Papel de los nuevos agentes inmunosupresores en el cáncer cutáneo no melanoma en pacientes trasplantados renales / The Role of New Immunosuppressive Drugs in Nonmelanoma Skin Cancer in Renal Transplant Recipients

INTRODUCCIÓN: El cáncer de piel no melanoma (CCNM) es la neoplasia maligna que se presenta con más frecuencia después de un trasplante de órgano sólido. La etiología del CCNM tras el trasplante es multifactorial. OBJETIVOS: Analizar la relación entre los nuevos agentes inmunosupresores y la aparición de CCNM en pacientes trasplantados renales. MÉTODO: Estudio observacional. Se examinaron una combinación de datos retrospectivos y prospectivos. Incluimos en el estudio 289 pacientes que habían recibido trasplante renal desde enero de 1996 hasta diciembre de 2010 en el Hospital Universitario Doctor Peset de Valencia. RESULTADOS: Tras una mediana de seguimiento de 72 meses 73 pacientes (25,2%) desarrollaron 162 CCNM. No hubo diferencias estadísticamente significativas en la incidencia de CCNM al comparar las distintas estrategias de inducción con anticuerpos mono o policlonales. La incidencia de tumores en pacientes con inhibidores mTOR fue menor que con el resto de tratamientos, aunque sin mostrar diferencias estadísticamente significativas. De 5 pacientes con CCNM recurrente que pasaron a tratarse con inhibidores mTOR (tras ser tratados previamente con inhibidores de la calcineurina), 3 continuaron presentando CCNM a pesar del cambio de tratamiento. CONCLUSIONES: La utilización de anticuerpos mono o policlonales en la terapia de inducción en pacientes trasplantados renales no se asocia a un mayor riesgo de CCNM. Si bien los inhibidores mTOR muestran menor riesgo de aparición de CCNM postrasplante queda por determinar si el cambio de tratamiento a inhibidores mTOR es un buena opción en el manejo de pacientes con múltiples CCNM

INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. OBJECTIVES: To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. METHOD: This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. RESULTS: Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. CONCLUSIONS: Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs

The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients.

INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. OBJECTIVES: To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. METHOD: This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. RESULTS: Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. CONCLUSIONS: Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs.

Influence of gestational diabetes mellitus on neonatal weight outcome in twin pregnancies.

AIMS: To evaluate the influence of gestational diabetes mellitus on neonatal birthweight, macrosomia and weight discrepancy in twin neonates. METHODS: An observational retrospective study was performed. One hundred and six women with gestational diabetes and twin pregnancy and 166 twin controls who delivered viable fetuses > 24 weeks were included. Impact of maternal pre-pregnancy BMI, smoking habit, method of conception, chorionicity, gestational age at delivery, mode of delivery and hypertensive complications were also analysed. The effect of maternal hyperglycaemia and metabolic control in gestational diabetes pregnancies was assessed. RESULTS: Gestational hypertension and pre-eclampsia were significantly higher in the group with gestational diabetes (21.5% vs. 6.3%, P = 0.007 and 6.2% vs. 0%, P = 0.025). There were no differences in the incidence of macrosomia (5.7% vs. 7.2%, P = 0.803), large for gestational age (10.3% vs. 13.2%, P = 0.570), small for gestational age (10.3% vs. 12.0%, P = 0.701), severely small for gestational age (6.6% vs. 7.8%, P = 0.814) or weight discrepancy (20.6% vs. 15.2%, P = 0.320) in the group with gestational diabetes compared with twin pregnancies without diabetes. There were no differences when comparing insulin-requiring gestational diabetes pregnancies and twins without diabetes for any of the neonatal weight outcomes. There was no relationship between third trimester HbA1c and neonatal birthweight or infant birthweight ratio. CONCLUSION: Gestational diabetes did not increase the risk of macrosomia or weight discrepancy of twin newborns. Furthermore, glycaemic control did not influence the rate of any of the weight outcomes in our study population. In twin pregnancies, gestational diabetes was associated with a higher risk of gestational hypertension and pre-eclampsia.

Body weight, weight gain and hyperglycaemia are associated with hypertensive disorders of pregnancy in women with gestational diabetes.

AIM: The aim of this study was to measure the capacity of glucose- and weight-related parameters to predict pregnancy-induced hypertensive disorders in women with gestational diabetes. METHODS: An observational study was conducted involving 2037 women with gestational diabetes. The associations of glycaemic and weight-related parameters with pregnancy-induced hypertensive disorders were obtained by univariate and adjusted multivariate analyses. Also, model predictability and attributable predictor risk percentages were calculated, and collinearity and factor interactions examined. RESULTS: Multivariate analyses revealed that hypertensive disorders were mainly predicted by average third-trimester glycated haemoglobin (HbA(1c)) levels ≥ 5.9%, by being overweight or obese before pregnancy and by excess gestational weight gain after adjusting for age, tobacco use, chronic hypertension, parity, urinary tract infections and gestational age at delivery. Prepregnancy body weight (overweight and obesity) had the strongest impact on pregnancy-related hypertensive disorders (attributable risk percentages were 51.5% and 88.8%, respectively). The effect of being overweight or obese on hypertensive disorders was enhanced by HbA(1c) levels and gestational weight gain, with elevated HbA(1c) levels multiplying the effect of being overweight before pregnancy. CONCLUSION: The average third-trimester HbA1c level is a novel risk factor for pregnancy-induced hypertensive disorders in women with gestational diabetes. HbA(1c) levels ≥ 5.9%, prepregnancy overweight or obesity and excess gestational weight gain are all independent risk factors of pregnancy-related hypertensive disorders in such women. In treated gestational diabetes patients, the strongest influence on hypertensive disorders is prepregnancy obesity.

Urinary neutrophil gelatinase-associated lipocalin after kidney transplantation: is it a good biomarker to assess delayed graft function?

Delayed graft function (DGF) is a common complication after transplantation. Its incidence is increased among patients receiving a graft from an expanded-criteria donor. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), an acute kidney injury marker, could in the first days after transplantation be an early marker of DGF. We collected urine samples from 38 renal transplant recipients on days 1, 3, 6, and 10 post-transplantation, and months 1 and 6 creatinine to determine uNGAL, serum creatinine, Cystatin C, and albumin/creatinine ratio. We divided the patients into 2 groups, based on whether they developed DGF. We observed that mean uNGAL concentrations, Cystatin C, serum creatinine, and albumin/creatinine ratio were significantly lower in the non-DGF cohort on all measured days. uNGAL at day 3 showed a positive correlation with serum creatinine at day 10 (R = 0.58; P < .00) and day 30 (R = 0.57; P = .016) as well as with the length of hospital stay (r = 0.47; P < .00). Receiver operating characteristic analyses performed to assess the potential of uNGAL to predict DGF showed an area under the curve for day 3 of uNGAL of 0.917 (confidence interval [CI], 0.79-1.00; P = .00), with an optimal cutoff level of 124 ng/mL, sensitivity of 80% (CI, 62%-97%), and specificity of 83% (62%-104%; P = .001). In the first days after transplantation, uNGAL could be an early marker of DGF, providing additional information to standard biomarkers and potentially helping clinicians to take early measures to mitigate DGF.

Diagnosis of acute cortical necrosis in renal transplantation by contrast-enhanced ultrasound: a preliminary experience.

PURPOSE: To evaluate the use of contrast-enhanced ultrasound (CEUS) for diagnosis of cortical necrosis in renal allografts. MATERIALS AND METHODS: We reviewed the medical records and imaging studies of five patients who underwent emergency transplantectomy and a histological diagnosis of cortical necrosis in the period between May 2009 and May 2011. US examinations included initially B-mode and color Doppler and then contrast-enhanced ultrasound with low mechanical index after injection of 2.4 ml of a second generation echo-signal enhancer. Renal transplant vascularization was evaluated during a period of 4 minutes including arterial, corticomedullary and nephrographic phases. Radiologic-pathologic correlation was obtained after transplantectomy in all cases. RESULTS: Five patients with an age range between 30 and 48 years. Post-transplant color Doppler ultrasound showed decreased renal parenchymal vascularization and difficulty to find the spectral waveforms with resistive indexes greater than 0.7 in 4 of 5 patients. CEUS showed enhancement of the main arteries, followed by the enhancement of medullary pyramids, but with an unenhanced peripheral cortical continuous band viewed in all phases, a similar finding to the peripheral rim sign, pathognomonic of cortical necrosis on CT or MRI. The pathologic assessment showed violet kidneys macroscopically with hemorrhagic foci in the outer cortical that drew a well-defined band, findings agreed with CEUS findings. CONCLUSION: CEUS can show the typical peripheral rim sign in cases of cortical necrosis allowing a reliable and fast diagnosis of this condition and it could obviate further imaging studies or biopsy, allowing an earlier decision of nephrectomy.

Progestin-only contraception and venous thromboembolism.

Combined oral contraceptives (COC) are the most popular contraceptive method in developed countries. Since their introduction there have been numerous changes and modifications in its composition with the aim to improve safety and tolerability while maintaining contraceptive efficacy. Most of the changes have been conducted on the progestin component, since most of the combinations include ethinyl estradiol as oestrogen. One of the adverse effects of COC is the increased risk of venous thromboembolism (VTE) in two clinical forms of presentation: deep vein thrombosis or pulmonary embolism. This review details the changes in haemostasis induced by progestin-only contraceptives and the risk of VTE in women who utilize this type of contraception; the relationship with other risk factors such as thrombophilia; the interactions of these contraceptives with anticoagulant treatment and finally the eligibility criteria for the use of hormonal contraception in women with previous VTE or thrombophilia carriers.

One-year follow-up of en bloc renal transplants from pediatric donors in adult recipients.

OBJECTIVES: The optimal use of kidneys from small pediatric cadaveric donors remains controversial. The aim of this study was to analyze short-term graft and patient survivals of en bloc kidney transplantations compared with single cadaveric adult donor kidney transplantations. PATIENTS AND METHODS: We compared the 1-year evolution of 14 adult recipients of en bloc pediatric kidney donors (EBKT) of median age 13.5±14.5 months (range=3 days to 48 months) with 182 recipients of ideal adult cadaveric donors (ADT) showing a median age of 30±21 years (range=14-45 years). RESULTS: Besides the different age and weight of the donors, EBKT recipients were more commonly women (P=.05) and received thymoglobulin induction treatment (P=.00). Delayed graft function was higher in EBKT (46.2% vs 22.2%, P=.05), with no differences in the incidences of acute rejection episodes. Mean serum creatinine values at 3, 6, and 12 months after transplantation were 1.1±0.3, 1.1±0.2, and 1.0±0.2 mg/dL in the EBKT group, compared with 1.3±0.5 (P=.16), 1.3±0.5 (P=.02), and 1.3±0.6 (P<.01) in the ADT group. Vascular allograft complications were more frequent among EBKT. Graft survival rate at 1 year was 92% in both groups, with no differences in patient survival (100% in EBKT vs 92% in ADT; P=.49). CONCLUSIONS: EBKT from small pediatric donors show excellent graft function and 1-year survival and should be considered for transplantation into adults.

Ambulatory blood pressure monitoring in renal transplant patients: should it be routinely performed?

INTRODUCTION: Arterial hypertension is common among kidney transplant patients. It increases cardiovascular risk and is a factor for progression of renal failure. Our objective was to perform ambulatory blood pressure monitoring (ABPM) in renal transplant patients with office hypertension. METHODS: Patients were divided into 2 groups according to their mean ABPM blood pressures with treatment: well-controlled hypertension (blood pressure [BP] <130/85 mmHg), and poorly controlled hypertension (BP>130/85 mmHg). A "nondipper pattern" was defined as a decrease of <10% or an increase, and a "raiser pattern," in which mean blood pressure was greater during the nocturnal than the diurnal period. "White coat effect" was considered when the mean of 3 BP measurements in the clinic was >140/90 mmHg among well-controlled hypertensive patients as documented by ABPM. RESULTS: ABPM was performed in 53 patients: 25 (47%) "well-controlled hypertensives" and 28 (53%) "poorly controlled hypertensives." Of the latter, 24 (85%) showed a nondipper or raiser pattern with only 4 revealing dipper patterns. We compared well-controlled with poorly controlled hypertensives. The latter cohort were older (54.4±9.3 vs 45.5±13.8 years; P=.009), received grafts from older donors (56.7±15.0 vs 45.8±17 years; P=.02); had worse renal function measured by serum creatinine (1.7±0.5 vs 1.4±0.4 mg/dL, P=.03) or the Modification of Diet in Renal Disease (MDRD)=4 formula (41.8±14.0 vs 55.4±20.5 mL/min/1.73 m2; P=.009), and displayed more proteinuria (0.30±0.33 vs 0.18±0.10 g/d, P=.08). Nondipper or raiser patients showed a higher mean body mass index (27.1 vs 21.7 kg/m2; P=.04). Among 25 well-controlled patients, 11 presented "white coat phenomenon." CONCLUSION: We observed an important "white coat" effect, a large prevalence of uncontrolled nocturnal hypertension, and a small but important incident of "masked hypertension." Factors related to hypertension control were patient age, donor age, renal function, induction use, and proteinuria.

Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gs{alpha} coding mutations and GNAS imprinting defects.

BACKGROUND: Pseudohypoparathyroidism (PHP) defines a rare group of disorders whose common feature is resistance to the parathyroid hormone. Patients with PHP-Ia display additional hormone resistance, Albright hereditary osteodystrophy (AHO) and reduced Gsalpha activity in easily accessible cells. This form of PHP is associated with heterozygous inactivating mutations in Gsalpha-coding exons of GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib typically have isolated parathyroid hormone resistance, lack AHO features and demonstrate normal erythrocyte Gsalpha activity. Instead of coding Gsalpha mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at least in some cases, by genetic mutations within or nearby this gene. PATIENTS: Two unrelated PHP families, each of which includes at least one patient with a Gsalpha coding mutation and another with GNAS loss of imprinting, are reported here. RESULTS: One of the patients with GNAS imprinting defects has paternal uniparental isodisomy of chromosome 20q, explaining the observed imprinting abnormalities. The identified Gsalpha coding mutations include a tetranucleotide deletion in exon 7, which is frequently found in PHP-Ia, and a novel single nucleotide change at the acceptor splice junction of intron 11. CONCLUSIONS: These molecular data reveal an interesting mixture, in the same family, of both genetic and epigenetic mutations of the same gene.

Renal allografts from donors older than 70 years are useful for single transplantation.

Kidney transplantation has been related in elderly recipients to a greater longevity compared with dialysis. Due to the scarcity of donors, transplantation of older patients depends on the acceptance of older donors. We compared the characteristics and evolution of transplants from donors >or=70 years (n = 53) with those from donors >55-<70 years (n = 201). Group D >or=70 included older recipients (65.37 +/- 4.9 vs 55.92 +/- 9.66 years; P = .000) and more women (62.3% vs 45.3%; P = .02), with more peripheral arterial disease (10.9% vs 2.4%; P = .011). No differences in donor characteristics were observed. Induction treatment with thymoglobulin or basiliximab was more common in D >or=70 (81.1% vs 57.3%; P = .006), with no differences in other immunosuppressive drugs. The incidence of delayed graft function (DGF) was similar (P = .82), with a trend to a lower incidence of acute rejection episodes among D>or=70 (11.8% vs 22.5%; P = 0.09). Serum creatinine and proteinuria levels did not differ during follow-up (P > .05). Patients in D >or=70 displayed more episodes of urinary sepsis (19.1% vs 6.4%; P = .008), but no differences were observed in cytomegalovirus (CMV) infection (P = .629), neoplasia (P = .118), ischemic cardiopathy (P = .642), or hospital readmission due to infections (P = .567). Graft survivals at 5 years were 70% and 75% (P = .279) among groups D >or=70 and D>55-<70, respectively, and patient survivals at 5 years were 88% and 88% (P = .63), respectively. In conclusion, our study showed that selected kidneys from donors older than 70 years were followed with excellent graft and patient survivals, permitting older patients on renal replacement therapy to benefit from renal transplantation.

Histological findings of early graft biopsies in old donor renal transplant patients receiving induction therapy.

Since recipients of transplants from elderly donors are exposed to an increased risk of delayed graft function (DGF) and acute rejection episodes, administration of induction treatment represents an alternative to preserve renal mass and improve graft survival. We compared the evolution and histological findings of early graft biopsies among 38 recipients treated with Thymoglobulim (33.6%) versus 75 (66.4%) with basiliximab. No differences were observes in the rate of DGF (P = .39). Forty kidneys were biopsed during the first 2 weeks after transplantation: 9 in the Thymoglobulin group (23.68%) and 31 in the basiliximab group (41.3%). Histological evaluation showed: acute tabular necrosis in 7 (78%) Thymoglobulin patients versus 14 (45%) basiliximab patients, with calcineurin nephrotoxicity in 2 (22%) and 1 (3.2%), respectively. An acute rejection episode was not diagnosed in the Thymoglobulin group, but 13 patients (17.3%) in the basiliximab group experienced this complication (P = .006). Banff classification showed: 6 grade IA (19.4%), 1 grade IB (3.2%), 3 grade IIA (9.7%), 1 grade IIB (3.2%), and 2 grade III (6.5%). Six of these patients required rescue treatment with Thymoglobulin. Serum creatinine and proteinuria levels between the 2 groups were not different (P > .05). There were no differences in cytomegalovirus (CMV) disease (P = .152), admission due to infection (P = .120), or neoplasia (P = .29). Graft and patient survivals at 3 years did not show a difference. The histological findings revealed that low doses of Thymoglobulin were much more effective to prevent renal inflammation and acute rejection episodes than basiliximab among renal transplant recipients, albiet without differences in survival at a mean of 3 years follow-up.

Beginning hemodialysis: do patients with a failed renal transplant start in worse condition?

OBJECTIVE: Predialysis management of patients with kidney transplant failure is a topic of growing interest. Herein we have reviewed a group of patients with a failed kidney transplant who returned to dialysis to compare them with patients with native kidney failure. PATIENTS AND METHODS: We analyzed 25 patients who returned to dialysis after a failed renal transplant (group A) and 38 patients initiating dialysis after native kidney failure (group B). RESULTS: We did not observe significant differences in the glomerular filtration rate (GFR), potassium, calcium, phosphorus, albumin, and hemoglobin levels between the 2 groups at the beginning of dialysis. Erythropoietin resistance index (ERI) was higher in group A. Progression of renal disease in the 2 years before dialysis was faster in group A, with a greater monthly decline in GFR and higher levels of systolic blood pressure. Renal transplant patients needed more evaluations in the 6 months before initiating dialysis: 1.75 +/- 0.97 vs 0.70 +/- 2.61 evaluations/month (P = .000). Also, the number of hospitalizations during the years before and after dialysis initiation was higher among group A. Patient survival after return to dialysis at 1 year was 75% in group A and 97% in group B (log-rank; P = .09). CONCLUSIONS: Patients with a failed kidney allograft initiated dialysis in similar condition to those with native kidney failure. The faster GFR decline may be related to immunosuppressive treatment. Transplant patients needed more frequent evaluations and more hospitalizations before and after dialysis initiation, indicating a higher morbidity rate.

Cytomegalovirus infection renal transplant recipients: risk factors and outcome.

OBJECTIVE: Cytomegalovirus (CMV) is the most common viral infection after allotransplantation; it can be a major cause of morbidity and mortality. Our aim was to analyze the main risk factors that lead to development of CMV infection and disease. PATIENTS AND METHODS: We retrospectively analyzed 207 patients who received a renal allograft from May 2003 to December 2007. Three patients (D-/R-) were excluded. CMV infection was defined by the detection of 2 or more positive tests for pp65 antigenemia and CMV disease by evidence of attributable symptoms in need of antiviral treatment. RESULTS: Thirty-two patients (15.7%) presented active CMV infections and another 35 (17.2%), CMV disease. The mean follow-up was 27.8 +/- 17 months. Prior to transplantation, 9.2% of patients were seronegative (D+/R-) and 77.9% seropositive (D+/R+). Compared with noninfected patients, those with CMV infection/disease were older and received an allograft from an older donor. Upon logistic regression analysis, recipient age older than 55 years, induction therapy with Thymoglobulin, and maintenance immunosuppression with cyclosporine were the major risk factors to develop CMV disease. An early acute rejection episode was more frequent and renal function measured by serum creatinine poorer until 18 months posttransplantation among CMV-infected versus noninfected patients. CONCLUSIONS: Our data showed that CMV infection is a common complication after kidney transplantation associated with older age, induction treatment with antilymphocyte globulin, worse renal function, and increased patient morbidity.

[Diagnosing neoplasia in a kidney transplant unit]. / Diagnóstico de neoplasias en una consulta de trasplante renal.

BACKGROUND AND AIM: Cancer is one of the major causes of death with functioning allograft among renal transplant patients. The increasing age of patients in the waiting list has derived in a higher risk of cancer in this population. The aim of this study was to analyze the incidence of cancer in the waiting list and kidney transplant patients. METHODS: Between November/1996 and November/2007 we assisted 825 patients in the outpatient renal transplant clinic, 467 were transplanted, 120 remained in the waiting list and 238 have been removed from the waiting list or died. RESULTS: During this period, 97 malignancies were diagnosed, 33 of 32 kidney transplant candidates and 64 of 62 renal transplant patients. The comparative analysis between this two groups showed that candidates had higher frequency of solid organ tumours compared with a higher incidence of skin cancer in transplanted patients. Mean time between transplant and cancer diagnosis was 42.6 +/- 32.7 months, 48% of malignancies were diagnosed within the first three years postransplant. When comparing kidney transplant patients with and without cancer diagnosis, the formers were older and had worse patient survival at five years. Allograft survival was similar for both groups. CONCLUSIONS: we want to emphasize the extreme importance of a detailed screening in the renal transplant candidates and transplanted patients due to a higher incidence of malignancies in this population.

Maternal glucose tolerance status influences the risk of macrosomia in male but not in female fetuses.

OBJECTIVE: To elucidate whether the risk of macrosomia, large for gestational age (LGA) and small for gestational age (SGA) is influenced by maternal body mass index and glucose tolerance differently in male and female fetuses. METHODS: A population study was conducted in 16 general hospitals from the Spanish National Health Service that included 9270 consecutive women with singleton pregnancies and without a former diagnosis of diabetes mellitus who delivered 4793 male and 4477 female newborns. Logistic regression analyses were performed to predict the effect of body mass index (BMI) category and glucose tolerance on macrosomia, large for gestational age newborns (LGA) and small for gestational age newborns (SGA) Separate analyses according to foetal sex were carried out for each outcome. The results were adjusted for maternal age, gestational age and pregnancy-induced hypertension. RESULTS: There were significant differences between males and females in the percentage of infants who had macrosomia, LGA or SGA. Maternal BMI category was positively associated with the risk of macrosomia and LGA in both male and female newborns. In addition, there was a negative association between maternal BMI and SGA that only reached significance in males. In contrast, gestational diabetes was only a predictor of macrosomia exclusively in male fetuses (OR 1.67, 95% CI 1.12 to 2.49) CONCLUSIONS: There is sexual dimorphism in the risk of abnormal birth weight attributed to maternal glucose tolerance status. A closer surveillance of foetal growth might be warranted in pregnant women with abnormal glucose tolerance carrying a male fetus.

Treatment of renal transplant failure.

INTRODUCTION: Among graft failures beyond months, we performed progressive reduction and complete withdrawal of immunosuppressive drugs and steroids over a period of 6 months. PATIENTS AND METHODS: We analyzed the treatment and complications associated with all late allograft failures in 34 patients (8.19%) out of 415 patients transplanted from November 1996 to November 2006. RESULTS: In 21 patients (61.8%), the progressive reduction of immunosuppressive treatment was effective and well tolerated; however, in 13 patients (38.2%) there was rejection of the allograft at 10.74 +/- 8.95 months (0.77-34.80) after the failure. With the reintroduction of these drugs, the rejection was controlled in seven patients, but in the other six we had to embolize the allograft, which had to be repeated in one case. Embolization was well tolerated, but in one case there was migration of one coil to the femoral artery. One patient treated with drug withdrawal experienced emphysematous pyelonephritis after repeated urinary infections, requiring a nephrectomy. Thirteen (38.2%) of the patients with late failures have been admitted for a second transplant; five of them showed HLA sensitization. CONCLUSIONS: Conservative treatment with progressive withdrawal of immunosuppression was effective and well tolerated in two-thirds of the patients with late renal allograft failure, but one-third of the patients rejected the graft and needed allograft embolization. Infection of the graft and HLA sensitization can complicate the course of these patients.

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