Treatments: Renal Leak (Renal Calcium Leak)

Treatment of renal leak aims to reduce the calcium lost into the urine and lower the risk of kidney stones, starting with fluids and diet and adding a thiazide medicine when needed.

The goal of treatment

In renal leak, the kidney tubules let too much calcium escape into the urine (hypercalciuria), which raises the risk of calcium kidney stones. Treatment is aimed at correcting that leak: reducing the amount of calcium in the urine and, with it, the chance of forming new stones. Because the parathyroid glands in renal leak are reacting to the calcium loss rather than causing it, treatment focuses on the kidney, not on the parathyroid glands.

The usual approach has two layers. Diet and fluid measures form the foundation, and a class of medicines called thiazide diuretics is added on top of that foundation when urine calcium stays high.

The foundation: fluids and diet

Diet and fluid measures come first and remain in place even when medicine is added. The main themes are plenty of fluid, less salt, less animal protein, and a normal (not low) amount of calcium.

• Fluids. Drinking enough to make dilute urine is one of the most important stone-prevention measures. The aim commonly cited is a urine output of at least about 2.5 liters a day, which for many people means drinking more than about 3.5 liters a day.

• Salt (sodium). Salt is a key factor in renal leak. When the kidney gets rid of extra sodium, it carries calcium out with it, so a high-salt diet makes the calcium leak worse. Roughly, every gram less of sodium per day lowers urine calcium by about 5 to 6 mg per day. Cutting salt also makes thiazide medicines work better.

• Calcium. It may seem logical to eat less calcium, but low-calcium diets backfire. They pull calcium out of the bones and let the intestine absorb more oxalate, which raises the risk of calcium oxalate stones. A normal calcium intake of about 1,000 to 1,200 mg a day is the usual target.

• Animal protein. A diet heavy in meat and other animal protein adds an acid load that draws calcium from bone and reduces the kidney's ability to hold on to calcium, so it raises urine calcium. Limiting animal protein helps.

After these changes have had time to work, a repeat 24-hour urine calcium test shows whether urine calcium has come down. If it is still high, medicine is usually the next step.

Thiazide medicines

Thiazide diuretics are the cornerstone medicine for renal leak. Although they are "water pills," they have a useful side effect in the kidney: they make the kidney tubules reabsorb more calcium, and the mild fluid loss they cause makes the kidney hold on to even more. In effect, they plug the leak.

Thiazides can cut urine calcium by up to about half. In randomized trials they reduced kidney stone recurrence by roughly 30 percent. Three well-known trials, using hydrochlorothiazide, chlorthalidone, and indapamide, each showed fewer new stones than placebo over about three years, and a combined analysis of the studies confirmed a reduction in stones per person per year. The effect depends on the dose, so the dose is often adjusted to bring the 24-hour urine calcium down to normal. Longer-acting versions (chlorthalidone and indapamide) can be taken once a day.

Thiazides are generally used for people who keep forming stones and have high urine calcium. They work poorly when salt intake stays high, because dietary sodium cancels out much of their effect.

Side effects

Thiazides can cause low potassium, low sodium, a higher blood calcium, higher uric acid, and changes in blood sugar and cholesterol, so blood tests are usually checked during treatment. Low potassium matters for stones in particular, because it lowers the amount of citrate in the urine, and citrate is a natural stone inhibitor.

A rise in blood calcium on a thiazide deserves attention in the context of a parathyroid evaluation. In renal leak, the medicine corrects the leak and the parathyroid hormone (PTH) level tends to fall. If the blood calcium climbs instead, it can point to primary hyperparathyroidism that was hidden by normal-looking blood calcium. This is why a supervised thiazide trial is sometimes used as part of the hyperparathyroidism workup.

The NOSTONE study

A large recent trial, called NOSTONE, gave 416 people with recurrent calcium stones either hydrochlorothiazide (at 12.5, 25, or 50 mg a day) or a placebo for about three years. The medicine lowered urine calcium as expected, but it did not significantly reduce stone recurrence, and higher doses did not do better.

That result may not apply fully to renal leak. The trial included many people who did not have high urine calcium, people with different kinds of stones, relatively low doses, and a short-acting once-daily form of the drug. Other studies continue to show fewer stones in carefully selected people with high urine calcium who also limit salt. Thiazides therefore remain a standard treatment, with the benefit depending on choosing the right people, using an adequate dose, and keeping salt intake down.

Potassium citrate

Potassium citrate is often added to a thiazide. It does two jobs:

• It replaces the potassium a thiazide can wash out, which restores the urine citrate that helps prevent calcium crystals from forming.

• On its own, it can lower urine calcium (by about 30 percent in one group studied) and raise urine citrate and urine pH, making calcium oxalate stones less likely to form.

Monitoring over time

Treatment is usually followed with repeat 24-hour urine tests and blood tests. These show whether urine calcium has come down, whether potassium and sodium stay in range, and whether blood calcium stays normal. Because high urine calcium and calcium loss can also affect the bones, bone density testing with a DEXA scan is sometimes part of the overall picture.

Key points

• Treatment of renal leak aims to reduce calcium loss into the urine and prevent kidney stones.

• Fluids, less salt, less animal protein, and a normal calcium intake form the foundation.

• Thiazide medicines help the kidney hold on to calcium and are the main medicine used; they work best with a low-salt diet.

• Potassium citrate is often added to replace potassium and raise urine citrate.

• Repeat urine and blood tests track the response, and a rising blood calcium on a thiazide can point toward primary hyperparathyroidism.