What is the best treatment for non-obstructive kidney stones?

  • Kidney stones are multi-factorial, i.e., unlike a disease like chicken pox, which is caused by a single virus and can thus be prevented or treated easily, there are numerous factors which can lead to kidney stone formation.

    Some of these are genetic, e.g. an inactivating mutation in the gene for the calcium-sensing receptor (CaSR). This can lead to increased calcium excretion and kidney stone formation.

    To keep it simple, take the analogy of a bottle of water to which common salt is being added continuously. If the concentration of salt is low, it will be in a dissolved state. Once the concentration of salt exceeds a limit (supersaturation), it will get crystallized. The same thing can happen at a lower concentration if there are any promoters of crystallization. Also, if the inner surface of bottle is rough (akin to damaged inner lining of kidney), these crystals can get adhered to it. Finally, when the bottle is continuously shaken (similar to regular aerobic exercise), the crystals do not settle at the bottom.

    Applying the above analogy to kidneys, when the urine is concentrated due to higher amount of salt excretion (calcium, oxalate, uric acid, phosphorus and sodium), or lower amount of water excretion (less fluid intake), these salts can get precipitated and form stones. The most common stone composition is calcium oxalate. Uric acid is the second most common component.

    The second factor is the relative influence of promoters (low urine pH, less glycosylated Tamm-Horsfall protein, cell debris, protein aggregates, other crystals etc.) and inhibitors (citrate, potassium, magnesium, bikunin, osteopontin, urinary prothrombin fragment 1, glycosylated Tamm-Horsfall protein, glycosaminoglycans, renal lithostathine etc.). If the promoters are high, salts can crystallize at a lower concentration also. On the other hand, when inhibitors are high, the salts do not crystallize even at a higher concentration.

    An acidic urine pH leads to uric acid crystallization and uric acid stone formation. Patients with metabolic syndrome (obesity, diabetes, hypertension and hypercholesterolemia) excrete a more acid urine. They are more prone for uric acid stone formation. These stones are radiolucent, i.e., not seen on X-rays.

    Many bacteria can produce an enzyme called urease, which breaks the urea in urine into ammonia and carbondioxide. These are finally converted into magnesium ammonium phosphate (struvite or triple phosphate) in an alkaline urine. Struvite can be rapidly growing and lead to large calculi filling the entire kidney. This stone is termed as staghorn calculus, because of its resemblance to the antlers of a stag. Studies are underway to elucidate the role of a very minute group of bacteria called nanobacteria which are commonly found in stones.

    Another important factor (may be the most important) is the damage to the lining layer of kidneys (tubules and urothelium). This injury can occur due to oxidative damage by reactive oxygen species, excessive oxalate excretion, nephrotoxic drugs, lack of vitamin A, etc. This area is a key subject of recent research. Due to not yet understood mechanisms, the crystals from loop of Henle enter the renal tissue and form plaques (Randall’s plaques) underlying the inner lining of kidney (urothelium). When the urothelium overlying the Randall’s plaques get denuded, calcium phosphate crystals get adhered to that exposed area. Over this nidus, calcium oxalate crystals and protein matrix get deposited to form the small attached calculus. This happens at a place called papilla (the place where thousands of small tubes called collecting ducts open into kidney’s calyces). Then layers of various crystals get deposited over time and stone enlarges.

    Any obstruction in urinary tract can lead to urine stagnation and stone formation. Common conditions include enlarged prostate, stricture urethra and pelvi-ureteric junction obstruction. All these conditions are curable with simple Urological interventions.

    As long as the stone is small and attached to papilla, it does not cause much damage. When the stone gets detached and blocks the urine draining pipe called ureter, the patient develops pain and kidney damage can occur (hydroureteronephrosis). Kidney damage can also occur when stones does not get detached but grows into large size by causing local inflammation, infection and blockage (hydroneophrosis).

    From the above explanation, you would have understood that only some of the factors can be controlled by us and a lot of other factors need much more research before we can fully conquer kidney stones.

    How can we prevent stones?

    1. Drink a lot of water and other fluids to keep urine output at least more than 2 liter per day. For this amount of urine excretion you need to drink at least 3-4 liters of fluid. A simple and practical guide is to keep the urine color very light yellow. The darker the urine color, the higher is the salt concentration.
    2. Reduce bad salts like calcium, oxalate, sodium, phosphorus and uric acid. Calcium is rich in dairy products and oxalate is rich in a lot of vegetables like spinach, beetroot, okra, leeks, rhubarb, cabbage etc, tea/coffee, chocolate and nuts. When we combine food containing calcium and oxalate, the excess salts get precipitated as calcium oxalate and get excreted in feces, and not through kidneys. That’s why the traditional teaching of calcium restriction failed to reduce stones. When calcium is restricted it increases oxalate excretion in kidneys, thus increasing stone formation. Moderation (not restriction) in calcium intake is required. Milk products should always be combined with other food intake and not taken in empty stomach.
    3. Reduce salt intake to less than 4 g per day. Yes, it should be less than a teaspoon for the whole day!
    4. Eat a lot of fruits. These are rich in stone inhibitors like potassium, citrate, magnesium, etc and also rich in antioxidants which protect against oxidative kidney damage.
    5. Reduce animal protein intake. Animal proteins have a lot of stone promoting contents. They also increase uric acid excretion.
    6. Do aerobic exercises daily. Sedentary lifestyle damages not only kidneys, but also all vital organs.
    7. Prevent and treat any urinary infection.
    8. Prevent and treat lifestyle diseases like diabetes, hypercholesterolemia and hypertension.

    All of these practices can reduce the formation of a kidney stone. In spite of all these efforts you can still form a stone. Many of the factors causing stones cannot be still found out using currently available technology. However, a complete evaluation including stone analysis, serum calcium, serum uric acid, serum parathyroid hormone, serum bicarbonate, and 24 hour urinary sodium, calcium, phosphorus, uric acid, magnesium, citrate, creatinine and urine pH can rule out common causes of stones. These tests will find out at least one abnormality in 97% of stone-formers.

    There are specific drugs to reduce calcium and uric acid excretion. Stone preventive salts like potassium, magnesium and citrate are available as supplements. Bacteria called Oxalobacter formigenes which degrade oxalate in food are available as capsules. When they colonize the gut, they reduce oxalate excretion.

    In recurrent stone formers, regular ultrasound scanning of urinary tract (KUB region) is a must to pick up and treat new stones early before they damage the kidney. This is a simple test with out any harmful side effects like radiation unlike x-rays and CT scans.

    Finally, whenever you undergo a stone removal procedure, make sure all the stones are removed completely. Residual stones or stone fragments are important causes for stone recurrences. Modern techniques like flexible ureterorenoscopy and laser (Retrograde Intra-Renal Surgery, RIRS) allow complete stone removal from every nook and corner of kidneys.

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