Complete Remission Of Proteinuria Research Articles

Plasma exchange improves graft survival in patients with recurrent focal glomerulosclerosis after renal transplant.

Recurrence of primary focal glomerulosclerosis (FGS) after renal transplantation is associated with poor graft survival. Plasma exchange (PE) can reduce proteinuria and even induce complete remission of proteinuria. It is, however, unknown whether the use of PE therapy improves long-term graft survival. In our center, PE has been used to treat recurrent FGS after renal transplantation since 1994. Thus far, 13 patients have been treated with PE for recurrent FGS and followed for up to 77 months after the onset of the recurrence. We reviewed the transplantation data in these patients, and, for comparison, ten patients who underwent transplantation between 1973 and 1991 and were not treated with PE served as historical controls. Recurrence of FGS occurred within 4 weeks of transplantation in 74% of the patients. PE was started within 14 days of the onset of proteinuria in 85% of the patients. Two patients lost their graft within the first month of transplantation due to untreatable rejection; the remaining 11 patients (85%) achieved complete (n=7) or partial (n=4) remission. Seven patients remained in remission after a short period of treatment with PE (< or =18 sessions in 2 months), whereas four patients needed prolonged treatment (median of 58 sessions). The need for prolonged PE was associated with a late (>30 days after transplantation) recurrence of FGS (P=0.02). A comparison with the historical control group revealed not only a significant reduction in proteinuria, but also significantly better long-term graft survival in the treated group, 85% and 30%, respectively, at 5 years (P=0.02). In conclusion, PE is an effective form of treatment for recurrent FGS, especially if initiated early. Failure to maintain stable remission after the initial period of PE does not necessarily imply a poor outcome, and sustained remissions can be achieved after prolonged treatment.

C1q nephropathy: A variant of focal segmental glomerulosclerosis

C1q nephropathy is a poorly understood and controversial entity with distinctive immunopathologic features. In order to better define the clinical-pathologic spectrum, we report the largest single-center series. Nineteen biopsies with C1q nephropathy were identified from among 8909 native kidney biopsies received from 1994 to 2002 (0.21%). Defining criteria included (1). dominant or co-dominant immunofluorescence staining for C1q, (2). mesangial electron dense deposits, and (3). no clinical or serologic evidence of systemic lupus erythematosus (SLE). The 19 patients were predominantly African American (73.7%), female (73.7%), young adults and children (range, 3 to 42 years; mean, 24.2 years). Presentation included nephrotic range proteinuria (78.9%), nephrotic syndrome (50%), renal insufficiency (27.8%), and hematuria (22.2%). No patient had hypocomplementemia or evidence of underlying autoimmune or infectious disease. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 17 (including six collapsing and two cellular) and minimal-change disease (MCD) in two. All biopsies displayed co-deposits of immunoglobulin G (IgG), with more variable IgM (84.2%), IgA (31.6%), and C3 (52.6%). Foot process effacement varied from 20% to 100% (mean, 51%). Twelve of 16 patients with available follow-up received immunosuppressive therapy. One patient had complete remission of proteinuria and six had partial remission. Four patients with FSGS pattern had progressive renal insufficiency, including two who reached end-stage renal disease (ESRD). Median time from biopsy to ESRD was 81 months. On multivariate analysis, the best correlate of renal insufficiency at biopsy and at follow-up was the degree of tubular atrophy and interstitial fibrosis (P = 0.0495 and 0.0341, respectively). C1q nephropathy falls within the clinical-pathologic spectrum of MCD/FSGS. Although further studies are needed to determine the pathomechanism of C1q deposition, we hypothesize that it may be a non-specific marker of increased mesangial trafficking in the setting of glomerular proteinuria.

Other immunosuppressive agents for focal segmental glomerulosclerosis

A prolonged course with corticosteroids represents the first therapeutic approach for nephrotic patients with focal segmental glomerulosclerosis (FSGS). In patients with contraindications to steroids or in those who do not respond to steroids or cyclosporine, cytotoxic agents, mycophenolate mofetil (MMF), plasmapheresis, and low-density lipoprotein (LDL) apheresis have been tried as alternative treatments. A short-term treatment with cytotoxic agents often is ineffective in steroid-resistant patients However, an aggressive and prolonged treatment with cytotoxic agents combined with corticosteroids proved to be effective in more than half of steroid-resistant children. In adults, the response to cytotoxic agents was good in steroid-responsive patients, but was poor in steroid-resistant patients. Better results were observed when cytotoxic therapy was prolonged for several months. The problem with these drugs is that long-term immunosuppression may be complicated by severe side effects including a major risk for cancer. Uncontrolled studies reported that MMF can induce some reduction of proteinuria , but complete remission of proteinuria was rare and no data on long-term follow-up evaluation with this drug are available. Good results have been reported with plasmapheresis, immunoadsorption, and lipopheresis. However, all the reports were uncontrolled, small sized, and with short-term follow-up evaluation. In conclusion, there are several therapeutic options for patients who respond to steroids and have further relapses of nephrotic syndrome, but how to treat steroid-resistant patients is still a matter of debate. Nevertheless, a 6-month trial with cytotoxic agents or MMF can be offered to steroid-resistant patients to identify the few patients who respond to these agents. The preliminary results with plasmapheresis or lipopheresis are promising but further studies are needed to assess the role of these treatments. © 2003 Elsevier Inc. All rights reserved.

Efficacy of cyclosporin in difficult‐to‐treat idiopathic membranous nephropathy

SUMMARY: Poor tolerance and the potential long‐term toxicity have limited the widespread use of corticosteroids and cytotoxic drugs in the treatment of idiopathic membranous nephropathy (IMN). Cyclosporin A (CyA) has been proven to be a less toxic alternative, but its efficacy needs further confirmation. Cyclosporin A (2–3mg/kg per day) in combination with low‐dose methylprednisolone (4mg/day) was given to 28 nephrotic patients with IMN who had failed to respond, or tolerate, or to complete treatments with steroids and/or cytotoxic drugs. the mean duration of treatment was 11 ± 7 months. Seven patients (25%) showed a complete remission of proteinuria, 17 (60%) a partial one, and four (15%) did not respond at all. the average time to achieve optimal remission was 4.2 ± 1.4 weeks following the initiation of therapy. In those who responded completely or partially, plasma creatinine (Per) did not change significantly from pre CyA levels during follow up (1.0 ± 0.3 vs 1.2 ± 0.3mg/dL, P=NS). the remaining four patients who had renal insufficiency already before CyA (mean Per: 2.1 ± 0.8mg/dL), showed a rapid deterioration of renal function after the initiation of CyA (mean Per: 3.1 ± 1.5 mg/dL, P&lt;0.01), and as a consequence, the drug was discontinued. A mul‐tivariate analysis on the clinical and histological features demonstrated that the degree of renal function impairment (P&lt;0.02), the percentage of obsolete glomeruli (P&lt;0.01), and the severity of interstitial fibrosis (P&lt;0.005) independently predicted the response to therapy. Low dose CyA is an effective and safe alternative treatment for patients with IMN and normal renal function. However, the drug should be given with caution to patients with established renal insufficiency.

Interferon-α in combination with ribavirin as initial treatment for hepatitis C virus–associated cryoglobulinemic membranoproliferative glomerulonephritis

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-α (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN. © 2001 by the National Kidney Foundation, Inc.

Recurrent focal glomerulosclerosis: natural course and treatment with plasma exchange.

Focal glomerulosclerosis (FGS) can recur after renal transplantation and prognosis is poor in untreated patients. A circulating plasma factor has been implicated in the pathogenesis of a recurrent FGS and treatment with plasma exchange has proven effective in decreasing proteinuria in some patients. We retrospectively studied the course of disease in patients with recurrent FGS, transplanted in our centre. Seven patients transplanted between 1991 and 1997, received treatment with plasma exchange, whereas 10 patients, transplanted between 1973 and 1991, were left untreated and served as historical controls. The time of onset of proteinuria (>3.5 g/day) was comparable in the untreated and treated patients (9 and 10 days respectively), as was the average proteinuria at that time (5.5 and 5.8 g/day respectively). In the untreated patients, proteinuria persisted and eventually all grafts were lost, on average 43 months after the diagnosis of a recurrence. In five cases (50%) the recurrence was the single cause of graft loss. The clinical course was different in the seven patients who were treated with plasma exchange. In five of these patients, the recurrence occurred within 3 weeks after transplantation. Plasma exchange was started 1-14 days after onset of proteinuria in these patients. Two lost their grafts after 0.7 and 1.0 months because of untreatable rejection. In the remaining three patients the plasma exchange resulted in abrupt disappearance of the proteinuria, and the response has been lasting for 2-3.2 years. In these patients the only histological abnormality was foot effacement on electron-microscopy. In two patients the recurrence became manifest at 9 weeks and 5.8 years after transplantation respectively. These two patients relapsed after the initial course of plasma exchange, but responded to repeated session, and are currently being treated once a month. They have been followed for 1. 7 and 1.4 years after the onset of proteinuria and their urinary protein levels are 0.23 and 1.2 g/10 mmol creatinine. The prognosis of untreated recurrent FGS is poor. Treatment with plasma exchange can lead to complete remission of proteinuria and relapsing patients may respond to repeated sessions. Best results are obtained when plasma exchange is started early, when there are no visible lesions on light-microscopy.

Prognosis after a complete remission in adult patients with idiopathic membranous nephropathy.

This review of the long-term outcome after a complete remission of proteinuria includes 82 adult patients with biopsy-proven idiopathic membranous glomerulonephritis (IMGN), who represented 25% of the total cases (82 of 323 cases) of IMGN in our registry. Complete remission was defined as at least two consecutive follow-up evaluations showing proteinuria of 0.3 g/d or less of protein. Before remission, 70% of the patients had nephrotic-range proteinuria (61% at presentation, 9% during follow-up), and 30% were always subnephrotic (protein level < 3.5 g/d). Mean total observation time was 101 +/- 56 months, with a postremission period of 69 +/- 60 months. Seventy-one percent of the patients remained in remission and 29% relapsed. In the relapse group, 46% relapsed to nephrotic-range proteinuria and 54% relapsed to subnephrotic levels. The plasma creatinine level remained stable in 86% of the patients (71 of 82 patients) but became or remained elevated despite a period of complete remission in the remaining 14% (8 of 82 patients). No patient went on to end-stage renal disease. Seventy-seven percent of the patients had no specific treatment within 6 months of remission, whereas 23% had steroid therapy alone or in combination with an immunosuppressive agent. In a multivariate analysis, the factors that favored both remission and its durability were persistent lower levels of proteinuria and female sex. Complete remission indicates an excellent long-term prognosis in patients with IMGN, but relapses are common and, in a small percentage, chronic renal insufficiency occurs. Thus, our data suggest that even this group of patients should be monitored on a regular basis.

Successful treatment with steroid pulse therapy in a case of immunotactoid glomerulopathy with hypocomplementemia

We report a case of immunotactoid glomerulopathy with severe hypocomplementemia. The patient was a 47-year-old woman who presented with pitting edema, proteinuria, and hypertension. Serological testings were negative or within normal limits except for hypocomplementemia. There were no findings of hematopoietic diseases, cryoglobulinemia, and systemic lupus erythematosus. The renal biopsy specimen showed membranoproliferative glomerulonephritis with numerous periodic acid- Schiff (PAS)-positive deposits. Under electron microscopy, however, microtubular structure was shown in the mesangial matrix and the subendothelial and subepithelial spaces of the peripheral capillary loops. These histological features were compatible with those of immunotactoid glomerulopathy. Although conventional oral steroid therapy failed to have an effect on proteinuria and hypocomplementemia over 3 months, steroid pulse therapy brought dramatic relief: complete remission of proteinuria and normalization of hypocomplementemia. These findings suggest that intensive immunosuppressive therapy may cure a kind of immunotactoid glomerulopathy with hypocomplementemia. (Am J Kidney Dis 1998 Jul;32(1):E4)

Cyclophosphamide provides no additional benefit to steroid therapy in the treatment of idiopathic membranous nephropathy

Thirty-six patients with idiopathic membranous nephropathy were retrospectively studied. The mean age was 47 years and the male to female ratio 25 to 11. Twenty-eight patients (77.8%) had nephrotic syndrome at first investigation. Nineteen patients received corticosteroids alone (group A) and 17 received corticosteroids combined with cyclophosphamide (group B). The mean period of follow-up was 58.9 months (range, 12 to 156 months). The two groups did not differ in clinical or laboratory features at the time of biopsy or at the start of treatment. In the entire series a complete remission of proteinuria occurred in 13 of 36 patients (36.1%) and a partial remission occurred in 13 (36.1%); 10 patients (27.8%) had no response. Optimal remission of proteinuria was usually recorded 6 to 12 months after the start of treatment. The two groups showed no statistical differences regarding the rate of complete (seven v six patients; P = not significant) or partial (six v seven patients; P = not significant) remissions. Two patients (one from each group) entered end stage renal failure during follow-up. At last assessment, the number of patients with complete remission (four v three patients; P = not significant), nonnephrotic proteinuria (nine v nine patients; P = not significant), or nephrotic syndrome (five v four patients; P = not significant) was similar in both groups. In addition, final plasma creatinine did not differ significantly between the two groups (1.8 ± 2.3 mg/dL v 2.6 ± 2.6 mg/dL; P = not significant). In conclusion, both treatment regimens were found to be equally effective in decreasing proteinuria and preserving renal function in adult idiopathic membranous nephropathy. Cyclophosphamide appeared not to offer any definite advantage over corticosteroids alone in the treatment of the disease.

Relationship between interstitial infiltrates and steroid responsiveness of proteinuria in membranous nephropathy

Mononuclear inflammatory cells were retrospectively analysed using monoclonal antibodies in the interstitium and glomeruli of 16 renal biopsy specimens from patients with nephrotic syndrome due to idiopathic membranous nephropathy (IMN). The aim of the study was to determine the composition of the infiltrate and to assess the ability to predict the response of proteinuria to corticosteroids. All patients had received prednisolone as a sole treatment. Nine patients had shown a complete or partial remission of proteinuria (group A) and seven did not respond at all (group B). Both groups were matched for age and degree of proteinuria; also both groups had normal renal function at the time of biopsy. Very few intraglomerular leukocytes, mostly monocytes/macrophages (MM) were found. The majority of interstitial T cell population and B cells were a minor component. No significant differences were found between the two groups regarding the types of the intraglomerular cells. However, interstitial T-cells, CD4+ve T helper/inducer cells, CD8+ve T cytotoxic/suppressor cells and MM were significantly higher in group A than in group B. Also HLA-DR expressing interstitial cells were much in excess in group A. In addition patients with complete remission of proteinuria had higher numbers of interstitial cells compared to those with partial response. There was no correlation between the numbers of types of intraglomerular and interstitial cells and the degree of proteinuria at presentation. Also no association was found between intraglomerular or interstitial cell population and subsequent relapse of proteinuria. In conclusion, interstitial but not intraglomerular mononuclear cells seem to determine the initial response of proteinuria to corticosteroids in patients with IMN.

Clinical course and outcome of idiopathic membranous nephropathy in Japanese children.

We retrospectively studied 12 Japanese children (8 boys, 4 girls) with idiopathic membranous nephropathy (IMN), aged 2.9-15.8 (mean 7.7) years at onset. All patients were identified through either screening or a routine urinalysis; proteinuria was present in all, haematuria, which was macroscopic in 4, in 11. Three had nephrotic syndrome (NS) at or soon after onset. Stages on electron microscopy, performed in 10 patients, were I in 3, II in 5 and III in 2. Steroids alone or with cyclophosphamide were administered to 5 patients, including the 3 patients showing NS. Complete remission of proteinuria occurred in 8 patients 0.3-1.6 (mean 0.6) years after onset, and proteinuria did not recur. After a follow-up of 1.6-11.6 (mean 5.9) years, these 8 patients were in complete remission and the remaining 4 had only mild proteinuria; none had hypertension or impaired renal function. Thus, we infer that IMN in Japanese children may have a better course and outcome than IMN in non-Japanese children. Based on a comparative study of Japanese (previously reported cases added to ours) and non-Japanese (mostly Caucasian) children with IMN, this was confirmed; it is possible that steroid therapy in Japanese patients is more effective in inducing remission of NS and preserving renal function.

Membranous Glomerulonephritis and Malignancy

The purpose of this review is to enhance the clinical awareness of the association between membranous glomerulonephritis and neoplasia. Controversy has persisted that has tended to minimize this association, therefore, we report our experience to shed some light on this controversy as well as to make diagnostic recommendations. One hundred seven adult patients with biopsy-proven membranous glomerulonephritis were selected for review. Twenty of these patients had a known secondary cause of membranous glomerulonephritis other than malignancy. Data were collected retrospectively on all these patients and nine were found who had or developed malignancy associated with membranous glomerulonephritis. Clinical data were analyzed to ascertain the onset of renal disease in relation to the malignancy as well as to determine the ultimate patient and renal outcome after treatment of the neoplasm. Of the 87 patients with presumed idiopathic membranous glomerulonephritis, nine (10.3%) had or developed a malignancy associated with their renal disease. The membranous glomerulonephritis was seen in patients with various solid tumors as well as hematologic malignancies. All patients presented with nephrotic-range proteinuria. Proteinuria manifested itself prior to or concomitantly with the diagnosis of the neoplasm in approximately 80% of cases. Follow-up data were available on seven patients: complete remission of proteinuria was seen in two patients associated with treatment of their tumors, one patient developed end-stage renal disease, and the remaining four patients had persistent proteinuria associated with tumor recurrence or metastasis. There appears to be a clear association between membranous glomerulonephritis and neoplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclophosphamide Provides No Additional Benefit to Steroid Therapy in the Treatment of Idiopathic Membranous Nephropathy

Thirty-six patients with idiopathic membranous nephropathy were retrospectively studied. The mean age was 47 years and the male to female ratio 25 to 11. Twenty-eight patients (77.8%) had nephrotic syndrome at first investigation. Nineteen patients received corticosteroids alone (group A) and 17 received corticosteroids combined with cyclophosphamide (group B). The mean period of follow-up was 58.9 months (range, 12 to 156 months). The two groups did not differ in clinical or laboratory features at the time of biopsy or at the start of treatment. In the entire series a complete remission of proteinuria occurred in 13 of 36 patients (36.1%) and a partial remission occurred in 13 (36.1%); 10 patients (27.8%) had no response. Optimal remission of proteinuria was usually recorded 6 to 12 months after the start of treatment. The two groups showed no statistical differences regarding the rate of complete (seven v six patients; P = not significant) or partial (six v seven patients; P = not significant) remissions. Two patients (one from each group) entered end stage renal failure during follow-up. At last assessment, the number of patients with complete remission (four v three patients; P = not significant), nonnephrotic proteinuria (nine v nine patients; P = not significant), or nephrotic syndrome (five v four patients; P = not significant) was similar in both groups. In addition, final plasma creatinine did not differ significantly between the two groups (1.8 +/- 2.3 mg/dL v 2.6 +/- 2.6 mg/dL; P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of the nephrotic syndrome with cyclosporin A

The three main causes of primary nephrotic syndrome are minimal change nephropathy, focal glomerulosclerosis and membranous nephropathy. Corticosteroids obtain remission of proteinuria in most patients with minimal change nephropathy. Many patients, however, show either frequent relapses or steroid dependency. A short course of cyclophosphamide or chlorambucil can achieve stable remission in many of these patients but alkylating agents cannot be repeated, their toxicity being cumulative. Analyses of the available studies showed that some 80% of patients can be maintained in remission with cyclosporin A (CsA) but relapse occurs when the drug is stopped. Severe side effects are rare. In particular, the mean values of creatinine clearance did not deteriorate in cyclosporin-treated patients and repeat renal biopsy showed only mild changes in some patients. There is no definite treatment for focal glomerulosclerosis. An analysis of 10 clinical trials showed that some 17% of nephrotic patients may enter complete remission of proteinuria and another 13% may attain partial remission of the nephrotic syndrome with CsA. There is concern over the use of this drug since cases of irreversible renal dysfunction have been reported. However, retrospective reviews of the available studies showed that the mean serum creatinine levels did not modify if patients had normal renal function when given CsA. A 6-month course of methylprednisolone and chlorambucil may obtain remission of the nephrotic syndrome in some 60% of patients with membranous nephropathy. Some trials have shown that CsA may improve proteinuria and there is also some suggestion that the drug might protect against renal function deterioration. Thus, when given at correct doses, CsA may exert an anti-proteinuric effect without deteriorating renal function, suggesting that the drug may represent a further tool in treating the primary nephrotic syndrome.

A prospective, randomized therapeutic trial for schistosomal specific nephropathy

In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.

Long-term Outcome of Patients with Membranous Nephropathy After Complete Remission of Proteinuria

To assess the prognostic significance of complete remission in patients with idiopathic membranous nephropathy, 33 patients were followed for a median of 96 months after remission of proteinuria. All patients had had a histological diagnosis of membranous nephropathy and a nephrotic syndrome. Only patients with a complete remission lasting for at least six months and with a follow-up of at least four years after remission were considered. No relapse of proteinuria developed in 17 patients (51%), 7 patients had relapse of non-nephrotic proteinuria (21%) and 9 (27%) relapse of nephrotic proteinuria. However proteinuria disappeared again in some patients so that at follow-up 73% of patients are in complete remission, 21% have non-nephrotic proteinuria and only 6% have nephrotic syndrome. All patients maintained a normal plasma creatinine over the years. It is concluded that complete remission of proteinuria is a strong predictor of long-term favourable outcome in patients with idiopathic membranous nephropathy.

Prognostic indicators in patients presenting with the nephrotic syndrome

Clinical data from 246 patients presenting with a nephrotic syndrome and biopsy-proven glomerular disorder were analyzed, using statistical survival techniques, to determine which of several variables (sex, age, plasma creatinine, diastolic blood pressure and 24-hour urinary protein loss) were associated with subsequent end-stage renal failure. The best prediction of outcome could be made at one year (N = 121); then plasma creatinine (P less than 0.001) and heavy proteinuria (P = 0.049) were the best determinants. For a given plasma creatinine level, heavy urinary protein was associated with a worse outcome. The incidence of end-stage renal failure was greatest three to four years from the date edema first developed. Plasma creatinine and urinary protein values, collected four-monthly throughout the study period, were analyzed as time-dependent covariates. A relationship was found between the prevailing risk of renal failure and earlier heavy proteinuria (P less than 0.001). Spontaneous complete remission of proteinuria was associated with a highly favorable outcome (P = 0.001) and normal, or impaired but stable, renal function.

Cyclosporin in the Treatment of Steroid-responsive and Steroid-resistant Nephrotic Syndrome in Adults

The effect of cyclosporin on proteinuria was studied in 11 patients with steroid-responsive nephrotic syndrome (10 minimal change nephropathy, one IgM nephropathy) and in four patients with steroid-resistant nephrotic syndrome from focal segmental glomerulosclerosis. Cyclosporin (mean initial dose 7.7 mg/kg per day) produced a complete remission of proteinuria in 15 nephrotic episodes in the ten patients with minimal-change nephropathy after a mean 14.3 days (range 7-23 days) of therapy. All patients remained in remission while receiving cyclosporin (mean duration of follow-up 147 days; range 40-230 days). However, when cyclosporin was discontinued on nine occasions in five patients, all relapsed after a mean 47.8 days (range 7-180 days). Four of the five patients were subsequently rechallenged with cyclosporin and all responded. Maintenance cyclosporin therapy to prevent relapse was not associated with any adverse effects, and there was no significant difference between the creatinine clearance before and after 30 days of therapy (86.9 +/- 19.3 and 81.7 +/- 23.5 ml/min respectively, P greater than 0.1). The patient with steroid-responsive IgM nephrotic syndrome did not respond to cyclosporin, and there was no significant effect of cyclosporin on proteinuria in the four patients with FSGS. Cyclosporin is an effective agent for the treatment of patients with frequently relapsing minimal-change nephropathy who became steroid dependent when cyclophosphamide is contraindicated. However, unlike cyclophosphamide, long-term remissions which persist after treatment is withdrawn are not obtained, and patients may be said to be cyclosporin dependent.