Manejo actual de las terapias continuas de reemplazo renal: Estudio epidemiológico multicéntrico / Current practice in continuous renal replacement therapy: An epidemiological multicenter study

OBJETIVO: Determinar las características más relevantes del manejo actual de las terapias continuas de reemplazo renal (TRRC), así como analizar la evolución de la función renal y la mortalidad de los pacientes tratados con estas terapias. MÉTODOS: Estudio observacional sin intervención de 3meses de duración en 2012 con un periodo de seguimiento de 90 días, realizado en 21 hospitales de Cataluña, en que se registraron escalas de gravedad, datos demográficos, clínicos y de las TRRC. CRITERIOS DE INCLUSIÓN: pacientes de ≥16 años ingresados en cuidados intensivos (UCI) tratados con TRRC. RESULTADOS: Se seleccionó a 261 pacientes. Un 35% tenía disfunción renal previa al ingreso. El principal motivo para iniciar las TRRC fue la oliguria, la modalidad más empleada fue la hemodiafiltración y la mediana de dosis prescrita al inicio fue de 35mL/kg/h. La mediana de tiempo de inicio de la TRRC desde el ingreso en UCI fue de un día. La mortalidad a los 30 y 90 días fue de 46 y 54%, respectivamente, y se relacionó con peores valores en las escalas de gravedad y con un inicio más tardío de la TRRC. Al alta hospitalaria, un 85% de los supervivientes había recuperado la función renal. CONCLUSIONES: El manejo de las TRRC en Cataluña se adecua a los estándares recomendados por las guías actuales. La mortalidad asociada a las TRRC se relaciona con un inicio más tardío. Un 85% de los pacientes tratados con TRRC recuperan la función renal al alta hospitalaria

OBJECTIVE: The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. METHODS: A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. Inclusion criteria: patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. Results A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. CONCLUSIONS: Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT

Current practice in continuous renal replacement therapy: An epidemiological multicenter study. / Manejo actual de las terapias continuas de reemplazo renal: Estudio epidemiológico multicéntrico.

OBJECTIVE: The aim of the study is to ascertain the most relevant aspects of the current management of renal replacement therapy (RRT) in critically ill patients, and to analyze renal function recovery and mortality in patients undergoing RRT. METHODS: A non-interventional three-month observational study was made in 2012, with a follow-up period of 90 days, in 21 centers in Catalonia (Spain). Demographic information, severity scores and clinical data were obtained, as well as RRT parameters. INCLUSION CRITERIA: patients aged ≥ 16 years admitted to Intensive Care Units (ICUs) and subjected to RRT. RESULTS: A total of 261 critically ill patients were recruited, of which 35% had renal dysfunction prior to admission. The main reason for starting RRT was oliguria; the most widely used RRT modality was hemodiafiltration; and the median prescribed dose at baseline was 35mL/kg/h. The median time of RRT onset from ICU admission was one day. The mortality rate at 30 and 90 days was 46% and 54%, respectively, and was associated to greater severity scores and a later onset of RRT. At discharge, 85% of the survivors had recovered renal function. CONCLUSIONS: Current practice in RRT in Catalonia abides with the current clinical practice guidelines. Mortality related to RRT is associated to later onset of such therapy. The renal function recovery rate at hospital discharge was 85% among the patients subjected to RRT.

Rotura completa de arteria poplítea de un mes de evolución, tras meniscectomía parcial artroscópica / Complete popliteal artery rupture one month after arthroscopic partial meniscectomy

Comunicamos una sección completa de arteria poplítea en relación a una meniscectomía parcial artroscópica realizada un mes antes. El paciente presentaba dolor distal progresivo e incapacitante. Se encontró rotura contenida de arteria poplítea y situación de isquemia subaguda al conservar flujo distal a través de dos ramas geniculadas. La lesión fue reparada mediante cirugía vascular abierta. La artroscopia es una técnica mínimamente invasiva, con bajas tasas de morbilidad. El paquete neurovascular poplíteo está próximo a la capsula articular posterior y es potencialmente vulnerable. Las lesiones vasculares tras artroscopia de rodilla son infrecuentes. No se ha encontrado en la literatura ningún caso de rotura completa de arteria poplítea de presentación subaguda como el que se presenta. Para evitar consecuencias catastróficas, es esencial tener presente la posibilidad de una lesión vascular tras artroscopia de rodilla, incluso en casos con varias semanas desde la intervención (AU)

A patient suffered a complete popliteal artery injury one month after a partial arthroscopic meniscectomy. The patient complained of progressive and severe distal pain. A complete lesion of the popliteal artery was found. Distal vascular flow was barely supported by two geniculate arteries. Vascular repair was performed using open vascular surgery. Although the popliteal neurovascular bundle is close to the posterior capsule of the knee and is obviously potentially vulnerable, injuries in arthroscopy of the knee are very rare. To avoid catastrophic consequences, the possibility of vascular injuries following arthroscopy of the knee, even several weeks after the surgery must not be ruled out (AU)

[Complete popliteal artery rupture one month after arthroscopic partial meniscectomy]. / Rotura completa de arteria poplítea de un mes de evolución, tras meniscectomía parcial artroscópica.

A patient suffered a complete popliteal artery injury one month after a partial arthroscopic meniscectomy. The patient complained of progressive and severe distal pain. A complete lesion of the popliteal artery was found. Distal vascular flow was barely supported by two geniculate arteries. Vascular repair was performed using open vascular surgery. Although the popliteal neurovascular bundle is close to the posterior capsule of the knee and is obviously potentially vulnerable, injuries in arthroscopy of the knee are very rare. To avoid catastrophic consequences, the possibility of vascular injuries following arthroscopy of the knee, even several weeks after the surgery must not be ruled out.

Involvement of cytosolic ascorbate peroxidase and Cu/Zn-superoxide dismutase for improved tolerance against drought stress.

In order to understand the role of cytosolic antioxidant enzymes in drought stress protection, transgenic tobacco (Nicotiana tabacum cv. Xanthi) plants overexpressing cytosolic Cu/Zn-superoxide dismutase (cytsod) (EC 1.15.1.1) or ascorbate peroxidase (cytapx) (EC 1.11.1.1) alone, or in combination, were produced and tested for tolerance against mild water stress. The results showed that the simultaneous overexpression of Cu/Znsod and apx or at least apx in the cytosol of transgenic tobacco plants alleviates, to some extent, the damage produced by water stress conditions. This was correlated with higher water use efficiency and better photosynthetic rates. In general, oxidative stress parameters, such as lipid peroxidation, electrolyte leakage, and H(2)O(2) levels, were higher in non-transformed plants than in transgenic lines, suggesting that, at the least, overexpression of cytapx protects tobacco membranes from water stress. In these conditions, the activity of other antioxidant enzymes was induced in transgenic lines at the subcellular level. Moreover, an increase in the activity of some antioxidant enzymes was also observed in the chloroplast of transgenic plants overexpressing cytsod and/or cytapx. These results suggest the positive influence of cytosolic antioxidant metabolism on the chloroplast and underline the complexity of the regulation network of plant antioxidant defences during drought stress.

Diagnóstico precoz del fracaso renal agudo / Early diagnosis of acute renal failure

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Herida por arma de fuego y hallazgo radiológico torácico / Gunshot wound and chest x-ray finding

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A glycoconjugate from corms of saffron plant (Crocus sativus L.) inhibits root growth and affects in vitro cell viability.

A glycoconjugate has been characterized from saffron corms (Crocus sativus L.) that inhibits the growth of roots of Nicotiana tabacum and Arabidopsis thaliana, at concentrations ranging from 1-100 micrograms m-3. Roots of seedlings grown in the presence 0.1 microgram m-3 glycoconjugate showed bulging of epidermal cells, whereas at 10 micrograms m-3, roots were completely devoid of hairs. At 100 micrograms m-3 glycoconjugate the cell walls of the root vascular tissues were thicker and, overall, the vascular tissue was enlarged. In addition, this glycan is cytotoxic to isolated tobacco cells and protoplasts, with 50% cell death induced by 0.5 and 2 micrograms m-3 glycoconjugate, respectively. Morphological and biochemical changes induced by the exposure to the glycoconjugate included cell size decrease, loss of regular cell shape, cytoplasm collapse, and release of intracellular proteins. This molecule at low concentrations (0.1 microgram m-3) mimics the effects of Yariv phenylglycosides and of mutant Arabidopsis which present defective or missing arabinogalactan-proteins (AGPs) in roots, indicating the glycoconjugate might interact with cell surface AGPs.

The evolution of photosynthetic capacity and the antioxidant enzymatic system during acclimatization of micropropagated Calathea plants.

The effects of an increased PPFD on photosynthesis, the functioning of the photosynthetic apparatus and the response of the antioxidant enzymatic system were studied during the ex vitro establishment of micropropagated Calathea 'Maui Queen' plantlets. Measured chlorophyll and carotenoids contents in ex vitro formed leaves were almost three times higher compared to the in vitro formed ones. At the end of the acclimatization, an inverse relation between PPFD and the chlorophyll (a+b)/carotenoids ratio was observed. During the first days after transplantation Calathea plants are not photosynthetically active, as is illustrated by the photosynthetic light response curves. With the appearance of new leaves, higher photosynthetic capacities were observed and light saturation point increased (days 17 and 25). Also the maximal photosynthetic efficiency enlarged as shown by the increased initial slope of the curves. F(v)/F(m) decreased directly after transplantation of the micropropagated plantlets, afterwards a recovery was observed, but highest F(v)/F(m) values were observed in low light (LL) plants. The photochemical quenching coefficient increased gradually during the first two weeks of the acclimatization. In high light (HL) plants, q(P) decreased directly after transfer, while this was not observed in LL and medium light (ML). During the acclimatization period to increasing light intensities significant changes in the activity of the antioxidant enzymatic system were observed. A decrease in superoxide dismutase (SOD) activity was measured during the first half of the acclimatization period followed by a recovery in ML and HL plants by day 35. Dehydroascorbate reductase (DHAR) activity decreased during acclimatization. At the end of the experimental period the lowest levels were measured in ML plants. Catalase (CAT) activity increased significantly during the first two weeks after transfer, a clear inverse relationship to PPFD was detected. The relation between the adquisition of full photosynthetic capacity and the activation of the enzymatic antioxidant system in the leaves of calathea plants during ex vitro acclimatization is discussed.

Production of a cytotoxic proteoglycan using callus culture of saffron corms (Crocus sativus L.).

Saffron corms have been demonstrated to contain a proteoglycan that inhibits growth of human tumor cells. In this study, we show strong evidence indicating that callus cultures of saffron corm also synthesize such glycoconjugate. This compound is cytotoxic against human cervical epithelioid carcinoma cells (IC50 = 7 mg ml-1), and consists of approximately 90% carbohydrate and 10% protein. In order to optimize the glycoconjugate purification to complete functional and therapeutic studies, we have designed an improved method consisting of anion-exchange chromatography and reversed-phase HPLC, which can be easily scaled-up.

Cd-induced oxidative burst in tobacco BY2 cells: time course, subcellular location and antioxidant response.

The relation between Cd and oxidative stress in BY2 cell cultures of tobacco was studied. In response to 5 mM Cd, a rapid generation of H2O2 has been detected in tobacco cell cultures by the oxidative quenching of the fluorescent reporter dye pyranine. This oxidative burst reached the maximum production of H2O2 after 10 min of treatment with Cd. This response could be considered as short term hypersensitive response previous to the oxidative stress caused by the metal at the cell plasma membrane. The observed antioxidant enzymatic response to the oxidative burst was preceded by an increased peroxidation of lipids with a significant increase in the activities of superoxide dismutase and ascorbate peroxidase. The results presented in this study point out to the plasma membrane as the primary target for the short term production of activated oxygen species in response to Cd in BY2 tobacco cells followed by a coordinated activation of the antioxidant enzymatic system.

Osteogenic protein-1 mRNA expression is selectively modulated after acute ischemic renal injury.

Osteogenic protein-1 (OP-1) is a morphogenetic factor highly expressed in the kidney and involved in tissue repair and development. Homozygous OP-1-deficient mice die shortly after birth due mainly to arrest of renal growth and differentiation. Because postischemic injury involves several repair mechanisms, this study examined whether kidney OP-1 mRNA expression is modulated after ischemia. Acute ischemic renal injury was achieved in rats by unilateral clamping of the renal pedicle followed by reperfusion. Rats were killed at 3, 6, 12, 24, and 48 h and 7 d after reperfusion, and kidneys were microdissected and analyzed by histology and Northern and Western blots. Changes in OP-1 mRNA were determined by measuring the ratio of OP-1/glyceraldehyde 3-phosphate dehydrogenase signals for each OP-1 transcript (4.0 and 2.4 kb) from ischemic, opposite, and sham-operated rats. The OP-1 mRNA content for transcript 4.0 kb was fivefold lower in the whole ischemic kidney compared with that in sham animals 24 h after reperfusion. In the ischemic medulla, OP-1 mRNA was strikingly downregulated 20-fold when compared with the ischemic cortex. Results for transcript 2.4 kb and for the other time points were comparable. OP-1 mRNA expression was also affected in the opposite medulla compared with the sham medulla. However, only in the ischemic medulla was the relative OP-1 content significantly lower at all time points. Similar results were obtained when analyzing OP-1 protein by Western blot at 24 h after reperfusion. Seven days after reperfusion, the levels of OP-1 mRNA returned to baseline. In conclusion, kidney OP-1 mRNA and protein are selectively downregulated in the medulla after acute ischemic renal injury. OP-1 modulation may be a key element for kidney repair.

Renal biopsy diagnosis in children presenting with haematuria.

We reviewed the clinical and renal biopsy findings in 322 children presenting during the years 1975-1996 with recurrent macro- or continuous microscopic haematuria persisting for > or =6 months, in whom non-glomerular causes were excluded. Family involvement was documented for first-degree relatives. All biopsies were examined by light microscopy, 317 by electron microscopy and 315 by immunofluorescence. Biopsies were classified as IgA nephropathy (78), Alport nephropathy (86), thin basement membrane nephropathy (TMN) (50), miscellaneous glomerulonephritis (32), hilar vasculopathy (28) and normal glomeruli (48). Although microscopic haematuria alone was more frequent in Alport nephropathy and TMN, the pattern of haematuria in individual patients did not predict histology. Of patients with familial haematuria, 79% of biopsies showed either Alport nephropathy or TMN. Hilar vasculopathy was observed both in isolation and in all abnormal histological categories.

Interactions of ultrapure bovine hemoglobin with renal epithelial cells in vivo and in vitro.

Using an ultrapurified hemoglobin (Hb) solution, we investigated the physiological effects and cellular processing of Hb in rat kidneys and in cultured opossum kidney (OK) cells. Rats infused with < 5.0 g/kg Hb showed no change in baseline serum creatinine (SCr) values (0.58 +/- 0.05 mg/dl) over 48 h, whereas transient acute renal failure followed infusion of 7.5 g/kg Hb (SCr 3.4 +/- 1.02 mg/dl, P = 0.02). Histology of Hb-infused kidneys demonstrated tubular epithelial cell injury. Renal injury was not caused by volume or oncotic load, cardiovascular effect, or ATP depletion. After Hb infusion, heme oxygenase, the rate-limiting enzyme in Hb catabolism, was induced in an organ-specific fashion. Inhibiting heme oxygenase activity with cimetidine did not alter Hb renal injury. Using OK cells, we determined that renal epithelia process Hb by fluid-phase endocytosis. Proton permeability of fluorescein Hb endosomes was unaltered compared with fluorescein dextran controls, demonstrating that Hb does not alter endosomal membrane integrity. These data suggest that Hb renal injury in rats occurs following large doses of ultrapure Hb, does not alter early steps in Hb endosomal processing by renal epithelia, and involves a mechanism that is not heme oxygenase dependent.

Evaluation of intercostal cryoanalgesia versus conventional analgesia in postthoracotomy pain.

The objective of the study was to evaluate the effects of cryoanalgesia in patients undergoing posterolateral thoracotomy. A double-blind randomized and prospective study was performed in 100 patients undergoing thoracotomy. They were randomized into two groups: Group A, 55 patients, who had undergone an intercostal cryoanalgesia and group B, control, 45 patients treated only with pharmacological analgesia ad libitum. In both groups we assessed pain in the first 7 postsurgical days, the amount of analgesia required, electromyography of the intercostal muscles involved and recording of maximal static respiratory pressures. Postsurgical pain was significantly lower (p < 0.001) in group A. No patient in group A needed major analgesia and the amount of aminopyrines required was significantly lower (p < 0.001) than those used in group B. Maximal static inspiratory pressure (PImax) showed no significant changes and no significant differences were found between the two groups. Maximal static expiratory pressure (PEmax) significantly decreased (p < 0.001) in the 1st and 2nd week and it was not related to the type of analgesia used. We advocate the use of cryoanalgesia since it significantly reduces pain as well as the doses of analgesia.

[Deletion of 17p11.2 chromosome in Spanish families with hereditary neuropathy and abnormal sensitivity to pressure]. / Deleción del cromosoma 17p11.2 en familias españolas con neuropatía hereditaria por vulnerabilidad excesiva a la presión.

Hereditary neuropathy with abnormal liability to pressure palsies (HNPP) is a dominant autosomally transmitted disease that gives rise to foci of peripheral nerve myelination, reducing conduction and leading to episodes of palsy and sensory changes that are all linked to sensitivity to pressure and traction on the affected nerve roots. The molecular basis of HNPP has been identified as a submicroscopic deletion of the 17p11.2 chromosome in exactly the same region that it is duplicated in Charcot-Marie-Tooth disease, type 1A (CMT1A). We report genetic analyses of 13 patients (belonging to 3 families) diagnosed of HNPP by means of physical examination and electrophysiologic and morphologic tests (the last in 3 cases only). Inter- and intrafamilial variation in symptomatology was studied. Some patients presented the usual clinical signs, such as recidivating brachial plexus palsy, permanent sensory polyneuropathy, foot deformities and others that might also be found in patients with CMT1A. All the patients showed electrophysiologic signs of underlying demyelinating polyneuropathy. Genetic study centered on detecting the deletion of 17p11.2 by segregation analysis with the polymorphic markers VAW409R3a (D17S122) and EW401HE (D17S61). Our results confirmed deletion at the CTM1A location of chromosome 17p11.2 in all 13 patients examined. These data suggest that the deletion of 17p11.2 plays a causal role in HNPP and that it is the most prevalent mutation in this disease; our findings constitute new evidence of the importance of the CMT1A/HNPP locus in the formation and control of peripheral myelin and in the ultimate functioning of peripheral nerves.

Attenuated varicella virus vaccine in children with renal transplants.

The long-term efficacy of varicella vaccine was studied in 34 children aged 2-18 years who were either on chronic dialysis (n = 17) or were renal transplant recipients (n = 17). Live attenuated virus (OKA line) was inoculated in a single 0.5-ml subcutaneous dose, without modification of the immunosuppressive therapy protocol for renal transplant recipients. The majority of children (85%) developed antibodies within the first 6 months, with IgG titres (enzyme-linked immunosorbent assay) greater than 1:40 (geometric mean 1:640). Of those children who were followed for longer than 2 years, 76% maintained their antibody titres. Reactions to the vaccine were minimal and the immunological protection was effective. Only 3 children developed a mild form of varicella in the post-vaccination period. We consider that seronegative children who are candidates for renal transplantation must be protected against varicella by attenuated varicella vaccination. When vaccination is performed after transplantation, no modification of immunosuppressive therapy is needed.

Invaginated vein graft as nerve conduit: an experimental study.

Vein grafts have been used for nerve repair in experimental and clinical studies. However, some concerns about their collapsability and the presence of valves which could block axonal growth have been put forth. We propose a modification to eliminate these potential problems by turning the vein inside out, obtaining an "invaginated" vein graft. We performed an experimental study on 61 adult Wistar rats, divided into 3 groups: control (non-operated) (n = 11); immediate repair, with 3 subgroups: invaginated vein graft (n = 10), vein graft (n = 10), and nerve graft (n = 10); and delayed repair, with 2 subgroups: invaginated vein graft (n = 10) and nerve graft (n = 10). Delayed repair was performed 3 to 4 weeks following division of the nerve. Electromyographical (EMG) assessment was performed in all operated animals at 2, 4, and 6 months after immediate reconstruction, and at 1 and 4 months after delayed repair. At the end of the study, all nerves were excised and a morphometric analysis was performed. We conclude that vein grafts are as useful as nerve grafts in immediate and delayed nerve repair, as there were no significant functional or histologic differences. We found no significant differences between invaginated vein grafts and non-invaginated vein grafts. However, electrophysiological results were slightly superior in the former. Regenerated axons were small, grouped in minifascicles with thin myelin sheaths. The venous adventitia did not interfere with axonal growth.

Permeability properties of rat renal lysosomes.

Although lysosomes maintain large pH gradients and may be subjected to significant osmotic gradients in vivo, little is known about their passive permeability properties. In recent studies, vacuolar H(+)-adenosine-triphosphatases (ATPases), such as those found in lysosomes, have been suggested to act as water channels. In addition, the erythrocyte and proximal tubule water channel CHIP28 is present on the plasma membrane of proximal tubule cells and may undergo endocytosis so that it is incorporated in lysosomes. We therefore examined water, proton, and small nonelectrolyte permeabilities in freshly purified lysosomes from rat renal proximal tubule. Lysosomes were purified by differential and Percoll gradient centrifugation. The preparation contained only lysosomes when examined by electron microscopy. Moreover, analysis by flow cytometry showed virtually all particles to be positive for acid phosphatase and cathepsin B activities. Permeabilities were measured on a stopped-flow fluorimeter by monitoring the self-quenching or pH-sensitive quenching of entrapped fluorescein derivatives. Osmotic water permeability (Pf) averaged 0.011 +/- 0.003 cm/s (n = 6), a value similar to that of biological membranes containing water channels. However, Pf was insensitive to the organic mercurial reagent p-chloromercuribenzene-sulfonate and to HgCl2 and exhibited an activation energy of 10.8 +/- 0.8 kcal/mol. These results indicate that water flux in lysosomes occurred via the lipid bilayer, and not via water channels. Addition of ATP led to lysosomal acidification (proton flux = 4.6 +/- 0.8 x 10(-11) mmol H+.s-1.cm-2), which was completely inhibited by 0.1 microM bafilomycin. Pf was insensitive to this agent as was the passive proton permeability (0.36 +/- 0.18 cm/s, n = 4). Permeabilities to small nonelectrolytes varied in proportion to the oil-water partition coefficient, confirming the applicability of Overton's rule to lysosomes. We conclude that proximal tubular lysosomes exhibit high Pf, which occurs via the lipid bilayer and not via vacuolar H(+)-ATPase.