renal-protective properties.In many studies,these indicators can reduce proteinuria and improve renal function.Clinical data,while promising,are heterogeneous in design,sample size,endpoints,and TCM formulation standardization.Safety concerns(notably with Tripterygium preparations)and potential herb-drug interactions with immunosuppressants remained important considerations.Conclusion TCM offers biologically plausible and multi-targeted adjuvant strategies for LN that may enhance therapeutic efficacy and reduce toxicity when combined with modern therapies.To translate these promises into clinical practice,future work should prioritize the standardization of TCM preparations,randomized controlled trials with clinically meaningful renal endpoints,elucidation of molecular mechanisms,and systematic evaluation of pharmacokinetic and safety interactions.Such integrative research will be essential to define the TCM’s role in evidence-based,patient-centered LN management.
基金Prof.Betty Diamond for sharing the duplicate extraction in the single-cell transcriptome profilingthe Project of Zhejiang Provincial Administration of Traditional Chinese Medicine,China(Grant Nos.:2020zz009 ,2021zx005)+1 种基金Advantage Discipline Construction Project from Zhejiang Provincial Hospital of Chinese Medicine,China(Grant No.:2D02311)the Health and Family Planning Commission of Zhejiang Province,China(Grant No.:2025KY971).
文摘Immune complex deposition is a critical factor in early renal damage associated with lupus nephritis(LN),and targeting plasma cell aggregation offers a promising therapeutic strategy.Ginsenoside com-pound K(i.e.,20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol)(CK),a derivative of ginsenoside,has indicated significant potential in alleviating renal damage in lupus-prone mice,potentially by modu-lating B cell dynamics in response to endoplasmic reticulum(ER)stress.In this study,CK(20 or 40 mg/kg)was orally administered to female MRL/lpr mice for 10 weeks.The effects of CK on B cell sub-populations,renal function,and histopathological changes were evaluated.Single-cell ribonucleic acid sequencing was employed to analyze gene expression profile and pseudotime trajectories during B cell-mediated renal injury.Additionally,in vitro B cell assays were conducted to explore the role of the sirtuin-1(SIRT1)-X-box binding protein 1(XBP1)axis in ER stress.Our findings demonstrated that CK effectively reduced anti-double stranded DNA(dsDNA)antibody levels,alleviated systemic inflamma-tion,improved renal function,and facilitated the clearance of deposited immune complexes.CK likely suppressed the unfolded protein response(UPR),delaying the differentiation of renal-activated B cells into plasma cells.It promoted B cell-specific SIRT1 activation and inhibited the splicing of XBP1 into its active form,XBP1s.CK also restored ER morphology by interacting with calmodulin(CALM)to maintain ER calcium storage,reinforcing SIRT1 functional integrity and promoting XBP1 deacetylation,thereby limiting plasma cell differentiation.In conclusion,CK mitigates plasma cell accumulation in the renal microenvironment by preventing SIRT1-mediated XBP1 splicing,offering a potential therapeutic approach for LN.
文摘Pediatric lupus nephritis(LN)is a challenging and severe condition in pediatrics.Traditional Chinese medicine(TCM)has shown significant advantages in improving immune disorders,reducing recurrence rates,and mitigating the toxic side effects of Western medications.However,it faces challenges such as the lack of a unified TCM syndrome differentiation system,insufficient standardization of dynamic syndrome differentiation,an incomplete efficacy evaluation system,and a lack of precise intervention methods.This study focuses on the clinical advantages of TCM.On 1 September 2024,the 35th Clinical Advantage Disease Series Salon was held in Zhengzhou,discussing the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.Experts in TCM and integrated Chinese-Western medicine,along with interdisciplinary researchers,conducted extensive and in-depth discussions.They proposed specific recommendations for TCM and integrated Chinese-Western medicine in treating pediatric LN and reached a consensus.Based on this,the study analyzes the challenges in treating pediatric LN from the perspective of its development patterns,and summarizes three key areas and six research directions to highlight the advantages of TCM and integrated Chinese-Western medicine in treating pediatric LN.It focuses on three key areas:The construction of a TCM system for pediatric LN,the prevention and treatment of complications,and chronic disease management.And it proposes six research directions:(1)Constructing a syndrome differentiation system for pediatric LN;(2)Formulating TCM and integrated Chinese-Western medicine guidelines for pediatric LN;(3)Researching the mechanisms of enhancing efficacy and reducing toxicity in integrated Chinese-Western medicine for pediatric LN;(4)Preventing and treating complications in pediatric LN;(5)Developing and researching TCM regimens for preventing and treating the recurrence of pediatric LN;(6)Strategies for the full-cycle chronic disease management of pediatric LN.Finally,the study summarizes and generalizes the technological layout and research directions for pediatric LN.Therefore,based on the series of salons on traditional Chinese medicine advantages for children LN diseases,this paper puts forward a research paradigm of scientific and technological breakthroughs for children LN,in order to provide reference for the construction and research direction of children LN diagnosis and treatment system with traditional Chinese medicine characteristics.
文摘Objective To investigate the pattern of monocyte chemoattractant prolein-1 (MCP-1) distribution in the renal interstitium and evaluate its pathogenic role in tubulo-interstitial lesions in patients with lupus nephritis, the distribution of MCP-1 in renal tissue was observed.Methods Eighteen female patients with biopsy-proven lupus nephritis were enrolled in this study. No intensive immunosuppresive therapy was used in these patients during the 3 months prior to renal biopsy. The distribution of MCP-1, infiltration of CD68+ (macrophage/monocyte), CD4+ and CD8+ cells in the tubulo-interstitium of patients with lupus nephritis was detected using immunohistochemical staining with specific antibodies. Renal specimens from patients with minimal change glomerulonephritis were used as controls. Results MCP-1 protein was widely distributed in the renal tissue of patients with lupus nephritis, mainly located at the baso-lateral surface of tubular epithelial cells (16/18 biopsies), and on the wall of interstitial blood vessels (9/18 biopsies). In contrast, tubular MCP-1 staining was weak and rare in renal tissue from controls (7.4±6.2% vs 26.7±22.8%, P<0.01). Tubulo-interstitial infiltration of CD68+, CD4+ and CD8+ cells was markedly increased in patients with lupus nephritis as compared to controls. The tubular expression of MCP-1 was strongly associated with the amount of CD68+ cell infiltration in the interstitium (r=0.5420, P<0.05) and the extent of interstitial fibrosis. There was no correlation between MCP-1 production in tubules and the degree of urinary protein excretion in patients with lupus nephritis (r=0.0547, P>0.05).Conclusions The expression of MCP-1 in the renal tubules and vascular wall was markedly increased in patients with lupus nephritis. The overproduction of MCP-1 in renal tissue may contribute to monocyte recruitment in the interstitium and thus result in tubulo-interstitial damage in lupus nephritis.
