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This is the second part of an article on the metabolic diagnosis of nephrolithiasis, the first part of which was published in the previous issue of this journal. Here we report on three clinical cases representative of a rational diagnostic workup of nephrolithiasis in specific clinical contexts: secondary hyperuricemia, cystinuria, and primary hyperoxaluria. Nephrolithiasis is one of the most frequent causes of hospitalization in nephrology and urology units in our country and is an important source of discomfort in affected patients. Despite the availability of modern, minimally invasive endourological procedures to remove stones from the urinary tract, prevention of stone recurrences remains an essential strategy. Chemical analysis of stones, whether passed spontaneously or removed surgically, is a crucial step in etiological diagnostics aimed at devising adequate prevention strategies. Modern endoscopic lithotripsy techniques provide complete fragmentation of stones and, compared to extracorporeal shock wave lithotripsy, have the advantage of avoiding painful elimination of fragments through the urinary tract. This means, however, that stone fragments are often unavailable for analysis, thereby depriving the nephrologist of an important tool for diagnosis. As a consequence, metabolic evaluation tends to be the only means of establishing the etiology of stones and preventing their recurrence. We conclude that close collaboration between nephrologists and urologists is a prerequisite for optimizing the diagnosis and treatment of stone disease. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we investigated whether cholecalciferol supplementation, prescribed to treat vitamin D deficiency in patients with nephrolithiasis, increased the risk of stone recurrence., Methods: Calcium excretion and urine supersaturation with calcium oxalate (βCaOx) and brushite (βbsh) were evaluated in 33 kidney stone formers (aged 56±17; 12 males), both before and after therapy with cholecalciferol, prescribed as oral bolus of 100.000-200.000 UI, followed by maintenance doses, repeated every week (5.000-10.000 UI) or month (25.000-50.000 UI). During the study, patients followed a dietary regimen which included a daily calcium intake of about 800-1000 mg., Results: Urinary nitrogen, sodium and ash-acid excretion did not significantly change during the study. After cholecalciferol supplementation, the main results were as follows: both serum calcium and phosphate did not vary significantly; 25(OH)VitD₃ increased from 11,8±5,5 to 40,2±12,2 ng/mL (p<0,01); 1,25(OH) ₂ VitD₃ increased from 41,6±17,6 to 54,0±16,0 pg/mL (p<0,01); PTH decreased from 75,0±27,2 to 56,7±21,1 pg/mL (p<0,01); daily urinary calcium increased from 2,7±1,5 to 3,6±1,6 mg/Kg b.w. (p<0,01), whereas fasting urinary calcium did not change significantly. After therapy, βbsh increased from 0,9±0,7 to 1,3±1,3 (p=0,02) and βCaOx did not vary significantly. Before cholecalciferol supplementation, 6/33 patients (18.2%) were hypercalciuric, whereas 13/33 patients (39,4%) showed hypercalciuria after supplementation (pX²=0,03)., Conclusions: Cholecalciferol supplementation for vitamin D deficiency may increase both urinary calcium and urine supersaturation in stone formers. If vitamin D supplements are needed in these patients, a careful monitoring of urine metabolic profile is warranted, in order to customize the metaphylaxis accordingly (hydration, potassium citrate, thiazides)., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Primary hyperparathyroidism (PHPT) may favor nephrolithiasis mainly through an increase in calcium and phosphate urinary excretion. Cinacalcet exhibits good efficacy to control hypercalcemia in PHPT, but it is not so far known whether it might be a useful tool to prevent stone recurrences. Of 67 patients with PHPT and recurrent nephrolithiasis, 55 underwent parathyroidectomy (PTX) and 12, not eligible to PTX, were prescribed Cinacalcet. All the patients were evaluated for mineral metabolism, including estimation of state of saturation for calcium oxalate (CaOx) and brushite (bsh), both at baseline and after either PTX or Cinacalcet. PTX compared to baseline reduced PTH (4617 vs 15786 pg/mL, p<0.01), calcemia (9.40.5 vs 11.30.9 mg/dL, p<0.01), calciuria (3.62.3 vs 9.24.5 mmol/24h, p<0.01), phosphaturia (18.47.1 vs 21.99.9 mmol/24h, p<0.05), CaOx (4.73.9 vs 9.86.8, p<0.01) and bsh (1.10.9 vs 3.22.2, p<0.01). Cinacalcet decreased both PTH (13379 vs 17187 pg/mL, p<0.05) and calcemia (9.70.6 vs 11.20.8 mg/dL, p<0.001), whereas no change was seen in calciuria (7.42.2 vs 7.42.4 mmol/24h, p=ns), phosphaturia (21.97.3 vs 23.06.5 mmol/24h, p=ns), CaOx (6.92.7 vs 5.42.5, p=ns) and bsh (1.71.1 vs 1.31.3, p=ns). We conclude that in patients with PHPT, PTX is able to decrease the risk for crystallization of calcium salts, whereas calcimimetic Cinacalcet did not. Therefore, in patients with PHPT complicated with nephrolithiasis only PTX can improve urine biochemistries thereby reducing the risk for recurrent calcium stone disease.

Renal stone disease often begins by renal colic. In order to manage this event adequately, several goals should be pursued: first, attenuate pain; second, favour progression and spontaneous expulsion of stones; third, prevent from obstructive and infectious complications. All of the aforementioned points pertain to medical management of this disease. Concerning prevention, it is widely agreed that pathogenesis of kidney stones is a consequence of abnormalities in urine environment, leading to a disequilibrium between promoters and inhibitors of crystallization. Therefore, the rationale for therapy is to make urine less conductive to stone formation, by both decreasing state of saturation and increasing inhibitory potential. In only some types of stone-forming salts it is possible to obtain undersaturation with the solid phase. Indeed, uric acid stones can be chemically dissolved by using alkali and allopurinol. To a lesser extent, this also applies to cystine stones, with the use of thiols and alkali. In these subsets, the aforementioned tools are also effective to prevent new stone formation. Much more challenging appears the treatment of calcium containing stones. About 10% of such stones is caused by systemic disorders and, in these cases, the prevention of new stones is successfully accomplished by curing the underlying disease. For instance, parathyroidectomy cures calcium nephrolithiasis in case of hyperparathyroidism. However, the majority of patients with calcium stones are idiopathic stone-formers, in whom metabolic abnormalities often occur, namely, hypercalciuria, hyperoxaluria, hypocitraturia. The correction of these abnormalities by using thiazide diuretics, alkaline citrates, potassium phosphate and bisphosphonates is based on the prevailing metabolic defect. Among the most recent available tools, Oxalobacter Formigenes and probiotics have been proposed to treat primary or secondary hyperoxalurias. In general, the treatment of stone disease reduces its recurrence rate, but only seldom results in stable remission. Anyway, less stones mean reduction of the need for urological procedures and the associated infective or obstructive complications. Of course, medical prevention implies financial efforts, but a careful cost to benefit analysis demonstrates that these are well justified.