Concurrent focal segmental glomerulosclerosis and membranous nephropathy

Focal segmental glomerulosclerosis and membranous glomerulonephropathy are two entities that may result in the nephrotic syndrome. Two young women exhibited concurrent focal segmental glomerulosclerosis and focal segmental membranous nephropathy on renal biopsy. Although the lesions were severe, both patients had asymptomatic proteinuria, normal renal function, and a benign clinical course. The concurrence of these glomerulopathies may portend a more benign clinical course than expected for a patient presenting with either lesion alone.     

膜性乙型肝炎病毒相关性肾炎与特发性膜性肾病临床对比分析

目的：探讨膜性乙型肝炎病毒相关肾炎（HBV-MN）的临床、病理特点及中医证候特征。方法：采用回顾性分析方法,比较27例HBV-MN和31例特发性膜性肾病（IMN）临床表现、肾脏病理及中医证候等方面的异同。结果：（1）临床表现：HBV-MN组发病年龄明显低于IMN组（P〈0.05）;两组临床表现构成比经Fisher精确卡方检验具有统计学差异（P〈0.05）。（2）肾脏病理：两组均以Ⅰ期、Ⅱ期膜性肾病常见,肾脏病理分期无统计学差异（P〉0.05）;光镜检查,两组肾小球、肾小管间质及肾血管等各项病理积分无统计学差异（P〉0.05）;免疫荧光检查,HBV-MN组表现为多种免疫复合物、多部位、高强度沉积,而IMN组主要以IgG、C3在上皮下和基底膜高强度沉积。（3）中医证候：本虚证中,两组均以脾肾气虚所占比例最高,而且两组本虚证候分布及各项本虚证候积分均无统计学差异（P〉0.05）;标实证中,HBV-MN组湿热证所占比例明显高于IMN组（P〈0.05）,而IMN组中血瘀证和水气证所占比例明显高于HBV-MN组（P〈0.05）。HBV-MN组湿热证候积分明显大于IMN组（P〈0.05）,而IMN组血瘀证候积分明显大于HBV-MN组（P〈0.01）。结论：HBV-MN多发于男性中、青年,主要临床表现为肾病综合征、慢性肾炎综合征合并肾病综合征;病理特征为多种免疫复合物、多部位、高强度沉积,以Ⅰ期、Ⅱ期膜性肾病常见;中医证候以脾肾气虚挟湿热为主。     

呈局灶节段性肾小球硬化的IgA肾病临床病理特点

目的探讨呈局灶节段性肾小球硬化（FSGS）的IgA肾病（IgAN）的临床和病理特点。方法选取我院1988年1月至2002年2月经肾活检确诊为IgAN的患者587例,其中呈FSGS85例,呈弥漫性系膜增生性肾小球肾炎（MsPGN）162例,呈弥漫性系膜增生性肾小球肾炎伴局灶节段性肾小球硬化（MsPGN伴FSGS）185例,比较3种类型IgAN临床和病理资料。结果FSGS型IgAN占同期所有IgAN的14．5％,临床类型以大量蛋白尿型为主,占37．64％。肾小球球囊黏连发生率高达74．12％,小管间质纤维化发生率97．65％,病理分级以LeeⅣ～Ⅴ级为主,免疫病理以IgA—MG型为主,与MsPGN伴FSGS型和MsPGN型的IgAN相比,FSGS型IgAN病程较长,高血压、肾功能不全发生率较高（P〈0．05）,而血尿的发生率与后两者无明显区别。结论呈FSGS型IgAN大量蛋白尿、高血压、肾功能不全的发生率高,病变较重,预后较差。     

Hepatitis B complicated focal segmental glomerulosclerosis

After the initial report of membranous glomerulopathy due to hepatitis B virus infection by Combes et al, other glomerular diseases - but rarely focal segmental glomerulosclerosis (FSGS) association with HBV infection - have been reported. Herein we present an 8-year-old boy with chronic HBV infection complicated FSGS. The patient was initially regarded as idiopathic FSGS and started on an immunosuppressive schedule. The elevation of liver transaminases in the course of the therapy revealed the immunotolerated perinatal HBV infection. It was considered that immunosuppressive agents have induced viral replication. The treatment was changed to lamivudine alone. The nephrotic syndrome has already been improved with the seroconversion of anti-HBeAg and reduced liver functional tests by the tenth month of the treatment. This case is peculiar for the seldom association of FSGS with chronic HBV infection and treatment modality particularly for the countries where this viral infection is endemic.     

Pregnancy-induced nephropathy: the significance of focal segmental glomerulosclerosis

The morphologic alterations of true preeclampsia are well described and distinct. Using available criteria to define reversible pregnancy-induced nephropathy (PIN), the pathologist can offer the clinician information useful in predicting remote renal function and hypertension. True PIN is a usually completely reversible lesion in the nullipara and carries little risk of future hypertension. Nephrosclerotic vascular lesions, however, whether arteriolar, interlobular, or glomerular and resembling focal segmental glomerulosclerosis (FSGS), signify underlying hypertensive disease. This review summarizes information concerning the nature of PIN and also surveys 20 biopsies in women who mainly had severe preeclampsia, often with persistent postpartum hypertension. This material was step-sectioned and specifically reviewed in an effort to find FSGS in women with PIN.     

Adriamycin nephropathy: a model of focal segmental glomerulosclerosis

Adriamycin nephropathy (AN) is a rodent model of chronic kidney disease that has been studied extensively and has enabled a greater understanding of the processes underlying the progression of chronic proteinuric renal disease. AN is characterized by podocyte injury followed by glomerulosclerosis, tubulointerstitial inflammation and fibrosis. Genetic studies have demonstrated a number of loci that alter both risk and severity of renal injury induced by Adriamycin. Adriamycin-induced renal injury has been shown in numerous studies to be modulated by both non-immune and immune factors, and has facilitated further study of mechanisms of tubulointerstitial injury. This review will outline the pharmacological behaviour of Adriamycin, and describe in detail the model of AN, including its key structural characteristics, genetic susceptibility and pathogenesis.     

Focal segmental glomerulosclerosis associated with type C virus hepatitis and decrement of proteinuria by interferon-alpha therapy]

Focal segmental glomerulosclerosis (FSGS) associated with type C virus (HCV) hepatitis has not been described in the literature to date. However, we experienced a 30-year-old man, who had had HCV hepatitis, developed nephrotic syndrome and was admitted to our hospital. The first renal biopsy showed FSGS which was diagnosed by light, immunofluorescent, and electron microscopic study. FSGS diagnosis was based upon the findings of focal segmental glomerular sclerosis associated with hyalinosis and foam cells, segmental deposition of IgM and C3 on glomeruli, and epithelial cell vacuolization in the Bowman's space. HCV hepatitis was treated with interferon-alpha (INF-alpha) over 6 months. The treatment brought the disappearance of not only HCV-RNA from the blood, but also the manifestation of nephrotic syndrome. Therefore, the second renal biopsy was performed, but did not reveal any great pathological improvement. Five months later after the remission, he again had an elevated HCV-RNA level and a relapse of nephrotic syndrome. He was retreated with the same therapy and achieved a second remission of nephrotic syndrome. FSGS associated with HCV hepatitis is described first and the implication of INF-therapy in the improvement of proteinuria is discussed.     

IgA nephropathy associated with hepatitis B virus antigenemia

The pathogenetic ability of hepatitis B virus (HBV) antigenemia to induce IgA nephropathy was examined in 10 patients with IgA nephropathy and HBV antigenemia. They had no previous history of liver diseases and their liver function tests were normal. All were positive for hepatitis + surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBcAg) with high titers, thereby indicating they were persistent carriers of HBV. Immunoperoxidase studies using monospecific polyclonal antibodies revealed HBcAg and HBsAg in the nuclei and cytoplasm of glomerular mesangial cells in 8 patients. These findings suggest immune complexes involving HBcAg and HBsAg may induce IgA nephropathy in persons who carry HBV.     

Intravenous pulse cyclophosphamide therapy in focal segmental glomerulosclerosis

AIMS: We herein report the results of intravenous pulse cyclophosphamide (IVCP) therapy of 5 patients with steroid-resistant focal segmental glomerulosclerosis (FSGS). All patients had been treated with oral and intravenous pulse methylprednisolone and failed to respond to steroids from onset and were considered as primary steroid-resistant. Before starting IVCP, all patients were also treated with other immunosuppressive drugs with or without steroids, but none of them responded to such therapies and no patient had any NPSH2 gene mutations. METHODS: IVCP was given monthly at a dose of 500 mg/m2 for 6 months. At the end of 6 months, IVCP was discontinued in case there was no response. Otherwise, IVCP was continued for every 2 months. Oral prednisone was given concurrently at 60 mg/m2 daily for 6 weeks and then 40 mg/m2 on alternate days for 4 weeks. Prednisone was then tapered to 10 mg/m2 alternate days and continued during the therapy period. RESULTS: Only 1 of these patients achieved remission after IVCP while 4 patients showed no response to IVCP. 2 patients who did not achieve remission progressed to end-stage renal disease (ESRD) and 2 others who had not been treated with cyclosporine before underwent cyclosporine therapy. None of our patients has suffered from adverse effects of IVCP. CONCLUSION: We found that IVCP had a limited beneficial effect in treatment of steroid-resistant FSGS and it may be suggested that IVCP can be tried to treat steroid-resistant patients, also for patients with primary steroid resistance and those who do not respond to other immunosuppressive therapies.     

Clinical and pathological features of idiopathic membranous nephropathy with focal segmental lesion

Objective To investigate the clinical-pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental lesion. Methods Two hundred and ninety-eight patients with biopsy-proven IMN in our hospital were retrospectively analyzed. The patients were divided into three groups: without focal segmental lesion group (FSL-), with focal segmental glomerulosclerosis group (FSGS) and with early focal segmental lesion group (EFSL). The differences of clinical and pathological features and prognosis in the 3 groups were studied. Results There were later pathological stage, higher ratio of chronic renal tubulointerstitial damage and global glomerular sclerosis in FSGS group than those in the other two groups (all P＜0.05). The male ratio in EFSL group was higher than that inFSL- group (P＜0.01), while the level of serum albumin was lower (P＜0.05). Compared withFSL- group, there was longer average course before renal biopsy, higher blood pressure and levels of Scr in FSGS group (all P＜0.05)．Furthermore, the remission rate in EFSL group was lower than that in FSGS group andFSL- group. Survival analysis showed that FSGS group had worse prognosis (FSGS toFSL-, P=0.005, FSGS to EFSL, P=0.008). The analysis of risk factors suggested that triacylglycerol (OR=1.519, P=0.017), glomerulosclerosis (OR=1.073, P=0.041) and FSGS lesion (OR=5.960, P=0.009) were independent risk factors for renal death. Conclusions There were some differences between EFSL and FSGS lesion, both in clinical manifestations and pathology. FSGS lesion was independent predictive factor for progression to renal death. And the lowest remission rate was in EFSL group.     

Nephrotic syndrome associated with focal segmental glomerulosclerosis in a patient with systemic lupus erythematosus and membranous glomerulonephritis in remission

Renal involvement is frequent in systemic lupus erythematosus (SLE). This lesion, termed lupus nephritis, has been reported clinically in at least 50% of the patients. It is generally assumed that in patients with SLE, renal abnormalities detected clinically are caused by lupus nephritis, especially lupus glomerulonephritis (GN). Thus, renal biopsy is performed not for diagnostic purposes, but rather for determining the type and extent of renal involvement. However, clinically significant renal abnormalities unrelated to lupus nephritis have rarely been described in patients with SLE. The reported case serves to emphasize this consideration. The patient was a 41-year-old woman who presented 11 years previously with severe hypertension, nephrotic syndrome, and a serum creatinine level of 2.9 mg/dL. Renal biopsy showed membranous GN and ischemic damage. After a prolonged remission induced by steroids and cyclophosphamide, the patient presented with nephrotic syndrome and a serum creatinine level of 2.1 mg/dL. Although she was normotensive at that time, there were features of SLE. Repeated renal biopsy showed focal segmental glomerulosclerosis without the changes of membranous GN or any type lupus GN. This case illustrates two interesting observations, ie, resolution of membranous GN and nonlupus renal lesions in patients with SLE.     

C1q nephropathy: a variant of focal segmental glomerulosclerosis

BACKGROUND: C1q nephropathy is a poorly understood and controversial entity with distinctive immunopathologic features. In order to better define the clinical-pathologic spectrum, we report the largest single-center series. METHODS: Nineteen biopsies with C1q nephropathy were identified from among 8909 native kidney biopsies received from 1994 to 2002 (0.21%). Defining criteria included (1). dominant or co-dominant immunofluorescence staining for C1q, (2). mesangial electron dense deposits, and (3). no clinical or serologic evidence of systemic lupus erythematosus (SLE). RESULTS: The 19 patients were predominantly African American (73.7%), female (73.7%), young adults and children (range, 3 to 42 years; mean, 24.2 years). Presentation included nephrotic range proteinuria (78.9%), nephrotic syndrome (50%), renal insufficiency (27.8%), and hematuria (22.2%). No patient had hypocomplementemia or evidence of underlying autoimmune or infectious disease. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 17 (including six collapsing and two cellular) and minimal-change disease (MCD) in two. All biopsies displayed co-deposits of immunoglobulin G (IgG), with more variable IgM (84.2%), IgA (31.6%), and C3 (52.6%). Foot process effacement varied from 20% to 100% (mean, 51%). Twelve of 16 patients with available follow-up received immunosuppressive therapy. One patient had complete remission of proteinuria and six had partial remission. Four patients with FSGS pattern had progressive renal insufficiency, including two who reached end-stage renal disease (ESRD). Median time from biopsy to ESRD was 81 months. On multivariate analysis, the best correlate of renal insufficiency at biopsy and at follow-up was the degree of tubular atrophy and interstitial fibrosis (P = 0.0495 and 0.0341, respectively). CONCLUSION: C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a non-specific marker of increased mesangial trafficking in the setting of glomerular proteinuria.     

Duration of optimal therapy for idiopathic focal segmental glomerulosclerosis

We conducted a retrospective study to evaluate the duration of optimal steroid therapy in idiopathic focal segmental glomerulosclerosis (FSGS). We evaluated 93 adult patients (n=65 males) with biopsy proven FSGS. Mean proteinuria was 5.4 +/- 2.8 gm/dL. Twelve patients were lost at follow-up. Of the remaining 81 patients, nephrotic range proteinuria was present in 48 (59%), and 21 (26%) presented with renal insufficiency. Of these patients, three (3.9%) experienced spontaneous remission. Seven patients were managed symptomatically with ACE inhibitors and never received steroids. Of the 71 patients, 32 received >16 weeks of steroid therapy, while 39 received <16 weeks of steroid therapy. Twenty-four patients (75%) who received >16 weeks of steroid therapy had a complete or partial remission, while only 18 (46%) of those with <16 weeks of steroid therapy had a steroid response (p=0.001). Patients with more than 25% interstitial fibrosis at biopsy also showed significantly lower remission rates (p=0.02). Hypertension, hematuria and degree of proteinuria did not significantly affect the response to steroid therapy. Univariate logistic regression analysis showed that the factors predictive of remission were: (1) steroid therapy duration (p=0.001); (2) serum creatinine (Cr) at onset (p=0.001) and; (3) presence of interstitial fibrosis (>25%) at initial biopsy (p=0.02). Multivariate logistic regression analysis showed that the only factor predictive of remission was steroid therapy duration >16 weeks (p=0.001). Therefore, we concluded that patients with idiopathic FSGS required treatment for at least 16 weeks, before labeling them as steroid non-responsive. Patients with interstitial fibrosis have a significantly poor response to therapy.     

APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy

Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.     

Pathophysiology of focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). In recent years, animal models and studies of familial forms of nephrotic syndrome helped elucidate some mechanisms of podocyte injury and disease progression in FSGS. This article reviews some of the experimental and clinical data on the pathophysiology of FSGS. KR is a Pediatric Nephrology Trainee supported by grant no. NIH T32 DK007110 30. FJK is supported in part by NIH DK63549-04.