Lobular Glomerulonephritis Research Articles

A recurrent fibronectin glomerulopathy in a renal transplant patient: a case report

Fibronectin glomerulopathy (FNG) is a rare, autosomal dominant renal disease with massive mesangial, and subendothelial fibronectin deposits. It presents proteinuria, often in the nephrotic range in the third to fourth decade, and slow progression to end-stage renal disease. The risk of recurrent disease in renal allograft is uncertain. A Japanese female with end-stage renal disease because of unknown origin received a renal transplant and was referred with proteinuria and mild deterioration of renal function four months after transplantation. Five allograft biopsies were underwent from one h to 12 months after the transplantation, including a biopsy 19 d after the transplantation, which revealed dense deposits suggesting fibronectin. A biopsy 134 d after the transplantation showed a feature of lobular glomerulonephritis corresponding FNG. The diagnosis was confirmed by IST4 positive and IST9 negative immunostaining together with typical fibrillary dense deposits in the mesangium and subendothelial spaces in electron microscopy. This is the first report of recurrent FNG in Japan.

The other end of spectrum in hypertension: ‘Idiopathic nodular glomerulosclerosis’

Dear Editor, Nodular glomerulosclerosis is observed in diabetes mellitus, dysproteinemias, lobular membranoproliferative glomerulonephritis, glomerular deposition disease, and chronic hypoxic states. Idiopathic nodular glomerulosclerosis (ING), which is a rare clinical entity, is diagnosed in the absence of these conditions. We report a case of ING in an elderly hypertensive lady. An 82-year-old woman was evaluated for chronic kidney disease. Her medical history included hypertension, permanent atrial fibrillation, and osteoarthritis. There was no personal or family history of diabetes mellitus, hepatitis, autoimmune, or connective tissue disease. She did not use any over-the-counter medications, herbal remedies, cigarettes, alcohol, or recreational drugs. On examination, her vitals revealed blood pressure of 140/93 mmHg, with an irregular heart rate of 74–86 beats/min. The rest of the physical examination was unremarkable. Laboratory parameters were significant for mild normocytic anemia with a hemoglobin level of 10.2 mg/dl, BUN of 65 mg/dl, and creatinine level of 1.7 mg/dl. Fasting blood glucose, 2-h glucose tolerance test, autoantibody screening, complements, hepatitis serology, and cryoglobulins were normal. Urinalysis was normal with random protein 18 mg/dl and creatinine 59.2 mg/dl. Serum protein electrophoresis confirmed by immunofixation revealed monoclonal IgM lambda quantitated at 0.11 g/dl; free kappa/lambda ratio was 1.17 (normal 0.26–1.65). Renal ultrasound demonstrated slightly asymmetric kidneys. Renal artery magnetic resonance angiography was normal. Light microscopy of left kidney biopsy showed 6 end-stage sclerotic glomeruli and 14 viable glomeruli. Nodular mesangial expansion, thickened peripheral capillary basement membranes, tubular atrophy, interstitial fibrosis, arteriolar intimal sclerosis, and patchy lymphoplasmacytic infiltrates were observed (Fig. 1). Congo red stain was negative. Immunofluorescence was positive for focal granular mesangial IgM deposits. Electron microscopy showed thickened glomerular basement membranes and expanded mesangial matrix, frequently forming mesangial matrix nodules. There were no electron dense deposits, and foot processes were fused in a patchy pattern. These findings were suggestive of diffuse and nodular glomerulosclerosis with moderate to severe arteriosclerosis. In the absence of other etiologies, it is possible that hypertension was responsible for nodular glomerulosclerosis in this patient. It is speculated that individuals with long standing hypertension have an increased or reset sensitivity to non-diabetic glycemic levels resulting in an exaggerated glomerulovascular response [1]. R. Kasmani (&) T. Thiyagarajan R. NarwalChadha K. Okoli F. Irani Department of Internal Medicine, St. Vincent Mercy Medical Center, Toledo, 2213, Cherry Street, Toledo, OH 43608, USA e-mail: rahilkasmani@hotmail.com

Immunotactoid glomerulopathy with microtubular deposits, with reference to the characteristics of Japanese cases

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed microtubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for kappa light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITG occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia.

Lobular membranoproliferative glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits associated with B cell small lymphocytic lymphoma

Lobular membranoproliferative glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits associated with B cell small lymphocytic lymphoma

A Study of Membranoproliferative Glomerulonephritis in Iran

The aim of this study was to review the morphologic patterns of membranoproliferative glomerulonephritis (MPGN) in 100 Iranian patients using light microscopy (LM) and electron microscopy (EM), and to compare the treatment and outcome in 13 patients with two biopsies. A retrospective study of 713 kidney biopsies of Iranian patients received between 1981 to 1994 was carried out. Of the 713 kidney biopsies, MPGN (n=106) and membranous glomerulopathy (n=112) made up the highest numbers of cases. Among 100 MPGN patients, 55 (55%) were MPGN type I, 10 were type II (10%), and 35 type III (35%). Eighty-three (83%) had nephrotic proteinuria, 39 (39%) had hematuria, and 52 (52%) were hypertensive. Complement levels were estimated in 58, with low C3 in 10. The glomerular involvement was irregular, with focal hypercellularity in 47 patients (47%), widely patent capillaries in 50 (50%), arteriosclerosis in 48 (48%), and with hyaline change in 25 (25%). Follow-up data (22-130 months) was available in 61 (61%) patients: 6 (10%) died after 14-56 months, 27 (44%) were on maintenance hemodialysis for 15-110 months, and three received transplants. Thirteen patients had detailed follow-up and a second biopsy after 24-120 months. All 13 presented with edema and nephrotic range proteinuria, with hematuria and hypertension in five and azotemia in four. Seven of the 13 patients received initial steroids, followed by antiplatelet or antihypertensive drugs. Four (type III) patients received antiplatelet and antihypertension drugs, and two (type III) received only antihypertensive drugs. In the first biopsy, glomerular changes by light microscopy were non-uniform in 7 of 10 (70%) type III MPGN cases. Vascular changes were absent or mild in 11, and moderate in two. In the second biopsies, 10 showed decrease in cellularity, with many open capillaries, persistence of deposits by EM in all, and progression of vascular sclerosis in eight, and tubulointerstitial changes in 10. Among the 13, six were clinically stable, another six received dialysis followed by transplant in three, and one had relapses with episodes of cryoglobulinemia. Three patients died. There is a high incidence of MPGN in Iranian patients, with a substantial number of type III MPGN cases. Second biopsies showed decreased cellularity, but increase in chronic tubulointerstitial and vascular cases. Steroids did not appear to benefit the outcome in types I and III MPGN patients compared to patients who received antihypertensive and antiplatelet treatment without steroids.

Microlamellar Structures in Lobular Glomerulonephritis Associated with Monoclonal IgG Lambda Paraproteinemia

We report a 49-year-old woman who developed lobular glomerulonephritis with prevalent deposition of material positive for IgG, C1q and lambda light chain, but which was not stained by Congo red. Glomeruli revealed massive electron-dense deposits with a microlamellar structure in the mesangial matrix and peripheral capillary loops. Clinically, the patient had nephrotic syndrome, microhematuria and hypertension. No Bence-Jones protein or cryoglobulin was found in the urine or serum. Anti-DNA antibody was positive, but systemic lupus erythematosus (SLE) was ruled out by repeated serological examinations. Immunoelectrophoresis of blood and urine revealed increased IgG-lambda paraprotein, but no free light chains were found. We reviewed 54 cases reported in the literature, which showed organized crystalline structures on ultrastructural examination, but were unassociated with amyloidosis, SLE, cryoglobulinemia or multiple myeloma. The present patient is the first reported to have exhibited a combination of glomerulonephritis with organized deposits, monoclonal IgG lambda paraproteinemia, and the presence of anti-DNA antibody.

Induction of recurrent glomerulitis with accentuated glomerular lobulation by intermittent repetition of unilateral Masugi nephritis.

In order to induce a glomerulitis with lobular features, antirabbit renal glomerular basement membrane hen serum was intravenously injected into rabbits repeatedly at intervals of 3 weeks, during the course of clamping of contralateral renal arteries for 20 min. The first injection induced disorganization of the glomerular architecture accompanied by proliferation of local fixed cells and following crowding of the proliferated cells towards the axis of the loops and peripheral recanalization which brought about a lobular appearance of glomerulus. And the repeated injections induced repetition of such processes, resulting in accentuation or exaggeration of the lobular features of the glomeruli. The glomerular lesions presented here resembled closely to those of human lobular glomerulonephritis. Accordingly, the results of this study will offer some clue to understanding of the genesis of the human glomerular disease.

Induction of a disease resembling lobular glomerulonephritis in man by means of recurrence of unilateral Masugi nephritis in rabbits

Induction of a disease resembling lobular glomerulonephritis in man by means of recurrence of unilateral Masugi nephritis in rabbits

Light-chain glomerulopathy with amyloid-like deposits

A 40-year-old man with rapidly progressive renal failure was found to have a lobular glomerulonephritis by renal biopsy. Immunofluorescent microscopy showed prominent glomerular deposition of both kappa and lambda light chains but no significant heavy-chain component. Ultrastructurally, electron-dense deposits in the mesangium and capillary basement membranes had a fibrillar appearance indistinguishable from amyloid. This case illustrates a "light-chain glomerulopathy" distinct from previously reported glomerulopathies associated with the deposition of light chains of a single subclass.

Déficit héréditaire en inhibiteur de la C1 estérase Lupus et glomérulonéphrite

Congenital deficit of the inhibitor of C1 esterase (C1 INH) usually presents by oedema of the lower limbs, abdomen and glottis (sometimes lethal), which explains its clinical denomination of angioneurotic oedema. The association of this condition with disseminated lupus erythematosis has been reported in 4 cases and with discoid lupus in 4 cases. Antinuclear factors were found in all these cases but there were only two documented cases of nephropathy (one diffuse proliferative glomerulonephritis and one local glomerulonephritis). The association of a deficit of C1 INH and membrano-proliferative glomerulonephritis has only been reported in 2 cases (one lobular glomerulonephritis and one glomerulonephritis with dense basal membrane deposits). Our case had C1 INH deficiency and proliferative lupic glomerulonephritis in the absence of other clinical and immunological signs of DLE. Nephropathy was not looked for in 9 cases of association of C1 INH deficiency and C3-shearing autoantibody (C3 NEF). A common genetic mechanism for these associations seems very improbable. The aptitude of patients with C1 INH deficiency to synthesise autoantibodies under the influence of infections factors, for example, could explain the higher incidence of lupus and glomerulopathies in these patients.

Diabetes and Glomerulopathies

To the Editor.— The article entitled, Acute Glomerulonephritis Complicating Diabetic Nephropathy, by Drs Olivero and Suki ( Arch Intern Med 137:732-734, 1977) reminded me of three nearly consecutive biopsies in diabetics that proved puzzling to Dr Paul Kimmelstiel and myself when we encountered them in 1968 (see Table). Report of Cases.—Case 1.— Patient 1 had a ten-day history of nausea and vomiting, and a three-day history of edema and dyspnea. Dr Kimmelstiel's biopsy interpretation was: The differential diagnosis lies between a diffuse diabetic glomerulosclerosis and lobular glomerulonephritis. In favor of the latter is the marked degree of cellularity, including polymorphonuclear leukocytes; against it are a clearly delineated basement membrane of peripheral capillaries. The possibility of a glomerulonephritis superimposed upon diabetic glomerulosclerosis must be considered. Case 2.— Patient 2 delivered a normal infant complicated by toxemia of pregnancy. Three months later, a biopsy was performed because of nausea, vomiting, persistent

Morphogenesis of axial sclerosis and fibrosis following proliferative glomerulitis and their significance for the nephrotic syndrome.

Mode of development of axial sclerosis and fibrosis of glomerular loops following proliferative glomerulitis was studied on the basis of renal biopsies. The analyses of biopsy specimens revealed that mild proliferative glomerulitis with preservation of capillary structure is followed by axial sclerosis or sclerosis of mesangial area of glomerular loops, whereas marked or severe proliferative glomerulitis characterized by disorganization of glomerular architecture due to proliferation of local fixed cells with reticular arrangement, chiefly of endothelial origin, following histolysis of loop walls results in crowding of proliferated cells accompanied by formation of fibers along them toward axis of the loop (axial fibrosis) and recanalization at its periphery. It was also clarified that when cell proliferation and following axial fibrosis of glomerulus are pronounced, lobulation of glomerular loops associated with further formation of centrolobular nodules is brought about, which is the lesion characteristic of lobular glomerulonephritis. Some clinical features concerning these processes were presented and discussed, and significance of glomerular lesions here presented for the nephrotic syndrome was considered.

Manifestations of systemic light chain deposition

In two patients with terminal renal failure, manifestations of disease developed in multiple organ systems. One had a previous diagnosis of multiple myeloma with kappa light chain proteinemia and proteinuria. The other had idiopathic lobular glomerulonephritis. Hepatic and neurologic abnormalities developed in both; in the latter gastrointestinal, cardiac and endocrine disease developed as well. Clinical and pathologic correlations suggest that the retention and tissue deposition of light chains produced the organ dysfunction, inasmuch as free kappa light chain determinants were demonstrated histologically in the clinically affected organs. The deposition in these patients may be an extreme example of a common but previously unrecognized form of plasma cell dyscrasia.

The different forms of glomerulonephritis morphological and clinical aspects, analyzed in 2500 patients.

Comparative morphological and clinical studies of 2,500 patients suffering from glomerulonephritis, enabled us to divide the different forms of diffuse glomerulonephritis into 3 distinct groups and to separate these groups from the focal glomerulonephritides. The different forms of diffuse glomerulonephritis in group I are: 1. endocapillary (acute) glomeruloenphritis (of the post-streptococcal type), 2. mesangioproliferative glomerulonephritis, 3. mesangioproliferative glomerulonephritis with focal crescents, 4. mesangioproliferative glomerulonephritis with focal scarring, 5. minimal proliferating intercapillary glomerulonephritis without nephrotic syndrome. It is emphasised that these forms can transform into one another, that they seldom occur with nephrotic syndrome, and with varying frequency with hypertension. Group II consists of: 1. minimal proliferating intercapillary glomerulonephritis with nephrotic syndrome, 2. focal sclerosing glomerulonephritis, 3. perimembranous glomerulonephritis, 4. membranoproliferative glomerulonephritis, 5. lobular glomerulonephritis. It is stressed that these glomerulonephritis forms usually do not develop out of group I type glomerulonephritis forms, and that in this group a nephrotic syndrome is the most prominent clinical syndrome. In the third group are 1. mesangioproliferative glomerulonephritis with diffuse crescents, 2. necrotising glomerulonephritis. It is shown that this form of glomerulonephritis does not usually develop from either group I of II forms. The fourth group of focal glomerulonephritis is uncommon. This disease is characterized by a necrotising and proliferative inflammatory lesion found segmentally and focally in the glomeruli. Most of the other glomeruli appearing normal. It is emphasised that in the literature the diagnosis focal glomerulonephritis is made far too often. This is because glomeruli in which the inflammatory process in a few lobules is of varying prominence, are included in the focal glomerulonephritis group. The classification of the different forms of glomerulonephritis into 3 groups here described, is thought of as a basic classification. It is compared with Ellis' classification (1942), with which it has much in common.

Renal size in various nephropathies.

Renal sizes in a group of 68 patients suffering from various nephropathies were compared to expected normal values.Kidneys with lipoid nephrosis and lobular glomerulonephritis were shown to be statistically increased in size, whereas no statistical difference was noted in cases of membranous, membranoproliferative and latent glomerulonephritis. These 2 relatively new entities should be included in the differential diagnosis of enlarged kidneys with no other apparent abnormality on excretory urography.

Membranoproliferative Glomerulonephritis: A Clinicopathologic Study

Summary Light and electron microscopic changes are described in three children with apparently diffuse glomerulonephritis in the subacute and chronic stages. Case 1 is a classic case of membrano-proliferative glomerulonephritis (MPG) with low serum complement and predominantly subendothelial osmiophilic deposits with mesangial interposition as well as immunologically proven deposits of complement. In spite of massive morphological changes and metamorphosis to lobular glomerulonephritis the patient recovered clincally. The second case is considered to be an atypical form of MPG there is great similarity to membranous (epimembranous) glomerulonephritis. However, the pronounced proliferative changes, especially in the subacute phase, do not allow this diagnosis. Classification of the third case with little cellular proliferation and few deposits as well as severe lesions of the glomerular basement membrane was first difficult. The electron microscopic changes proove an Alport' Syndrome. In all three cases no previous disease was known. Streptococcal and viral infections are suggested as the cause in the available literature. However, an agent must be considered that is active over a long period of time while being of low pathogenicity. In many cases diagnosis can only be made by electron microscopy.

Membranoproliferative hypocomplementemic glomerulonephritis.

The diagnosis of membranoproliferative glomerulonephritis is made by its distinctive glomerular morphology. Early there may be an acute glomerulonephritis and late, a lobular glomerulonephritis. Hypocomplementemia often accompanies the disease in children. Onset is usually in childhood as a nephrotic or acute nephritic syndrome or a chance proteinuria. Origin is unknown and onset may be insidious. The disease is typically long standing with, terminally, rapid deterioration. Children may have a long interval of ‘silent’ nephritis. Activation of C3 by an alternate pathway involving a nephritic factor and the C3 proactivator produces the hypocomplementemia but has not been demonstrated to produce the nephritis. No treatment is consistently successful. The disease can recur in a renal transplant.

Steroid-Resistant Idiopathic Nephrotic Syndrome

Fifteen patients with idiopathic nephrotic syndrome unresponsive to steroid therapy were treated with azathioprine (4 mg/kg/ day) for periods ranging from 23 to 83 days. Pretreatment biopsies were obtained in each, and four histologic types of glomerulonephritis were found: membranous glomerulonephritis, seven patients; diffuse proliferative glomerulonephritis, four patients; focal glomerulonephritis, two patients; and lobular glomerulonephritis, two patients. None achieved complete remission; two had a partial remission with marked decrease in proteinuria, loss of edema, and increase in serum albumin to near normal levels; three others improved with a lesser decrease in proteinuria and loss of edema, but no rise in serum albumin level. Of the other ten, six remained stable, three deteriorated, and one died. Responders included two with membranous glomerulonephritis, two with proliferative glomerulonephritis, and one with lobular glomerulonephritis. Neither patient with focal glomerulonephritis responded. Azathioprine therapy may be helpful in some patients with idiopathic nephrotic syndrome unresponsive to

Renal transplantation between HL-A identical donor-recipient pairs. Functional and morphological evaluation.

16 patients underwent renal transplantation from a sibling donor who was prospectively determined to be ABO compatible and HL-A identical with the recipient. Unidirectional mixed leukocyte reactions were performed; in each instance, lymphocyte stimulation in either direction was not observed. The plasma creatinine 10-68 months after transplantation in these 16 patients ranged between 0.9 and 1.9 mg/100 ml. The creatinine clearance ranged from 48 to 113 ml/min, and the blood urea nitrogen (BUN) ranged between 12 and 35 mg/100 ml. Urine protein excretion varied from 0.11 to 1.86 g/day. Six patients exhibited no detectable clinical episodes of acute rejection; they were treated with azathioprine alone and each of them demonstrated normal or near normal renal histology when biopsy specimens were obtained more than 6 months after transplantation. Nine patients experienced acute rejection episodes that required the use of steroid therapy. The severity of these rejection episodes was variable; they included a mild reduction in renal function with an immediate steroid-induced restoration of function and eventual discontinuance of steroid therapy to severe reduction in function requiring prolonged and moderate doses of steroids without return to normal renal function. Renal histological observations in this group ranged from mild to marked cellular and structural changes which fit the criteria of the rejection. One patient demonstrated a gradual loss of renal function with heavy proteinuria. Biopsy of this allograft demonstrated the recurrence of original disease, i.e., lobular glomerulonephritis. The marked variability in the clinical course and allograft morphology in these 16 patients could be explained by antigenic differences at non-HL-A loci. The presence of minor histocompatibility loci has been well documented in other mammalian species and they are most certainly present in man. The need for their identification and definition is stressed.

Evolution of recurrent lobular glomerulonephritis in a human kidney allotransplant. Combined light-, immunofluorescence-, and electron microscopic studies of serial biopsies.

Recurrent lobular glomerulonephritis in an allotransplanted kidney was studied by light microscopy, immunofluorescent techniques and electron microscopy. Three successive biopsies of the graft and the nephrectomy of the transplant were performed. The histological and clinical evolution of the lobular glomerulonephritis of the graft paralleled that of the lobular glomerulonephritis of the donor kidney. The clinical evolution of the recurrent lobular glomerulonephritis in the grafted kidney of the recipient was comparable to that of the original lobular glomerulonephritis, of the recipient's own kidney. Serial biopsies showed that immunoglobulin deposits appeared prior to cellular proliferation. This observation is consistent with the hypothesis that immune complexes have a primary role in the pathogenesis of human glomerulonephritis.