Peritonitis due to Neosartorya pseudofischeri in an elderly patient undergoing peritoneal dialysis successfully treated with voriconazole.

Aspergillus peritonitis is a rare life-threatening complication of peritoneal dialysis (PD). We report a case of symptomatic Neosartorya pseudofischeri peritonitis in a 60-year-old woman treated by continuous ambulatory peritoneal dialysis (CAPD) for 13 months, who performed peritoneal exchanges independently. This is believed to be the first published case of N. pseudofischeri in an elderly patient. Comprehensive treatment included early removal of the PD catheter and the use of voriconazole (200 mg Vfend twice daily) for a period of 5 weeks. This case supports the need for more effective prophylaxis and treatment of non-Candida fungal infections in CAPD patients. Our conclusions from this case and a review of the literature are that infection with this fungus can cause substantial morbidity and is best treated with prompt catheter removal, aggressive antifungal therapy with voriconazole or amphotericin B, and vigilant observation for complications. Our report describes for what is believed to be the first time the administration of voriconazole to treat a Neosartorya peritonitis case.

Increased cardiac troponin T and C-reactive protein levels in end-stage renal disease are associated with obstructive sleep apnea.

BACKGROUND: Increased cardiac troponin T (cTnT) and C-reactive protein (CRP) levels predict mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis. Obstructive sleep apnea (OSA) is associated with severe cardiac stress and systemic inflammation. We hypothesized that in patients with ESRD elevated levels of cTnT and CRP are consequences of unrecognized OSA. METHODS: After diagnostic polysomnography, serum levels of cTnT and CRP were assessed in two groups of patients. The first group with normal renal function which served as a control group, was recruited from routine patient referrals to the sleep laboratory at the University Hospital Magdeburg. The second group consisted of patients with ESRD on thrice-weekly maintenance hemodialysis treatment (hemodialysis group). RESULTS: After screening, 15 patients in each group were eligible for inclusion. OSA (apnea hypopnea index (AHI) > or = 10) was associated with significantly elevated serum CRP levels of 5.1 +/- 4.9 mg/l in the control group and 11.6 +/- 10.2 mg/l in the hemodialysis group, compared with patients in the respective groups without OSA. In the control group, cTnT levels were below the lower detection limit, independent of OSA severity. Patients with ESRD but without OSA had low cTnT levels, similar to those of patients in the control group (0.014 +/- 0.01 ìg/l), whereas patients with ESRD and OSA had significantly elevated serum cTnT levels (0.38 +/- 0.3 microg/l, p < 0.05). CONCLUSIONS: OSA is associated with higher CRP levels in patients with normal or impaired renal function, but cTnT is elevated in OSA patients with impaired renal function only. In this pilot study, both parameters suggest an important role of sleep related breathing disorders on cardiac stress and chronic inflammation.

[Restless legs syndrome in patients on dialysis for kidney insufficiency: effect of medication]. / Restless-Legs-Syndrom bei dialysepflichtiger Niereninsuffizienz: Einfluss der Medikation.

BACKGROUND AND OBJECTIVES: Many patients on dialysis have a restless legs syndrome (RLS). Drugs may cause as well as relieve RLS symptoms. It was the aim of this study to examine the effect of the prescribed drugs on the occurrence of RLS in patients on hemodialysis. PATIENTS AND METHODS: The cohort consisted of 82 out-patients undergoing dialysis (38 men and 44 women; mean age 65,4 [21 - 93] years) during 2002 and 2003. In addition to blood analysis the criteria of RLS were analysed, using the Johns Hopkins restless legs severity scale (JHRLSS) and the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG). Periodic limb movements in sleep (PLMS) were measures by a special device. RESULTS: 25 of 82 patients had RLS symptoms, using the JHRLSS, in 23 this was confirmed by the IRLSSG criteria. PLMS occurred in 46 of 81 patients. The occurrence of RLS correlated significantly with the intake of drugs that could potentially increase RLS severity. But there was no strong correlation with drugs that could potentially decrease it. There was no association between medication and the occurrence of PLMS. There was also no correlation with laboratory parameters. CONCLUSION: In patients on dialysis those drugs which can potentially worsen RLS should be prescribed with care.

Predicting outcome and survival in patients with Wegener's granulomatosis treated on the intensive care unit.

OBJECTIVE: This study was designed to search for risk factors predicting mortality of patients with Wegener's granulomatosis (WG) treated on the intensive care unit (ICU). METHODS: Seventeen patients admitted to the ICU of an University Hospital for an acute illness related to WG were analysed retrospectively over 4 years. A variety of clinical and laboratory variables were recorded. Contingency table analyses, univariate logistic regression, and discriminate analysis were performed to determine which factors influenced a negative outcome. RESULTS: Reasons for ICU admission were respiratory failure (n = 10), severe haemoptysis (n = 13), sepsis (n = 9), acute renal failure (n = 6), and gastrointestinal bleeding (n = 1). Patients were treated for a median of 6 days (range 4-121 days). During the stay in the ICU, five patients died within 24-121 days (overall mortality 29.4%). Causes of death were cerebral haemorrhage (n = 2), pulmonary embolism (n = 1), and sepsis (n = 2). Significantly associated with death were: Acute Physiology and Chronic Health Evaluation II (APACHE II) score>24 [p = 0.004, odds ratio (OR) 0.568, 95% confidence interval (CI) 0.327-0.989], period of time in the ICU>10 days (p = 0.001, OR 0.795, 95% CI 0.589-1.072), and treatment with cyclophosphamide during the stay in the ICU (p = 0.013, OR 0.799, 95% CI 0.651-0.980). No association was found for higher age, C-reactive protein (CRP), pulmonary involvement, serum creatinine, and requirement of haemodialysis. CONCLUSIONS: The prognosis for WG patients in the ICU is serious, but the majority can survive. To achieve a more favourable outcome, patients should stay in the ICU for as short a time as possible. The occurrence of renal failure did not influence the outcome in our patients.

Vitamins are associated with survival in patients with end-stage renal disease: a 4-year prospective study.

BACKGROUND: Patients with end-stage renal disease are at high risk from premature death due mainly to cardiovascular disease and infections. Established risk factors do not sufficiently explain this increased mortality. We, therefore, investigated total mortality prospectively in a single-centre study in patients on hemodialysis and assessed the prognostic value of baseline disease status, laboratory variables including emerging risk factors, and the influence of vitamin treatment. METHODS: Patients (n = 102) were followed-up for 4 years or until death (n = 49). Survival was calculated by the Kaplan-Meier method. Cox-proportional hazards model was used to determine independent predictors of total mortality. RESULTS: The known risk factors age, baseline clinical atherosclerotic disease, low albumin and increased cardiac troponin T were significantly associated with mortality. Patients who received multivitamins during follow-up had a significantly lower mortality risk than those not receiving this treatment (hazard ratio 0.29, 95% confidence interval 0.15-0.56). These associations remained significant after adjustment for age, cardiovascular disease, albumin and cardiac troponin T at baseline. CONCLUSIONS: The present study suggests that multivitamin supplementation in patients with end-stage renal disease is closely associated with reduced mortality due to all causes. These observations have to be validated in randomized clinical intervention trials.

[Diagnostics and therapy of diabetic nephrology]. / Diagnostik und Therapie der diabetischen Nephropathie.

In Germany, 36% of all new chronic dialysis patients have diabetic nephropathy. The majority are type 2 diabetics. Early intervention has the greatest effect. Incipient nephropathy can be diagnosed by evidence of microalbuminuria (30-300 mg albumin/g creatinine). Proteinuria on the standard test strip (>300 mg/g) indicates manifest nephropathy followed by progressive renal failure. Important cofactors for progression are hypertension, hyperglycemia, and smoking. Low normal blood pressure levels (<130/80 mmHg without and <125/75 mmHG with proteinuria) based on ACE inhibitors/AT1 blockers are the goal. Combination therapies are frequently necessary. This can often reverse microalbuminuria. Chronic renal failure requires special attention (e.g. bone metabolism, anemia, acidosis). Timely initiation of renal replacement therapy (GFR <15 ml/min) reduces morbidity and mortality. In addition to hemo- and peritoneal dialysis, early kidney and in individual cases of type 1 diabetes combined kidney/pancreas transplantation is appropriate.

Plasma serotonin and histamine levels in hemodialysis-related pruritus are not significantly influenced by 5-HT3 receptor blocker and antihistaminic therapy.

BACKGROUND: Elevated plasma histamine levels are considered to play a part in the pathophysiology of hemodialysis-related pruritus. However, antihistaminic therapy often fails to provide sufficient relief. Elevated serotonin levels in patients on dialysis therapy have also been described but the effects of 5-HT3 receptor antagonists on hemodialysis-related pruritus remain controversial. METHODS: we conducted a study to determine plasma histamine and serotonin levels before and after treatment with 5-HT3 receptor antagonists (tropisetron 5 mg and ondansetron 8 mg) and an antihistamine (cetirizine 10 mg). Eleven hemodialysis patients with a history of pruritus participated in this study,10 healthy volunteers served as control group. RESULTS: Histamine and serotonin values were normal in patients and controls. Treatment with cetirizine did not significantly reduce histamine levels in patients or in controls. Tropisetron and ondansetron likewise did not alter serotonin levels in patients. Tropisetron treatment did not significantly change serotonin levels in controls. CONCLUSION: Histamine and serotonin are no major mediators of pruritus in hemodialysis patients. Elevated histamine levels are occassionally seen and may be due to the increased mast cell number found in a subgroup of hemodialysis patients. Our findings explain the only marginal relief of antihistamines and the controversial antipruritic effect of serotonin receptor antagonists in hemodialysis-related pruritus.

Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.

OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Short- and long-term effects of fish oil on proteinuria, morphology and renal hemodynamics in the Milan normotensive rat model of spontaneous glomerulosclerosis.

BACKGROUND/AIMS: A diet rich in polyunsaturated Omega3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short- and long-term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. METHODS: Eight rats each were pairfed FO- versus cholesterol-enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2-week trial: 1 rat on the FO and 1 rat on the control diet; 32-week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. RESULTS: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75+/-2.19 vs. 6.87+/-1.91 ml/min/g, p<0.05), and the prostaglandin E2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1. 76+/-0.18 vs. 0.91+/-0.19, p<0.05). During the long-term trial proteinuria in the FO animals progressed faster and to a higher level (176.5+/-32.2 vs. 82.7+/-36.7 mg/24 h at week 32, p<0.01). After 32 weeks the renal blood flow was significantly lower in th FO group 2.8+/-1.1 vs. 4.6+/-1.9 ml/min/g, (p<0.05), and the rats had an accelerated development of nephrosclerosis, with sclerotic lesions in 60.3+/-6.6% of the glomeruli as compared with 46.5+/-9.8% in the cholesterol and 39.8+/-5.9 in the control group (p<0.05). CONCLUSION: The short-time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

Supplementation with vitamin B12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease.

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin B6. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (<180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B12 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.

Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease.

BACKGROUND: Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. RESULTS: Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.

A prospective randomised European multicentre study of medium-long run mortality and morbidity comparing acetate-free biofiltration and bicarbonate dialysis.

In recent years, the progressive increase in the mean age of the population entering chronic dialysis treatment has been responsible, on the one hand, for the growing number of patients undergoing regular dialysis, and on the other, for the high number of "critical" patients, both as a result of their age and the presence of concomitant morbidity. Thus, dialysis treatment today is not only aimed at waste removal and water-electrolyte homeostasis, but also at a reduction in morbidity and mortality, and at improving the patients' quality of life, thanks to the use of biocompatible materials and the achievement of good cardiovascular tolerance to treatment. Consequently, diffusive-convective dialysis procedures have been on the increase, since they combine better depuration with the use of biocompatible high-flux membranes. Acetate-free biofiltration (AFB) is a diffusive-convective dialysis procedure which utilises a high-flux membrane, AN69, post-dilution infusion of a sodium bicarbonate solution (NaHCO3), and a dialysate which is completely free of any buffer, and thus also free of acetate, which may have various negative effects on the patient. A number of studies have already shown the better hemodynamic stability and the reduction of intradialytic side-effects during AFB. All these, however, were short-term studies. To verify the beneficial effects of AFB in the long run, a three year multicentre randomised European trial has been proposed to compare bicarbonate hemodialysis (BD), a technique used in nearly 80% of the world's dialysis population, and AFB. The specific aim of the investigation is to verify, in a large number of patients, the results of hemodialysis treatment in terms of morbidity, mortality and quality of life. The study involves 80 hemodialysis units across Italy, France, Germany, Spain, Slovenia and Croatia, with enrollment of about 400 patients considered "critical" for at least one of the following reasons: age, diabetes, dialysis cardiovascular instability. Fifty percent of the patients are to undergo AFB with the AN69 membrane and bicarbonate solution infusion (NaHCO3 145 or 167 mEq/lt), and the other fifty percent are to be treated by BD, with any membrane except the nonmodified cellulosic one. Biochemical, cardiological, and nutritional parameters will be considered throughout the study. Mortality, morbidity both in terms of intra- and interdialysis symptoms - and hospitalisation rate, as well as the patients' quality of life, evaluated by the SF36 questionnaire, will be analysed.

Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.

BACKGROUND: This study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated. METHODS: Blood was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglyceridemic patients [HTG; triglycerides (TG) < 2.2 mmol/liter] before hemodialysis, during (1.5 hr after the beginning of anticoagulation) and at the end of treatment. In each sample, lipid values and CETP activity were measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties of LDL, fractions obtained from NTG and HTG patients were incubated with human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. RESULTS: In comparison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01) and small in size (P < 0.001). These LDL induced the cholesterol esterification rates (50 micrograms/mL LDL-protein) in a twofold greater unsaturation in macrophages when compared to LDL from NTG patients (P < 0.04). The rates in fibroblasts were reduced by approximately half (P < 0.05). During hemodialysis, LDL were decreased in size (P < 0.001) and depleted in TG (P < 0.01), particularly in the hypertriglyceridemic state. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained during hemodialysis were incubated with cells, esterification rates particularly in macrophages were markedly accelerated in comparison to the unmodified lipoprotein at baseline (P < 0.05). CONCLUSION: LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL were related to the cellular uptake, these LDL were a superior substrate for murine macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by the specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, increased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis in vivo could contribute to the high prevalence of premature atherosclerosis found in HTG patients with ESRD.

Prevention of glomerular hypertrophy and glomerulosclerosis in Milan normotensive rats by low-protein diet, but not by low-dose captopril treatment.

Milan normotensive rats, which spontaneously develop marked proteinuria (PU) and glomerulosclerosis (GS), were either kept on a normal-protein diet, a normal-protein diet with additional low-dose captopril (CAP), which did not affect blood pressure, or on a low-protein diet. After 8 months PU (79 +/- 25 mg/day) GS (3 +/- 2%) and total glomerular volume (TGV; 27.9 +/- 2.9 mm3/kidney) were significantly lower (p < 0.05) in the low-protein diet group than in both the normal-protein group (PU 583 +/- 210 mg/day, GS 12 +/- 5%, TGV 34.6 +/- 8 mm3/kidney) and the low-CAP group (PU 611 +/- 224 mg/day, GS 16 +/- 6%, TGV 41.8 +/- 8.6 mm3/kidney). In conclusion, the development of glomerular hypertrophy and GS in Milan normotensive rats was reduced by the low-protein diet, but not by low-CAP treatment.

Physiological aspects of genome variability in tissue culture. I. Growth phase-dependent differential DNA methylation of the carrot genome (Daucus carota L.) during primary culture.

Investigations were performed on growth phase-dependent EcoRII site-specific DNA methylation of the carrot genome during primary culture to elucidate physiological aspects of genome DNA variability in tissue culture. While DNA methylation of the root cambium and the secondary phloem and petioles of carrot leaves were strikingly different, the methylation level of the secondary phloem seemed to be independent of cultivar origin, the age of the plants and the extent of secondary root growth. As was shown earlier a change in the differentiated state of the secondary phloem by tissue culture leads to changes in genome modification. Whereas de novo methylation was observed during the first 2 weeks of growth initiation, the results presented demonstrate genome de-methylation during the transition to stationary growth indicating differential εnome methylation during different phases of culture. The presence of kinetin in the nutrient medium of the primary culture was found to be antagonistic to changes in genome modification in general. De novo methylation and subsequent de-methylation of the carrot genome are discussed as gross changes obviously essential to molecular genome differentiation during tissue culture.

[Cyclophosphamide bolus therapy in lupus nephritis]. / Cyclophosphamid-Bolustherapie bei Lupusnephritis.

A pilot study of 21 patients (17 women; 4 men; mean age 35 [18-59] years), randomized into two groups, was undertaken to test how many cycles of intravenous pulse cyclophosphamide administration were required in lupus nephritis to achieve remission. It was planned that patients randomized to group A should be treated for 3 months, those in group B for over 12 months. In the first cycle the cyclophosphamide dosage was 500 mg/m2, in the subsequent cycles, 4 weeks apart, it was raised by 250 mg/m2 to a maximum of 1,000 mg/m2, if the WBC count was over 2,000/microliters. Three women in group B gave up treatment prematurely after 5-8 cycles, because a remission had occurred. In group A only one patient went into remission after only three cycles. Of the total of 18 patients in both groups whose data could be evaluated, 15 achieved remission after an average of 7.3 cycles and a cumulative total cyclophosphamide dosage of 9.3 g. The disease progressed in two patients, one died. No recurrence has so far been observed after a follow-up period of 1-41 months. Three patients had infections and two had developed leukopenia as side effects. Pulse cyclophosphamide has thus been shown to be an effective treatment in lupus nephritis, but it must be continued for more than 3 months.

[Cyclophosphamide bolus therapy in lupus nephritis--status of the clinical study]. / Cyclophosphamidbolus-Therapie bei Lupusnephritis--Stand der Therapiestudie.

In order to establish a low-dose cumulative cyclophosphamide therapy for lupus nephritis, 21 patients were either randomized for at least 3 i.v. cyclophosphamide pulses until remission occurred or for 12 pulses. 18/21 patients developed a remission after an average of 7.3 pulses and a cumulative cyclophosphamide dose of 9.3 g. Side effects were only mild.