[Complications associated with percutaneous renal biopsy in Spain, 50 years later]. / Complicaciones asociadas a la biopsia renal percutánea. Experiencia en España 50 años después.

BACKGROUND: The renal biopsy is essential for the diagnostic of glomerular disease However, it is an aggressive procedure with risk of complications. OBJECTIVES: The aim of our study was to evaluate the complications directly related to percutaneous renal biopsy procedure in our centre. METHODS: This retrospective study was performed using the data obtained from all patients who underwent percutaneous renal biopsy of the native kidney from January 1992 to December 2008. A semiautomatic 18 G needle biopsy was used until 2004 and thereafter we used a 16 G needle. From January 2009 to January 2010 we prospectively analyzed changes induced by renal biopsy. We analysed age, sex, indication for biopsy, histopathological diagnosis, hypertension, serum creatinine, GFR-MDRD-4, proteinuria, hemoglobin pre and post biopsy. Minor complications were defined as a decrease in hemoglobin levels greater than 1 g/dL. Mayor complications were: need for blood transfusion, surgery, nephrectomy, angiography, embolization, or death. The renal biopsy was performed by the nephrologist with the help of ultrasound. Anticoagulant therapy was removed prior to the biopsy. RESULTS: Total number of renal biopsies were 867. Seven hundred and ninety five renal biopsies were performed between 1992 and 2008. The prospective part of the study included 70 additional biopsies. Considering all patients, the mean age was 46.8 ± 19 and 60.7% were male. There were only six major complications (0.75%). Three of these mayor complications occurred in liver transplanted patients and required vascular embolization or nephrectomy. The remaining 3 major complications were observed in: one patient with liver disease, another patient had trait of hemophilia and a third patient required nephrectomy which after examination demonstrated epithelioid hemangioma. During the prospective analysis the rate of major and minor complications did not change, 1.4 and 2.0 % respectively. Switching from 18 to 16 G biopsy needle did not result in an increase of major complications. CONCLUSIONS: Major complications derived from all renal biopsy during the last 18 years were observed in only 0.75-1.4 %. Major complications occurred mainly in liver transplant patients. The use of 16 G needle provided greater diagnostic yield than the 18 G and it did not cause an increase in complications.

Influence of Pre-renal Transplant Secondary Hyperparathyroidism on Later Evolution After Transplantation.

Persistence of secondary hyperparathyroidism (SHPT) is common after renal transplantation. Good diagnosis and treatment are important to avoid complications. The objective of our work was to perform a retrospective analysis of the evolution of SHPT after renal transplantation. We selected patients who had received a kidney transplant at our hospital between 2000 and 2014. The biochemical variables of chronic kidney disease-metabolic bone disorders (CKD-MBD) were collected at pretransplantation and at 3, 6, 12, and 24 months post-transplantation. Treatments related to SHPT were also analyzed. Five hundred forty-three renal transplants were included. The average preoperative parathyroid hormone (PTH) was 241.14 pg/mL, 115.7 pg/mL at 3 months, and at 12 and 24 months postoperatively, PTH levels stabilized to 112 pg/mL. Treatment related to SHPT was present in 27.3% of patients during the preoperative period, 40.4% at 3 months postoperatively, 24.2% at 12 months postoperatively, and 23.2% at 24 months postoperatively. There was a significant association between requiring some type of treatment preoperatively and the rest of the postoperative periods (P < .005). The sample was later divided into 3 groups based on preoperative PTH (1: <150 pg/mL, n = 223 [41.1%]; 2: 150-300 pg/mL, n = 173 [31.9%]; 3: >300 pg/mL, n = 147 [27.1%]) and their evolutions were compared. Higher levels of postoperative PTH in group pre-PTH 3 were observed. Group 3 also presented with greater need for treatment in the postoperative periods, with significant association (P < .05). A regression analysis was performed and found that postoperative PTH were dependent on preoperative PTH adjusted by glomerular filtration. In conclusion, parameters related to CKD-MBD (mainly PTH) after kidney transplant, dependent on preoperative levels and glomerular filtration. Patients with a greater grade of SHPT presented with higher levels of postoperative PTH despite receiving more intensive treatment.

Cancer incidence and survival in kidney transplant patients.

Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer. This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC. We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007. Results were contrasted with a cohort of patients from the same center without malignancies. The mean follow-up of patients in our series was 10 years. The mean age at presentation of the malignancy was 61 +/- 5 years. The malignancy and NMSC incidences were 6% and 5%, respectively. Patients with malignancy had a longer posttransplant time and greater recipient and donor age. In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 3.1, P = .004); greater patient age (HR 1.09, P < .001), longer posttransplant time (HR 1.2, P = .004) and tacrolimus treatment (HR 4.4, P = .001). Risk factors associated with developing any malignancy were: patient age (HR 1.06, P < .001), number of grafts (HR 3.2, P = .019), tacrolimus treatment (HR 2.5, P = .035), and time posttransplantation (HR 1.2, P = .011). The mean times to development of an NMSC, solid organ malignancy, on PTLD were 7.5, 6.1, or 3.9 years, respectively. The mean survival time from the diagnosis of any malignancy was 9.6 months (95% confidence interval, 0.12-30) for solid organ malignancies and 1 month (95% confidence interval, 0.24-1.87) for PTLD.

[Epidemiological study on chronic renal failure elderly patients on hemodialysis]. / Estudio epidemiológico de pacientes ancianos con insuficiencia renal crónica en hemodiálisis.

Hemodialysis shows an increased prevalence in elderly patients, a population which often presents poor nutrition, high prevalence of cardiovascular, neurological and osteoarticular diseases and psycho-social problems. The objective of this epidemiological, cross-sectional and multicenter study, in patients older than 65 years (n 625) and >75 years (n 558) from 29 Spanish medical institutions was to perform an epidemiological analysis It included demographic information, as well as data regarding chronic renal failure, functional and psychological abilities (Katz Index, Lawton and Karnofsky Scales), dialysis logistics and clinical parameters. The study analyzed data from 1,183 patients (678 female), mean age 75.4+/-5.5 years; mean duration of dialysis 4.3+/-5.1 years (57.7% were referred by the GP: general practitioner). The most frequent etiologies were diabetic nephropathy (21.2%) and vascular renal disease (20.9%). The main comorbilites were high blood pressure (75.6%), Diabetes Mellitus (32.9%) and vascular (29.0%) and osteoarticular (27.3%) diseases. The great majority of patients lived at their family home (85.0%), travelled to their dialysis units alone (80.8%) and by ambulance (56.7%), and it took them less than an hour to arrive (87.5%). Over 75% of patients were fully functional (79.4% under 75 years and 71.6% over 75); meanwhile 10.5% were partially impaired and 13,8% severely impaired. Karnofsky performance scale scored less than 70 in 59.4% of the patients. Analytical parameters rated Hb >or= 11 g/dL for 81.7% of patients; ferritin >or= 100 ng/dL for 98.5%; PTH 150-300 pg/mL for 31.9%; albumin >3.5 g/dL for 75.6%; and serum phosphor <5.5 mg/dL for 70.6%. For the dialysis Kt/V the mean value was 1.4+/-0.3 with a mean duration of dialysis session of 11.7+/-4.0 hours/week. High permeability membranes were used in 52.3% of patients and internal arteriovenous fistula in 74.0%. Around 75% of elderly patients on hemodialysis fulfill age-suitable daily living activities and display adequate dialysis quality parameters.

24-Hour Proteinuria Versus Spot Protein-Creatinine Ratio for Kidney Transplant Management in Clinical Practice.

BACKGROUND: 24-hour proteinuria (24h-P) has been the most widespread test for clinical follow-up of proteinuria after kidney transplantation (KT), but urine collection is often not properly collected. Spot protein-creatinine ratio (P/Cr) has become the alternative to 24h-P for proteinuria evaluation in many KT units. However, its reliability, equivalence to 24h-P, and prognostic value regarding allograft outcome remain unknown. Therefore, the aim of this study was to evaluate the correlation and agreement between both methods for assessing proteinuria and to analyze which of them is a better predictor of graft survival. METHODS: We collected proteinuria measurements from KT patients in our center. 24h-P was adjusted for body surface area. Pearson correlation test and the Bland-Altman method were used to analyze correlation and agreement. Survival analysis was performed with the use of the Kaplan-Meier method and multivariate Cox proportional hazard model. RESULTS: A total of 8,549 urine samples were analyzed from 472 patients in whom 24h-P and P/Cr were simultaneously measured. A significant correlation was observed between 24h-P and P/Cr (r = .76; P < .001); however, the agreement between methods showed that P/Cr overestimated proteinuria compared with 24h-P, particularly when the latter was >1 g/24 h. The Cox regression multivariate model showed an increased risk of graft loss associated with proteinuria when assessed by either 24h-P (hazard ratio [HR] 6.53, 95% confidence interval [CI] 2.49-17.1) or P/Cr (HR 3.34, 95% CI 1.04-10.7). CONCLUSIONS: P/Cr is an method interchangeable with 24h-P for detecting proteinuria after KT. When proteinuria increases, the P/Cr overestimates 24h-P, even though it also has a significant and similar prognostic value for predicting graft survival.

Prevalence and Survival of Cancer After Pancreas-Kidney Transplantation.

BACKGROUND: Malignancy is an important cause of mortality in solid organ transplantation. There have been few studies of de novo solid organ malignancy (NSOM) after pancreas-kidney transplantation (PKT). The aim of this study was analyze the prevalence of NSOM and transplant outcomes. METHODS: We studied the development of NSOM after PKT in our center from May 1990 to February 2017. We analyzed demographic characteristics, prevalence of cancer, and survival after cancer diagnosis. We excluded nonmelanoma skin cancer and patients with history of malignancy before transplantation. RESULTS: We included 194 patients who received 206 PKTs (184 simultaneous PKTs and 22 pancreas after kidney transplants) with triple immunosuppressive therapy and basiliximab in more than 95%. The mean age at transplantation was 39 ± 7 years and 74% were male patients. Twelve patients developed malignancies (6.1%). Median time from transplant to NSOM was 6.6 (interquartile range [IQR] 0.2-11.7) years. The malignancies were 2 cecal appendix tumors, 2 hematologic tumors, 2 breast tumors, 1 melanoma, 1 native kidney tumor, 1 brain tumor, 1 bladder tumor, 1 prostate tumor, and 1 leiomyosarcoma. Thirty-five of the 194 patients of the whole cohort died throughout the follow-up, 4 of whom died after NSOM diagnosis (11.4%). Patient and grafts survivals were lower in recipients with tumor compared with recipients without tumor, but the difference was not statistically significant: renal graft survival was 80% vs 90% at 10 years (P = .86); and pancreatic graft survival was 45% vs 70% at 10 years (P = .15), respectively. The mean patient survival time from the diagnosis of cancer was 36.6 (IQR 18-54) months. Patient survival after NSOM diagnosis was 90% at 1 year and 50% at 5 years. CONCLUSION: The prevalence of NSOM in our PKT recipients is low, despite the scarce series of published data for comparison. Also hematologic tumors rate is very low, possibly influenced by age and type of induction.

Sleep disorders are underdiagnosed in patients on maintenance hemodialysis.

BACKGROUND: Sleep apnea-hypopnea syndrome (SAHS) is a cardiovascular risk factor. The aim of this study was to evaluate sleep disorders using polysomnography on a non-selected population of patients on maintenance hemodialysis. METHODS: Overnight polysomnography was performed on 32 hemodialysis patients (24 men/8 women, 54 +/- 16 years), and on 19 healthy subjects of similar age, sex and body mass index who were used as controls. RESULTS: In hemodialysis patients, the most frequent sleep disorder was SAHS in 44% (14/32), followed by insomnia in 41% (13/32). Compared to healthy controls, patients on hemodialysis showed less slow-wave sleep and rapid eye movement sleep (23 vs. 36%, p = 0.001), less sleep efficiency (71 vs. 87%, p = 0.0079) and a higher periodic limb movement index (39.7 vs. 9.1; p = 0.003). An increase in apnea-hypopnea index (18.9 vs. 4.3; p = 0.007) and dips in the SaO(2) (> or =4%) per hour of sleep (22.6 vs. 6.4; p = 0.021) were also significantly greater in hemodialysis patients than controls. 72% of the cases of SAHS were diagnosed solely by means of polysomnography. CONCLUSIONS: The patients on hemodialysis showed poor sleep quality with a significant increase in the apnea-hypopnea index and in the number of dips in SaO(2). SAHS was underdiagnosed in a large percentage of the hemodialysis patients.

C-reactive protein and low albumin are predictors of morbidity and cardiovascular events in chronic kidney disease (CKD) 3-5 patients.

BACKGROUND: Overall and cardiovascular mortality are significantly higher in hemodialysis patients with elevated C-reactive protein (CRP). The aim of this study was to determine whether CRP is a marker of overall and cardiovascular morbidity in chronic kidney disease (CKD) 3-5 patients. METHODS: 90 chronic kidney disease 3-5 patients were prospectively followed during a period of 24 months. Cardiovascular events were defined as episodes of myocardial infarction, stroke, angina pectoris and/or peripheral vascular disease. Morbidity was analyzed in terms of both the need for hospital admission (> 48 h) and total number of days of hospitalization during the follow-up period. CRP was stratified into tertiles of low (< 8 mg/l), medium (8-10.5 mg/l) and high (> 10.5 mg/l). The use of some drugs such as ACE inhibitor and ARAII were also recorded. RESULTS: During the follow-up period, 23 patients (25%) required hospital admission. New cardiovascular events were observed in 20 patients (22%), 10 patients died during the follow-up. Adjusted Cox regression analysis revealed that CRP and serum albumin significantly predicted the risk of cardiovascular events. Similarly, high CRP, low serum albumin and low hemoglobin levels predicted morbidity as measured by the number of hospitalizations. Hemoglobin and albumin levels were lower in patients with high CRP (> or = 10.5 mg/l, highest tertile) as compared with low CRP levels (< or = 8 mg/l, lowest tertile). Patients receiving treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor Type 1 antagonist (ARA-II) had significantly lower levels of CRP than those who were not under such treatment (n = 46, CRP = 8.7 (5.1-29.8) vs n = 44, CRP = 10.4 (6.1-37.2), p < 0.05) (Figure 1). CONCLUSIONS: Our results show that CRP and low albumin, markers of inflammation, predict cardiovascular events and morbidity in CKD 3-5 patients before initiation of chronic hemodialysis.

Anemia associated with pegylated interferon-alpha2a and alpha2b therapy in hemodialysis patients.

AIMS: Anemia is a well-known side effect of interferon therapy since interferons are potent inhibitors of erythropoiesis. The aim of this study was to compare the anemia associated with pegylated interferon (PEG-IFN) (alpha2a versus alpha2b therapy in hemodialysis patients (HD) with chronic hepatitis C. METHODS: In order to study the anemia, doses of erythropoietic growth factors (EGF), hemoglobin (Hb) and erythropoietin resistance index (ERI) were compared at baseline and after PEG-IFN-alpha2a or alpha2b therapy in 16 HD patients with chronic C hepatitis. Pharmacokinetic studies were performed in 4 of those treated with PEG-IFN-alpha2b and 2 patients treated with PEG-IFN-alpha2a. Secondary end-points were viral response and serious adverse events. RESULTS: At 4-6 months after the beginning of therapy, both PEG-IFN-alpha induced a significant increment in the erythropoietin resistance index. This increment was significantly higher in patients treated with PEG-IFN-alpha2a when compared with alpha2b (45 vs 9.9, p = 0.012). The pharmacokinetics of PEG-IFN-alpha2a and alpha2b in HD patients were different, the C(max), C(min) and the area under the serum concentration time curve, were all higher in patients treated with PEG-IFN-alpha2a compared with PEG-INF-alpha2b. Discontinuation of therapy occurred in 2 (28.5%) of the 7 patients in the PEG-IFN-alpha2a group and in 4 (44%) of the 9 patients in the PEG-IFN-alpha2b group. Three (42%) subjects in the alpha2a group and 5 (55%) in the alpha2b group had a response at the end of the 48 weeks of therapy. In 4 (44.4%) of the 9 patients treated with alpha2b the viral response was sustained. CONCLUSIONS: In summary, patients treated with PEG-IFN-alpha2a have a major inhibitory effect on erythropoiesis. This could be explained by the different pharmacokinetic properties of PEG-IFN-alpha2a and alpha2b. Further studies are needed to clarify how these findings influence the efficacy, safety and cost-effectiveness of the PEG-IFN-alpha2.

[Acute rejection of kidney transplant is associated with induction of replicative senescence in CD8+ T lymphocytes]. / Senescencia replicativa en células T CD8+ de pacientes con rechazo agudo en trasplante renal.

Acute renal rejection repeatedly activates immunocompromised CD8 + T cells. Maintained activation of CD8 + T cells can induce a process of replicative senescence. In the present study, we will evaluate in CD8 lymphocytes from patients undergoing acute renal rejection characteristics of replicative senescence such as: a) low expression of CD28 molecule; b) telomere shortening and c) increase production of proinflammatory cytokines. The study was carried out in CD8 + T cells from 14 patients transplanted without clinical evidences of acute renal rejection, 14 patients kidney transplanted with clinical and anatomopathological evidences of acute renal rejection, 8 healthy controls. The results shown that in peripheral blood and renal biopsy of patients with acute renal rejection there is a significant increment of the population of T cells CD28-CD8+, with short telomere length, as compared with healthy controls and patients without acute renal rejection. The presence of senescent cells was associated with high levels of IL-10 and IFN-Y in plasma and urine. In conclusion our study suggest that the CD8 + T cells of patients with acute renal rejection suffer a process of replicative senescence.

Klotho Prevents Translocation of NFκB.

Klotho protein is a ß-glucuronidase capable of hydrolyzing steroid ß-glucuronides. Two molecules are produced by the Klotho gene, a membrane bound form and a circulating form. This protein is recognized as an antiaging gene with pleiotropic functions. The activation of cellular systems is associated with the pathogenesis of several chronic and degenerative diseases associated with an inflammatory state. Inflammation is characterized by an activation of NFκB. Klotho suppresses nuclear factor NFκB activation and the subsequent transcription of proinflammatory genes. This review focuses on the current understanding of Klotho protein function and its relationship with NFκB regulation, emphasizing its potential involvement in the pathophysiologic process.

Donor-Specific Antibodies After Starting Hemodialysis in Nonrenal Solid Organ Transplant Recipients: Role of TH17.

BACKGROUND: Nonrenal transplantation could cause a progressive deterioration in renal function until need dialysis. It is important to know if these patients increased their risk to develop de novo donor-specific anti-HLA antibody (DSA) after starting hemodialysis (HD) and if so, try to find the mechanism. MATERIAL AND METHODS: In this double-phase study, we first analyzed the incidence of development DSA in nonrenal transplant recipients after starting HD by a retrospective study. Secondly, a prospective study was designed to analyze the pharmacokinetics of immunosuppressive drugs and the cytokine profile of these patients. RESULTS: Of 179 pancreas transplant recipients, 16 needed to start HD, and 62.5% of these patients developed de novo DSA after starting HD, with 80% of them class I DSA. In the second phase of the study, the plasma levels of the immunosuppressive drugs as measured by a limited sampling strategy of 3 sample time points (C0, C2, and C4) were stable. The cytokine profile showed that there was an increase in Th1 cytokine (interferon gamma of 0.045 ng/mL) and also in Th17 cytokines (transforming growth factor ß >10 ng/mL). CONCLUSION: Our data suggest that the development of DSA after starting HD in nonrenal transplant recipients could be mediated by Th17 immune response mechanisms.

Antibody-mediated pure red-cell aplasia (PRCA): the Spanish experience.

BACKGROUND: The incidence of antibody (Ab)-mediated pure red-cell aplasia (PRCA) in patients with chronic kidney disease (CKD) has increased between 1998 and 2002. After initially responding to treatment with recombinant human erythropoietic agents for CKD-associated anemia, patients became treatment-refractory and severely anemic. Although most PRCA cases have occurred in Europe, the varying epidemiologies among individual countries have not been well characterized. METHODS: We investigated Ab-mediated PRCA in 12 Spanish patients treated with epoetin alfa alone or prior to treatment with epoetin beta (n=1) or darbepoetin alfa (n=1). Serum Abs against epoetin alfa were detected by radioimmunoprecipitation (RIP) assay or bioassay. Following diagnosis of PRCA, erythropoietic treatment was stopped and patients received immunosuppressive therapy alone (n=11) or in combination with renal transplant (n=1). RESULTS: Treatments were administered for 16 months (average) before diagnosis of PRCA in bone marrow aspirates (n=8) or biopsies (n=4). At diagnosis, patients had an average of 0.68% blood reticulocytes and blood hemoglobin (Hb) level of 7.13 g/dL. Eight patients had anti-epoetin Abs detected by RIP, and 5 had neutralizing Abs measured in the bioassay. As of December 2003, 4 patients had died, 3 had no recovery, and 5 had recovered from anemia (blood Hb level, 9.9 g/dL). All 5 recovering patients received corticosteroid therapy alone, and 1 received a renal transplant as well as corticosteroids. CONCLUSIONS: Sudden onset of treatment-refractory anemia in CKD patients suggests a course of treatment cessation followed by diagnostic procedures for Ab-mediated PRCA, and immunosuppressive therapy. This study may serve as a model for a centralized global PRCA registry.

[Cardiovascular risk in hemodialysis in Spain: prevalence, management and target results (MAR study)]. / Riesgo cardiovascular en hemodiálisis en españa: prevalencia, pautas de actuación y objetivos (estudio MAR).

Cardiovacular disease is the main cause of morbidity and mortality in hemodialysis (HD) patients. However, there are no reliable data neither on the prevalence of cardiovacular disease nor its risk factors in Spain. The Morbidity and mortality Anemia Renal study (MAR) is a two-year multicenter, open-label, prospective cohorts study. Its main objective is to assess the general morbidity and mortality, particularly of a cardiovascular cause, and its relationship with the degree of anemia. Secondary objectives are: a/ the description of current clinical practices in anemia, dialysis, vascular access, and CV risk factor management; and b/ the description of hospitalization and mortality causes. This paper describes the prevalence of cardiovascular disease and risk factors of the HD population in Spain. A total of 1.710 patients were included (60% male, aged 64.4 years, 16.2 months on HD). The mean co-morbidity Charlson index was 6.5 +/- 2.3. Cardiovascular disease was the most prevalent comorbidity, 16.7% had a coronary disease, and 13.9% had different degrees of heart failure, while 11.6% had arrhythmia, 1.7% stroke and 5.5% peripheral artery disease. The prevalence of hypertension was 75.8%, 74.4% of patients received antihypertensive drugs, and still 40% of patients had an inadequate blood pressure control. The investigators considered as dyslipidemic 34.1% of patients, and prescribed treatment to 69.5% of them, while the remaining 30.5% (10.4% of the total) had hyperlipidemia with no drug therapy. Eleven percent was active smoker, and 26.6% former smoker. There was 47.4% of patients with a corporal mass index above 25. Secondary hyperparathyroidism with PTH above of 300 pg/ml was present in 22.2% of patients. Despite the EBPG and K-DOQI recommendations, only 68.8% of prevalent hemodialysis patients attained a hemoglobin (Hb) above 11 g/dl, 89.4% ferritin levels above 100 ng/ml, 66.5 degrees/a a transferrin saturation index (TSI) above 20%, and 61.1% met all three objectives. In summary, this first cross-sectional analysis has allowed us to know in detail the standard practice in multiple aspects of management of HD population in Spain. It has also established clear differences in the prevalence of cardiovascular disease and risk factors from the US registries. Last but not least we have identified therapeutic opportunities to improve the course and prognosis of our patients.

Development of Donor-Specific Anti-HLA Antibodies After Restarting Hemodialysis Due to Graft Failure.

BACKGROUND: Incidents of renal replacement therapy (RRT) from renal transplants are on the rise. Some authors have associated the development of donor-specific anti-HLA antibodies (DSA) with the end of immunosuppression treatment (IS) and/or the performing of a transplantectomy. The objective of this study was to analyze the characteristics of transplant patients having high immunological risk who restarted RRT and the subsequent development of DSA. METHODS: We selected incidents on RRT carried out between 1980 and 2012 in our center: 146 cases; they presented non-DSA cytotoxic antibodies prior to returning to RRT. Survival time for the graft was 77.2 months; the average follow-up period for DSA development was 131.9 months. DSA in 76 cases (52.1%). Of 146 grafts, 72 underwent transplantectomy and 41 presented DSA after returning to RRT. In 17 of these cases (41.5%), the development of DSA occurred prior to the transplantectomy. Fifty-one cases of DSA were registered at the date of completion of the IS treatment, and 40 appeared after discontinuation (median 36 weeks) and 11 with previous appearance. IS was completed, with a median of 13 weeks after the return to RRT. RESULTS: No association was found between DSA development and order of graft, transplantectomy, or premature loss of the graft (≤15 months) after the return to RRT. There were significant differences between the number of HLA incompatibilities of the donor and the development of DSA. CONCLUSIONS: The development of DSA in high-immunological risk patients after restarting RRT is not related to transplantectomy.

Tyrosine-phosphatase and glutamate-decarboxylase antibodies after simultaneous pancreas kidney transplantation: do they have an impact on pancreas graft survival?

INTRODUCTION: The pathogenesis of type 1 diabetes mellitus (T1DM) is associated with auto-antibodies. These auto-antibodies contribute to pancreatic ß-cell destruction. Tyrosine-phosphatases (IA-2) and glutamic acid decarboxylase (GAD65) are the most frequently used by clinicians. When T1DM patients develops advanced chronic kidney disease, simultaneous pancreas-kidney (SPK) transplantation becomes the best option. However, pancreatic graft survival is limited. The role of the auto-antibodies on pancreas graft survival remains controversial. OBJECTIVE: The aim of this study was to assess pancreas graft survival according to the presence of GAD65 and IA-2 auto-antibodies after SPK transplantation. METHODS: We analyzed all SPK transplantations performed in our hospital since January 1990 to December 2013 with at least 30 days of pancreas graft survival. We collected demographic and clinical variables from donors and recipients. Graft failure was defined as complete insulin independence after transplantation. Pancreatic graft survival was analyzed using the Kaplan-Meier method. RESULTS: Overall, 152 SPK transplantations were performed during the period. One hundred sixteen were accessed for de novo post-transplantation auto-antibodies. Also, 17.8% (n = 27) were positive for anti-GAD65, 13.8% (n = 20) for IA-2, 3.9% (n = 6) were positive for both, and the rest were negative for any auto-antibody (n = 63). Kaplan-Meier survival curves estimated a worst pancreas graft survival for patients with positive IA-2 antibodies versus those patients with negative auto-antibodies and GAD65+auto-antibodies (P = .003 and .022, respectively, by log-rank). Mean pancreas graft survival rates at first and fifth year were 72% and 64%, respectively, for those patients with positive IA-2. CONCLUSIONS: IA-2 antibodies after SPK transplantation are associated with long-term graft lost compared with the rest of the groups. Monitoring of these auto-antibodies after SPK may help to identify patients with a higher risk of graft failure.

Influence of vitamin D on parathyroid function in the elderly.

UNLABELLED: The effect of age and vitamin D status on parathyroid function was studied in 129 healthy subjects between 20 and 89 yr old, with normal serum creatinine (less than 0.11 mmol/L), and living in Cordoba, Spain. Serum calcium and phosphorus as well as 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] decreased, whereas serum alkaline phosphatase increased, with age. Serum PTH also increased significantly with age when measured with either a carboxyl-terminal (cPTH) or an intact [PTH(1-84)] assay. The increase in cPTH, however, exceeded largely the increase in PTH(1-84) (+120% and +30% in subjects above 80 yr vs. young adults, respectively). Serum PTH(1-84) was negatively correlated with serum (ionized) calcium, 25OHD, and insulin-like growth factor I (IGF-I) but not with serum 1,25-(OH)2D. Serum 1,25-(OH)2D decreased with age and was highly correlated with serum 25OHD, cPTH, and IGF-I. In multiple regression analysis 50-60% of the variation of total and free 1,25-(OH)2D could be explained by serum 25OHD, PTH(1-84), and especially IGF-I, suggesting a possible role of decreasing GH and IGF-I concentrations in the mineral homeostasis of the elderly. Calcium infusion (1.5 mg/kg body weight over 10 min) decreased serum PTH(1-84) to below normal concentrations in young adults (nadir 14% of basal concentration), whereas the nadir in elderly subjects with secondary hyperparathyroidism was only 32% of basal concentration. The relative decrease was, however, identical in both age groups when simultaneous changes in ionized calcium were taken into account. Basal serum PTH(1-84) in selected elderly subjects (50 +/- 10 ng/L or 5 +/- 1 pmol/L, n = 10) decreased significantly (2.7 +/- 0.9 pmol/L, P less than 0.01) after 3 iv injections of 1,25-(OH)2D during 1 week without changes in serum (ionized) calcium. The PTH suppressibility after calcium infusion did not further improve. IN CONCLUSION: elderly patients with normal serum creatinine had a small (+30%) but significant increase in intact serum PTH concentration but the mean concentration still remained within the normal range. The PTH secretion remained normally suppressible by acute calcium infusion. Treatment with 1,25-(OH)2D decreased basal calcium-PTH setpoint without further additional effects during calcium infusion.

A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.

OBJECTIVE: To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in serum creatinine during the previous 2 years. METHODS: A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. RESULTS: Mean age of the group was 54 +/- 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4-6 mmHg lower. CONCLUSION: In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function. The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.

Behaviour of the contact phase of blood coagulation in the adult respiratory distress syndrome (ARDS).

In order to assess the role of the kallikrein-kinin (K-K) system in the pathogenesis of the adult respiratory distress syndrome (ARDS) we have prospectively determined coagulation contact phase, blood gas and hemodynamic parameters in patients with ARDS at 0, 36 and 72 h from diagnosis. Compared to normal values, significantly lower mean levels of factor XII (71.4 +/- 9.8%, p less than 0.0005), prekallikrein (PPK) (52 +/- 5.7%, p less than 0.0005), high molecular weight kininogen (HMWK) (73 +/- 2%, p less than 0.0005) and alpha 2-macroglobulin (alpha 2-M) (51 +/- 7.1%, p less than 0.0005) were found in ARDS patients. The functional kallikrein inhibitory activity (KKI) and C1-esterase inhibitor antigenic (CIINH) were significantly higher in these patients (113.2 +/- 5, p less than 0.005 and 124.7 +/- 7.6, p less than 0.0005 respectively) compared with normal values during the entire study period. The KKI/CIINH ratio decreased significantly in our ARDS patients at 0, 36 and 72 h (p less than 0.025; p less than 0.05 and p less than 0.005 respectively). We found a significant correlation between PPK levels and oxygenation index (r = 0.69, p less than 0.001), PPK and the static thoracic compliance values (r = 0.64, p less than 0.001). There was also a significant correlation between PPK levels and Qs/Qt (r = -0.89, p less than 0.001). ARDS patients that survived presented a stability in the PPK values in successive tests. Nevertheless non-survivors showed a progressive decrease in PPK levels during the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)