Citrobacter koseri. Una endoftalmitis exógena inusual / Citrobacter koseri, an unusual exogenous endoftalmitis

Citrobacter koseri es un bacilo gramnegativo que causa endoftalmitis de forma muy infrecuente y agresiva, asociando mal pronóstico visual. Solo el 6% de las endoftalmitis son por gramnegativos y nuestro germen representa un pequeño porcentaje. Presentamos un varón de 65 años que trabaja en un laboratorio de animales. Acude a urgencias por pérdida de visión del ojo izquierdo debido a una hemorragia vítrea y desprendimiento de retina. Se practica una vitrectomía y 3 días después, desarrolla una endoftalmitis. Se realiza tratamiento intravítreo con inyecciones de vancomicina y ceftazidima así como tratamiento antibiótico tópico. Veinticuatro horas después, regresa con perforación corneal y una extrusión del cristalino. Ante la gravedad del cuadro se realiza una evisceración. El cultivo de las muestras confirman el microorganismo. Suponemos que la puerta de entrada del germen fueron las esclerotomías por el material de sutura expuesto, tras la manipulación de heces de roedores.(AU)

Citrobacter koseri is a bacillus that causes infrequent endophthalmitis. Six percent of cultures in endophthalmitis are Gram -, and as in these, Citrobacter koseri is associated with a poor visual prognosis. We present a 65-year-old man who works in an animal laboratory. He went to emergencies with loss of vision in his left eye due to a vitreous hemorrhage. A vitrectomy was performed and 3 days later, endophthalmitis was diagnosed. Vancomycin and ceftazidime were applied in eye drops and in two intravitreal injections. Twenty-four hours later he returned with a lens extrusion. Due to the severity of the condition, an evisceration was performed. Subsequently, the samples confirm the microorganism. We assume that the entry point for the bacterium was the sclerotomies through the exposed suture material, after handling rodent feces.(AU)

Citrobacter koseri, an unusual exogenous endoftalmitis.

Citrobacter koseri is a bacillus that causes infrequent endophthalmitis. 6% of cultures in endophthalmitis are Gram -, and as in these, C. koseri is associated with a poor visual prognosis. We present a 65-year-old man who works in an animal laboratory. He went to emergencies with loss of vision in his left eye due to a vitreous hemorrhage. A vitrectomy was performed and 3 days later, endophthalmitis was diagnosed. Vancomycin and Ceftazidime were applied in eye drops and in two intravitreal injections. 24 h later he returned with a lens extrusion. Due to the severity of the condition, an evisceration was performed. Subsequently, the samples confirm the microorganism. We assume that the entry point for the bacterium was the sclerotomies through the exposed suture material, after handling rodent feces.

Management of conjunctival perforation and late Seidel after XEN® surgery. / Manejo de la perforación conjuntival y Seidel tardío poscirugía XEN®.

CLINICAL CASE: The case concerns a 78 year-old woman with a history of XEN® surgery, in whom a conjunctival perforation was observed at the implant level at 18-months of follow-up, for which surgical intervention was decided. During surgery a short subconjunctival portion was found (0.5mm). An unsuccessful attempt was made to extract it by traction, but the XEN® broke easily. Finally, it was decided to cut it to scleral level, and suture the conjunctiva. During the first week there was a decrease in intraocular pressure (6mmHg), to subsequently increase to 25, and deciding to start medical treatment. DISCUSSION: Conjunctival exposure of the XEN® stent is a rare but potentially serious complication. To avoid it, a meticulous surgical technique is important when implanting it. If this occurs, it is important to identify the cause. If it is due to a short subconjunctival portion, a therapeutic alternative is to cut the implant at this level to avoid further complications.

Efficacy of the SENSIMED Triggerfish® in the postoperative follow-up of PHACO-ExPRESS combined surgery. / Eficacia del SENSIMED Triggerfish® para el seguimiento postoperatorio de la cirugía combinada FACO-ExPRESS.

OBJECTIVE: To determine the usefulness of the SENSIMED Triggerfish® system in the postoperative control of combined phacoemulsification and ExPRESS implant (PHACO-ExPRESS) surgery in patients with cataract and chronic open angle glaucoma (COAG) during a 2 months follow-up. METHODS: A prospective study conducted on 15 eyes that were subjected to PHACO-ExPRESS combined surgery. Using the SENSIMED Triggerfish® system, two records of the circadian patterns of intraocular pressure (IOP) were performed, one before and one after surgery. A record was made of the best corrected visual acuity (BCVA), comorbidities, previous IOP, and 7-30-60 days after surgery, as well as any hypotensive drugs and complications. RESULTS: The final sample was 12 eyes. The mean pre-operative BCVA (log MAR chart) before surgery was 0.5±0.2, and after surgery 0.14±0.1 (P=.02). The previous IOP was 18.7±3.8mmHg with 2.9±0.7 drugs. The mean IOP at 7, 30, and 60 days after surgery decreased to 13±4.1mmHg (P=.002), 13.5±2mmHg (P=.001), and 13.9±2.5mmHg (P=.001), respectively. The amplitudes of the circadian curves changed significantly after surgery (P=.007). The mean values between daytime and night-time periods decreased significantly from 146.8±80.9 mVeq and 61.2±92.mVeq before surgery to 36.4±36 mVeq (P=.000), and -23,2±47.6mVeq (P=.014) after surgery, respectively. There were complications in one patient. CONCLUSIONS: The SENSIMED Triggerfish® monitoring system showed changes in the curves of the circadian patterns, as well as decreased mean amplitudes after the combined PHACO-ExPRESS technique, suggesting that it may become a useful tool for postoperative follow-up of COAG.

Prospective study of filtering blebs after XEN45 surgery. / Estudio prospectivo de las ampollas de filtración poscirugía de implante XEN45.

OBJECTIVE: To qualitatively analyse the evolution of filtering blebs after XEN surgery, by using anterior segment optical coherence tomography (AS-OCT). METHODS: A prospective study was performed on filtering blebs of 30 eyes with cataracts and glaucoma, surgically operated on using phacoemulsification and XEN45 implantation (PHACO-XEN). AS-OCT was used to analyse bleb morphology and reflectivity at 3, 6, and 12 months after surgery. Functionality was studied considering an intraocular pressure (IOP)≤18mmHg without antihypertensive medication. RESULTS: The IOP enabled the blebs to be classified into non-functional: flat (6.67%) and encapsulated (3.33%); and functional (90%), which were then divide by their morphology into cystic (5/27), diffuse (2/27), and layered (20/27). Cystic types had a mean IOP of 12.8, 12.6, and 14.0mmHg at 3, 6 and 12 months, respectively. In the diffuse type, the mean IOP was 13.0, 11.5 and 13.0mmHg at 3, 6 and 12 months, respectively. In the layers pattern the mean IOP was 14.45, 14.55 and 14.8mmHg at 3, 6 and 12 months respectively. The percentage of blebs with high reflectivity was 48.15%, 62.96%, and 77.78%, at 3, 6 and 12 months, with a mean IOP of 14.23, 14.59, and 15.14mmHg in each time period, respectively. CONCLUSION: AS-OCT could be a good predictor of bleb functionality in PHACO-XEN surgery. Those with a cystic pattern or low reflectivity seem to have better post-operative success. Nevertheless, more long-term studies are required.

Qualitative analysis of repaired filtering blebs with anterior segment-optical coherence tomography. / Análisis cualitativo de ampollas de filtración reparadas mediante tomografía de coherencia óptica de segmento anterior.

OBJECTIVE: To provide a qualitative analysis of filtering blebs after being surgically repaired due to late blebs leaks. METHODS: Blebs were studied 6 months after surgical reparation using AS-OCT Triton (Topcon®). An analysis was made of the morphological pattern and internal structures of blebs, including the covering, in 10 patients. The images were obtained using OCTs at a wavelength of 1050nm. RESULTS: According to the Hirooka classification, three different patterns were found in the structure of blebs, which made it possible to correlate them with their functionality. A full covering was observed in 70% of the cases, and they showed sub-epithelial cysts (cystoid pattern). Two cases showed a full conjunctival retraction without Tenon's covering. The walls were thin, with a de-structured bleb (diffuse pattern) being visualised. In the third group, the image showed a partial conjunctival retraction with Tenon's covering. There were some sub-epithelial diffuse cysts with walls following a laminar pattern. CONCLUSION: Using AS-OCT, it is possible to study the bleb's characteristics in detail, as well as the cover, in the case of blebs requiring repair due to late leaks, using conjunctival advancement. It allows for the early visualisation of conjunctival retractions that were not visible in a slit lamp, and to predict the functionality of the blebs by their morphology.

Combined phacoemulsification and XEN45 surgery from a temporal approach and 2 incisions. / Cirugía combinada mediante facoemulsificación e implante XEN45 con acceso temporal y 2 únicas incisiones.

OBJECTIVE: To assess the safety and effectiveness of phacoemulsification combined with XEN45 implant surgery in patients with cataract and open-angle glaucoma, with 12-month follow-up. METHODS: A prospective study conducted on 30 eyes requiring phacoemulsification with, at least, 2 medications to control intraocular pressure (IOP). Phacoemulsification combined with XEN45 implant surgery was performed within 15minutes of administering subconjunctival mitomycin C. Surgery was performed through 2 temporal incisions, separated by 90°, using the inferior to enter the XEN45 and to implant it in the superior nasal region. A record was made of the best corrected visual acuity, IOP before and 1 day, 1 month, 3 months, 6 months, 9 months, and 12 months after surgery, the number of antiglaucomatous medications, and complications. RESULTS: The best corrected visual acuity was 0.37±0.2 and 0.72±0.15 before and 12 months after surgery, respectively. The pre-operative IOP was 21.2±3.4mmHg, with 3.07 drugs, decreasing by 61.65% on the first day, 37.26% at 1 month, 35.05% at 3 months, 31% at 6 months, 30.6% at 9 months, and 29.34% at 12 months. The number of medications decreased by 94.57%. Complications occurred in 3 eyes, 2 of them were excluded because we could not complete the implantation (280° subconjunctival haemorrhage and XEN extrusion when trying to reposition). In a third case, the bleb was encapsulated at 5 months after surgery. CONCLUSIONS: The phacoemulsification combined with XEN45 implant surgery can effectively reduce IOP and the number of drugs in mild-moderate open-angle glaucoma, as they rehabilitate the VA. The use of only 2 micro-invasive incisions makes it simple, quick and safe, with few complications at 12 months follow-up from surgery.

A form of apolipoprotein a-I is found specifically in relapses of focal segmental glomerulosclerosis following transplantation.

Recurrence of idiopathic focal segmental glomerulosclerosis (FSGS) following kidney transplantation occurs in a large percentage of patients. Accurate prediction of recurrence and elucidation of its pathogenesis are major therapeutic goals. To detect differential proteins related to FSGS recurrence, proteomic analysis was performed on plasma and urine samples from 35 transplanted idiopathic FSGS patients, divided into relapsing and nonrelapsing. Several proteins were detected increased in urine of relapsing FSGS patients, including a high molecular weight form of apolipoprotein A-I, named ApoA-Ib, found exclusively in relapsing patients. This finding was verified by Western blot individually in the 35 patients and validated in an independent group of 40 patients with relapsing or nonrelapsing FSGS, plus two additional groups: FSGS-unrelated patients showing different proteinuria levels (n = 30), and familial FSGS transplanted patients (n = 14). In the total of 119 patients studied, the ApoA-Ib form was detected in 13 of the 14 relapsing FSGS patients, and in one of the 61 nonrelapsing patients. Only one of the 30 patients with FSGS-unrelated proteinuria tested positive for ApoA-Ib, and was not detected in familial patients. Urinary ApoA-Ib is associated with relapses in idiopathic FSGS and warrants additional investigation to determine its usefulness as biomarker of relapse following transplantation.

Anemia control in kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta (mircera): the Anemiatrans Group.

BACKGROUND: Kidney transplant, the gold standard treatment for chronic kidney disease (CKD), is increasingly complicated by anemia. Once-monthly dosing of methoxy polyethylene glycol-epoetin beta provides stable, sustained hemoglobin levels in CKD patients. The present study evaluated anemia control in recipients treated with methoxy polyethylene glycol-epoetin beta to correct or as conversion treatment from other erythropoiesis-stimulating agents (ESAs). PATIENTS AND METHODS: This observational, retrospective study included kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta according to investigators' clinical practice. Information about demographics, CKD, anemia, blood analyses, treatment, and adverse events were collected from patients' medical charts at baseline as well as months 1, 3, and 6. RESULTS: From October 2009 to March 2010, the 285 patients in the study included: an overall mean age of 52.8±13.9 years with 146 females (51.2%) and 152 patients (55.1%) in stage 3 CKD. Forty-five patients (15.8%) were in the immediate posttransplant period; 51, naïve- treatment (17.9%) and 189, converted subjects (66.3%). Eighty-two of the converted patients (48.0%) had previously received darbepoietin; 81 (47.4%), epoetin beta; and 8 (4.7%), epoetin alfa. The mean doses of methoxy polyethylene glycol-epoetin beta at baseline were 75.0±22.4 µg per month, 95.8±45.5 µg per month, and 118.9±58.9 µg per month among naïve, converted, and immediate posttransplant patients, respectively. Mean hemoglobin content varied from baseline to month 6, namely 10.2±0.7 versus 11.8±0.9 g/dL in naïve (P<.001) and 11.4±1.3 versus 12.0±1.2 g/dL in converted patients (P=.001). Patients in the immediate posttransplant period showed mean hemoglobin values maintained between 10.4±1.7 g/dL at baseline and 11.5±1.2 g/dL at month 3. The only study-drug-related adverse event was hypertension. No patient died during the study. CONCLUSION: These preliminary results suggested that hemoglobin stability can be achieved and maintained after correction or conversion to once-monthly methoxy polyethylene glycol-epoetin beta in kidney recipients. It was well tolerated; the safety profile was that expected and comparable with shorter acting ESAs.

Alteraciones del metabolismo mineral en la enfermedad renal crónica estadios III, IV y V(no en diálisis) / No disponible

• Con la progresión de la Enfermedad Renal Crónica (ERC)tiene lugar la aparición de alteraciones del metabolismo mineral.• La secuencia clásica de eventos se inicia con el déficit de síntesis de calcitriol y la retención de fósforo. Como consecuencia de ello, desciende el calcio serico y se estimula la hormona paratiroidea (PTH), produciendo en el hueso la Enfermedad Ósea de Alto Remodelado (AR), conocida como Osteítis Fibrosa, y en el otro extremo tenemos las formas de Bajo Remodelado (BR). Descritas más tardíamente, e inicialmente asociadas a la intoxicación alumínica, hoy las vemos principalmente en la población añosa y/o diabética, que en un ambiente urémico, presentan niveles relativamente bajos de PTH para mantener un remodelado óseo normal, también se incluye la Osteomalacia, que tras la desaparición de la intoxicación alumínica es rara de observar.• En las formas de AR el hiperparatiroidismo facilita la salida de calcio (Ca) y fósforo (P) del hueso, en tanto que el hueso adinámico limita la incorporación de Ca y Pal tejido óseo. Por lo tanto, ambas formas facilitan la disponibilidad de Ca y P, que se acaba depositando en (..) (AU)

• With progression of chronic kidney disease (CKD), disorders of mineral metabolism appear.• The classic sequence of events begins with a deficit of calcitriol synthesis and retention of phosphorus. As a result of this, serum calcium decreases and parathyroid hormone (PTH) is stimulated, producing in the bone the high turnover (HT)bone disease known as osteitis fibrosa while on the other extreme we find the forms of low turnover (LT) bone disease. Described later and initially associated with aluminum intoxication, these diseases are now seen primarily in older and/ordiabetic patients, who in a uremic setting have relatively low levels of PTH to maintain normal bone turnover. Osteomalacia is also included in this group, which after the disappearance of aluminum intoxication is rarely observed.• LT forms of hyperparathyroidism facilitate the exit of calcium(Ca) and phosphorus (P) from bone, whereas the adynamic bone limits the incorporation of Ca and P into bone tissue. Therefore, both forms facilitate the availability of Ca and (..) (AU)

[Changes in mineral metabolism in stage 3, 4, and 5 chronic kidney disease (not on dialysis)]. / Alteraciones del metabolismo mineral en la enfermedad renal cronica estadios III, IV Y V (no en dialisis).

UNLABELLED: With progression of chronic kidney disease (CKD), disorders of mineral metabolism appear. The classic sequence of events begins with a deficit of calcitriol synthesis and retention of phosphorus. As a result of this, serum calcium decreases and parathyroid hormone (PTH) is stimulated, producing in the bone the high turnover (HT) bone disease known as osteitis fibrosa while on the other extreme we find the forms of low turnover (LT) bone disease. Described later and initially associated with aluminum intoxication, these diseases are now seen primarily in older and/or diabetic patients, who in a uremic setting have relatively low levels of PTH to maintain normal bone turnover. Osteomalacia is also included in this group, which after the disappearance of aluminum intoxication is rarely observed. LT forms of hyperparathyroidism facilitate the exit of calcium (Ca) and phosphorus (P) from bone, whereas the adynamic bone limits the incorporation of Ca and P into bone tissue. Therefore, both forms facilitate the availability of Ca and P, which ends up being deposited in soft tissues such as arteries. The link between bone disease and vascular calcifications in CKD is now a well-established phenomenon. 2. Diagnostic strategies Calcium, Phosphorus They have little capacity to predict underlying bone disease, but their regular measurement is decisive for therapeutic management of the patient, especially in the dose titration stages of intestinal phosphorus binders, vitamin D analogs or calcimimetics. Ideally, Ca++ should be used, but total Ca is routinely used. It is recommended to adjust albumin levels in the event of hypoalbuminemia (for each g/dL of decrease in albumin, total serum Ca decreases 0.9 mg/dL). The following formula facilitates rapid calculation of corrected total calcium: Corrected total Ca (mg/dL) = total Ca (mg/dL) + 0.8 [4-albumina (g/dL)]. Parathyroid hormone "Intact" PTH is the biochemical parameter that best correlates with bone histology (levels measured with the Allegro assay from Nichols Institute Diagnostics, no longer available). Various assays are currently available that use antibodies against different fragments of the molecule, but they have significant intermethod variability and have not been validated. A whole PT assay (1-84) is currently unavailable. A consensus to establish uniform criteria for PTH measurement remains to be established. During the dose titration stages of intestinal phosphorus binders, vitamin D analogs or calcimimetics, more frequent measurement may be required based on clinical judgment. Calcifediol (25(OH)D3) It is important to maintain adequate levels of 25(OH)D3 (> 30 ng/mL), since they will be the substrate for production of 1- 25(OH)2 D3, and their deficiency aggravates hyperthyroidism. Determining 25(OH)D3 levels every 6-12 months is a recommended guideline. Other markers of bone turnover (osteocalcin, total and bone alkaline phosphate, free pyridolines in serum, and C-terminal telopeptide of collagen) do not improve the predictive power of PTH and therefore their systematic use is not justified. Radiologic studies Radiologic studies are of little diagnostic utility, because biochemical changes precede radiologic changes. Systematic radiologic evaluation of the skeleton in asymptomatic patients is not justified at present. They are useful as the first step in the study to detect vascular calcifications and amyloidosis due to b2-microglobulin and in symptomatic and at risk patients to detect vertebral fractures. Bone densitometry: Dual energy x-ray absorptiometry (DEXA) is the standard method to determine bone mineral density (usually in the femoral neck and vertebrae). It provides information on changes in bone mineral content, but not on the type of underlying bone disease. It is useful for follow-up of bone mass or for the study of bone mass changes in the same patient. Its value as a predictor of the risk of fracture has not been demonstrated in patients on kidney replacement therapy or with advanced chronic kidney disease. It is indicated in patients with fractures or risk factors for osteoporosis. Bone biopsy: The "gold standard" for diagnosis of bone disease. With improved knowledge of the value of noninvasive parameters, its use is infrequent. INDICATIONS: Pathological fractures in the presence or absence of minor trauma. Symptomatic patients in the presence of incongruent clinical parameters. A typical case is the presence of unexplained hypercalcemia from systemic disease, with inconclusive serum PTH values (between 120-450 pg/mL as an estimated range). Evaluation and follow-up of cardiovascular calcifications There are no consensuated clinical practice guidelines for the evaluation and follow-up of extraosseal calcifications in CKD. The clinical tools for evaluation and follow-up of cardiovascular disease are used based on clinical judgment. The periodicity of follow-up has not been established . 3. Recommended biochemical values The biochemical values recommended in clinical practice guidelines for the evaluation of bone mineral metabolism are summarized in Figure 3. The recommended PTH values do not fully coincide with the K/DOQI guidelines. The wide variability in PTH values depending on the assays used has led us to expand the recommended PTH range in stage 3 and 4 CKD. 4. Treatment 4.1. Diet. The recommended diet for the patient with CKD is traditionally based on protein restriction and phosphorus restriction for control of mineral metabolism. A favorable circumstance is that there is a close relationship between protein and phosphorus intake. In CKD stages 3, 4 and 5, it is recommended to restrict phosphorus intake to between 0.8-1 g/day when serum levels of phosphorus and PTH are above the recommended range. This is approximately equivalent to a diet of 50-60 g of protein. This reasonable antiproteinuric strategy that also restricts phosphorus intake is nutritionally safe. What should we tell them to eat? In a practical and oversimplified way, we recommend the following daily intake: Animal proteins: 1 serving (100-120 g), dairy products: 1 serving (equivalent to 200-240 mL of milk or 2 yoghourts), bread, cereals, pastas (1 cup of pasta, rice or legumes + some bread or cookies), vegetables and fruits relatively freely, but with moderation. 4.2. Medication Vitamin D supplements should be provided if serum levels are less than 30 ng/mL. In Spain, vitamin D3 (cholecalciferol) is marketed as Vitamin D3 Berenguer 2,000 IU/mL of solution. Combinations of calcium with cholecalciferol are also available. Most of the dosage forms contain approximately 500 mg of Ca+ and 400 IU of cholecalciferol. Alternatively, calcifediol (25(OH)D3), as Hidroferol 100 mcg/mL, has been used, although the dose range is very variable and has not been established. 4.3. Phosphorus binders. Use if hyperphosphatemia occurs. Start with calcium-containing phosphorus binders (calcium carbonate or calcium acetate), which also provide calcium if dietary intake is inadequate. Do not exceed 1.5 g of Ca++ per day. The most used are calcium carbonate and calcium acetate. Calcium acetate shows a similar binding potency to calcium carbonate but with a lesser calcium overload, and thus would have certain advantages as well as its greater effect at different pH ranges. However, gastric intolerance is more frequent with this dosage form. Aluminum hydroxide may sometimes be required to control phosphoremia or the occurrence of hypercalcemia. Serum aluminum values should be maintained below 30 mcg/L. Avoid use for longer than 6 months and daily doses greater than 1.5 g. Sevelamer is associated with an increased risk of acidosis and has not been approved for use in predialysis stages. Lanthanum carbonate has been recently marketed in Spain, although its indication for use in the predialysis stage of CKD is still not approved. 4.4. Vitamin D derivatives. Indicated when PTH levels are elevated. A prerequisite for their use is that Ca and P serum levels are adequately controlled. Vitamin D derivates available in Spain are 1,25(OH)2D3 (Calcitriol)and 1a(OH)D3 (a-Calcidiol). Doses should be titrated until PTH levels are normalized. Phosphate binder doses often need to be increased because these vitamin D derivatives increase intestinal absorption of calcium and phosphorus. Low doses do not cause hypercalcemia or hyperphosphatemia and do not worsen the course of renal function. Recommended doses: Calcitriol 0.25 mcg every 48 hours and alpha-Calcidiol 0.50 mcg every 48 hours. Soon to be available on the Spanish market is the oral dosage form of paricalcitol (recommended initial dose of 1 mcg/24 h), with a lesser hypercalcemic and hyperphosphoremic effect. Clinical use of calcimimetics in the predialysis state is not yet recommended and is currently under investigation.

Pharmacokinetics and pharmacodynamics in renal transplant recipients under treatment with cyclosporine and Myfortic.

INTRODUCTION: Efficacious prophylaxis of acute rejection episodes (ARE) requires adequate exposure to each component of the immunosuppressive treatment from the first days after renal transplantation. The aim of the present study was to evaluate the correlation between cyclosporine (CsA) and mycophenolic acid (MPA) exposure based upon pharmacokinetics (PK) and pharmacodynamics (PD) and 6-month biopsy-proven acute rejection (BPAR) episodes and chronic allograft nephropathy on 6 month protocol biopsies. PATIENTS AND METHODS: We examined twenty-two first or second de novo renal transplant recipients treated with steroids, Sandimmune Neoral (CsA) and Myfortic (720 mg twice a day). PK (C0, C2, and AUC(0-12h)) for both drugs were determined on days 7, 90, and 180. Calcineurin activity, interleukin-2 and interferon-gamma synthesis as well as %CEM were tested at days 7 and 180. CsA dosages were adjusted by C2 monitoring. Collected data included: BPAR during the first 6 months and Banff histological parameters on the 6-month protocol biopsies. RESULTS: Eighteen of 22 patients completed 1 year follow-up under treatment. The 6-month BPAR was 18% (4/22). Six-month protocol biopsies in 50% of 14 recipients showed chronic allograft nephropathy 1. At day 7, CsA C2 and AUC median values were 138 ng/mL and 6377 ng x h/mL, while C0 MPA was 1.0 microg/mL and AUC = 23.9 microg x h/mL. CsA C2 medians at 3 and 6 months were 1468 and 1720 ng/mL. MPA-AUC reached therapeutic targets at 3 months (32.3 microg x h/mL) and was 48.3 microg x h/mL at 6 months. Patients with BPAR showed lower CsA AUC (P = .06) and a significantly lower baseline inhibition of calcineurin activity (P < .005) than patients with no BPAR. An increase in mesangial matrix in 6-month protocol biopsies correlated with higher CsA C2 (P = .01). All biomarkers evaluated were significantly inhibited compared with the standard population. CONCLUSIONS: When Myfortic is administered together with CsA, it is advisable to begin with higher doses (720 mg x 3 days) to reach adequate PK targets and improve BPAR rates. To prevent chronic allograft nephropathy, lower CsA C2 should be targeted from 3 months.

Quality of life in renal transplant recipients following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium.

INTRODUCTION: Tolerance to immunosuppresant treatment has considerable impact on adherence to therapy and on the outcome of renal transplantation. Recent data indicate better gastrointestinal tolerance to enteric-coated mycophenolate sodium (EC-MPS) than to the classic mycophenolate mofetil (MMF) formulation. AIM: This study assessed the effect of conversion therapy from MMF to EC-MPS on gastrointestinal tolerance and quality of life in renal transplant recipients. METHODS: This open observational study analyzed the outcomes of conversion from MMF to EC-MPS among renal transplant patients with gastrointestinal complaints. At baseline (B) and at 8 weeks postconversion patients were assessed by the Gastrointestinal Quality of Life Index (GIQLI) questionnaire as well as by clinical evaluation (acute rejection, infection) and analytical determinations. RESULTS: We analyzed 18 recipients of cadaveric renal transplants of mean age of 54 +/- 9 years including 61% men and one retransplant. Our patients had stable renal function with mean creatinine of 1.9 +/- 0.7 mg/dL. Baseline treatment included cyclosporine-MMF-prednisone (33%) or FK-MMF-prednisone (66%). Bioequivalent conversion was carried out at 50 +/- 29 months posttransplantation. Conversion to EC-MPS resulted in an improvement in overall quality of life (total score: baseline 106.61 vs 8 weeks 116.89; P < .01). Improvements were observed in the following GIQLI subscales: gastrointestinal symptoms (3.12 vs 3.48, P < .001), physical function (2.54 vs 2.76, P = .003), medical treatment (2.17 vs 2.50, P = .031), and emotion (3.08 vs 3.39, P = .001). No changes were observed in the social function subscale. The hemogram and renal function remained stable; there were no episodes of rejection or infection. CONCLUSION: Conversion from MMF to an EC-MPS formulation was associated with improvements in gastrointestinal complaints and quality of life among renal transplant recipients.

Epidemiology and outcomes of multiple antibiotic-resistant bacterial infection in renal transplantation.

BACKGROUND: Mutiresistant bacterial infections are an emerging problem in the nosocomial setting. Our objectives were to describe the incidence, outcome, and risk factors for acquisition of multiresistant bacteria among renal transplant recipients. METHODS: We prospectively followed patients undergoing kidney transplantation over a 3-year period. We collected demographic features, underlying chronic diseases, and main transplant characteristics and complications. Multiple antibiotic resistance was defined for the most important bacteria: Enteric gram-negative bacilli resistant to betalactamics, cephalosporins, and quinolones; Staphylococcus aureus resistant to methicillin, cotrimoxazole, and clindamcin; Enterococcus spp resistant to ampicillin and quinolones; nonfermentator bacilli resistant to all antibiotics except aminoglycosides and collistin. RESULTS: Overall, 416 patients included 65 double transplants (62 kidney-pancreas and three kidney-liver) of mean age 48.5 years, and 57% men. Infection with multiresistant bacteria was observed in 58 patients (14%). Most frequent multiresistant bacteria were: Escherichia coli (n = 33), Klebsiella spp (n = 15), Citrobacter spp (n = 8), Enterobacter spp (n = 5), Morganella morganii (n = 2), Pseudomonas aeruginosa (n = 16), Acinetobacter baumanii (n = 2), Enterococcus spp (n = 9) and methicillin-resistant S. aureus (MRSA, n = 2). Age greater than 50 years, hepatitis C virus infection, double kidney-pancreas transplantation, requirement for posttransplant hemodialysis, surgical reoperation, and requirement for nephrostomy were independent variables associated with multiresistant bacterial infection. Most used antibiotics for treatment were: carbapenems (65%), amikacin (12%), linezolid, piperacillin-tazobactam, vancomycin, collistin, and fosfomycin. Infection with multiresistant bacteria was associated with a worse prognosis (graft loss or death, 19% vs 8%, P = .009). CONCLUSIONS: The incidence of infection with multiresistant bacteria in our renal transplant cohort was high, being most frequently cephalosporin-resistant enteric gram-negative bacilli and multiresistant P aeruginosa. Methicillin-resistant S. aureus incidence was low. Infection with multiresistant bacteria conferred a worse prognosis.

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

Cardiovascular risk profile in nondiabetic renal transplant patients: cyclosporine versus tacrolimus.

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.

Muscle angiogenic growth factor gene responses to exercise in chronic renal failure.

Patients with chronic renal failure (CRF) have impaired exercise capacity even after erythropoietin treatment. We recently showed that although this is explained in part by reduced convective O(2) delivery to muscles, there is also an impairment of O(2) transport from muscle capillaries to the mitochondria. Given the importance of the capillary surface area for capillary mitochondrial O(2) transport and reports of reduced capillarity in CRF, we hypothesized that the angiogenic gene response to exercise is impaired in such patients. Six patients with CRF and six control subjects matched for age, size, and sedentary lifestyle exercised on a single occasion for 1 h at similar work intensities averaging 50% of maximal capacity. Exercise was confined to the knee extensors of a single leg by means of a specially designed leg-kick ergometer. A percutaneous biopsy of the quadriceps was taken within 30 min of cessation of exercise and compared with a similar biopsy done at different times without any prior exercise for 24 h. Conventional Northern blots were prepared and probed for vascular endothelial growth factor (VEGF; the major putative angiogenic growth factor for muscle), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-beta(1). Data during both rest and exercise were successfully obtained in four subjects of each group. We also assessed muscle capillarity and mitochondrial oxidative capacity to relate to these changes. Mitochondrial oxidative capacity was normal, whereas capillary number per fiber was 12% lower than in normal subjects. VEGF mRNA abundance was increased after exercise by about one order of magnitude, with no reduction in response in CRF. For bFGF and TGF-beta(1), exercise elicited no response in either group. Reduced muscle capillarity in CRF does not, therefore, stem from reduced transcription of VEGF. To the extent that VEGF is important to exercise-induced angiogenesis in muscle, we suspect a posttranscriptional aberration in this response occurs in CRF to explain reduced capillarity.