This observational study aims to look at the connections between kidney stones, insulin resistance, and inflammation. The researchers hypothesize that people who form calcium kidney stones and have insulin resistance may have higher levels of inflammation because they have more visceral fat (fat around the abdominal organs).

The study will recruit 20 people who have had calcium kidney stones but don't have diabetes, and 20 healthy people who haven't had kidney stones. All the participants will come to the research center at the University of Chicago Medicine. Participants will have a dual-energy X-ray absorptiometry (DEXA) scan to measure their visceral fat, and give blood and urine samples. The blood will be tested for insulin resistance, inflammatory markers, and other metabolic factors. The urine will be analyzed for substances that increase kidney stone risk.

The main goal is to see if the kidney stone formers with insulin resistance have more visceral fat compared to those without insulin resistance and the healthy participants. The researchers will also compare inflammatory marker levels between groups, and look at how visceral fat, inflammatory markers, insulin resistance, and urine stone risk factors are related.

The findings may help explain how kidney stones are connected to metabolic conditions like diabetes and cardiovascular disease. Researchers hope this information will help identify stone formers at risk early and develop preventive treatments in the future.

Participants will be recruited from the University of Chicago Medicine Kidney Stone Clinic (stone formers) and research participant registries (controls). After providing informed consent, participants will complete the following procedures:

Pre-Study:

1. One week prior, participants will discontinue vitamin C, multivitamins, calcium supplements, and diuretics.
2. One day prior, participants will complete a 24-hour urine collection and food frequency questionnaire at home.

Study Visit:

2. Participants will be admitted to the University of Chicago's Clinical Research Center (CRC) in a fasted state.

3. Three timed (45 minute) urine and blood specimen collections will occur.

4. Three seated blood pressure measurements will be taken.

5. Anthropometric measurements including height, weight, waist and neck circumference will be obtained.

6. A dual-energy X-ray absorptiometry (DEXA) scan will be performed to measure visceral fat content and bone density.

7. A brief clinical history will be obtained, including data on kidney stone episodes, procedures, and current stone burden.

8. Participants will remain fasted until all biological samples have been collected. Water intake will be allowed ad libitum.

Sample Analysis:

Urine:

1.24-hour and timed urine samples will be analyzed for kidney stone risk chemistries including volume, pH, solutes (calcium, oxalate, uric acid, citrate, etc).

2. Urine supersaturations for calcium oxalate, calcium phosphate, and uric acid will be calculated using EQUIL2 software.

3. Urine albumin and creatinine will be measured.

4. Remaining urine will be stored at -80°C for potential future assays.

Blood:

1. Serum glucose will be measured at the CRC laboratory.
2. Serum insulin, C-peptide, glucagon, GLP-1, and inflammatory markers (high-sensitivity CRP [C-reactive protein], IL-6, MMPs [matrix metalloproteinases], TNF-alpha, endotrophin) will be measured at the Diabetes Research and Training Center at the University of Chicago.
3. Other serum chemistries (electrolytes, calcium, creatinine, HbA1c, lipids) will be measured at the clinical laboratory.
4. Remaining serum will be stored at -80°C.

Inclusion Criteria:

• Stone formers:
• Age 18-70
• History of at least one calcium-based kidney stone
• Healthy Controls:
• Age 18-70
• No history of kidney stone or family history of kidney stones

Exclusion Criteria (for both groups):

• History of primarily uric acid
• Cysteine, or struvite stones
• History of diabetes or impaired glucose tolerance
• Previous thiazide use
• Anyone on a medication that cannot be stopped that may affect urine composition
• Previous bariatric surgery or ileostomy
• Primary hyperparathyroidism and elevated serum calcium.

Kidney Stone Former Group:

Age 18-70 years old History of at least one calcium-based kidney stone

Control Group:

Age 18-70 years old No personal history of kidney stones No family history of kidney stones

Exclusion Criteria for Both Groups:

History of primarily uric acid, cysteine, or struvite stones History of diabetes or impaired glucose tolerance Previous thiazide diuretic use Medications that cannot be stopped that may affect urine composition Previous bariatric surgery or ileostomy Primary hyperparathyroidism and elevated serum calcium