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.

Optimization of expanded donors using dual kidney transplantation: case-control study.

BACKGROUND: Cadaveric donation is now experiencing a trend toward the use of expanded criteria donors (ECD) who may not yield a suitable kidney for single organ transplantation which has occasionally led to their use as dual renal transplantations. MATERIAL AND METHODS: We undertook a case-control study to analyze our experiences between May 2007 and March 2011 with 80 kidneys from ECD who were older than 65 years. Of these, 40 were used as single transplants (STX) and the other 40 as dual cases (DTX). Criteria to determine STX versus DTX were established by biopsy results and other donor factors. RESULTS: The mean age of the ECD for STX was 68.7 ± 3.0 years and for DTX, 74.2 ± 4.3 years (P < .001), with more women among DTX (75%) versus STX (40%; P < .001). The DTX kidneys showed higher biopsy scores than the STX organs. DTX were older than STX recipients, but there were no differences in cold ischemia time, delayed graft function, hemorrhagic complications or reinterventions. DTX recipients achieved better CrCl at 1, 3, 6, and 12 months, although only significantly so at 6 months (53.4 ± 19.5 Ml/min versus 44.5 ± 15.6 mL/min; P < .05). Death-censored graft survival was 90% at 3 years for both groups. CONCLUSIONS: DTX offered good results for graft survival and renal function, despite the more complicated surgery and worse quality of the allografts. DTX allowed the use of ECD kidneys that showed less satisfactory histologic and donor characteristics.

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.

Síndrome de Sjögren y fracaso renal agudo tras cirugía oral / Sjögren’s syndrome and acute renal failure following oral surgery

El síndrome de Sjögren primario es una enfermedad inflamatoria multisistémica que suele cursar con lesiones de las glándulas exocrinas originando síntomas de sequedad oral y ocular. La expresión clínica también incluye manifestaciones generales, afección extraglandular y desarrollo de linfoma. La asociación de enfermedad renales frecuente. Habitualmente, la lesión observada corresponde a nefritis túbulo-intersticial. En cambio, es rara la afectación glomerular, así como los casos de fracaso renal agudo severo. Presentamos el caso de una mujer con síndrome de Sjögren primario que desarrolla un cuadro de insuficiencia renal aguda grave por glomerulonefritis crioglobulinémica con respuesta favorablea la terapia con esteroides, ciclofosfamida, plasmaféresisy rituximab (AU)

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 pectrum of the disease includes general symptoms, extraglandular manifestations and lymphoma. The renalinvolvement is frequent. Interstitial nephritis is the most common renal manifestation, but glomerular involvement and acute renal failure may rarely occur. We describe acase of a female patient with primary Sjögren´s syndrome complicated by severe acute renal failure due to cryoglobulinaemic glomerulonephritis. Treatment with steroids, cyclophosphamide, plasma exchange and rituxim absuccessfully lead to recovery of acute renal failure (AU)

[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.

Rhabdomyolysis due to enzyme deficiency in muscles

Rhabdomyolysis is a syndrome characterized by injure of skeletal muscle with the release of intracellular constituents into the circulation. Acute renal failure is a common complication and is the leading cause of morbidity and mortality in these patients. The most common aetiology is traumatisms, muscle compressions and extreme exertions. Most commonly, the cause of rhabdomyolysis is evident from the careful clinical history. Nevertheless, when the precipitant is not obvious the diagnosis is difficult and a raised clinical suspicion is required. We should investigate used medication or drugs, infections, electrolyte abnormalities and a number of inherited enzyme deficiencies, in which cases the muscle is unable to use available energy. We report two clinical cases of acute renal failure due to rhabdomyolysis by metabolic myopathies due to a carnitine palmitoyltransferase deficiency on the one hand and by myophosphorylase deficiency on the other. We describe their clinical features and progress (AU)

La rabdomiólisis es un síndrome producido por la lesión del músculo estriado con liberación al torrente sanguíneo de gran cantidad de productos intracelulares. Es frecuente el desarrollo de fracaso renal agudo que, además, constituye el principal factor de morbimortalidad en estos pacientes. Entre las causas más frecuentes destacan los traumatismos, la compresión muscular o la realización de ejercicio físico intenso. Son casos que se reconocen fácilmente al realizar una adecuada historia clínica. Sin embargo, en ausencia de un desencadenante claro, el diagnóstico es difícil y suele requerir un alto grado de sospecha. Deben investigarse consumo de drogas y fármacos, infecciones, trastornos electrolíticos y determinados defectos enzimáticos en los que el músculo es incapaz de utilizar la energía disponible. Presentamos dos casos de fracaso renal agudo debido a rabdomiólisis por miopatías metabólicas, secundarios a déficit de carnitina-palmitoil-transferasa en un caso y de miofosforilasa en el otro. Se revisa esta enfermedad insistiendo en las formas de presentación y medidas preventivas (AU)

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.

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.

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.

[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.

[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.

Síndrome nefrótico por lesiones mínimas en el adulto / Minimal changes nephrotic syndrome in adults

La glomerulopatía por cambios mínimos también conocida como enfermedad de cambios mínimos (NCM) es la causante del 10-15% de los síndromes nefróticos de los adultos. La ausencia de lesiones histológicas con técnicas de microscopia óptica e inmunofluorescencia son características de la enfermedad junto con la evolución a curación en un buen porcentaje de casos. Las alteraciones de fusión de los pies de los podocitos en los estudios de microscopia electrónica han permitido avances en el conocimiento de la patogenia ya que es en los podocitos donde se han centrado la mayoría de los estudios de proteómica y genómica que han identificado genes y proteínas responsables de las enfermedades glomerulares encuadradas en NCM. • El plan terapéutico inicial consiste en la administración de corticoides a dosis de 1 mg/kg/día , que consigue remisiones entre el 81-90%. El tiempo mínimo de administración de corticoides debe estar comprendido entre 8 y 16 semanas. • En casos corticorresistentes se debe considerar la administración de un ciclo de fármacos citotóxicos , siendo el más empleado la ciclofosfamida a dosis de 2 mg/kg/día durante 8-12 semanas. Los inhibidores de la calcineurina (ciclosporina A y tacrolimus) son de gran utilidad , si bien teniendo en cuenta que la recidiva de la enfermedad es frecuente al suspender estos fármacos y que son potencialmente nefrotóxicos. El MPA puede considerarse una alternativa aunque existen pocos datos. . • En casos corticodependientes o recaedores frecuentes, además de los corticoides y citotóxicos esta indicada la ciclosporina A administrada a largo plazo en dosis progresivamente decrecientes y existen cada vez más indicios de que el MPA con buen perfil de eficacia-tolerancia podría ser una opción terapéutica satisfactoria pendientes en el momento actual, de estudios controlados que acrediten grado de evidencia científica. (nivel de evidencia C)

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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.