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1.  Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design 
BMC Nephrology  2011;12:8.
Background
The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing.
Methods/Design
The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT.
Discussion
This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases
Trial Registration
ClinicalTrials.gov, NCT00814255
doi:10.1186/1471-2369-12-8
PMCID: PMC3045306  PMID: 21310077
2.  Follow-up of phase I trial of adalimumab and rosiglitazone in FSGS: III. Report of the FONT study group 
BMC Nephrology  2010;11:2.
Background
Patients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. Antifibrotic agents may slow or halt this process. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study.
Methods
21 patients -- 12 males and 9 females, age 16.0 ± 7.5 yr, and estimated GFR (GFRe) 121 ± 56 mL/min/1.73 m2 -- received adalimumab (n = 10), 24 mg/m2 every 14 days or rosiglitazone (n = 11), 3 mg/m2 per day for 16 weeks. The change in GFRe per month prior to entry and after completion of the Phase I trial was compared.
Results
19 patients completed the 16-week FONT treatment phase. The observation period pre-FONT was 18.3 ± 10.2 months and 16.1 ± 5.7 months after the study. A similar percentage of patients, 71% and 56%, in the rosiglitazone and adalimumab cohorts, respectively, had stabilization in GFRe, defined as a reduced negative slope of the line plotting GFRe versus time without requiring renal replacement therapy after completion of the FONT treatment period (P = 0.63).
Conclusion
Nearly 50% of patients with resistant FSGS who receive novel antifibrotic agents may have a legacy effect with delayed deterioration in kidney function after completion of therapy. Based on this proof-of-concept preliminary study, we recommend long-term follow-up of patients enrolled in clinical trials to ascertain a more comprehensive assessment of the efficacy of experimental treatments.
doi:10.1186/1471-2369-11-2
PMCID: PMC2823728  PMID: 20113498
3.  Diagnostic yield of renal biopsies: a retrospective single center review 
BMC Nephrology  2009;10:11.
Background
Previous studies have examined the spectrum of diseases identified with a kidney biopsy and the complications of the procedure. However, few studies have examined the utility of the test to clarify the diagnosis and guide treatment of pediatric patients. This retrospective, single-center chart review was performed to test the hypothesis that at least 80% of native kidney biopsies provide clinically valuable information that rationally guides diagnosis and patient management.
Methods
200 biopsies performed between January 1, 2000 and June 30, 2008 were reviewed. A scheme composed of six categories was devised to classify the utility of each kidney biopsy.
Results
196 complete case files were available for review. Twenty-four (12.2%) biopsies did not shed light on the diagnosis and were unhelpful in patient management – 21 biopsies (10.7%) were non-diagnostic and 3 (1.5%) failed to yield enough tissue for examination. The number of unhelpful biopsies did not cluster in any specific disease entity.
Conclusion
Our findings provide guidance to nephrologists about the total risk of a kidney biopsy, including uninformative results, when seeking informed consent for the procedure. The results suggest an appropriate balance has been reached which maximizes the use of kidney biopsies while minimizing the risk of this invasive procedure (word count: 202).
doi:10.1186/1471-2369-10-11
PMCID: PMC2693431  PMID: 19460162
4.  Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome 
BMC Nephrology  2007;8:11.
Background
Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.
Methods
A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation.
Results
13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFRe was 127 ± 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.
Conclusion
IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.
doi:10.1186/1471-2369-8-11
PMCID: PMC1959515  PMID: 17683621
5.  Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-β, and nitrite excretion 
BMC Nephrology  2002;3:2.
Background
Angiotensin converting enzyme inhibitors are routinely prescribed to patients with chronic kidney disease because of their known renoprotective effects. We evaluated the effect of short-term therapy with the angiotensin converting enzyme inhibitor, enalapril, in early Alport syndrome, defined as disease duration less than 10 years and a normal glomerular filtration rate.
Methods
11 children with early Alport syndrome were investigated. Two consecutive early morning urine specimens were collected at the start of the study for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion. Patients were treated with enalapril, ≅ 0.2 mg/kg/day, once a day for 14 days. Two early morning urine specimens were collected on days 13 and 14 of enalapril treatment and two weeks later for measurement of urinary creatinine, total protein, albumin, TGF-β, and nitrite excretion.
Results
Prior to treatment, urinary excretion of transforming growth factor-β and nitrite, the major metabolite of nitric oxide, was within normal limits in all patients. Administration of enalapril for 2 weeks did not alter urinary albumin, transforming growth factor-β, or nitrite excretion.
Conclusion
These findings suggest that early Alport syndrome represents a disease involving exclusively intrinsic glomerular barrier dysfunction. At this stage of the illness, there is no evidence of angiotensin II-mediated proteinuria or increased production of transforming growth factor-β and, therefore, routine treatment with an angiotensin converting enzyme inhibitor may not be warranted.
doi:10.1186/1471-2369-3-2
PMCID: PMC65703  PMID: 11869456
Alport syndrome; angiotensin converting enzyme inhibitors; transforming growth factor-β; urinary nitrite excretion

Results 1-5 (5)