Diagnosis and Management of Stone Disease

Clinical and laboratory manifestations:

Symptomatic urolithiasis classically presents with unilateral flank pain of sudden onset.

The pain is precipitated by the passage of a kidney stone from the renal pelvis to the ureter, and is due to ureteral spasm and can be accompanied by nausea and vomiting. The location of the pain depends on the location of the kidney stone: a stone in the upper ureter may cause pain to radiate anteriorly to the abdomen; whereas, a stone in the lower ureter can cause pain to radiate to the ipsilateral testicle in men or to the ipsilateral labium in women. If the stone is lodged at the ureterovesical junction (UVJ), the patient may experience urinary frequency and urgency. Less commonly, urolithiasis can manifest as gross hematuria without pain.

On physical examination, the patient will be in obvious pain and may constantly adjust position in an unsuccessful attempt to alleviate the discomfort. Ipsilateral CVA tenderness may be present. Signs and symptoms of sepsis can occur in cases of obstruction with infection.

Serum chemistries are usually normal, but leukocytosis may be present due to stress or infection. Although the urinalysis will often reveal hematuria and pyuria (and occasionally crystalluria); the absence of red cells in the urine does not exclude a stone, particularly in cases where a stone causes complete ureteral obstruction.

Imaging

Helical computed tomography scan (HCT) is the preferred radiographic test to confirm or exclude the diagnosis of symptomatic urolithiasis.HCT does not require radiocontrast and can visualize uric acid stones (traditionally considered “radiolucent”). Typically, the HCT will show a ureteral stone or evidence of recent passage (eg, perinephric stranding or hydronephrosis). HCT can detect small stones that may be missed by IVU. Although US has the advantage of avoiding radiation, it can only image the kidney and proximal ureter. Thus, ureteral stones can be missed on US. US may also miss renal stones that are <3 mm in size.

The conventional abdominal x-ray (KUB) is inadequate for diagnosis. KUB can miss a stone in the ureter or kidney (even when radio-opaque), and provides no information on obstruction or recent stone passage. For the evaluation of residual stone fragments in patients who have undergone percutaneous nephrostolithotomy, HCT is more sensitive than KUB (100% versus 46%).

Differential diagnosis

In general, a kidney stone must pass into the ureter to cause pain. Therefore, the isolated presence of a renal stone on radiographic imaging is an inadequate explanation for acute abdominal or flank pain. The differential diagnosis of a patient with suspected renal colic includes musculoskeletal pain, herpes zoster, acute cholecystitis, duodenal ulcer, appendicitis, diverticulitis, pyelonephritis, abdominal aortic aneurysm, gynecologic disease, and ureteral obstruction due to blood clot, sloughed papilla,or ureteral stricture.

Management in the acute setting:

Medical treatment:

Because renal colic is excruciating, analgesia is a primary goal in the acute setting. Randomized controlled trials suggest that parenteral nonsteroidal anti-inflammatory drugs (NSAIDs are as effective as narcotics in treating renal colic. Newer medications that may be effective include antispasmodics, trigger point injection with lidocaine, desmopressin, and NSAIDs combined with nitrates. Medical therapy has also been directed at treating kidney stones or hastening ureteral stone passage. Alkalinization of the urine may dissolve uric acid stones and some experts believe that volume expansion will increase the likelihood of stone passage. Although more trials are needed, alpha-blockers and calcium-channel blockers also may facilitate the passage of ureteral stones.

Surgical treatment:

Larger and more proximal ureteral stones are less likely to pass spontaneously and are more likely to require urologic intervention. Most urologists prefer to wait several days before intervention unless there is evidence for infection, low likelihood of spontaneous passage (eg, size is >6 mm), the presence of an anatomic abnormality that would prevent passage, or unrelenting pain. Infection in the setting of obstruction is a surgical emergency and mandates emergency drainage.

The initial urologic approach may be directed at the relief of obstruction (generally by cystoscopic placement of a ureteral stent) rather than stone removal.

Extracorporeal shock wave lithotripsy (ESWL) is the least invasive option, and is most effective for smaller calcium stones (<1 cm) located in the renal pelvis or proximal ureter. Cystoscopic stone removal by basket extraction or fragmentation is invasive, but effective, and can now be used to remove stones in the proximal ureter or kidney.

Percutaneous nephrostolithotomy is more invasive, but may be necessary for large stone burdens or stones that cannot be removed cystoscopically; this is the gold standard for making a patient stone-free. It is rare that a patient requires open ureterolithotomy or nephrolithotomy.

Clinical and metabolic evaluation:

1. Stone composition

2.History and laboratory testing

3.The metabolic evaluation should include a determination of serum electrolytes, creatinine, calcium, phosphorus, and uric acid. Although usually normal, low serum bicarbonate should prompt consideration of type 1 renal tubular acidosis, which is classically associated with calcium phosphate stones. Intact parathyroid hormone should be measured if the serum calcium is elevated or in the high-normal range, if the serum phosphorus is low, or if the urinary excretion of calcium is elevated.

A urinalysis should be performed as part of the initial evaluation. A urine pH >7 with phosphate crystals suggests calcium phosphate or struvite stones. The presence of  hexagonal cystine crystals is pathognomic for cystinuria.Uric acid or calcium oxalate crystalluria can be seen in normal subjects and is, therefore, less informative.

The cornerstone of the metabolic evaluation is the 24-hour urine collection. The factors that should be measured include total volume, creatinine (to assess the adequacy of collection), calcium, oxalate, citrate, uric acid, sodium, potassium, phosphorus, and pH. The stone-forming patient should wait at least 6 weeks before performing a 24-hour urine collection because individuals frequently alter their dietary habits immediately after an episode of urolithiasis. In addition,2 collections are necessary at baseline because of substantial day-to-day variability in urinary parameters Therefore, the metabolic evaluation may be completely normal. In this case, no intervention is required. However, repeat imaging in one year to assess active stone formation, in conjunction with another 24-hour urine, is warranted in patients who present with severe disease.

Prevention of stone recurrence, (Calcium oxalate urolithiasis)

Dietary advice should be based on the results of the 24-hour urine collection. For example, dietary oxalate restriction or discontinuation of vitamin C supplementation is unnecessary in a calcium oxalate stone former with a low urinary excretion of oxalate. Of note, there is no evidence that dietary calcium restriction alone is helpful in preventing the formation of calcium stones and there is substantial evidence that it may be harmful. Observational data showing an inverse relation between dietary calcium and the risk of incident kidney stones suggests that dietary calcium may bind to oxalate in the gut, thereby limiting intestinal oxalate absorption and subsequent urinary oxalate excretion. Indeed, the inhibitory effect of calcium ingestion on urinary oxalate excretion has been demonstrated in oxalate loading studies. The role of calcium supplements deserves comment because their use is so common

The patient should be instructed on how many additional 8 oz glasses of water to drink each day with the goal of producing over 2 liters of urine daily.

Decreasing purine intake (meat, chicken, and seafood) will reduce the urinary excretion of uric acid. For low urinary citrate, the patient should increase intake of potential alkali (fruits and vegetables) and decrease intake of acid-producing foods such as animal protein.

Drug therapy

Medications are indicated for the stone forming patient whose urinary abnormalities persist despite attempted lifestyle changes. Because the goal of therapy is to prevent the additional formation and growth of calcium oxalate stones, and because an existing calcium stone will not dissolve, the passage of another stone does not necessarily reflect therapeutic failure. As with dietary modification, the 24-hour urine collection is essential to select intervention and to gauge the success or failure of treatment. Thiazide diuretics can lower urinary excretion of calcium by 150 mg/day or more, and treatment with a thiazide may reduce the rate of stone recurrence by up to 90%.The diuretic dose is usually started at 25 mg/day of chlorthalidone or hydrochlorothiazide (or its equivalent), but many patients will require 50 to 100 mg/day to achieve satisfactory reductions in urinary calcium excretion. Without dietary sodium restriction, the reduction in urinary calcium excretion obtained with treatment may be inadequate. In addition, serum potassium levels should be closely monitored during therapy because hypokalemia can result in a decrease in urinary citrate excretion. Of interest, thiazide diuretics may be beneficial even in patients without overt hypercalciuria Calcium stone formers with hyperuricosuria may be treated with Allopurinol (100 to 300 mg per day).

Allopurinol may reduce new stone formation by up to 80% in individuals with isolated hyperuricosuria. Theoretically, Alkali therapy with potassium citrate may also be beneficial, since raising the urine pH will convert uric acid to the more soluble urate salt (thereby decreasing the potential formation of a uric acid nidus). However, no trials have addressed this intervention.

Urinary citrate excretion can be increased by administration of an alkali load in the form of Potassium citrate or Potassium bicarbonate (30 to 80 mEq per day).In one study, stone recurrence in a group of hypocitraturic patients treated with potassium citrate decreased from 1.2 to 0.1 per patient year (versus no change with placebo).To date, no satisfactory drug treatment exists to decrease the urinary excretion of oxalate. For patients with increased intestinal absorption of oxalate secondary to bowel disease, clinicians sometimes administer oxalate binders such as calcium carbonate or Colestipol. Experimental therapies include the oral administration of oxalate consuming bacteria and the administration of high dose Pyridoxine (to reduce the endogenous production of oxalate).

Conclusion

Even if stone composition is known, a thorough evaluation requires at least two 24-hour urine specimens collected at least 6 weeks after resolution of an acute episode. Subsequent 24-hour urine collections are necessary to gauge the adequacy of treatment. Prevention of stone recurrence is an achievable goal with individualized therapy and regular follow-up.

Prepared by Mostafa Tabassomi M.D.