A Phase 1 Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ManNAc in Subjects With Primary Podocyte Diseases

* INCLUSION CRITERIA: 1. Kidney biopsy manifesting MCD, FSGS (including collapsing glomerulopathy) or MN. Prior kidney biopsy is a requirement for inclusion. Kidney biopsy materials will be reviewed by NIH pathology (Dr. Avi Rosenberg, or another member of his team in his absence) to confirm the diagnosis. With regard to FSGS, all histologic variants, including collapsing, tip, cellular, perihilar and NOS will be included; primary, adaptive, and genetic FSGS will be included; viral-associated and drug-associated FSGS will be excluded. The rationale for including multiple primary nephrotic diseases is that the pharmacokinetics is likely to be similar and all these diseases have a need for effective therapy with low toxicity profile. 2. Age \>18 years weighing more than 40 kg of either sex. The rationale for excluding children is that we lack safety data for patients with nephrotic and/or reduced GFR and that we have no evidence for benefit in proteinuric subjects. 3. Subjects must either not be taking immunosuppressive therapy (e.g., prednisone, cyclosporine, tacrolimus or mycophenolate mofetil) or, alternatively, be able to tolerate a stable dose of such a therapy from day -30 to day +31. If medically necessary, immunosuppressive therapy will be adjusted during the study. Subjects who are on renin angiotensin pathway inhibitor therapy will not be asked to discontinue their current regiment and will be included in the study. 4. Weight \>40 kg. Subjects 40-50 kg will only be placed in the low-dose Cohort A. Subjects \>50 kg can be placed in either Cohort A (3,000 mg/day) or Cohort B (6,000 mg/day). The rationale is to adhere to the maximum allowable starting dose of 193.5 mg DEX-M74/kg body weight/day, derived from preclinical animal toxicology studies. 5. Subjects with random void urine protein/creatinine ratio \> 1 g/g. 6. Subjects with an estimated glomerular filtration rate (eGFR) .15 mL/min/1.73 m\^2 will be included. The rationale is that we wish to determine the effect of eGFR on ManNAc and Neu5Ac (sialic acid) metabolism (including plasma PK). We will compare 2 eGFR groups: subjects with stage 4 CKD (eGFR 15-29 mL/min/1.73m\^2), and individuals with stage 1, 2, or 3 CKD (eGFR grearter than or equal to 30 mL/min/1.73m\^2). Therapy for individuals with stage 4 CKD is a particularly compelling unmet need, as many therapies become problematic (e.g. calcineurin inhibitors will further lower GFR and intensification of renin-angiotensin-aldosterone system inhibitors may lower GFR and raise serum potassium levels). eGFR will be assessed using serum creatinine (Cr) and cystatin C (CystC) using the CKD-EPI Cr/CystC equation for adults. 7. Subjects must be able to comply with requirements of the protocol, including blood collection, drug administration, and effective communication with study staff. 8. Heterosexual couples must use at least one effective form of birth control, unless a hysterectomy, tubal ligation, or vasectomy has been performed. These may include the following: barrier methods, oral or an injection (for example, Norplant or Depo-Provera) contraception medication, and intrauterine devices. EXCLUSION CRITERIA: <!-- --> 1. Unwilling or unable to provide informed consent. 2. Subject who requires use of intravenous diuretics to control edema, as this may result in fluid shifts between the intravascular space and the remainder of extracellular fluid volume. Oral diuretics will not be exclusionary, and we reserve the option to use intravenous diuretics during the study if this becomes necessary. 3. Subject has a psychiatric illness or neurological disease that would interfere with the ability to comply with the requirements of this protocol. This includes, but is not limited to, uncontrolled/untreated psychotic depression, bipolar disorder, schizophrenia, substance abuse or dependence, antisocial personality disorder, panic disorder, or behavioral problems, which interfere with effective communication. 4 Vulnerable subjects, including those with impaired cognitive function or are incarcerated will be excluded; 5\. Compromised venous access, such that it would interfere with peripheral intravenous access suitable for taking blood samples. 6\. Subject has a severe disease manifestation that would interfere with the ability to comply with the requirements of this protocol. 7 Subjects with a positive HIV test including antibody or viral load. 8\. Individuals whose blood contains HBV surface antigen or HCV antibody. 9\. Subject has hepatic laboratory parameters (AST, ALT, GGTP) greater than 3 times the upper limit of normal. 10\. Subject is anemic with hematocrit .less than or equal to 30 (for both men and women). 11\. Subject shows evidence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, metabolic (including diabetes mellitus), or gastrointestinal disease, or has a condition that requires immediate surgical intervention. 12\. Subject is pregnant or breastfeeding at any time during the study. 13\. Subject has received treatment with another investigational drug, investigational device, or approved therapy for investigational use less than 60 days prior to ManNAc dosing. 14\. Subject has a hypersensitivity to ManNAc or in the judgment of the investigator, has a condition that places the subject at increased risk for adverse effects. 15\. Subject has been treated with ManNAc, sialic acid, intravenous immunoglobulin (IVIG), and/or other supplements containing sialic acid (e.g., St. John s Wort, sialyllactose) less than 60 days prior to planned ManNAc dosing.