Medical and medical/urologic approaches in acute and chronic urologic stone disease

Urinary stone disease is a condition with far-reaching implications. Patients with their initial instance of acute renal colic enter the health care system through 2 routes. Severe cases are generally seen in the emergency room, whereas more tolerable cases may be seen by primary care physicians. Patients with urinary stone disease are then managed in the long-term by a urologist. Timely and appropriate treatment of patients with urinary stone disease is essential to prevent the development of sepsis and progressive renal insufficiency. This article reviews the epidemiology, pathogenesis, presentation, and short- and long-term management of acute and chronic urinary stone disease.     

Risk factors for nephrolithiasis in patients with familial idiopathic hypercalciuria

PURPOSE: About 40% of patients with nephrolithiasis have idiopathic hypercalciuria, sometimes associated with a family history of kidney stones. In these families, little is known about the frequency of, and risk factors for, stone formation among hypercalciuric patients. We therefore conducted a prospective study of 216 subjects from 33 families with idiopathic hypercalciuria. MATERIALS AND METHODS: We recorded the age, weight, and history of calcium stones in all subjects, and measured 24-hour urine volume and excretion of calcium, uric acid, sodium, magnesium, urea, citrate, phosphate, and sulfate on a nonrestricted diet. We performed a more complete metabolic evaluation in many of the hypercalciuric subjects (calciuria/weight >0.1 mmol/kg/d). Multivariate logistic regression analysis was performed to identify independent risk factors for stone formation. RESULTS: The prevalence of self-reported nephrolithiasis was 46% (61/132) in hypercalciuric subjects and 11% (7/63) in normocalciuric subjects (P <0.0001). In multivariate analysis, age (odds ratio [OR] per 10 years of age = 1.3; 95% confidence interval [CI]: 1.1 to 1.6), urine calcium excretion (OR = 1.3 per mmol/d increase; 95% CI: 1.2 to 1.5), and uric acid excretion (OR = 3.3 per mmol/d increase; 95% CI: 1.4 to 7.5) were independent risk factors for nephrolithiasis. The risk of nephrolithiasis increased progressively with greater levels of hypercalciuria. CONCLUSION: We found a significant dose-effect association between calciuria and stone disease in patients with familial hypercalciuria. Other factors associated with stone formation included higher uric acid excretion, probably reflecting higher food intake, and age, probably reflecting the length of exposure to hypercalciuria and hyperuricosuria.     

Effect of second messenger systems on oxalate uptake in renal epithelial cells

The oxalate transport system along with protein phosphorylation appears to be deranged in stone formers. This study was undertaken to characterize in LLC-PK₁ cells in culture the effect of altering specific intracellular second messenger systems on oxalate uptake. Cellular uptake experiments were performed at 37°C in buffer [265 mM mannitol, 5 mM NaOH, 5 mM KOH, 10 mM Ca-EGTA, 25 mM HEPES/TRIS, pH=7.4 or in Hank's balanced salt solution (HBSS)] containing 200 M labeled oxalate (1-¹⁴C, 0.3 Ci). Cells were preincubated with DAG (final concentration of 100 M), phorbol myristate acetate (10 M), forskolin (50 M), 8-bromo-cyclic AMP (50 M), trifluoroperazine (20 M) and low molecular weight heparin (1 mg/ml) for 10 min in the presence and absence of the anion transport inhibitor DIDS (100 M) and the effect(s) on oxalate uptake at 10, 25 and 45 min incubation were determined. Chemicals (DAG, forskolin, TPA and 8-bromo-cAMP) which stimulate protein kinase A or C activity resulted in an increased uptake of oxalate while inhibitors of these systems (trifluoroperazine and low molecular weight heparin) resulted in decreased oxalate uptake. The results dernonstrate that oxalate uptake in renal tubular cells is modulated by protein kinase C and A dependent mechanisms.     

酒石酸钾预防草酸钙肾结石形成的研究

体外实验证明酒石酸钾对一水草酸钙晶体的生长和聚集有抑制作用。动物实验发现酒石酸钾能够降低鼠肾组织中钙及草酸的沉积。２７例患者口服酒石酸钾期间，２４小时尿钙、磷和草酸明显下降，尿枸橼酸和尿ＰＨ显著上升，实验证明，酒石酸钾能够抑制草酸钙肾结石的形成，是一种有希望的防石药物。     

Reduction of vitamin D induced stone formation by calcium

Investigations were carried out as to whether cytoprotective agents such as calcium antagonists can influence vitamin D induced nephrolithiasis. Increased vitamin D levels are found in 10–30% of all calcium oxalate stone formers. Male rats were assigned to one of the following groups: (1) 1,25-dihydroxycholecalciferol (DHCC) (n=8), (2) 1,25-DHCC+calcium antagonist Goe 6070 (a new 1,4-dihydronaphthyridine, Goedecke, Berlin) (n=8), or (3) control (n=8). 1,25-DHCC was administered for 6 days (120 pmol/24 h s.c.), Goe 6070 (1 mg/kg/24 h) by gavage. Clearance studies were performed on day 6. Kidneys were taken for histological examination and determination of calcium tissue content. 1,25-DHCC induced substantial concrement formation, which could be significantly limited by Geo 6070. The calcium tissue content was also reduced (0.17 vs. 0.04 mg/100 mg dry weight). 1,25-DHCC induced a dramatic fall in the glomerular filtration rate (GFR) (3.84 ml/min per kilogram). This reduction could be almost completely inhibited by the concomitant application of Goe 6070 (9.4 ml/min per kilogram; control 10.7 ml/min per kilogram). Goe 6070 did not influence the calcium handling. The results demonstrate a protective effect of Goe 6070 on vitamin D induced nephrolithias. The histological pattern (intracellular and membrane-bound concretions) and the fact that biochemical parameters were not influenced significantly by Goe 6070 indicate that cellular processes are important for 1,25-DHCC-induced nephrolithiasis.     

Lipids and Membranes in the Organic Matrix of Urinary Calcific Crystals and Stones

The ultrastructure of the organic matrix of demineralized urinary stones was examined by standard transmission and scanning electron microscopy as well as after malachite green-glutaraldehyde fixation. Crystal ghosts of both calcium oxalate and calcium phosphate were made of amorphous material and were dispersed in a matrix containing amorphous, fibrillar, and membranous substances. Malachite green positive material was seen to be associated with the ghosts, as well as with the membranous and fibrillar components of the organic matrix. Calcium oxalate and calcium-phosphate crystals, induced in human urine in vitro were also found to be associated with an organic matrix containing lipids and proteins. It is suggested that the intimate association between crystals and lipids is a result of the involvement of cellular membranes in the nucleation of these crystals. Received: 28 August 1995 / Accepted: 22 December 1995     

Medullary sponge kidney

Medullary sponge kidney is a benign asymptomatic developmental anomaly of the kidney mostly seen in adult females. Presentation in childhood is uncommon. Urinary tract infection, nephrolithiasis, hematuria and hypercalciuria are the common complications. We report a eleven-year-old female child who presented with recurrent urinary tract infection and nephrolithiasis and was found to have bilateral medullary sponge kidney.     

Pitfalls in parathyroid evaluation in patients with calcium urolithiasis

Summary Primary hyperparathyroidism is a major cause of calcium urolithiasis and is easily recognised when it is classically manifested. However, subtle presentations of primary hyperparathyroidism may cause confusion with other causes of calcium stone disease or cause diagnostic difficulty. Several pitfalls of parathyroid evaluation and treatment are illustrated by four cases of calcium urolithiasis. Cases 1 and 2 represent ineffective or useless parathyroid surgery rendered for renal hypercalciuria and absorptive hypercalciuria, respectively. Cases 3 and 4 had mild or intermittent hypercalcaemia. The correct diagnosis of primary hyperparathyroidism was made in Case 3 by parathyroid venous sampling and bone densitometry. In Case 4, the thiazide provocative test was used to establish the diagnosis of primary hyperparathyroidism.This work was supported by grants from the USPHS 1-RO1-AM-16061 and 5-MO1-RR00633.