Management of stone disease needs individualization. Clinical presentation, proper history, and laboratory tests help to identify whether one needs urgent surgical or medical treatment.
Medical management is indicated for clinically stable patients with non-obstructive urinary stones, recurrent stone formers, and the patients with underlying systemic diseases. Detailed history of patient illness including family history, drug history, and history of previous similar illness and previous interventions needs to be recorded. Assessment of risk factors for stone disease  should be carried out. Medical management of stone disease includes laboratory evaluation and treatment. As the laboratory evaluation of renal calculi has been discussed by Ranabir, Baruah and Ritu Devi in this issue,[8
] we will focus on medical treatment.
Medical treatment of kidney stones includes dietary management, disease-specific therapies, and medical expulsion therapy (MET) of stones.
Fluid intake and dietary changes are important measures in preventing recurrence of kidney stones. Many trials have shown that increasing urine volume to at least 2 L/day OR 2 lit/day can reduce the recurrence of stone disease by up to 40–50%.[9
] Fluid intake mainly should include water. As tea and coffee contain oxalate, milk (which binds free oxalate) should be added to them. However, increasing the urine volume has a disadvantage of reducing urinary citrate.
A small reduction in urinary oxalate has been found to be associated with significant reduction in the formation of calcium oxalate stones; hence, oxalate-rich foods like cucumber, green peppers, beetroot, spinach, soya bean, chocolate, rhubarb, popcorn, and sweet potato should be avoided. Many studies have found calcium restriction to increase the risk of stone disease; therefore, dietary calcium restriction is not recommended.
Hypocitraturia is a proven risk factor for stone formation and is found in about 16–63% of calcium stone formers.[10
] Oral potassium citrate (Kcit) has been shown to be useful in increasing urinary citrate and reducing the stone recurrence. Dietary replacement with high citrate as a substitute to Kcit has been studied. Lemon juice when delivered as a lemonade therapy was found to increase urinary citrate.[12
] Odvina found orange juice to increase urine pH and urinary citrate.[13
] Kang et al
. compared 11 patients taking Kcit with 11 matched patients on lemonade therapy and found both the therapies to increase urinary citrate. However, the effect with Kcit was significantly better than the effect with lemonade.[14
] Yilmaz et al
. studied tomato, orange, lemon, and mandarin juice for nutritional content.[15
] Surprisingly, fresh tomato juice was found to have the highest citrate and low oxalate content. Reduction of animal protein intake is suggested in both calcium oxalate and uric acid stone formers.
Calcium oxalate stones
In patients with idiopathic hypercalciuria, thiazide diuretics have shown to reduce the recurrence rates by up to 70%.[9
] It is the only medical therapy directed at reducing urinary calcium.[16
] Citrate supplements as detailed earlier are useful. Pyridoxine sometimes can be useful in patients with primary hyperoxaluria, but not in idiopathic hyperoxaluria.[17
] Oxalobacter formigenes
is an oxalate degrading bacterium found in human gastrointestinal tract. It is thought that increased colonization of the gut might lead to decreased absorption of dietary oxalate and decrease in urinary oxalate excretion. Colonization with O. formigenes
showed benefit in uncontrolled studies;[18
] however, a prospective, randomized, placebo control, double-blind trial refuted such benefits.[20
Uric acid stones
The aim of treatment in uric acid stones is to increase the solubility of uric acid in urine. It is achieved by increasing the urine volume and by alkali therapy. Allopurinol is a useful adjunct to the therapy.
Struvite stones form in alkaline urine from infection with urea-splitting microorganisms. Antibiotics are the mainstay of the therapy with occasional use of acetohydroxamic acid.[17
This is a rare stone type. The aim of treatment is to reduce the concentration of free cystine and increase its solubility in urine. A high fluid intake up to 4-5 L/day OR 4-5 lit/day and alkalinization of urine with target urine pH >7 is desirable. Chelating agents like D-penicillamine or tiopronin are indicated when 24-hour urine cystine concentration exceeds 2000 μmol/l.[17
General stone-expulsive therapies
MET is treatment with combination of drugs which facilitates the spontaneous passage of ureteric calculi. Ureteric colic is an emergency and management depends upon the severity of obstruction and degree of renal function deterioration. Approximately 90% of stones <5 mm and 15% of stones between 5 and 8 mm pass spontaneously within 4 weeks, while 95% of those larger than 8 mm require urological intervention.[21
] The American Urology Association Nephrolithiasis Clinical Guidelines panel in its recent guidelines have found MET to facilitate and accelerate the spontaneous passage of ureteric stones and the stone fragments generated by shock wave lithotripsy.[22
Smooth muscles of lower ureter innervated by alpha adrenoreceptors and abundance of calcium channels, which on stimulation causes peristalsis of ureter, maintain basal tone. Calculus in distal ureter causes ureteric spasm and increases contraction by activating these receptors. Mechanical effects include submucosal edema and associated inflammation. Combination therapy used includes alpha adrenoreceptor blockers, calcium channel blockers, corticosteroid, analgesics, and hydration.
In a recent prospective, randomized study which compared three drugs as MET for distal ureteral calculi, patients with symptomatic distal ureteral stones >4 mm were randomly assigned to three treatment groups : p0 hloroglucinol and corticosteroid, tamsulosin and corticosteroid, and nifedipine and corticosteroid.[23
] Tamsulosin and corticosteroid was the most efficacious combination – stones passed more quickly and the need for analgesics was reduced.[23
] A randomized, controlled, prospective study has also shown tamsulosin to be a useful addition to shock wave lithotripsy.[1
Alpha adrenergic receptors are densely located in the smooth muscles of ureter. Alpha-1a-receptors predominate in bladder outlet, prostate, and proximal urethra, whereas alpha-1d-receptors are seen in lower ureter and detrussor muscle of bladder.[24
] Drugs which block these receptors cause smooth muscle relaxation and inhibits peristalsis and relieves spasm.
Tamsulosin is effective in expulsion therapy as it increases the passage rate and reduces the passage time for stones up to 10 mm.[25
] In a study of tamsulosin in renal colic, 100% expulsion rate was seen in the treatment group and 70% in the control group. The mean expulsion time in the treatment group was 65.7 h (range 2–288 h) compared with 111.1 h for the control group (range 12–240 h).[25
] In this study, the mean stone size was 6.7 (SD 2.1) mm in the treatment group, compared with 5.8 mm in control subjects (P
=0.047). A recent study using sustained release alfuzosin 10 mg once daily was found to be effective in enhancing the ureteral stone spontaneous passage rate, particularly for upper ureteral stones. The patients treated with alfuzosin required fewer analgesics and less surgical interventions like ureteroscopic lithotripsy and/or extracorporeal shock wave lithotripsy.[27
Calcium channel blockers (CCBs) cause inhibition of calcium channels in distal ureter and decrease the contraction and spasm caused by distal ureter calculus.[28
] A study of combination therapy with nifedepine and deflazacort in distal ureter stone resulted in stone expulsion in 79% of the treatment group and in only 35% of control subjects. The average stone size was 5.8 mm (range 3.5–10 mm) for the treatment group and 5.5 mm (range 3–10 mm) for the control group. CCBs can facilitate spontaneous passage for stones up to 10 mm, though no correlation was found between stone size and expulsion time in the treatment group.[29
A comparative study between nifedepine and tamsulosin reveals a better stone expulsion rate of 97.1% in tamsulosin versus 77.1% in nifedepine group. Average expulsion times were 72 h and 120 h (P
<0.001) in the two groups, respectively, despite the presence of larger stones in the tamsulosin group (tamsulosin 7.2 mm vs. nifedepine 6.2 mm; P
Steroids are also found to be useful as medical expulsive agents in distal ureteric stones. Calculus in distal ureter causes inflammation and submucosal edema which further aggravates the obstruction due to the stone per se. Being anti-inflammatory agents, steroids reduce the inflammation and neutrophil-induced damage. This class of drug, in combination with other agents described earlier, improves stone passage and reduces stone expulsion time.[30
Patients receiving MET, who do not pass their stones within 4 weeks, should be reffered to a urologist since delay in definitive management may increase the rate of complications, including renal dysfunction, urosepsis, and intractable pain.[32
] Side effect profile should be considered before initiation, and during therapy.