The clinico-pathologic features of hepatitis B virus-associated glomerulonephritis

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 311 patients with various forms of primary glomerulonephritis and 43 patients with lupus nephritis. HBs antigenaemia was detected in 69 of the 311 patients (22 per cent) with primary glomerulonephritis and this prevalence of HBsAg carrier was significantly higher than that in the general population (p less than 0.001). These patients had no clinical or biochemical findings to suggest acute or chronic liver disease. A higher HBs antigenaemia carrier rate was not observed in patients with lupus nephritis. Three glomerulopathological entities, membranous nephropathy, IgA nephropathy, and mesangial proliferative glomerulonephritis, were found to be associated with a higher prevalence of HBs antigenaemia compared with the general population (p less than 0.001). Glomerular deposits of HBsAg and/or hepatitis core antigen (HBcAg) were detected in 41, 61, and 60 per cent of renal biopsy specimens from patients with membranous nephropathy, IgA nephropathy, and mesangial proliferative glomerulonephritis associated with persistent HBs antigenaemia respectively. During the mean study period of 40 months (range 12-180), 14 per cent of these patients with hepatitis-associated glomerulonephritis developed progressive renal failure, although none required maintenance dialysis. Our study suggests that hepatitis B virus antigenaemia may play a significant role in the development of specific forms of glomerulonephritis and that these hepatitis B virus-associated glomerulonephritides can run an indolent but relentless progressive clinical course.     

Plasmapheresis in the treatment of rapidly progressing glomerulonephritis

The authors are of the opinion that plasmapheresis (PP) combined with immunosuppressant therapy is an effective and a relatively safe method for the treatment of rapidly progressing glomerulonephritis (RPGN). Introduction of PP in multimodality treatment of RPGN made it possible to arrest rapidly progressing renal failure in all 6 treated patients. After PP treatment was over, renal function was recovered completely in 3 patients. One patient manifested the retention of renal failure of medium degree while rare hemodialysis sessions permitted one to control water-electrolyte disorders. In two patients the discontinuation of PP treatment resulted in the progress of renal failure. The data obtained do not make it possible to relate the improvement of renal function exclusively to the action of PP, since all the patients received immunosuppressants. Nevertheless, in 2 cases, the improvement could be attributed to PP, for its discontinuation in these patients (without any changes in the remaining treatment) brought about again the progress of renal failure.     

The treatment of ANCA-associated rapidly-progressive glomerulonephritis and Goodpasture syndrome with therapeutic apheresis

Therapeutic plasma aphresis (plasmapheresis) is one form of treatment that is frequently used in practice of Nephrology. Plasmapheresis is the most important part of the therapies for Goodpasture's syndrome and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis which are causes of rapidly progressive glomerulonephritis. The reason why the effectiveness of plasmapheresis therapy cannot be clearly demonstrated in renal involvement in these diseases is that it does not appear to be possible to recruit an adequate number of patients and plasmapheresis is not effective in advanced disease if early treatment is not initiated.     

Profile of crescentic glomerulonephritis in Natal--a clinicopathological assessment

Crescentic glomerulonephritis is invariably associated with a fulminant syndrome of rapidly progressive renal failure which generally progresses to end-stage renal failure within weeks or months of onset. A widely differing aetiological background has been reported from Western countries. Work from the African continent is sparse. In a study from the province of Natal in South Africa between 1981 and 1987, 27 cases of crescentic nephritis were identified from a total of 458 patients who underwent renal biopsy at King Edward VIII and Addington hospitals. Poststreptococcal nephritis was the commonest aetiological factor (n = 8). There were six black patients in this group. Nine patients were classified as idiopathic and of these five were black. Four patients (one black) had antiglomerular basement membrane disease. Of the 24 patients subjected to variable combinations of immunosuppression, antiplatelet agents, dialysis and plasmapheresis, 11 improved, observed over four months to four years. Oliguria and severe renal failure at presentation signified a poor prognosis.     

Management of membranoproliferative glomerulonephritis type II with plasmapheresis

Membranoproliferative glomerulonephritis type II (MPGN II) is a rare kidney disease identified microscopically by electron-dense deposits surrounded by complement component C3 in glomerular basement membranes. MPGN II usually leads to renal failure, and patients with MPGN II experience a high rate of recurrence following renal transplantation. No treatment modalities have been proven successful if recurrence does occur. The sera of most patients with MPGN II contain complement C3 nephritic factor (C3NF), an IgG autoantibody directed against C3 convertase (C3bBb) that results in constitutive breakdown of C3. C3NF may be important in the pathogenesis of the disease. Since C3NF is IgG, we predicted that C3NF could be removed from the serum through plasmapheresis. We describe the use of long-term plasmapheresis to maintain good renal function in a 15-year-old girl with rapidly progressive recurrent MPGN II. After 73 plasmapheresis procedures over 63 weeks, her serum creatinine remained stable, and her creatinine clearance trended upward. Serial biopsies of the transplanted kidney demonstrated persistent MPGN II but no development of tubular atrophy. During the course of therapy, serum C3NF activity decreased; furthermore, C3NF activity was detected in the removed plasma. We have shown that plasmapheresis is a safe and effective method for delaying the onset of chronic renal failure in recurrent MPGN II. The efficacy may be due to the removal of serum C3NF.     

Gene polymorphisms of renin-angiotensin system in patients with kidney diseases

Blockade of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, has been well appreciated as a renoprotective treatment in proteinuric glomerular diseases. However, not all patients with glomerular diseases respond well to this therapy. Single nucleotide polymorphisms (SNPs) in angiotensin-converting enzyme (ACE) and angiotensinogen may be involved in the inter-individual difference in the responsiveness to the renoprotective efficacy of the RAS blockade. This review focuses on the interface between genomics and therapeutics in the renin-angiotensin system in IgA nephropathy, the most prevalent form of primary glomerulonephritis and one of the major causes of end-stage renal disease in the world.     

Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.

The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.     

Clinico-pathological correlations and long-term follow-up of 253 United Kingdom patients with IgA nephropathy. A report from the MRC Glomerulonephritis Registry.

The Medical Research Council's Glomerulonephritis Registry was used to study clinicopathological correlations and renal survival in patients with IgA nephropathy reported between 1978 and 1985. IgA nephropathy was the histological diagnosis in 9.3 per cent of all renal biopsies reported to the registry during this period, and in 18.1 per cent of those with a primary glomerulonephritis. The 10-year cumulative renal survival rate accounting for censored data (Kaplan-Meier) was 83.3 per cent. Univariate analysis of survival curves (log-rank test) found the following parameters to be significantly correlated with poor renal survival: serum creatinine > 120 mumol/l (p < 0.001), hypertension (p < 0.001), serum albumin < 40 g/l (p < 0.005), proteinuria > 1 g (p < 0.025), age > 30 years (p < 0.025), and focal mesangial proliferation (p < 0.05). There was no significant difference in renal survival between males and females. Multivariate analysis (Cox's proportional hazards model) revealed that only a serum creatinine of > 120 mumol/l and a serum albumin of < 40 g/l were independently predictive of outcome. These findings indicate marked similarities between the UK experience of IgA nephropathy and the published European experience. IgA nephropathy is not a benign condition in the UK and patients with impaired renal function and/or those with a reduced serum albumin are significantly more likely to progress to end-stage renal failure within 10 years.     

Acute poststreptococcal glomerulonephritis progressing to rapidly progressive glomerulonephritis

We have reported a rare, well documented case of poststreptococcal glomerulonephritis followed by rapidly progressive glomerulonephritis after weeks of stable renal function. The patient was successfully treated with steroids, azathioprine, and plasmapheresis. Progression of stable proliferative poststreptococcal glomerulonephritis to rapidly progressive glomerulonephritis appears to be uncommon.     

小儿常见肾脏疾病尿电导率的变化分析

目的：检测小儿常见肾脏疾病尿电导率的变化,探讨该指标的临床意义。方法选择2011年3月至2012年3月本院小儿肾脏内科收治的首次诊断为肾脏疾病患儿986例及同期健康体检儿童350例的尿液,利用 Sysmex 公司的全自动尿液分析仪 UF-1000i 分别测定其尿电导率的变化。根据临床诊断将肾脏疾病患儿分为肾病综合征组、肾小球肾炎组、肾功能不全组、紫癜性肾炎组和狼疮性肾炎组。其中216例进行肾穿刺活检。根据肾穿刺活检病理诊断结果将患儿分为系膜增生性肾小球肾炎组、毛细血管内增生性肾小球肾炎组、膜性肾病组、IgA 肾病组、IgM 肾病组、过敏性紫癜性肾炎组和狼疮性肾炎组。结果1．肾病综合征组、肾小球肾炎组、肾功能不全组、紫癜性肾炎组、狼疮性肾炎组患儿的尿电导率明显低于健康对照组,差异具有统计学意义（P ＜0．05）。2．系膜增生性肾小球肾炎组、毛细血管内增生性肾小球肾炎组、膜性肾病组、IgA 肾病组、过敏性紫癜性肾炎组和狼疮性肾炎组患儿尿电导率明显低于健康对照组,差异具有统计学意义（P ＜0．05）。3．IgM 肾病组与健康对照组相比,尿电导率差异无统计学意义（P ＞0.05）。结论尿电导率可以作为小儿肾脏功能和尿液浓缩功能的重要指标。     

554例IgA肾病患者临床特征分析

目的 探讨IgA肾病的特征及不同肾功能分期的临床特点。方法 选取经临床和肾脏病理明确诊断为IgA肾病的患者,收集所有病例的一般情况及临床资料,分析不同年龄层IgA肾病患者临床表现分布、不同慢性肾脏病（CKD）分期患者的临床特点,以及进展性肾功能不全IgA肾病患者的血清肌酐水平与临床各指标的相关性。结果 共纳入554例I...     

Renal pathology and proteinuria determine progression in untreated mild/moderate chronic renal failure

The progression of renal failure was analyzed in 108 patients with mild to moderate renal impairment, none of whom had received any form of dietary protein, phosphate restriction or immunosuppressive treatment. The reciprocal of plasma creatinine was plotted against time using a minimum of six plasma creatinine values taken over at least six months (mean 13 values over 41 months). Plots indicated there was linear deterioration in 70 patients, non-linear deterioration in 15 and stable renal function in 24. Progressive renal failure was common in patients with glomerulonephritis, diabetic nephropathy, chronic pyelonephritis and polycystic kidney disease. Most patients with hypertensive nephrosclerosis, analgesic nephropathy and renal impairment following acute renal failure were stable. Among those with progressive impairment the mean rates of deterioration were significantly faster for patients with glomerulonephritis and diabetic nephropathy compared to those with chronic pyelonephritis, polycystic kidney disease and undiagnosed renal disease (p less than 0.01). Hence the underlying renal pathological changes appear to be important in determining progression of renal failure and also the subsequent rate of deterioration. For those with linear progression of renal failure there was a significant correlation between 24-h urinary protein excretion and the rate of deterioration. This relationship held for glomerulonephritis and chronic pyelonephritis as separate diagnostic groups only. Proteinuria, therefore, may be a useful prognostic index for the rate of progression of established renal failure. Calcium phosphate product correlated poorly with the rate of deterioration. We were unable to demonstrate a relationship between spontaneous protein intake and deterioration of renal function. However, patients prescribed high protein diets were not included in dietary analysis and we cannot, therefore, exclude the possibility that a high dietary protein intake may accelerate renal failure. Similarly we were unable to show a significant relationship between blood pressure and progression of renal failure although there were weak correlations between mean arterial pressure and rate of deterioration for chronic pyelonephritis and glomerulonephritis.     

Tonsillectomy and steroid pulse therapy for IgA nephropathy

IgA nephropathy (IgAN) is the common cause of primary glomerulonephritis worldwide. The clinical course of IgAN is extremely variable and ranges from asymptomatic microscopic hematuria to rapidly progressive renal failure. The pathogenetic mechanisms of IgAN are still unclear, but a hypothesis consisting of two pathways has been proposed. The first pathway is continuous antigenic stimulation of the innate immune system by the tonsillar mucosa via the mucosa-bone marrow axis. In the second pathway, the anomalous stimulated immune response in the bone marrow results in the production of aberrantly glycosylated IgA1 and its subsequent deposition within the mesangial area. Based on the hypothesis, tonsillectomy plus steroid pulse therapy were introduced. A recent meta-analysis showed that tonsillectomy with or without steroid pulse therapy resulted in clinical remission with favorable long-term efficacy in IgAN patients. Tonsillectomy plus steroid pulse therapy now seems to be an effective treatment for IgAN patients with hematuria and minimal proteinuria, and it is more effective in patients with less severe histological findings. The efficacy of the combination therapy depends on the duration of the IgAN. Randomized, controlled trials are needed to examine the efficacy of tonsillectomy plus steroid pulse therapy in different clinical stages of IgAN.     

The natural history of membranous nephropathy in the West of Scotland

Membranous nephropathy was diagnosed in 54 patients between January 1975 and June 1983 in the Royal Infirmary, Glasgow. It was the commonest cause of the nephrotic syndrome and, with IgA nephropathy, the commonest primary glomerular disease. A cause was found in 10 patients. The last seven patients diagnosed were enrolled in the MRC trial. The natural history of the remaining 37 patients with idiopathic membranous nephropathy was studied. After an average observation period of 64 months, 50 per cent had stable renal function with or without proteinuria and 50 per cent had progressive renal failure or had died of other causes (five patients). Of the factors examined only heavy proteinuria and hypertension were significantly more common in patients who developed progressive renal failure. No patient who entered remission relapsed. Vascular complications were an important cause of morbidity and mortality. Incidence of events of arterial occlusion was significantly higher in these patients compared with patients with IgA nephropathy. Treatment of patients with membranous nephropathy should, therefore, be judged not only by its efficacy in preventing progressive renal failure, but also by its effect on vascular disease and by its toxicity.     

The effect of combination therapy with interferon and cryofiltration on mesangial proliferative glomerulonephritis originating from mixed cryoglobulinemia in chronic hepatitis C virus infection.

Cryofiltration, which has developed from double filtration plasmapheresis (DFPP) with a cooling unit, is an on-line technique to remove cryoglobulin. We report on a patient who suffered from progressive edema and renal insufficiency caused by cryoglobulinemic membranoproliferative glomerulonephritis (MPGN), probably due to chronic hepatitis C virus (HCV) infection. To remove cryoglobulins and terminate the HCV infection, we utilized combination therapy with cryofiltration and interferon-alpha injection with corticosteroids. Interferon-alpha was capable of decreasing proteinuria but not diminishing cryoglobulin. Additional cryofiltration could remove cryoglobulin to an undetectable level. This combination therapy was partially successful to reduce proteinuria and prevent the progressive deterioration of renal function. The major adverse effects of this therapy were bleeding and myelosuppression. We conclude that this combination therapy may be effective and should be considered as treatment for cryoglobulinemic MPGN.     

Recovery of both acute massive pulmonary hemorrhage and acute renal failure in a systemic lupus erythematosus patient with lupus anticoagulant by the combined therapy of plasmapheresis plus cyclophosphamide

Acute massive pulmonary hemorrhage (AMPH) is a rare and highly fatal complication in systemic lupus erythematosus (SLE). We report here survival in a case of AMPH in a SLE patient with both rapidly progressive glomerulonephritis and lupus anticoagulant. The AMPH occurred while the nephritis was refractory to 2 courses of pulse methylprednisolone therapy. After combined therapy with plasmapheresis plus cyclophosphamide, circulating immune complex levels declined, AMPH recovered, and serum creatinine levels returned to normal. In conclusion, the combined therapy of plasmapheresis plus cyclophosphamide should be considered for treating AMPH especially in those SLE patients with rapidly progressive glomerulonephritis.     

Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis: a clinicopathologic study.

In 51 patients with type 1 and 9 patients with type 2 membranoproliferative glomerulonephritis, we found a male predominance in both types, a wide age range but with younger patients having predominantly type 2 disease, and clinical presentations that varied and included the nephrotic syndrome, an abnormal urinalysis only, acute nephritis, and recurrent hematuria. Hypertension and impaired renal function at the time of first evaluation, which were present in more than one-third of the patients, presaged a poor prognosis; in most of these patients end-stage renal failure or worsening of renal function occurred. Acute nephritis at onset was also related to a deteriorating course and was especially frequent in patients with type 2 membranoproliferative glomerulonephritis. Retrospective analysis of treatment regimens, in which patients were given an average of 1 year of therapy with prednisone alone or combined with cytotoxic agents, showed no effect in patients who had progressive forms of the glomerulopathy.     

Plasmapheresis in antineutrophil cytoplasmic antibody-associated systemic vasculitis.

Small vessel vasculitis syndromes associated with antineutrophil cytoplasmic antibodies frequently cause a necrotizing and crescentic glomerulonephritis with the potential to progress rapidly to permanent renal failure. These conditions are conventionally treated with immunosuppressive drugs, but the possibility that humoral factors are important in their pathogenesis has led to the evaluation of plasmapheresis as an adjunctive therapy. Both controlled and uncontrolled studies have suggested that the routine addition of plasmapheresis is unnecessary. However, when renal function is impaired to the point that dialysis is required, the addition of plasma exchange increases the chance of renal recovery. The superiority of this approach over pulses of methylprednisolone remains to be confirmed.     

Renal expression of intercellular adhesion molecule-1 in different forms of glomerulonephritis.

1. Expression of intercellular adhesion molecule-1 was investigated in five normal kidneys and 47 renal biopsies with the use of monoclonal antibody 7F7 and immunoperoxidase staining. 2. In the normal kidney, intercellular adhesion molecule-1 was expressed on endothelial cells of glomerular and peritubular capillaries, on Bowman's capsule, on some interstitial cells and weakly in the mesangium. 3. Increased glomerular staining was detected in early cases of rapidly progressing glomerulonephritis (5/8) and in some cases of non-IgA mesangioproliferative glomerulonephritis (5/9), IgA nephropathy (3/5), Henoch-Schoenlein purpura (2/2), lupus nephritis (5/6) and focal segmental glomerulosclerosis (1/3). A decrease in intercellular adhesion molecule-1 expression was noted in advanced rapidly progressive glomerulonephritis (3/8), two cases of membraneous nephropathy, one severe mesangioproliferative glomerulonephritis biopsy, the two membranoproliferative glomerulonephritis biopsies and in sclerotic loops in focal segmental glomerulosclerosis. 4. Expression de novo on tubular epithelial cells occurred in rapidly progressive glomerulonephritis, in membranoproliferative glomerulonephritis, and to a lesser extent in some cases of membraneous nephropathy, minimal change disease, IgA nephropathy, focal segmental glomerulosclerosis, a severe case of mesangioproliferative glomerulonephritis and in the mixed essential cryoglobulinaemia case. In 63% of positive tubuli, intraluminal cells which expressed CD18, the common beta-chain of leucocyte-function-associated antigen-1, Mac-1 and p150,95, were present. 5. Intercellular adhesion molecule-1 was also found on the majority (59%) of infiltrating mononuclear cells in all forms of glomerulonephritis.     

IgA-dominant postinfectious glomerulonephritis: a new twist on an old disease

IgA-dominant acute postinfectious glomerulonephritis (APIGN) is an increasingly recognized morphologic variant of APIGN, particularly in the elderly. In contrast to classic APIGN, in which there is typically glomerular deposition of IgG and C3 or C3 only, IgA is the sole or dominant immunoglobulin in IgA-dominant APIGN. Because the vast majority of reported cases occur in association with staphylococcal infections, the alternative designation 'IgA-dominant acute poststaphylococcal glomerulonephritis' has been applied. Diabetes is a major risk factor, likely reflecting the high prevalence of staphylococcal infection in diabetics, particularly involving skin. Patients typically present with severe renal failure, proteinuria and hematuria. Prognosis is guarded with less than a fifth of patients fully recovering renal function. This variant of APIGN must be distinguished from IgA nephropathy. Features that favor IgA-dominant APIGN over IgA nephropathy include initial presentation in older age or in a diabetic patient, acute renal failure, intercurrent culture-documented staphylococcal infection, hypocomplementemia, diffuse glomerular endocapillary hypercellularity with prominent neutrophil infiltration on light microscopy, stronger immunofluorescence staining for C3 than IgA, and the presence of subepithelial humps on electron microscopy. The pathogenetic mechanism of selective IgA deposition in patients with poststaphylococcal glomerulonephritis likely involves specific host responses to the inciting pathogen.