Scientists dig into mysterious kidney scarring

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

* EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS * INCLUSION CRITERIA: ---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. * EXCLUSION CRITERIA: ---None -WHOLE EXOME/GENOME SEQUENCING * ELIGIBLITY FOR WHOLE EXOME/GENOME SEQUENCING: * Subjects with kidney disease * Unexplained kidney disease, family history of kidney disease, or other kidney disease suggestive of a genetic origin, excluding FSGS * Age greater than or equal to 2 years * Subjects without kidney disease * Family member with unexplained kidney disease, family history of kidney disease, or other kidney disease suggestive of a genetic origin, excluding FSGS * Age greater than or equal to 18 years * Able to provide informed consent * RITUXIMAB AND CYCLOSPORINE. (CLOSED FOR SUBJECT RECRUITMENT.) * INCLUSION CRITERIA FOR ADULT PATIENTS PARTICIPATING IN PILOT STUDY OF COMBINATION RITUXIMAB AND CYCLOSPORINE: * 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. * INCLUSION CRITERIA FOR MINORS (BETWEEN AGES 4 AND 18 YEARS): * 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. * EXCLUSION CRITERIA: * Age \< 4 years. * Prior intolerance of rituximab or other monoclonal antibody therapy, including severe infusion reaction or hypersensitivity to murine proteins. * History of cardiac arrhythmias, unless cardiology consult approves the use of rituximab. * Treatment with rituximab within the last two years. * Prior intolerance of cyclosporine. * Subjects with post-adaptive FSGS (including obesity-associated FSGS, reflux nephropathy, reduced nephron mass). There is not a strong rationale for the use of immunologic therapy in this population. * Subjects with genetic FSGS due to a high penetrance mutation, e.g. NPHS2 mutation. There is not a strong rationale for the use of immunologic therapy in this population. * Medication-associated FSGS. * Recurrent FSGS following renal transplant * Chronic viral infection, such as HIV-1, hepatitis B, and hepatitis C. The safety of aggressive immunologic therapy in these diseases is in question. * Chronic bacterial infection. At baseline, if the patient gives a history of BCG vaccination or prior positive PPD, we will consult with an infectious disease clinician before enrolling the patient. * Active malignancy * Poorly controlled hypertension is defined as home BP measurements \>140/90 or controlled blood pressure requiring 4 or more medications. The rationale is that blood pressure elevation is common on cyclosporine therapy. * Women and girls who are pregnant or trying to become pregnant or are unwilling to practice birth control. Rituximab is in pregnancy class C: no systematic evidence of safety. In humans, cyclosporine crosses the placenta. Cyclosporine lacks genotoxic effects in human and animal studies. However, growth restriction and prematurity occur in up to 40% of neonates born to mothers with organ transplants who are treated with cyclosporine, but no congenital abnormalities have been documented. * Women and girls who are breastfeeding (possible immune suppression in infants as well as the unknown effects on growth or association with carcinogenesis.) * Predicted requirement for live vaccines over the 24 months following enrollment. * ANALYSIS OF LIPID-CONTAINING PARTICLES CHARACTERISTICS UNDER NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (NMR-S) AMONG NEPHROTIC SUBJECTS * INCLUSION CRITERIA: * 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. * EXCLUSION CRITERIA: * We will exclude subjects with any of the following: * Diabetes mellitus * Body mass index (BMI) greater than or equal to 40, * Pregnant or breastfeeding women * Untreated or uncontrolled thyroid disorder * Active oncologic condition * Acute infections * Chronic infections including HIV * Subjects receiving lipid lowering medications for secondary prevention (e.g. coronary artery disease, stroke, heart failure) * Subjects receiving estrogen therapy or contraceptive therapy * Subjects receiving cyclosporine, azathioprine or sirolimus * Subjects who are unable to eat the required meals due to allergy, intolerance, or dietary preferences * Subjects with history of pancreatitis * Subjects with reported history of triglycerides \>1000 mg/dl * Subjects unable or unwilling to give their consent