Potassium Citrate for Medullary Sponge Kidney Stones: Long-Term Study Summary

The study “ Long-Term Treatment with Potassium Citrate and Renal Stones in Medullary Sponge Kidney” by Antonia Fabris et al. (2010) is a retrospective clinical analysis of patients with medullary sponge kidney (MSK) seen at a nephrology clinic in Verona, Italy. The scientific paper looks at how long-term treatment with potassium citrate (KC) affects stone formation and urinary stone risk factors in this group. This summary is a paraphrase and simplification of that scientific paper only; it does not add new data or interpretations beyond what the authors reported. Fabris, Lupo, Bernich, Abaterusso, Marchionna, Nouvenne, Gambaro, and colleagues describe stone rates before and after KC therapy and compare patients with and without standard urinary stone risk factors.

Medullary sponge kidney (MSK) is a kidney malformation where the inner parts of the kidney (the medulla and papillae) have cystic changes and a “sponge-like” structure. It is typically associated with nephrocalcinosis (calcium deposits in the kidney tissue) and recurrent renal calcium stones. The study notes that incomplete and overt distal renal tubular acidosis (dRTA, a disorder of acid secretion in the distal tubule) are reported in 33 to 40% of MSK cases in some studies, although lower rates of overt dRTA have also been found. Hypercalciuria (high urine calcium) is also frequent, reported in 30 to 50% of patients.

The authors explain that incomplete distal renal tubular acidosis (idRTA), hypocitraturia (low urinary citrate), and hypercalciuria likely work together with the structural abnormalities of the Bellini ducts to trigger stone formation in MSK. Patients with MSK often have reduced bone density, as the group had shown in an earlier paper, linking MSK, tubular dysfunction, and bone health.

Clinically, the most common sign of MSK is recurrent calcium oxalate and/or calcium phosphate nephrolithiasis. There is no specific, unique treatment for stones in MSK, so patients are usually managed like other recurrent calcium stone formers. They receive “stone clinic” recommendations, such as high fluid intake and dietary advice, and, because of frequent hypocitraturia and incomplete dRTA, are often advised to take alkali citrate (like potassium citrate). Before this 2010 scientific paper, however, the effect of potassium citrate on stone recurrence specifically in MSK had not been systematically studied.

This scientific paper is a retrospective observational study. The authors reviewed records from 1998 to 2007 at the Verona University Hospital Nephrology Division. During that period, 12% of calcium stone formers were found to have medullary sponge kidney, diagnosed using intravenous urography or uro-CT, based on classic MSK images and by ruling out other causes of nephrocalcinosis. Only patients with at least 1 year of follow-up were included, resulting in 97 participants with MSK.

All patients underwent detailed clinical and laboratory evaluation. The researchers collected information on family history of stones, personal history of kidney stones, urologic procedures, urinary tract infections (UTIs), and symptoms before referral and during follow-up. Standard blood tests (including calcium, phosphate, electrolytes, parathyroid hormone, and creatinine clearance) were performed. Two 24-hour urine collections were done 4–6 weeks apart on a usual diet, measuring volume, pH, sodium, chloride, potassium, citrate, calcium, phosphate, magnesium, uric acid, and oxalate. When available, stones were chemically analyzed.

The authors defined stone risk factors (SRFs) as: hypercalciuria, hyperuricosuria, hypocitraturia, or hyperoxaluria, based on specific 24-hour urine thresholds. Morning urine pH was checked, and blood gas analysis was done in selected patients to rule out overt distal renal tubular acidosis.

Patients were divided into three groups:

• Group A: 65 MSK patients with at least one SRF who received potassium citrate for more than 1 year.
• Group B: 10 MSK patients with SRFs who did not accept or were not compliant with potassium citrate and therefore received only general stone clinic advice.
• Group C: 22 MSK patients without any SRFs, managed only with stone clinic advice.

Potassium citrate treatment followed a structured protocol. A crystal preparation was given in 2–3 daily doses, starting at 20 mEq (about 2 g) of citrate per day. If tolerated and if 24-hour citraturia stayed below 450 mg/24 h, the dose was increased in 10 mEq steps, as long as 24-hour urine pH remained below 7.5. Patients were monitored monthly until the dose was stable and then every 6 months. All groups were advised to follow a balanced diet rich in fruits and vegetables, with about 1 g/kg protein, 1 g calcium, and less than 6 g sodium chloride per day, and to increase fluid intake.

Stone episodes, urinary tract infections, and urologic procedures were counted for the period before treatment and during follow-up. A stone episode was defined as the passage of a stone or its surgical extraction or fragmentation.

At baseline, all patients in groups A and B had hypercalciuria, and most had hypocitraturia (83% in group A and 80% in group B). Group C patients had much lower baseline calcium excretion and higher citrate excretion, and many had never formed stones or had only occasional episodes.

In group A, potassium citrate treatment averaged 29 ± 8 mEq (about 2.9 ± 0.8 g) citrate per day and was generally well tolerated. After at least 12 months of therapy, group A showed:

• About a 50% decrease in calciuria (urinary calcium)
• About a 75% increase in citraturia (urinary citrate)
• An increase in urinary potassium
• A rise in urine pH (from 6.44 ± 0.33 to 6.91 ± 0.52)

The authors note that “KC therapy led to a 50% decrease in calciuria and a rise in citrate (75%) and potassium.” Diuresis increased by almost 200 mL/day, and sodium excretion decreased by about 17%, suggesting good adherence to both KC and diet and fluid recommendations. In groups B and C, who did not receive KC, there was still an increase in urine volume (about 300 mL/day) and a modest reduction in urinary sodium, reflecting compliance with general advice, but no major change in citrate or calcium, like in group A.

A key finding is the change in stone event rates. Before the use of potassium citrate, group A patients experienced an average of 0.58 stones per year per patient. During long-term potassium citrate treatment, this rate decreased to 0.10 stones per year per patient, as reported by the authors. The authors described this change as a substantial reduction in observed stone events within this cohort.

Group B, which had SRFs but did not take KC, had a more modest and not statistically significant change in stone rates under the stone clinic regimen alone. Group C, without SRFs, started with a very low stone rate (around 0.01 stones per year per patient) and remained low over follow-up.

The number of urinary tract infections and the need for extracorporeal shock wave lithotripsy (ESWL, a procedure to break stones) also decreased in group A during follow-up. No ESWL was needed in group A after KC was started, whereas ESWL had been required before treatment in a small percentage of MSK patients.

By comparing groups with and without SRFs, the authors identified two apparent clinical patterns in MSK:

• A “typical” MSK form with SRFs, many small recurrent stones, higher stone rates (before treatment), frequent hypercalciuria and hypocitraturia, and reduced bone density.
• An “indolent” MSK form without SRFs, with few or no stones, low stone recurrence, normal bone density, and diagnosis often made because of hematuria, vague loin pain, burning sensation, or incidental ultrasound findings.

The authors conclude that “two clinical phenotypes among patients showing typical MSK features during radiologic study exist” and that treatment with potassium citrate, together with standard stone clinic measures, is effective in preventing renal stones in the typical MSK patient with SRFs. They also discuss a possible link between incomplete distal renal tubular acidosis, bone mineralization problems, hypercalciuria, and stone formation, but they note that their study is retrospective and cannot fully prove causal pathways

Within the limits of a retrospective, nonrandomized study, this scientific paper suggests that long-term potassium citrate use is associated with favorable changes in urine chemistry and lower observed stone event rates in patients with medullary sponge kidney who have urinary stone risk factors. In these patients, potassium citrate use coincided with higher urinary citrate, lower urinary calcium, increased urine pH, and fewer reported stone episodes over extended follow-up.

At the same time, the data show that there is a subset of MSK patients without clear urinary stone risk factors who may have a mild or almost silent course, with very low stone rates and normal bone density. For this group, the authors did not use potassium citrate routinely and did not see frequent recurrences over long follow-up.

The authors also acknowledge important limitations: the retrospective design, lack of randomization, small size of the non-KC group, incomplete imaging and bone density data, and the fact that they could not fully separate the effects of potassium citrate from those of the dietary and fluid regimen. They point out that kidney, ureter, and bladder (KUB) x-rays and ultrasound are not very sensitive for small stones, so some stone events might not have been captured by imaging alone. Even with these limitations, the consistent drop in calciuria, rise in citrate, and marked fall in stone rates with KC suggest a real treatment effect in typical MSK with SRFs, as described directly in the scientific paper.

In this 2010 clinical study of 97 individuals with medullary sponge kidney, long-term potassium citrate use combined with a standard diet and fluid guidance was associated with fewer recurrent calcium stone events in patients who had urinary stone risk factors such as hypercalciuria and hypocitraturia. The intervention was linked with changes in urine chemistry, including lower calcium excretion, higher citrate levels, and increased urine pH, and was generally well tolerated during extended follow-up. The study also highlights that some patients with medullary sponge kidney and no identifiable stone risk factors experienced very low stone rates and normal bone density, consistent with a milder clinical pattern. All statements above reflect findings reported by Fabris et al. without adding new interpretations.