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Christoph Aufricht

Publications and source records attributed to Christoph Aufricht.

At least 19 recordsLinked to original sources

Risk factors for peritonitis in pediatric peritoneal dialysis: a single-center study.

Recent US registry data and a European multicenter study described increased risk of peritonitis in young children on peritoneal dialysis (PD). No underlying age-specific risk factors could be defined in these reports. Therefore, we analyzed risk factors for peritonitis in children treated by PD as primary renal replacement therapy at the Kinderdialyse, Vienna, and particularly searched for age-specific aspects. Thirty children (15 boys, mean age 4.6 years) received PD [21 automated peritoneal dialysis (APD), nine continuous ambulatory peritoneal dialysis (CAPD)] for 13 months (3-49 months). During the total observation period of 395 dialysis months, 27 peritonitis episodes were diagnosed (1:14.6 months or 0.82/patient per year). Of our population, 43% remained peritonitis free; seven patients suffered from more than one peritonitis episode. Ten potential risk factors [age, gender, PD modality, duration of PD, exit-site status, urine volume, residual glomerular filtration rate (GFR), Kt/V, normalized protein catabolic rate (nPCR), albumin] and four indices of peritonitis outcome (peritonitis incidence, peritonitis burden, risk of suffering more than one episode of peritonitis and chance of staying free from peritonitis) were analyzed. Our study identified six risk factors in univariate analysis, namely age, APD treatment, exit-site infections, low urinary volume, low residual GFR and low nPCR, which were significantly correlated with two or more of the outcome indices. Multivariate analysis identified exit-site infection and residual urine volume as strong independent predictors. In summary, our study identified several age-dependent and age-independent risk factors for peritonitis in pediatric PD. These data demonstrate that the risk for peritonitis in small children is not pre-determined but might be open to therapeutic interventions, such as optimizing exit-site care, dialysis prescription and nutrition management.

Aging↗

Heat-shock protein 70: molecular supertool?

The cellular stress response decreases cellular injury, either via primary induction of cytoresistance or by secondary enhancement of cellular repair mechanisms. The most frequently studied and best understood effectors of the cellular stress response are the heat shock proteins (HSP). HSP are among the oldest tools in the cellular protein machinery, demonstrating extremely high conservation of the genetic code since bacteria. Molecular chaperons, with the HSP-70 being the prototype, cooperate in transport and folding of proteins, preventing aggregation, and even resolubilizing injured proteins. Increasing evidence supports a role for HSP during the recovery from renal ischemia, in particular in cellular salvage from apoptotic cell death and cytoskeletal restoration. Recent studies also report the potential for biomolecular profiling of newborns for the risk of acute renal failure. In peritoneal dialysis novel data suggest the use of HSP expression for biocompatibility testing. More importantly, HSP are prime therapeutic candidates for clinical situations associated with predictable insults, such as organ procurement in transplant medicine and repetitive exposure to hyperosmolar and acidotic peritoneal dialysis fluids. The next challenge will be to define the regulatory pathways of the cellular stress response in these models to introduce novel therapeutic interventions, such as new pharmaceutics enhancing the HSP expression.

Animals↗

[Referral to the pediatric dialysis unit -- the earlier the better?].

Whereas recent research has demonstrated clear evidence for beneficial effects of early referral to the nephrologist in chronic renal insufficiency in adults, no such data exist for the pediatric population. In this study, we therefore correlated patient age and residual renal function at first presentation to a specialized pediatric nephrologist with the extent of secondary uremic complications and the further course of renal function. From March 2003 until March 2004, 43 children (34 boys, aged 10.1 +/- 6.3 yrs) with congenital-urologic (n = 26), congenital-nephrologic (n = 13) or acquired (n = 4) renal diseases had been followed for 3.9 yrs (14 days to 17.5 yrs) at the Kinderdialyse Wien, with a residual renal function of 35 +/- 20.5 ml/min/1.73 m(2) at first presentation. With regards to uremic secondary complications, the majority of children exhibited involvement of at least two systems at first presentation. Thereafter, children with congenital diseases who were referred to the specialized pediatric nephrology unit within the first year of live demonstrated a significantly better course of residual renal function (1.8% vs -0.7%, p = 0.034) than children who were referred later. These data confirm recent registry reports on chronic renal insufficiency in children. Only about a third of the children of our population were presented to a specialized pediatric nephrology center within their first year of life (despite a congenital disease in 90% of them). Thus, therapeutic interventions might be currently offered at a delayed time point in the majority of children.

Austria↗

Management of congenital hydronephrosis with ureteropelvic junction obstruction: the Vienna-AKH experience 1986-2001.

One of the most common causes of congenital hydronephrosis is obstruction of the ureteropelvic junction. The obstruction can be detected with prenatal ultrasonography screening and treated before renal function is reduced; the obstruction may also resolve spontaneously. Currently, there is no test for predicting the outcome of this obstruction. Management guidelines for neonates with asymptomatic obstruction of the ureteropelvic junction are based on expert opinions, but not on evidence-based data. In our retrospective study, we evaluated management and outcome of 26 renal units in 23 infants (15 boys, 8 girls) with congenital obstruction of the ureteropelvic junction treated in our institution between 1986 and 2001. These infants had isolated hydronephrosis on prenatal and postnatal sonography, showed an obstructive curve pattern in the postnatal diuretic nephrogram and had at least one follow-up nephrogram during a follow-up period of at least 1.5 years. Of these renal units, 16 demonstrated normal function (Group I), five moderate function (Group II) and five severely reduced function (Group III). In group I, 6 of 12 primarily conservatively managed kidneys resolved spontaneously and remained normal in function. In group II, all infants were operated and 83% improved their kidney function. In group III, all infants were operated but none demonstrated relevant improvement. These data support the current expert opinion of the Arbeitsgemeinschaft Pädiatrische Nephrologie (APN), that ureteropelvic junction obstruction in neonates with normal renal function can be managed primarily conservatively with close monitoring. In neonates with moderately--but not with severely--reduced renal function, early surgery is effective in the prevention of deterioration.

Austria↗

HSP-72 expression in pre-transplant donor kidney biopsies and post-transplant outcome.

In experimental transplant models, upregulation of renal heat shock proteins (HSP) represents a new therapeutic tool to improve allograft survival. In this clinical study, we hypothesized that HSP-72 expression in pretransplant donor kidney biopsies predicts posttransplant outcome. Expression of HSP-72 in pretransplant biopsies was assessed by immunohistochemistry and in situ hybridization in 82 consecutive renal transplantations and clinical data were collected prospectively during the first six months posttransplant. Renal tubular expression of HSP-72 was low and not influenced by donor-, graft-, or procedure-related risk factors. Neither strength nor pattern of pretransplant HSP-72 staining discriminated allografts with complicated (40%) posttransplant courses from those without complications (60%). The low HSP-72 expression in pretransplant donor kidney biopsies failed to predict delayed graft function or acute rejection. These findings suggest that constitutive HSP-72 gene expression at the time of engraftment does not play a role in graft protection.

Adult↗

Changes of blood pressure and left ventricular mass in pediatric renal transplantation.

Cardiovascular events are among the most frequent causes for long-term morbidity and mortality in children after renal transplantation. The aim of this study was to analyze the effects of post-transplant changes in arterial hypertension, as assessed by 24-h ambulatory blood pressure measurement (ABPM), on myocardial architecture, as assessed by echocardiography. In a retrospective chart review analysis, 39 children were identified in whom 24-h ABPM and echocardiography had been assessed within a 3-month interval after a mean of 4 years post transplantation; 20 repeated pairs of measurements after a mean of 2 years of follow-up were available to analyze the longitudinal effects of post-transplant changes of blood pressure control on left ventricular mass index (LVMI). Arterial hypertension (59%) and left ventricular hypertrophy (50%) were highly prevalent in children after renal transplantation. Renal allograft function and number of antihypertensive medications, but not ABPM variables, were correlated with LVMI at the initial observation. However, at repeat assessment, a significant correlation between ABPM and LVMI was found. In the longitudinal assessment, left ventricular remodeling was dependent on change of dosage of cyclosporine and interval changes of blood pressure levels. Hence, control of blood pressure correlates with changes of LVMI in children with renal allografts. These results clearly underline the importance of blood pressure control for the maintenance of the myocardial architecture.

Adolescent↗

Upper urinary tract: when is obstruction obstruction?

PURPOSE OF REVIEW: Obstruction can either be defined as a condition that hampers optimal renal development, or, more conservatively, as a restriction to urinary outflow that, when left untreated, will cause progressive renal deterioration. Currently, management is mostly based on the latter definition, but still remains controversial. Relevant work published before 2002 is considered because of a lack of recent literature. RECENT FINDINGS: Almost all reports comparing the primary conservative treatment of suspected obstruction versus early surgical intervention show comparable results, but there are different interpretations. The approach of 'watch and wait' for a unilateral hydronephrotic kidney with normal function is usually quite safe, with a very low risk of the permanent loss of renal function when accompanied by close monitoring, but it is certainly not without risk. At this time, the main underlying problems are that all currently applied diagnostic methods only detect effects secondary to obstruction, and the currently used definition of obstruction is based on a longitudinal observation period. The most relevant publication in the observation period was an in-depth report on a workshop in which the need for valid prospective markers for renal maldevelopment and 'significant' obstruction was expressed. SUMMARY: The optimal management of infants with congenital hydronephrosis and suspected obstruction will remain controversial until new diagnostic methods are able to discriminate between 'harmful' and 'harmless' obstruction. Most experts currently advocate primary conservative management, with close follow-up and surgical intervention only if there are signs of reduced function of the obstructed kidney.

Child↗

Overexpression of HSP-72 confers cytoprotection in experimental peritoneal dialysis.

BACKGROUND: Peritoneal dialysis is complicated by mesothelial cell injury due to low biocompatibility of peritoneal dialysis fluid (PDF). We have previously demonstrated that heat shock protein (HSP)-72 is potently up-regulated in response to PDF exposure of mesothelial cells in in vitro and in vivo models of peritoneal dialysis. The aim of this study was to evaluate potential cytoprotective effects of overexpression of HSP-72. METHODS: Cytoprotection was assessed by comparing cellular viability between pretreated versus nonpretreated human mesothelial cells (Met 5a; ATCC, Manassas, VA, USA, and primary cell cultures) subjected to extended, usually lethal PDF exposure times (120 min, CAPD2; Fresenius, Bad Homburg, Germany). Pretreatment was performed with exposure to PDF (60 min, CAPD2; Fresenius) or heat (15 min, 41.5 degrees C), and by transient transfection with HSP-72. RESULTS: When mesothelial cells were pretreated by nonlethal exposure to PDF or heat, HSP-72 was markedly up-regulated (>5-fold, P < 0.01). Pretreated human mesothelial cells were significantly protected against subsequent "lethal" exposures to PDF, as assessed by dye exclusion (>50% reduction, P < 0.05) and lactate dehydrogenase (LDH) release (>30% reduction, P < 0.05). Comparable cytoprotection (50% reduction by dye exclusion) was indicated by overexpression of HSP-72 in cultered human mesothelial cells (>5-fold) after transient transfection with HSP-72. This cytoprotection was confirmed at a cellular basis by double staining techniques with HSP-72 and ApopTag (apoptosis detection kit). CONCLUSION: Our study therefore shows that the mesothelial stress response confers cytoprotection in experimental peritoneal dialysis, mediated by the induction of HSP-72, and that the stimulus of the pretreatment does not have to be identical to the subsequent injury. These data offer the basis for an attractive novel therapeutic approach against PDF toxicity.

Cell Line, Transformed↗

ACE inhibition in the treatment of children after renal transplantation.

Currently, there are no data available on long-term effects of angiotensin-converting enzyme inhibitors (ACE-I) on graft function in children after renal transplantation. We therefore analyzed all children who were transplanted at our institution between 1989 and 1998 and followed for at least 2 years. Those treated with ACE-I, mainly because of failure of other antihypertensive medications, were compared to those without ACE-I. The ACE-I-treated children ( n=19) showed significantly better blood pressure control during the 1st year of follow-up ( p<0.05). In children with chronic allograft dysfunction ( n=8), treatment with ACE-I stabilized graft function, with improvement in creatinine clearance in 50% ( p<0.01). Serum potassium and hemoglobin levels remained stable. One patient discontinued ACE-I because of renal artery stenosis. Taken together, ACE-I were effective and safe in the treatment of hypertension in children following renal transplantation. Children with chronic allograft dysfunction experienced a stabilizing effect on graft function.

Adolescent↗

[Chronic peritoneal dialysis in children. Results of the Vienna Pediatric Dialysis Department].

BACKGROUND: Peritoneal Dialysis (PD) has been increasingly used as primary renal replacement therapy in children over the last 10 years. The aim of this study was to investigate complications of PD and compare the collected data with our own historical data and data from the literature. PATIENTS AND METHODS: 33 children (17 boys, mean age 4.9 years) who underwent PD for the first time due to chronic renal failure between 1994 and 2003 were enrolled in this retrospective survey. RESULTS: 398 months on PD in total, with a mean time of 12 months per patient were investigated. The occurrence rate of peritonitis was one per 14.2 months and for exit-site-infection one per 13.2 months. 23 children underwent renal transplantation, one child was switched to hemodialysis, two children died (one because of PD-unrelated circumstances), reflecting a 1-year survival rate of 94%. CONCLUSIONS: Peritoneal dialysis has become the most frequently used modality of renal replacement therapy in children, with a trend towards smaller children and infants. PD can be managed safely and successfully in children of all age groups, including even newborns.

Age Factors↗

Serum lipid pattern unifies following renal transplantation in children.

Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls ( n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children.

Child↗

Urinary tract infections beyond the early post-transplant period in pediatric renal graft recipients.

BACKGROUND: Urinary tract infection is a frequent bacterial complication after renal transplantation in adults and children, however there are only very limited data on children beyond the early post-transplant period. In this study we investigated urinary tract infections in pediatric outpatients who had received transplants more than six months previously. Incidence, risk factors and impact on short-term graft function were analyzed. METHODS: 47 children who had received a total of 58 allografts were analyzed between 1997 and 2000. At the time of analysis they had had their transplants for an average of 3.5 years (range 0.5-9.4). Urinary tract infection was defined as the presence of both significant bacteriuria (> 10(5) CFU/ml) and symptoms. RESULTS: Of the 47 patients, 15 (32%) had from 1 to 7 urinary tract infections each. In total 35 infections were recorded. Median age at urinary tract infection was 5.5 years (range 1.8-24.2). Gender, donor source, immunosuppression and underlying disease (urologic vs non-urologic) did not influence the incidence of urinary tract infection. Creatinine but not C-reactive protein rose significantly during the infection. CONCLUSIONS: Our data suggest that urinary tract infection remains a frequent but mostly benign complication in the pediatric transplant population, even beyond the early post-transplant period. More extended studies are needed to assess the long-term effects on graft function.

Adolescent↗

Urinary heat shock protein-72 excretion in clinical and experimental renal ischemia.

Renal ischemia not only causes injury but also induces repair mechanisms, such as the cellular induction of the 72-kilodalton heat shock protein HSP-72. The aim of this study was to determine whether HSP-72 is excreted in urine after ischemic renal injury. The first urine of six pediatric allograft recipients was examined for proteinuria and urinary HSP-72 excretion. Sprague-Dawley rats were treated with renal ischemia or hyperthermia and renal cortex and urinary HSP-72 levels were determined. HSP-72 was excreted in the first urine of renal allografts. In rats, renal HSP-72 was induced both by renal ischemia or hyperthermia. However, only renal ischemia resulted in urinary excretion of HSP-72. Urinary excretion of HSP-72 indicates an increased renal stress response and loss of tubular cell integrity after clinical and experimental renal ischemia.

Animals↗

Effect of cisapride on rate-corrected QT intervals in children on peritoneal dialysis.

The aim of this study was to investigate whether cisapride significantly increases corrected QT (QTc) intervals on resting 12-lead electrocardiograms (ECGs) in children on peritoneal dialysis. Medical records of children who were treated with chronic peritoneal dialysis and who had ECGs while off and on cisapride were obtained and reviewed. QTc on all 12-lead ECGs and past medical history were analyzed by two blinded pediatric cardiologists. A total of 79 ECGs (68 off/11 on cisapride) for 11 children on peritoneal dialysis were included. Of 11 children, 5 developed a prolongation of QTc, 2 of them beyond the normal range (453 and 478 ms). Mean data of QTc off versus on cisapride were 394+/-24 ms and 414+/-36 ms, respectively ( P=0.041). In 4 of the 5 children concomitant medications could be identified as factors to explain prolongation of the QT interval. No child had evidence of any arrhythmia or conduction defect on ECG. This retrospective study found mild but significant increases in QTc intervals with cisapride in children on chronic peritoneal dialysis, mostly due to concomitant medications.

Child↗

HSP-25 and HSP-90 stabilize Na,K-ATPase in cytoskeletal fractions of ischemic rat renal cortex.

BACKGROUND: We recently designed an in vitro system based on differential Triton-extractability of Na,K-ATPase from the cytoskeletal protein fraction isolated from rat renal cortex after renal ischemia. In the present study, we hypothesized that heat shock protein (HSP)-70, HSP-25 and HSP-90 work synergistically to stabilize the cytoskeletal anchorage of Na,K-ATPase. METHODS: Cellular proteins were fractionated by differential centrifugation into cytoskeletal pellets (I-PEL) obtained early (exhibiting abnormally high Triton extractability of Na,K-ATPase) and non-cytoskeletal supernatants (R-SUP) obtained late (exhibiting high abundance of HSP) after renal ischemia. For assessment of the role of HSP-70, HSP-25 and HSP-90 upon in vitro re-compartmentalization, I-PEL was either incubated in R-SUP with/without HSP antibodies, or in buffer with/without HSPs at different titers and combinations. Effects were evaluated by changes of Triton extractability of Na,K-ATPase after co-incubation. RESULTS: R-SUP was shown to contain significant amounts of HSP-70, HSP-25 and HSP-90. Incubation of I-PEL in R-SUP reduced Triton extractability of Na,K-ATPase. Addition of antibodies against each HSP significantly abolished these effects of R-SUP. Incubation of I-PEL with purified HSP-70, HSP-25 or HSP-90 each partly reproduced the effects of R-SUP, whereas the combination of all three HSP demonstrated a strong and more than additive effect on the cytoskeletal stabilization of Na,K-ATPase. CONCLUSIONS: The molecular mechanisms responsible for postischemic re-compartmentalization of Na,K-ATPase in rat renal cortex likely involves interactions between HSP-70, HSP-25 and HSP-90, stress proteins known to be induced in the ischemic kidney.

Acute Kidney Injury↗

Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation.

PURPOSE OF REVIEW: This review is on renal function in patients with spina bifida. Risk factors for renal injury as well specific issues concerning the treatment of chronic renal failure, renal replacement therapy and kidney transplantation are discussed. Relevant work published earlier than 2000 is also considered because of a lack of recent literature. RECENT FINDINGS: Data from adult and paediatric surveys show renal damage to be the single most prevalent cause of morbidity and mortality; even in children, 30-40% exhibit evidence of renal damage. Additional factors such as chronic infection and stone formation will then render the kidney more vulnerable to progressive loss of renal mass and subsequent chronic renal failure. As in other patients with renal insufficiency, the control of hypertension, preferably with angiotensin-converting enzyme inhibitors, and adequate nutrition are mainstays of nephrological care. The modality of dialysis in these patients is complicated by ventriculoperitoneal shunts or urinary stomata in peritoneal dialysis, or difficult vascular access in haemodialysis. Renal transplantation is now considered the optimal treatment for end-stage renal disease in all age groups. Although more prone to complications, recent data on patients with meningomyelocele or severely abnormal lower urinary tracts demonstrate excellent patient and graft outcomes. SUMMARY: The common goal in caring for these patients must be the prevention of progressive renal damage. However, once kidney failure has occurred, good and safe techniques for renal replacement therapy are available to bridge the time to transplantation, which is undoubtedly the best treatment for these patients.

Child↗

Ischemic conditioning prevents Na,K-ATPase dissociation from the cytoskeletal cellular fraction after repeat renal ischemia in rats.

Recent studies have suggested that heat shock proteins (HSPs) are involved in the restoration of the cytoskeletal anchorage of Na,K-ATPase after renal ischemia. To determine their role in ischemic conditioning, we investigated whether cytoskeletal Na,K-ATPase was stabilized during repeat ischemia concurrent with 25-kD and 70-kD HSPs induction. Anesthetized rats either underwent single unilateral renal ischemia or were conditioned with bilateral renal ischemia and, after 18 h of reflow, were then subjected to repeat unilateral renal ischemia. Renal cortex was harvested, and effects of single versus repeat ischemia were compared by Triton X-100 extraction, by immunohistochemistry, and by an in vitro assay of Na,K-ATPase association with isolated cytoskeletal fractions. In contrast to single ischemia, repeat ischemia did not result in increased Triton X-100 extractability of Na,K-ATPase. Levels of 25-kD and 70-kD HSPs were significantly induced by ischemic conditioning and redistributed into the cytoskeletal fraction after single and repeat ischemia. Immunohistochemistry also showed significant disruption of Na,K-ATPase within proximal tubules only after a single episode of ischemia, whereas repeat ischemia did not alter the pattern of restored Na,K-ATPase localization in conditioned renal cortex. The preserved association of Na,K-ATPase with the cytoskeletal fraction of conditioned renal cortex was effectively abolished in vitro by addition of antibodies against 25-kD or 70-kD HSP. These results suggest that 25-kD and 70-kD HSPs induced by ischemic conditioning stabilize the cytoskeletal anchorage of Na,K-ATPase during repeat renal ischemia.

Animals↗