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Papers by Charles Pickles

Journal of Cognitive Psychotherapy, Nov 1, 2009

Clinical Pediatrics, Sep 29, 2017

Pediatric Nephrology, May 20, 2023

Aims Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investig... more Aims Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investigated for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN). It is a dual acting, highly selective antagonist of both the endothelin A receptor (ET A R) and the angiotensin II subtype 1 receptor (AT 1 R). The Phase 2 EPPIK study will examine the long-term antiproteinuric and nephroprotective potential and safety of sparsentan in pediatric patients with FSGS, minimal change disease (MCD), IgAN, IgA vasculitis (IgAV), and Alport syndrome (AS). Methods The global, open-label, single-arm, multicenter study will evaluate the safety, efficacy, and pharmacokinetics (PK) of sparsentan in~57 patients (aged 1 to <18 years), including 30 with FSGS and/or MCD (population 1) and~27 with IgAN, IgAV, or AS (population 2) over 108 weeks (figure 1). See table 1 for inclusion/exclusion criteria. Sparsentan will be administered in a novel liquid formulation at a dose adjusted to body weight. Results Primary endpoints include safety (incidence of treatment-emergent adverse events) and efficacy (change in urine protein/creatinine ratio [UP/C] from baseline over 108 weeks) with sparsentan treatment. Secondary endpoints include PK outcomes, change from baseline over 108 weeks in albumin/ creatinine ratio and estimated glomerular filtration rate (eGFR), and the proportion of patients with FSGS/MCD who achieve partial remission (defined as UP/C £1.5 g/g and >40% reduction in UP/C).

American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Mar 1, 2022

Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial co... more Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial compartment producing a distinct set of clinical phenotypes. Primary focal segmental glomerulosclerosis (FSGS), for instance, is characterized by glomerular scarring with proteinuria and hypertension while nephronophthisis (NPHP) is associated with interstitial fibrosis and tubular atrophy, salt wasting, and low- to normal blood pressure. For both diseases, an expanding number of non-overlapping genes with roles in glomerular filtration or primary cilium homeostasis, respectively, have been identified. TTC21B, encoding IFT139, however has been associated with disorders of both the glomerular and tubulointerstitial compartment, and linked with defective podocyte cytoskeleton and ciliary transport, respectively. Starting from a case report of extreme early-onset hypertension, proteinuria, and progressive kidney disease, as well as data from the Genomics England 100,000 Genomes Project, we illustrate here the difficulties in assigning this mixed phenotype to the correct genetic diagnosis. Careful literature review supports the notion that biallelic, often hypomorph, missense variants in TTC21B are commonly associated with early-onset hypertension and histological features of both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension might shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.

Pediatric Nephrology, Aug 7, 2015

Background Early management of congenital nephrotic syndrome invariably includes the frequent adm... more Background Early management of congenital nephrotic syndrome invariably includes the frequent administration of intravenous human albumin solution. The safety and feasibility of intravenous administration of albumin in the patients' home setting has not previously been reported. Case-Diagnosis/Treatment We report a series of seven paediatric patients whose parents were trained in the administration of albumin via a central venous catheter at home, with the aim of minimising hospital admission or attendances. We describe the clinical course of these patients and complication rates ascribed to this strategy. Conclusions Our results demonstrate that home albumin infusion can be performed safely.

Nephrology Dialysis Transplantation, May 1, 2022

Case reports in pediatrics, 2016

Linear IgA disease of childhood (LAD) also known as chronic bullous disease of childhood is an au... more Linear IgA disease of childhood (LAD) also known as chronic bullous disease of childhood is an autoimmune disease with IgA deposition at the basement membrane zone leading to a vesiculobullous rash. It has a clinical appearance which frequently is described as resembling "strings of pearls" or rosette-like. Diagnosis is usually clinical but sometimes biopsy is required. Dapsone is widely considered to be the first line therapy in the treatment of LAD. A 5-year-old girl presented with 4-day history of a widespread painful rash and pyrexia. The rash transformed into painful blisters. A recent contact with chickenpox was present. She remained apyrexial but hemodynamically stable and was treated as chickenpox patient with secondary infection. Due to persistent symptoms after repeated attendance she was reviewed by Dermatology team and diagnosed with linear IgA disease also known as chronic bullous disease of childhood. This was based on the presence of blistering rash with ros...

Journal of Cognitive Psychotherapy, Nov 1, 2009

Clinical Pediatrics, Sep 29, 2017

Pediatric Nephrology, May 20, 2023

Aims Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investig... more Aims Sparsentan is a novel Dual Endothelin Angiotensin Receptor Antagonist (DEARA) being investigated for focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN). It is a dual acting, highly selective antagonist of both the endothelin A receptor (ET A R) and the angiotensin II subtype 1 receptor (AT 1 R). The Phase 2 EPPIK study will examine the long-term antiproteinuric and nephroprotective potential and safety of sparsentan in pediatric patients with FSGS, minimal change disease (MCD), IgAN, IgA vasculitis (IgAV), and Alport syndrome (AS). Methods The global, open-label, single-arm, multicenter study will evaluate the safety, efficacy, and pharmacokinetics (PK) of sparsentan in~57 patients (aged 1 to <18 years), including 30 with FSGS and/or MCD (population 1) and~27 with IgAN, IgAV, or AS (population 2) over 108 weeks (figure 1). See table 1 for inclusion/exclusion criteria. Sparsentan will be administered in a novel liquid formulation at a dose adjusted to body weight. Results Primary endpoints include safety (incidence of treatment-emergent adverse events) and efficacy (change in urine protein/creatinine ratio [UP/C] from baseline over 108 weeks) with sparsentan treatment. Secondary endpoints include PK outcomes, change from baseline over 108 weeks in albumin/ creatinine ratio and estimated glomerular filtration rate (eGFR), and the proportion of patients with FSGS/MCD who achieve partial remission (defined as UP/C £1.5 g/g and >40% reduction in UP/C).

American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Mar 1, 2022

Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial co... more Monogenic disorders of the kidney typically affect either the glomerular or tubulointerstitial compartment producing a distinct set of clinical phenotypes. Primary focal segmental glomerulosclerosis (FSGS), for instance, is characterized by glomerular scarring with proteinuria and hypertension while nephronophthisis (NPHP) is associated with interstitial fibrosis and tubular atrophy, salt wasting, and low- to normal blood pressure. For both diseases, an expanding number of non-overlapping genes with roles in glomerular filtration or primary cilium homeostasis, respectively, have been identified. TTC21B, encoding IFT139, however has been associated with disorders of both the glomerular and tubulointerstitial compartment, and linked with defective podocyte cytoskeleton and ciliary transport, respectively. Starting from a case report of extreme early-onset hypertension, proteinuria, and progressive kidney disease, as well as data from the Genomics England 100,000 Genomes Project, we illustrate here the difficulties in assigning this mixed phenotype to the correct genetic diagnosis. Careful literature review supports the notion that biallelic, often hypomorph, missense variants in TTC21B are commonly associated with early-onset hypertension and histological features of both FSGS and NPHP. Increased clinical recognition of this mixed glomerular and tubulointerstitial disease with often mild or absent features of a typical ciliopathy as well as inclusion of TTC21B on gene panels for early-onset arterial hypertension might shorten the diagnostic odyssey for patients affected by this rare tubuloglomerular kidney disease.

Pediatric Nephrology, Aug 7, 2015

Background Early management of congenital nephrotic syndrome invariably includes the frequent adm... more Background Early management of congenital nephrotic syndrome invariably includes the frequent administration of intravenous human albumin solution. The safety and feasibility of intravenous administration of albumin in the patients' home setting has not previously been reported. Case-Diagnosis/Treatment We report a series of seven paediatric patients whose parents were trained in the administration of albumin via a central venous catheter at home, with the aim of minimising hospital admission or attendances. We describe the clinical course of these patients and complication rates ascribed to this strategy. Conclusions Our results demonstrate that home albumin infusion can be performed safely.

Nephrology Dialysis Transplantation, May 1, 2022

Case reports in pediatrics, 2016

Linear IgA disease of childhood (LAD) also known as chronic bullous disease of childhood is an au... more Linear IgA disease of childhood (LAD) also known as chronic bullous disease of childhood is an autoimmune disease with IgA deposition at the basement membrane zone leading to a vesiculobullous rash. It has a clinical appearance which frequently is described as resembling "strings of pearls" or rosette-like. Diagnosis is usually clinical but sometimes biopsy is required. Dapsone is widely considered to be the first line therapy in the treatment of LAD. A 5-year-old girl presented with 4-day history of a widespread painful rash and pyrexia. The rash transformed into painful blisters. A recent contact with chickenpox was present. She remained apyrexial but hemodynamically stable and was treated as chickenpox patient with secondary infection. Due to persistent symptoms after repeated attendance she was reviewed by Dermatology team and diagnosed with linear IgA disease also known as chronic bullous disease of childhood. This was based on the presence of blistering rash with ros...