Pathogenesis of Glomerulosclerosis

Inclusion Criteria

• •EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS
• •---An unlimited number of subjects with known or suspected glomerular or tubulointerstitial disease will be eligible for study. No sex, race or ethnic selection will be applied. It is anticipated the African-Americans will predominate, given the increased risk of FSGS (focal segmental glomerulosclerosis) in this population.
• •* First void urine protein to creatinine ratio \> 2g/g despite optimal use of an ACE inhibitor or ARB (or possibly both), last dose increase at least 4 weeks before qualifying proteinuria determination
• •* Women must use reliable birth control method to avoid pregnancy while participating in the study.
• •* Subjects who have failed to respond with a complete remission or partial remission after at least 8 weeks of prednisone at a dose of at least 60 mg or are steroid dependent or relapse off steroids.
• •* Subjects who have compelling contraindications to the use of glucocorticoids, such as morbid obesity, defined as BMI \>35 or diabetes mellitus
• •* Subjects with idiopathic FSGS or collapsing glomerulopathy
• •* Subjects with eGFR greater than or equal to 50 mL/min/1.73 m\^2 at screening or at some time in preceding 6 months.
• •* Estimated average protein to creatinine ratio \>2.0 g/g despite use of an ACE inhibitor or ARB. At least one-first void urine will be obtained and must have a urine protein/creatinine ratio \>2.0 g/g to exclude the diagnosis of orthostatic proteinuria
• •* Girls who are going through puberty and/or have menstrual periods must use reliable birth control method to avoid pregnancy while participating in the study
• •* Failed to respond with a complete remission or partial remission after at least 8 weeks of prednisone at a dose of at least 1 mg/kg or are steroid dependent or relapse off steroids.
• •* Compelling contraindications to the use of glucocorticoids, such as morbid obesity, defined as 99th percentile for age and sex, or diabetes mellitus
• •* Subjects with idiopathic FSGS or collapsing glomerulopathy
• •* Subjects with eGFR greater than or equal to 50 mL/min/1.73 m\^2 at screening or at some time in preceding 6 months.
• •* We will enroll adult subjects (greater than or equal to 18 years of age), male or female, and of all racial backgrounds/ethnicities. In this cohort, we will include subjects with kidney disease or without kidney disease (healthy volunteers). We will start with subjects with preserved glomerular filtration rate (eGFR-Cr greater than or equal to 60 ml/min/1.73m2) but may expand to include individuals with lower GFR in a later study. We will estimate glomerular filtration rate (eGFR) using the 2009 CKD-EPI creatinine equation.
• •* In respect to proteinuria, we will accept both urine protein-to-creatinine ratio (uPCR) or urine protein excretion rate (PER) per 24 hours as a selection criteria. We will divide enrolled subjects in 3 groups as shown below:
• •* Group 1. Subjects with nephrotic range proteinuria (uPCR greater than or equal to 2 g/g or PER greater than or equal to 3 gr/24hs.) and eGFR-Cr greater than or equal to 60 ml/min/1.73m2, regardless of their albumin levels.
• •* Group 2. Subjects with sub-nephrotic range proteinuria (uPCR greater than or equal to 0.2 g/g but \< 2 g/g or PER greater than or equal to 300 mg/24hs. but \< 3 gr/24hs.) and eGFR-Cr greater than or equal to 60 ml/min/1.73m2, regardless of their albumin levels.
• •* Group 3. Volunteers with normal eGFR and normal protein excretion and normal fasting clinical lipid testing.
• •* For those subjects undergoing lipid lowering therapies for primary prevention, including statins, fibrates, niacin, ezetimibe, bile acid resins, fish oil or red yeast rice, we will stop those treatments at least 4 weeks but no more than 6 weeks prior their admission. Lipid lowering therapy will not be stopped for more than 8 weeks. We will not enroll subjects who are receiving statins or other lipid lowering therapies for secondary prevention. Also, we will not enroll subjects with history of triglycerides levels \>1000 mg/dl.
• •* The blood and urine sample collection and brief interruption of statin treatment performed in this pilot study to involve no more than minimal risk to individual subjects, with no prospect of direct benefit to subjects, but likely to yield generalizable knowledge to further society's understanding of the lipoprotein profiles of nephrotic and non-nephrotic subjects.