New York University School of Medicine Drug Development Educational Program: 2-Year Benchmark.

Drug development (DD) is a multidisciplinary process that spans the translational continuum, yet remains an understudied entity in medical schools and biomedical science institutes. In response to a growing interest and unmet need, we implemented a DD course series that details identification of viable molecular targets, clinical trial design, intellectual property, and marketing. Enrollment is open to faculty, postdoctoral trainees, and MD, PhD, and MS students. After 2 years, 37 students and 23 students completed the fall and spring courses, respectively. Pre/post-surveys demonstrated gained knowledge across course topics, with mean survey scores increased by 66% (p < 0.001) after each course. Lectures for each course were consistently rated highly, with a mean course rating of 4.1/5. Through this program, trainees will have a more innovative approach toward identification of therapeutic targets and modalities. Furthermore, they will learn to integrate technology and biomedical informatics to find creative solutions in the DD process.

Development of urologic de novo malignancies after renal transplantation.

OBJECTIVES: The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS: We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS: We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS: There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.

Renal transplantation in HIV-infected patients: experience at a tertiary hospital in Spain and review of the literature.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has decreased the morbidity and mortality in HIV-infected patients. The kidney transplantation (KT) survival rate is similar to that of HIV-negative transplant recipients. The consensus criteria for the selection of HIV patients for transplantation include: no opportunistic infections, CD4 lymphocyte count greater than 200 cells/µL, and an undetectable viral load. In Spain, HIV-infected patients present with different characteristics compared to American recipients; this could influence posttransplantation outcomes. OBJECTIVE: This study analyzed the outcome and the clinical characteristics of HIV-infected patients who received KT in Spain in the HAART era. METHODS: We retrospectively reviewed the clinical charts of seven adult HIV-infected recipients of primary renal allografts between January 2001 and June 2012. Patient inclusion criteria met the American and Spanish guidelines. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The median age was 44.8 years (interquartile amplitude = 9.4). The predominant mode of transmission was intravenous drug use (71.4%) and hepatitis C virus coinfection (71.4%). The most frequent cause of end-stage renal disease was glomerulonephritis (57.1%). Six patients (85.7%) were on HAART. All patients had controlled HIV infections with undetectable viral load and a median CD4 lymphocyte count of 504 cells/µL (IQA 599). Patients were followed for a median of 16.0 months (range, 3.0 to 96.6 months). Delayed graft function and acute rejection rates were 60% and 40%, respectively. The median creatinine level at the last follow-up was 1.58 mg/dL (IQA 1.15). In one case, a high-grade Epstein-Barr virus-related B cell lymphoma was diagnosed at 83 months after renal transplantation. CONCLUSIONS: Kidney transplantation in HIV-infected patients is a safe, effective treatment for selected patients. Midterm graft survival was comparable to that of HIV-negative patients.

[Fever as the presenting manifestation of colon cancer: a case series of 11 patients]. / Fièvre révélatrice d'un cancer colique: 11 observations.

INTRODUCTION: Fever happens frequently in colon cancer but it is rarely the presenting manifestation. PATIENTS AND METHODS: We report a case series of patients with colon cancer revealed by fever in the three military hospitals in Paris. RESULTS: Of the 11 patients studied, seven were men and four were women, and their mean age was 70 years. Cancer was localized in the sigmoid colon (n=6), left colon (n=3) and right colon (n=2). Cancer staging (UICC TNM classification 2002) was respectively pTis (n=1), I (n=4), II (n=3) and III (n=3). Fever was the only reason for admission and two patients had a recurrent fever of unknown origin. All patients but one had bacterial infection. Blood cultures grew up in six cases, Escherichia coli (n=3), Streptococcus gallolyticus (ex bovis) (n=2) and anaerobic bacteria (n=1). There was one case of infective endocarditis caused by S. gallolyticus. Imaging showed a liver abscess (n=3) and a colon cancer complicated by an abscess (n=3). In seven patients, a familial history of colon cancer and symptoms of underlying colic disease were present (neglected rectal bleeding, iron deficiency anaemia, clinical evidence of an abdominal mass). CONCLUSIONS: Fever may reveal colon cancer at an early stage. Its main cause is a bacterial infection, such as bacteremia or abscess. Fever of unknown origin is a rare presentation. Detailed history, careful clinical examination and analysis of imaging contribute to recommend the prescription of colonoscopy.

Economic impact of the introduction of machine perfusion preservation in a kidney transplantation program in the expanded donor era: cost-effectiveness assessment.

BACKGROUND: Kidney transplantations (KT) from expanded criteria donors (ECD) show a higher rate of delayed graft function (DGF) that increases postoperative costs because of the prolonged hospital stay as well as the needs for dialysis and additional diagnostic procedures. Hypothermic machine perfusion (MP) might be superior to cold storage (CS) to reduce the relative risks of DGF and primary nonfunction (PNF) as well as to increase 1-year graft survival. OBJECTIVE: The aim of the study was to determine the relative cost-effectiveness of two different storage methods: MP versus CS. METHODS: A probabilistic decision tree was developed to compare MP and CS as graft preservation methods. The structure of the model was populated by review of the literature and outcomes of KT from ECD in our center. The model estimated budget impact and incremental cost-effectiveness ratio in terms of DGF and PNF cases. The cost comparison of methods for KT preservation included: hospitalization and intermediate care unit stay; post-KT dialysis; graft removal; immunosuppressive regimen; treatment of acute rejection episodes; as well as costs of preservation solutions and pulsatile preservation device or storage containers. RESULTS: Resource consumption for CS stratified by graft function varied from $8,159 for immediate graft function (IGF) recipients to $10,865 for DGF recipients to $25,933 for PNF recipients. Meanwhile, resource consumption for MP varied from $9,522 for IGF to $12,228 for DGF to $27,297 for PNF recipients. The main components of resource consumption were hospitalization stay (41.5%-53.9%); graft explantation (20.2%), and the need for dialysis (16.0%). The budget impact per patient for the introduction of MP was $505. However, the incremental cost-effectiveness ratio was $3,369 for each DGF- or PNF- saved case. CONCLUSIONS: The introduction of the MP preservation technology in a KT program form ECD is cost-effective in terms of savings for DGF and PNF cases.

The effects of mineral metabolism markers on renal transplant outcomes.

BACKGROUND: Hyperparathyroidism is a common complication of chronic renal failure. A functioning kidney graft improves hyperparathyroidism but it can persist to some degree for years. Persistent hyperparathyroidism associated with hypercalcemia and hyperphosphatemia have been associated with poor graft and patient survivals. The purpose of the present work was to assess the association between calcium/phosphate mineral metabolism markers and graft outcomes. PATIENTS AND METHODS: Among 389 renal transplantations performed in our center between January 2000 and June 2008, 331 patients had functioning grafts at 12 months, the subjects of this study. Measurements of intact parathyroid hormone (iPTH), serum calcium and phosphate, tubular phosphate reabsorption, and urinary calcium excretion were performed at 1, 3, 6, and 12 months. The mean follow-up was 84.0 ± 31.8 months. RESULTS: During the follow-up period, 63 grafts (19.0%) were lost, 30 patients (9.0%) died, and 80 recipients (24.2%) presented at least one cardiovascular event. Univariate Cox proportional analysis showed high iPTH levels at 1 and 12 months after transplantation to not be associated with worse patient or graft survival or an higher risk of cardiovascular events. Serum phosphate and calcium concentrations as well as calcium-phosphate products during the first year after transplantation were not associated with graft and patient outcomes or cardiovascular events. However, serum calcium at 12 months showed an inverse association with graft survival after adjusting for other variables (hazard ratio 0.61; 95% confidence interval 0.40-0.94; P = .026). CONCLUSIONS: iPTH levels and serum phosphate concentrations and calcium-phosphate products during the first year after transplantation were not associated with graft outcomes. The inverse association between adjusted calcium and graft survival should be studied further.

Anemia at 1 year after kidney transplantation has a negative long-term impact on graft and patient outcomes.

BACKGROUND: Anemia, a common complication after kidney transplantation, has a controversial impact on graft or patient survivals or the appearance of cardiovascular disease. The present study investigated the incidence and risk factors for anemia in the first year after transplantation and its effects on graft and patient outcomes. PATIENTS AND METHODS: Among 389 patients transplanted between January 2000 and June 2008, the 331 with functioning grafts at 1 year were included in the study. The mean follow-up was 84 ± 31.8 months. Anemia was defined according to the World Health Organization as a hemoglobin < 13 g/dL in men and < 12 g/dL in women. RESULTS: The 88 patients (26.6%) with anemia included 21 (6.3%) who were receiving erythropoiesis stimulant agents. The predictive factors for anemia were: initial immunosuppression with cyclosporine (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.25-3.47; P = .005), serum creatinine (mg/dL) at discharge (OR 1.7; CI 95% 1.26-2.15 P = .000), and 1-year serum albumin (g/dL; OR 0.21; CI 95% 0.10-0.71 P = .001). Donor age in years (OR 1.02; CI 95% 1.00-1.03, P = .054) was close to significance. Cox multivariate analysis showed 1-year hemoglobin (g/dL) to be associated with graft (hazard ratio [HR] 0.81, 95% CI 0.69-0.96, P = .003) and patient survivals after adjusting for other variables (HR 0.74; 95% CI 0-59-0.96, P = .023). But it was only a cardiovascular risk factor when serum creatinine was not included in the model. CONCLUSIONS: Approximately one quarter of patients with functioning grafts show anemia at 1-year. Graft function, initial immunosuppression, serum albumin, and perhaps donor age were risk factors for anemia, which had a negative impact on graft and patient survival, and could be a risk factor for cardiovascular disease.

[Effects of two methods of heat therapy on the acute vascular response and hemodynamics in healthy subjects]. / Efectos de dos métodos de termoterapia sobre la respuesta vascular aguda y parámetros hemodinámicos en un grupo de sujetos sanos.

OBJECTIVE: Recently, non-pharmacological resources to relieve pain like hot packs and ultrasound (US) have become common in clinical practice. However, little experimental evidence is available about the possible mechanisms through which these methods bring about pain relief. We aimed to determine the effects of hot packs and US on the acute vascular response and on hemodynamic parameters in healthy subjects. MATERIALS AND METHODS: We conducted an experimental study in 20 healthy subjects (10 men and 10 women; mean age, 22.54±1.70 years). The two interventions were randomly applied: a) hot packs (n=10): 15min at 60°C and b) US (n=10): 15min at 1Mhz. Before and after each intervention, the following vascular parameters were measured in the brachial artery using Doppler ultrasonography with a 7MHz probe: arterial compliance, elastic modulus, beta stiffness index, systolic and diastolic arterial diameters, systolic flow velocity and diastolic flow velocity, systolic/diastolic ratio, resistance index, and pulsatility index. The following hemodynamic parameters were monitored: heart rate and blood pressure (systolic, diastolic, and mean). RESULTS: After the application of hot packs, we observed changes in diastolic flow velocity and in the pulsatility index (P<05). After the application of US, we observed changes in diastolic flow velocity, systolic/diastolic ratio, resistance index, and arterial compliance (P<05). No changes in hemodynamic parameters were observed after either intervention. CONCLUSIONS: Applying hot packs or US modifies the physiology of the vascular system but does not affect hemodynamic parameters in healthy subjects.

Utilization of elderly kidney donors (>70 years) does not affect graft survival in the medium term.

BACKGROUND: The need for organs for renal transplantation has encouraged the use of grafts from increasingly older donors. Earlier studies performed in Spain have shown the suitability of donors aged 60-65 years. In this single-center study, we evaluated our results using donors >70 years old. METHODS: We evaluated 401 primary transplantations performed from January 2000 to December 2009. Their initial immunosuppression was a tacrolimus-based (n = 324), cyclosporine-based (n = 70) or calcineurin inhibitor-free (n = 7) regimen patients. Recipients were classified according to the donors age: <50 (42.6%); 50-70 (39.7%) and >70 (17.5%) years. RESULTS: There were no differences in recipient or donor gender, time on dialysis, cold ischemia, delayed graft function, or acute rejection episodes. However, the mean age was higher among patients who received grafts from donors >70 years old; 42.5 ± 12.4 years for <50, 58.1 ± 8.2 years for 50-70, and 65.7 ± 7.2 years for >70; (P = .000). The serum creatinine at 12 months was increased according to the age of the donor; 1.4 ± 0.6, 1.8 ± 0.6, 70 and 1.7 ± 0.5 mg/dL, respectively (P = .001). The graft survival rates at 5 years were 81%, 74%, and 70%, respectively (P = .519). Upon multivariate analysis only HLA-DR mismatches, delayed graft function, and acute rejection episodes were associated with graft loss. Patient survival rates (86%) at 5 years were similar among recipients from donors aged 50-70 and >70 years, but higher (96%) for those who received a graft from a donor <50 years (P = .003). CONCLUSIONS: Nearly 20% of donors were >70 years old in our study. Their kidneys displayed excellent short-term outcomes.

Cholecalciferol supplements improve vitamin D deficiency in renal transplant recipients.

Most renal transplant recipients display vitamin D deficiency or insufficiency. The KDIGO guidelines suggest that this deficit should be treated as in the general population. Since there are few studies about the effects of cholecalciferol in de novo renal transplant recipients, we sought to assess these effects in long-term kidney graft recipients. Among 37 renal transplant recipients (19 males, 18 females) at a mean of 105±82 months posttransplantation, vitamin D insufficiency or deficiency was treated with cholecalciferol (400-800 IU/d) plus calcium supplements (600-1200 mg/d of elemental calcium). These subjects were compared with 37 untreated recipients for a period between 6 and 12 months. At baseline, there were no differences between the groups in age at transplantation, sex, length of follow-up after grafting, function measured by estimated glomerular filtration rate (44.4±16.8 treated vs 42.0±15.0 mL/min/1.73 m2 untreated; P=.527); iPTH (157±103 treated vs 176±118 pg/mL untreated; P=.461); 25OHD (14.7±4.7 treated vs 15.7±9.7 ng/mL untreated; P=.584); or 1.25OHD (34.1±26.0 treated vs 34.0±13.0 pg/mL untreated; P=.950). When compared with baseline values, iPTH (157±103 vs 144±89 pg/mL; P=.11) and 1.25OHD levels at 6 months (34.1±26.0 vs 35.9±26.3 pg/mL; P=.282) showed no change but 25OHD levels (14.7±4.7 vs 22.6±7.4 ng/mL; P=.000) and phosphate tubular reabsorption (64%±17% baseline vs 69%±14% at 6 months; P=.030) were increased in the treated patients. There were no differences in the parameters studied in untreated patients. Among the 27 recipients followed at 12 months, iPTH was decreased compared with baseline values (157±103 vs 124±62 pg/mL; P=.024) and 25OHD remained stable with respect to the values at 6 months (21.1±5.3 ng/mL). No adverse effects of cholecalciferol were observed such as those to increase urinary calcium excretion. Low doses of cholecalciferol improved vitamin D status and decreased iPTH levels at 12 months. Higher doses than those used in our study are needed to increase serum 25OHD concentrations above 30 ng/mL.

Effects of the new immunosuppressive agents on the occurrence of malignancies after renal transplantation.

INTRODUCTION: The risk of malignancies in renal transplant recipients is considerably greater than in the general population. The purpose of the present study was to investigate the effects on the appearance of malignancies of 3 immunosuppressive periods: azathioprine (AZA), cyclosporine (CsA), and tacrolimus (TAC). PATIENTS AND METHODS: This study included 1029 first renal transplant recipients of mean age at transplantation of 44.6±14.9 years with a mean follow-up of 95.6±84.2 months. Initial immunosuppression was AZA-based (n=198), CsA-based (n=524), and TAC (n=307). A total of 280 recipients were also treated with mycophenolate mofetil or mycophenolic acid. RESULTS: There were 157 patients (15.3%) who displayed≥1 malignancy; there were 95 skin (9.2%) and 74 (7.8%) non-skin malignancies with presentations at 74±62 and 107±77 months, respectively (P=.003). The skin malignancies included squamous cell carcinomas (n=41), basal cell carcinomas (n=41), Kaposi sarcomas (n=7), and melanomas (n=4). Among the solid tumors, lymphoproliferative disorders (n=15), digestive tract (n=14), kidney and urinary tract (n=11), lung (n=10), and breast (n=3) carcinomas. The cumulative incidences at 5, 10, and 15 years were 6%, 10%, and 18% for skin and 3%, 7%, and 14% for non-skin malignancies, respectively. Multivariate analysis showed that age at transplant in years (P=.000) and male gender (P=.000) were the only variables associated with skin malignancies; age at transplant in years (P=.004) and treatment with OKT3 (P=.000) were associated with non-skin malignancies. Malignancies were the cause of death in 18% of recipients who died with functioning grafts. CONCLUSION: Malignancies are an important cause of morbidity and mortality among renal transplant recipients. The new immunosuppressive agents do not increase the risk of malignancies. Special surveillance is needed for older, male recipients.

Mycophenolate mofetil absorption quotient: interest to clinical practice.

Use of mycophenolate mofetil (MMF) in kidney transplantation has led to significant improvements in the acute rejection index and graft survival. Posttransplant MMF levels are known to be of value for discriminating patients at risk of acute rejection. Trough MMF levels were measured in 153 patients who had undergone kidney transplantation more than 1 year before and showed stable graft function. MMF dosage was adjusted based on hematologic or gastrointestinal toxicity. The quotient between the weight-adjusted dose and through MMF levels was calculated in order to establish absorption type. We analyzed the diagnostic value of this quotient in relation to creatinine proteinuria, hematologic and gastrointestinal toxicity based upon percentiles of 10, 25, 50, 75, and 90, which were used as cutoff points. Mean MMF levels were 3.79 +/- 3.3 mg/L. Mean quotient value was 6.55 +/- 9.2. A significant correlation was found between MMF dosage and MMF trough levels (r = .34, P < .01). However, no correlation was seen between MMF dosage and the quotient. There were no significant differences in the analyzed parameters and the percentiles established as cutoff points. However, patients with gastrointestinal toxicity had a larger quotient (9.07 +/- 7.45.3 vs 5.28 +/- 4.9). The relationship between MMF dose and levels does not establish differences in kidney function and proteinuria among stable transplant patients; patients with diarrhea may show decreased absorption.

Complete switch to everolimus in long-term kidney transplants: evolution of the renal function.

INTRODUCTION: The use of M-tor inhibitors plus withdrawal of anticalcineurins after 3 months of posttransplantation is usually linked to improvements in renal function. The long-term effects of substitution of anticalcineurinis by everolimus remain unknown. The aim in this study was to evaluate the evolution of renal function and the proteinuria after a complete switch of long-term functioning allograft patients to everolimus. We treated 30 renal transplanted patients with everolimus, at a mean time posttransplantation of 123.8 +/- 74.2 months. The 27 patients, including 17 treated with tacrolimus and 10 with cyclosporine, who were controlled for at least 6 months were included in this study. Seventeen of them were diagnosed to display chronic allograft nephropathy (CAN). RESULTS: The patients with CAN showed a basal creatinine of 1.81 +/- 0.4; with after a year, 1.61 +/- 0.38; and after 2 years, 1.56 +/- 0.49 mg/dL (P < .05). No significant changes were observed among patients without CAN: 1.1 +/- 0.32, 0.97 +/- 0.15, and 0.97 +/- 0.15 mg/dL, respectively. In CAN patients, the protein/creatinine quotient was: basal = 0.30 +/- 0.13, one year = 0.63 +/- 0.68, and 2 years = 0.48 +/- 0.34. In the other patients the values were 0.2 +/- 0.07, 0.73 +/- 0.7, and 0.32 +/- 0.17, respectively, after a late switch to everolimus. CONCLUSION: The improved renal function occurred mainly in patients with CAN. Patients who did not suffer from it showed a greater rise in proteinuria. Nevertheless, both groups experienced decreased proteinuria after 2 years.

Evolution of rejection rates and kidney graft survival: a historical analysis.

INTRODUCTION: New immunosuppressive regimens have dramatically reduced rejection rates but this positive effect has not been followed by an improvement in long-term graft outcomes. The aim of the present work was to investigate the incidence of graft rejection and graft outcomes with various immunosuppressive protocols. PATIENTS AND METHODS: Included in our study were 1029 first renal transplantations performed at our unit between November 1979 and December 2007. Basal immunosuppression included azathioprine (AZA) in 198 recipients, cyclosporine (CsA) in 524 recipients, and tacrolimus (TAC) in 307 recipients. RESULTS: Recipient and donor ages increased progressively from the AZA to the TAC era. Delayed graft function was less frequent among AZA than CsA and TAC recipients (29.8 vs 39.3% vs 42.0%; P = .014). The incidence of acute rejection episodes was 68.7% on AZA, 38.2% on CsA, and 11.4% on TAC (P = .000). Graft survival rates at 1, 5, and 10 years were 69%, 56%, and 46% on AZA, 82%, 69%, and 54% on CsA, and 88%, 77%, and 60% on TAC, respectively (P = .001). However, the differences disappeared when only grafts surviving >12 months were analyzed. On multivariate analysis, the variables associated with worse graft outcomes after 12 months were older recipient age, male gender, longer time on dialysis, lower body weight, and higher serum creatinine level at 6 months. CONCLUSIONS: New immunosuppressants have decreased the incidence of acute rejection. But this was not followed by a significant improvement in graft outcomes after 12 months. The beneficial effects on rejection are possibly affected by the older age of donor and recipient and the worse early graft function.

Vitamin D deficiency in kidney transplant recipients: risk factors and effects of vitamin D3 supplements.

INTRODUCTION: The Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines in chronic kidney disease (CKD) give some recommendations about diagnosis and treatment of vitamin D deficiency. These guidelines may also be applied to renal transplant recipients. The aim of the present study was to assess the vitamin D status and the effects of vitamin D3 supplements among a cohort of kidney graft recipients. PATIENTS AND METHODS: Five hundred nine renal transplant recipients with a follow-up of more than 12 months were included in this retrospective cross-sectional study. A total of 189 patients were treated with vitamin D3 supplements, 171 with calcitriol (0.25 or 0.5 microg x 3 weekly) and 18 with cholecalciferol (400 IU/d). RESULTS: 25OHD deficiency was present in 38.3% of patients, insufficiency in 46.9%, and normal levels in 14.7%. There were no differences in the prevalence of deficiency or insufficiency between patients who were not treated or those who were treated with vitamin D3 supplements. Upon multivariate analysis, 25OHD concentrations correlated with gender, length of follow-up, season of 25OHD determination, iPTH and 1.25OHD concentrations, and treatment with ACEI/ARB (R(2) = 0.17; P = .000). CONCLUSIONS: 25OHD deficiency or insufficiency is frequent after renal transplantation even in sunny regions. The clinical significance of such a high prevalence of apparent 25OHD deficiency/insufficiency is unclear and requires further study.

Secondary hyperparathyroidism after kidney transplantation: a cross-sectional study.

INTRODUCTION: The purpose of the present study was to investigate the prevalence of hyperparathyroidism among a population of kidney graft recipients. PATIENTS AND METHODS: We investigated biochemical bone parameters of 509 renal transplant recipients with a mean follow-up of 113 +/- 76 months. Among these patients, 257 patients were treated with either vitamin D or calcium supplements or both. RESULTS: The mean estimated glomerular filtration rate (eGFR) was 47.2 +/- 18.4 mL/min/1.73 m(2) and the mean intact parathyroid hormone (iPTH) level was 144 +/- 149 pg/mL. A total of 70 patients (13.7%) had hypercalcemia defined by a corrected serum calcium >10.2 mg/dL. When the patients were classified according to iPTH concentrations following the Kidney Disease Outcome Quality Initiative (K/DOQI) clinical practice guidelines: 22.4% had iPTH <70 pg/mL; 30.8% between 70 and 110 pg/mL; 16.5% between 110 and 150 pg/mL; 24.3% between 150 and 300 pg/mL; and 6.9% >300 pg/mL. There were no differences in biochemical bone parameters between those that were or were not on calcium and vitamin D supplements, but there was a higher percentage of patients with normal iPTH among the treated group (28.0% vs 16.7%; P = 0.003). In patients not receiving calcium and/or vitamin D supplements, multiple linear regression demonstrated that only time on dialysis, eGFR, and serum 25-hydroxyvitamin D (25OHD) levels were significantly predictive of iPTH concentrations (R(2) = 0.21; P = .000). CONCLUSIONS: About 80% of patients displayed high iPTH concentrations. The persistence of hyperparathyroidism was associated with graft dysfunction, longer time on dialysis, and low concentrations of 25OHD. Treatment with vitamin D produced a slight improvement in the prevalence of hyperparathyroidism.

Management of chronic kidney disease after renal transplantation: is it different from nontransplant patients?

BACKGROUND: The Kidney Disease Quality Initiative (K/DOQI) of the National Kidney Foundation has published guidelines for the diagnosis and management of chronic kidney disease (CKD). Renal transplant recipients frequently have CKD and complications similar to native kidney disease patients. The purpose of the present study was to compare the management of CKD complications of transplant recipients and nontransplant patients. PATIENTS AND METHODS: Eighty three renal transplant recipients with CKD stages 4T and 5T were compared with 83 nontransplant CKD patients matched by CKD stage. RESULTS: There were no differences between the groups in serum hemoglobin, prevalence of anemia, and percentage of patients treated with erythropoiesis-stimulating agents, but serum ferritin levels were higher among recipients (186.3 +/- 161.3 vs 119.1 +/- 113.4 ng/mL; P = .003). Mean blood pressure (BP) was similar in both groups but a systolic BP > 130 mm Hg was more frequent among recipients (83.3% vs 72.6%). More recipients were treated with either angiotensin-converting enzyme (ACE)-inhibitors or angiotensin receptor antagonist (43.3% vs 8.4%; P < .001). Low-density lipoprotein cholesterol was lower in recipients (108.9 +/- 30.3 vs 120.8 +/- 39.5 mg/dL; P = .033) and a higher percentage was on statin treatment (44.6% vs 28.9%; P = .053). Serum calcium was higher in transplant recipients (9.5 +/- 0.8 vs 8.9 +/- 0.7 mg/dL; P < .005) and phosphate was lower (3.9 +/- 0.9 vs 4.2 +/- 1.1; P = .043); there were no differences in intact parathyroid hormone blood levels. CONCLUSIONS: The management of renal transplant recipients is no worse than that of nontransplant patients. However, in both populations, some parameters are far from the target recommended by the guidelines.

Prophylaxis and treatment of cytomegalovirus infection postrenal transplantation in two Madrid units.

INTRODUCTION: Complete prevention of cytomegalovirus (CMV) disease continues to be an unresolved problem in renal transplantation. MATERIALS AND METHODS: From January 2005 to May 2006, we implemented a protocol for early detection and preemptive treatment of CMV infection as detected by antigenemia or polymerase chain reaction determined every 2 weeks during the first 3 months posttransplant and monthly thereafter. Prophylaxis was given to all CMV-negative patients who received CMV-positive kidneys and to those who received polyclonal or monoclonal antibody induction therapy. RESULTS: Among 100 transplants, 15 subjects received prophylaxis due to poly- or monoclonal antibody induction and/or negative recipient serology using a mean valgancyclovir dose of 485 +/- 276 mg/d for an average duration of 129 days. After completion of the prophylaxis four patients (26.6%) required preemptive therapy for asymptomatic virus reactivation; the mean dose of drug in these patients had been 450 +/- 275.56 mg, with a treatment time that was significantly shorter than those not suffering reactivation (91.75 vs 143.45 days). In addition, preemptive therapy was given for virus reactivation in seven patients, for illness with mild viral syndrome in two, with moderate illness and positive pretransplantation serology in one. The average treatment time was 79 days and the mean dose was 375 mg. CONCLUSION: In those not at risk, CMV infections occurred among 11.7% of patients in our early detection program. Prophylaxis for at-risk patients should continue for more than 3 months to prevent reactivation.

[Recurrence of p-ANCA positive vasculitis with lung hemorrhage in a patient on hemodialysis]. / Recidiva de vasculitis p-ANCA positiva con hemorragia pulmonar en paciente en hemodiálisis.

Relapses of p-ANCA vasculitis during chronic dialysis treatment are infrequent. We report a patient with a pulmonary-renal syndrome and p-ANCA vasculitis who relapsed one year after starting hemodialysis treatment. Treatment with steroids and cyclosphosphamide successfully controlled the relapse, though cyclophosphamide had to be discontinued because of leucopenia. Clinical features of renal vasculitis, relapse after dialysis, the usefulness of ANCA titles as possible predictors and therapeutic options are discussed.