Association between membranous glomerulonephritis and Crohn's disease

We report the case of a 37 year old man who suffered from Crohn's Disease (CD), and was receiving treatment with mesalazine (5-ASA). Nine years after the diagnosis, because of detecting a slight proteinuria, a renal biopsy is made, being the anatomo-pathologic result compatible with membranous glomerulonephritis (MGN). Checking previous literature we have only found two cases reported of MGN in coincidence with Inflammatory Bowel Disease (IBD), one in association with Ulcerative Colitis and the other with Crohn's Disease in a 12 years old boy. This is, therefore, the second case presenting MGN associated with CD and the first in an adult patient.     

Extramembranous glomerulonephritis and myelodysplastic syndrome

Membranous glomerulonephritis (MGN) is the main cause of nephrotic syndrome in adults and is usually idiopathic. We report a case of nephrotic MGN associated with a myelodysplastic syndrome (MDS) in a 43 year old man. The initial treatment consisted of oral corticosteroids (1 mg/kg/day). Within 3 months proteinuria decreased from 22.4 g/day to 3.96 g/day and the blood cell count was normalized. Renal biopsy disclosed type I MGN. Ponticelli's protocol was started with a favorable effect: negative proteinuria, normal blood cell count and normal bone marrow cellularity. The association between MGN and MDS is quite rate. The possible links between the two conditions are reviewed.     

Membranous Glomerulonephritis with ANCA-Associated Necrotizing and Crescentic Glomerulonephritis

Background and objectives: Only rare cases of concurrent membranous glomerulonephritis (MGN) and antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis (NCGN) have been reported.Design, setting, participants, & measurements: The authors report the clinical and pathologic findings in 14 patients with MGN and ANCA-associated NCGN.Results: The cohort consisted of eight men and six women with a mean age of 58.7 yr. ANCA positivity was documented by indirect immunofluorescence or ELISA in all patients. Indirect immunofluorescence was positive in 13 patients (seven P-ANCA, five C-ANCA, one atypical ANCA). ELISA was positive in nine of 10 patients (five MPO-ANCA, three PR3-ANCA, one MPO- and PR3-ANCA). Clinical presentation included heavy proteinuria (mean 24-hr urine protein 6.5 g/d), hematuria, and acute renal failure (mean creatinine 4.4 mg/dl). Pathologic evaluation revealed MGN and NCGN, with crescents involving a mean of 32% of glomeruli. On ultrastructural evaluation, the majority of cases showed stage I or II membranous changes. Follow-up was available for 13 patients, 12 of whom were treated with steroids and cyclophosphamide. At a mean follow-up of 24.3 mo, five patients progressed to ESRD, seven had stabilization or improvement in renal function, and one had worsening renal function. Five patients, including three with ESRD, died during the follow-up period. The only independent predictor of progression to ESRD was serum creatinine at biopsy.Conclusions: MGN with ANCA-associated NCGN is a rare dual glomerulopathy seen in patients with heavy proteinuria, acute renal failure, and active urine sediment. Prognosis is variable, with 50% of patients reaching endpoints of ESRD or death.Membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome in white adults, accounting for more than one third of cases (1). At the time of presentation, the majority of patients with MGN have preserved renal function (2). Microscopic evaluation of the urine sediment reveals microscopic hematuria in approximately 50% of cases; however, red blood cell casts are not a feature of this disease. Pathologically, MGN is characterized by the formation of subepithelial immune complex deposits with resultant changes to the glomerular basement membrane (GBM), most notably GBM spike formation. Approximately 75% of cases of MGN are thought to represent primary disease, whereas the remaining 25% of cases represent secondary forms of MGN, most commonly related to systemic lupus erythematosus (SLE), infection (i.e., hepatitis B or C virus), malignancy, or drugs. The natural history of MGN is variable, with approximately one third of patients progressing to ESRD within 10 yr (2).Pauci-immune necrotizing and crescentic glomerulonephritis (PNCGN) is characterized by glomerular necrosis and crescent formation in the absence of significant intracapillary proliferation and in the presence of no more than a “paucity” of glomerular immune complex deposits. The majority of patients with PNCGN, with or without associated systemic vasculitis, have circulating antineutrophil cytoplasmic antibodies (ANCAs), which have been directly implicated in the pathogenesis of this form of glomerular injury. In contrast to patients with MGN, those with PNCGN typically present with rapidly progressive glomerulonephritis (RPGN) and an active urine sediment with red blood cell casts (3,4). PNCGN is an aggressive disease with a 1-yr mortality rate of up to 80% in the absence of immunosuppressive therapy. The prognosis of PNCGN is dramatically improved by immunosuppressive regimens that include corticosteroids and cyclophosphamide (CY).The occurrence of ANCA-associated NCGN and primary MGN in the same patient is rare, with only a handful of reports in the literature (5–10). Herein, we detail the clinical, pathologic, and outcome data of 14 patients with this rare dual glomerulopathy and review the previously reported cases.     

Clinicopathological study of nephropathy in patients with rheumatoid arthritis]

We carried out a retrospective study to investigate the clinical and pathological findings in 31 patients with rheumatoid arthritis (RA). In clinical findings, 17 patients showed nephrotic syndrome, five had isolated proteinuria, two had proteinuria and hematuria and seven had renal failure. In pathological findings, there were 16 patients with membranous nephropathy (MN), two with proliferative glomerulonephritis (DPGN), two with minor glomerular abnormality (MGA), six with amyloidosis, 2 with tubulointerstitial nephritis, and three patients had accompanying lupus nephritis. Eleven of 16 with MGN had been treated with gold, bucillamine or D-penicillamine, so they were diagnosed as drug induced MGN. In the other five patients, we could not decide which drugs induced the nephropathy. The 2 cases of MGA were associated with nephrotic syndrome and acute renal failure, which were caused by non-steroidal antiinflammatory drugs. There were two cases of non-Ig A DPGN, which was regarded as the native nephropathy in RA. The three cases with lupus nephritis were diagnosed as systemic lupus erythematosus by the criteria of the American Rheumatism Association (ARA). In conclusion, the nephropathy in patients with RA was varied and renal biopsy was a useful examination.     

Membran?se Glomerulonephritis

Membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome and is most often idiopathic but can be caused by cancer, drugs, infections and autoimmune disorders. MGN is a podocytopathy induced by circulating autoantibodies against podocytes. Recently, the M-type phospholipase A₂ receptor has been identified as the major antigen in human idiopathic MGN. Spontaneous remission of MGN occurs in up to 30% of patients; however, patients without spontaneous remission and with high proteinuria have a worse renal prognosis. There are ongoing controversies about the timing of immunosuppression and the best therapeutic regimen. Besides supportive therapy high risk patients should be treated with cyclophosphamide or cyclosporin A in combination with glucocorticoids.     

'Idiopathic' hematuria. A prospective evaluation

Evaluation of the patient with isolated hematuria is often problematic. Sixty-five patients with this entity were studied prospectively with renal biopsy; serum IgA levels, skin biopsy for IgA immunofluorescence, and HLA typing were also studied in most patients. Previously, all patients had had a non-contributory history and physical examination, normal results of structural evaluation, serologic and clotting studies, and proteinuria of less than 1000 mg/d (less than 1 g/d). Seventy-eight percent were found to have abnormal renal biopsy results and were divisible into two patient groups: those with IgA nephropathy (49%, 32/65) and those with multiple nonspecific abnormalities (29%, 19/65). Ancillary testing, demographic data, and clinical data, other than abnormal amounts of proteinuria, were not distinguishable between these groups and patients with normal renal biopsy results (22%, 14/65). Etiologic differentiation of the hematuria was possible only by renal biopsy. At present, renal biopsy in this group of patients makes no difference therapeutically or, probably, prognostically. It should not, therefore, be considered necessary for routine management of asymptomatic hematuria.     

Successful Treatment of Membranous Glomerulonephritis with Rituximab in Calcineurin Inhibitor-Dependent Patients

Background and objectives: Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs.Design, setting, participants, and measurements: Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m²). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal.Results: After rituximab, proteinuria decreased significantly (2.5 ± 0,76 basal versus 0.85 ± 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 ± 15 basal to 106.4 ± 20 at 3 mo with a mean increase of 15.3% [range 0–20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission.Conclusions: In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.Membranous glomerulonephropathy (MGN) is the most frequent cause of nephrotic syndrome in adults. There is general agreement that patients with persistent nephrotic syndrome are at risk of developing progressive renal insufficiency (1–4). In these patients, prospective randomized clinical trials have demonstrated that the calcineurin inhibitors (CNIs) cyclosporine (5,6) and tacrolimus (7) induce complete or partial remission of proteinuria in more than 70% of patients. However, more than 60% of patients treated with CNI suffer subsequent relapses or become treatment dependent (5–8) and need prolonged therapy to maintain remission, which exposes them to the nephrotoxic effects of this drugs. Consequently, for these patients, there is a need for the development of new treatment strategies aimed at reducing the risk of chronic nephrotoxicity. MGN is an antibody-mediated disease induced by deposits of immunoglobulins and complement components on the subepithelial layer of the glomerular capillary wall (9). This immune deposition promotes injury to the glomerular filtering barrier, proteinuria, and eventual renal failure (10). Infiltration of CD-20+ cells has also been demonstrated in renal biopsies of patients with MGN (11). Results in experimental MGN have shown that the inhibition of B cell function is associated with beneficial effects on proteinuria, (12) and human studies clearly demonstrated that the inhibition of B cells with alkylating agents induces remission of the nephrotic syndrome (13). The availability of monoclonal antibodies targeted to the cell surface antigen CD-20 of B cells permits an analysis of the effect of more selective and specific B cell inhibition in the outcome of several antibody-mediated diseases in clinical studies (14). In recent years, observational studies have shown that the administration of the anti-CD20 monoclonal antibody rituximab can reduce urinary protein excretion and preserve renal function in patients with MGN and persistent nephrotic syndrome (15–19).This pilot observational study was conducted in patients with MGN with normal renal function, who experienced long-term dependence on CNI despite previous treatment with high-dose immunoglobulins and mycophenolate mofetil. The study aim was to evaluate whether a single course of rituximab could allow either dose reduction or withdrawal of CNI.     

Proteinuria: potential causes and approach to evaluation

Proteinuria may be associated with a renal or systemic disease, or it may be isolated. The latter occurs in asymptomatic patients without evidence of any disease or abnormality of the urine sediment. Isolated proteinuria may be subdivided into two broad groups: (1) benign forms, with a favorable-to-excellent prognosis and (2) persistent forms, some of which have a worrisome prognosis. Functional proteinuria may occur in disorders with altered renal hemodynamics, usually resolves, and is not associated with progressive renal disease. Idiopathic transient proteinuria is typically discovered on routine screening and usually disappears on subsequent testing. In idiopathic intermittent proteinuria, a significant number (50%) of urine samples exhibit abnormal rates of protein excretion. Although structural abnormalities may be observed on renal biopsy, progressive renal insufficiency is unusual. In orthostatic proteinuria, the rate of protein excretion completely normalizes in the recumbent position. Long-term studies show this to be a benign condition. In persistent isolated proteinuria, at least 80% of random urine samples exhibit abnormal protein excretion. This represents a heterogeneous group, but a significant proportion of these patients have prominent renal pathologic findings and progress to serious renal disease. Proteinuria with significant renal disease may be non-nephrotic or nephrotic range. The former does not exclude glomerular disease, but tubulointerstitial or vascular disorders are also likely when proteinuria is less than 2 g/24 hours. Patients with nephrotic-range proteinuria generally have a glomerular disorder. Distinction between benign and more ominous forms of proteinuria requires careful evaluation.     

Proteinuria in benign nephrosclerosis

Benign nephrosclerosis seldom is associated with significant proteinuria or reduced renal function. This study demonstrated that, despite the finding of benign nephrosclerosis on a renal biopsy specimen, concomitant proteinuria is predictive of a poor prognosis. Twelve patients, ranging in age from 24 to 59 years, with hypertension, proteinuria (greater than 1 g/d), and findings of benign nephrosclerosis on renal biopsy specimens were studied retrospectively. In three of these patients, the hypertension and proteinuria were diagnosed during pregnancy. Follow-up was possible in 11 patients. Nine patients became nephrotic in the course of their disease. Two patients had endstage renal disease and required maintenance dialysis treatment. Seven patients had decreased renal function as shown by the increase in serum creatinine levels. Thus, the combination of hypertension, proteinuria (greater than 1 g/d), and benign nephrosclerosis may be indicative of a progressive condition with a high percentage of patients having renal failure.     

Testicular radiation for primary seminoma in a solitary testis

Orchiectomy is the standard of care for patients with a second primary testicular tumor. We report a case of a man, with previous history of stage I left testicular germ cell tumor, who developed a contralateral seminoma and desired preservation of the remaining testis. Partial orchiectomy was not feasible due to tumor size and percutaneous needle biopsy revealed classical seminoma. He was treated with radiotherapy to the testis. Post treatment biopsy revealed no evidence of disease. At 32 months follow-up, he has not required androgen replacement. He has preservation of total testosterone level and libido.     

Renal biopsy findings and clinicopathologic correlations in rheumatoid arthritis

Objective. To evaluate renal biopsy findings and clinicopathologic correlations in patients with rheumatoid arthritis (RA). Methods. Retrospective study of renal biopsy specimens from 110 RA patients in whom the clinical renal disease was probably due to RA itself and/or to antirheumatic therapy. Results. The most common histopathologic finding was mesangial glomerulonephritis (GN) (n = 40), followed by amyloidosis (n = 33), membranous GN (n = 19), focal proliferative GN (n = 4), minimal-change nephropathy (n = 3), and acute interstitial nephritis (n = 1). Amyloidosis was the most common finding in patients with the nephrotic syndrome. In patients with isolated proteinuria, amyloidosis, membranous GN, and mesangial GN were almost equally common. Although mesangial GN was found in almost two-thirds of the RA patients with hematuria (with or without proteinuria), there still remained a 1 in 5 chance that the biopsy would reveal membranous GN or amyloidosis. Membranous GN was closely related to gold or D-penicillamine therapies, whereas mesangial GN probably related to RA itself. Conclusion. The renal morphologic lesion in RA patients with isolated proteinuria and those with hematuria cannot be accurately predicted on the basis of clinical symptoms and signs. Biopsy is thus useful in differential diagnosis, assessment of prognosis, and decision-making with regard to treatment.     

How often is NIDDM complicated with non-diabetic renal disease? An analysis of renal biopsies and the literature

Summary According to extensive autopsy studies, non-diabetic renal disease seems to be rare in diabetes mellitus, but recent publications suggest a significant prevalence of non-diabetic renal disease in non-insulin-dependent diabetic (NIDDM) patients, especially in the absence of retinopathy. The purpose of this study was to evaluate the prevalence of non-diabetic renal disease in NIDDM patients in renal biopsies from clinical practice, in patients suspected of having non-diabetic renal disease. In addition we systematically reviewed the literature. Biopsies were evaluated at the University Department of Pathology, Aarhus, Denmark, but had been collected at several departments of nephrology. In total 33 consecutive biopsies were available from 1988–1995 (mean age of patients: 62 years (range 39–75) (mean known diabetes duration 8 years (range 1–25); the main clinical reason for a biopsy was proteinuria. Renal function changes ranged from slight elevation of serum creatinine to uraemia. In addition 9 original papers, including our own material 580 patients were examined. On the basis of careful morphological evaluation according to international criteria, no patient exhibited an unequivocal sign of non-diabetic glomerular disease. Two patients had strongly but not completely convincing evidence of glomerulonephritis. One patient had some evidence of glomerulonephritis. These 3 patients also exhibited diabetic lesions. One patient with end-stage renal disease showed evidence of interstitial nephropathy without glomerular lesions. Thus, in 4 patients evidence of non-diabetic lesions was found. In the remaining 29 patients typical diffuse (n = 9) or nodular (n = 20) diabetic lesions were found. Twenty patients showed evidence of diabetic retinopathy. One of the patients with evidence of non-diabetic renal disease had simplex retinopathy. In the literature a considerable bias exists towards including patients with non-diabetic renal disease. In non-biased materials with proteinuria the prevalence of non-diabetic renal disease is very similar to our series. In microalbuminuric patients non-diabetic renal disease seems to be very rare. It can be concluded that in our material non-diabetic renal disease is uncommon in NIDDM patients, even if a clinician has suggested renal disease of other origin. A considerable bias towards including non-diabetic renal disease in NIDDM patients exists in the literature. The indication for biopsy should be evaluated carefully, and biopsy should by no means be routinely performed in NIDDM patients with proteinuria. [Diabetologia (1996) 39: 1638–1645]     

Primary microvascular lesions of the kidney or pre-hypertensive nephroangiosclerosis. 25 cases

Isolated non inflammatory lesions of renal microarteries (eventually with mild thickening of tubular basement membranes, but with negative immunofluorescent glomerular studies) were observed in 25 patients (22 males) in whom renal biopsy have been performed for proteinuria (P). Selection criteria were: pathological lesions by definition; absence of hypertension (HT) in clinical and at the time of biopsy; minimum follow up of 4 years after the first statement of the proteinuria (4 to 29 years; mean 14 years). Three groups have been isolated: 1. 3 patients have had an acute glomerulonephritis followed by disappearance of proteinuria. It reappears 1 to 5 years later. HT was discovered 2, 8 and 11 years after the proteinuria. Renal failure occurred 1 and 3 years after HT. 2. 14 patients had hereditary or acquired vascular risk factors (obesity, smoking, ethylism). In 7, HT occurred 3 to 15 years after P. In 2, renal failure occurred 4 to 8 years later. 3. 8 patients had no vascular risk factor; in 3 of them Ht developed 7, 13 and 20 years after the first statement. A positive immunofluorescence with IgM or C3 on renal arterioles had been found in only 3 of the 10 patients who in group 2 and 3 became hypertensive. A proteinuria may precede the occurrence of HT without being induced by glomerulonephritis. Group 2 and 3 suggest that these renal lesions of arterial sclerosis precede and may be a factor of HT. Indeed, this entity may be considered as a prehypertensive condition.     

TREATMENT OF "PRIMARY" RENAL AMYLOIDOSIS WITH MELPHALAN

Eight patients with " primary " amyloidosis presenting as renal disease are described. This diagnosis was made in 4% of 169 adults having renal biopsy for heavy proteinuria. Careful examination of the renal biopsy specimens, preferably including electron microscopy, is essential to detect this disease, which is not confined to the older-age groups. Selective proteinuria does not exclude amyloid. In view of increasing evidence that primary amyloid has an immunoglobulin origin, these patients were carefully screened for abnormal proteins and evidence of reticuloendothelial-system disease. Paraproteinæmia was found in a 64-year-old man and Bence Jones proteinuria in a 34-year-old woman whose marrow contained an excess of plasma cells. In the face of rapidly deteriorating renal function the latter patient was treated with melphalan and showed improved renal function over the next four years. Immunosuppressive therapy has an uncertain value in primary amyloid, but should be considered, especially when there is associated paraproteinæmia or para-proteinuria.     

Renal biopsy in lupus patients with low levels of proteinuria

OBJECTIVE: Early and accurate detection of kidney involvement in systemic lupus erythematosus (SLE) improves outcomes. Renal biopsy is required for definitive diagnosis of lupus nephritis (LN). In the absence of acute renal failure (ARF), moderate levels of proteinuria (> 1000 mg/24 h) have been recommended by some to justify biopsy. We investigated whether patients with lower levels of proteinuria without ARF have significant renal disease and should be routinely biopsied. METHODS: We retrospectively evaluated 21 SLE patients with 24-h urine protein < 1000 mg who underwent kidney biopsies. Indications for biopsy included new-onset proteinuria, increasing proteinuria, or hematuria (> 5 red blood cells per high power field). No patient had ARF. RESULTS: Sixteen of 21 (77%) biopsies were diagnostic of LN: 3 class II, 10 class III (5 superimposed class V), 2 class IV (one superimposed class V), and one with class V. One patient had thrombotic microangiopathy. The remaining 4 (23%) patients had non-lupus renal disease. Thirteen patients with class III or greater LN required alterations in therapeutic regimen because of biopsy findings. Of 7 patients without hematuria at the time of biopsy, 4 (57%) had class III, IV, or V LN. One patient without hematuria and < 500 mg/24 h proteinuria had class III LN. CONCLUSION: We found significant renal involvement (Class III, IV, or V LN) in SLE patients with < 1000 mg proteinuria with or without hematuria. Our findings suggest that biopsy be strongly considered in this patient population.     

A clinical-histological study of individuals with diabetes mellitus and proteinuria

Coexistent renal pathology with diabetic glomerulosclerosis was found in 38 of 136 (28%) consecutive renal biopsies performed primarily for proteinuria in individuals with diabetes mellitus. The histological lesions found were glomerulonephritis (14), focal tubulointerstitial disease (23), and amyloidosis (1). Significant microscopic haematuria was present in 66% of all patients and did not help to distinguish non-diabetic disease. The severity of diffuse diabetic glomerular disease was independently associated with duration of diabetes, raised plasma creatinine, the presence of hypertension, clinical retinopathy and neuropathy, but not with type of diabetes, degree of proteinuria or glycosylated haemoglobin at the time of biopsy. Diffuse interstitial fibrosis was related to the severity of glomerular disease and, if severe, also with a significantly (p less than 0.01) higher plasma creatinine. Coexisting renal disease was found to be associated with a significantly higher plasma creatinine (p less than 0.01) independent of the severity of diabetic glomerulopathy. Coexistent pathology is a not uncommon finding in renal biopsies from diabetic patients with proteinuria. These lesions and their underlying causes may not only influence the renal function and natural history of renal disease in diabetic individuals, but may also determine the response of proteinuria to therapy.     

Protein S and C antigen levels in proteinuric patients: dependence on type of glomerular pathology

The cause of the thrombotic tendency in nephrotic patients is unknown. Recent reports of thrombotic complications in patients with deficiencies of protein C or protein S (natural inhibitors of coagulation) have raised the possibility that decreased levels of these proteins may play a role in the hypercoagulable state of nephrotic patients. We measured the levels of protein C, total protein S, and free protein S antigens in 42 patients (21 nephrotic and 21 non-nephrotic) with one of four types of glomerular pathology: diabetic nephropathy (DM), focal glomerular sclerosis (FGS), membranous glomerulonephritis (MGN), and chronic renal failure due to hypertension (CRF). Protein C and total protein S antigen levels were significantly higher in FGS and MGN than they were in DM or CRF. Free protein S levels were lower in DM than they were in MGN. Protein C, total protein S, and free protein S levels did not significantly correlate with either serum albumin or degree of proteinuria. The mean levels of the three proteins did not differ between nephrotic and non-nephrotic patients. Free protein S and protein C were, however, significantly correlated (P less than .005 and P less than .002, respectively) with the type of glomerular pathology, independent of differences in age, sex, serum albumin, or degree of proteinuria. These data suggest that abnormalities of free protein S and protein C are related to the nature of the underlying renal disease, rather than to the degree of proteinuria.     

Coexistent findings of renal glomerular disease with Hashimoto's thyroiditis

Aim and Background Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disease with a female preponderance. Renal involvement in HT is not uncommon. In the present study, we aimed to define the frequency and characteristics of the glomerular diseases associated with HT and further the understanding of any common pathogenesis between HT and glomerular disease. Materials and Methods We reviewed retrospectively 28 patients with HT who were referred to our Department because of unexplained haematuria, proteinuria or renal impairment from 2007 to 2011. Routine laboratory investigations including blood count, serum biochemistry, urinalysis and 24‐h urinary protein excretion were performed on all patients. Renal biopsy was performed in 20 patients with HT, and the specimens were examined by light microscopy and immunofluorescence staining. Results We detected four cases of focal segmental glomerulosclerosis (FSGS), four membranous glomerulonephritis (MGN), two minimal‐change disease (MCD), three immunoglobulin A nephritis (IgAN), three chronic glomerulonephritis (CGN) and one amyloidosis. In three patients, the renal biopsy findings were nonspecific. Daily urinary protein excretion and glomerular filtration rates were found to be independent of the level of thyroid hormone and thyroid‐specific autoantibodies. Conclusion Glomerular pathologies associated with HT are similar to those in the general population, the most common lesions being MGN, FSGS and IgA nephritis.     

Primary seminoma in the middle mediastinum

Primary mediastinal seminoma is a relatively rare tumor usually located in the anterior mediastinum. We report here an extremely rare case of a 66-year-old man with primary seminoma in the middle mediastinum. A physical examination showed lymphadenopathy in the right supraclavicular area. A chest CT confirmed the presence of a tumor occupying the retrotracheal space. A histological examination demonstrated metastatic seminoma from the open biopsy of the lymph node. Abdominal, pelvis, and cerebral CT scan and testicular ultrasound were negative. Thus, primary mediastinal seminoma in the middle mediastinum with supraclavicular lymph node metastasis was diagnosed.     

Membranous glomerulonephritis with extra-renal disorders in children.

Thirty of 85 children with membranous glomerulonephritis (MGN) had associated extraglomerular disorders. The relation of these associations to membranous glomerulonephritis (MGN) is discussed. The causal relationship of acute hepatitis (5 cases), persistent hepatitis B antigenemia (6 cases), systemic lupus erythematosus (2 cases) and syphilis (1 case) may be ascertained; in similar conditions a definite antigen (Ag) has been found in MGN deposits. The association with SS or SA hemoglobinopathy (3 cases) ans with a preceding streptococcal infection (4 cases) raises the possible responsibility of renal tubular epithelium (RTE) Ag and of a streptococcal Ag. D-penicillamine therapy (1 case) is a well-known cause of MGN although the acting Ag remains unknown. Four children had serum sickness-like symptoms, two had hematologic disorders and two had proximal tubular dysfunction, one of them with proven anti-tubular and anti-alveolar basement membrane antibodies. A decrease in plasma C4, Clq, and factor B with normal C3 was frequently observed. The multiple Ag previously described as causative of MGN are recalled. The prevalent incidence of HBsAg is stressed, and the necessity for further investigations in patients with MGN in order to find an underlying disease is emphasized.