* INCLUSION CRITERIA:
Individuals must meet all the following inclusion criteria to be eligible to participate in this study:
1. Prior kidney biopsy demonstrating FSGS, MCD, or MN obtained within 10 years prior to the screening visit.
2. Age \>=18 years weighing more than 50 kg.
3. If the patient is on any immunosuppressive therapy, he/she should be on them for at least 3 months prior to study evaluation and should be on a stable dose for at least 4 weeks before start of trial, with no plans to alter the regimen during 12 weeks of study period, except to stabilize levels and/or for any safety concerns.
4. Subjects will be allowed to continue with standard of care (SOC) non-immunosuppressant antiproteinuric agents to include RAAS inhibitors, mineralocorticoid antagonists (MRA), sodium-glucose co-transporter-2 inhibitors (SGLT2i), non-dihydropyridine calcium channel blockers (NDHP-CCBs), Sparsentan, and glucagon-like peptide-1 (GLP-1) receptor agonists, in addition to other SOC adjuvant therapies such as diuretics, if they are able to maintain a stable dose throughout the trial. Subjects and their primary nephrologists will be encouraged to optimize their SOC treatments as much as possible prior to trial commencement. Subjects must be on a stable dose for at least 4 weeks before start of trial. Subjects should attempt to keep stable doses of both immunosuppressants and anti-proteinuric drugs throughout trial duration, to avoid confounding effects. Patients not receiving any of these SOC agents either due to allergy or intolerance will still be eligible.
5. Subjects must have a spot random urine PCR of \>=2 g/g on each of 3 measurements collected on at least 2 separate days during screening and baseline period plus a 24-hr urine protein collection of \>=2 g/day. The rationale for using this degree of proteinuria is that proteinuria beyond this threshold value significantly increases the risk of progressive decline of renal functions in the absence of effective therapies to mitigate this risk. Conversely, this threshold value could also allow for the selection of a cohort of patients who are most likely to benefit from ManNAc therapy.
6. Subjects with an estimated glomerular filtration rate (eGFR) \>=30 mL/min/1.73/m\^2 using the race-free CKD-EPI 2021 equation based on creatinine and cystatin-C. The rationale is that below this eGFR threshold, sialic acid, the key metabolite of ManNAc markedly accumulates and may potentially result in systemic toxicity. Prior pharmacokinetic studies have shown that renal elimination of sialic acid is primarily through glomerular filtration, and it is neither reabsorbed nor secreted in the renal tubules. Hence decline in eGFR below 30 mL/min/1.73m\^2 directly correlates with markedly rising blood sialic acid levels, in addition, these subjects may not benefit as much from ManNAc therapy as they have advanced disease pathology, which may be irreversible. Future studies with personalized precision ManNAc dosing may benefit the patient population with eGFR \<30 mL/min/1.73m\^2.
7. Subjects of reproductive potential must be willing to use at least one effective form of birth control throughout the trial period, unless they have had a permanent birth control procedure/intervention including but not limited to hysterectomy, tubal ligation and/or vasectomy. These may include the following: barrier methods (such as condoms), oral or depot injection (for example, Norplant or Depo-Provera) contraception medication, and/or intrauterine devices.
8. Evidence of a personally signed and dated informed consent indicating that the patient has been informed of all pertinent aspects of the study and their willingness to comply with all aspects of the study and their willingness to comply with all aspects of the study protocol, including treatment plan, laboratory tests, baseline and follow-up visits and procedures that include completion of daily diaries to record symptoms and medication intake.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
1. Individuals who are unwilling or unable to provide informed consent.
2. Individuals who, at screening, have unstable nephrotic syndrome based on review of records and clinical assessment by investigators will be excluded.
The rationale for this criterion is that patients presenting with unstable nephrotic syndrome may need to be initiated on various medications including immunosuppressives as well as non-immunosuppressive drugs which can significantly change the level of proteinuria. Additionally, fluid shifts due to diuretic use for treating edema can alter GFR which could confound the pharmacokinetics and pharmacodynamics of the investigational drug.
3. Individuals who acutely require optimization of volume status with intravenous diuretics to control volume overload, as this may result in fluid shifts between the intravascular space and the remainder of extracellular fluid volume. This might alter drug pharmacokinetics and pharmacodynamics as mentioned above in # 2.
4. Individuals with a psychiatric illness or neurological disease that in the judgement of the investigators would interfere with the ability to adhere 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 might interfere with effective communication.
5. Vulnerable individuals, including those with impaired cognitive function or are incarcerated.
6. Individuals whose renal biopsy show evidence of an additional pathology other than FSGS, MCD, and/or MN.
7. Renal biopsy showing interstitial fibrosis and tubular atrophy (IFTA) \>50% per biopsy report.
8. Individuals with uncontrolled hypertension with blood pressures consistently \>140/90 mmHg on 3 or more community clinic blood pressure measurements.
9. Individuals with clinical evidence of any type of active infection including but not limited to HIV, Hepatitis B and/or Hepatitis C or patients who are positive on screening test for HIV including antibody or viral load, HBV surface antigen and/or HCV antibody. If a patient is positive for HCV antibody, then an HCV viral load will be measured to identify subjects with active infection. Additional tests may include those to screen for active CMV, Infectious Mononucleosis (Epstein-Barr Virus), parvovirus B19 and/or COVID-19 infection as per investigator judgement.
10. Individuals with evidence and/or documented history of progressive deterioration of liver functions, including the production of clotting factors, removal of toxic metabolic products, bile excretion for at least 6 months, routine hepatic laboratory indices including but not limited to (AST, ALT, or GGT) greater than 3 times the upper limit of normal, and/or individuals with a documented history and/or diagnosis of chronic liver disease.
11. Individuals with hypertriglyceridemia \>500 mg/dL.
12. Individuals with a documented history of malignancy (identified within the last 5 years and/or on active therapy at time of screening).
13. Individuals with a documented history of Type I or Type II Diabetes Mellitus
14. Individuals with a documented history of any cardiac, connective tissue, and/or hematologic diagnoses that, in the judgment of the investigators, may be associated with FSGS, MCD, and/or MN.
15. Individuals who are currently taking, or who have taken within the last 6 months, medications known or suspected to cause drug-induced podocytopathies, including interferons, lithium, heroin, and anthracyclines, will be excluded at the discretion of the investigators.
16. Individuals who are pregnant, will be breastfeeding or refuse birth control anytime during the study.
17. Individuals who have received treatment with another investigational drug, investigational device, or approved therapy for investigational use less than 60 days prior to planned ManNAc dosing.
18. Individuals with hypersensitivity to ManNAc.
19. Individuals who have been treated with ManNAc, sialic acid, IVIG, and/or other supplements containing sialic acid (e.g., sialyllactose) less than 60 days prior to planned ManNAc dosing.
20. Individuals who received a renal or any other solid organ and/or bone marrow/stem cell transplantation.
21. Individuals who, in the judgment of the investigator, have a condition that places the subject at increased risk for AEs or have any other illness or clinical condition that might confound the results of the study or pose an additional risk in administering study drug to the subject.
22. Patients who need systemic immunosuppressive or glucocorticoid therapy for non-renal indication at any time throughout the trial.
23. Any patient receiving B-cell depleting therapy, monoclonal antibody therapy, cyclophosphamide, and/or plasmapheresis within 6 months of screening.
24. A documented history of active alcohol and/or substance abuse within the past 2 years.
25. Any patient with rapidly progressing glomerulonephritis (RPGN) and/or crescentic glomerulonephritis on renal biopsy.
