Atif Awan - Academia.edu (original) (raw)

Papers by Atif Awan

Research paper thumbnail of Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: a cross-sectional web-based survey

BMJ Open

BackgroundAcute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure ... more BackgroundAcute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN.Patients, design and settingWe collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate.ResultsThirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m2 3–6 months later (p<0.0...

Research paper thumbnail of Long‐term outcome of transplant ureterostomy in children: A National Review

Pediatric Transplantation

Research paper thumbnail of Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland

Journal of Inherited Metabolic Disease

Research paper thumbnail of OC10 ‘I have a dead person’s kidney in me’: the struggles of self-identity among adolescent kidney recipients in ireland

Abstracts

The aim of this study was to determine the prevalence of depression in obese and overweigth adole... more The aim of this study was to determine the prevalence of depression in obese and overweigth adolescents and, to evaluate the relationships between depression and cardiomethabolic risk factors in obese and overweight adolescents. Method We performed a retrospective cross-sectional analysis of the data from overweight or obese adolescents 11 to 18 years of age who were evaluated in our clinic from January 2012 to December 2015. Depression was evaluated by Children's Depression Inventory. Hypertension, dyslipidemia, hyperinsulinemia, hyperglycaemia and insulin resistance were defined as cardiometabolic risk factors. For statistical analysis, Chi-square test and logistic regression analysis were used.

Research paper thumbnail of GP14 Adolescents use of metaphors to narrate their experience’s of living with chronic kidney disease: an irish perspective

Abstracts

cells whereas levels of miR-145 and-223 appeared to be reduced. Conclusions We have demonstrated ... more cells whereas levels of miR-145 and-223 appeared to be reduced. Conclusions We have demonstrated for the first time that miRNA are detectable in CF iPSC derived bronchospheres with altered expression following a directed differentiation approach of iPSC into proximalised airway epithelium. Expression patterns in iPSC may be different to patient bronchial epithelial cells previously described and warrants further investigation.

Research paper thumbnail of P98 An unusual case of alport syndrome in mother and daughter

Abstracts

Aim The author describes a case of cholelithiasis occurring in an 18 month old female who was exp... more Aim The author describes a case of cholelithiasis occurring in an 18 month old female who was exposed to intravenous ceftriaxone for 5 days. Four weeks after ceftriaxone therapy, all but one stone had resolved. Case report An 18 month old female presented to the emergency department with high grade pyrexia and rigors. Physical examination and investigations did not reveal a focus for infection. Bloods: White Cell Count 46.6, Neutrophils 41.7 CRP 120. The patient was commenced on ceftriaxone as empirical treatment. Intermittent high grade pyrexia continued for 5 days. On day 5 an abdominal ultrasound was performed which demonstrated multiple gallbladder calculi within a normal thickness gallbladder. The appearance of the common bile duct was normal. The patient was discharged on day 7 having been apyrexial for 48 hours and clinically well. The patient represented 4 weeks later with high grade pyrexia. The patient was commenced on IV augmentin at presentation; gentamicin was added on day 3. A repeat ultrasound was performed and demonstrated resolution of all but one echogenic focus in the gallbladder. Ulstrasound of the abdomen at 8 weeks demonstrated complete resolution of the calculi. Discussion Cholelithiasis and choledocholithiasis were considered to be uncommon in infants and children but have been increasingly diagnosed in recent years due to the widespread use of ultrasonography. 1 Ceftriaxone induced pseudolithiasis is an uncommon but recognized side effect of therapy and tends to resolve with cessation of therapy. 2 In the paediatric population, where gallstones are uncommon, paediatricians and radiologists need to be aware of this association in order to avoid unnecessary intervention. 3

Research paper thumbnail of Management of bone disease in cystinosis: Statement from an international conference

Journal of Inherited Metabolic Disease

Research paper thumbnail of Klippel-Feil syndrome as a novel feature of Schimke immunoosseous dysplasia

American Journal of Medical Genetics Part A

Research paper thumbnail of Monogenic causes of chronic kidney disease in adults

Research paper thumbnail of Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study

Transplantation, Jan 20, 2018

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft ... more BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivaria...

Research paper thumbnail of Plasma EBV microRNAs in paediatric renal transplant recipients

Journal of nephrology, 2018

Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To dat... more Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients. Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM). Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2-3p and 1...

Research paper thumbnail of Clinical Relapses of Atypical HUS on Eculizumab: Clinical Gap for Monitoring and Individualised Therapy

Case reports in nephrology, 2018

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A ... more Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there was evidence of ongoing C5 cleavage and clinical relapses when immunologically challenged. Eculizumab is an effective therapy for aHUS, but the recommended doses may not be adequate for all patients, highlighting the need for ongoing efforts to develop a strategy for monitoring of treatment efficacy and potential individualisation of therapy.

Research paper thumbnail of Renal transplant outcomes in primary FSGS compared with other recipients and risk factors for recurrence: A national review of the Irish Transplant Registry

Clinical transplantation, 2018

Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FS... more Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FSGS) post-transplantation. Our objective was to describe Irish outcomes for transplantation after end-stage renal disease (ESRD) due to p-FSGS, specifically rates of, and treatments for, r-FSGS. Irish patients with biopsy-proven FSGS were identified from the Irish National Kidney Transplant database (1982-2015). Medical record review was performed to identify predictors of r-FSGS and treatments for r-FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r-FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, TX, USA). Thirty-eight transplant recipients had biopsy-proven p-FSGS, 16 received a second transplant. A total of 3846 transplants formed the comparator group. r-FSGS complicated 60.5% (23/38) of first transplants. Eight...

Research paper thumbnail of Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Kidney international, Nov 24, 2017

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic ... more Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated co...

Research paper thumbnail of Seizures following renal transplantation in childhood

Pediatric Nephrology, Apr 30, 1999

Few studies have investigated the incidence of seizures following renal transplantation in childh... more Few studies have investigated the incidence of seizures following renal transplantation in childhood. The aim of this study was to determine this incidence and to identify risk factors. Retrospective casenote analysis was carried out on 119 transplants performed in 109 children over 10 years. Twenty-one transplants (in 20 children) were complicated by seizures, the majority of which occurred in the first 55 days after transplantation. Seizures were more common in the 5-to 10-year-old age group (P=0.03), but were no more common in those with a prior history of seizure (P=0.69). Their aetiology was predominantly multifactorial; hypertension (n=15), fever/infection (n=4) and acute allograft rejection (n=6) were commonly identified risk factors; 2 were secondary to intracerebral pathology. Most seizures were short lived, required minimal therapy and had a good long-term neurological outcome. In conclusion, seizures are relatively common following paediatric renal transplantation. Parents are now routinely counselled of this risk.

Research paper thumbnail of A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H-Related 3 Gene in Atypical Hemolytic Uremic Syndrome

Journal of the American Society of Nephrology : JASN, Jun 21, 2015

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor... more The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology-mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic di...

Research paper thumbnail of Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome

Pediatrics, 2015

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, le... more Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated agai...

Research paper thumbnail of Migration of Tenckhoff Catheter into an Occult Inguinal Hernia

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis

Research paper thumbnail of HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

Journal of the American Society of Nephrology : JASN, Jan 27, 2014

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome i... more Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 c...

Research paper thumbnail of Seizures following renal transplantation in childhood

Pediatric Nephrology, 1999

Few studies have investigated the incidence of seizures following renal transplantation in childh... more Few studies have investigated the incidence of seizures following renal transplantation in childhood. The aim of this study was to determine this incidence and to identify risk factors. Retrospective casenote analysis was carried out on 119 transplants performed in 109 children over 10 years. Twenty-one transplants (in 20 children) were complicated by seizures, the majority of which occurred in the first 55 days after transplantation. Seizures were more common in the 5-to 10-year-old age group (P=0.03), but were no more common in those with a prior history of seizure (P=0.69). Their aetiology was predominantly multifactorial; hypertension (n=15), fever/infection (n=4) and acute allograft rejection (n=6) were commonly identified risk factors; 2 were secondary to intracerebral pathology. Most seizures were short lived, required minimal therapy and had a good long-term neurological outcome. In conclusion, seizures are relatively common following paediatric renal transplantation. Parents are now routinely counselled of this risk.

Research paper thumbnail of Aetiology, course and treatment of acute tubulointerstitial nephritis in paediatric patients: a cross-sectional web-based survey

BMJ Open

BackgroundAcute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure ... more BackgroundAcute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, treatment and courses of acute TIN.Patients, design and settingWe collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate.ResultsThirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m2 3–6 months later (p<0.0...

Research paper thumbnail of Long‐term outcome of transplant ureterostomy in children: A National Review

Pediatric Transplantation

Research paper thumbnail of Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland

Journal of Inherited Metabolic Disease

Research paper thumbnail of OC10 ‘I have a dead person’s kidney in me’: the struggles of self-identity among adolescent kidney recipients in ireland

Abstracts

The aim of this study was to determine the prevalence of depression in obese and overweigth adole... more The aim of this study was to determine the prevalence of depression in obese and overweigth adolescents and, to evaluate the relationships between depression and cardiomethabolic risk factors in obese and overweight adolescents. Method We performed a retrospective cross-sectional analysis of the data from overweight or obese adolescents 11 to 18 years of age who were evaluated in our clinic from January 2012 to December 2015. Depression was evaluated by Children's Depression Inventory. Hypertension, dyslipidemia, hyperinsulinemia, hyperglycaemia and insulin resistance were defined as cardiometabolic risk factors. For statistical analysis, Chi-square test and logistic regression analysis were used.

Research paper thumbnail of GP14 Adolescents use of metaphors to narrate their experience’s of living with chronic kidney disease: an irish perspective

Abstracts

cells whereas levels of miR-145 and-223 appeared to be reduced. Conclusions We have demonstrated ... more cells whereas levels of miR-145 and-223 appeared to be reduced. Conclusions We have demonstrated for the first time that miRNA are detectable in CF iPSC derived bronchospheres with altered expression following a directed differentiation approach of iPSC into proximalised airway epithelium. Expression patterns in iPSC may be different to patient bronchial epithelial cells previously described and warrants further investigation.

Research paper thumbnail of P98 An unusual case of alport syndrome in mother and daughter

Abstracts

Aim The author describes a case of cholelithiasis occurring in an 18 month old female who was exp... more Aim The author describes a case of cholelithiasis occurring in an 18 month old female who was exposed to intravenous ceftriaxone for 5 days. Four weeks after ceftriaxone therapy, all but one stone had resolved. Case report An 18 month old female presented to the emergency department with high grade pyrexia and rigors. Physical examination and investigations did not reveal a focus for infection. Bloods: White Cell Count 46.6, Neutrophils 41.7 CRP 120. The patient was commenced on ceftriaxone as empirical treatment. Intermittent high grade pyrexia continued for 5 days. On day 5 an abdominal ultrasound was performed which demonstrated multiple gallbladder calculi within a normal thickness gallbladder. The appearance of the common bile duct was normal. The patient was discharged on day 7 having been apyrexial for 48 hours and clinically well. The patient represented 4 weeks later with high grade pyrexia. The patient was commenced on IV augmentin at presentation; gentamicin was added on day 3. A repeat ultrasound was performed and demonstrated resolution of all but one echogenic focus in the gallbladder. Ulstrasound of the abdomen at 8 weeks demonstrated complete resolution of the calculi. Discussion Cholelithiasis and choledocholithiasis were considered to be uncommon in infants and children but have been increasingly diagnosed in recent years due to the widespread use of ultrasonography. 1 Ceftriaxone induced pseudolithiasis is an uncommon but recognized side effect of therapy and tends to resolve with cessation of therapy. 2 In the paediatric population, where gallstones are uncommon, paediatricians and radiologists need to be aware of this association in order to avoid unnecessary intervention. 3

Research paper thumbnail of Management of bone disease in cystinosis: Statement from an international conference

Journal of Inherited Metabolic Disease

Research paper thumbnail of Klippel-Feil syndrome as a novel feature of Schimke immunoosseous dysplasia

American Journal of Medical Genetics Part A

Research paper thumbnail of Monogenic causes of chronic kidney disease in adults

Research paper thumbnail of Epidemiology of and Risk Factors for BK Polyomavirus Replication and Nephropathy in Pediatric Renal Transplant Recipients: An International CERTAIN Registry Study

Transplantation, Jan 20, 2018

BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft ... more BK polyomavirus-associated nephropathy (BKPyVAN) constitutes a serious cause of kidney allograft failure, but large-scale data in pediatric renal transplant recipients and a comprehensive analysis of specific risk factors are lacking. We analyzed data of 313 patients in the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, with an observation period of 3.3 years (range, 1 - 5). The net state of immunosuppressive therapy was assessed by the modified Vasudev score. Presumptive BKPyVAN (defined as sustained (>3 weeks) high-level BK viremia >10 copies/mL) within 5 years posttransplant occurred in 49/311 (15.8%) of patients, and biopsy-proven BKPyVAN in 14/313 (4.5%). BKPyV viremia was observed in 115/311 patients (36.7%), of whom 11 of 115 (9.6%) developed viremia late, ie, after the second year posttransplant. In 6/48 patients (12.5%) with high-level viremia and in 3/14 (21.4%) with BKPyVAN this respective event occurred late. According to multivaria...

Research paper thumbnail of Plasma EBV microRNAs in paediatric renal transplant recipients

Journal of nephrology, 2018

Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To dat... more Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients. Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM). Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2-3p and 1...

Research paper thumbnail of Clinical Relapses of Atypical HUS on Eculizumab: Clinical Gap for Monitoring and Individualised Therapy

Case reports in nephrology, 2018

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A ... more Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system. A humanised anti-C5 monoclonal antibody (eculizumab) is available for the treatment of aHUS. We present the first description of atypical HUS in a child with a coexistent diagnosis of a POL-III leukodystrophy. On standard eculizumab dosing regime, there was evidence of ongoing C5 cleavage and clinical relapses when immunologically challenged. Eculizumab is an effective therapy for aHUS, but the recommended doses may not be adequate for all patients, highlighting the need for ongoing efforts to develop a strategy for monitoring of treatment efficacy and potential individualisation of therapy.

Research paper thumbnail of Renal transplant outcomes in primary FSGS compared with other recipients and risk factors for recurrence: A national review of the Irish Transplant Registry

Clinical transplantation, 2018

Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FS... more Primary focal segmental glomerular sclerosis (p-FSGS) is commonly complicated by recurrence (r-FSGS) post-transplantation. Our objective was to describe Irish outcomes for transplantation after end-stage renal disease (ESRD) due to p-FSGS, specifically rates of, and treatments for, r-FSGS. Irish patients with biopsy-proven FSGS were identified from the Irish National Kidney Transplant database (1982-2015). Medical record review was performed to identify predictors of r-FSGS and treatments for r-FSGS. Transplant outcomes were compared to outcomes in all renal transplants performed during the same time period using registry data. Demographic and clinical predictors of r-FSGS were identified. Statistical analysis was performed using Stata (version 13, College Station, TX, USA). Thirty-eight transplant recipients had biopsy-proven p-FSGS, 16 received a second transplant. A total of 3846 transplants formed the comparator group. r-FSGS complicated 60.5% (23/38) of first transplants. Eight...

Research paper thumbnail of Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Kidney international, Nov 24, 2017

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic ... more Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated co...

Research paper thumbnail of Seizures following renal transplantation in childhood

Pediatric Nephrology, Apr 30, 1999

Few studies have investigated the incidence of seizures following renal transplantation in childh... more Few studies have investigated the incidence of seizures following renal transplantation in childhood. The aim of this study was to determine this incidence and to identify risk factors. Retrospective casenote analysis was carried out on 119 transplants performed in 109 children over 10 years. Twenty-one transplants (in 20 children) were complicated by seizures, the majority of which occurred in the first 55 days after transplantation. Seizures were more common in the 5-to 10-year-old age group (P=0.03), but were no more common in those with a prior history of seizure (P=0.69). Their aetiology was predominantly multifactorial; hypertension (n=15), fever/infection (n=4) and acute allograft rejection (n=6) were commonly identified risk factors; 2 were secondary to intracerebral pathology. Most seizures were short lived, required minimal therapy and had a good long-term neurological outcome. In conclusion, seizures are relatively common following paediatric renal transplantation. Parents are now routinely counselled of this risk.

Research paper thumbnail of A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H-Related 3 Gene in Atypical Hemolytic Uremic Syndrome

Journal of the American Society of Nephrology : JASN, Jun 21, 2015

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor... more The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination. We describe a novel CFH/CFHR3 hybrid gene secondary to a de novo 6.3-kb deletion that arose through microhomology-mediated end joining rather than nonallelic homologous recombination. We confirmed a transcript from this hybrid gene and showed a secreted protein product that lacks the recognition domain of factor H and exhibits impaired cell surface complement regulation. The fact that the formation of this hybrid gene arose as a de novo event suggests that this cluster is a dynamic area of the genome in which additional genomic di...

Research paper thumbnail of Case Report: Benefits and Challenges of Long-term Eculizumab in Atypical Hemolytic Uremic Syndrome

Pediatrics, 2015

Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, le... more Atypical hemolytic uremic syndrome (aHUS) is caused by dysregulation of the complement system, leading to complement overactivation. A humanized anti-C5 monoclonal antibody, eculizumab, has been available for the treatment of aHUS since 2011. The long-term safety and efficacy of this novel drug in the pediatric population remain under review. We present a child with a hybrid CFH/CFHR3 gene who, having had multiple disease relapses despite optimal treatment with plasma exchange, commenced eculizumab therapy in August 2010. She remains relapse free in follow-up at 52 months, and treatment has been well tolerated. The risk of meningococcal disease during this treatment is recognized. Despite vaccination against meningococcal disease and appropriate antibiotic prophylaxis, our patient developed meningococcal bacteremia 30 months into treatment. She presented with nonspecific symptoms but recovered without sequelae with appropriate treatment. We recommend that children be vaccinated agai...

Research paper thumbnail of Migration of Tenckhoff Catheter into an Occult Inguinal Hernia

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis

Research paper thumbnail of HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

Journal of the American Society of Nephrology : JASN, Jan 27, 2014

Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome i... more Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ≤589 c...

Research paper thumbnail of Seizures following renal transplantation in childhood

Pediatric Nephrology, 1999

Few studies have investigated the incidence of seizures following renal transplantation in childh... more Few studies have investigated the incidence of seizures following renal transplantation in childhood. The aim of this study was to determine this incidence and to identify risk factors. Retrospective casenote analysis was carried out on 119 transplants performed in 109 children over 10 years. Twenty-one transplants (in 20 children) were complicated by seizures, the majority of which occurred in the first 55 days after transplantation. Seizures were more common in the 5-to 10-year-old age group (P=0.03), but were no more common in those with a prior history of seizure (P=0.69). Their aetiology was predominantly multifactorial; hypertension (n=15), fever/infection (n=4) and acute allograft rejection (n=6) were commonly identified risk factors; 2 were secondary to intracerebral pathology. Most seizures were short lived, required minimal therapy and had a good long-term neurological outcome. In conclusion, seizures are relatively common following paediatric renal transplantation. Parents are now routinely counselled of this risk.