Treatment of lupus nephritis by mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN. METHODS: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis. MMF was administered in the dose of 1.5-2 g/24 h and prednisone at 10-20 mg/day. The treatment effects were followed over a 12-month period. RESULTS: After 3 months of therapy significant reduction in proteinuria was achieved (2.1 +/- 2.4 g/24 h vs. 1.0 +/- 1.0 g/24 h, p < 0.01) and maintained to the end of the study. In parallel, a significant rise in serum albumin, a fall of cholesterol and a significant increase in mean glomerular filtration rate were noted. Complete remission was achieved in 16 patients (45.7%), including all patients in class III and V plus 10 patients in class IV. Not a single adverse effect was observed. CONCLUSION: MMF combined with low doses of steroids is an effective and safe treatment for the maintenance of stable remission of LN.

Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study.

BACKGROUND/AIMS: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. METHODS: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. RESULTS: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9-8.4) to 1.28 g/day (IQR 0.5-2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13-6.48) to 0.84 (IQR 0.42-2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 +/- 3.46 to 2.16 +/- 2.46, between the first (visits 1-2) and last (vists 4-5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 +/- 31.8 to 65.3 +/- 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. CONCLUSION: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

[Therapy of lupus nephritis with mycophenolate mofetil].

INTRODUCTION: Mycophenolate mofetil is an immunosuppressive agent used in transplantation and subsequently in a variety of autoimmune conditions. It inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on the kidney. The major experience in systemic lupus erythematosus has focused on proliferative lupus nephritis. MATERIALS AND METHODS: In our study we treated 8 female patients having proliferative lupus nephritis with combination therapy of prednisone (1 mg/kg body weight) and mycophenolate mofetil (2 g per day). Complete remission was defined as a value for urinary protein excretion that was less than 0.5 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration and improved or stable serum creatinine. Partial remission was defined as a daily proteinuria below 2g in the previously nephrotic patient or minimum 30% from starting values, with normal urinary sediment, serum albumin of minimum 30 g/L and stable serum creatinine. RESULTS: Two patients had a complete remission after 7 and 2 months respectively. Five patients had a partial remission after 5.2 +/- 4.3 months of therapy. One patient did not react to therapy. There were no side effects during the course of therapy. DISCUSSION: Considering the fact that 7/8 patients have had nephrotic range proteinuria and that 50% of patients were refractory on standard induction therapy, the results of this study are a good indicator of value of mycophenolate mofetil in the therapy of proliferative forms of lupus nephritis. CONCLUSION: Mycophenolate mofetil has satisfactory results in the treatment of proliferative forms of lupus nephritis with minimal side effects.

[Evaluation of effects of the intravenous cyclophosphamide treatment of primary glomerulonephritis and the estimation of complications].

INTRODUCTION: Primary glomerulonephritis can be treated by the intravenous use of cyclophosphamide. The aim of our study is to evaluate the effect of the drug in the treatment of mentioned diseases and the follow-up of complications. MATERIAL AND METHODS: There are 30 patients included in this study, mean-age of 46.83 years. Renal biopsy was performed in 25 patients. Membranoproliferative glomerulonephritis was diagnosed in 36.67% of patients, mesangioproliferative in 16.67%, rapidly progressive in 13,33%, membranous in 10%, chronic in 10%, primary focal segmental glomerulosclerosis in 3,33% and 10% of patients were unclassified They have been treated with cyclophosphamide in intermittent "pulse" doses: once a month fbr the first 6 months and once in 3 months, for 18 months or longer, after that. RESULTS AND DISCUSSION: The drug was given in the recommended dose of 0.5-lg/m of body-surface area, in the combination with a low-dose corticosteroides. Hematological and renal fimnctional tests were checked before every "pulse" dose. Concerning the development of the renal ailure the fivorable effect occurred in 50% of patients. Proteinuria was found in all patients (80% >3.5 gr/24 h). The favorable effect occurred in 80% patients. At the end, serum proteins were normal in 76.67% patients. 30% of patients normalized the erythrocyte sedimentation level. Remission has not been achieved in 23.33% of patients, 10% of patients developed relapse. 20% of patients died infections were the most common complication and they occurred in 30% of patients. Sepsis, leucopenia, Herpes Zoster infection and hemorrhagic cystitis have not occurred in any patient. Malignant tumor was found in 6.67% of patients.

[Therapy of lupus nephritis with mycophenolate mofetil].

INTRODUCTION: Mycophenolate mofetil is an immunosupressive agent used in transplantation and subsequently in a variety of autoimmune conditions. It inhibits both B and T lymphocyte proliferation, and also has nonimmune effects on the kidney. The major experience in systemic lupus erythematosus has focused on proliferative lupus nephritis. MATERIALS AND METHODS: In our study we treated 8 female patients with proliferative lupus nefritis with combination therapy of prednisone (1 mg/kg body weight) and mycophenolate mofetil (2 g per day). Complete remission was defined as a value for urinary protein excretion that was less than 0.5 g per 24 hours, with normal urinary sediment, a normal serum albumin concentration and improved or stable serum creatinine. Partial remission was defined as a daily proteinuria below 2 g in a previously nephrotic patient or minimum 30% from starting values, with normal urinary sediment, serum albumin of minimum 30 g/L and stable serum creatinine. RESULTS: Two patients had a complete remission after 7 and 2 months respectively. Five patients had a partial remission after 5.2+/-4.3 months of therapy. One patient did not react on therapy. There were no side effects during the course of therapy. DISCUSSION: Considering the fact that 7/8 patients have had nephrotic range proteinuria and that 50% of patients were refractory on standard induction therapy, results of this study are good indicator of value of mycophenolate mofetil in the terapy of proliferative forms of lupus nephritis. CONCLUSION: Mycophenolate mofetil gives satisfactory results in the treatment of proliferative forms of lupus nephritis with minimal side effects.

[Comparative study of the efficacy of different regimens of intermittent subcutaneous dosing of erythropoietin beta in treatment of renal anemia in chronic dialysis patients].

INTRODUCTION: The use of erythropoietin (EPO) in the treatment of renal anemia is justified by more than 15 years of experience. Clinical trials have shown that subcutaneous erythropoietin beta (Recormon - F. Hoffmann-La Roche) therapy once weekly, or even once every two weeks has proven successful. The aim of this study was to evaluate the efficacy of different regimes of Recormon therapy in maintaining stable levels of hemoglobin (Hb) and hematocrit (HCT) in hemodialysis patients. MATERIAL AND METHODS: An open, comparative, multicenter study was divided into three arms of patients and lasted for 24 weeks. 98 patients with stable Hb level (>100 g/l), were treated with a stable dose of Recormon, and had a ferritin level > 200 microg/l and transferrin saturation >20%. During the first 8 weeks all were on the usual 2-3 times weekly epo dosage. 8 weeks later, 70 patients received epo once weekly, while 28 patients (group 1) maintained the same regimen for the entire study period. After another 8 weeks, 21 of those 70 patients receiving epo once weekly, received it once every two weeks (group 3), while 49 patients continued once weekly regimen to the end of the trial (group 2). The primary efficacy parameter was the percentage of patients maintaining their target Hb and HCT levels (>100 g/l and >30% for HB and HCT respectively). RESULTS: 86 patients (87.75%) completed the study (25 from group 1, 42 from group 2 and 19 from group 3). One patient was excluded because he was transplated during the study, one due to uncontrolled hypertension, while 10 patients, all from the same center, were excluded due to protocol violation (4-week gap in epo therapy due to problems with epo supply). Efficacy analysis included per-protocol population (86 patients). Hb levels remained stable (>100 g/l) in all three groups. Although there were statistically significant differences in Hb levels between visits (p=0,026), there were no statistically significant differences between groups throughout the study (p=0,439). HCT levels remained stable (>30%) in all three groups throughout the study, without statistically significant differences between visits (p=0,053) and between groups (p=0,155). The average epo doses were not statistically significantly different between visits (p=0,676) or between groups (p=0,512). The main tolerability parameters: sitting systolic (SSBP) and diastolic (SDBP) blood pressures were monitored at all visits. Statistical analysis showed that there were no differences in SSBP or SDBP between visits or groups of patients throughout the study. CONCLUSION: All three dosing regimens of subcutaneous epo beta were statistically equivalent in maintaining target Hb and HCT levels. Once weekly or once every two weeks administration of epo beta does not lead to dose increase, and provides greater opportunities to individualize treatment for every single patient and may lead to better compliance.

[Goodpasture's syndrome--case report]. / Goodpastureov sindrom--prikaz slucaja.

INTRODUCTION: Goodpasture's syndrome is a rare, autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis and production of anti-GBM (glomerular basement membrane) antibodies. The etiology of this syndrome is still unknown. Goodpasture's syndrome usually starts with pulmonary hemorrhage, which is followed by symptoms of kidney disease. Laboratory findings often include: anemia, microhematuria, proteinuria, increased levels of urea and creatinine and anti-GBM antibodies. Diagnosis of this syndrome can be established by presence of pulmonary hemorrhage, pulmonary radiography, kidney biopsy and positive result of circulating anti-GBM antibodies. Treatment of this syndrome should be initiated as soon as possible using a combination of corticosteroids, cytostatics and plasmapheresis. CASE REPORT: The first symptoms in a nineteen-year-old female patient were caused by anemia. Two months later she reported symptoms of pulmonary hemorrhage. At that point of time she already had renal insufficiency and was immediately hospitalized. The same day we started therapy with corticosteroids, endoxan and plasmapheresis was initiated Recovery of pulmonary function was obtained, but kidney function was lost. DISCUSSION AND CONCLUSIONS: The most important thing in regard to Goodpasture's syndrome is quick diagnosis. Because of that, if patients report any kind of pulmonary hemorrhage, this syndrome must be considered At that point of time, kidney function is usually not irreversibly damaged. The second important thing in Goodpasture's syndrome is that treatment must be very aggressive using a combination of immunosuppressives and plasmapheresis. This is the only chance for these patients to avoid hemodialysis or death.

[Major characteristics of immunoglobulin A nephropathy]. / Glavne karakteristike imunoglobulin A nefropatije.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is one of the most common forms of primary glomerulonephritis in many countries. Most clinical features of IgAN point to a renal problem, such as recurrent macroscopic hematuria or asymptomatic microscopic hematuria and proteinuria. Pathologic features of IgAN present with different types and different degrees of glomerular, tubulointerstitial and vascular lesions. The aim of this study was detailed analysis of clinical and laboratory findings, as well as findings of immunofluorescence and light microscopy. We also investigated associations between these factors. MATERIAL AND METHODS: We investigated 60 patients who underwent renal biopsy. The study was partly retrospective and partly prospective. RESULTS: The average age of patients was 34.19 years. Male female ratio was 2.33:1. IgAN was most frequently asymptomatic (83.33%) as microhematuria and proteinuria, while gross hematuria was found in 16.667%. Renal biopsy material was analyzed by light microscopy revealing changes in all glomerular structures. Immunofluorescence microscopy demonstrated dominant IgA deposits. This study established association of glomerulosclerosis with clinical features of disease. DISCUSSION AND CONCLUSIONS: IgAN frequently develops in the 4th decade of life, mostly in males and presents as asymptomatic (83.33%). Pathohistological changes include all glomerular structures. There is no specific serological test for IgAN, but pathological changes affect clinical features of the disease, as proteinuria and increase of creatinine concentration.

Tubulointerstitial dysfunction in early post-transplant period.

Dysfunction of a transplanted kidney may develop at any time in the post-transplant period. The aim of this study was to differentiate levels of early dysfunction of a transplanted kidney. The study included 45 examinees undergoing kidney transplantation. They were divided into four groups, in regard to length of hospitalization and post-transplant complications: group I (up to 15 days, complication-free); group II (up to 15 days, with complications); group III (up to 30 days); group IV (up to 60 days). The control group included patients undergoing abdominal surgery, without uropoetic system disorders. The following parameters were examined on a daily basis a month after transplantation on average: creatinine clearance, creatinine and urea. Statistical analysis of these parameters revealed the following levels of renal dysfunction: control group--circulatory tubular dysfunction without azotemia; group I--polyuric acute tubular necrosis; group II and group III--severe or moderately severe polyuric acute tubular necrosis and group IV--polyuric acute tubular necrosis.

A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients.

BACKGROUND: Lanthanum carbonate (LC) (Fosrenol) is a novel new treatment for hyperphosphatemia. In this phase III, open-label study, we compared the effects of LC and calcium carbonate (CC) on the evolution of renal osteodystrophy (ROD) in dialysis patients. METHODS: Ninety-eight patients were randomized to LC (N = 49) or CC (N = 49). Bone biopsies were taken at baseline and after one year of treatment. Acceptable paired biopsies were available for static and dynamic histomorphometry studies in 33 LC and 30 CC patients. Blood samples were taken at regular intervals for biochemical analysis and adverse events were monitored. RESULTS: LC was well tolerated and serum phosphate levels were well controlled in both treatment groups. The incidence of hypercalcemia was lower in the LC group (6% vs. 49% for CC). At baseline, subtypes of ROD were similarly distributed in both groups, with mixed ROD being most common. At one-year follow-up in the LC group, 5 of 7 patients with baseline low bone turnover (either adynamic bone or osteomalacia), and 4 of 5 patients with baseline hyperparathyroidism, had evolved toward a normalization of their bone turnover. Only one lanthanum-treated patient evolved toward adynamic bone compared with 6 patients in the CC group. In the LC group, the number of patients having either adynamic bone, osteomalacia, or hyperpara decreased overall from 12 (36%) at baseline to 6 (18%), while in the calcium group, the number of patients with these types of ROD increased from 13 (43%) to 16 (53%). CONCLUSION: LC is a poorly absorbed, well-tolerated, and efficient phosphate binder. LC-treated dialysis patients show almost no evolution toward low bone turnover over one year (unlike CC-treated patients), nor do they experience any aluminum-like effects on bone.

[Radioconstrast nephropathy]. / Radiokontrastna nefropatija.

INTRODUCTION: Hospital-acquired acute renal failure increased in the last years from about 5 to 6.4%, while mortality remained high and according to newest investigations it is about 60% on average. Radiocontrast-induced nephropathy is the third cause of death in hospital-acquired acute renal failure. RISK FACTORS FOR RADIOCONTRAST-INDUCED NEPHROPATHY: Risk factors for radiocontrast-induced nephropathy include: the existing kidney disease, diabetes, dehydratation, multiple myeloma, older age and earlier kidney damage by contrast substances. COURSE OF RADIOCONTRAST-INDUCED NEPHROPATHY: The clinical course of radiocontrast-induced nephropathy may manifest from asymptomatic picture to development of oliguric form of acute renal failure. PREVENTION AND TREATMENT MODALITIES OF RADIOCONTRAST-INDUCED NEPHROPATHY: Modalities of prevention and treatment of radiocontrast-induced nephropathy are as follows: adequate hydration of patients, appropriate application of diuretics, calcium channel blockers nonionizing radiocontrast and preventive haemodialysis. EXPERIMENTAL STUDIES IN PREVENTION AND TREATMENT OF RADIOCONTRAST-INDUCED NEPHROPATHY: Experimental studies indicate application of atrial natriuretic peptide, endothelin, prostaglandin. CASE REVIEW: Two patients treated at the Clinic for Nephrology and Clinical Immunology in Novi Sad, presented with radiocontrast-induced nephropathy. In one patient it appeared after panaortography and in the second after computerized tomography of the abdomen. In both cases aggravation occurred due to already existing renal failure caused by radiocontrast substances. CONCLUSION: The problem is particularly important because there is a large number of patients in whom there is a risk of radiocontrast-induced nephropathy and it is necessary to carry out adequate prophylaxis and accurate assessment of kidney function before application of radiocontrast substances.

[Immunoglobulin A nephropathy and disease prognostic factors]. / Imunoglobulin A nefropatija i faktori prognoze bolesti.

INTRODUCTION: Immunoglobilin A nephropathy (IgAN) is a clinicopathological entity characterized by diffuse glomerular mesangial deposition of IgA as the predominant immunoglobulin. Renal biopsy reveals a spectrum of changes in glomerula, tubulointerstitium and blood vessels. 20-50% of all patients develop end-stage renal failure 20 years after onset of disease. The aim of this study was to investigate the incidence of IgAN and to analyze clinicopathological changes and prognosis of IgAN. MATERIAL AND METHODS: The study included 60 patients with biopsy-proved IgAN without some other systemic diseases or Henoch-Schonlein purpura. We analyzed clinical features of the disease, laboratory findings, findings of immunofluorescence and light microscopy and prognosis of IgAN. The study is partly retrospective and partly prospective. RESULTS AND DISCUSSION: Incidence of the disease in the period 1981-1997 was 9.78%. At the moment of renal biopsy 63.16% of patients had normal renal function, 31.58% had stage I and 5.25% had stage II chronic renal failure. At the end of study 21.05% of investigated patients were included into the worse stage of renal failure in regard to the initial stage. Progression of renal damage correlated with special tubulointerstitial damage and heavy proteinuria. CONCLUSIONS: In this study we found severe histopathological changes in the group with already impaired renal function and these changes correlated with laboratory findings, clinical features and prognosis. Normal renal function at the moment of renal biopsy pointed to risk for further damage. Changes in the tubulointerstitium and mesangium, heavy proteinuria and hypertension affect the disease prognosis. Evolution to the higher stage of renal failure was 1.24% per year and this requires long-term follow-up of patients with IgAN.

[Long term survival of patients with lupus nephritis]. / Dugogodisnje prezivljavanje bolesnika s lupusnim nefritisom.

Lupus nephritis is a clinical manifestation of Systemic Lupus Erythematosus with most prominent influence on the course of the disease. The most predictive parameters for development of renal failure are: type of hystological changes, degree of interstitial inflammation, serum creatinine concentration at the time of diagnosis and therapeutical protocols used in the treatment. Single center experience in a group of 220 lupus patients is presented in this paper. In 130 patients (59%) lupus nephritis was diagnosed by clinical and laboratory tests, while 74 kidney biopsies were performed. Proliferative type of lupus nephritis (class IV in 54% of cases and class III in 18.9%) was more frequent than the other histological types. During a long term follow up (range 1-17 years, mean 7.6 years) renal failure developed in 17 patients (24%), while 11% of patients developed uremia and required dialysis. Development of renal failure was influenced by histological changes with predominance of class IV lupus nephropathy, disseminated disease with more ARA criteria for systemic lupus erythematosus classification present at the time of kidney biopsy, more frequent lupus flares, persistence of low complement levels during the first year of follow-up and even earlier.