Does Potassium Citrate Affect Metabolism in Kidney Stone Patients?

The study “Impact of Potassium Citrate on Urinary Risk Profile, Glucose and Lipid Metabolism of Kidney Stone Formers in Switzerland” by Anna Wiegand et al. (2020) follows adults in the Swiss Kidney Stone Cohort (SKSC) who had a history or high risk of kidney stones. This overview presents a plain-language summary of the original scientific paper. The authors, Wiegand, Fischer, Seeger, Fuster, Dhayat, Bonny, Ernandez, Kim, Wagner, and Mohebbi, examined how oral potassium citrate affects urinary risk factors for stones, blood sugar, and lipid measures, and whether the active vitamin D hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] relates to urinary citrate levels.

The authors note that urolithiasis (kidney stones) affects about 10% of people in developed countries and is linked with later loss of kidney function and higher cardiovascular risk. Recurrence is common—up to 40% within five years and 75% over 20 years after a first stone event.

They explain that kidney stone formation is driven by high urinary supersaturation with salts such as calcium oxalate and calcium phosphate. In this context, hypercalciuria (high urinary calcium) and hypocitraturia (low urinary citrate) are the most important metabolic risk factors, followed by hyperoxaluria and hyperuricosuria. Citrate is a strong inhibitor of crystallization in urine and reduces stone risk by binding calcium and lowering the amount of free calcium available for crystal formation.

Citrate supplementation (often as potassium citrate) is already used as metaphylaxis (prevention of recurrence) in kidney stone formers (KSFs). It increases urinary citrate and raises urinary pH, which helps prevent uric acid, calcium oxalate, and cystine stones. At the same time, citrate is also a key metabolite in energy pathways. Endogenous citrate supports fat (lipid) production and can slow part of glycolysis (the main glucose breakdown pathway). Because of this role in metabolism, the authors wanted to know if giving citrate as a drug changes blood sugar or lipid markers in humans, especially in KSFs.

They also highlight earlier animal data suggesting that 1,25(OH)2 D3 may increase urinary citrate by reducing citrate oxidation in kidney cells and modulating citrate transport. However, whether blood 1,25(OH)2 D3 levels relate to urinary citrate in human KSFs had not been tested.

This was an observational study using prospectively collected data from the Swiss Kidney Stone Cohort (SKSC). Adults (≥18 years) with recurrent stones or a first stone plus at least one risk factor (such as early onset, family history, non–calcium oxalate stones, gastrointestinal disease, osteoporosis, metabolic syndrome, diabetes, or chronic kidney disease) were included. All participants gave informed consent and were followed at baseline, three months, and yearly.

For this analysis, 428 kidney stone formers were evaluated. Patients were divided into two groups: those treated with potassium citrate (including potassium citrate or potassium citrate/hydrogen carbonate) and those who were not. Only “citrate-naïve” patients (no prior citrate therapy) were included.

Key measurements included:

• Twenty-four-hour urine tests (volume, pH, sodium, potassium, calcium, phosphate, magnesium, citrate, oxalate, uric acid, ammonium)
• Blood tests (fasting glucose, haemoglobin A1c [HbA1c], cholesterol, creatinine, estimated glomerular filtration rate [eGFR], calcium, phosphate, 25-hydroxyvitamin D3 [25(OH)D3], 1,25(OH)2 D3, parathyroid hormone [PTH], serum bicarbonate, and electrolytes)
• Body mass index (BMI)

Hypocitraturia was defined as 24-hour urinary citrate <1.50 mmol, and hypercalciuria, hyperoxaluria, and hyperuricosuria were defined using sex-specific 24-hour thresholds. Statistical comparisons used standard tests (chi-squared, Fisher’s exact test, t-tests, and non-parametric tests), with significance set at P < 0.05.

Out of 428 KSFs, 43 patients (10.0%) received potassium citrate at a mean dose of 3819 ± 1796 mg/day, corresponding to 12.5 ± 5.9 mmol/day. Hypocitraturia was present in 19.3% of patients, but only 14 of the 43 citrate-treated patients (about one-third) actually had hypocitraturia at baseline. The rest were normocitraturic but likely treated for other indications such as hypercalciuria, renal tubular acidosis, chronic diarrheal states, or specific stone types.

As expected, urinary citrate excretion increased significantly in the potassium citrate group, from 2.4 ± 1.3 to 3.3 ± 2.1 mmol/24 h over three months. Urinary potassium and urine pH also rose in this group, showing that patients were taking the medication as prescribed.

Between-group analysis showed that the mean increase in urinary citrate was clearly higher in treated patients (mean change 1.0 ± 1.7 mmol/24 h) compared with untreated patients (0.2 ± 1.3 mmol/24 h). Urinary magnesium also increased more in the potassium citrate group. The authors characterized these findings as a beneficial shift in the urinary risk profile, driven mainly by increases in anti-lithogenic factors such as citrate and magnesium.

Interestingly, urinary calcium excretion did not significantly change after potassium citrate therapy, in contrast to some earlier studies that saw a drop in urinary calcium. The authors suggest that lower PTH levels after therapy and relatively low baseline calcium in some hypocitraturic patients may have limited any further fall in urinary calcium.

Despite citrate’s known roles in energy metabolism, the study found no evidence that oral potassium citrate changed key markers of glucose or lipid metabolism over three months. In treated patients:

• Fasting glucose stayed around 5.5 mmol/L
• HbA1c stayed at 5.5%
• Total cholesterol stayed at 4.5 mmol/L
• BMI stayed around 27.6–27.8 kg/m²

The authors state that “exogenous citrate administration had no effect on cholesterol, fasting glucose, HbA1c and BMI.” Similar stability in these measures was seen in patients who did not receive potassium citrate.

When patients were grouped by urinary citrate status, 78 (19.3%) had hypocitraturia. Hypocitraturic patients had significantly lower serum bicarbonate (25.8 ± 3.2 vs. 26.9 ± 2.6 mmol/L), suggesting a tendency toward renal tubular acidosis or enteric bicarbonate loss. There was also a trend toward more inflammatory bowel disease in hypocitraturic patients, fitting with the idea of enteric bicarbonate loss.

Normocitraturic patients had higher 24-hour urine volume and higher excretion of calcium, potassium, phosphate, sodium, and uric acid compared with hypocitraturic patients, reflecting different metabolic profiles.

The authors tested whether 1,25(OH)2 D3 levels were associated with urinary citrate. They used multiple linear regression models, including 1,25(OH)2 D3 alone and together with eGFR. No significant relationship was found in either model.

This means that, in this cohort of KSFs, higher or lower active vitamin D hormone levels did not predict how much citrate was excreted in urine

Because this is an observational study, it cannot prove cause and effect, but it does provide useful clinical signals directly from patient data. The main practical implications, as described by the authors, are:

• Potassium citrate supplementation clearly improved the urinary stone risk profile by increasing citrate, potassium, and pH, and by boosting anti-lithogenic factors such as citrate and magnesium.
• Over a three-month period, potassium citrate did not worsen fasting glucose, HbA1c, cholesterol, or BMI. The authors reported that, over the three-month observation period, potassium citrate use was not associated with unfavorable changes in the measured glucose or lipid markers.
• Hypocitraturia appears to be linked with lower serum bicarbonate and possible acid-base disturbances, which may hint at underlying renal tubular acidosis or gastrointestinal bicarbonate loss.
• 1,25(OH)2 D3 did not show an anti-lithogenic effect on urinary risk profile in this cohort, since it was not associated with urinary citrate excretion.

The researchers also point out several limitations, including the relatively short three-month follow-up window, non-standardized indications and doses of potassium citrate (physicians chose them individually), and incomplete information on other medications. They call for future randomized controlled trials with larger sample sizes and more structured interventions to confirm these findings and explore longer-term metabolic effects.

In this study of 428 Swiss kidney stone formers, potassium citrate use was associated with higher urinary citrate, magnesium, potassium, and urine pH, all of which are considered markers of lower stone risk. Over three months, no meaningful changes were observed in fasting glucose, HbA1c, cholesterol, or BMI, and urinary calcium remained stable. The data also showed that hypocitraturia was linked with lower serum bicarbonate, while 1,25(OH)2 D3 levels did not predict urinary citrate excretion. Taken strictly from the findings reported in this paper, potassium citrate use was associated with favorable changes in urinary risk markers without measurable short-term metabolic disruption in this cohort. Longer and controlled studies are needed to evaluate long-term outcomes.