Crescentic glomerulonephritis in children

Data on patients with crescentic glomerulonephritis (>50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7–15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR<30 ml/min per 1.73 m²) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%–79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m². In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P<0.05). Outcome was not, however, related to the percentage of glomeruli affected (P>0.05). Although the effectiveness of the individual components of the treatment regimens used was difficult to assess, one-third of patients at the latest follow-up had a GFR of more than 30 ml/min per 1.73 m².     

Treatment of crescentic glomerulonephritis

Summary: Acute crescentic-rapidly progressive glomerulonephritis is an uncommon but devastating disease which comes in several forms. That associated with anti-glomerular basement membrane (GBM) antibodies is most vexing to treat and has by far the worst prognosis. Despite conventional wisdom that plasma exchange and immunosuppression are optimal therapy, the cost constraints and issues raised in the present review suggest that this needs to be readdressed. Non-anti-GBM disease appears to respond well to aggressive immunosuppression and/or plasma exchange. A possible zided benefit of plasma exchange in patients with vasculitis on dialysis needs to be further addressed, especially in terms of a possible differential effect of very large doses of pulse methylprednisolone (30 mg/kg) as opposed to smaller doses.     

The impact of recurrence of primary glomerulonephritis on renal allograft outcome

Twenty‐yr patient and death‐censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non‐recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.     

A patient with membranoproliferative glomerulonephritis diagnosed by the third biopsy via endocapillary proliferative glomerulonephritis and focal membranoproliferative glomerulonephritis

We present a girl with type I membranoproliferative glomerulonephritis (MPGN) diagnosed by the third renal biopsy. The first renal biopsy was performed at age 11.2 years after microscopic hematuria (which was revealed by school urinary screening) had persisted for 3 months, along with a low level of serum C₃. Pathological examination of the biopsied specimen revealed endocapillary proliferative glomerulonephritis with multiple humps. The serum C₃ level increased to within the normal range 2 months after the first renal biopsy, and the microscopic hematuria disappeared at age 12.3. However, microscopic hematuria, proteinuria, and the low serum complement level reappeared at age 12.8. Pathological examination of a further renal biopsy that was performed at age 13.2 revealed focal MPGN with humps. Prednisolone therapy was subsequently initiated. Fluvastatin was added to her treatment regime when she developed hypercholesterolemia at age 13.6 and was continued even after normal cholesterol levels were reestablished. Pathological examination of the third renal biopsy, which was performed at age 15.2, revealed type I MPGN with humps. Serum C₃ normalized 6 months after the cessation of prednisolone at age 15.9. It is clinically important that patients with nontypical acute glomerulonephritis should be observed over a long period and repeated renal biopsies should be performed.     

Efficacy and safety of 'rescue therapy' with mycophenolate mofetil in resistant primary glomerulonephritis--a multicenter study.

BACKGROUND: Studies of mycophenolate mofetil (MMF) in primary glomerulonephritis have varied in their inclusion criteria, regimen and follow-up compromising assessments of efficacy and optimal dose. METHOD: This multicentre study analysed the safety and efficacy of MMF monotherapy in a large cohort with primary glomerulonephritis that was resistant to other conventional therapies. A total of 98 patients with biopsy-proven primary glomerulonephritis resistant to other drugs received MMF monotherapy for 1 year. Primary outcome measures were urinary protein excretion and the number of patients with complete or partial remission of proteinuria. Secondary analyses were time to remission and changes in the slope of creatinine clearance. RESULTS: Fifty-four percent of the patients achieved either complete or partial remission of proteinuria with no significant differences between glomerulonephritis types. Median (range) dose of MMF was 2 g/day (1.5-2 g/day) Mean (SD) treatment time to remission was 141.5 (+/-61.1) days with no significant differences between glomerulonephritis types. Serum albumin increased (P<0.01), whereas proteinuria (P<0.01) serum LDL-cholesterol (P<0.01) and mean blood pressure (P<0.05) decreased post-treatment. No significant changes were observed in glomerular filtration rate (GFR), serum creatinine or slopes of GFR. The reduction of urinary protein excretion was significantly higher in patients with basal nephrotic proteinuria and preserved renal function; it did not arise from an increased dose of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, since, among responders, mean blood pressure significantly decreased and the number of anti-hypertensive drugs could be reduced. CONCLUSIONS: MMF monotherapy causes a moderate decrease in proteinuria in >50% of the patients who do not have other treatment options. The response to therapy is largely influenced by a preserved renal function and requires sustained MMF treatment.     

Acute Postinfectious Crescentic Glomerulonephritis: Clinicopathologic Presentation and Risk Factors

Background: Glomerular crescent formation is a feature of the most severe forms of human glomerulonephritis. The postinfectious form of rapidly progressive glomerulonephritis with crescents is a form of immune complex glomerulonephritis which seem to have a better prognosis. A relatively poorer prognosis for crescentic postinfectious glomerulonephritis in South Africa has been reported. In the present study, we have tried to determine the mode of presentation, and the prognostic factors for renal and patient outcome for cases with postinfectious crescentic glomerulonephritis (CGN). Methods:Between 1990 and 2000 a total number of 128 patients with CGN were managed at our center, among them 23 cases were diagnosed as postinfectious CGN. They were followed-up for a mean period of 40.1 ± 28.9 months. Among them 12 were males and 11 were females. The median age was 12.35 years (range 4–55 years). The median serum creatinine at presentation was 7.24 mg/dl (range 1.3–14.5 mg/dl). We studied the clinical, laboratory and histopathological data ^.of our cases and their impact on the renal and patient outcome. Results:By univariate study the risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors. The risk factors that significantly affected patient mortality were hypertension and serum creatinine at last follow-up. Conclusion: postinfectious CGN is a severe form of glomerulonephritis that usually presents with rapidly progressive renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction.     

Recurrent Idiopathic Membranous Nephropathy After Kidney Transplantation: A Surveillance Biopsy Study

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. MN can recur after kidney transplantation causing proteinuria, allograft dysfunction and graft failure. In this study we assessed the incidence of MN recurrence utilizing surveillance graft biopsies. The study included 1310 renal allograft recipients from 2000 to 2006. Glomerular diseases were the cause of kidney failure in 28% of patients and 23 (2%) had idiopathic MN. Recurrent MN was diagnosed in eight of 19 patients included in this analysis (42%) 13 ± 20 months (median = 4; range 2–61 months) after transplant. The initial clinical manifestations of recurrent MN were mild or absent. Urine protein excretion was 825 ± 959 (64–2286) mg/day and three patients had no proteinuria. Five of seven patients who did not receive additional immunosuppression for MN had significant increases in proteinuria during follow up and three became nephrotic. At diagnosis, light microscopic changes were subtle or absent. All patients had granular glomerular basement membrane deposits of IgG but little or absent C3 by immunofluorescence. Subepithelial deposits were observed in all cases by electron microscopy. In conclusion, idiopathic MN recurred in 42% of patients after transplantation. The initial clinical and histologic manifestations are subtle but the disease is progressive.     

来氟米特联合糖皮质激素治疗系膜增生性肾小球肾炎的临床研究

目的探讨来氟米特（LEF）治疗系膜增生性肾小球肾炎（MsPGN）的临床效果、安全性和副作用。方法选择经病理证实为MsPGN的慢性肾脏疾病患者19例，采取激素联合LEF治疗。用药期间监测血尿常规、24h尿蛋白定量、肝肾功能等并记录所有不良反应，6个月后行疗效和安全性的评价。结果17例（89．47％）完全缓解，2例（10．53％）部分缓解，0例无效；1例出现皮疹，1例发生轻度脱发，未见肝功能异常。结论LEF联合糖皮质激素治疗MsPGN疗效明显、耐受性好，其在维持缓解期的长期疗效及安全性有待更长期的观察。     

Impact of clinical and histopathological factors on outcome of egyptian patients with crescentic glomerulonephritis

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.     

不同增殖性肾炎细胞增殖与凋亡的关系

目的 观察细胞增殖与凋亡在膜增生性肾小球肾炎(MPGN)、弥漫增生性狼疮性肾炎(LN)和急性感染后肾炎(APGN)的表现。方法 用原位末端标记方法对12例MPGN,15例LN和13例APGN患者肾活检组织中肾小球内凋亡细胞进行了观察,并用免疫组化方法同时对增殖细胞(PCNA染色阳性细胞)进行了分析。结果 在肾小球细胞增殖的同时,MPGN和LN患者表现出明显的凋亡不足的征象,而APGN患者则伴活跃的细胞凋亡。凋亡细胞数在APGN明显大于MPGN和LN,而增殖细胞与凋亡细胞的比值则以MPGN最大。结论 不同的增生性肾炎由于病因和病变性质不同,虽然都表现出细胞增殖,但其凋亡机制的反应性存在着明显的差异,这可能是上述三种增生性肾炎预后不同的因素之一。     

Infection-related glomerulonephritis: understanding mechanisms

The epidemiology of infection-related glomerulonephritis is undergoing striking changes, particularly in developed countries. The incidence of acute poststreptococcal glomerulonephritis (PSAGN) is decreasing because of the successful treatment of streptococcal infections. In contrast, because of the emergence of antibiotic-resistant staphylococcus strains, such as methicillin-resistant Staphylococcus aureus (MRSA), the incidence of Staphylococcus aureus infection-associated glomerulonephritis (SAAGN) is on the rise. In this review, we focus on the pathogenesis of PSAGN and SAAGN, but also emphasize the clinical importance of differentiating between two major forms of infection-related glomerulonephritis: postinfectious glomerulonephritis (such as PSAGN) and glomerulonephritis associated with active infection (such as SAAGN).     

Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti‐CD20 Monoclonal Antibodies

Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti‐CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2–21] months vs. 83[6–149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64–4898) at diagnosis to 4489 (898–13 855) (p = 0.038). Twelve months post‐Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.     

Expression of chemokines and their receptors in nephrotoxic serum nephritis.

BACKGROUND: Chemokines play a major role in leukocyte infiltration in inflammatory kidney diseases. The specificity of the chemokine action is determined by the restricted expression of the corresponding receptors on leukocytes. We therefore simultaneously studied the expression of CC-chemokine and CC-chemokine receptor 1-5 (CCR 1-5) mRNA in an accelerated model of nephrotoxic nephritis in CD-1 mice. METHODS: Kidneys were harvested at day 0, 2 and 7. Induction of nephritis was confirmed by assessment of albuminuria by ELISA and by histological evaluation. RNA was prepared from cortex and isolated glomeruli. RNase protection assays were performed to study the expression of chemokines, RNase protection assays as well as quantitative RT-PCR assays to study the expression of chemokine receptors. RESULTS: In the cortex of nephritic kidneys mRNA for MCP-1 was increased 5-fold on day 2 and increased 4-fold on day 7 as compared to controls. mRNA for RANTES was increased 5-fold on day 7 and mRNA for IP-10 6-fold on day 7. The increase of mRNA for the chemokine receptors CCR1 and 5 was between 2-fold and 3-fold determined by RNase protection assay and for CCR1, 2 and 5 between 2- and 4-fold as determined by RT-PCR. In isolated glomeruli we found by RT-PCR an increase of CCR1, CCR2 and CCR5 of between 3 and 12-fold. CONCLUSION: These results show that chemokines and their specific chemokine receptors are increased in parallel in this model of glomerulonephritis, consistent with the potential role of the chemokine system in leukocyte recruitment to the immune injured kidney.     

Prevention of pre-eclampsia in high risk women with renal disease: A prospective randomized trial of heparin and dipyridamole

Summary: Twenty-one women with primary glomerulonephritis and a history of a poor outcome in previous pregnancies were randomized to receive heparin, 15 000 units subcutaneously and dipyridamole, 400 mg daily ( n = 10) or no treatment ( n = 11) from 14 weeks of gestation. the women were well matched in terms of the type of underlying glomerulonephritis and previous pregnancy complications. the treated group showed a significantly lower incidence of hypertension ( P <0.03) and of overall maternal complication ( P <0.03). the days spent in hospital prior to delivery were 18 in the treated group and 27 in the control group ( P <0.01). In all other parameters which were measured the outcome was better in the treated group although these did not achieve statistical signficance. In the control group the pregnancy complications were similar to those in previous pregnancies but very few complications occurred in treated patients. Heparin and dipyridamole were used because of the activation of coagulation in preeclampsia and because of the prominence of fibrin in renal and uterine vessels in pre-eclampsia. As heparin suppresses both the action and the production of endothelin, the benefit of treatment could have reflected endothelin inhibition.     

移植肾肾病复发和新发患者的临床病理分析

目的：探讨肾移植术后肾病复发和新发患者的临床及病理特点.方法：选取南京军区福州总院行移植肾活榆的患者111例,其中A组为移植肾肾病复发和新发51例;B组为慢性移植物肾病60例;C组为与A组患者接受同一供肾38例.观察患者术前一般状况、术后穿刺前1周的检验结果及移植肾1、3、5年的存活情况并分析结果.结果：①A组肾病类型及例数：IgAN 15例,FSGS 10例,MPGN 9例,MsPGN 9例,MN 6例,SLE-LN2例.②穿刺前1周SCr、BUN及蛋白尿：A组明显大于C组.③A组移植肾5年存活率明显低于C组,三组移植肾1年、3年存活率无明显差异.结论：①复发和新发肾病以IgAN、FSGS、MPGN较为常见;②肾病复发和新发患者在肾功能异常时,肾功能及蛋白尿均较同一供肾组严重;③复发和新发肾病对移植肾短期存活无明显影响,但可降低其长期存活率.     

IgM-immune complex glomerulonephritis associated with sarcoidosis

We present a case of proliferative glomerulonephritis with peculiar IgM deposition associated with sarcoidosis. A 62-year-old woman, who had been diagnosed with sarcoidosis 3 years previously because of abnormalities on chest X-ray radiophotographs and lymph node pathology, was admitted to our hospital for the evaluation of proteinuria and microscopic hematuria. Laboratory findings showed renal dysfunction (creatinine clearance, 52 ml/min), a moderate range of urinary protein (1.51 g/day), and increased serum lysozymes (20.7 μg/ml; normal range, 3.4–8.6 μg/ml). Serum calcium level was within the normal range. Renal biopsy revealed immune complex glomerulonephritis (IgM deposition type) with a membranoproliferative pattern, without granuloma or calcium deposition. Corticosteroid (initial dose of prednisolone [PSL], 1 mg/kg per day) was administered, but neither renal function nor urinary protein improved. She then became nephrotic and her renal function gradually deteriorated. To our knowledge, among uncommon glomerulonephritides with sarcoidosis, five cases of immune complex glomerulonephritis with IgM deposition have been reported. Immune complex glomerulonephritis with IgM deposition is unusual and could be related to sarcoidosis; it may be a characteristic pathology which could provide a clue to elucidate the pathogenesis of sarcoidosis.     

Glomerular diseases in children

A total of 411 children, aged from 0.3 to 18 years, suffering from glomerular diseases, were studied by renal biopsy between 1976 and 1985. The clinical presentation included nephrotic syndrome (79% of cases), renal failure (43%), and arterial hypertension (38%). In all, 177 cases presented with primary nephrotic syndrome; all had complicated courses and most were either corticosteroid-dependent or-resistant. Only 26.6% had minimal change disease on renal biopsy; 56.5% had focal-segmental sclerosis; and immunofluorescent deposits were observed in half of the group. Acute poststreptococcal (36 cases), mesangiocapillary (80 cases), and lupus (34 cases) glomerulonephritis occurred frequently; IgA glomerulopathy (10 cases) and haemolytic uraemic syndrome (6 cases) were uncommon. Glomerular crescents were observed in 71 cases. These observations illustrate the types of glomerular diseases seen in Iranian children.     

Long-term outcome of adult-onset minimal-change nephropathy

BACKGROUND.: Adult-onset minimal-change nephropathy has been associated witha slower response to corticosteroids and a less benign prognosiswhen compared to children. However, there are few long-termoutcome data reported. METHODS.: We have reviewed retrospectively 51 idiopathic adult-onset minimal-changenephropathy patients investigated and treated at a single centre. RESULTS.: Male to female ratio was 1:1.4, mean age at diagnosis was 37years, and average length of follow-up was 14.1 years. Significantcomorbidity was identified in 33%. A raised serum creatininewas found in 55% but returned to normal almost invariably uponremission. At presentation, hypertension was found in 47% ofpatients, microscopic haematuria in 33%, hypercholesterolaemiaand hypertriglyceridaemia in 96%, and hyperuricaemia in 42%.Remission (complete or partial) was achieved by 46, 70 and 92%within 4, 8 and 21 weeks respectively, in patients treated withsteroids; steroid resistance was encountered in 8%. The timeto remission was positively correlated with age (P=0.002) andinitial albumin level (P=0.005), and negatively correlated tothe number of subsequent relapses (P=0.029); 33% of patientshad a spontaneous remission at some time during the diseasecourse. Patients with multiple relapses were treated with cyclophosphamideand 63% of them had remained in remission after 5 years. Hypertensionwas present in 25% of patients after an average interval of11 years. At the time of the final follow-up, only three patientshad a raised creatinine and all but three patients were in completeremission. CONCLUSIONS.: Adult-onset minimal-change nephropathy shares the same goodlong-term outcome as the childhood counterpart, with sustainedremission and preserved renal function.