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Outpatient metabolic evaluation of patients with recurrent kidney stones.

We have designed an outpatient, comprehensive metabolic evaluation program for patients with recurrent kidney stone disease. This protocol can be expected to detect and identify specific biochemical abnormalities contributing to kidney stone formation in about 95% of these patients. Individualized therapy can then be started based on the particular metabolic defect discovered in each patient. This diagnostic and treatment program will stop new kidney stone formation in these high-risk patients virtually completely. For each stone-related hospitalization eliminated, the average savings are at least $2,700. The total potential savings in our small community alone are over $460,000! Our metabolic stone evaluation protocol is the only one with which we are familiar that was designed and implemented exclusively at the community hospital level. It is readily adaptable to other medical facilities.

Ambulatory Care↗

Recurrent kidney stones: causes and diagnostic criteria in patients from Campania (southern Italy).

A study was carried out on 180 recurrent kidney stone formers from the Campania region of southern Italy. The data showed that this hypercalciuric population was similar to that in previous studies; however, there was no difference in terms of parathyroid activity when compared with normal controls. The slightly depressed serum levels of vitamin D in hypercalciurics indicate that gut calcium absorption is not directly related to vitamin D levels. We found no difference in the prevalence of metabolic abnormalities associated with stone formation between the patients in this series and those in previous studies.

Acidosis, Renal Tubular↗

Recurrent kidney stone: a 25-year follow-up study in persons with spinal cord injury.

OBJECTIVES: To document the recurrence rate of kidney stones in patients with spinal cord injury and to assess the potential contributing factors and long-term renal function outcome. METHODS: A consecutive sample of 77 patients with initial kidney stones followed up on a yearly basis between 1973 and 1999 was used to estimate stone recurrence, stratified by demographic and clinical characteristics. Longitudinal data analyses were performed to assess the change in renal function over time among various post-treatment outcomes. RESULTS: During an average of 7 years (range 1 to 21) of follow-up after the initial stone episode, 19 patients with recurrence, 15 with residual stones, and 43 who were stone free were documented. It was estimated that approximately 34% of the patients with an initial stone would develop a second stone episode within 5 years. This figure did not significantly change during the past 25 years (P = 0.18). Stone recurrence was two or more times greater for men than for women, for whites than for blacks, and for tetraplegics than for paraplegics, but the differences were not statistically significant (P >0.05). Renal function did not significantly decline over time for any of the post-treatment outcomes of the initial stones. CONCLUSIONS: Despite marked improvement in urologic rehabilitation, little progress has been made during the past 25 years in reducing stone recurrence in persons with spinal cord injury. Future studies are required to determine the critical components of the causal pathway to stone formation, which may lead to the establishment of effective prophylactic interventions.

Adolescent↗

Idiopathic calcium nephrolithiasis. 2. Differences between hypercalciuric and normocalciuric persons with recurrent kidney stone formation and persons without such a history.

Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without such a history to examine the factors that predispose normocalciuric patients to stone formation. The urine calcium excretion rate was higher in the normocalciuric patients than in the control subjects (227 v. 183 mg/24 h; P less than 0.01), but the urine calcium concentration was not significantly different. The urine magnesium and citrate excretion rates and concentrations were lower in the normocalciuric patients than in the control subjects (P less than 0.001), while the urine uric acid and oxalate excretion rates and concentrations and the urine saturation with brushite (CaHPO4-2H2O) were not significantly different. These results suggest the importance of slight increases in the urine calcium excretion rate together with decreased urine magnesium and citrate excretion rates in normocalciuric persons with recurrent calcium stone formation. The urine of the hypercalciuric patients was more highly saturated with brushite than the urine of the normocalciuric patients and the control subjects, and the excretion rates of uric acid and oxalate were increased in the hypercalciuric patients. The hypercalciuric patients had a higher urine creatinine excretion rate than the normocalciuric patients and a higher daily urine volume than the control subjects, which suggests that differences in lean body mass or fluid and food intake, or both, may be important determinants of these differences in crystalloid excretion. As in the normocalciuric patients, the urine citrate excretion rate and concentration were decreased in the hypercalciuric patients compared with the control subjects.

Adult↗

Idiopathic calcium nephrolithiasis. 1. Differences in urine crystalloids, urine saturation with brushite and urine inhibitors of calcification between persons with and persons without recurrent kidney stone formation.

The propensity of urine to promote calcium stone formation was compared in 64 patients with recurrent idiopathic calcium nephrolithiasis and 30 healthy individuals without such a history. The rates of excretion of urine crystalloids, the urine saturation with brushite (CaHPO4-2H2O), the ability of the urine to calcify collagen in vitro, and the concentration of urine inhibitors of collagen calcification were measured. The patients had a reduced urine citrate excretion rate in addition to an increased urine calcium excretion rate, while the rates for urine magnesium, phosphate, uric acid and oxalate were not significantly different in the two groups of subjects. The urine concentration of magnesium, phosphate and uric acid was decreased in the patients because of the higher urine volume. The urine creatinine excretion rate correlated with the rates of excretion of urine calcium, magnesium, phosphate, uric acid and oxalate in both groups, which suggested that increased lean body mass, possibly associated with greater food intake, may be an important determinant of crystalloid excretion. The urine of the patients was significantly more saturated with brushite than the urine of the control subjects and resulted in greater collagen calcification when incubated in vitro. The urine concentration of inhibitors of collagen calcification, however, was not significantly different in the two groups. Thus, the urine of patients with recurrent idiopathic calcium nephrolithiasis is more highly saturated with brushite, largely as a result of an increased urine calcium excretion rate, and contains a lower concentration of magnesium and citrate, substances that tend to prevent the precipitation and growth of crystals in urine.

Adult↗

Loss of regulation of circulating 1,25-dihydroxyvitamin D with paradoxically decreased serum phosphate levels in individuals with recurrent kidney stones.

A low serum phosphate concentration is characteristic in individuals in whom kidney stones form, this being related to serum 1,25-dihydroxyvitamin D, parathyroid hormone and urinary phosphate excretion. In order to determine whether these parameters are related to recurrence of stone formation, they were analyzed in single and recurrent stone formers as well as controls. An inverse correlation between serum levels of phosphate and 1,25-dihydroxyvitamin D was observed in control subjects, indicating that a drop in serum phosphate results in upregulated circulating 1,25-dihydroxyvitamin D level in controls. While the circulating low phosphate level upregulated the 1,25-dihydroxyvitamin D level in single stone formers, the elevation was less than expected from the drop in serum phosphate in recurrent stone formers. The results thus suggest that loss of upregulation of 1,25-dihydroxyvitamin D by serum levels of phosphate might be important for stone formation. The possibility of deregulation of 1,25-dihydroxyvitamin D to maintain physiological requirements in stone formers and prevent further nephrolithiasis therefore warrants attention.

Adult↗

Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands.

The lack of overt elevation of serum calcium concentration in some patients suffering from primary hyperparathyroidism is an intriguing clinical phenomenon. Previous studies have substantiated abnormal parathyroid tissue in these patients, but the extent and mode of derangements remained largely undefined. The parathyroid tissues from patients of normocalcemic primary hyperparathyroidism (NCPHPT) and those having normal parathyroid glands, hypercalcemic primary hyperplasia, secondary hyperplasia, and adenoma were compared by undertaking quantitative immunohistochemistry analysis on tissue microarray. The statistic results suggested that the parathyroid tissue of NCPHPT approximates more to normal gland than to its counterpart in other groups of parathyroid proliferative diseases in terms of the lack of significant alterations of calcium-sensing receptor (CaSR), chromogranin A (CGA), parathyroid hormone (PTH), and proliferation index (Ki67). On the other hand, the depressed vitamin D receptor (VitDR) and elevated cyclin D1 (CyD1) of NCPHPT indicated the inherent functional abnormalities in parathyroid cells. Our results imply that inherent functional disengagement may exist between CaSR and CyD1 or between CaSR and VitDR or both in parathyroid cells of symptomatic NCPHPT. Lack of enhanced release of CGA and PTH and discordance between proliferative activity and CyD1 expression in parathyroid cells may further hinder the development of hypercalcemia.

Calcium↗

International comparison of cost effectiveness of medical management strategies for nephrolithiasis.

Although medical therapy is known to reduce the risk of kidney stone recurrence, the cost effectiveness of medical prophylaxis is controversial. We evaluated medical treatment strategies including dietary measures (conservative), empiric medical therapy (empiric) or directed medical therapy (directed) based on comprehensive metabolic evaluation (CME) for patients with recurrent kidney stones, and compared the costs of these strategies using cost data from ten different countries. We previously established rates of stone formation in recurrent stone-formers, risk reduction of medical therapy, sensitivity of CME and rates of spontaneous stone passage from a comprehensive literature search (Lotan et al. 2004 J Urol 172: 2275). The costs of medication, surgical therapy, emergency room visits and CME for ten different countries were obtained from a published report of an international cost survey (Chandhoke 2002 J Urol 168: 937) as well as from our own county hospital in the US. Medication costs in the US were obtained from two national pharmacy chains. A decision tree model was created to compare the costs of different treatment strategies assuming cost accrual for metabolic evaluation, medical therapy and surgery or emergency room visits. For medical therapy, we assumed the distribution of medication use described in the published report, consisting of potassium citrate (60%), thiazide (30%) and allopurinol (10%). A nearly 20-fold difference in the costs of shock-wave lithotripsy, ureteroscopy and medication was found among different countries. From the model (US dollars/patient/year), conservative therapy alone was the most cost effective approach followed by empiric and directed medical therapy in all countries except in the UK. In the UK, the cost of drug therapy (estimated at dollar 29/patient/year) resulted in empiric therapy being the most cost effective strategy for recurrent stone formers. The low likelihood of surgical intervention, as well as the low relative cost of surgery to medication, contributed to the higher cost of empiric and directed medical therapy strategies. Of note, despite the higher cost, drug treatment strategies were associated with significantly lower stone recurrence rates. We found that drug treatment strategies are more costly than conservative treatment but produce good control of stone formation. In all but one country (UK), dietary therapy was the most cost effective approach due to the relatively low cost of surgery compared with medication. The differential resource allocation to different components of a healthcare system (i.e. subsidized medication versus surgical treatment) in different countries determines the cost effectiveness of various treatment strategies.

Cost-Benefit Analysis↗

Stone recurrences in kidneys made stone-free by percutaneous extraction.

Of 100 renal units which were made stone-free by percutaneous stone extraction in 1985, 86 (86.0%) were re-examined radiologically up to 5 years after operation. The re-examination was performed because of symptoms or as part of a regular check-up or after calling the patient. Intrarenal calcifications were diagnosed in 27 of 86 (31.4%) of the renal units, but only in 11 (12.8%) were there stones requiring treatment.

Adolescent↗

Normocalcemic hyperparathyroidism, kidney stones, and idiopathic hypercalciuria.

Eighty-four patients with recurrent kidney stones, serum calcium levels in the upper normal quartile, and most of whom with hypercalciuria had their parathyroids surgically explored. Parathyroid adenomata were found in 19 patients, hyperplasia in 39, and normal parathyroids in 26. Postoperatively there was a significant fall in serum calcium and urinary calcium excretion in all three groups. At clinical follow-up 2 to 5 years postoperatively there was no case of kidney stone recurrence among the adenoma patients. In the hyerplasia group there were recurrences tn 25 percent. The corresponding figure for the patients with normal parathyroids was 48 percent. The concept of normocalcemic primary hyperparathyroidism and the relationship between this syndrome and idiopathic hypercalciuria are discussed. Some prinicpal therapeutic measures are recommended.

Adult↗

Kidney stones. Medical management and newer options for stone 'removal'.

Patients with recurrent kidney stone disease or stone formers at increased risk of recurrence deserve a thorough metabolic workup. This should be based on a careful history and include urinalysis, serum chemistry studies, and analysis of 24-hour urine collections. Measures to prevent recurrent stone formation are aimed at correcting the metabolic imbalances detected in the workup. A variety of drugs are available that target one or more of the metabolic abnormalities that may be involved. For "surgically active" renal and ureteral stone disease, newer techniques make surgery unnecessary in most cases. Extracorporeal shock wave lithotripsy is becoming the preferred technique for disintegration of upper urinary tract stones. Percutaneous ultrasonic lithotripsy and electrohydraulic disintegration also are widely used. For lower urinary tract stones, the ureteroscope permits either extraction under visualization or ultrasonic disintegration.

Allopurinol↗

Role and relevance of genetic testing in patients with kidney stones: a review from EAU Section of Endourology.

PURPOSE OF REVIEW: Kidney stones have a high heritability. More than 40 genes have been identified causing monogenic forms of kidney stone disease (KSD). Kidney stone formers with genetic variants implicated in monogenic forms of KSD often suffer from early onset, high recurrence rates, and chronic kidney disease. Some patients may also exhibit extrarenal disease requiring attention. RECENT FINDINGS: Recent analysis of KSD patients identified a likely monogenic cause in pediatric populations in 17-30% of participants while in adult unselected populations 2.7-8% had a positive finding. More patients carry single genetic variants in monogenic forms that are classically considered as autosomal recessive but may cause an intermediate genetic risk for the development of KSD possibly in interaction with environmental or lifestyle factors. Genome-wide association studies have identified additional risk loci associating with KSD. Their clinical relevance are currently investigated. Patients with recurrent kidney stone episodes may be at elevated risk of progressive chronic kidney disease. SUMMARY: Monogenic causes of KSD are prevalent in patients less than 25 years of age and in some patients with high-risk metabolic profiles. These patients should undergo genetic testing to enable a precise molecular genetic diagnosis and personalized therapy as well as family counseling and screening.

Humans↗

Case management study Walter Reed Army Medical Center. A 37-year-old soldier with right flank pain.

The objective of this study was to discuss the appropriate diagnostic and treatment approach to an active duty patient presenting with recurrent kidney stones. A 37-year-old active duty infantryman, stationed in Iraq, was evacuated by air to Waiter Reed Army Medical Center for workup of recurrent kidney stones and hypercalcemia. A diagnosis was made and the definitive treatment was performed. During this report, we will illustrate the various aspects of diagnosis that are involved with the workup of kidney stones and hypercalcemia as well as discuss the available treatment options. Relevant military issues include proceeding with the initial management regimen and recognition of appropriate reasons for initiation of referral consultation.

Adult↗

[Study of the diuretic efficacy and tolerability of therapy with Rocchetta mineral water in patients with recurrent calcium kidney stones].

The diluition of urine decreases the risk of stone formation by lowering the concentration of calcium, oxalate and uric acid, but involves a simultaneous decrease of the concentration of the inhibitors of crystallization. On the other hand the ion content of the drinking water used for stone prevention could by itself modify urine composition. We tested the effect of the administration of a mild-calcium high-bicarbonate content water on urine composition of a group of calcium renal stone formers. A group of 40 calcium renal stone formers was instructed to drink 3 l/day of a mild-calcium (57 mg/l) and high-bicarbonate (180 mg/l) content water (Rocchetta) for a 7 day period. A 24-h collection was obtained before and after water administration for analyses of calcium, magnesium, oxalate and citrate. Urine volume was significantly increased after water administration (1601 +/- 357 vs 1878 +/- 339). Daily urinary calcium, magnesium and citrate were significantly increased, whereas daily urinary oxalate was unchanged after water administration. In conclusion the mild-calcium high-bicarbonate content water administration seems suitable for stone prevention because of the increased excretion of urinary inhibitors counterbalancing increased urinary calcium excretion.

Diuretics↗