NIH Clinical Center logo     America's Clinical Research Hospital File folder iconExplore the NIH
Clinical Center
Search the Studies - NIH Clinical Research Studies

Protocol Details

Pathogenesis of Glomerulosclerosis

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

94-DK-0127

Sponsoring Institute

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 4
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Retrovirus;
PCR;
Renal Failure;
HIV;
Rituximab

Recruitment Keyword(s)

None

Condition(s)

AIDS Associated Nephropathy;
Focal Glomerulosclerosis;
HIV Infections

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Diabetes and Digestive and Kidney Diseases

The present protocol seeks to advance our understanding of glomerular diseases characterized by progressive glomerulosclerosis in the absence of established immune-mediated renal injury. To this end, we will enroll patients with primary podocytopathies (minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy) and diabetic nephropathy, as well as patients with the clinical diagnosis (prior to renal biopsy) with one of these conditions. The protocol has three modules, with two consents and two assents. There is no ceiling on patient recruitment for modules 1 and 2. We want to recruit 16 patients for module 3.

1) EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS: This protocol will serve as a screening protocol for specific treatment protocols. It will also allow us to provide second opinions about selected glomerular diseases, to collect research samples (blood, urine, and archival kidney tissue) and treat selected patients with renal disease using standard therapy. These studies will allow us to test particular hypotheses and may provide the opportunity to generate new hypotheses that could be tested in other protocols.

2) RESEARCH RENAL BIOPSY IN PATIENTS WITH GLOMERULOSCLEROSIS: We will carry out renal biopsy for research purposes (limited to previously-diagnosed collapsing glomerulopathy) or to obtain additional renal tissue for research from a biopsy performed for clinical indications (includes diagnosed or suspected minimal change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, diffuse mesangial sclerosis, and diabetic nephropathy). This tissue will be used for studies of the podocyte transcriptome, and other glomerular and tubular processes, and for studies to identify viral causes of primary podocyte diseases.

3) Obesity-Associated Kidney Disease. We will collaborate with Dr. Mona Khurana in studies of lean and obese young adults carried out at Children s National Medical Center. We will assist her in the measurements of iothalamate and para-aminnohippurate clearance, in order to determine glomerular filtration rate and renal plasma flow.

--Back to Top--

Eligibility

Module 1: EVALUATION AND TREATMENT OF GLOMERULOSCLEROSIS

INCLUSION CRITERIA:

Children of all ages and adults, including pregnant women, and impaired subjects, all with kidney disease. For pathogenetic studies, we will also include healthy volunteers, including children greater than 12 yrs of age and adults.

EXCLUSION CRITERIA:

None

Module 2: RESEARCH RENAL BIOPSY

1) Clinically-indicated renal biopsy, with use of a portion of a second biopsy core for research.

INCLUSION CRITERIA:

All adults or children with past renal biopsy which demonstrated a glomerulosclerotic disease or in all adults or children without prior renal biopsy and clinical suspicion of glomerulosclerotic disease.

EXCLUSION CRITERIA;

Pregnant women.

2) Clinically-indicated renal biopsy, obtaining a third biopsy core for research purposes.

INCLUSION CRITERIA:

All adults with past renal biopsy which demonstrated a glomerulosclerotic disease or in all adult patients without prior renal biopsy and high pre-test likelihood of a glomerulosclerotic disease.

EXCLUSION CRITERIA:

Pregnant women, patients with a single kidney, impaired subjects, and children less than 18 yr.

3) Research renal biopsy, performed largely or exclusively for research purposes.

INCLUSION CRITERIA:

Adults with collapsing glomerulopathy.

EXCLUSION CRITERIA:

Pregnant women, patients with a single kidney, impaired subjects, and children less than 18 yr.

Module 3: RENAL FUNCTION AND STRUCTURE IN LEAN, OVERWEIGHT, AND OBESE YOUNG ADULTS

INCLUSION CRITERIA:

Young adults aged 18 to 21, including lean young adults with BMI less than 25 kg/m2 and obese young adults with BMI greater than 30 kg/m2. Participants with a history of hyperlipidemias or high fasting glucose will still be eligible for the study as these co-morbidities are often consequence of being obese.

EXCLUSION CRITERIA:

Young adults with proteinuria (random urine protein to creatinine ratio greater than 0.2, microalbuminuria (spot urine albumin to cretinine ratio greater than 20 mg/g), creatinine clearance less than 80 mL/min/1.73m2, chronic kidney disease, high blood pressure (systolic blood pressure greater than 140 and diastolic blood pressure greater than 90 on 3 blood pressure readings obtained at least one week apart), diabetes, and pregnant women.

Module 4: PILOT STUDY OF RITUXIMAB AND CYCLOSPORINE

INCLUSION CRITERIA: (Up to 20 patients)

Inclusion criteria for adult patients

-Estimated average proteinuria greater than 3.5 g/d 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.

-Patients 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.

-Patients who have compelling contraindications to the use of glucocorticoids, such as morbid obesity, defined as BMI greater than 35 or diabetes mellitus

-Patients with idiopathic FSGS or collapsing glomerulopathy

-Patients with MDRD 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 greater than to 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 greater than to 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

-Compelling contraindications to the use of glucocorticoids, such as morbid obesity, defined as 99th percentile for age and sex or diabetes mellitus

-Patients with idiopathic FSGS or collapsing glomerulopathy

-Patients with Schwartz eGFR equal to or greater than or equal to50 mL/min/1.73 m2 at screening or at some time in preceding 6 months.

EXCLUSION CRITERIA:

-Age less than 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.

-Prior total lifetime rituximab dose exceeding 1500 mg/m2.

-Prior intolerance of cyclosporine.

-Patients 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.

-Patients with genetic FSGS due to a high penetrance mutation, e.g. NPHS2 mutation. There is not a strong rational 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, defined as home BP measurements greater than140/90 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.


--Back to Top--

Citations:

Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome

The nephropathology in human immunodeficiency virus infection

Histopathological changes in simian immunodeficiency virus infection

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Jeffrey B. Kopp, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10 RM 3N116
10 CENTER DR
BETHESDA MD 20814
(301) 594-3403
jeffreyk@mail.nih.gov

Lilian V. Howard, C.R.N.P.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
BG 10-CRC RM 3-1604
10 CENTER DR
BETHESDA MD 20814
(301) 594-0298
lh357n@nih.gov

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT00001392

--Back to Top--

QUESTIONS?

Contact the Patient Recruitment and Public Liaison Office for:

  • Details on how to participate in a study
  • Details on how to refer a patient to a study

NIH Clinical Studies Information Request


Contact the Office of Communications for:

  • General information about the NIH Clinical Center

www.cc.nih.gov/contact.shtml


Contact the Department Clinical Research Informatics, (DCRI) for:

  • Technical questions about Adobe Acrobat and the PDF format
  • Technical questions about this web server

webmaster@cc.nih.gov