Membranous nephropathy. Long-term follow-up and association with neoplasia.

Sixty-six patients of all ages whose renal biopsy appearances satisfied strict criteria for the histopathological diagnosis of membranous nephropathy were studied and followed for a mean of 5-4 years (range 1 to 20 years). From initial investigation seven patients were found to have associated neoplasia, and in two patients the condition followed treatment with a mercurial diuretic and gold. One patient was Australia antigen positive. Two patients developed renal vein thrombosis, but in both this appeared to follow not precede their nephrotic syndrome. In the remaining 56 patients there was no associated factor. During the follow-up period, approximately one-quarter of the patients (15) died, nine from renal failure; one-quarter (10) had a persistent nephrotic syndrome, another one-quarter (15) proteinuria of lesser degree. The final one-quarter (16) are now in complete remission. The prognosis of the 54 patients with an initial nephrotic syndrome was poorer than the 12 with lesser proteinuria and no oedema at onset; five of 11 children were in complete remission when last seen. All but one of the nine patients who developed terminal chronic renal failure 4 to 18 years from onset had an unremitting nephrotic syndrome, eight of the 10 currently alive with a persistent nephrotic syndrome have reduced renal function. Renal functional deterioration did not occur in the absence of proteinuria. There was only slight correspondence between the stage of biopsy appearance, glomerular filtration rate at time of biopsy, time of the biopsy from apparent onset, or status at last follow-up. Staging is therefore of limited prognostic value. Twenty-two patients were treated with corticosteroids for 2 to 36 months; we detected no short or long-term benefit when compared to patients not so treated.     

Restrictive use of immunosuppressive treatment in patients with idiopathic membranous nephropathy: high renal survival in a large patient cohort

BACKGROUND: Immunosuppressive treatment initiated at an early stage in patients with idiopathic membranous nephropathy (iMN) improves renal survival. Treatment should ideally be restricted to high-risk patients. AIM: To evaluate the efficacy of a restrictive immunosuppressive treatment strategy for patients with iMN. DESIGN: Prospective cohort study evaluating a predefined treatment protocol. METHODS: From 1988, we adopted a restrictive treatment strategy: immunosuppressive treatment, mainly consisting of cyclophosphamide and steroids, was advised only in patients with renal insufficiency or severe intolerable nephrotic syndrome. We evaluated this strategy in a large patient cohort. To exclude any bias, we included all adult patients with iMN biopsied in the study period with a serum creatinine (Scr) < 135 micromol/l, a proteinuria > or = 3.0 g/day and/or a serum albumin (Salb) < or = 30 g/l at the time of biopsy. Analysis was according to the intention-to-treat principle. RESULTS: We studied 69 patients. At the time of biopsy, mean age was 51 years, Scr 90 micromol/l, Salb 23 g/l and proteinuria 6.7 g/day. Average follow-up was 5.5 years. Thus far 33 (48%) patients have received immunosuppressive therapy, mainly because of renal insufficiency (n = 24). Status at the end of follow-up was: complete remission n = 22 (32%), partial remission n = 24 (35%), nephrotic syndrome n = 15 (22%), persistent proteinuria n = 1 (1.4%), ESRD n = 6 (8.7%), death n = 1 (1.4%; due to bladder carcinoma after cyclophosphamide therapy). Patient survival was 100% at 5 and 7 years. Renal survival was 94% at 5 years and 88% at 7 years. DISCUSSION: In patients with iMN, a restrictive treatment policy assures a favourable prognosis, while preventing exposure to immunosuppressive therapy in >50% of the patients.     

Progression and Remission in the Nephrotic Syndrome Associated with Quartan Malaria in Uganda

The clinical history of the nephrotic syndrome associated withquartan malaria in Uganda has been defined by analysis of agroup of 115 patients. This group was derived from 156 patientswho presented with the nephrotic syndrome by the exclusion ofall patients in whom there were reasons to suspect that theaetiology was other than malarial. Despite a common immunopathologicalmechanism the clinical history varied. The prognosis was foundto be related to the appearance of the initial biopsy. The over-allmortality was 24 per cent, 26 per cent remained in protein-freeremission when last seen, and the remainder had persistent proteinuria.The potential for remission was related to the severity of theglomerular changes seen in the initial biopsy and remissiononly occurred in patients whose initial biopsy showed mild proliferativechanges. Full remission with loss of proteinuria was associatedwith the disappearance of protein deposits demonstrable by immunofluorescence, and occurred without substantial alteration inthe glomerular changes on light microscopy. Progression to renalfailure and death was only seen in those patients whose initialbiopsy showed marked glomerular proliferation or membrano proliferativechanges. Partial remission to light proteinuria whether it occurredspontaneously or following treatment conferred a definite improvementin the prog nosis. Assessment of the value of treatment withimmuno-suppressive drugs and other agents both of this disease,and also, possibly, of other types of glomerulo nephritis causedby soluble complexes, must take into account the value of apartial remission and the limited potential for healing in thosepatients with marked glomerular changes. ¹ Present address: St. Thomas's Hospital, London, S.E. 1.     

Schonlein--Henoch Nephritis

We report the clinical and laboratory findings of 88 patientswith renal manifestations of Schönlein-Henoch syndrome,all of whom were studied by renal biopsy. Sixty-six were referredto us from other centres because of diagnostic or therapeuticproblems. The patients' ages ranged from two to 19 years. Evidenceof recent streptococcal infection was obtained in 33 children,but their illness was indistinguishable from that of the remainder.Serum C3 levels were normal in all patients. Differential renalclearances of plasma proteins showed moderately or poorly selectiveproteinuria in most patients and appeared to have little prognosticvalue. The clinical manifestations of renal involvement were usuallyapparent early in the course of the illness, occurring withinone month of onset in 75 patients. They ranged in severity frommicroscopic haematuria alone to a nephrotic syndrome which oftenfollowed an acute nephritic onset. Children with severe renalinvolvement tended to be older and to have more prolonged systemicmanifestations, as well as troublesome alimentary symptoms. Light microscopy of renal biopsy specimens revealed minimalchanges in 15 patients, the remainder showing proliferativeglomerulonephritis ranging in severity from minor lesions offocal distribution to diffuse involvement, including crescents.The Electronmicroscopic appearance in specimens from 33 patientsis also described. The duration of follwup ranged from three months to 16 yearsfrom onset. Three children died within nine months of onset;of 59 survivors who were followed up for more than two yfiirs,34 were normal when last seen, 17 had minor urinary abnormalities,six had heavy proteinuria with or without hypertension, andtwo had deteriorating renal function. It was not possible todemonstrate any favourable effect of corticosteroids or cytotoxicdrugs, used singly or in combination. There was a fairly good correlation between the severity ofclinical presentation and the morphological appearances. Nochild with microscopic haematuria alone showed more than minorfocal lesions while, on the other hand, the occurrence of epithelialcrescents in more than 45 per cent of glomeruli was invariablyassociated with a nephrotic syndrome. A clinical presentationwhich included both nephritic and nephrotic features, and theinvolvement of more than 45 per cent of glomeruli with crescentswere identified as the two factors of greatest prognostic significance. ¹Present address: Department of Paediatrics and Child Health,27 Blundell Street, Leeds LS1 3ET ²Present address: Derbyshire Children's Hospital, North Street,Derby     

The Nephrotic Syndrome in Adults with 'Minimal Change' Glomerular Lesions

We describe 49 patients who developed a nephrotic syndrome afterthe age of 15 years, and who showed a ‘minimal change’pattern in their renal biopsies. Patients with sclerosing lesionsaffecting only part of the glomerulus were excluded, but 39biopsies showed some minor changes. Glomerulosclerosis affectingwhole glomeruli was present in 21 biopsies, and related stronglyto increasing age. Focal tubular atrophy and vascular changeswere also common but less related to age. Mesangial matrix increasewas not age-related, and presumably is a component of the glomerulardisease. At onset, these patients showed features differing from thosefound in nephrotic children with similar histology: the sexincidence of the adults was equal, non-selective differentialprotein clearances (51 per cent) hypertension (31 per cent)and diminished renal function (70 per cent) were all more common.No clinical tests distinguished these patients clearly fromother adult nephrotics, and renal biopsy remains essential intheir management. The subsequent behaviour of the adult patientshowever, resembled that of the childhood group very closely.Forty four patients were treated with prednisolone for at leasteight weeks, and 82 per cent responded with early loss of proteinuria.Of the 36 responding patients, 70 per cent later relapsed, 63per cent repeatedly. Five corticosteroid-resistant, and 12 corticosteroidintolerantpatients were treated with cyclophosphamide: one died aftera pulmonary embolus, but 14 lost their proteinuria and 11 remainin remission. Follow-up data were available for all 49 patients for up to19 years (mean 4.1 years). Nine patients were dead, only onein uraemia but three from probable complications of treatment.Ten still relapse and require corticosteroid treatment, butonly one now has persistent symptomless proteinuria. Twenty-nineare well, off all treatment.     

Proteinuric Glomerular Disease in Adults: Cumulative Life Tables over Twenty years

Outcome in 425 patients with persistent proteinuria has beenassessed over a period of five to 20 years. Nephrotics and non-nephroticsare analysed separately. Clinical and laboratory findings donot correlate with renal histology. Seventy-eight patients had minimal histological lesions andfour died (only one in renal failure). Fifty-one patients hadendothelial cell proliferation, and 20-year survival was 70per cent; renal failure occurred within five years in all 17who progressed, and was independent of nephrotic status. Inboth membrano-proliferative disease (98 patients) and membranousglomerulopathy (59 patients) 20-year survival was 20 to 30 percent. Epithelial cell proliferation (85 patients) had the worstprognosis, and survival after 12 years was negligible. In these last three groups decay in survival was almost linearagainst time and independent of nephrotic status. In focal proliferativedisease 20-year survival in nephrotics (31 patients) was only30 per cent, contrasting with non-nephrotics (23 patients) with80 per cent survival. Of 105 patients presenting with proteinuria without symptoms,in 30 the proteinuria was postural and biopsies were not done.The other 75 showed a range of histological changes and prognosissimilar to the group with symptoms.     

Idiopathic Membranous Nephropathy

The clinical and histopathological features of 37 patients withidiopathic membranous nephropathy are presented. Males werefour times as commonly affected as females and the age at presentationranged from nine to 70 years. The period of observation variedfrom three months to 23 years. Twenty-eight patients (76 percent)presented with the nephrotic syndrome and nine patients (24per cent) presented with non-nephrotic proteinuria. At the endof the study, of the patients presenting with the nephroticsyndrome, seven (25 per cent) were in remission, seven (25 percent) remained nephrotic, nine (32 per cent) showed only proteinuriaand five (18 per cent) were dead or on dialysis. Altogethereight patients (28 per cent) developed renal failure. The ninepatients who presented with non-nephrotic proteinuria appearedto do better, and none developed renal failure. The occurrence of spontaneous remission makes assessment ofbenefit from immunosuppressivet herapy difficult. However, analysisof our data and a review of the literature suggest that in thiscondition oral prednisone, cyclophosphamide and azathioprinehave no significant therapeutic properties. Histological assessment confirmed the occurrence of mild (Grade1) changes in patients biopsied soon after presentation, andtubular atrophy increased with the duration of illness. Immunofluorescenceconfirmed deposition of mainly IgG and complement. Repeat biopsiesin 14 patients showed no histological improvement and remissionwas not accompanied by resolution of histological abnormalities.     

Nephrotic syndrome and acute interstitial nephritis associated with the use of diclofenac.

Commonly reported renal complications of non-steroidal anti-inflammatory drugs (NSAID) include acute renal failure and/or acute interstitial nephritis; in rare cases a nephrotic syndrome was also observed. In most cases this was due to the development of secondary membranous nephropathy. Following withdrawal of the drug the nephrotic syndrome usually resolved rapidly. We report a 65-year-old woman who developed a nephrotic syndrome and acute renal failure during 6 months of treatment with the NSAID diclofenac. Renal biopsy revealed both, membranous nephropathy and interstitial nephritis. After discontinuation of diclofenac and treatment with prednisone 1 mg/kg/day, furosemide 400 mg/day and simvastatin at a dose of 20 mg/day, creatinine clearance gradually increased and after 5 months of treatment complete remission of the nephrotic syndrome was observed.     

Proteinuric glomerular disease in adults: cumulative life tables over twenty years

Outcome in 425 patients with persistent proteinuria has been assessed over a period of five to 20 years. Nephrotics and non-nephrotics are analysed separately. Clinical and laboratory findings do not correlate with renal histology. Seventy-eight patients had minimal histological lesions and four died (only one in renal failure). Fifty-one patients had endothelial cell proliferation, and 20-year survival was 70 per cent; renal failure occurred within five years in all 17 who progressed, and was independent of nephrotic status. In both membrano-proliferative disease (98 patients) and membranous glomerulopathy (59 patients) 20-year survival was 20 to 30 per cent. Epithelial cell proliferation (85 patients) had the worst prognosis, and survival after 12 years was negligible. In these last three groups decay in survival was almost linear against time and independent of nephrotic status. In focal proliferative disease 20-year survival in nephrotics (31 patients) was only 30 per cent, contrasting with non-nephrotics (23 patients) with 80 per cent survival. Of 105 patients presenting with proteinuria without symptoms, in 30 the proteinuria was postural and biopsies were not done. The other 75 showed a range of histological changes and prognosis similar to the group with symptoms.     

The Natural History of Diabetic Renal Disease: A FOLLOW-UP STUDY OF A SERIES OF RENAL BIOPSIES

Thirty-one diabetics, on whom renal biopsies had been performedapproximately 11 years previously, were reviewed in order todetermine the natural history of diabetic renal disease overa long period. At the time of biopsy it was shown that neitherrenal function nor proteinuria was closely related to the histologicalchanges. Although all those with heavy proteinuria had advancedrenal changes, some patients with serious biopsy lesions hadno proteinuria. The worst prognosis was demonstrated among those patients withmarked (Grade II and Grade III) renal changes when this wasassociated with heavy proteinuria (more than 3 g per 24 hours):all such patients died during the follow-up period, usuallyfrom renal failure. When proteinuria was smaller in amount theprognosis was variable, regardless of the histological changes,and renal function sometimes remained unaltered for many years. The factors responsible for the onset of rapid deteriorationof renal function are not known. Hypertension was a late featureand was not usually demonstrated until the renal failure wasquite advanced. Both the age of the patients and the durationof the diabetes seemed unrelated to the prognosis. Impairment of vision due to advanced diabetic retinopathy wasa fairly constant accompaniment of chronic renal failure, andtogether with coronary artery disease, makes the value of chronicdialysis and transplantation in such patients rather uncertain.     

Nephrotic range proteinuria--a good predictive index of disease in IgA nephropathy?

A combined retrospective and prospective study of 86 patients with IgA nephropathy was conducted to determine whether the level of proteinuria was a good predictive index of progressive disease. The patients fell into three groups: Group A, 31 patients with proteinuria of less than 1 g/day, Group B, 31 patients with proteinuria of 1 to 3.5 g/day; and Group C, 24 patients with proteinuria of more than 3.5 g/day. The groups are comparable in age of presentation, sex ratio, and duration of study and showed no difference in serum creatinine levels, creatinine clearance, incidence of hypertension or incidence of impaired renal function. Compared with the patients in the other groups, those in Group C did not have increased incidence of progressive disease. Nevertheless, they have a higher incidence of nephrotic syndrome (p less than 0.001), a lower incidence of macroscopic haematuria (p less than 0.05), lower serum albumin (p less than 0.05) and heavier proteinuria (p less than 0.01). Severity of proteinuria had no significant correlation with the severity of renal histopathologic changes. Clinical observations divided the 24 patients with nephrotic range proteinuria into three well-defined groups with different prognoses. Six patients had progressive disease with decreasing proteinuria. Five of these remained hypertensive and their initial renal biopsy showed advanced pathologic changes. Thirteen patients had persistent proteinuria although the renal function remained unchanged. Three of these were treated with steroid but failed to respond, and their renal histopathologic changes were usually moderate. The remaining five patients showed good response to steroid treatment although two became steroid-dependent. Their renal histopathology showed mild alteration. Our findings suggest that severe proteinuria in IgA nephropathy does not inevitably indicate a poor prognosis.     

Morphogenesis and course of renal amyloidosis

Based on an analysis of the clinicolaboratory findings and morphological examination of 93 patients with renal amyloidosis the proteinuric stage was diagnosed in 24, the nephrotic in 35, and the azotemic in 34 patients. Elevation of the arterial blood pressure was revealed in 40% of the patients. During the first year since proteinuria was diagnosed, the nephrotic syndrome developed in 50% of the patients; renal failure in 75% of cases developed over 9 years. The 5-year survival since proteinuria was diagnosed amounted to 72%, the 10-year survival to 34%. The 5-year survival among patients with the nephrotic syndrome constituted 49%, whereas the 10-year survival was attained only in single cases. One year after blood creatinine became elevated only 30% of the patients were still alive. As the disease progressed, there was a gradual increase in amyloid impregnation of the glomeruli alone, while amyloidosis of the tubules was most pronounced in the nephrotic stage. No complete correlation was found between the gravity of the morphological picture of glomerular involvement and blood creatinine level which is undoubtedly influenced by alterations in the exoglomerular structures.     

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 beneficial effects of lymphocytapheresis for treatment of nephrotic syndrome.

A considerable permeability factor (or factors) derived from circulating T cells has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was followed with corticosteroid therapy with or without cyclosporine A in 5 patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a dramatic decrease of proteinuria (-30% and -94%) in their urine protein/creatinine ratio. Three out of 4 patients had a complete or partial remission (proteinuria <1g/day) within 8 weeks following immunosuppressive therapy. During the LCAP, T cells, especially activated T cells, decreased significantly in the response group. The other 2 patients, 1 with FSGS and 1 with MN, however, had no response to LCAP and following immunosuppressive therapy or low-density lipoprotein apheresis and suffered from end-stage renal failure or death by pneumonia. These results suggested that LCAP might have a beneficial effect on the treatment of NS, especially MCNS and in some patients with FSGS, despite varying responses to LCAP and concomitant immunosuppressive therapy.     

烷化剂在1例特发性膜性肾病合并肾病综合征的循证应用

目的报告应用烷化剂对1例特发性膜性肾病(IMN)合并肾病综合征(NS) 患者进行的循证治疗过程。方法计算机检索Cochrane图书馆(2005年第3期)、MEDLINE(1978-2005)、 CBM disc(1978～2005),查找烷化剂治疗IMN合并NS及与病情缓解有关的系统评价、临床随机对照试验等,获取最佳证据用于临床治疗。结果高质量的临床证据表明,烷化剂能明显提高IMN合并NS患者蛋白尿的完全缓解率,其中糖皮质激素 环磷酰胺(MP CTX)的方案是较安全和有效的,但其能否提高肾脏的长期存活率尚不确定。据此,笔者结合临床经验及患者意愿,对患者实施MP CTX免疫抑制治疗,6个月后患者蛋白尿情况有所缓解,目前仍在随访中。结论 MP CTX方案能明显提高IMN合并NS患者的蛋白尿缓解率,但能否提高患者肾脏长期存活率,尚有待进一步观察。     

Treatment and outcome of adult patients with primary focal segmental glomerulosclerosis in five UK renal units

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the least studied of the causes of idiopathic nephrotic syndrome, and there are few specific guidelines for treatment. AIM: To review data from five UK renal units to investigate whether adult patients with FSGS were treated uniformly, and to examine the effect of treatment on proteinuria and survival. DESIGN: Retrospective record review. METHODS: We examined electronic records of patients with idiopathic FSGS for information on baseline clinical parameters, treatment regimens and outcomes. RESULTS: Of 136 patients with primary FSGS and nephrotic range proteinuria, 76 (56%) were treated with prednisolone and of this group, 59% were treated with additional immunosuppression. Among the treated patients, the total remission rate (complete and partial) was 67%, and one hospital achieved a remission rate of 80%. Treated patients had a significantly higher remission rate than those who were not treated. Remission was associated with a 5-year survival off dialysis of 94%, compared with 53% if remission was not achieved. Baseline serum creatinine and remission were independently associated with survival off dialysis in a multivariate Cox proportional hazards model. DISCUSSION: Patients with primary FSGS and nephrotic range proteinuria, who are treated with corticosteroids, are more likely to enter remission than those who are not treated. Remission rates of up to 80% can be achieved with prolonged treatment, and remission is an independent predictor of survival off dialysis. Patients who do not achieve remission have a poor prognosis. Further clarification of optimal treatment regimens requires additional, prospective studies.     

Types of lupus nephritis exacerbations: prognostic significance

AIM: To characterize the course of lupus nephritis (LN) in terms of demographic indices (sex, age of renal disease onset), the presence of antiphospholipid syndrome (APS) and to ascertain a prognostic role of the disease exacerbations. MATERIAL AND METHODS: A total of 121 LN patients were followed up from 1997 to 2004 (mean duration of the follow-up 5.6 +/- 6.4 years). A LN course was characterized by the presence of a complete or partial remission, exacerbation of the disease, repeated hospitalisations. Two types of exacerbations were considered: proteinuric, running with progressive proteinuria and normal renal function (type 1); functional, running with elevation of blood creatinine (type 2). RESULTS: Exacerbations were observed in one third of the examinees, 70% of them ran with renal dysfunction. Exacerbations occurred more frequently in males than in females (50 vs 27%, respectively; p = 0.08) and in patients with early onset of LN (at the age of 40 years and younger, 80 vs 60%, respectively; p < 0.05). Exacerbations of type 2 occurred in males, in patients with early onset of renal damage and in APS association. It is shown that LN exacerbations, their incidence and type (a functional type) have a negative influence on renal survival of the patients. CONCLUSION: Identification of groups of LN patients at high risk of exacerbations and unfavourable prognostic role of exacerbations dictates the necessity of due immunosuppressive therapy for maintenance of remission.     

The course and prognosis of mesangioproliferative glomerulonephritis

AIM: A retrospective analysis of a clinical course of mesangioproliferative glomerulonephritis (MPGN) in patients with glomerular deposition of IgA (IgA nephropathy--IgA-N), with glomerular deposition of other Ig to determine prognostic factors of MpGN progression including IgA-N and to examine the patients' sensitivity to immunodepressive therapy. MATERIAL AND METHODS: 2000 patients with primary MPGN followed up from 1980 to 1999 from the disease onset to development of chronic renal failure (creatinine > 2.5 mg%). Factors affecting kidney survival were studied using the Cox regression model, factors predicting sensitivity to immunodepressive therapy--using multiple logistic regression. RESULTS: IgA-N differed by the course and prognosis from other forms of MPGN. In IgA-N urinary syndrome and macrohematuria were encountered more frequently, in other forms of MPGN more frequent was nephrotic syndrome. Prognosis of patients with IgA-N was worse than in MPGN patients without IgA deposition: 10-year "renal survival" (creatinine < 2.5 mg%) was 64 and 97% (p < 0.05), respectively. Prognosis-deteriorating factors for MPGN patients were the following: male sex, nephritis onset in 40-year-olds and older subjects, acute nephritic syndrome (creatinine > 1.5 mg%), high proteinuria, hematuria (> 50 in sight), the presence of synechia and TIC in renal biopsy, location of immune deposits both in the mesangium and basal glomerular membranes. The responders to the immunodepressive therapy had 10-year renal survival 100%. Positive results of immunodepressive therapy were observed significantly more frequently in patients with normal level of creatinine, moderate hematuria, absence of synechias and TIC in renal biopsy, given large total course dose of corticosteroids and cytostatics. Efficiency of oral cyclophosphamide and its intravenous pulse-therapy did not differ significantly. In pulse therapy an average cumulative dose was lower 6 times, side effects occurred 3 times less frequently. CONCLUSION: The importance of morphological information for prognosis and predicting sensitivity of MPGN patients to immunosuppressive therapy necessitates renal biopsy before therapy. Intravenous pulse therapy with cyclophosphamide is preferable as an active treatment in patients with sclerosis in renal biopsy.     

雷公藤多苷片联合缬沙坦治疗IgA肾病蛋白尿的疗效

目的探讨雷公藤多苷片联合缬沙坦治疗IgA肾病蛋白尿的临床疗效。方法将23例原发性IgA肾病患者（24 h尿蛋白定量1.0～3.0 g.d-1）按随机数字表法分为观察组12例与对照组11例。对照组给予缬沙坦胶囊80～160 mg,1次.d-1,顿服;观察组在此基础上给予雷公藤多苷片1 mg.Kg-1.d-1,分3次口服。疗程均为3个月。比较2组治疗后24 h尿蛋白定量缓解情况。结果对照组完全缓解1例,显著缓解3例,部分缓解3例,无效4例,总有效率63.64%。观察组完全缓解3例,显著缓解5例,部分缓解4例,无效0例,总有效率100.00%。2组总有效率相比差异有统计学意义（χ2=5.282,P=0.037）。结论雷公藤多苷片联合缬沙坦治疗IgA肾病蛋白尿的临床疗效确切,能更好地降低IgA肾病患者蛋白尿水平,保护患者的肾脏功能,且不良反应少。     

Treatment of Idiopathic Membranous Nephropathy. Is the Anti-CD20 Antibody Rituximab a Reasonable Option?

BACKGROUND: Membranous nephropathy (MN) is characterized by proteinuria and other symptoms of the nephrotic syndrome. In many cases, the etiology is unknown. Whether and how to treat MN is still a controversial question. Despite the use of corticosteroids and alkylating agents, up to 40% of patients still progress to end-stage renal failure. CASE REPORT: A 40-year-old male patient with biopsy-proven idiopathic MN was initially treated with prednisolone and chlorambucil because of a proteinuria of 22 g/d. Treatment with cyclosporine was started because the nephrotic syndrome failed to improve. Proteinuria was reduced to a minimum of 4 g/d. Cyclosporine was stopped after 17 months leading to a fast relapse. Therapy with an ACE inhibitor and AT(1) receptor antagonist and retreatment with cyclosporine improved proteinuria. Cyclosporine was terminated after a total of 24 months. 5 months later, relapse occurred with a high proteinuria of 34 g/d. The monoclonal anti-CD20 antibody rituximab (375 mg/m(2)) was given four times every 4 weeks. 4 weeks and 4 months after the end of treatment, proteinuria decreased to 780 mg/d and < 150 mg/d, but renal function remained impaired (creatinine clearance 65 ml/min, stage 2 according to K/DOQI). Now, remission of proteinuria (< 150 mg/d) has been stable for almost 2 years. However, renal insufficiency progressed further (creatinine clearance 45 ml/min, stage 3 according to K/DOQI). CONCLUSION: Rituximab offers the possibility for a targeted treatment of idiopathic MN. Based on the existing evidence and experience from this case, rituximab can be recommended as a new treatment option for MN, possibly before starting any treatment with cytotoxic agents and high-dose prednisolone carrying the risk of severe side effects. However, long-term results of this treatment are still lacking.