Case of scleroderma with rapid progressive glomerulonephritis associated with both MPO-ANCA and anti-GBM antibodies

A 66-year-old male with scleroderma developed rapidly progressive glomerulonephritis (RPGN). Renal pathology revealed crescentic glomerulonephritis with interstitial inflammation and fibrosis. Immunofluorescent micrography showed linear deposition of IgG along the glomerular capillary wall. Both anti-glomerular basement membrane antibody (anti-GBM Ab), and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) were detected by an enzyme-linked immunosorbent assay (ELISA). These findings were compatible with ANCA-related vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation of the serum creatinine level (5.9 mg/dL), and a high titer of MPO-ANCA (530 EU) and anti-GBM Ab (21 EU). He was started on methylprednisolone pulse therapy and temporary hemodialysis. Since the immunosuppressive therapy lowered both antibody titers steadily and improved renal function, hemodialysis was discontinued 4 weeks after the therapy. It has been reported that some scleroderma patients developed rapid progressive glomerulonephritis due to ANCA-associated vasculitis in addition to the typical scleroderma renal crisis. There have been few reports of a scleroderma patient associated with RPGN, in whom both MPO-ANCA and anti GBM antibodies were detected.     

Tubulointerstitial mast cell infiltration in glomerulonephritis

Mast cells are involved in chronic inflammation and tissue fibrosis. To determine whether these cells are also involved in tubulointerstitial injury in glomerulonephritis, we assayed mast cell infiltration in the kidneys of 107 patients with primary or secondary glomerulonephritis. Using a monoclonal antihuman tryptase antibody, we detected mast cells in the renal cortical tubulointerstitium, the periglomerular areas, and the medullary interstitium, but not in glomeruli. Renal cortical tubulointerstitial mast cells, including periglomerular area, were estimated as 0.8+/-1.6 cells/mm2 in minimal change nephrotic syndrome (n=7), 1.5+/-0.7 cells/mm2 in minor glomerular abnormalities without nephrotic syndrome (n=7), 6.5+/-7.7 cells/mm2 in membranous nephropathy(n=10), 12.9+/-15.5 cells/mm2 in lupus nephritis (n=15), 13.4+/-8.3 cells/mm2 in focal segmental glomerular sclerosis (n=6), 18.5+/-21.1 cells/mm2 in ANCA-related nephropathy (n=5), 19.8+/-14.2 cells/mm2 in membranoproliferative glomerulonephritis (n=5), 21.3+/-17.7 cells/mm2 in immunoglobulin A (IgA) nephropathy (n=42), and 33.0+/-33.8 cells/mm2 in diabetic nephropathy (n=10). Except for patients with the rapidly progressive glomerulonephritic syndrome (RPGN), the number of infiltrating mast cells significantly correlated with the serum concentration of creatinine at the time of renal biopsy (r=0.59; P < 0.0001) and with the intensity of tubulointerstitial injury as measured by leukocyte infiltration (r=0.72; P < 0.0001) and fibrosis (r=0.75; P < 0.0001). In contrast, mast cell infiltration did not correlate with urinary protein excretion. In relation to serum creatinine concentration, the number of mast cells was fewer in patients with RPGN than in those with chronic glomerulonephritis. These data suggest that mast cells may contribute to the renal deterioration in glomerulonephritis by inducing chronic tubulointerstitial injury.     

Renal amyloidosis associated with extracapillary glomerulonephritis and vasculitis in a patient with inflammatory bowel disease treated with infliximab

A 70-year-old woman with an 11-year history of indeterminate inflammatory bowel disease developed rapidly progressive glomerulonephritis (RPGN) 3 months after the initiation of infliximab therapy. A renal biopsy showed Congo red-positive homogenous deposits in the mesangial area, glomerular capillary walls and arterial walls. Cellular and fibrocellular crescents were observed in 7 of 28 functioning glomeruli. There were findings of active tubulointerstitial nephritis and vasculitis of the small arteries. On electron microscopy, amyloid fibrils were observed in the deposits. Immunohistochemistry showed positive staining for amyloid A (AA) protein. After cessation of infliximab therapy, she was treated with methylprednisolone pulse therapy followed by oral prednisolone therapy. Thereafter, her RPGN was improved. This is a rare case of co-existent focal extracapillary glomerulonephritis with vasculitis and AA renal amyloidosis. Considering the temporal association of drug use with new onset of RPGN in our patient, we suggest a causal link between infliximab and RPGN due to extracapillary glomerulonephritis and vasculitis.     

Rapidly progressive glomerulonephritis: analysis of prevalence and clinical course

Over a period of 68 months we observed 33 patients with biopsy-confirmed severe crescentic glomerulonephritis (GN) and another 5 patients who fulfilled the clinical criteria of rapidly progressive glomerulonephritis (RPGN; no biopsy confirmation) in a region comprising approximately 930,000 inhabitants. Additional 7 patients with Wegener's granulomatosis (WG)/microscopic polyarteritis (MP) from the same region were not seen by nephrologists. The calculated annual incidence of crescentic GN/RPGN is 0.7/100,000. Of the 38 patients 13 had classical WG, 7 MP, 3 systemic lupus erythematosus, 5 Sch?nlein-Henoch purpura, 3 Goodpasture's syndrome, 2 IgA glomerulonephritis. Of note is the high prevalence of WG/MP and the relative frequency of Sch?nlein-Henoch purpura. At the last follow-up, 3 patients were dead (8%), 7 patients were on dialysis (18%), 7 patients had elevated serum creatinine (18%) and 21 patients had normal serum creatinine (55%). We conclude that: (i) RPGN is more frequent than reported; (ii) WG and MP account for more than 50% of cases of RPGN; (iii) renal functional prognosis is good in WG/MP, but less favorable in RPGN of other causes; (iv) severe hypertension is not a feature of RPGN; (v) WG/MP, and not Goodpasture's syndrome, is the most common cause of pulmonary hemorrhage in association with RPGN; (vi) death from infection or malignoma is uncommon (not observed in this series); (vii) de novo IgA GN may occur in patients in remission from WG (2 observations).     

Long-term treatment and prognosis of rapidly progressive glomerulonephritis

Short-term prognosis of rapidly progressive glomerulonephritis (RPGN) has improved since immunosuppressive therapy was introduced. The long-term course of the disease was investigated in 46 consecutive and unselected patients over a period of 15 years (1970-1986) with a mean observation time of five years (+/- 45 months). Most of the 46 patients had idiopathic RPGN (61%). Initially, hemodialysis needed 25 of the 46 patients (54%). Immunosuppressive therapy (plasma exchange, methylprednisolone pulses, steroids, cyclophosphamide, azathioprine) was administered in 36 of the 46 patients (78%). A remission was achieved in only 19 of the 36 patients who received immunosuppression (53%) and no spontaneous improvement was seen. Factors indicating poor prognosis were initial high serum creatinine, high percentage of crescents in glomeruli, glomerular sclerosis, and immunohistologic staining of the IgG at the tubuli. In 11 patients with remission, immunosuppression was discontinued and 6 had a relapse. Long-term immunosuppression was given to 8 patients with remission. Their renal function was not normal (creatinine 240 +/- 77 mumol/l), but none had a relapse (p = 0.01). It is concluded that the treatment of RPGN requires long-term attendance and repeated immunosuppression comparable to a systemic immune disease.     

A nationwide survey of rapidly progressive glomerulonephritis in Japan: etiology, prognosis and treatment diversity

Background

The etiology, prevalence, and prognosis of rapidly progressive glomerulonephritis (RPGN) including renal vasculitis vary among races and periods.

Method

To improve the prognosis of Japanese RPGN patients, we conducted a nationwide survey of RPGN in the nephrology departments of 351 tertiary hospitals, and found 1772 patients with RPGN (Group A: diagnosed between 1989 and 1998, 884 cases; Group B: diagnosed between 1999 and 2001, 321 cases; and Group C: diagnosed between 2002 and 2007, 567 cases). ANCA subclasses, renal biopsy findings, treatment, outcome and cause of death were recorded.

Result

The most frequent primary disease was renal-limited vasculitis (RLV) (42.1%); the second was microscopic polyangiitis (MPA) (19.4%); the third was anti-GBM-associated RPGN (6.1%). MPO-ANCA was positive in 88.1% of RLV patients and 91.8% of MPA patients. The proportion of primary renal diseases of RPGN was constant during those periods. The most frequent cause of death was infectious complications. The serum creatinine at presentation and the initial dose of oral prednisolone decreased significantly in Groups B and C compared to Group A. However, both patient and renal survival rates improved significantly in Groups B and C (survival rate after six months in Group A: 79.2%, Group B: 80.1%, and Group C: 86.1%. Six-month renal survival in Group A: 73.3%, Group B: 81.3%, and Group C: 81.8%).

Conclusion

Early diagnosis was the most important factor for improving the prognosis of RPGN patients. To avoid early death due to opportunistic infection in older patients, a milder immunosuppressive treatment such as an initial oral prednisolone dose reduction with or without immunosuppressant is recommended.     

Clinical findings on ANCA-associated renal vasculitis from the Japan RPGN registry obtained via a questionnaire survey

Renal involvement with significant organ damage is common in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). As a result, it is independently referred to ANCA-associated renal vasculitis. Clinically, ANCA-associated renal vasculitis is characterized by rapidly progressive glomerulonephritis. Pathologically, it is defined by pauci-immune type necrotizing and crescentic glomerulonephritis. According to previous reports from all over the world, the etiology, prevalence, and prognosis of RPGN including ANCA-associated renal vasculitis varies among races and periods. To elucidate the clinical characteristics of Japanese RPGN patients, a registry derived from a questionnaire survey was established in 1999 and maintained until 2006. As a result, 1,772 cases were collected, analyzed, and reported previously. In this mini-review, we outline the characteristic clinical findings of Japanese patients (Asian) with ANCA-associated renal vasculitis, based on the registry data.     

Rapidly progressive glomerulonephritis: classification, pathogenetic mechanisms, and therapy

Immunopathologic studies over the past two decades have demonstrated that rapidly progressive glomerulonephritis (RPGN) can result from glomerular deposition of anti-GBM antibody, immune complexes, or from some as yet undefined mechanism that does not involve glomerular antibody deposition. The latter process may be cell mediated and resembles a small vessel vasculitis. Most cases of idiopathic RPGN are not accompanied by pathogenic glomerular immunoglobulin deposition. Recent experimental studies of immune mechanisms of glomerular injury have identified several new processes that can induce damage to the capillary wall sufficient to result in crescentic glomerulonephritis (GN). These include direct effects of anti-GBM antibody alone and of the complement C5b-9 (membrane attack) complex, nephritogenic effects of inflammatory effector cells that involve reactive oxygen species and glomerular halogenation, and injury mediated by sensitized lymphocytes independently of antibody deposition. Macrophages have been shown to participate in both intracapillary and extracapillary fibrin deposition and crescent formation as well as to mediate capillary wall damage. The role of resident glomerular cells and cell-cell interactions in glomerulonephritis is still under active investigation. Despite these several advances in understanding immune injury to the glomerulus, therapy for RPGN remains largely empiric. Although the prognosis in RPGN has clearly improved over time, no form of disease-specific therapy has been clearly shown yet to be beneficial in a controlled study. Interpretation of the existing literature on therapy is complicated by the availability of only historical rather than concurrent controls, lack of attention to several variables known to affect disease outcome, and uncertainty regarding bias in favor of reporting positive results. Available data suggests that optimal outcomes may be achieved in anti-GBM nephritis by treatment with steroids, immunosuppression and plasma exchange, particularly when therapy is directed at patients with mild but rapidly progressive disease before oliguria or severe azotemia develop. Pulse steroids are probably the most cost-effective therapy for the idiopathic form of RPGN, but treatment with cytotoxic agents should be considered if clinical or histologic evidence of vasculitis is present.     

Four cases of anti-myeloperoxidase antibody-related rapidly progressive glomerulonephritis during the course of idiopathic pulmonary fibrosis

We report here 4 cases of rapidly progressive glomerulonephritis (RPGN) which developed during the management of idiopathic pulmonary fibrosis. In each patient, pulmonary disease preceded the onset of nephritis by 1 to 6 years. All patients had a high titer of serum autoantibodies against myeloperoxidase (MPO-ANCA) when the diagnosis of RPGN was made. Although the association of pulmonary fibrosis with ANCA-related glomerulonephritis has been occasionally described in the past literature, the sequence of pulmonary and renal injury has not been well defined. The present report demonstrates that idiopathic pulmonary fibrosis exists as a preceding condition in some patients with MPO-ANCA-related nephritis.     

Value of the baseline Geriatric Nutritional Risk Index in evaluating the prognosis of maintenance peritoneal dialysis patients

Objective To explore the value of baseline geriatric nutritional risk index (GNRI) in evaluating the prognosis of patients with end-stage renal disease (ESRD) who underwent peritoneal dialysis (PD). Methods The clinical data of patients who underwent PD catheterization and started PD therapy at the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 30, 2018 were collected retrospectively. The follow-up endpoint was death or hemodialysis. The follow-up deadline was March 1, 2019. The GNRI cut-off value was determined according to the ROC curve, and the patients were divided into GNRI≤90.5 group and GNRI＞90.5 group. The differences of clinical data and laboratory tests were compared between the two groups. Kaplan-Meier survival curves were used to compare the difference in PD rate between the two groups during follow-up, and the factors that affecting patients PD withdrawal were analyzed by Cox regression. Results The GNRI cut-off value was determined to be 90.5 based on the ROC curve. Until the deadline for follow-up, the drop-out rate of GNRI≤90.5 group was significantly higher than the GNRI＞90.5 group (35.88% vs 21.58%, P=0.003). Kaplan-Meier survival curves showed a higher rate of maintaining PD in the GNRI＞90.5 group than that in GNRI≤90.5 group during follow-up (P=0.021). Cox univariate regression showed that male, GNRI and serum Alb were protective factors for PD patients, and Scr was a risk factor. After multiple factors correction, male and GNRI were also the protective factors for PD patients. Conclusion As an objective indicator of nutritional evaluation, baseline GNRI can be used as a prognostic indicator for PD patients.     

ANCA-associated systemic vasculitis in Japan: clinical features and prognostic changes

Background

This study was conducted to standardize treatment and determine patient and renal outcome in Japanese anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis/rapidly progressive glomerulonephritis (AAV/RPGN) patients, because the prognosis of AAV/RPGN patients in Japan had been poor compared with that of other countries.

Methods

The participants in this retrospective cohort study were 824 ANCA-positive RPGN patients, 705 of whom were only myeloperoxidase (MPO)-ANCA positive.

Results

Among the early-years cohort (group?A; cases diagnosed between 1988 and 1998), patients frequently died due to opportunistic infection. Therefore, we recommended a reduced dose of prednisolone (oral prednisolone dose <0.8?mg/kg/day) with or without cyclophosphamide for initial treatment of Japanese RPGN patients. After this recommendation, 1-year survival of the patients improved: 75% in group?A, 79% in group?B (between 1999 and 2002), and 81% in group?C (after 2003). During the entire observation period, average serum creatinine level at the start of treatment decreased, and improvement of 1-year renal survival was also found (72% in group?A, 83% in group?B, and 83% in group?C), while the recurrence rate was significantly increased in group?C (0.05/patient-year in group?A, 0.07/patient-year in group?B, and 0.13/patient-year in group?C).

Conclusions

Oral prednisolone dose <0.8?mg/kg/day with or without cyclophosphamide as an initial treatment could improve patient survival in older Japanese AAV/RPGN patients. However, maintenance treatment avoiding relapse should be established to improve renal outcomes.     

The spectrum of diseases associated with necrotizing glomerulonephritis and its prognosis

Necrotizing glomerulonephritis (NGN) represents small-vessel vasculitis in the kidney. To assess the diseases associated with necrotizing glomerular changes and their prognosis we studied all 32 patients who had this histologic finding on kidney biopsy from 1969 to 1982 and compared them to those patients who had crescentic, diffuse, or focal and segmental glomerulonephritis without necrosis (n = 29). The diseases associated with NGN were systemic lupus erythematosus (n = 6/15), Henoch-Sch?nlein purpura (n = 3/4) Goodpasture's syndrome (n = 4/7), Wegener's granulomatosis (n = 6/6), polyarteritis (n = 4/5), infective endocarditis (n = 2/3), and idiopathic rapidly progressive glomerulonephritis (n = 7/21). Necrotizing glomerulonephritis occurred significantly more often in the vasculitides than in all the other disorders put together. The most difficult diagnosis problem occurred in patients with renal disease and pulmonary hemorrhage (n = 9), in three of whom diagnosis was uncertain even after autopsy (two autopsies done within one month and one within three months of presentation). A fourth patient had a linear staining for IgG along the glomerular basement membrane (GBM) on kidney biopsy but was subsequently diagnosed as having Wegener's granulomatosis. Comparison of patients with without NGN revealed no difference in outcome (death or dialysis) one year after biopsy (38% v 43%) or in serum creatinine levels one year later (4.6 v 4.8 mg/dL). The prognostic effect of NGN was not obscured by unequal distribution of other adverse prognostic factors in the two groups. The most important prognostic characteristics we identified for outcome were serum creatinine at biopsy (chi 2 = 24.0, P less than .0004) and the sum of activity and chronicity indexes on biopsy (chi 2 = 12.7, P = .0004). These variables were similarly distributed in patients with and without necrosis, mean serum creatinine levels at biopsy being 4.3 v 4.2 mg/dL and sum of indexes 7.8 v 8.0. Other factors such as clinical diagnosis and therapy were not important prognostically and therefore could not explain our results. We conclude that NGN in patients with active proliferative glomerulonephritis has multiple causes. Diagnostic difficulties occurred in those with anti-GBM-negative pulmonary hemorrhage. The appearances of small-vessel vasculitis in the kidney did not appear to have prognostic significance.     

Pathological classification and prognosis of renal damage caused by antineutrophil cytoplasmic antibody associated vasculitis

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.     

Systemic hypertension in patients with glomerulonephritis

Although systemic hypertension is very common in patients with glomerulonephritis there is a dispute if this alteration is consequence of the glomerulonephritis "per se" or is a consequence of the renal failure secondary to the glomerular lesion. With the aim to analyze the factors associated with systemic hypertension, 196 patients with different forms of nephritis were studied. The systemic arterial pressure was measured by standard sphygmomanometer, renal function was evaluated by the determination of the serum creatinine concentration or creatinine clearance. The diagnosis of the type of glomerulonephritis was made on the basis of an examination of kidney biopsy specimens. The prevalence of arterial hypertension among patients with glomerulonephritis was 62.7%. The hypertensive patients were older (hypertensive = 30.6 +/- 12.8; normotensive = 25.4 +/- 1.6 years; P = 0.03). The prevalence of arterial hypertension was lower in patients with minimal glomerular lesion (12.5%), though their ages were also lower (18.1 +/- 3.6 and 29.1 +/- 1.03 years; P = 0.03). Arterial hypertension did not correlate with the serum levels of creatinine and albumin; creatinine clearance and 24-h proteinuria. IN CONCLUSION: In the patients with glomerulonephritis, the presence of arterial hypertension was associated with a higher mean age whereas the intensity of proteinuria, the level of renal function or the type of glomerulonephritis was not different between the two groups.     

Anti-glomerular basement membrane antibody disease in Japan: part of the nationwide rapidly progressive glomerulonephritis survey in Japan

Anti-glomerular basement membrane (anti-GBM) antibody disease is a rare, but well characterized cause of glomerulonephritis. It is defined by the presence of autoantibodies directed at specific antigenic targets within the glomerular basement membrane. This pattern of rapidly progressive glomerulonephritis and alveolar hemorrhage is often referred to as Goodpasture’s syndrome. The prognosis for patients with anti-GBM antibody disease is poor. In Japan, to improve the prognosis of patients with rapidly progressive glomerulonephritis (RPGN), we conducted a nationwide survey of patients with RPGN and investigated the initial symptoms, laboratory findings including renal biopsy findings, treatment methods, and outcomes. Among patients with RPGN, patients with anti-GBM antibody disease were rare: 6.6% (47/715). Alveolar hemorrhage (Goodpasture’s syndrome) was observed in 23.4% of patients with anti-GBM antibody disease. Most patients with anti-GBM antibody disease had renal failure at the time of diagnosis. The mean serum creatinine level of patients with renal-limited anti-GBM antibody disease was 7.07 ± 4.21 mg/dl and that of patients with Goodpasture’s syndrome was 7.99 ± 4.31 mg/dl. The mean level of crescent formation was 78.99 ± 23.54% in patients with anti-GBM antibody disease, and a cellular crescent form was observed in 63.2% of those patients. The prognosis for patients with anti-GBM antibody disease is poor; the renal survival rate at 6 months after onset was 20.9%, and the mortality at 6 months after onset was 23.3%. To improve the prognosis for anti-GBM antibody disease, it may be necessary to detect this disease in the early stages and to treat it without delay. Presented at the 36th Eastern Regional Meeting of the Japanese Society of Nephrology.     

MPO-ANCA-positive anti-glomerular basement membrane antibody disease successfully treated by plasma exchange and immunosuppressive therapy

Anti-glomerular basement membrane (GBM) antibody disease is clinically manifested as rapidly progressive glomerulonephritis (RPGN) with crescentic changes. The renal prognosis is poor. We report here the case of a 61-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive anti-GBM antibody disease. This patient was referred to our hospital because of RPGN. Anti-GBM antibody was positive with a titer of 38 EU. The MPO-ANCA titer was 65 EU. Chest imaging examination revealed pulmonary multiple nodules. ANCA-associated vasculitis was suspected. Renal pathology revealed cellular crescents in 13 out of 17 glomeruli. Immunofluorescence with anti-IgG antibody, anti-C3 antibody, and anti-fibrin antibody showed linear staining along the glomerular capillary walls. Based on these findings, the patient was diagnosed with anti-GBM antibody disease. Hemodialysis was started because of uremic syndrome with elevated serum creatinine (6.84 mg/dL). In addition, treatment with plasma exchange using 3.6 L (90 mL/kg) of fresh frozen plasma combined with an oral dose of 40 mg of prednisolone was initiated. Within 3 weeks, both types of autoantibodies became undetectable. Subsequently, this patient achieved dialysis independence and remission of glomerulonephritis. No adverse effects were observed. In patients with MPO-ANCA-positive anti-GBM antibody disease, intensive therapy predominantly with plasma exchange might be operative, even though renal function is less likely to recover.     

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.     

Detection of urinary macrophages expressing the CD16 (Fc gamma RIII) molecule: a novel marker of acute inflammatory glomerular injury

BACKGROUND: The CD16 antigen is the Fc gamma receptor III. CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi) that constitute a minor population in the peripheral blood of healthy individuals. Little is known about the expression of CD16 antigen on Mo/M phi in glomerulonephritis. METHODS: Flow cytometric analyses were performed on urine and blood samples obtained from 209 patients with various renal diseases. Patients variously suffered from rapidly progressive crescentic glomerulonephritis (RPGN), membranoproliferative glomerulonephritis (MPGN), postinfectious acute glomerulonephritis (AGN), Henoch-Sch?nlein purpura nephritis (HSPN), IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), lupus nephritis (LN), acute interstitial nephritis, hereditary nephropathy, idiopathic renal hematuria (IRH), and renal stone. RESULTS: The CD16+ M phi population of cells was present in the urine of hematuria-positive patients with proliferative glomerulonephritis, including AGN, IgAN, RPGN, MPGN, and LN with acute inflammatory lesions, such as endocapillary proliferation, tuft necrosis, and cellular crescents. In contrast, the urinary CD16+ M phi population was negligible in hematuria-positive patients with nonproliferative renal disease, including hereditary nephropathy, IRH, and renal stone and also in patients with proliferative glomerulonephritis lacking acute inflammatory lesions. Total urinary M phi of these patients were much less than those of patients having proliferative glomerulonephritis with acute inflammatory lesions. Transient expansion of the CD16+ M phi population in urine was observed during the acute exacerbation of urinary abnormalities, whereas the disappearance of CD16+ M phi closely preceded the amelioration of urinary abnormalities in patients with proliferative glomerulonephritis. In 38 of the 98 patients positive for CD16+ M phi population in urine, the CD16+ Mo population was negligible in peripheral blood. Immunohistochemically, CD16+ M phi were present in the glomeruli of active proliferative glomerulonephritis, whereas such cells were absent in inactive proliferative glomerulonephritis or nonproliferative glomerular diseases. CONCLUSION: CD16+ M phi may be effector cells involved in the acute inflammation common to all types of proliferative glomerulonephritis. Furthermore, the detection of CD16+ M phi in urine, as well as urinary M phi counts, may serve as a useful indicator of the active stage of proliferative glomerulonephritis.     

Risk factors in idiopathic renal vasculitis and glomerulonephritis

In this retrospective study, we analyzed clinical laboratory, and pathologic variables to determine their value in predicting survival and survival free of renal failure for 170 consecutive patients with idiopathic renal vasculitis and glomerulonephritis evaluated during a 15 year period. Of the 170 patients, 108 had focal segmental necrotizing glomerulonephritis alone (FSNGN), 33 had FSNGN and small-artery vasculitis, and 29 had FSNGN and medium-sized artery vasculitis. Considerable overlap of clinical, laboratory, and pathologic findings existed among the three groups. Overall patient survival was 81% at one year, 61% at five years, and 44% at ten years, significantly less than expected survival. Overall survival free of renal failure, by definition, was lower than patient survival. There were no differences among these three groups in patient survival or survival free of renal failure. Multivariate analysis identified leukocytosis and serum creatinine level as independent predictors of patient survival and survival free of renal failure. In addition, univariate analysis identified age and hypertension as significant risk factors but did not add independent predictive value for these two end points. In patients with serum creatinine levels less than 4 mg/dl, the effect of increasing levels of leukocyte count was significantly associated with poorer outcomes for both patient survival (P = 0.006) and survival free of renal failure (P = 0.024). Outcomes for these two end points were worse for patients with lower serum creatinine levels (less than 4.0 mg/dl) and high leukocyte counts (greater than 16,000/mm3) than for those with serum creatinine levels greater than or equal to 4.0 mg/dl.     

A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive rapidly progressive glomerulonephritis

We report a case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year-old woman was admitted to our hospital for evaluation of RPGN. Laboratory evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl), cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype 1). After admission, the patient's renal function and anemia deteriorated rapidly, then prednisolone(30 mg/day) was started. After treatment her renal function gradually improved, then a renal and liver biopsy was performed. The renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3, and fibrinogen along the glomerular basement membrane and mesangial matrix. The pathogenesis of RPGN in this case may relate to the deposition of immune complexes in the glomeruli because immunofluorescent examination was revealed to be the immune-complex type, but not pauci immune type nephritis. Liver histology revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal vasculitis. Although her renal function was improved after treatment with prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the 120th hospital day. Suddenly she died because of pulmonary hemorrhage on the 180th hospital day. These findings suggest that various HCV-induced immunological abnormalities, such as positive MPO-ANCA, cryoglobulinemia and hypocomplementemia, play an important role in the pathogenesis of this RPGN, although we could not demonstrate deposition within glomeruli of immune complexes containing HCV. The effect of interferon therapy on such immunological abnormalities remains to be documented. Since interferon is known to have immunomodulatory effects, we selected corticosteroid therapy. Future studies need to focus on the optimal treatment strategy for hepatitis C virus-associated glomerulonephritis.