Antibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults

Autoantibodies to Tamm-Horsfall protein associated with renal damage and urinary tract infections in adults. Forty-seven adults with urinary tract infection (UTI), 9 with recent acute pyelonephritis and 38 with previous renal infection, were investigated for the presence of autoantibodies to Tamm-Horsfall protein (THP). All patients except 6 had or had had vesicoureteric reflux (VUR). In patients with recent acute pyelonephritis, only IgA antibodies were significantly elevated. Among the patients with previous UTI, more than 6 months before the time of testing, a graded response was found for IgG and IgM specific antibodies, with the lowest value in those with renal damage and elevated serum creatinine and the highest in those with a normal X-ray. A negative correlation was found between IgG antibodies to THP and elevated serum creatinine (r = -0.76, P < 0.02). No significant correlation was found between VUR itself and antibodies to THP. A low IgG antibody level to THP in patients with a history of previous UTI seems to be a useful indicator of renal scarring. Possible immunologic mechanisms behind the low antibody level and the renal damage are discussed.Auto-anticorps anti-protéine de Tamm-Horsfall associés à des lésions rénales et à des infections urinaires chez l'adulte Quarante-sept adultes atteints d'infection urinaire, 9 ayant une pyélonéphrite aiguë récente et 38 une infection rénale antérieure ont été étudiés pour la présence d'auto-anticorps anti-protéine de Tamm-Horsfall (THP). Tous les malades sauf six avaient ou avaient eu un reflux vésico-urétéral. Chez les malades ayant un antécédent récent de pyélonéphrite seul les anti-corps IgA étaient significativement élevés. Parmi les malades dont l'antécédent d'infection urinaire remontait à plus de six mois une réponse a été obtenue pour les anti-corps spécifiques IgG et IgM, avec la valeur la plus faible chez ceux qui étaient atteints de lésions rénales et avaient une créatininémie élevée et la valeur la plus élevée chez ceux qui étaient indemnes de lésions radiologiques. Une corrélation négative a été observée entre les anti-corps IgG anti THP et l'augmentation de la créatininémie (r = -0,76, P < 0,02). Il n'a pas été observé de corrélation significative entre le reflux par lui-même et les anti-corps anti THP. Un taux faible d'anti-corps IgG anti THP chez des malades ayant des antécédents d'infection urinaire peut être un indicateur utile de lésions rénales. Les mécanismes immunologiques qui peuvent sous tendre le taux faible d'anti-corps et les lésions rénales sont discutés

Citrate treatment reduces endothelial death and inflammation under hyperglycaemic conditions

Hyperglycaemia and glucose degradation products (GDPs) are closely associated with oxidative stress and inflammation in diabetic patients, a condition that leads to endothelial dysfunction and cardiovascular problems. We evaluated the effect of citrate and gluconate on glucose- and GDP-induced endothelial inflammation by measuring changes in viability, inflammation and function in primary human umbilical vein endothelial cells (HUVECs). The extent of apoptosis/necrosis was measured by flow cytometry and visualised with confocal microscopy by staining with annexin V or propidium iodide, respectively. Protein kinase C-βII (PKC-βII) activation was evaluated with Western blotting. Incubation with glucose (30 mM) and GDP (50 µM) significantly increased PKC-βII expression, endothelial cell death and inflammation. The addition of citrate decreased hyperglycaemia-induced apoptosis (p = 0.021), necrosis (p = 0.04) and reduced PKC-βII expression (p = 0.021) down to background levels. Citrate improved endothelial function by reducing the inflammatory markers (p = 0.01) and by decreasing neutrophil diapedesis (p = 0.012). These results suggest that citrate may have therapeutic potential by reducing hyperglycaemia-induced endothelial inflammation and abolishing endothelial dysfunction

Mass transfer of calcium across the peritoneum at three different peritoneal dialysis fluid Ca2+ and glucose concentrations.

Mass transfer of calcium across the peritoneum at three different peritoneal dialysis fluid Ca2+ and glucose concentrations.BackgroundIn peritoneal dialysis, the rate of ultrafiltration has been predicted to be a major determinant of peritoneal calcium (Ca2+) removal. Hence, dialysis fluid glucose concentration should be an important factor governing the transperitoneal Ca2+ balance. The aim of this study was to test the effect of various dialysate glucose levels and selected dialysate Ca2+ levels on Ca2+ removal in peritoneal dialysis patients.MethodsPatients (N = 8) received, during a 7-week period, 2L of lactate (30mmol/L)/bicarbonate (10mmol/L)–buffered peritoneal dialysis solutions containing either 1.5% glucose and 1.0mmol/L Ca2+ or 2.5% glucose and 1.6mmol/L Ca2+, or 4% glucose and 2.5mmol/L Ca2+, respectively, provided in a three-compartment bag (trio system). Patients underwent standardized (4-hour) dwells, one for each of the three dialysates to assess permeability-surface area product (PS) or mass transfer area coefficients (MTAC) for ionized and “freely diffusible” Ca2+, lactate, glucose, bicarbonate, phosphate, creatinine, and urea.ResultsThere was a clear-cut dependence of peritoneal Ca2+ removal on the rate of ultrafiltration. For large peritoneal to dialysate Ca2+ gradients (2.5mmol/L Ca2+ in 4% glucose) a close fit of measured to simulated data was predicted by the three-pore model using nonelectrolyte equations. For low transperitoneal Ca2+ concentration gradients, however, directly measured Ca2+ data agreed with the simulated ones only when the peritoneal Ca2+ PS was set lower than predicted from pore theory (6mL/min).ConclusionThere was a marked ultrafiltration dependence of transperitoneal Ca2+ transport. Nonelectrolyte equations could be used to simulate peritoneal ion (Ca2+) transport provided that the transperitoneal ion concentration gradients were large. Based on our data 1.38mmol/L Ca2+ in the dialysis fluid would have created zero net Ca2+ gain during a 4-hour dwell for 1.5% glucose, whereas 1.7 and 2.2mmol/L Ca2+ would have been needed to produce zero Ca2+ gain for 2.5% glucose and 3.9% glucose, respectively

Infusion fluids contain harmful glucose degradation products

PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients

Mathematical modelling of post-filter ionized calcium during citrate anticoagulated continuous renal replacement therapy.

Background/aimsPost-filter ionized calcium (iCa) measured on a blood gas analyzer (BGA) during regional citrate anticoagulated continuous renal replacement therapy (CRRT) are needed to control the regime. This increases the workload and requires attention including interpretation of blood analyses. Two algorithms were developed to calculate the post-filter iCa instead. The first algorithm used measured systemic total calcium and the second used a selected set of values from an initial blood gas sample as input.MethodsCalculated post-filter iCa values were compared to real blood gas analyses. 57 patients treated at the intensive care unit at Skåne University Hospital in Lund during 2010-2017 were included after applying inclusion and exclusion criteria. Clinical and machine parameters were collected from the electronic medical records. Non-quality checked data contained 1240 measurements and quality checked data contained 1034 measurements.ResultsThe first algorithm using measured systemic total calcium resulted in slightly better precision and trueness with an average difference between the predicted and measured post-filter iCa concentration of 0.0185±0.0453 mmol/L for quality checked data, pConclusionThe algorithms were able to estimate in range postfilter iCa values with great trueness and precision. However, they had some difficulties to estimate out-of-range postfilter iCa values. More work is needed to improve the algorithms especially in their citrate-modelling

Blood treatment apparatus adapted to preserve parts thereof

A blood treatment apparatus adapted to preserve a blood treatment unit (20) between blood treatment sessions. The blood treatment apparatus is configured to i) perform a blood treatment session and thereby use the blood treatment unit (20), ii) fill the blood treatment unit (20) with a preservation fluid comprising at least one treatment fluid concentrate of a type that is used to prepare the treatment fluid, iii) maintain the preservation fluid in the blood treatment unit (20) until a next blood treatment session is prepared, iv) dispatch the preservation fluid from the blood treatment unit (20) in preparation of a next blood treatment session, and v) perform a next blood treatment session and thereby extend the use of the blood treatment unit (20). A related method is also described