Idiopathic membranoproliferative glomerulonephritis in Japanese children

The course of idiopathic membranoproliferative glomerulonephritis (MPGN) in 41 Japanese children (21 boys, 20 girls) is reported. The mean follow-up period was 8 years, 9 months; 29 children with MPGN (71%) were identified by school urinary screening; 32 patients had type I MPGN, 2 type II and 7 type III; 10 patients were treated with multiple low-dose cocktail therapy (MLD), 8 with MLD followed by high-dose alternate-day (ALD) prednisolone and 21 with high-dose ALD prednisolone alone. In 1 patient, MPGN progressed to end-stage renal failure. The serum creatinine level in all of the remaining 40 patients was ≤ 1.3 mg/dl at the last follow-up. Urinalysis was normal in 24 (59%). Of the 17 patients who still had urinary abnormalities, 4 had nephrotic syndrome. The incidence of remission of urinary abnormalities was highest in the patients treated with high-dose ALD prednisolone. Rebiopsy was performed in 33 patients, and revealed slight histological improvement in 11 (33%) patients, moderate improvement in 8 (24%), marked improvement in 5 (15%) and deterioration or no improvement in 9 patients (27%). Relatively few side effects of treatment were observed. The superior outcome of the MPGN patients in this compared with other studies may be the result of earlier detection and treatment.     

Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk

Previous studies suggested that membranoproliferative glomerulonephritis (MPGN) type II has a worse renal survival and an unacceptable risk of recurrence post transplantation. We hypothesised that other factors may determine this risk. We analysed all cases (n=70) of MPGN diagnosed by renal biopsy in Ireland from 1972 to 1995. We used Cox regression analysis to determine factors that were independently predictive of renal failure. MPGN II had more crescent formation and mesangial proliferation (P<0.05). Mean follow-up duration was 13.8 years, during which time 41 (58.6%) developed end-stage renal failure (ESRF). The median time to ESRF was 8.3 years (95% confidence interval 5.7-10.9) and 5-, 10-, and 20-year probabilities of ESRF were 32, 54, and 70%, respectively. Multivariate analysis revealed that severity of interstitial fibrosis (P<0.05), crescent formation (P<0. 01) and mesangial proliferation (P<0.05) were independently associated with ESRF. Decade of diagnosis, age, MPGN type, and creatinine or complement level at baseline did not predict renal survival in this model. In 21 (49%) of the 43 renal transplants, MPGN recurred. Younger age at initial diagnosis (P<0.01) and the presence of crescents on the original biopsy (P<0.005) were independently associated with recurrence on multivariate analysis. MPGN type was not associated with recurrence in this model. Contrary to previous reports, after controlling for crescent formation, MPGN II was not associated with more ESRF or recurrence in the allograft. It is therefore the more aggressive glomerular changes associated with MPGN II, rather than the disease type per se, that determine outcome.     

Postpartum renal failure in a patient with membranoproliferative glomerulonephritis type II

The previously reported detrimental effects of pregnancy on the course of membranoproliferative glomerulonephritis type II (MPGN type II) are limited and are usually considered to be mild. Based on these reports, a 19-year-old female with the diagnosis of MPGN type II who had stable renal function (creatinine 0.9 mg/dl) and a mild nephrotic syndrome with hypertension for 5 years of close follow-up was advised to complete her pregnancy. After a full-term pregnancy, complicated only by moderate nephrotic syndrome, a healthy female infant was born. Two weeks after delivery, the patient presented with acute renal failure and malignant hypertension, without evidence of hemolysis of hepatic failure. Immunologic parameters, including, C3, C4, antinuclear antibodies, circulating immune complexes as well as antibodies to glomerular basement membrane antigen and tubular basement membrane antigen were negative. Peritoneal dialysis was initiated and a renal biopsy was performed which showed MPGN type II with 50% crescents. Despite pulse therapy with methylprednisolone, renal function did not improve, resulting in the need for chronic dialysis. Although no specific nephritogenic mechanism was shown, the course of this patient should be considered when counseling female patients with MPGN type II, regarding the possibility of pregnancy exacerbating their disease, or resulting in rapidly progressive renal failure.     

Results of a controlled drug trial in membranoproliferative glomerulonephritis

A prospective randomized drug trial was carried out on 59 patients with confirmed membranoproliferative glomerulonephritis (MPGN). The treatment group (27 patients) received cyclophosphamide, coumadin, and dipyridamole for 18 months, and the control group (32 patients) received no specific therapy. Complications of the renal disease such as hypertension and fluid retention were treated similarly in both groups. Entrance criteria included confirmed renal pathology demonstrating either types I or II MPGN, a corrected creatinine clearance (CCr) of less than 80 ml/min/1.73 m2, and/or proteinuria greater than 2 g/day. Actuarial survival was not different between the treatment and the control groups in either MPGN type and was 85% in type I and 90% in type II at 2 years. The change in renal function, as measured by both the slope of CCr and the plasma creatinine reciprocal (1/Cr) at 6, 12, and 18 months was not significantly different between treatment and control groups in either types I or II when tested by both parametric and nonparametric analysis. The age, sex, and initial level of CCr did not influence the rate of decline. Control and treatment group proteinuria was not different at any time point in either types I or II MPGN. The small numbers of type II MPGN cases do not give sufficient power to allow conclusions regarding this therapy in type II. We can conclude that this treatment is ineffective in altering the natural history of type I MPGN.     

Comparison of pulse and oral steroid in childhood membranoproliferative glomerulonephritis

BACKGROUND: There has been no controlled study comparing efficacy of pulse versus oral steroid therapy in childhood membranoproliferative glomerulonephritis (MPGN). This study aimed to compare these therapies and renal outcome over a long-term period for MPGN. METHODS: Outcome measures in 11 patients with MPGN treated with pulse methylprednisolone (MP) were compared with 8 patients with MPGN treated with oral prednisolone (P). RESULTS: Nineteen children with idiopathic MPGN (mean age 9.75 years, range 3.7-14 years) were followed for a mean period of 68.21 months (range 4-124 months). Both treatment groups were similar in demographic, clinical, laboratory and histopathological characteristics on presentation. In the pulse MP group, only 1 patient out of 11 progressed to end-stage renal failure (ESRF), compared with 4 patients out of 8 in the oral P group (p=0.041). For long-term renal survival, those patients with more than 8 years of follow-up were further evaluated. Twelve patients had completed 8 years of follow-up; in the pulse MP group, 1 of 7 patients, compared with 4 of 5 patients in the oral P group progressed to ESRF (p=0.039). Chronic damage in the presentation biopsy and lack of remission in patients with nephrotic syndrome (NS) were positively associated with adverse renal outcome (p=0.02, p=0.006, respectively). CONCLUSIONS: Pulse MP therapy may be superior to oral P therapy in children with MPGN in preserving renal function without any increase in steroid-related side effects. Chronic damage in the presentation biopsy and lack of remission of NS are adverse features.     

Development of hypertension in IgA nephropathy as a marker of a poor prognosis

We have studied 209 patients with IgA nephropathy. 26 were hypertensive at the time of renal biopsy, and 59 patients developed hypertension during follow-up. Survival statistics show that only 45% of the patients will remain normotensive 10 years after renal biopsy. The presence of hypertension at renal biopsy correlated well with the usual parameters of a poor prognosis. The same markers predicted a later development of hypertension in patients who were normotensive at the time of renal biopsy. When hypertension is established, the prognosis is poor. Three years after diagnosis of hypertension, the renal survival was found to be 70% in the 59 patients we have followed. It is also possible that the markers of a poor prognosis actually predict the progression rate rather than the prognosis, because in time, some patients with initially mild manifestations of the disease will progress to end-stage renal failure.     

Long-term follow-up of Argentinean patients with hemolytic uremic syndrome who had not undergone dialysis

We examined the records of patients with hemolytic uremic syndrome, who had not undergone dialysis during the acute stage, with the aims of evaluating: (1) the outcome after at least 5 years of follow-up; (2) the value of peak serum creatinine as a prognostic marker; (3) the relationship between outcome and time to normalization of renal function. From 1968 to 2000, 1,179 patients were assisted. Forty-two patients (3.6%) died during the acute stage, 478 patients (40.5%) required dialysis and 659 patients (55.9%) did not undergo dialysis; 529 non-dialysis patients were lost to follow-up. The remaining 130 patients were classified into four groups: group I, complete recovery; group II, with two subgroups, IIa, microalbuminuria, and IIb, proteinuria and/or high blood pressure, both with normal renal function; group III, chronic renal failure; and group IV, end-stage renal disease. We analyzed the relationship between final outcome and: (1) peak creatinine (the highest of at least two determinations) during the acute stage and (2) time to normalization of urea and/or creatinine after the acute stage. After a mean follow-up time of 147.1 months (range 60-362 months), group I had 83 patients (63.9%), group IIa had 27 (20.8%), group IIb had 15 (11.5%) and group III had 5 (3.8%). The value of peak serum creatinine concentration was available for 57 patients. On the last clinical visit, eight out of 26 (30.7%) patients with peak serum creatinine equal to or higher than 1.5 mg/dl were in groups IIb and III versus one out of 31 (3.2%) patients with lower values (P < or = 0.007). Finally, six out of 28 patients (21%) whose renal function had normalized after 15 days from diagnosis were in groups IIb-III versus 8/82 (9.7%) whose renal function had normalized within 15 days (P = 0.18). After a mean period of follow-up of 12 years, 15% of a selected patient group had developed proteinuria, high blood pressure or chronic renal failure, and 21% had developed microalbuminuria. Peak serum creatinine during the acute stage was useful as a prognostic indicator. Patients whose renal function required more time to normalize did not have a worse outcome.     

Effect of acetylsalicylic acid and dipyridamole in primary membranoproliferative glomerulonephritis type I

Primary membranoproliferativeglomerulonephritis (MPGN) has a poor long-termprognosis, with 40 per cent of patientsreaching end-stage renal failure after 10 yearsof observation. Approximately 35 per cent ofpatients die due to complications of thenephrotic syndrome. This study investigates theeffect of acetylsalicylic acid (ASA) combinedwith dipyridamole on proteinuria and renalfunction in nephrotic MPGN patients withnormal/moderately reduced glomerular filtration rate(GFR). Fourteen patients with biopsy-proventype I MPGN received ASA (1000 mg/day) anddipyridamole (300 mg/day) for 24 months.Proteinuria was reduced from 6.8 ± 2.4 g/dayto 1.1 ± 0.6 g/day (p < 0.001). Serumalbumin levels increased from 2.2 ± 0.5 g/dLto 3.7 ± 0.4 g/dL (p < 0.001) duringthe study period after 24 months compared tobaseline. Serum creatinine and GFR did notsignificantly change in patients treated withacetylsaliclylic acid and dipyridamole duringthe observation period (p < 0.05). Ourstudy suggests that ASA combined withdipyridamole significantly reduces proteinuria without impairing renal function in patientswith MPGN.     

Prognostic factors in children with membranoproliferative glomerulonephritis type I

The clinical outcome of patients with membranoproliferative glomerulonephritis (MPGN) varies, with some patients progressing to end-stage renal disease. The aim of this retrospective study was to analyze the initial clinical signs and laboratory test results associated with an MPGN prognosis. The study cohort consisted of 47 patients with idiopathic MPGN Type I treated at the National Institute of Pediatrics, Mexico City, between 1971 and 2001. The median follow-up was 3 years. The three different outcomes of interest were death, renal failure, and nephrotic syndrome. The patients’ ages ranged between 4 and 16 years. All patients had different degrees of proteinuria, hyperlipidemia, and microscopic/macroscopic hematuria, and 85.1% of them showed hypocomplementemia. Clinical outcomes varied, however, the most common was nephrotic syndrome, either alone or combined with other syndromes, which accounted for 74.5% of all cases. Fifteen patients died. Treatment with methylprednisolone improved the patient’s condition, while the use of chloroquine or cyclophosphamide worsened it. Twenty-two patients had some degree of renal failure; glomerular filtration rate (GFR) levels and albumin values were negatively associated to renal failure, while treatment with methylprednisolone decreased the probability of renal failure. Nephrotic syndrome persisted in 18 patients; hemolytic complement and hemoglobin values were negatively associated with nephrotic syndrome, while macroscopic hematuria was positively associated with it. Signs that suggested a poor prognosis during diagnosis were low GFR, low albumin, low hemolytic complement, and macroscopic hematuria. Treatment with methylprednisolone seemed to improve prognosis, however, this needs to be confirmed with randomized studies.     

Renal outcome of type 2 diabetes in South Africa--a 12-year follow-up study.

AIMS: Previous studies of type 2 diabetes mellitus have indicated a benign renal outcome after long-term follow-up. The aim of this study was to determine how often renal failure due to diabetic nephropathy was a cause of death in patients with type 2 diabetes. METHODS: Prospective observational study of 59 South African patients with type 2 diabetes over a 12-year period. During the study repeated clinical evaluations were accompanied by measurements of serum creatinine, serum cholesterol, random blood sugar, and urine protein/creatinine ratios. RESULTS: The mean duration of diabetes at the end of the study was 17.8 years. There was a wide variation in the time from clinical diagnosis of diabetes to macroproteinuria (mean 9.7 years, SD 5.9, range 0 - 21) and the rate of deterioration of renal function. This rate correlated with poor control of blood pressure, a glucose level of > 14 mmol/l, heavy proteinuria, a high retinopathy score, a body mass index of < 28 and the number of pack years of smoking. At the end of the study 47 patients (79.7%) had died. Of these deaths 17 (28.8%) were due to chronic renal failure. CONCLUSIONS: In contrast to other studies we have shown that in a developing country renal failure in type 2 diabetic patients is a major cause of death. Determining the prognosis for an individual patient is difficult as there are wide ranges in the time of onset of proteinuria, the rise in serum creatinine and the time to ultimate progression to end-stage renal failure.     

Recurrent membranoproliferative glomerulonephritis after second renal graft treated with plasmapheresis and rituximab

We present a case of a 45-year-old man who suffered from idiopatic membranoproliferative glomerulonephritis (MPGN) in the native kidney that relapsed after his first and second renal grafts. The patient was diagnosed in 1990 with lobular MPGN type I, receiving his first renal graft in 1996. In 2001, a biopsy showed recurrence of MPGN type I (rMPGN). He underwent a second renal graft in 2008. In January 2010, he experienced increased proteinuria and creatinine. Upon electron microscopy of a renal graft biopsy we diagnosed a new rMPGN. At the time of the biopsy, complement levels were normal, although C3 and C4 decreased further. We administered 12 plasmapheresis (PP) sessions and four doses of rituximab. Due to persistent renal impairment, we performed a new biopsy 3 months later, showing less severity of the acute lessions. He received a new cycle of treatment (PP + rituximab). One year later, his renal function was stable with a creatinine ranging between 2 and 2.5 mg/dL and a protein/creatinine ratio less than 1 mg/mg. We concluded that the treatment stopped the disease progression.     

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.     

Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy.

Nineteen patients with biopsy proven membranoproliferative glomerulonephritis type I (MPGN I) and a minimum of three years of follow-up (mean 6.5 +/- 0.7 years) have been treated with an uncontrolled regimen of limited corticosteroids. Initial therapy ranged from 20 mg per os (po) every other day to 30 mg/kg/day i.v. for three consecutive days, depending on clinical disease severity. Therapy was then decreased based on each patient's improving clinical status. At diagnosis creatinine clearance (CCr) was less than 80 ml/min/1.73 m2 in 12 patients and less than 50 in 2. All patients had hematuria and proteinuria, with 15 in the nephrotic range. Hypertension, present at diagnosis in 13, developed in five others following institution of prednisone, and was controlled medically. Renal biopsy was repeated after two years of therapy prior to cessation of treatment (mean total treatment duration 38 +/- 3 months). Follow-up biopsy revealed decreased glomerular inflammatory activity in 88% of patients. All patients have now been off prednisone for 40 +/- 9 months. The mean CCr is 126 +/- 5 ml/min/1.73 m2. Eight patients have normal urinalyses. These data suggest that early therapy with a limited course of corticosteroids, and control of associated hypertension, may forestall progressive renal insufficiency in children with MPGN type I.     

Long-term effects of arterial stenting on kidney function for patients with ostial atherosclerotic renal artery stenosis and renal insufficiency.

It is uncertain whether renal artery stent placement in patients with atherosclerotic renovascular renal failure can prevent further deterioration of renal function. Therefore, the effects of renal artery stent placement, followed by patency surveillance, were prospectively studied in 63 patients with ostial atherosclerotic renal artery stenosis and renal dysfunction (i.e., serum creatinine concentrations of >120 micromol/L (median serum creatinine concentration, 171 micromol/L; serum creatinine concentration range, 121 to 650 micromol/L). Pre-stent renal (dys) function was stable for 28 patients and declining for 35 patients (defined as a serum creatinine concentration increase of > or =20% in 12 mo). The median follow-up period was 23 mo (interquartile range, 13 to 29 mo). Angioplasty to treat restenosis was performed in 12 cases. Five patients reached end-stage renal failure within 6 mo, and this was related to stent placement in two cases. Two other patients died or were lost to follow-up monitoring within 6 mo, with stable renal function. For the remaining 56 patients, the treatment had no effect on serum creatinine levels if function had previously been stable; if function had been declining, median serum creatinine concentrations improved in the first 1 yr [from 182 micromol/L (135 to 270 micromol/L ) to 154 micromol/L (127 to 225 micromol/L ); P < 0.05] and remained stable during further follow-up monitoring. In conclusion, stent placement, followed by patency surveillance, to treat ostial atherosclerotic renal artery stenosis can stabilize declining renal function. For patients with stable renal dysfunction, the usefulness is less clear. The possible advantages must be weighed against the risk of renal failure advancement with stent placement.     

Changes in renal function in patients with familial amyloid polyneuropathy treated with orthotopic liver transplantation.

BACKGROUND: Familial amyloid polyneuropathy (FAP) is an autosomal dominant disease caused by a point mutation in the gene encoding transthyretin, which is secreted by the liver. Orthotopic liver transplantation (OLT) has been proposed to prevent disease progression. Little is known about long-term changes in renal function and lesions after OLT. METHODS: The renal function of 33 patients with FAP was evaluated (proteinuria, serum creatinine, creatinine clearance) before OLT and over a period of at least 5 years afterwards. A pre-transplantation renal biopsy was performed in 14 patients and a follow-up biopsy in eight patients. RESULTS: Before transplantation, mean serum creatinine concentration was 86 micromol/l (47-126 micromol/l) and creatinine clearance was 71.9+/-31.6 ml/min/1.73 m(2). Proteinuria was detected in 54% of patients (0.3-4 g/day). Pre-transplant renal biopsies (n = 14) revealed glomerular, tubular and vascular amyloid deposits in 90, 58 and 66% of patients, respectively. Eleven patients (33%) died after OLT. Death occurred most frequently in patients having weight losses >7 kg (P<0.05). After transplantation, 25 patients (76%) suffered acute renal failure but only one required dialysis. One month after transplantation, the mean serum creatinine concentration was 134.1+/-73 micromol/l and remained constant during follow-up. Eight patients underwent a second renal biopsy 2 years after transplantation. No significant changes in deposits or renal toxicity due to calcineurin inhibitors were detected. CONCLUSION: Although liver transplantation in FAP does not affect existing renal amyloid deposits, it prevents the progression of renal disease.     

Transition of children with membranoproliferative glomerulonephritis to adolescence and adulthood

Background Many chronic renal diseases in children, including membranoproliferative glomerulonephritis (MPGN), often continue into adulthood, and these patients require continuing management. Despite the importance of the topic, there has been limited discussion about the problems of transition in children with continuing renal disease. We report our experience in patients with MPGN, as they matured from childhood to adolescence and adulthood, so-called “carry-over” cases. Methods The clinical course of diffuse MPGN in 27 children was retrospectively reviewed. Patients were over 18 years old at the end of follow-up. Results The mean follow-up period was 12.6 years; 20 children (74%) were identified by school urinary screening. The clinical course was favorable, and none of the patients progressed to end-stage renal failure during follow-up. However, eight patients (30%) continued to demonstrate proteinuria; two patients were nephrotic. Four patients were non-compliant and discontinued medication by themselves. Three patients were still on low dose of alternate-day (ALD) prednisolone. Twenty patients finished the treatment and were followed for an average of 4.6 years. Only one demonstrated trace amounts of proteinuria 1 year after discontinuing ALD prednisolone. Conclusions MPGN often continues during maturation from childhood to adulthood, and patients are usually referred to adult nephrologists. Good communication between pediatric and adult nephrologists is important. In addition, more in depth explanation and reeducation about their disease and its management are helpful when these patients reach adolescence. These measures will improve their care and help to assure compliance with their medication regimen.     

Membranoproliferative glomerulonephritis and circulating cryoglobulins

Background

Previous studies on membranoproliferative glomerulonephritis (MPGN) and cryoglobulinemic glomerulopathy (CG) were based upon case series that were performed before hepatitis C virus (HCV) infection was routinely investigated. Therefore, it remains unknown how far HCV contributes to MPGN or CG, and there have only been a few reports about HCV-negative idiopathic MPGN.

Patients and methods

Thirty-five patients with MPGN diagnosed by renal biopsy who underwent examination for HCV infection at our institute between 1990 and 2008 were recruited for this study. Patients with HCV infection at presentation were included, but patients with complications such as underlying lymphoproliferative disorders, autoimmune diseases like lupus nephritis, infection, and liver disease due to hepatitis B virus or alcohol abuse were excluded. A total of 35 patients were enrolled and they were divided into two groups according to the presence/absence of circulating cryoglobulins (cryo). The 23 patients who had cryo-negative and HCV-negative idiopathic MPGN were divided into subgroups with type 1 and type 3 disease.

Results

In the cryo-positive group (n = 9), 7 patients were positive for HCV infection, while 2 patients were negative. In the cryo-negative group (n = 26), 3 patients were positive for HCV infection, while 23 patients were negative (idiopathic MPGN). Compared with the cryo-negative group, the cryo-positive group had several characteristics such as more severe thrombocytopenia, higher serum immunoglobulin (Ig)G and IgM levels, lower levels of hemolytic complement (CH50) and complement component (C)4, predominant IgM staining, and type 1 histology. Patients with cryo-negative and HCV-negative ‘idiopathic’ MPGN showed predominant staining for IgG in both type 1 and type 3 cases, unlike the predominant staining for IgM in the cryo-positive group. Compared with type 3 cases, type 1 cases had a younger age, lower levels of CH50, C3 and C4, and less proteinuria. In the cryo-positive group, 4 patients (44.4 %) died, with death from B cell lymphoma and liver failure in 2 patients each, while 1 patient (8 %) developed end-stage renal failure requiring dialysis. In contrast, all patients in the cryo-negative group remained alive during follow-up, although 4 patients (2 type 1 cases and 2 type 3 cases) required dialysis.

Conclusion

Cryo-positive MPGN shows a close relationship with HCV infection and IgM, resulting in a poor prognosis. Cryo-negative and HCV-negative idiopathic MPGN has a close relationship with IgG staining, and type 1 cases feature characteristics such as a younger age, more severe hypocomplementemia, and less proteinuria than in type 3 cases.     

Conservative versus immunosuppressive treatment of patients with idiopathic membranous nephropathy.

BACKGROUND: Treatment of idiopathic membranous glomerulonephritis (MGN) is a controversial issue. Whereas some authors recommend early immunosuppressive treatment of all patients with nephrotic syndrome, others do not support aggressive therapies, based on the spontaneous long-term favorable outcome of most patients. However, 20 to 50% of untreated patients develop progressive renal insufficiency. METHODS: All of the patients with biopsy-proven MGN who developed renal insufficiency at our Hospital during the period of 1975 to 2000 were studied. Selected patients (N=39) were separated into two groups according to the two different therapeutic policies followed at our department: a conservative approach during the first period, 1975 to 1989 (group I, N=20), and a course of immunosuppressive therapy (oral prednisone for six months and concurrent oral chlorambucil, 0.15 mg/kg/day, during the first 14 weeks) during the second period, 1990 to 2000 (group II, N=19). RESULTS: There were no significant differences between both groups at the time of renal biopsy, nor at the onset of renal function decline. All group I patients showed a progressive renal insufficiency; at the end of the follow-up 13 patients (65%) were on chronic dialysis, 2 (10%) showed advanced renal failure, and 5 (25%) had died. In contrast, most of group II patients showed an improvement or stabilization of serum creatinine (SCr; 2.3 +/- 0.9 mg/dL at onset of treatment, 2 +/- 1.5 mg/dL at the end of follow-up) together with decreased proteinuria (11.2 +/- 3.3 vs. 5.2 +/- 6.7 g/24 h). At the end of the follow-up 58% of group II patients had a SCr value < or =1.5 mg/dL and 36% showed a complete or partial remission, whereas no patient in group I showed remission. After four years of follow-up the probability of renal survival without dialysis was 55% in group I and 90% in group II (P < 0.001), and after seven years the renal survival was 20% and 90%, respectively (P < 0.001). Side effects of immunosuppressive treatment were uncommon but severe, as two patients suffered Pneumocystis carinii pneumonia. CONCLUSION: A course of immunosuppressive treatment administered early at the onset of renal function decline induces a favorable effect in most of patients with MGN and deteriorating renal function. Untreated patients progressed without exception toward advanced renal failure.     

Effect of aspirin and dipyridamole on proteinuria in idiopathic membranoproliferative glomerulonephritis: a multicentre prospective clinical trial

Idiopathic membranoproliferative glomerulonephritis (MPGN) hasa poor prognosis, with 90% of patients requiring dialysis treatmentafter 20 years regardless of therapy. Up to 34% of patientsmay die due to thrombotic complications or sepsis. This studyinvestigates the influence of aspirin plus dipyridamole on proteinuriaand renal function in nephrotic MPGN patients with moderatelyreduced glomerular nitration rate. Eighteen patients with biopsy-proven MPGN (15 type I, 3 typeII) and nephrotic syndrome were randomly assigned to receiveprotein restriction, anti-hypertensive therapy (control group)or in addition aspirin and dipyridamole (treatment group). Patientswere prospectivly followed for a mean of 36 months. Serum creatinine remained unchanged after 36 months comparedto baseline in both groups. In the treatment group proteinuriawas reduced from 8.3±1.4 to 1.6±0.7g/day (P<0.05).In control patients proteinuria decreased from 7.1±1.6to 4.3±1.1 g/day. After 36 months proteinuria was significantlylower in the treatment group compared to control (P<0.02Mann-Whitney rank sum test). In conclusion, aspirin plus dipyridamole may be of value inreversing nephrotic syndrome and associated risks in patientswith MPGN and moderately reduced renal function.     

Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages

BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome.