Search

BackgroundMycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure.MethodsA multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 (‘IMPACT’ study).ResultsOf the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20–132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0–65.9) mg*h/L versus pantoprazole: 43.8 (35.6–53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5–49.2) mg*h/L versus pantoprazole: 45.9 (35.5–59.3) mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group.ConclusionsThe co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations.

Background and Aims Diarrhea is a common side effect of mycophenolate treatment in renal transplant recipients. In patients with mycophenolate induced diarrhea, one of the options is switching mycophenolate to azathioprine. In this study, we aimed to define the safety and efficacy of switching from mycophenolate to azathioprine for mycophenolate related diarrhea in renal transplant recipients. Method A total of 177 patients, 59 of whom were switched to azathioprine due to diarrhea and 118 of which were matched control group without diarrhea that continued mycophenolate treatment, participated in this study. We analyzed the effect of switching to azathioprine from mycophenolate on amelioration of diarrhea and graft survival. Results We observed that 89.8% of the patients who switched to azathioprine due to diarrhea had improved diarrhea complaints. Patients switched to azathioprine due do diarrhea had lower glomerular filtration rate (59 [15-125] vs. 74 [23-150] mL/min, p Conclusion Although switching mycophenolate to azathioprine was an effective approach to improve diarrhea, this approach is associated with increased risk of graft loss.

Background and Aims Lupus nephritis (LN) develops in about 50% of patients affected by Systemic Lupus Erythematosus (SLE) and it is associated with higher morbidity and mortality risk. Approximately 10 % of LN patients is expected to reach end stage renal disease (ESRD). Proteinuria at 1 year has been demonstrated as the best predictor factor of long-term renal outcome. We compared the effects of two different induction therapies (Euro Lupus protocol [EL] vs Mycophenolate [MMF]) in terms of eGFR, proteinuria, serum albumin and complement activation in LN patients related to our centre. Method We retrospectively reviewed the records of 34 adult patients with LN from 2011 to 2019. Patients were divided in two groups according to therapeutic strategy chosen: EL (n=21 patients, group 1) and MMF (n=13, group 2). Data with normal distribution are expressed as average ± standard deviation, while data with non normal distribution are referred to as median and interquartile range [IQR]. Basal values of eGFR, proteinuria, albumin and complement were compared to 1 year values with Student t-test for normal variables or with Wilcoxon test for non normal variables. Results The mean age of the patients was 41.27±17.43 years, there was a predominance of female (85,3%) LN was diagnosed at 32±16 years old. According to LN classification, 88.2% of them was affected by III, IV, V and mixed LN class Basal values of eGFR (estimated with CKD-EPI method) were similar between groups 1 and 2 (86.12±52.86 vs 73.75±30.35, P=0.4890) as well as proteinuria (2.00 [0.48-4.57] vs 0.71 [0.28-1.39] g/24h, P=0.3284). After one year of follow up, eGFR did not show significant differences between two groups, while proteinuria was significantly lower in group 1 (2.)). 00 [0.48-4.57] vs 0.44 [0.19-0.91] g/24h, P=0.0034) than in group 2 (0.71 [0.28-1.39] vs 0.15 [0.08-0.77] g/24h, P=0.4687) (fig.1). Moreover, we recorded in group 1 higher values of albumin after one year of follow up (3.20 [2.52-3.94] vs 4.33 [3.99-4.57] g/dl, P=0.0195) (fig.2) and C3 consumption (35.00 [1.00-81.25] vs 89.00 [2.00-112.50] mg/dl, P=0.0067) (fig.3), while group 2 did not show any statistically significant differences. Conclusion In patients affected by LN, EL protocol demonstrated to be more effective than MMF in reducing one year after proteinuria, thus improving albumin and C3 serum titer.

Background and Aims Lupus nephritis (LN) poses a considerable impact on the morbidity and mortality of SLE patients. Long term comparative outcome data with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) based regimen from the Indian subcontinent is sparse. We assessed the renal and patient survival of these patients for the types of induction CYP or MMF and the two maintenance therapies – MMF or Azathioprine. We determined the predictors of death and dialysis dependency in the study population. Method In this retrospective study, we analysed outcomes of 100 LN patients, total 67 (26 class III, 25 class IV, 6 class III+V, and 10 class IV+V)) treated with CYP (euro lupus-40 and NIH- Dharmendra Bhadauria 27), and 33 with MMF based regimen with the steroid between July 2008 to June 2018. The class distribution of the patients in the two groups was similar. The data were archived regarding demography, clinical, histopathological features, and the treatment given of all 100 biopsy-proven LN patients. Outcomes between two regimens CYP and MMF in terms of remission, dialysis dependency, and patient survival were compared. The renal survival and patient survival at the end of follow-up between two groups were also analysed. Results The clinical characteristics were similar in both groups, except the activity index was high in CYP patients (6.13 ±4.48 Vs. 4.61 ± 2.80); however, the chronicity index was similar. The overall remission was 70% at the end of induction. The CR, PR, and NR in the CYP group was 46.2%, 23.9 %, 29.9% respectively; however, in the MMF group was 57.6%, 12.1%, and 30.3%, respectively. More patients died in CYP (14.9%) than those in MMF (9.1 %) patients. The 1-, 2-, 3-, 4-, 5- and 10-years patient survival in the CYP induction was 89.5%, 86.2%, 86.2%,83.8%, 83.8% and 83.8% however in MMF was 93.9%, 93.9%, 89%, 89%, 89% and 89% respectively. The most common cause of death was sepsis 9/13(69.2%), followed by uremia. The high serum creatinine, low Hb, male, thrombocytopenia, microscopic haematuria, leukocyturia, nephrotic proteinuria, lack of remission in 12 months, dialysis, doubling of creatinine on follow-up were significant predictors of mortality. The 1-, 2- 3-, 4-, 5- and 10- years renal survival (event death-censored, but dialysis dependency) in CP group was 98.5%, 96.7%, 94.7%, 92.4%, 92.4% and 84 % respectively however in the MMF was 96.8 %, 96.8%, 91.9%, 91.9%, 91.9%, and 78.8% respectively. (Figure 1)At the end of the study, dialysis dependency in the MMF group and CYP group was 7.5% and 12.1 %, respectively (NS). In the maintenance therapy, 3/56(5.3%) had to double of creatinine in MMF, and 7/34 (20.5%) in the AZA group (p=0.03). Conclusion Long term outcomes in terms of patient and renal survival of LN patients treated with CP and MMF based induction is similar. Serum creatinine doubling was more with MMF than AZA based maintenance. The majority of death occurred during induction, and sepsis was the most common cause of death.

Background and Aims Considering the particular pharmacokinetic (PK) profile of mycophenolate (MMF/MPS) with the important contribution of enterohepatic recirculation (EHC) and the potential alteration in tacrolimus (TAC) exposure, a PK study in solid-organ transplant patients who had undergone intestinal resection was carried out. Method This is a prospective single-center study of MMF/MPS and TAC exposure changes after bowel resection and after reconstruction. Whole blood samples were collected at the following time points: 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose. Areas under the curves (AUCs) were determined in both conditions: with ileostomy and after bowel reconstruction. Results Six renal and two cardiac transplant recipients were included. Four subjects completed both pre- and post-reconstruction surgery procedures. Different intestinal anatomic resections were performed (Table 1). Patients with terminal ileostomy showed an under exposure to MMF/MPS. In three patients, initial MPA levels were on target, but they decreased >80% after 4 hours post-drug administration. After bowel reconstruction, the AUC increased maintaining MMF/MPA levels during 12h (Table 2). Before bowel reconstruction, TAC trough levels were within therapeutic target but, after reconstruction, AUCs normalized by dose were much higher than the expected. Conclusion Transplant recipients with ileostomy showed infra-exposure to mycophenolate. After 4 hours post-dose, MMF/MPA was undetectable because of the absence of EHC, which was recovered after anatomical correction. TAC exposure was higher after bowel reconstruction suggesting changes in the absorption. The use of mTORi in such clinical situations would be an alternative.

BackgroundMonitoring of mycophenolic acid (MPA) levels may be useful for effective mycophenolate mofetil (MMF) dosing. However, whether commonly obtained trough levels are an acceptable method of surveillance remains debatable. We hypothesized that trough levels of MPA would be a poor predictor of area under the curve (AUC) for MPA.MethodsA total of 51 patients with lupus nephritis who were on MMF 1500 mg twice a day and had a 4-h AUC done were included in this study. MPA levels were measured prior to (C0) and at 1 (C1), 2 (C2) and 4 (C4) h, followed by 1500 mg of MMF. The MPA AUC values were calculated using the linear trapezoidal rule. Regression analysis was used to examine the relationship between the MPA trough and AUC. Differences in the MPA trough and AUC between different clinical and demographic categories were compared using t-tests.ResultsWhen grouped by tertiles there was significant overlap in MPA, AUC 0-4 and MPA trough in all tertiles. Although there was a statistically significant correlation between MPA trough levels and AUC, this association was weak and accounted for only 30% of the variability in MPA trough levels. This relationship might be even more unreliable in men than women. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with increased MPA trough levels and AUC at 0-4 h (AUC0–4).ConclusionTrough levels of MPA do not show a strong correlation with AUC. In clinical situations where MPA levels are essential to guide therapy, an AUC0–4 would be a better indicator of the adequacy of treatment.

Background. FTY720 (fingolimod), a novel immunomodulator, has demonstrated potential for prevention of acute rejection in combination with cyclosporine.Methods. This study evaluated FTY720 2.5 mg versus mycophenolate mofetil (MMF) in a combination regimen with standard tacrolimus and corticosteroids in de novo renal transplant recipients for the composite efficacy within 6 months of transplantation.Results. Incidence of treated biopsy-proven acute rejection was 22.9% with FTY720 and 18.5% with MMF. Increased incidence of macular oedema, transient decrease in heart rate and low rate of infections were seen in the FTY720 arm.Conclusion. FTY720 combined with tacrolimus and steroids did not show a significant therapeutic advantage over MMF for the prevention of acute rejection in de novo renal transplant recipients. © The Author 2011. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

BACKGROUND Uncontrolled mesangial cell (MC) proliferation within the context of glomerular disease contributes to the development of glomerulosclerosis. Mesangial autocrine growth factor stimulation has been described as a pathogenic factor. We investigated the effects of mycophenolic acid (MPA), the active metabolite of the immunosuppressant mycophenolate mofetil (MMF), on proliferation factors of cultured rat MCs. MPA was tested on the expression of platelet-derived growth factor-B (PDGF-B) and its receptor beta (PDGFR-beta), the immediate early gene (IEG) c-fos and the early growth response gene-1 (Egr-1), and AP-1 activation. METHODS Growth-arrested rat MCs were stimulated with 10% fetal calf serum (FCS) or 10-25 ng/ml platelet-derived growth factor-BB (PDGF-BB) in the presence or absence of MPA (0.019-10 microM) with or without guanosine (100 microM). MC proliferation was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation and direct cell counting. Cytotoxicity of MPA was evaluated using the MTT and LDH tests. Protein expression of PDGF-B and its receptor PDGFR-beta was quantified by western blot analysis. The effect of MPA on gene expression of PDGF-B, Egr-1 and c-fos was determined by the reverse transcriptase-polymerase chain reaction (RT-PCR). AP-1 activation was analysed by an electrophoretic mobility shift assay (EMSA). RESULTS Exposure of MCs to MPA caused a concentration-dependent inhibition of FCS-induced cell proliferation (cell number increase) with an IC50 of 0.44 +/- 0.03 microM and DNA synthesis with an IC50 of 0.52 +/- 0.02 microM without cell cytotoxicity in the therapeutic range. MPA decreased the PDGF-B protein expression and mRNA self-induction of PDGF-B but did not alter the protein expression of PDGFR-beta. MPA strongly inhibited the PDGF-BB-induced mRNA expression of Egr-1 decreasing to 7.6 +/- 2.5% after 30 min (P

Background. The calcimimetic drug cinacalcet offers a novel therapeutic option to treat post-transplant hypercalcemia and hyperparathyroidism; however, the interaction with calcineurin inhibitors and mycophenolate has not been evaluated. Methods. In the present study the effects of cinacalcet on the pharmacokinetics of cyclosporine A (CsA), tacrolimus (Tac) and mycophenolate were investigated in 14 renal transplant recipients with stable renal function (mean creatinine 126.4 ± 45.3 µmol/L). The patients were treated with either CsA (n = 8) or Tac (n = 6) in combination with mycophenolate/azathioprine and steroids. Twelve-hour pharmacokinetic investigations to measure CsA and its six main metabolites, Tac and mycophenolate concentrations were performed before and after 1-week treatment with 30 mg cinacalcet once daily. Results. Cinacalcet treatment induced a significant 14.3 ± 12.1% decrease in Tac AUC0−12 (P = 0.039). TacCmax,Tmax and T1/2 also tended to decrease. The pharmacokinetics of CsA and mycophenolate were not significantly affected by concomitant treatment with cinacalcet. However, the secondary CsA metabolite, AM19, showed a significant increase of 9.0 ± 9.5% during cinacalcet treatment (P = 0.040). Renal function decreased significantly from 78 ± 11 to 72 ± 12 mL/min (P = 0.019) and correlated with the increased levels of metabolite AM19 in the CsA group. Renal function was unchanged in the Tac group. Conclusion. Cinacalcet treatment showed a moderate effect on the Tac, but not CsA or mycophenolate, pharmacokinetics after 1-week concomitant treatment. This interaction appears to have minor clinical relevance. However, it is advisable to monitor renal function in CsA-treated patients due to the observed decrease in renal function.

Patient and graft survival following renal transplantation have improved markedly over the past decade, meaning that physician attention has turned more towards minimizing short- and long-term toxicities associated with immunosuppressive regimens. Gastrointestinal (GI) adverse events are common following renal transplantation and all immunosuppressive regimens have been associated with such events. Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) are potential components of immunosuppression regimens, and are associated with the most successful outcomes in kidney transplantation. The effects of MMF and EC-MPS are likely mediated via the active metabolite mycophenolic acid (MPA). The GI events caused by both MMF and EC-MPS may, in part, be related to MPA, independent of the formulation or route of administration. MPA may produce GI events either through direct action or through the action of it metabolites. However, many other factors may cause GI events observed following renal transplantation. These include the surgery itself and concurrent diseases such as diabetes, and bacterial, viral, fungal and parasitical infections. Additionally, numerous concomitant non-immunosuppressive agents, including antibiotics hypoglycaemic and proton-pump inhibitors, can be associated with GI events. In a recent trial in renal transplant patients with severe diarrhoea, approximately 50% of patients achieved resolution of diarrhoea through methods other than altering their immunosuppressive regimens. Indeed altering of the immunosuppressive regimen may lead to the risk of acute rejection. Thus, in order to reduce the risk of rejection and subsequent damage to the graft, it is important to consider other causes of GI events in renal transplant patients before altering immunosuppressive regimens.

Mycophenolic acid (MPA) is a relatively new immuno-suppressive drug, used since the nineties for theprevention of rejection in kidney transplantation.MPA has not only proved effective in preventingrejection, being even superior to azathioprine, but alsoseems to cause less adverse effects than otherimmunosuppressive drugs [1]. Because of these favour-able experiences with MPA in renal transplantation,the drug is currently used in patients with liver, lungand bone marrow transplantation as well. Given itsfavourable profile, MPA has also been used inautoimmune diseases. Following many cases andopen series on the successful use of MPA, mostly inthe form of mycophenolate mofetil (MMF), in renal,rheumatological, gastrointestinal, ophthalmological,dermatological and neurological autoimmune diseases,the first controlled studies have been published or areunderway.MPA is the active metabolite of the two currentlyavailable formulations: mycophenolate mofetil (MMF,Cellcept ) and the slow release formulation enteric-coated mycophenolate sodium (EC-MPS, Myfortic ).The mode of action and the pharmacokinetics of MPAare elegantly described by Allison [2]. In short, MPA isa non-alkylating drug that suppresses the immuneresponse by inhibiting the proliferation of activatedlymphocytes. MPA blocks the enzyme inosine mono-phosphate dehydrogenase (IMPDH), which is essentialfor the de novo synthesis of the purine guanine, andthereby inhibits lymphocytes from proliferating. Whilelymphocytes depend completely on IMPDH forsynthesis of guanine, most other human cells useother pathways for this synthesis, and are therefore notor less affected by the anti-proliferative effect of MPA.In addition, MPA has anti-fibrotic effects, as reviewedby Eugui [3].Following oral ingestion, both MMF and EC-MPSare resorbed and hydrolysed to MPA, which isconjugated in the liver into inactive mycophenolicacid glucuronide before being almost completelycleared by the kidney. Altered pharmacokinetics inpatients with renal insufficiency might explain theincreased rate of adverse effects, which can bemanaged by decreasing the dose of MMF [4]. MPAis not substantially cleared by peritoneal or haemodial-ysis [4].We hereby review the clinical experience with MPAin the treatment of renal diseases.

Background. After renal transplantation, patients with insufficient graft function may require phosphate binders. It is still unknown if sevelamer, a new calcium-free phosphate binder, interferes with the uptake of immunosuppressants. We studied its effects on the pharmacokinetics of cyclosporin A (CsA) and mycophenolate mofetil. Methods. We examined 10 adults and eight children with stable renal graft function and stable CsA trough levels. A 12 h pharmacokinetic profile (10 observation points) was conducted without sevelamer, after a single dose and after 4 days of treatment with it. CsA levels were measured with both a monoclonal antibody assay (CEDIA) and a polyclonal antibody assay (FPIA), mycophenolic acid (MPA) levels by EMIT assay and CsA metabolites AM1, AM9 and AM4N by a modified HPLC method. Results. Sevelamer had no significant effect on CsA kinetics [area under the curve (AUC), peak concentration (C max ), time of C max ]. The AUC of AM1 was decreased by 30% and C max by 25% after 4 days of sevelamer intake. MPA levels were significantly reduced by a mean of 25% of the AUC (P < 0.05) and by 30% of the C max after a single dose of sevelamer. Conclusions. A single sevelamer dose reduces the C max and the AUC of MPA. Its intake for several days does not significantly influence CsA kinetics.

Background. Although new immunosuppressive agents have improved the results of renal transplants (RTs), long-term graft loss remains high. We evaluated the impact of different immunosuppressive regimens on patient and graft survival. Methods. Data from 3365 patients receiving cadaver RTs in Spain during the years 1990, 1994 and 1998 were retrospectively analysed. All data were entered into a specially designed database. Graft and patient survival rates were estimated by the Cox regression method and results expressed as percentage survival. A maximum-likelihood estimate of the projected graft half-life (median value) was calculated by Weibull regression. Results. In 1990 graft and patient survival differed significantly from the other treatment years (P ¼ 0.0006 and P ¼ 0.0101, respectively). The risk of graft loss was significantly higher for cyclosporine (CsA), prednisone (P) and azathioprine (Az) than for CsA þ P, which in turn was higher than for CsA þ P plus polyclonal antibodies [antilymphocyte globulin (ALG)/antithymocyte globulin (ATG)]. Risk of patient death was also significantly higher for CsA þ P þ Az than for CsA þ P. No significant differences between treatment groups were found in graft and patient survival for 1994 and 1998. The projected median graft life for patients with the most used immunosuppressive regimen for each year was 12.9 years for CsA þ P þ Az and 15.6 years for CsA þ P plus mycophenolate mofetil (MMF). Conclusions. Triple therapy with Az in 1990 and 1994 and with MMF in 1998 were the most frequently used immunosuppressive regimens in the Spanish kidney transplant population. The best results were seen after induction therapy with polyclonal antibodies.

Background. Mycophenolate mofetil (MMF) has been successfully used to improve or prevent the development of systemic lupus erythematosus (SLE) in both humans and in several lupus-prone mice. In the present study, we evaluated mechanisms through which MMF may exert its therapeutic effect on the development of systemic autoimmunity. Methods. (NZB 3 NZW)F1 female mice were continuously treated with 100 mgukguday (high dose) or 30 mgukguday (low dose) MMF beginning at 3 months of age. The development of an autoimmune syndrome was evaluated by measuring immunoglobulin (Ig) isotypes of autoantibodies and their levels, as well as by evaluating immunopathological kidney abnormalities and mortality curves. Results. At both doses, MMF efficiently modulated the development of SLE. Although the higher dose of MMF directly inhibited the production of autoantibodies, 30 mgukguday MMF promoted qualitative but not quantitative changes in autoantibodies in (NZB 3 NZW)F1 female mice. These qualitative changes were manifested as a selective reduction in total or antigen-specific IgG2a antibody levels. Conclusions. The mechanisms through which MMF controls the development of SLE in (NZB 3 NZW)F1 females is highly dependent upon immunosuppressor dose. Interestingly, lower dose MMF selectively reduced IgG2a antibody levels, suggesting that this dose may modulate TH1 CD4q activity.

Mycophenolate mofetil (MMF) is increasingly used for prevention of allograft rejection and to treat immune disorders. We report the development of an acute inflammatory syndrome in two patients with Wegener's granulomatosis after MMF was introduced, because of persistent renal and systemic disease activity despite cyclophosphamide treatment. Within 1 week both patients developed an acute inflammatory syndrome, characterized by fever, arthralgias and muscle pain. No infection could be detected and no indications for increased Wegener's activity were present. MMF was stopped resulting in a rapid and complete resolution of the syndrome. A rechallenge with 2 g of MMF in the second patient resulted in a relapse of the syndrome within 4 days. There was an association between symptoms and increased levels of mycophenolic acid (MPA) acyl glucuronide and serum interleukin-6, suggesting the induction of inflammatory cytokines by MPA acyl glucuronide as the cause of the syndrome. Therefore, special attention should be given to side effects such as fever, arthralgias and muscle pain when treating patients with Wegener's granulomatosis during the active phase. Because this side effect of MMF may also occur after solid organ transplantation and in other immune disorders, pharmacokinetic profiling of MPA and MPA acyl glucuronide is needed in future studies with MMF.

of glucose concentration on angiotensin 11-induced hypertrophy of proximal tubular cells in culture. Biochem Biophys Res Commun 1991; 176: 902-909 14. Flyvbjerg A, Bornfeldt KE, Marshall SM, Arnqvist HJ, Orskov H. Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. Diabetologia 1990; 33: 334-338 15. Wolf G, Sharma K, Chen Y, Ericksen M, Ziyadeh FN. High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-0. Kidney Int 1992; 42: 647-656 16. Crowley ST, Brownlee M, Edelstein D et al. Effects of nonenzymatic glycosylation of mesangial matrix on proliferation of mesangial cells. Diabetes 1991; 40: 540-547 17. Nakamura T, Fukui M, Ebihara I et al. mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes 1993; 42: 450-456 18. Ayo SH, Radnik RA, Glass WF et al. Increased extracellular matrix synthesis and mRNA in mesangial cells grown in highglucose medium. Am J Physiol 1991; 260: F185-F191 19. Ziyadeh FN, Sharma K, Ericksen M, Wolf G. Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-/?. J Clin Invest 1994; 93: 536-542 Nephrol Dial Transplant 1995: Editorial Comments

Background A small proportion of patients with initially steroid-sensitive nephrotic syndrome relapse frequently, despite treatment with cyclophosphamide and/or cyclosporin. We investigated the efficacy of mycophenolate mofetil (MMF) in this group. Methods Seven patients with nephrotic syndrome due to minimal change nephropathy (MCN) or classical focal segmental glomerulosclerosis (FSGS) who had suffered multiple relapses over many years despite treatment with several different agents were commenced on MMF 1 g twice daily, together with a reducing dose of corticosteroids. Results Six patients went into complete remission and the seventh into partial remission. At 1 year, five remained in complete remission. The median (range) serum albumin concentration rose from 19 g/l (16-42 g/l) pre-MMF to 42 g/l (25-45 g/l) after 12 months (P=0.023), and the median (range) dose of prednisolone fell from 40 mg/day (30-60 mg/day) to 7.5 mg/day (0-40 mg/day) at 12 months (P=0.0008). Conclusion MMF appears to be of benefit in the treatment of multiply relapsing nephrotic syndrome caused by MCN or FSGS. Controlled trials are required to establish the role of MMF in these disorders.