Secondary IgA nephropathy presenting as nephrotic syndrome with glomerular crescentic changes and acute renal failure in a patient with autoimmune hepatitis

Patients with end-stage liver disease are prone to hemodynamic and immunologic renal injury, the latter at times manifesting as glomerulonephritis. Elevated serum immunoglobulin A (IgA) levels and mesangial IgG-IgA deposits are common in these patients, but are often clinically silent. We report a patient with autoimmune hepatitis and secondary IgA nephropathy (IgAN) who presented with nephrotic syndrome, acute renal failure (ARF), with 30% of the renal glomeruli having undergone crescentic change, and with IgA2 deposits in the glomerular mesangium. This article discusses secondary IgAN pathogenesis and its therapeutic management.     

Renal involvement in juvenile chronic arthritis: clinical and pathologic features

Over an 18-year period, renal involvement was diagnosed in 13 patients, who represent 1% of the total juvenile chronic arthritis population referred to us. All had severe arthritis. This study illustrates the importance of renal biopsy and indicates that renal involvement in juvenile chronic arthritis is a heterogeneous group of diseases, with a variety of causes. In eight patients with nephrotic syndrome, renal biopsy revealed amyloidosis. One rapidly died of diffuse amyloidosis and infection. The other seven received chlorambucil. Disappearance of proteinuria was noted in three of them. Four patients have persistent proteinuria but normal serum creatinine. It is suggested that, despite the long-term oncogenic risk of the drug, chlorambucil may be beneficial in patients with amyloid deposits. In one patient, the nephrotic syndrome was attributed to systemic lupus erythematosus, and in another, the chance association of an arthritis and nephrotic syndrome with minimal glomerular changes was considered. Although drug responsibility is difficult to determine in these patients receiving several medications in association, the renal involvement presented by the remaining three patients was probably related to drug(s). Moreover, it is possible that the effect of the association of medications is deleterious to the kidney. Drug-induced nephropathy is usually reversible when drugs are stopped. Unfortunately, because of persistent joint pain, these patients will continue to require pain-relieving drugs over prolonged periods.     

Rapidly progressive glomerulonephritis in IgA/IgG cryoglobulinemia

Mixed IgA/IgG cryoglobulins were found in the serum of a 48-year-old man suffering from rapidly progressive glomerulonephritis (RPGN) with crescent formation. The type-II cryoglobulins were composed of monoclonal IgA1-kappa and polyclonal IgG, with the IgA possessing antibody activity against the IgG. The RPGN was of the immune complex type with granular deposits of IgA, IgG, and C3 on immunofluorescence microscopy and preponderant subendothelial deposits on electron microscopy. Occluding protein thrombi could be demonstrated in several glomerular capillary loops. Removal of the cryoglobulins from the patient's serum by plasmapheresis and immunosuppression was paralleled by a remarkable improvement in renal function with fall of serum creatinine values from 13.6 mg/dl (1,202.2 mumol/l) to 2.8 mg/dl (247.5 mumol/l), a resolution of the glomerular lesions, and clinical improvement as well. Our observations suggest that the crescentic glomerulonephritis may be due to an immune complex-like deposition of the cryoproteins. We conclude that crescentic glomerulonephritis in IgA/IgG cryoglobulinemia has to be considered as an autoimmune form of RPGN.     

Remission of the nephrotic syndrome in a patient with renal amyloidosis due to rheumatoid arthritis treated with prednisolone and methotrexate

A 46-year-old woman developed nephrotic syndrome secondary to rheumatoid arthritis (RA). A renal biopsy showed deposition of amyloid fibrils in the subendothelial space of the glomerular capillary walls. After treatment with prednisolone (PSL, 40 mg/day), the levels of C- reactive protein (CRP) and serum amyloid A decreased to within normal limits for 2 weeks. However, the nephrotic syndrome persisted for 6 months after the therapy. To maintain the suppression of disease activity and to reduce PSL, methotrexate (5 mg/week) was added. The nephrotic syndrome resolved gradually, and the level of serum albumin returned to normal. Although renal prognosis of patients with nephrotic syndrome due to amyloidosis caused by RA has been considered poor, adequate and long-term treatment of RA with antiinflammatory drugs, including PSL and methotrexate, is useful for patients with secondary amyloidosis complicated by RA. (Am J Kidney Dis 1998 Nov;32(5):E7)     

Idiopathic IgA nephropathy with diffuse crescent formation

OBJECTIVE: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. METHODS: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. RESULTS: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 +/- 264 micromol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50-95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans' capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 micromol/l), and only 5 were dialysis-dependent. CONCLUSIONS: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.     

Successful treatment of post-MRSA infection glomerulonephritis with steroid therapy

A 48-year-old man without underlying disease developed mediastinitis and was treated by mediastinal drainage. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in a culture of the abscess material. He was treated with anti-MRSA antibiotics and the MRSA infection improved. Four weeks after the onset of MRSA infection, he developed rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome (NS). A renal biopsy showed endocapillary proliferative glomerulonephritis with IgA-predominant glomerular deposition. These clinicopathological findings were consistent with those in glomerulonephritis following MRSA infection (post-MRSA infection glomerulonephritis). The level of serum creatinine increased to 6.3 mg/dl, 7 weeks after the onset of RPGN. At that time, the eradication of MRSA infection was considered. He was given middle-dose steroid therapy. Thereafter, his RPGN with NS improved. MRSA infection did not recur. If the disease activity of post-MRSA infection glomerulonephritis persists after the disappearance of MRSA infection, the application of immunosuppressive therapy with steroids may be useful.     

Case of rheumatoid arthritis with various histological lesions of the kidney

We experienced a case of rheumatoid arthritis with nephrotic syndrome. A renal biopsy specimen from this patient showed various renal histological changes. The patient was a 50-year-old man who was diagnosed as having rheumatoid arthritis in 1987. We performed a renal biopsy because he had persistent proteinuria from March in 2002. The renal biopsy specimen showed amyloid AA and P protein deposition in the glomeruli. Moreover mild mesangial proliferation was recognized. IgA-deposition in the mesangial area, and granular-deposition of IgG along the glomerular capillary wall were also observed. In electron microscopy, electron dense deposits were recognized in the mesangial area and subepithelium of the glomerular basement membrane. From these findings, we diagnosed amyloid nephropathy, IgA nephritis and membranous nephropathy. Renal biopsy of patients with RA is useful not only for precise diagnosis, but also for selection of the appropriate treatment.     

Clinicopathological study of membranous glomerulonephritis in patients with rheumatoid arthritis]

Of 103 patients with membranous glomerulonephritis proved by renal biopsy, 11 (10.7%) had rheumatoid arthritis. Nine of these 11 patients received systemic treatment with anti-rheumatic remedies including gold, D-penicillamine and bucillamine. Two others were administered only token of nonsteroidal antiinflammatory drugs. Renal function of the patients was well maintained and within normal limits. Four patients showed nephrotic syndrome, while mild to moderate proteinuria was found in the other 7. Hematuria was minimal to mild, and it was not a major symptom. Six patients resolved proteinuria completely and 2 patients incompletely after discontinuation of chrysotherapy. Nine cases of the membranous lesion in patients with rheumatoid arthritis were stage 1. Thus it was often difficult to identify the glomerular change only by light microscopy. IgA nephropathy and AA amyloidosis were associated in one patient respectively. Our data lead us to conclude that chrysotherapy would cause membranous lesions, but rheumatoid arthritis itself also induce membranous glomerulonephritis.     

Case of MPO-ANCA-associated vasculitis with membranous nephropathy

We experienced a rare case of membranous glomerulopathy(MN) with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis. A 79-year-old woman was admitted to our hospital because of pyrexia, microscopic hematuria, massive proteinuria and positive MPO-ANCA on June, 2007. We diagnosed her as MPO-ANCA-associated vasculitis accompanied by nephrotic syndrome. Intravenous methylprednisolone sodium succinate (500 mg/day for three days)therapy and oral prednisolone (40 mg/day) improved her fever, hematuria, serum CRP and MPO-ANCA titer. Renal biopsy was performed and light microscopic examination of a renal biopsy specimen containing 21 glomeruli revealed global sclerosis in 3 and thickened basement membrane in 18 of the glomeruli. Fibrocellular crescents were found in 2 and segmental necrosis in 1. Immunofluorescence microscopy showed granular staining with IgG and C3 along the capillary walls. Electron microscopic examination disclosed subepithelial dense deposits in the thickened glomerular basement membrane. To investigate the pathogenesis of MN, IgG subclass was examined by means of immunofluorescence microscopy. IgG1 and IgG4 were deposited on the glomerular capillary walls, which suggested secondary MN. However, this patient refused to take any medicines and had no disease such as infection or cancer which cause secondary MN. MPO staining was performed to investigate the relation of MPO-anti-MPO antibody immune complex in the pathogenesis of MN. The results showed only a few MPO-positive cells in the glomeruli and MPO stains on the glomerular capillary walls near the MPO-positive cells. These findings suggested that the patient had MPO-ANCA-associated glomerulonephritis superimposed on idiopathic MN. In the case of nephrotic syndrome with MPO-ANCA, we should consider the coexistence of other types of glomerulonephritis, especially MN.     

A case of renal cell carcinoma associated with rapidly progressive glomerulonephritis

A 74-year-old man was admitted to our hospital because of a treatment for his right renal tumor. The abdominal CT scanning revealed a mass in the right kidney, and a right selective renal arteriography demonstrated a hypervascular tumor. On admission, urinalysis revealed proteinuria (3-4 g/day) and microscopic hematuria, and serum electrolytes were normal. Serum creatinine and urea nitrogen levels were 1.6 mg/dl and 30 mg/dl, respectively. A percutaneous right renal biopsy specimens showed crescentic glomerulonephritis. Direct immunofluorescence studies showed strong linear staining for IgG and IgA along the glomerular capillary walls. Electron microscopy showed increased mesangial matrix and swollen epithelial cells, but no dense deposits in the para-mesangial area and in the glomerular basement membrane. The patient underwent right radical nephrectomy. Histologic examination of the resected specimen revealed renal cell carcinoma. Postoperatively, he developed rapidly progressive renal failure and the renal function could not be recovered. Using the indirect immunofluorescence technique, we could not confirm the presence of a serum anti-glomerular basement membrane antibody, although the examination could not be carried out until the initiation of hemodialysis therapy. Some cases of glomerulopathies associated with renal cell carcinoma were previously reported, but the case of crescentic glomerulonephritis was very rare.     

A case of immunotactoid glomerulopathy with IgA2, kappa deposition ameliorated by steroid therapy

We report a case of idiopathic immunotactoid glomerulopathy with IgA2, kappa light chain deposition, ameliorated by steroid therapy. A 28-year-old male patient was admitted to our hospital due to exacerbation of nephrotic syndrome. The onset of his renal disease was at 24 years of age and the renal biopsy revealed membranoproliferative glomerulonephritis with moderate-degree deposition of IgA, IgG, IgM, C3 and C1q. Prednisolone therapy was started at the dose of 50 mg/day and effective for nephrotic syndrome and renal dysfunction. Two years later, the proteinuria and microscopic hematuria gradually exacerbated during reduction of prednisolone. The second renal biopsy showed mesangioproliferative glomerulonephritis with predominant deposition of IgA and C3. The glomerular proliferative changes were successfully suppressed by steroid treatment. On electron microscopy, a microtubular deposit with an average width of 40 nm and double-tracked appearance was observed in the mesangial and subendothelial areas. Immunohistochemical examination revealed that the deposit was predominantly composed of IgA2 subclass and kappa light chain. Selective deposition of IgA2 subclass and kappa light chain indicated that the glomerular lesion should be induced by monoclonal immunoglobulin, although it could not be detected in the serum and urine clinically. Immunoglobulin subclass staining of renal biopsy specimens provides an important clue for understanding the pathogenesis of immunotactoid glomerulopathy or fibrillary glomerulonephritis.     

Transformation of membranous glomerulonephritis into crescentic glomerulonephritis with glomerular basement membrane antibodies. Serial determinations of anti-GBM before the transformation

This case report describes a patient who initially had a pleuritis and arthalgias. During the follow-up he developed first a membranous glomerulonephritis with nephrotic syndrome and subsequently a crescentic, rapidly progressive glomerulonephritis with glomerular basement membrane antibodies (anti-GBM). An analysis of the serum samples obtained during the follow-up revealed no infections at the onset of renal failure. However, anti-GBM could be demonstrated in the serum samples obtained 2 months before the deterioration of the renal function. The anti-GBM did not react with alveolar BM and the patient had no signs of pulmonary hemorrhage. The etiology and the sequence of the pathological events of rapidly progressive glomerulonephritis is discussed in the light of these observations.     

Treatment of glomerulonephritis in the elderly

With the increasing use of renal biopsy in the elderly, glomerulonephritis is now known to be a common finding. Whereas membranous glomerulonephritis and minimal change disease are common in younger and older adults, primary amyloidosis and crescentic glomerulonephritis are more common in the elderly. Other glomerulonephritides such as focal segmental glomerulosclerosis or IgA nephropathy are very uncommon in the elderly. Because of the serious consequences of the nephrotic syndrome and acute and chronic renal failure in the elderly, aggressive treatment with immunosuppression should not be withheld. Caution should always be taken because of the presumed greater morbidity and mortality from such treatment in the elderly.     

Superimposition of post-streptococcal acute glomerulonephritis on the course of IgA nephropathy: predominance of Th1 type immune response

A 23-year-old man was admitted with macrohematuria and systemic edema appearing after an acute upper respiratory tract infection. He had been diagnosed 6 years earlier with IgA nephropathy (IgA-N). On admission, hypertension, nephrotic syndrome and hypocomplementemia were evident together with a high titer of anti-streptokinase (ASK). Renal biopsy showed severe glomerular mesangial proliferation, segmental endocapillary proliferation and crescent formation. Immunofluorescence microscopy (IF) showed strong deposition of C3 and reduced deposition of IgA. Electron microscopy showed a so-called "hump" on the epithelial side of the glomerular basement membrane.These features were consistent with post-streptococcal acute glomerulonephritis (PSAGN) superimposed on IgA-N. Following 2 weeks of observation, blood pressure, C3 level and ASK titer returned to normal ranges, although nephrotic syndrome was still evident, which necessitated oral prednisolone (30 mg/day) therapy. Another biopsy taken 2 months later demonstrated regression of endocapillary proliferation and IF showed decreased deposition of C3. Immunohistochemical staining of the specimen taken on admission revealed the presence of numerous T cells and macrophages in the interstitium. Macrophages were also seen in the glomerular tuft. Many interstitial infiltrating cells were positive for interferon-gamma, but their number diminished after treatment. Our findings suggest that PSAGN complicating pre-existing IgA-N activates cellular immunity and augments renal tissue injury.     

A patient with severe renal amyloidosis associated with an immunoglobulin γ-heavy chain fragment

The authors report a patient with progressive renal dysfunction caused by severe renal amyloidosis associated with a γ-heavy chain variable region (V_H) fragment. The patient was a 71-year-old woman who had renal insufficiency without nephrotic syndrome. Laboratory data showed a monoclonal IgG λ component in her serum and urine. Renal biopsy results showed massive amyloid deposition in the mesangial region, but the glomerular basement membranes and epithelial cells were preserved. Because immunohistochemical studies using antibodies against a number of known amyloid fibril proteins failed to detect the amyloid protein, the amyloid protein extracted from a small piece of the biopsied renal tissue was subjected to biochemical analysis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the extracted amyloid protein showed a prominent band at 11-kDa, and this protein was identified by amino acid sequence analysis as a γ-heavy chain variable region fragment (V_H3 subgroup) without the first N-terminal residue. Our results indicate that the patient's renal amyloidosis was associated with a γ-heavy chain variable region fragment. Microextraction and biochemical characterization of amyloid fibrils was of great use for reaching a definitive diagnosis.     

Mesangial IgA nephropathy and idiopathic nephrotic syndrome

A 17-year-old male presented with nephrotic syndrome associated with microscopic hematuria. Renal biopsy showed only minor glomerular abnormalities (light microscopy). Immunohistology demonstrated strong mesangial deposition of IgA. Electronmicroscopy disclosed widespread effacement of foot processes in combination with isolated osmiophilic mesangial deposits. The patient responded to standard corticosteroid therapy with complete disappearance of proteinuria. Microscopic hematuria, however, persisted. Five months after steroid therapy was stopped, the nephrotic syndrome relapsed. It was again steroid-responsive with persisting microhematuria. From clinical and morphological data we conclude that the patient has concomitant idiopathic nephrotic syndrome (minimal change glomerulonephritis) and mesangial IgA glomerulonephritis. The simultaneous presence of these two diseases may give some hint as to their pathogenesis. In both, abnormalities in T cell regulation have been found. If these were indeed involved in the pathogenesis of the two glomerular diseases, a higher than expected probability for the two entities to coexist in the same patient is to be expected.     

A case of primary amyloidosis associated with giant cell infiltration within a Bowman's capsule]

A 67-year-old man was hospitalized with a diagnosis of nephrotic syndrome. Physical findings at admission were generalized edema and macroglossia. Urinalysis showed massive proteinuria, + +occult blood, and granular and broad casts. Ig A lambda monoclonal gammopathy was noted in the serum. There was no evidence of myeloma in the bone marrow aspirate, scintigram or X-ray of the bone. A biopsy specimen of the kidney showed massive deposits of structureless material in the glomeruli. Marked cell infiltration was also observed in the interstitium. Multinucleated giant cells were occasionally seen in the Bowman's capsules and the interstitium. There were reactive changes in the Bowman's capsule adjacent to the giant cell. The deposits were proved to be amyloid by positive staining with Congo red and apple-green birefringence by polarized light. In addition, microfibrills seen on electron microscopy displayed deposits. Amyloid depositions were observed in other tissues such as gingiva, skin and tongue. Staining of amyloid with Congo red was resistant to potassium permanganate, and amyloid was positively stained with lambda-light chain of immunoglobulin. These findings indicated that the patient had primary amyloidosis. Infiltration of the multinucleated giant cell has been reported only in patients with familial amyloidosis and secondary amyloidosis associated with rheumatoid arthritis. To our knowledge the present case is a first report of the giant cell infiltration in a Bowman's capsule in primary amyloidosis.     

Anti-glomerular basement membrane antibody-mediated glomerulonephritis remarkably improved by pulse therapy with methylprednisolone, plasmapheresis and continuous heparin infusion

The patient, a 28 year-old-man, was admitted to a hospital because of general fatigue and fever. He was pointed out renal dysfunction and was transferred to Nagasaki University Hospital. The laboratory data on admission showed moderate azotemia (BUN 43 mg/dl, Cr 5.4 mg/dl). A percutaneous renal biopsy on admission revealed a diffuse crescentic glomerulonephritis. A direct immunofluorescence of renal biopsy showed a linear pattern for IgG along the glomerular basement membrane. Radioimmunoassay of his serum for circulating anti-GBM antibody was strongly positive. Aggressive treatment with pulse therapy (methylprednisolone), plasmapheresis, and continuous heparin infusion was performed. He had markedly recovered from renal failure and escaped hemodialysis. The patient is making satisfactory process after 3 years.     

Fibrillary glomerulonephritis associated with monoclonal gammopathy of undetermined significance showing lambda-type Bence Jones protein

A 79-year-old woman was admitted to our hospital because of leg edema due to a nephrotic syndrome. Urinary and serum immunoelectrophoresis showed positive for the lambda type of Bence Jones protein. A bone marrow aspiration test revealed mild plasmacytosis (6.4% of the total cells). These findings confirmed her diagnosis of monoclonal gammopathy of undetermined significance (MGUS). Her renal biopsy specimen revealed mild mesangial cell proliferation and an increase in the mesangial matrix. Immunofluorescence studies showed positive staining for IgG, IgA, C3, and kappa and lambda light chains in the capillary wall and mesangium area. Electron microscopy showed that the electron deposits in the thickened basement membrane were formed by randomly arranged 16- to 18-nm nonbranching fibrils. A Congo red stain for amyloid was negative. These findings corresponded with the diagnosis of fibrillary glomerulonephritis. Therefore, this case showed a rare combination of fibrillary glomerulonephritis and MGUS.     

Waldenstr?m's macroglobulinemia associated with amyloidosis and crescentic glomerulonephritis

An unusual case of Waldenstr?m's macroglobulinemia associated with amyloidosis and crescentic glomerulonephritis is described. At autopsy, crescent formation was present in 80% of the glomeruli, and the breaks in the glomerular basement membranes were found at the same place as the deposition of amyloid.