Controlled Trial of Prednisone in Adult Patients with the Nephrotic Syndrome

Abstract

Organization of TrialThe nephrotic syndrome was considered to be present when all the following criteria were met: (a) oedema-still present or recently observed; (b) proteinuria-5 g. or more per day, measured by biuret or turbidimetric method, not Esbach's method; and (c) hypoproteinaemia-serum albumin less than 3 g./100 ml. Only those patients were admitted to the trial who: (a) were aged 15 or over; (b) had suffered from the nephrotic syndrome, as defined above, for not more than one year; (c) had not been previously treated for this condition with steroids or with corticotrophin; (d) were still excreting in the urine, at the end of a preliminary period of four weeks, at least 1 g. of protein per day; (e) showed neither pathological nor strong clinical evidence of a cause for the nephrotic syndrome other than glomerulonephritis; (f) had nc past history of episodes of the nephrotic syndrome except during the year immediately preceding admission to the trial; and (g) had not received, steroids or corticotrophin for any condition during the, past year.A history of proteinuria extending over more than a year, without other features of the nephrotic syndrome, did not entail exclusion from the trial, nor did uraemia, hypertension, or urinary infection.In order to obtain sufficient data within a reasonable period a multi-centre trial was necessary. A total of 125 patients who satisfied all the clinical and histologicaL criteria for entry were admitted to the trial in 19 centres over a period of three and a half years. An almost equal number of patients suffering from the nephrotic syndrome had to be rejected for a variety of clinical reasons. Clinical information on patients admitted to the trial was recorded on a standard form, and they were observed for a month before being allocated to "steroid" or "non-steroid" groups. Histological ClassificationThe nephrotic syndrome has a great number of possible causes, but in any large series about three-quarters of the patients are suffering from one form of glomerulonephritis or another. Even within the category of glomerulonephritis, however, there is great histological diversity, and this is associated with differences in aetiology and probably in

The Treatment of Minimal Change Disease in Adults

“…The work by Coggins 26 compared alternate-day prednisone (average dose=125 mg/d) for 2 months with placebo in 28 adult MCD patients. As observed in the work by Black et al, 25 steroid-treated patients remitted more rapidly, with 12 of 14 treated patients in complete remission before 2 months compared with 6 of 14 controls. However, there was no difference in overall remission rates over 77 months of follow-up.…”

“…18,19 Controlled Trials of Corticosteroid Use in Adults with MCD There are two randomized trials that have explored the use of corticosteroids in adults with MCD. In 1970, Black et al 25 published a multicenter controlled study comparing prednisone (at least 20 mg/d for at least 6 months) with no steroid treatment in 125 adults with NS, 31 of whom had MCD. The steroid group showed a rapid decrease in proteinuria and improvement in edema within the first month of treatment compared with control.…”

“…24 As discussed below, the few controlled studies that have been performed in MCD patients show similar long-term remission rates between treated and nontreated patients. 25,26 Given the risk of adverse events caused by current treatment modalities, one may ask whether MCD patients should be treated or not. However, the significant comorbidities associated with NS (hyperlipidemia, 27 infections, 16,28 skin breakdown from edema, risk of thromboembolic events, 29,30 AKI, and worsened quality of life) prompt most physicians to recommend treatment for MCD patients.…”

Spicular arrangement of amyloid in renal biopsy

“…Firstly proteinuria has been reported to disappear on treating the cause of the amyloid (Lowenstein and Gallo, 1970) and the rate of renal damage will certainly be decreased. Secondly, although some series have shown no response of membranous nephropathy to steroids either alone (Black, Rose, and Brewer, 1970) or in combination with azathioprine (Rose and Black, 1971), small series in which there has been response to steroid therapy have been reported (Rastogi, Hart-Mercer, and Kerr, 1969;Bariety, Samarcq, Lagrue, Fritel, and Milliez, 1968). The use of these drugs with their potentially dangerous side effects should be avoided whenever possible, and some workers even consider that steroids may actually accelerate the progress of renal amyloid deposition (Cohen, 1967), although Maxwell, Adams, and Goldman (1964) found no evidence of either improvement or deterioration with this treatment.…”

Effects of Methylprednisolone on Hydrogen Ion Absorption in the Canine Stomach

“…For years it was held that glucocorticoids were potentially ulcerogenic, but recent reviews of randomized, double-blind trials provide no support for this contention (3,4). As Conn and Blitzer (4) point out however, the lack of proof for an association between glucocorticoids and peptic ulcers does not summarily exclude a role for steroids in ulcerogenesis because in controlled trials an increased incidence of peptic ulcers was observed in patients with nephrotic syndrome (5) or cirrhosis (6) who received glucocorticoids, or in other patients receiving a total dose which exceeded 1,000 mg. It has been suggested that the reduced serum binding capacity resulting from the hypoalbuminemia in nephrosis and cirrhosis may lead to high blood levels of unbound steroids.…”