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.

Continuously evaluating performance in deceased donation: the Spanish quality assurance program.

The Spanish Quality Assurance Program applied to the process of donation after brain death entails an internal stage consisting of a continuous clinical chart review of deaths in critical care units (CCUs) performed by transplant coordinators and periodical external audits to selected centers. This paper describes the methodology and provides the most relevant results of this program, with information analyzed from 206,345 CCU deaths. According to the internal audit, 2.3% of hospital deaths and 12.4% of CCU deaths in Spain yield potential donors (clinical criteria consistent with brain death). Out of the potential donors, 54.6% become actual donors, 26% are lost due to medical unsuitability, 13.3% due to refusals to donation, 3.1% due to maintenance problems and 3% due to other reasons. Although the national pool of potential donors after brain death has progressively decreased from 65.2 per million population (pmp) in 2001 to 49 pmp in 2010, the number of actual donors after brain death has remained at about 30 pmp. External audits reveal that the number of actual donors could be 21.6% higher if all potential donors were identified and preventable losses avoided. We encourage other countries to develop similar comprehensive approaches to deceased donation performance.

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.

[Sjögren's syndrome and acute renal failure after oral surgery]. / Síndrome de Sjögren y fracaso renal agudo tras cirugía oral.

Primary Sjögren s syndrome is a multisystemic inflammatory disorder that mainly affects the exocrine glands and usually presents as dryness of the mouth and eyes. The wide clinical spectrum of the disease also includes general symptoms, extraglandular manifestations and lymphoma. It is frequently associated with renal diseases. Interstitial nephritis is the most common renal manifestation, but glomerular involvement and acute renal failure may also (rarely) occur. We describe a case of a female patient with primary Sjögren s syndrome complicated by severe acute renal failure due to cryoglobulinemic glomerulonephritis. Treatment with steroids, cyclophosphamide, plasma exchange and rituximab successfully led to recovery from acute renal failure.

Assessment of an educational program for adolescents about organ donation and transplantation.

The aim of this study is to determine the effectiveness of an educational program in 157 students with a mean age of 15.36 years at three schools in Malaga. The program included the evaluation of two tests before and after four sessions in an intervention group as compared with a control group. The educational program on organ donation and transplantation led to very positive changes, raising the level of awareness and the number of persons prepared to donate their organs and those of their relatives, as well as the number of participants who discussed the matter at home. Finally, evaluation of this experience showed that inclusion of education about organ donation and transplantation in secondary education can be considered positive.

Increased organ donations from people born outside Spain.

Organs donated from persons born outside Spain are becoming increasingly numerous. These persons now account for 26.1% of all donors in the "Malaga sector," an area of tourism with a high percentage of immigrants. Acceptance to donation among persons from Europe and South America is similar to that of Spanish persons but lower among those born in Africa. We must recognize the great help that cultural mediators provided not only by assistance with the language barrier but also by generating confidence among families and understanding their emotions, feelings, and traditions, mainly during interviews with families from different social and cultural miliere. To be efficient, the interpreters or cultural mediators need to have received specific training in the organ donation process and to be involved and convinced that organ donation and transplantation is the best solution for severe health problems.

Organ donors with exceptional medical conditions also count!

All organ donors, even those who have died under exceptional conditions, can provide at least one valid organ for transplantation. It is thus necessary to evaluate the outcomes of donors with unusual diseases. We reviewed 909 organ donors at six hospitals over the last 15 years. Of these, 29 (3.19%) were considered to be exceptional either because of prior disease, the circumstance of death, or complications arising during admission. Among the 53 organs transplanted from all these donors (except two), the mean number of valid organs per donor was 1.88 rather than 2.36 for standard donors. One patient who received a liver transplant died due to the same infection as that diagnosed in the donor. The remaining recipients experienced no primary graft failure or transmission of problems present in the donor.

Profile of organ donors not authorized for judicial reasons.

Loss of donors as a consequence of a coroner's refusal to authorize is an unusual problem that prevents organs becoming available for transplantation. Of 1123 effective donors, 433 (38.5%) died of accidental death. In these latter, it was therefore necessary to request judicial authorization for donation during the coroner's examination. Organ extraction was not performed because of judicial refusal in 15 of these donors (3.46% of the total number of judicial extractions requested and 1.33% of the total number of donors). Despite the lack of differences in the cause of death profile in the four provinces, large differences were noted between the provinces, with most judicial refusals in Malaga (10 refusals; 6.6% of the total judicial refusals), followed by Granada with five refusals (2.9%), Seville with two refusals (1.7%), and zero in Almería. To minimize these judicial refusals, we propose joint action protocols between transplant coordinators, judges, and coroners for these donors to be examined in the hospital prior to extraction and in the operating room during extraction. Any external lesion of judicial interest can then be examined, photographed, and evaluated.

[Glutamin concentrations in patients treated with cisplatin have a predicting value of renal failure development]. / Concentraciones de glutamina en pacientes tratados con cisplatino predicen el desarrollo de insuficiencia renal.

Glutamine is an amino acid (AA) whose mission is carrying nitrogen. Abnormalities in protein and AA metabolism has been observed in patients with acute renal failure. Several clinical trials had showed abnormalities in plasma AA and its elimination in uremic environment. Moreover, renal failure disturbs hepato-splachnic circulation of glutamin, tyrosine and proline. Cisplatin is a key drug in the chemotherapy pharmacology, and the nephrotoxicity due to tubular injury, is one of its most important side effects, which sometimes is irreversible and leads to substitutive renal treatment. The goal of this work is to find predictive factors of renal failure secondary to cisplatin. Fifty four patients treated with cisplatin were studied. The plasma AA concentration and another plasmatic and urine parameters were measured in three different days after each pulse of chemotherapy. Plasma AA modifications through the pulses and reabsortion percentages of everyone were analysed too. Significant differences were observed in 13 AA reabsortion percentages and 16 plasmatic concentration. Glutamin concentration through the pulses was higher in 13 patients, (24%) who presented renal failure (Plasmatic glutamin concentration higher than 1000 mM/L at the third day after cisplatin administration was highly predictive value about getting renal failure, with significant difference from patients with o normal renal function. Others parameters analysed did not rise significant predictive values, so as it was not found relation between hyperaminoaciduria and renal function. It is concluded that cisplatin leads to renal failure in a 24% of this patients. Glutamin, concentrations higher than 1000 mM/L at the third day after cisplatin administration have a high predictive value about getting renal failure; so, it is suggested this could be a early marker of cisplatin nephrotoxicity before the serum creatinine is elevated, in order to get an early and suitable treatment of it.

[Giant renal arteriovenous malformation: a suspicious bruit]. / Malformación arteriovenosa gigante intrarrenal: un soplo sospechoso.

Arteriovenous (AV) malformations remain relatively rare clinical lesions consisting in abnormal shunts between the arterial and venous vascular systems. Both,congenital or acquired fistulas, are unusual causes of renal or heart failure. Congenital AV fistulas usually present with hematuria, while acquired ones are more likely to present with hemodynamic changes, such as hypertension, cardiomegaly and congestive heart failure. Here we present a 61 year-old woman studied before by probable pulmonary arteriovenous fistula and referred to nephrologist with a six-month history of dyspnea and peripheral edema. Physical examination was remarkable for an apical systolic ejective murmur as well as another bruit over the right pulmonary base. Blood tests showed a sCr of 1.7 mg/dl with normal urinalysis. On imaging, renal duplex ultrasound showed a pulsatile hiliar mass on the right kidney with an arterial flow of 300 cm/sec that was identified as a giant AV fistula on MRA. An echocardiogram revealed severe pulmonary hypertension with a cardiopulmonary output of 12,9 l/min that doubled the systemic one (6,49 l/min). In view of the large size of the AV fistula occupying the majority of the parenchyma, endovascular approach was turned down and a laparoscopic nephrectomy was performed successfully. There was an immediate clinical improvement and 45 days after the procedure, a control-echocardiogram showed normalization of the cardiopulmonary parameters with minimal changes in glomerular filtration rate.

[Intravenous cyclophosphamide in lupus nephritis: twenty years reducing dose]. / Ciclofosfamida intravenosa en nefritis lúpica: veinte años reduciendo dosis.

The prognosis for patients with proliferative glomerulonephritis associated with systemic lupus erythematosus has dramatically improved over recent decades. We review our experience with intermittent pulse therapy with intravenous cyclophosphamide (IC) in 97 patients (75 female) aged over 20 years. The series was divided into three groups. Group A (n=39) received monthly IC pulses (begin 1 g) for up to 24 months between 1985-1991. Group B (n=47) received monthly IC pulses (1 g) for six months with additional quarterly doses for a maximum of 18 months, depending on the therapeutic response (from 1991). From 1999, Group C (n=11) patients were treated with low-dose IC (3 g in three months) followed by azathioprine (2 mg/kg) or mycophenolate mofetil (1.5-2.0 g/day) for 12-18 months. The total IC doses (g) administered were: Group A, 15.1+/-9.0; Group B, 8.5+/-3.5; and Group C, 3.0+/-0.0. These figures show the trend progressive reduction in exposure to IC. Overall, treatment with the different IC regimens achieved satisfactory control of lupus nephritis in 76% of the patients. Comparison of the values at baseline and after 24 months showed that the serum creatinine (mg/dl) fell in Group A from 1.77+/-1.06 to 1.09+/-0.63, in Group B from 1.22+/- 0.85 to 0.95+/- 0.45, and in Group C from 0.90+/-0.23 to 1.17+/-0.54 (p<0.05). In the same period, proteinuria (g/day) fell in Group A from 6.19+/-4.31 to 0.79+/-1.76, in Group B from 4.43+/- 3.17 to 2.08+/-3.65, and in Group C from 5.43+/- 3.37 to 3.22+/-4.00 (p=0.05). There was not differences between the three groups in both variables. The adverse effects were mainly viral and bacterial infections, with no intergroup differences. Avascular osteonecrosis requiring hip replacement and early menopause were more frequent in Group A. Nine patients died, seven due to cardiovascular causes and two with infection. No differences were detected between the three groups when analyzing the overall patient survival at 5, 10 and 15 years (95%, 92%, and 84%, respectively). The likelihood of maintaining serum creatinine within normal ranges or less than twice the baseline range was similar in the three groups at 5, 10 and 15 years (92%, 72% and 66%, respectively). There were 47 episodes of relapse, with no differences between the three groups. In Summary, treatment with different regimens of intermittent IC is relatively safe and efficient to control the disease and lupus nephritis in SLE patients even with progressively smaller doses. The price paid concerned infectious complications, and bone and ovarian toxicity. New alternatives should at least maintain the same efficacy, but with fewer adverse effects and relapses.

Systemic lupus erythematosus in Europe at the change of the millennium: lessons from the "Euro-Lupus Project".

The "Euro-Lupus Cohort" is composed by 1000 patients with systemic lupus erythematosus (SLE) that have been followed prospectively since 1991. These patients have been gathered by a European consortium--the "Euro-Lupus Project Group". This consortium was originated as part of the network promoted by the "European Working Party on SLE", a working group created in 1990 in order to promote research in Europe on the different problems related to this disease. The "Euro-Lupus Cohort" provides an updated information on the SLE morbidity and mortality characteristics in the present decade as well as defines several clinical and immunological prognostic factors.

Expanded criteria donors for kidney transplantation: quality control and results.

Although the number of kidneys from expanded criteria deceased donors (ECDs) is growing in most transplant centers, the limits for acceptance of these kidneys and the safety standards have still not been fully established. We evaluated 342 kidney transplants performed between January 1999 and December 2004. In 77 (22.5%) of these, the kidneys were from ECDs, that is, donors age >60 years and with one of the following characteristics: hypertension, death due to cerebrovascular accident (CVA) or glomerular filtration rate (GFR) <70 mL/min. The results of the ECD transplants were compared with 265 transplants during the same period from standard donors (SDs), that is, donors age <60 years and GFR > 70 mL/min. All the ECD kidneys underwent biopsy and were accepted for transplantation only if the score was <7. The ECDs (66.5 +/- 4.3 years) in comparison with the SDs (48.0 +/- 16.0 years) had a greater frequency of death due to CVA (94.8% vs 49.8%) and a lower GFR (80.4 +/- 25.0 vs 111 +/- 41.6 mL/min; P < .05). Of the ECDs, 97.4% had a history of hypertension versus 24.3% of the SDs. Kidney biopsies were performed in 116 SD kidneys because the donor age was >55 years or there was a history of hypertension. The median score for the kidney biopsies of the ECD kidneys was 3 versus 2 for the SD kidneys. Graft survival was not significantly different until the fifth year. The GFR at 12 months was significantly different (SDs, 58.0 +/- 22.7 vs ECDs, 48.9 +/- 16.5 mL/min; P < .05). Although the GFR in the ECD kidneys was lower than that of the SD kidneys, it could still be adequate for recipients older than 50 years of age. Accordingly, the acceptance criteria for ECD kidneys based mainly on the kidney biopsy score and donor GFR benefit the recipients.

Expanded donor criteria due to age: an effort rewarded.

The life expectancy of the current Spanish population is 78 years, with some 20% of the population aged over 65 years. The continuing increase in the demand for transplants has led to widening of the criteria for acceptance of donors without worsening the results, but without reducing transplant waiting lists or mortality. This has resulted in the need to include the concept of the expanded criteria donor (ECD). We undertook a retrospective study of 77 donors from a hospital with no neurosurgery service from January 2000 to December 2005. Four of the donors younger than 60 years of age (n = 38) were not appropriate (10.5%), whereas five of the donors older than 60 years of age (n = 39) were not appropriate (12.8%; P = NS). The older donors provided 47 used kidneys (60.2%) and 22 livers (56.4%), slightly fewer than those obtained from the younger donors, though the difference was not significant. Thus, ECDs, those older than 60 years of age, did not result in a significant loss of kidneys or livers available for transplantation. Other factors associated with systemic vascular disease and accompanying disorders could be determinant when predicting the usefulness of organs for transplantation.

Differential analysis of donor characteristics for pancreas and islet transplantation.

Suitable selection of donors is key to the success of human islet isolation and transplantation. Although several important donor-related factors have been identified previously, they needed to be confirmed in our setting. The aims of this study were: (1) to compare the characteristics of islet donors with those of pancreas donors (national transplant registry). (2) to compare the characteristics of islet donors resulting in a successful isolation in our facility with the characteristics of pancreas donors, and (3) to compare the characteristics of islet donors at this facility, whether or not isolation was successful, with donors elsewhere whose islets were transplanted and included in the Collaborative Islet Transplant Registry. The 35 islet isolations completed at our facility were analyzed for various characteristics. Significant differences were seen in donor age body mass index (BMI), and body weight between our islet donors and our pancreas donors (P < .001). These differences were maintained in the subgroup analysis corresponding to donors of successful isolations compared to pancreas donors (P < .01). Most successful isolations in our islet isolation facility were associated with donors of BMI >25. The percentage of successful isolation (>300,000 IEq) was higher among donors with a body weight >90 kg. We concluded that there was little overlap between the donor profiles for pancreas transplantation and for islet transplantation. More specific selection criteria relative to both BMI and body weight for islet donors may result in greater success of pancreas islet isolation and transplantation.

Pancreas donation for islet transplantation.

Islet transplantation, though still in the experimental phase, is a therapeutic option that has opened new expectations for the control of diabetes mellitus. Initial results are encouraging for the significant advantages compared with whole pancreas transplantation for selected patients with type 1 diabetes mellitus, with or without kidney failure. However, the success of transplantation, both at centers with more experience and others with less, is limited by the difficulty in obtaining a suitable number of donors and by laboratory isolation techniques. Significant advances require changes in donor selection, perfusion, oxygenation, and transfer of the pancreas, and in the process of isolation, purification, and culture in the laboratory. Of the 32 pancreases sent to the islet isolation laboratory from different hospitals in Andalusia, a viable percentage of islets was finally available in 19. However, in only 4 (18%) procedures were the preparations considered optimal for implantation in 2 recipients.

Multifactorial snowball effect in the reduction of refusals for organ procurement.

Interviewing the family of a possible organ donor is a legal requirement in Spain, but it is the stage at which most potential donors are lost. Multiple factors influence the family's acceptance or rejection of this option, including awareness of the wishes of the deceased, personal preconceived attitudes of family members, as well as issues related to the hospital and its health care personnel, whose attitudes are a key factor in obtaining permission. We examined all 651 donation situations in a single hospital that included a family interview over the last 15 years. Among these 651 cases, 191 families refused donation (29.3%). The rate of donation refusal has fallen from 46.3% to 12.5% over these 15 years. To better understand the evolution of donor characteristics, interviewees, and the setting, we divided the sample into three 5-year periods to analyze key variables collected from the family interviews. The results showed that at the same time as the donor profile has changed, namely, fewer brain trauma cases and more victims of stroke as well as older mean age and more coexistent diseases, these has been an improvement in the factors related to the information and opinion of both the families and the donor about this process. The main reasons for refusal of donation have changed from negation of brain death, religious factors, and the desire to maintain the body intact during the 1990s, to sociocultural reasons in minority ethnic groups, to presumed refusal during life, and to family disagreements during the more recent years.

Organ donation: a comparison of donating and nondonating families.

The family interview to determine the wishes of the deceased during life about organ donation is not only a legal requirement, it is also the stage at which most potential donors are lost. Minimizing these losses necessitates awareness of all the variables involved in the family interview so that, before starting the interview, one understands the important key points affecting the outcome. We showed that some variables among 268 interviews are susceptible to intervention: the information and treatment perceived by the family members during the hospital stay and the preparation of the interview, such that a suitable number of the closest members of the family with a decision capacity is always present. Other noncontrollable factors that are important in the final decision included the social and demographic level, the prosocial attitude of the deceased, and prior knowledge and opinions about organ donation. Informative events within the hospital to improve the predisposition and collaboration of health care professionals were key to improving the public's perception of organ donation and achieving greater confidence in health care centers and their staff. Furthermore, the family interview must be planned by the transplant coordinators to limit improvisation.

[Mycophenolate mofetil in high risk IgA glomerulonephritis]. / Micofenolato mofetil en la glomerulonefritis IgA de alto riesgo.

Mesangial IgA glomerulonephritis (MIgAGn) is the most common biopsied primary glomerulonephritis worldwide, with a poor long-term prognosis for renal function in over a third of all patients. No proven therapy currently exists for MIgAGn. Recent studies have suggested some benefit with mycophenolate mofetil (MMF), especially in hypertensive patients with kidney failure and proteinuria, though other studies have failed to corroborate these findings. We report eight adult patients with biopsy proven MIgAGn followed in a single hospital. They all received angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Compassionate use of MMF was based on the presence of clinical and analytical data suggesting a high risk of short- to medium-term progression to chronic renal failure. MMF treatment was stopped after two and three months in two patients who had advanced renal failure at the start of therapy because of disease progression and greater fluid retention. Several months later they both required dialysis and kidney transplantation. The mean duration of MMF therapy in the other six patients was 15 (range: 10-18) months. The mean serum creatinine concentration fell from 1.82 +/- 0.47 to 1.55 +/- 0.41 mg/dl (p = 0.04). Protein loss in 24-hour urine collection fell from 1.95 +/- 1.35 to 0.77 +/- 0.58 g/day (p = 0.02). These results in this low number of patients showed that treatment with MMF in high-riks patients with MIgAGn and early stage kidney failure generally stabilized the disease and reduced proteinuria. MMF was well tolerated and may be of some benefit in a subgroup of patients with MIgAGn and a poor prognosis.