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.

Renal handling of urate and the incidence of gouty arthritis during cyclosporine and diuretic use.

The incidence of gouty arthritis and the role of renal urate handling and diuretic use were studied in 85 cadaveric kidney graft recipients with a graft functioning for at least two years. The incidence of gout was 24% in patients using cyclosporine (CsA, n = 55); no patient using azathioprine (Aza, n = 23) had gout. In patients using CsA, the fractional urate clearance decreased between 1 and 3 months after transplantation, thereafter remaining stable at a significantly lower level than in patients using Aza, pointing toward a specific effect of CsA on tubular urate handling. This impaired fractional urate clearance was not reversible up to 18 months in 7 patients after conversion from CsA to Aza, suggesting irreversible tubular damage. Multiregression analysis showed that the impaired fractional urate clearance and the use of furosemide were significant contributors to the occurrence of gout in patients using CsA.

Effect of immunomodulator thymopentin on impaired seroresponse to influenza vaccine in patients on haemodialysis.

In a double-blind placebo-controlled multicentre study, the effect of the immunomodulator thymopentin (TP5) on the antibody production to trivalent influenza vaccine was tested in 108 patients on chronic intermittent haemodialysis (HD). Antibody production was determined in pre- and postvaccination sera. Compared to a group of 35 young healthy adult control subjects, HD patients showed a clearly impaired seroresponsiveness to all three vaccine components, regardless of treatment with TP5 or placebo. We conclude that TP5 administration is not able to enhance humoral immunity in patients on chronic intermittent HD.

Amplification of the nephrotoxic effect of cyclosporine by preexistent chronic histological lesions in the kidney.

In contrast to its importance in improving renal graft survival, nephrotoxicity is the most serious side effect of cyclosporine. Dosage reductions of CsA mitigate its nephrotoxic effect. However, CsA nephrotoxicity is still a problem in clinical transplantation. In this study the relationships among preexistent chronic histological lesions, donor age, and renal function after transplantation in 100 CsA treated renal allograft patients are described. Multivariate data analysis revealed a significant statistical effect of the presence of preexistent chronic histological lesions on nonimmediate function (-.42, less than 0.0001) that was relatively twice as large as the effects of cold ischemia time (-.21, less than 0.05). Also in predicting creatinine clearance at 1 and 3 months, preexisting chronic histological lesions had the most important effect (-.39, less than 0.0001; -.57, less than 0.0001, respectively), whereas the presence or absence of rejection episodes was less predictive (.24, less than 0.001; .20, less than 0.01, respectively). Preexistent chronic histological lesions had also significant effects in predicting conversion to azathioprine and prednisolone, because of CsA nephrotoxicity (-.42; less than 0.0001). The degree of CsA nephrotoxicity therefore varies according to the presence of preexistent chronic histological lesions. Because of the increase of these lesions with age, one has to be aware of an exaggerated CsA toxicity, especially in the older donor age group and in older patients treated with CsA for various reasons.

Plasma alpha-human atrial natriuretic peptide and volume status in chronic haemodialysis patients.

The relationship between inferior vena cava diameter (VCD), collapse-index (CI) determined by echography, and alpha-human atrial natriuretic peptide (alpha-h-ANP) concentrations were studied in 19 chronic haemodialysis patients. A significant correlation was found between VCD and alpha-h-ANP before dialysis (r = 0.78; P less than 0.0001). No such correlation was found between CI, left atrial diameter and left ventricular end-diastolic diameter, and alpha-h-ANP values. In nine patients who according to vena cava indices were hypervolaemic before dialysis (group I), alpha-h-ANP concentrations were significantly greater than in ten normo- or hypovolaemic patients (group II): 392.8 +/- 134.1 pg/ml and 168.0 +/- 62.5 pg/ml respectively. Although the same amount of fluid was ultrafiltrated in both groups, alpha-h-ANP decreased significantly in group I only, whereas in group II the decrease was not significant: 392.8 +/- 134.1 to 185.2 +/- 81.7 (P less than 0.001); 168.0 +/- 62.5 to 130.0 +/- 59 respectively. After achieving normovolaemia alpha-h-ANP concentrations in patients with a mitral valve insufficiency grade I was doubled compared to normovolaemic patients without mitral valve insufficiency, suggesting that alpha-h-ANP release will also occur from the left atrium. In the latter group alpha-h-ANP values were approximately doubled compared to healthy controls. The highly significant correlation between VCD before dialysis and changes in alpha-h-ANP during dialysis with fluid removal underlines the value of vena cava diameter in estimating volume status.