John C. Lieske, M.D.

The purpose of this study is to evaluate DCR-PHXC in patients with primary hyperoxaluria type 1 (PH1) or type 2 (PH2) and severe renal impairment, with or without dialysis.

This study is being done to obtain samples from patients with primary hyperoxaluria, cystinuria, adenine phosphoribosyl transferase (APRT) deficiency, and Dent disease, and from their family members, for use in future research.

This is a global, prospective, observational, longitudinal study designed to characterize the long-term safety of lumasiran in PH1 patients in the real-world setting. The data collected in this
study will also be utilized to further characterize the natural history and real-world clinical management of patients diagnosed with PH1, as well as the long-term effectiveness of lumasiran. Patients will be managed and treated per routine clinical practice. This protocol does not recommend the use of any specific treatments, visits, or procedures. No medication is provided as part of study participation.

Patients are expected to contribute data for the duration of the study or until study discontinuation (e.g., due to death, withdrawal of consent, loss to follow-up, study termination, enrollment in a clinical trial with an investigational treatment during the study). Study data will be collected at the time of a routine clinical encounter, or by referencing the medical record, and entered into the electronic data capture (EDC) at least once every 12 months using electronic case report forms (eCRFs). If patients attend more than 1 visit per year, sites can enter multiple follow-up visits. In addition to the prospective data collection, a chart review of up to 5 years relative to the time of enrollment in the study will be conducted to collect retrospective data, where available. In cases where diagnosis was more than 5 years prior to enrollment data will also be collected at the time of diagnosis, if available.

We hypothesize that clinical studies to investigate the role of individual proteins in kidney stone pathogenesis have likely been confounded by an unknown variety of underlying renal pathologies. Therefore, we propose to examine urinary protein crystallization inhibitors in patient populations that have been carefully phenotyped relative to renal stone precursor lesions by direct endoscopic visualization. In collaboration with Project #1, our second major goal is to use these accurately phenotyped patients in order to adapt modern dual-energy CT technology to develop a reliable noninvasive technique to accurately and noninvasively determine stone composition and visualize the earliest kidney stone precursor lesions. Our long-term goal is to improve CT technology so that it can be used to allow large-scale clinical protocols of accurately phenotyped, hence, homogeneous, patient populations.

In a subset we will sample sterile stone, dental plaque, blood and urine samples for detailed microbiome analysis in order to determine the contribution of micro organisms to stone pathogensis.

The purposee of this study is to identify patients with biopsy-proven renal diseases that might have antibodies directed against kidney-antigens, or other circulating biomarkers, that contribute to disease pathogenesis including, but not limited to: amyloidosis, acute tubular necrosis, diabetic nephropathy, focal segmental glomerular sclerosis, IgA nephropathy, interstitial nephritis, membranous nephropathy, minimal change disease, immunoglobulin- and complement-mediated glomerular disease, and ANCA vasculitis.  Serum (up to 10 ml) will be obtained within two weeks of renal biopsy either as waste from the Mayo Clinic Rochester Central Clinical Laboratory or a referring laboratory, or if stored serum is not available from a prospective blood draw after patient consent.  The serum will be biobanked in the Clinical Specialty Laboratory for current and future test development and/or research studies.

The purpose of this study is to determine the natural history of the hereditary forms of nephrolithiasis and chronic kidney disease (CKD), primary hyperoxaluria (PH), cystinuria, Dent disease and adenine phosphoribosyltransferase deficiency (APRTd) and acquired enteric hyperoxaluria (EH). The investigator will measure blood and urinary markers of inflammation and determine relationship to the disease course. Cross-comparisons among the disorders will allow us to better evaluate mechanisms of renal dysfunction in these disorders.

The purpose of this study is to collect medical information from a large number of patients in many areas of the world with primary hyperoxaluria (PH), Dent disease, Cystinuria and APRT deficiency. This information will create a registry that will help us to compare similarities and differences in patients and their symptoms. The more patients we are able to enter into the registry, the more we will be able to understand the Primary Hyperoxalurias,Dent disease, cystinuria and APRT and learn better ways of caring for patients with these diseases.

The purpose of this study is to obtain sufficient fresh kidney tissue from patients with history of kidney stones or without a history of kidney stones to perform assay transposase accessible chromatin (ATAC), cellular indexing of transcriptomes and epitomes (CITE), and RNA expression and protein (REAP) sequencing studies on fresh, snap frozen versus paraffin embedded samples.  Differential expression of renal interstitial cells, genes and encoded proteins will be confirmed by flow cytometry, qPCR, and immunofluorescence/immunohistochemistry respectively.  In addition, random urine and plasma/serum will be biobanked for biomarker studies to correlate with findings in the kidney tissue.

The primary objective of Part 1 of this study (healthy volunteers) is to evaluate the safety and tolerability of SYNB8802.  The primary objective of Part 2 of this study (patients with Enteric Hyperoxaluria) is to assess the effect of SYNB8802 on UOx amount excreted.

The objective of this study is to collect data on stone formation and the degree of nephrocalcinosis in patients (≥ 2 years of age) with genetically confirmed PH3 and relatively intact renal function and to explore the potential relationship between Uox and new stone formation.

This is a natural history study of adults, adolescents, and children (≥ 2 years of age) with genetically confirmed primary hyperoxaluria type 3 (PH3) who have a history of stone events during the last 3 years and/or the presence of pre-existing stones detected by renal ultrasound at Screening.

The relationship between the level of Uox and the incidence of kidney stones and/or nephrocalcinosis in patients with PH3 has not been established. The goal of this study is to record 24-hour Uox levels and the incidence of new stone formation and/or the degree of nephrocalcinosis in patients with PH3 over time.

This study aims to evaluate the safety and tolerability of a single dose of DCR-PHXC in patients with PH3 and to characterize the plasma PK of a single dose of DCR-PHXC in patients with PH3. It also aims to assess the efficacy of a single dose of DCR-PHXC in reducing oxalate burden in patients with PH3. 

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ALN-GO1 in healthy adult volunteers and subjects with PH1.

Evaluate the safety, tolerability, and efficacy of 28 days of treatment with ALLN-177 for reducing urinary oxalate excretion in patients with secondary hyperoxaluria and kidney stones.

The purpose of this study is to evaluate the safety, tolerability, and effectiveness of different doses of ALLN 177 for reducing urinary oxalate excretion in patients with secondary hyperoxaluria and recurrent kidney stones.

This study will evaluate the efficacy and safety of OC5 in patients with PH.

The purpose of this study is to evaluate the safety and effectiveness of oral administration of the oxalate metabolizing enzyme Oxazyme (OC4) to degrade food-borne oxalate and prevent its absorption from the gastrointestinal tract. In addition, by reducing oxalate concentrations in the gastrointestinal fluid, oxalate secretion from blood to the intestinal tract may be increased. Both effects would decrease blood levels of oxalate, and therefore decrease oxalate excretion in the urine.

The purpose of this study is to assess the acceptability and accuracy of the smart phone food record App ‘HealthWatch 360’ in collecting food intake data from subjects. The nutritional analysis obtained will be compared with that of a 24 hour recall to assess accuracy.

The purpose of this study is to evaluate the long-term effectiveness and safety of DCR-PHXC in children and adults with Primary Hyperoxaluria Type 1 (PH1) and Primary Hyperoxaluria Type 2 (PH2) that have completed a previous DCR-PHXC clinical trial.

The purpose of this study is to assess the burden that patients and their caregivers face to due primary hyperoxaluria (PH).

To characterize the microbiome in 4 groups of subjects (primary hyperoxaluria type I (PH1), idiopathic CaOx stone, enteric hyperoxaluria (EH) and healthy participants) by comparing the number of species and diversity of the microbial populations and pathway for oxalate metabolism by paralleling the gene expression of enzymes involved in oxalate degradation by gut bacteria.

The purpose of this study is to determine the effectiveness, durability, and long-term safety of Reloxaliase in patients with Enteric Hyperoxaluria.

The purpose of this study is to determine the efficacy and safety of ALLN-177 in patients with enteric hyperoxaluria.

The purpose of this study is to test specific analytical performance characteristics of the beta trace protein (BTP) assay on the BN ProSpec System to generate performance data necessary for regulatory submission to the U.S. Food and Drug Administration and international regulatory submissions; therefore, data generated is subject to audit by regulatory agencies.

The purpose of this study is to evaluate the effectiveness and safety of Lumasiran in Children and Adults with Primary Hyperoxaluria Type 1 (PH1).

The purpose of this study is to evaluate the effectiveness, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in patients with Advanced Primary Hyperoxaluria Type 1 (PH1).

Primary hyperoxaluria is an inborn error of metabolism that results in marked overproduction of oxalate by the liver. The excess oxalate causes kidney failure and can cause severe systemic disease due to oxalate deposition in multiple body tissues.

Metabolic pathways that lead to oxalate are poorly understood, but recent evidence suggests that hydroxyproline may play a role. Sources of hydroxyproline include the diet and bone turnover. If hydroxyproline can be confirmed as a signficant factor in primary hyperoxaluria, diet modification might be of value in reducing the severity of disease.

This protocol, in which hydroxyproline labelled with a cold isotope is infused intravenously in patients with primary hyperoxaluria, will allow us to measure the amount of oxalate produced from hydroxyproline. The contribution of hydroxyproline metabolism to the amount of oxalate excreted in urine in will be able to be determined for patients with each of the known types of primary hyperoxaluria.

The purpose of the first stage of this study is to evaluate safety, tolerability, and pharmacodynamics of NOV-001 in adult healthy volunteers.  The purpose of the second stage of this study is to evaluate safety, tolerability, and early effectiveness in patients with enteric hyperoxaluria.

The proposed study is designed to evaluate the efficacy, safety, tolerability, and PK of DCR-PHXC versus placebo in patients with PH1 and PH2.

The purpose of this study is to better understand your PH1 condition and how it has affected your body from the time of diagnosis until present. This study is being done for research purposes only.

Evaluate the efficacy and safety of ALLN-177 in reducing plasma and urinary oxalate levels in adult and pediatric patients with enteric hyperoxaluria and hyperoxalemia or primary hyperoxaluria.

The purpose of this trial is to investigate the impact of increased fluid intake and increased urine output on the recurrence rate of urinary stone disease (USD) in adults and children. The primary aim of the trial is to determine whether a multi‐component program of behavioral interventions to increase fluid intake will result in reduced risk of stone disease progression over a 2‐year period.

The purpose of this study is to determine the natural history of the hereditary forms of nephrolithiasis and chronic kidney disease (CKD), primary hyperoxaluria (PH), cystinuria, Dent disease and adenine phosphoribosyltransferase deficiency (APRTd) and acquired enteric hyperoxaluria (EH). The investigator will measure blood and urinary markers of inflammation and determine relationship to the disease course. Cross-comparisons among the disorders will allow us to better evaluate mechanisms of renal dysfunction in these disorders.

The purpose of this study is the diagnostic validation of GFRNMR using a prospective single center study design in the actual daily routine setting of clinical practice.

The purpose of this study is to collect medical information from a large number of patients in many areas of the world with primary hyperoxaluria (PH), Dent disease, Cystinuria and APRT deficiency. This information will create a registry that will help us to compare similarities and differences in patients and their symptoms. The more patients we are able to enter into the registry, the more we will be able to understand the Primary Hyperoxalurias,Dent disease, cystinuria and APRT and learn better ways of caring for patients with these diseases.

Patients with Dent disease have suppressed levels of FGF 23 which contributes to hypercalciuria, kidney stones, nephrocalcinosis and renal failure. Supplementation with phosphorus may reduce hypercalciuria.

This study will help the investigator determine whether certain genetic mutations, more than others, are a cause of more severe disease in Dent Disease.

This study is being done to obtain pathology reports from all patients in the Dent disease registry who have had a kidney biopsy. The investigator will collect the biopsy slides and reports in an attempt to determine if they have any common findings.

In this study the investigators propose to use a daily dose of 45 mg (30 mg at 8 AM and 15 mg at 4 PM). This relatively small well-tolerated dose is likely to persistently increase urine volume and reduce urine supersaturation and to be well tolerated by patients with kidney stone disease and normal renal function. The twice-daily (8 AM and 4 PM) regimen is designed to produce a maximal AVP inhibition on waking with a gradual fall-off of effect during the night. To this end, a higher dose is used in the morning, with a lower dose in the afternoon.