Mycophenolate as maintenance therapy for lupus nephritis with impaired renal function.

BACKGROUND: Mycophenolate (MF) is effective as a maintenance therapy after induction therapy in patients with lupus nephritis (LN). However, little is known about its role in patients with impaired renal function. The purpose of this study was to evaluate the efficacy and safety of MF as a maintenance therapy for LN and its association with renal function. METHODS: Data were obtained for 56 Spanish patients who were receiving MF as a maintenance therapy for LN. Patients were classified into two groups according to renal function at the initiation of MF treatment: group 1 [estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2)] and group 2 (eGFR <60 ml/min/1.73 m(2)). The primary endpoints of the study were the rates of renal relapse and responses, and their relationship with baseline renal function. Secondary outcomes were the appearance of side effects during treatment. RESULTS: At initiation of MF treatment, the only differences between the groups were for age, hemoglobin levels, anti-DNA antibody titer, proteinuria, and renal function. In group 1 (n = 38), the eGFR was 98 ± 34 ml/min/1.73 m(2) and in group 2 (n = 18) the eGFR was 43 ± 14 ml/min/1.73 m(2). Only 3 cases had an eGFR <30 ml/min/1.73 m(2). No significant differences were observed in the rate of relapse at 6 months (group 1: 20%; group 2: 23%) or at 12 months (group 1: 25%; group 2: 17%). Response rates were also similar in both groups. Side effects were unremarkable. CONCLUSIONS: MF is effective and safe as a maintenance therapy for LN both in patients with normal renal function and in those with renal impairment.

Mycophenolate as induction therapy in lupus nephritis with renal function impairment.

BACKGROUND: Mycophenolate (MF) is effective as induction therapy for lupus nephritis (LN) in patients with normal renal function; however, little is known about its role in patients with impaired renal failure. The purpose of this study was to evaluate the response to MF in LN and its association with baseline renal function. METHODS: Data were obtained for 90 patients from 12 Spanish renal units who were receiving MF as induction therapy for LN. Patients were classified into 2 groups: group 1 (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73 m(2)) and group 2 (eGFR <60 ml/min/ 1.73 m(2)). The primary outcome measure was the percentage of patients who achieved any response and its relationship with initial eGFR. The secondary outcome measures were the percentage of patients who achieved a complete response (CR) or partial response (PR) and the appearance of relapses during treatment and side effects. RESULTS: At initiation of MF treatment, there were no differences in the main parameters between group 1 (n = 63; eGFR 87 ± 23 ml/min/ 1.73 m(2)) and group 2 (n = 27; eGFR 44 ± 12 ml/min/1.73 m(2)). Exposure to prednisone and MF was similar. The percentages of patients who achieved a response in groups 1 and 2 were, respectively, 69.2 and 43.8% at 6 months and 81.3 and 73.7% at 12 months. CR was more frequent in group 1, whereas PR was similar in both groups. Four patients relapsed and side effects were unremarkable. CONCLUSIONS: MF is effective and safe as induction therapy for LN, and response is even achieved in patients with baseline renal impairment.

[Clinical and biochemical characteristics of predialysis patients in terms of 25 hydroxy vitamin D levels]. / Características clínicas y bioquímicas de pacientes en prediálisis con respecto a los niveles de 25 hidroxivitamina D.

INTRODUCTION: Decreased levels of 25 hydroxyvitamin D (25[OH]D) have been reported in patients with chronic kidney disease (CKD). The pleiotropic effects of vitamin D are known to go beyond mineral metabolism. OBJECTIVES: The aims of this study were to: 1) Determine the 25(OH)D levels in predialysis outpatients. 2) Find out the clinical and biochemical characteristics of patients with 25(OH)D deficiency, and predictive factors for the deficiency. PATIENTS AND METHODS: An observational study in 79 predialysis outpatients was performed. Clinical and biochemical parameters were analysed in terms of nutrition, inflammation and mineral metabolism in relation to serum levels of 25(OH)D. Levels of 25(OH)D lower than 15ng/ml were considered to be deficient. RESULTS: Serum levels of 25(OH)D were deficient in 41 patients (52%). The comparative study regarding levels of vitamin 25(OH)D showed the group of patients with a deficiency, i.e. those with less than 15ng/ml, were older (70 ± 11.97 vs. 61 ± 14.5; p = 0.005), had a greater body mass index, BMI, (30±4.06 vs. 27.1 ± 5.08; p = 0.003) and increased proteinuria (1.42g/24h (0.53-2.96) vs. 0.51 (0.20-1.48), p = 0.009). This group included a greater number of diabetic patients: 20 (76.9%) vs. 6 (23%), p = 0.002. They had a higher level of parathyroid hormone (PTH): 359 (239-658) vs. 233 (129-323), p = 0.000; and more patients were under treatment with Calcitriol: 28 (62.2%) vs. 17 (37.8%), p = 0.024. In the multivariate analysis, high levels of PTH (OR 13.38; CI 95% [2.94-60.89]; p=0.001), increased proteinuria (OR 4.41; CI 95% [1.12-17.25]; p = 0.033); and being diabetic (OR 5.713; CI 95% [1.43-22.77]; p = 0.014) were independent predictor factors for patients with 25(OH)D deficiency. CONCLUSIONS: In our study, we observed a high prevalence of 25(OH)D deficiency among patients with CKD. The increased levels of PTH, the increase of proteinuria and the presence of diabetes were independent predictors for 25(OH)D deficiency.

[Factors which influence phosphorus removal in hemodialysis]. / Factores en la eliminación de fósforo en hemodialisis.

BACKGROUND: The sustained elevation of phosphorous among patients with end-stage renal failure is associated with elevated mortality rates. Phosphate binding agents are usually necessary to control serum phosphate levels. Phosphate removal during dialysis is limited largely due to the intracellular location of most inorganic phosphorous. The membrane surface, the frequency and the duration of therapy have proved to be very important factors in the serum phosphate control. THE AIM of our work is to investigate the influence on phosphate removal of factors that normally participate in the haemodialysis session: Plasma phosphate level (Php), treatment duration, membrane surface, high or low-flux membranes, the vascular access, dialysate flux , the volume of blood passing through the dialyzer (L) in each dialysis session and the blood flow during the first hour of dialysis. On 16 patients, we also had the possibility of comparing phosphate removal with 1.8 m(2) high-flux haemodialysis, 1.8 m(2) on-line hemodiafiltration and the on-line technique with the new Helixone dialyzer Fresenius Fx100. METHODS: 108 haemodialysis patients, 62% men, 38% women aged 21-82 years (61+/-14;mean+/-sem),) were selected for the study. Mean treatment time 4.14+/-0.41 hours (range 3.5-5 hours). The vascular access was an arterio-venous fistula in eighty five (78%) and a double lumen tunnelled catheter 23 (22%). Patients were studied under their normal every day conditions. High-flux membrane was used by 31 (30%) patients and low-flux membrane by 77 (70%). Membrane surface was: 1.7 m2:17 (16%); 1.8 m2:77 (71%); 2,1 m2:14 (13%). Dialysate flux was: 500 ml/min. 55 patients; 700 ml/min: 53 patients. In 16 out of 108 patients we had the possibility of using on-line hemodiafiltration with ultrapure bicarbonate-buffered dialysate. Phosphate mass removal (MPO4) was calculated using the formula:MPO4=0.1 t-17+50 Cds 60+11Cb 60 (1), where t is treatment time in minutes, Cds60 and Cb60 are phosphate concentrations in dialysate and plasma measured at 60 min from the beginning of hemodialysis in mg/dl, and MPO4 is the estimated phosphate removed in mg/treatment. RESULTS: We found a good correlation between phosphate removal and serum phosphate levels (p=0.01), but not with the membrane surface or treatment duration. Phosphate removal was 640+/-180 mg/session with low-flux membrane and 700+/-170 mg/session with high-flux membrane (p=0.280). The MPO4 was 720+/-190 mg/treatment in patients with a AV fistula and 620+/-180 in patients with a tunnelled catheter (p=0.023). We found a good correlation between phosphate removal and the volume of blood (L) that passed the dialyzer in each session (r=0.001) but we did not find a correlation between phosphate removal and KT/Vurea, the dialysate flux or the ultra filtration. On-line technique did not increased the MPO4(733+/-280 mg, p=0.383). The on-line technique with the new dialyzer (Fresenius Fx100), increased the phosphate removal to 759+/-199 mg/session (p=0.057). CONCLUSION: Phosphate removal during dialysis is influenced by Plasma phosphate levels, the volume of blood that passed the dialyzer and the vascular access. Uniformity on time and membrane surface could explain the abs cense of influence in our case. The ultra filtration, dialysate flux, membrane permeability or on-line hemodiafiltration does not influence the phosphate removal. The new membrane helixone with 2,1 m2 (Fresenius Fx100) increases phosphate removal probably because the membrane surface is higher.

[Sclerosing encapsulating peritonitis: a latent threat. Changes of posture in surgery treatment]. / Peritonitis esclerosante: una amenaza latente. Cambio de actitud en el tratamiento quirúrgico.

UNLABELLED: Sclerosing Encapsulating Peritonitis (SEP) is a rare but serious complication of continuous ambulatory peritoneal dialysis (CAPD) with a high morbi-mortality. We describe our experience with patients was diagnostic of SEP, their characteristics in CAPD and their clinic evolution after diagnosis. 190 CAPD patients were follow-up during 17 years. Eight patients (4.2%) developed SEP. Average age 45+/-14 years (range 29-64 years), four was male. Time in CAPD was 72+/-29 months (range 24-120 months). All patients have peritonitis previously (mean 3+/-1). We observe a change in peritoneum characteristics (D/P Cr 4), with an average of 0.6+/-0.1 at one year of CAPD, versus 0.82+/-0.08 at the end of CAPD, with statistic significance (p<0.001). There are increases in use of hypertonic bags: 53%+/-28 at beginning versus 91%+/-27 at end, with statistic significance (p<0.009). All patients show tendency to hyperphosphoremia (mean 6.7+/-0.7 mg/dl), with product calcium-phosphorus 68.4+/-8.3. Five patients (62.5%) have a previous renal transplant, one lost due to early graft thrombosis and two lost due to acute rejection. Six patients (75%) have a previous abdominal surgery, although was extra peritoneal in all cases. The diagnosis of SEP was clinic suspicion in all cases, suggestive radiological data (intestinal handle group) and laparoscopy showing SEP (cocoon) with histological confirmation (fibrosis and peritoneal calcification) in four cases. The treatment was medical in six cases associated with surgery in four of them. The medical treatment was tamoxifen and/or corticosteroids, associated with total parenteral nutrition in two patients and enteral nutrition in one. Surgery in six patients: three as urgent surgery (all died) and three as programme surgery (two live still). Etiology of died was: three for sepsis, one for peritonitis after bowel perforation, one for severe problems of nutrition. The average survival of three patients alive was 38+/-17 months, two of them had programme surgery, and one with functioning transplant we opt for conservative treatment. The actuarial survival at 24 months was 51%. CONCLUSION: The SEP is a serious entity with high mortality. Although our short experience doesn't can indicate a concrete treatment, our personal impression is that early surgery associated with corticosteroids treatment may improve the prognostic.

Treatment of hirudin overdosage in a dialysis patient with heparin-induced thrombocytopenia with mixed hemodialysis and hemofiltration treatment.

We report a patient who developed type II heparin-induced thrombocytopenia (HIT) and accidentally received a recombinant hirudin (r-hirudin) overdosage. Treatment with hemodialysis (HD) using high-flux polysulfone dialyzer and hemofiltration was performed. Length of treatment was adjusted, monitoring activated partial thromboplastin time (aPTT) to 1.5-2.5 times the mean of the normal range. She developed deep venous thrombosis and occlusion of vascular access. Only after cessation of heparin lock catheter, platelet count began to increase. After one year of treatment with acenocoumarol and additional low-dose r-hirudin, neither bleeding nor thrombotic episodes have been reported.

[Telemedicine and follow up of peritoneal dialysis patients]. / Utilidad de la telemedicina en el seguimiento de los pacientes en diálisis peritoneal.

UNLABELLED: Mean-term experience in the use of Telemedicine in Peritoneal Dialisis (PD) patients is limited as well as its cost-benefit. The main objective of this work is to evaluate Telemedicine utility in mean-long term control of stable PD patients, analyzing if the televisit (TV) could substitute 50% of the programed inhospital consults (HC) the time spent in both visit modalities, the quality of patient-personel contact as well as how image and sound have been perceived. Visit resolution was analyzed taking into account the need of HC after a TV; We also have studied if it would be possible to retrain patients in the dialisis technique with telemedicine, and we have checked the patient perceived quality and calculate the real and social costs. METHODS: during 18 months, the system has been implanted to 19 patients with 7 +/- 4 follow up (range 3-17). A Falcon videoconference kit at patient's place was used, connected to the home television set. In the hospital there was a computer with a videoconference card, webcam and software meeting point which permits the control of patient's camera from the hospital. Both are connected by a 3RDSI line system. A monthly programmed HC or TV has been made. If more controls had been required, they have been made by TV Time spent was recorded on each TV and patients and staff questionary were inquired. RESULTS: (a) PATIENTS: mean age 44 +/- 8 years, 13 (68%) male. 12 (63%) had elemental educational level and 7 (37%) mean-superior. 17 (89%) were actively working. The PD technique was: CAPD 6 (32%) and APD13 (68%). (b) Televisits: 103 TV have been made. 22 +/- 9 minutes were spent on each TV less than in the HC, 33 +/- 8 minutes (p < 0.01). There were technical problems related with lines in 21 TV, but only in 4 the connection was not possible. 92 TV (89%) were made on time, 99 (96%) had a good image quality and 96 (93%) had a correct sound. 100% of patients perceived TV as close to HC. In 90 TV (87%) medical treatment was modified. Only in 4 cases (3.9%) patients needed an hospital visit. According to patient's valuation, TV replaced correctly to HC in 97 instances (94%) and in 97 (97%) in staff opinion. In all cases (100%) catheter exit site could be evaluated as well as edema presence. Retraining was possible in all cases. There was a save in nurse's time and patient's time and also, a save in physical hospital space. Initial investment apart, the daily cost increment was scarce (1.5 Euro) taking into account that there is a save in time for patients and personnel, save in physical space in hospital and in sanitary transport. CONCLUSION: Telemedicine is useful from the clinical point of view in the mean-term for stable patients in PD. Daily cost increment is scarce and there is a save in time for patients and personnel, save in physical space in hospital and in sanitary transport.

Peritoneal sodium mass removal in continuous ambulatory peritoneal dialysis and automated peritoneal dialysis: influence on blood pressure control.

BACKGROUND/AIM: Sodium and water retention is common in peritoneal dialysis patients and contributes to cardiovascular disease. As peritoneal sodium removal depends partly on dwell time, and automated peritoneal dialysis (APD) often uses short dwell time exchanges, the aim of this study was to compare the 24-hour peritoneal sodium removal in APD and standard continuous ambulatory peritoneal dialysis (CAPD) patients and to analyze its possible influence on blood pressure control. METHODS: A total of 53 sodium balance studies (30 in APD and 23 in CAPD) were performed in 36 stable peritoneal dialysis patients. The 24-hour net removal of sodium was calculated as follows: M = ViCi - VdCd, where Vd is the 24-hour drained volume, Cd is the solute sodium concentration in Vd, Vi is the amount of solution used during a 24-hour period, and Ci is the sodium concentration in Vi. Peritoneal sodium removal was compared between APD and CAPD patients. Residual renal function, serum sodium concentration, daily urinary sodium losses, weekly peritoneal Kt/V and creatinine clearance, 4-hour dialysate/plasma creatinine ratio, proportion of hypertonic solutions, net ultrafiltration, systolic and diastolic blood pressures, and need for antihypertensive therapy were also compared between the groups. RESULTS: Peritoneal sodium removal was higher (p < 0.001) in CAPD than in APD patients. There were no significant differences in residual renal function, serum sodium concentration, urinary sodium losses, peritoneal urea or creatinine clearances, 4-hour dialysate/plasma creatinine ratio, or proportion of hypertonic solutions between groups. The net ultrafiltration was higher in CAPD patients and correlated strongly (r = 0.82; p < 0.001) with peritoneal sodium removal. In APD patients, peritoneal sodium removal increased significantly only in those patients with a second daytime exchange. The systolic blood pressure was higher (p < 0.05) in APD patients, and the proportion of patients with antihypertensive therapy was also higher in APD patients, although no significant relationship between blood pressure values and amount of peritoneal sodium removal was found. CONCLUSIONS: The 24-hour sodium removal is higher in CAPD than in APD patients, and there is a trend towards better hypertension control in CAPD patients. As hypertension control and volume status are important indices of peritoneal dialysis adequacy, our results have to be considered in the choice of the peritoneal dialysis modality.

[Influencing factors in the control of phosphorus in peritoneal dialysis. Therapeutic options]. / Factores que influyen en el control del fósforo en diálisis peritoneal. Opciones terapéuticas.

UNLABELLED: Impaired phosphate excretion resulting in hyperphosphatemia is one of the earliest consequences of chronic renal failure. To control serum phosphate levels, we can use the following therapies: 1) Restriction of dietary phosphate (but on CAPD, obligatory protein losses via peritoneal fluid makes impractical any reduction of phosphate diet. 2) Reduction of phosphate absorption, using phosphate binders. 3) Peritoneal phosphate removal. OBJECTIVE: 1) To evaluate the factors affecting peritoneal phosphate removal such as plasma phosphate, peritoneal membrane transport type, peritoneal dialysis modality prescription (CAPD or APD) and daily dialysate volume. 2) To test the best calcium concentration in the peritoneal dialysis fluid (5, 6 or 7 mg/dl) in order to permit the use of calcium carbonate or acetate without the risk of hypercalcemia or hyperparathyroidism. METHOD: Phosphate was measured in seventy 24-hour dialysate collections, 33 from patients on CAPD and 37 from patients on APD. 24-hour peritoneal phosphate removal (mg/24 hours) and weekly peritoneal phosphate clearance was calculated (L/week). The peritoneal membrane was studied by the peritoneal equilibrium test (PET), using a 2.27% glucose. We calculated also the peritoneal calcium balance in 25 daily peritoneal fluid collections from patients using a calcium dialysate concentration of 5, 6 or 7 mg/dl each one. IPTH levels and doses of vitamin D were compared at 6 months in patients using a calcium concentration of 5, 6 or 7 mg/dl from the beginning of peritoneal dialysis (5 patients of each calcium dialysate concentration). RESULTS: Weekly peritoneal phosphate clearance (WPC) were higher or APD than on CAPD (51 +/- 21 vs 41 +/- 14, p < 0.005). Daily dialysate volume was also higher on APD (14 +/- 4 vs 7.8 +/- 1.8 L/day, p < 0.001). WPC was higher on APD when a mild-day exchange was done (61 +/- 23 vs 45 +/- 15, p < 0.005), instead an equal total daily volume of the dialysate. Peritoneal calcium balance was significantly more negative in patients using a calcium in the dialysis fluid of 5 than 6 or 7 mg/dl (-125 +/- 7 vs -18 +/- 41 vs -11 +/- 49, p < 0.001). At 6 months, patients using a calcium fluid concentration of 5 mg/dl increased iPTH levels (from 160 +/- 101 to 332 +/- 153, p < 0.001) and vitamin D needs (from 0 to 1.87 +/- 0.37 mcg/week, p < 0.001). In summary, peritoneal phosphate clearance depends on plasma phosphate levels, daily volume of dialysate prescribed and peritoneal membrane transport characteristics. It can be improved by increasing the total peritoneal fluid. On APD, a mild-day exchange may improve phosphate clearance, without total volume increase. The risk of secondary hyperparathyroidism can be decreased with a calcium fluid concentration of 6 mg/dl, which was shown to be better than 5 mg/dl when calcium phosphate binders are not correctly taken.

[Treatment of the diffuse and focal proliferative forms of lupus nephropathy with intravenous cyclophosphamide. Intravenous cyclophosphamide in systemic lupus erythematosus]. / Tratamiento de las formas proliferativa difusa y focal de la nefropatía lúpica con ciclofosfamida por vía intravenosa. Ciclofosfamida por vía intravenosa en el lupus eritematoso sistémico.

The objective is to evaluate the therapeutic effect and toxicity of IV Cyclophosphamide on the evolution of diffuse and focal proliferative forms of lupus nephritis. It's a prospective, descriptive and non-controlled study. We treated 12 patients (M/F = 1:11, aged 30.07 +/- 14.15) diagnosed by renal biopsy with diffuse proliferative (n = 10) and focal (n = 2) lupus nephritis. All patients received IV Cyclophosphamide. A dose of 1 g/sg.m of body surface area was administered monthly for the first three months and each three months until two years. The follow-up was 34 +/- 24.83 months (range 6-67). Seven patients completed two years of treatment with Cyclophosphamide with a further follow-up of 18.71 +/- 12.36 months (range 6-67). Renal function either improved or remained unchanged. Proteinuria, hematuria and immunologic markers decreased or normalized at three years. The patients who finished the period of two years with CFIV remained stable. There were neither infections nor hemorrhagic cystitis. We conclude that with the scheme of CFIV used by us good therapeutics effects will be obtained with minimum secondary toxicity in a follow-up of three to five years.

Gastroparesis: an important cause of hospitalization in continuous ambulatory peritoneal dialysis patients and the role of erythromycin.

Gastroparesis is a disabling complication in diabetic patients. It has been reported as the second most frequent cause of hospitalization in diabetic patients on continuous ambulatory peritoneal dialysis (CAPD). We analyzed infectious and noninfectious complications in our CAPD patients. We included 31 patients (12 diabetics and 19 nondiabetics) with an average time on CAPD of 14 +/- 7 months. The incidence of peritonitis was 1.68 episodes/patient/year in diabetics and 0.84 in nondiabetics. Nine (75%) diabetic patients had peritonitis, 5 (42%) had vomiting, and 4 (33%) had ischemic heart disease. The hospitalization index (days/year) was greater in diabetics: 11.83 +/- 11.36 versus 4.16 +/- 8.84 in nondiabetics (p < 0.05). Vomiting was the first cause of admission in diabetics. We were unable to control severe gastroparesis with cisapride and metoclopramide in 4 patients. Erythromycin, 100 mg/2-L bag of dialysate, improved symptoms in all of them. We concluded that gastroparesis is an important cause of morbidity in CAPD patients. Intraperitoneal erythromycin can improve symptoms if other prokinetic drugs fail.