Papers by Maria Herthelius
Clinical Journal of the American Society of Nephrology, 2018
Background and objectives Data on recovery of kidney function in pediatric patients with presumed... more Background and objectives Data on recovery of kidney function in pediatric patients with presumed ESKD are scarce. We examined the occurrence of recovery of kidney function and its determinants in a large cohort of pediatric patients on maintenance dialysis in Europe. Design, setting, participants, & measurements Data for 6574 patients from 36 European countries commencing dialysis at an age below 15 years, between 1990 and 2014 were extracted from the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Recovery of kidney function was defined as discontinuation of dialysis for at least 30 days. Time to recovery was studied using a cumulative incidence competing risk approach and adjusted Cox proportional hazard models. Results Two years after dialysis initiation, 130 patients (2%) experienced recovery of their kidney function after a median of 5.0 (interquartile range, 2.0–9.6) months on dialysis. Compared with ...
Infection and Immunity, 1989
A persistent vaginal colonization with a pyelonephritogenic strain of Escherichia coli, induced b... more A persistent vaginal colonization with a pyelonephritogenic strain of Escherichia coli, induced by administration of amoxicillin, was established in four adult cynomolgus monkeys. This colonization mimicked the one seen in urinary tract infection-prone human females. Attempts to eliminate the E. coli colonization and restore normal conditions were made. Either suspensions of lactobacilli or vaginal fluid from a healthy unmanipulated monkey was administered as repeated vaginal flushes for 5 to 9 days. A total elimination of vaginal E. coli was observed in two of six experiments with lactobacilli, and a decrease was observed in the other four. A better result was obtained with flushes of vaginal fluid, which eliminated the E. coli colonization in eight of eight experiments. In two of these, a single flush was sufficient to obtain a decolonization. The ability of fresh vaginal fluid to eliminate E. coli from the vagina could be transferred from one monkey to another. This study demonst...
Blood, 2013
Introduction Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic, a... more Introduction Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic, and progressive disease of thrombotic microangiopathy (TMA). Plasma exchange/plasma infusion (PE/PI) has been shown to lack efficacy in patients (pts) with aHUS. Despite PE/PI, up to 65% of pts sustain permanent renal damage, progress to end-stage renal disease, or die within 1 year (yr) of diagnosis. Among aHUS pts with long disease duration and CKD receiving chronic PE/PI, significant improvements in hematologic parameters and renal function were achieved in a clinical trial of eculizumab (Ecu). The current analysis was undertaken to gain better insight into the timing of hematologic and renal improvements in a 26-week (wk), Phase 2 trial with a long-term extension. Methods aHUS pts ≥12 yrs of age with long disease duration and CKD receiving chronic PE/PI were enrolled. This analysis assessed the percentage of pts achieving each of the following outcomes – all for ≥2 consecutive measure...
Blood, 2011
193FN2 INTRODUCTION: aHUS is a genetic, systemic disease with a devastating prognosis caused by c... more 193FN2 INTRODUCTION: aHUS is a genetic, systemic disease with a devastating prognosis caused by chronic uncontrolled complement activation leading to thrombotic microangiopathy (TMA), progressive organ damage and premature mortality. In a 26-wk phase II trial, pts receiving ECU, a terminal complement inhibitor, had a highly significant increase in platelet count (a measure of TMA improvement) (primary endpoint: 73×109/L increase; p=0.0001). 13/15 pts with low platelet count at baseline (BL) (ITT) had platelet normalization at Wk 26. 15/17 pts (88%) achieved TMA event-free status (≥12 wks of stable platelet count, no PE/PI and no new dialysis). 13/13 pts treated with ECU for 26 wks had platelet normalization at Wk 26 and 15/15 treated with ECU for 26 wks achieved TMA event-free status. Median TMA intervention rate was 0 (no. of PE/PI and new dialysis events/pt/day). Importantly, 4/5 pts on dialysis with PE/PI discontinued dialysis with ECU. ECU was well tolerated (Legendre. ASN 2010)...
Infectious Diseases, 2019
BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are c... more BK-virus (BKV) associated nephropathy (BKVAN) and BKV associated haemorrhagic cystitis (HC) are complications of BKV infection/reactivation in renal and allogeneic haematopoietic stem cell transplantation (HSCT) patients, respectively. The task of how to manage these diseases was given to the chair by the Swedish Reference Group for Antiviral Therapy (RAV). After individual contributions by members of the working group, consensus discussions were held in a meeting on 23 January 2018 arranged by RAV. Thereafter, the recommendations were published in Swedish on November 2018. The current translation to English has been approved by all co-authors. High BKV serum levels suggest an increased risk for BKVAN and potential graft failure. For detection of BKVAN, careful monitoring of BKV DNA levels in serum or plasma is recommended the first year after renal transplantation and when increased creatinine serum levels of unknown cause are observed. Notably, a renal biopsy is mandatory for diagnosis. To reduce the risk for progression of BKVAN, there is no specific treatment, and tailored individual decrease of immunosuppression is recommended. For BKV-HC, BKV monitoring is not recommended, since BK-viruria frequently occurs in HSCT patients and the predictive value of BKV in plasma/serum has not been determined. However, the risk for BKV-HC is higher for patients undergoing myeloablative conditioning, having an unrelated, HLA-mismatched, or a cord blood donor, and awareness of the increased risk and early intervention may benefit the patients. Also for BKV-HC, no specific therapy is available. Symptomatic treatment, e.g. forced diuresis and analgesics could be of use.
Pediatric Nephrology, 2017
Background Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatr... more Background Chronic kidney disease-associated mineral bone disorder (CKD-MBD) is common in pediatric kidney disease patients and a risk factor for future cardiovascular disease (CVD). Fibroblast growth factor-23 (FGF23) and Klotho are novel key players in CKD-MBD, and has been suggested to be involved in the development of CVD. Methods This prospective cohort study included 74 pediatric patients; 31 with CKD (age range 0.8-18.8 years, glomerular filtration rate (GFR) range 9-68 mL/min/1.73 m 2) and 43 transplanted patients (CKD-T; age range 3.3-17.7 years, GFR range 10-99 mL/min/1.73 m 2) examined annually for 3 years. We assessed longitudinal patterns and predictors of FGF23 and soluble Klotho, as well as associations to cardiac remodeling and function using echocardiographic pulse wave Doppler (PWD) and color-coded tissue Doppler imaging (cc-TDI).
Nephrology Dialysis Transplantation, 2015
Nephrology Dialysis Transplantation, 2016
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 9, 2016
The impact of different dialysis modalities on clinical outcomes has not been explored in young i... more The impact of different dialysis modalities on clinical outcomes has not been explored in young infants with chronic kidney failure. Cohort study. Data were extracted from the ESPN/ERA-EDTA Registry. This analysis included 1,063 infants 12 months or younger who initiated dialysis therapy in 1991 to 2013. Type of dialysis modality. Differences between infants treated with peritoneal dialysis (PD) or hemodialysis (HD) in patient survival, technique survival, and access to kidney transplantation were examined using Cox regression analysis while adjusting for age at dialysis therapy initiation, sex, underlying kidney disease, and country of residence. 917 infants initiated dialysis therapy on PD, and 146, on HD. Median age at dialysis therapy initiation was 4.5 (IQR, 0.7-7.9) months, and median body weight was 5.7 (IQR, 3.7-7.5) kg. Although the groups were homogeneous regarding age and sex, infants treated with PD more often had congenital anomalies of the kidney and urinary tract (CAK...
Acta Paediatrica, 2016
Little is known about the health-related quality of life (HRQoL) of children with lower urinary t... more Little is known about the health-related quality of life (HRQoL) of children with lower urinary tract dysfunction (LUTD) and chronic kidney disease (CKD). We investigated LUTD and other possible predictors of impaired HRQoL in children with conservatively treated moderate-to-severe CKD or with a kidney transplant.
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2016
Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may e... more Complement activation occurs during enterohemorrhagic Escherichia coli (EHEC) infection and may exacerbate renal manifestations. In this study, we show glomerular C5b-9 deposits in the renal biopsy of a child with EHEC-associated hemolytic uremic syndrome. The role of the terminal complement complex, and its blockade as a therapeutic modality, was investigated in a mouse model of E. coli O157:H7 infection. BALB/c mice were treated with monoclonal anti-C5 i.p. on day 3 or 6 after intragastric inoculation and monitored for clinical signs of disease and weight loss for 14 d. All infected untreated mice (15 of 15) or those treated with an irrelevant Ab (8 of 8) developed severe illness. In contrast, only few infected mice treated with anti-C5 on day 3 developed symptoms (three of eight, p < 0.01 compared with mice treated with the irrelevant Ab on day 3) whereas most mice treated with anti-C5 on day 6 developed symptoms (six of eight). C6-deficient C57BL/6 mice were also inoculated w...
Pediatric nephrology (Berlin, Germany), Jan 23, 2015
This study compares glomerular filtration rate (GFR) equations in children based on standardized ... more This study compares glomerular filtration rate (GFR) equations in children based on standardized cystatin C (CYSC) and creatinine (CREA) and their combinations with renal clearance of inulin (C-inulin). A total of 220 children with different renal disorders were referred for C-inulin (median 84 ml/min/1.73 m(2)). Bias, precision (interquartile range, IQR), and accuracy (percentage of estimates ±30 % of C-inulin; P30) were evaluated for two cystatin C equations, CAPACYSC and BergCYSC, for creatinine equations, SchwartzCREA and GaoCREA, the arithmetic mean of CAPACYSC and SchwartzCREA (MEANCAPA+Schwartz), BergCYSC and SchwartzCREA (MEANBERG+SCHWARTZ) and the composite equation ChehadeCYSC+CREA. Overall results of CAPACYSC, BergCYSC, SchwartzCREA, GaoCREA, MEANCAPA+Schwartz, MEANBERG+SCHWARTZ and ChehadeCYSC+CREA were: median bias -7.6/-4.9/-3.7/-2.3/-4.6/-4.0/-10.1 %, IQR 20.0/19.9/21.7/22.4/21.0/20.9/23.3 ml/min/1.73 m(2) and P30 86/86/80/83/89/91/83 %. The cystatin C equations, MEAN...
Pediatric nephrology (Berlin, Germany), 2006
The underlying mechanisms of urinary-tract infections (UTI) in renal transplant recipients are st... more The underlying mechanisms of urinary-tract infections (UTI) in renal transplant recipients are still not fully understood. In otherwise healthy children, bladder dysfunction increases the susceptibility to UTI. The aim of this study was to evaluate lower-urinary-tract function in children and adolescents after renal transplantation. Sixty-eight recipients of renal transplants, 5-20 years of age and 1-15 years after transplantation, were evaluated for their bladder function with a questionnaire, uroflowmetry and bladder ultrasound, and for renal function (glomerular filtration rate) by measuring clearance of inulin or iohexol. Forty-nine patients (72%) had some type of abnormality of bladder function. Abnormal bladder capacity was found in 26%, abnormal urinary flow in 50% and residual urine in 32% of the patients. There was no significant difference in bladder or renal function in children with urinary-tract malformations compared with those with normal urinary tract. Furthermore, t...
Kidney international, Jan 4, 2015
Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characteri... more Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA...
Pediatric Nephrology, 2011
There are still concerns about renal transplantation in small children. The aim of this study was... more There are still concerns about renal transplantation in small children. The aim of this study was to identify prenatal data, underlying diseases, patient and graft survival, graft function and growth in young renal transplant recipients at our center. A retrospective analysis was performed on 50 kidney transplants performed during the period 1981-2008 in children weighing &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;13 kg. Their median age at transplantation was 1.4 (range 0.4-3.7) years and the median weight was 9.5 (3.4-12.1) kg. The underlying diseases were congenital in 88% of the patients and acquired in 12%. Ten-year patient survival was 88% (82% before 1998 and 95% since 1998). Ten-year graft survival was 82% (75 and 95%, respectively). Graft function (glomerular filtration rate) deteriorated from a mean of 75-48 ml/min/1.73 m(2) within 10 years. There was rapid catch-up growth within the first years post-transplant, from a median height of -2.44 standard deviation score (SDS) at transplantation to -0.74 SDS after 3 years. In small children, patient and graft survival were as good as those in older children. Renal function deteriorated during the first years post-transplant but stabilized within a few years. In most children, there was a substantial improvement in growth within the first years after transplantation.
The Lancet, 1989
Retrospective studies suggest that circumcision of newborn boys will reduce the frequency of male... more Retrospective studies suggest that circumcision of newborn boys will reduce the frequency of male early infantile urinary tract infection (UTI) by about 90%. If they are correct, this will be the first known instance of a common potentially lethal disease being preventable by extirpation of a piece of normal tissue. To reconcile the phenomenon with existing views of evolution and biology, it is suggested that the effects of one unphysiological intervention are counterbalancing those of another--ie, colonisation of the baby&#39;s gastrointestinal tract and genitals in maternity units by Escherichia coli strains of non-maternal origin, to which the baby has no passive immunity. As an alternative to circumcision to prevent early infantile male UTI, more natural colonisation could be promoted by strict rooming-in of mother and baby or by active colonisation of the baby with his mother&#39;s anaerobic gut flora.
Journal of Urology, 2010
All previously published papers were reproduced with the permission of the publisher.
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Papers by Maria Herthelius