Urine pH in renal calcium stone formers who do and do not increase stone phosphate content with time

Background. Calcium phosphate (CaP) renal stones appear to beincreasing in prevalence, and are caused by high urine CaP supersaturation,which arises from genetic hypercalciuria and high urine pH.Renal damage from stones or procedures, or treatments for stonecould raise urine pH; alternatively pH may be intrinsicallyhigh in some people who are thereby predisposed to CaP stones. Methods. To distinguish these alternatives we sequenced changesin urine pH and stone CaP content asking which occurs firstin patients whose stones showed progressive increase in CaPover time. From 4767 patients we found 62 in whom we could documenttransformation from calcium oxalate (CaOx) to CaP stones, and134 CaOx controls who did not transform. Laboratory and clinicalfinding were contrasted between these groups. Results. Even when patients were forming relatively pure CaOxstones, those destined to increase stone CaP had higher urinepH than controls who never did so. Their higher pH was presentbefore and during treatments to prevent new stone formation.Shock wave lithotripsy was strongly associated with increasingstone CaP but urine pH bore no relationship to number of procedures. Conclusion. We conclude that high pH may not be acquired asa result of stones or their treatments but may precede transformationfrom CaOx to CaP stones and arise from diet or possibly heredity.     

Hemiacidrin: a useful component in the treatment of infectious renal stones

Experimental irrigation of 15 infectious renal stones with hemiacidrin resulted in complete dissolution of 11 stones within 5 days. Three of the undissolved stones had a calcium oxalate (CaOx) content of more than 10%. Stones containing calcium phosphate (CaP) and magnesium ammonium phosphate (MAP) and weighing less than 500 mg were most easily dissolved. Twenty-five stones placed in 10 ml of hemiacidrin resulted in complete dissolution of 13 and partial dissolution of 11. Even this experiment showed that the CaOx content was of importance for the outcome of hemiacidrin treatment. After treatment the MAP and CaP fractions had decreased and CaOx increased. In 36 clinical irrigations of residual concrements of known chemical composition, 5 resulted in total stone dissolution and 21 in a reduced stone volume, whereas the result was inconclusive in 3. Seven stones were not affected by the treatment, these stones were usually composed of CaP and CaOx. There was a good correlation between the dissolution test and the clinical response to hemiacidrin treatment. Based on these findings it is suggested that hemiacidrin might be a useful complement to the modern techniques of stone fragmentation such as extracorporeal shock wave lithotripsy and percutaneous surgery, at least for infectious stones with a CaOx content of less than 10%.     

Evaluation of urine composition and calcium salt crystallization properties in standardized volume-adjusted 12-h night urine from normal subjects and calcium oxalate stone formers

The volume of 12-h night urine from ten normal men (NM), ten normal women (NW) and 31 male calcium stone formers (SFM) was adjusted to 750 ml and analysed with respect to supersaturation with calcium oxalate (CaOx) and calcium phosphate (CaP), inhibition of CaOx crystal growth and aggregation, as well as the CaOx and CaP crystallization propensity. Concentrations of oxalate and glycosaminoglycans and AP(CaOx) index, an estimate of the CaOx ion-activity product, were higher and the concentration of citrate lower in NM than in NW. In SFM the directly assessed risk of CaOx crystallization was higher and the inhibition of CaOx crystal growth lower than in NM. There were no differences between the groups regarding inhibition of CaOx crystal growth by 74% dialysed urine or inhibition of CaOx crystal aggregation. SFM with mixed CaOxCaP stones had a higher concentration of phosphate and a higher AP(CaP) index at pH 7.0 than SFM with CaOx stones.     

Stone disease: Diagnosis and medical management

The majority of calcium stones are composed of calcium oxalate (CaOx), with 70% of these associated with calcium phosphate (CaP). The basic prerequisite is urine sufficiently supersaturated with CaOx, CaP or both. This is balanced against inhibitors or modifiers that prevent crystallisation. Risk factors for the disease include: hypercalciuria, hyperoxaluria, hypocitraturia, a high pH and a low urine volume. Diagnostic workup is mainly required in patients with complicated, recurrent disease. Complicated stones include recurrent CaOx stones, struvite (infection stone), cystine and uric acid stones. Diet can have a significant impact on urine composition and is frequently used in the management of stone patients. Various modifications, including increased fluid intake, are recommended according to the type of stone implicated.     

Changes in stone composition according to age in Tunisian pediatric patients

The epidemiology of renal stones has changed all over the world toward a predominance of calcium oxalate stones. However, studies evaluating the influence of age and gender on the distribution of the various types of urinary calculi are scarce. We will present the results of a study based on 205 calculi (from 122 boys and 83 girls) analyzed by infrared spectroscopy between 1993 and 2007. 90% of stones were collected by surgery, whereas only 6% by spontaneous passage. The biological exploration was performed in only 126 cases. Etiology was metabolic in 13.5%. 10.7% of stones were infectious, 13.1% were endemic and 54.9% were idiopathic. 7.8% were secondary to urinary stasis with malformation but no infection. Calcium oxalate (CaOx) was the predominant constituent in 54.7% of stones, followed by calcium phosphate and purines 14.6% in each of the cases. We found an increasing prevalence of calcium oxalate stones with age in both genders (42.9% in infant vs. 59.3% in child) (P < 0.05). Struvite stones were more frequent in infant than children. Purine stones were predominant in 20% of cases, but its prevalence decreases with age. The increase in calcium oxalate stone in school age children and the decrease in struvite and purine stones confirm the change on the etiology of urolithiasis according to age.     

Role of the urinary calcium in the growth of calcium stone

We analyzed the relationship between the rate and clinical factors. The growth rate per year of the stone was measured by Nabeshima's method in 29 male patients with renal calcium stones including 7 pure calcium oxalate (CaOx) stones and 22 mixed calcium oxalate and calcium phosphate (CaOx-CaP) stones. The 24-hour urinary excretion of calcium, phosphate, uric acid and magnesium were assayed under an ambulatory free diet in 5 patients with CaOx stones and 15 with CaOx-CaP stones. The relationship between the growth rate and the urinary excretion of stone-forming parameters was examined. We found a significant positive correlation between the growth rate of calcium stones and the urinary excretion of calcium (p<0.02). In addition, the growth rate of CaOx-CaP stone was significantly higher than that of pure CaOx stone (p<0.05). In conclusion, urinary calcium is important for the growth of renal calcium stones.     

Brushite stone disease as a consequence of lithotripsy?

The incidence of calcium phosphate (CaP) stone disease has increased over the last three decades; specifically, brushite stones have been diagnosed and treated more frequently than in previous years. Brushite is a unique form of CaP, which in certain patients can form into large symptomatic stones. Treatment of brushite stones can be difficult since the stones are resistant to shock wave and ultrasonic lithotripsy, and often require ballistic fragmentation. Patients suffering from brushite stone disease are less likely to be rendered stone free after surgical intervention and often experience stone recurrence despite maximal medical intervention. Studies have demonstrated an association between brushite stone disease and shock wave lithotripsy (SWL) treatment. Some have theorized that many brushite stone formers started as routine calcium oxalate (CaOx) stone formers who sustained an injury to the nephron (such as SWL). The injury to the nephron leads to failure of urine acidification and eventual brushite stone formation. We explore the association between brushite stone disease and iatrogenic transformation of CaOx stone disease to brushite by reviewing the current literature.     

Presence of lipids in urine,crystals and stones: implications for the formation of kidney stones

BACKGROUND: Cell membranes and their lipids play critical roles in calcification. Specific membrane phospholipids promote the formation of calcium phosphate and become a part of the organic matrix of growing calcification. We propose that membrane lipids also promote the formation of calcium oxalate (CaOx) and calcium phosphate (CaP) containing kidney stones, and become a part of their stone matrix. METHODS: Human urine, crystals of CaOx and CaP produced in the urine of healthy individuals, and urinary stones containing struvite, uric acid, CaOx and CaP crystals for the presence of membrane lipids were analyzed. Crystallization of CaOx monohydrate at Langmuir monolayers of dipalmitoylphosphatidylglycerol (DPPG), dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidylglycerol (DOPG), palmitoyloleoylphosphatidylglycerol (POPG) and dimyristoylphosphatidylglycerol (DMPG) was investigated to directly demonstrate that phospholipid assemblies can catalyze CaOx nucleation. RESULTS: Urine as well as CaOx and CaP crystals made in the urine and various types of urinary stones investigated contained some lipids. Urine of both CaOx and uric acid stone formers contained significantly more cholesterol, cholesterol ester and triglycerides than urine of healthy subjects. However, urine of CaOx stone formers contained more acidic phospholipids. The organic matrix of calcific stones contained significantly more acidic and complexed phospholipids than uric acid and struvite stones. For each Langmuir monolayer precipitation was heterogeneous and selective with respect to the orientation and morphology of the CaOx crystals. Crystals were predominantly monohydrate, and most often grew singly with the calcium rich (10-1) face toward the monolayer. The number of crystals/mm2 decreased in the order DPPG> DPPC and was inversely proportional to surface pressure and mean molecular area/molecule. CONCLUSIONS: Stone forming conditions in the kidneys greatly impact their epithelial cells producing significant differences in the urinary lipids between healthy and stone forming individuals. Altered membrane lipids promote face selective nucleation and retention of calcium oxalate crystals, and in the process become a part of the growing crystals and stones.     

A hypothesis of calcium stone formation: an interpretation of stone research during the past decades

An interpretation of previous and recent observation on calcium salt crystallization and calcium stone formation provide the basis for formulation of a hypothetical series of events leading to calcium oxalate (CaOx) stone formation in the urinary tract. The various steps comprise a primary precipitation of calcium phosphate (CaP) at high nephron levels, establishment of large intratubular and/or interstitial (sub-epithelial) aggregates of CaP. These crystal masses subsequently might be dissolved during periods with low urine pH. On the denuded surface of subepithelial or intratubularly trapped CaP, release of calcium ions can result in very high ion-activity products of CaOx, particularly during simultaneous periods with peaks of CaOx supersaturation. Crystals of CaOx may result from nucleation in the macromolecular environment surrounding the apatite crystal phase. In the presence of low pH, low citrate and high ion-strength of urine, formation of large CaOx crystal masses can be accomplished by self-aggregation of Tamm–Horsfall mucoprotein. Following dislodgment of the initially fixed CaOx stone embryo, the further development into to clinically relevant stone is accomplished by CaOx crystal growth and CaOx crystal aggregation of the retained stone material. The latter process is modified by a number of inhibitors and promoters present in urine. The retention of the stone is a consequence of anatomical as well as hydrodynamic factors.     

双源CT多参数比较一水草酸钙结石与混合钙结石的临床价值

目的:探讨双源CT多参数比较上尿路一水草酸钙结石与混合钙结石的临床价值,为临床个体化治疗泌尿系结石提供影像学依据。方法:回顾性分析2018年1月至2019年6月在本院收治的120例上尿路结石患者的临床资料。按照结石离体行红外光谱分成一水草酸钙组(42例)和混合钙结石组(78例),所有患者术前均行双源CT检查,获得两组结...     

The pathogenesis of calyceal diverticular calculi

Controversy exists over whether metabolic factors or urinary stasis predominate in the pathogenesis of calyceal diverticular calculi. We performed a study to better define the effects urinary stasis and metabolic abnormalities have in the pathogenesis of calyceal diverticular stones. Twenty-nine patients who underwent percutaneous treatment of calyceal diverticular calculi were studied. All patients underwent 24 h urine collection to evaluate metabolic risk factors. In three patients, urine was sampled directly from the diverticulum for metabolic studies. The urinary stone risk parameters of the patients with calyceal diverticular stones (Tic SF) were similar to those of a well-characterized cohort of calcium oxalate stone formers (CaOx SF). When compared to a group of normal people, the Tic SF and CaOx SF were significantly more hypercalciuric and their urine was significantly more supersaturated with calcium oxalate. Urine aspirated directly from the diverticulum had the lowest SSCaOx when compared to ipsilateral and contralateral renal pelves. The urinary risk profiles of patients with diverticular calculi are similar to those of CaOx SF, suggesting a metabolic etiology of diverticular stones. However, the SS CaOx of urine aspirated directly from the diverticula is significantly lower than that of the renal pelves; these data support the hypothesis that urinary stasis significantly contributes to the pathogenesis of calyceal diverticular calculi. Taken together, it seems likely that calyceal diverticular calculi arise from a combination of metabolic abnormalities and urinary stasis.     

Kidney stones during pregnancy: an investigation into stone composition

Kidney stones can be a source of considerable morbidity for pregnant women. Although there is a body of literature confirming that different stone compositions predominate for different age and sex cohorts, there have been no similar reports characterizing the nature of stone disease during pregnancy. We performed a multi-institutional study to define the composition of renal calculi diagnosed during pregnancy. We retrospectively reviewed the records from two stone referral centers of all patients diagnosed with a de novo kidney stone during pregnancy who underwent a procedure for the purpose of stone removal from June 2001 through September 2007. A total of 27 patients were identified, with a mean age of 26.8 years (range, 21-34). Twenty patients (74%) had no history of prior stone formation. Seven patients (26%) had previously formed stones, although none of these patients had a known kidney stone at the time they became pregnant. Stones were removed in the first, second, third trimester and immediately post-partum in 4, 52, 22, and 22% respectively. Stone removal was performed without complication in all cases. Analysis found that in 74% of all cases (20 patients) stones were composed predominantly of calcium phosphate (hydroxyapatite). In 26% of cases, (7 patients) the stones were composed predominantly of calcium oxalate. Of the seven patients with prior stone history, three patients had previously formed calcium phosphate stones and four patients had previously formed calcium oxalate stones. Calcium oxalate calculi are the most common stone in non-pregnant women of a comparable age as our subjects. However, our present data suggest that stones detected during pregnancy are most commonly composed of calcium phosphate (hydroxyapatite). Indeed, it is the minority of stones that are composed of calcium oxalate. Although the reason for this unusual preponderance of calcium phosphate calculi is unclear, physiologic alterations that occur during pregnancy may be influential.     

Bacteriology of infected stones

Urinary calculi were cultured using a method which distinguishes surface contamination from bacteria actually residing within the stone. Culture results were correlated with the results of the stone analysis. The majority of stones were struvite and invariably infected, primarily with a urea-splitting bacteria, such as Proteus mirabilis, which caused recurrent urinary infection. In contrast, most oxalate stones were sterile. Occasionally an oxalate stone was secondarily infected and caused relapsing urinary infection.     

Clinical implications of abundant calcium phosphate in routinely analyzed kidney stones

BACKGROUND: To better portray the clinical phenotype of kidney stone patients with high calcium phosphate (CaP) stone abundance, we present here clinical and laboratory findings of large numbers of stone formers (SF) with stone CaP ranging from 0% to 100%. Our purpose was to inform clinicians and highlight areas that seem to deserve further research. METHODS: We calculated average percent CaP (CaP%) in all stones of 1201 patients, and classified them into CaOx (N= 1011) or CaP (N= 190). Sex differences, stone formation rates, urine stone risk factors, extracorporeal shock wave lithotripsy (ESWL) treatments, and relapse during treatment were quantified in relation to stone CaP content. RESULTS: CaP% has risen for three decades, especially among women. ESWL rates adjusted for numbers of stones and duration of stone disease were higher in CaP SF (0.6 vs. 1.86 and 0.73 vs. 1.82, CaOx vs. CaP, men and women, respectively, P < 0.001), and especially when stones contained brushite (2.90 vs. 1.02 and 3.11 vs. 1.35, brushite vs. not, males and females, respectively, P < 0.001). Urine pH and CaP supersaturation rose in proportion to CaP% in a dose response manner. Relapse rates of CaP and CaOx SF did not differ, and both did well with medical prevention. CONCLUSION: Stone CaP% has risen for three decades. CaP SF, particularly with brushite stones, receive more ESWL treatments than CaOx SF, not explained by stone number or duration of stone disease. Urine supersaturations explain the high CaP%. High CaP% does not hamper medical stone prevention.     

Composition of renal stones and their frequency in a stone clinic: Relationship to parameters of mineral metabolism in serum and urine

Summary Stone analyses (kidney, upper urinary tract) of the department of Urology, University of Erlangen, from a four-year-period (1974–1977) have been recorded with emphasis to stone composition, sex and age of the pertinent stone forming patients.During this time period there were no substantial changes as regards the per cent frequency of the various stone types. The most frequent type was calcium oxalate (CaOx), followed by uric acid, calcium phosphate (CaP), struvite and cystine. Stone analyses were mostly requested for patients between 46 and 55 years of age. Stone incidence in our clinic is calculated to be 1.22 times higher in males than females, especially beyond 36 years of age. The frequency peaks are: pure (=100 per cent) CaOx 36–45 years; CaOx with additional mineral phases (mostly CaP) 46–55 years; uric acid 56–65 years; CaP 26–35 years.From those patients who underwent further investigations in searching for metabolic abnormalities serum concentrations, urine mineral clearances in fasting urine samples, and activity products of stone forming mineral phases in sequentially collected specimens from 24 h and 2 h fasting urine had been measured and compared with values from healthy control subjects. In urolithiasis (idiopathic) there is a normal parathyroid hormone blood level, a generally lower serum inorganic phosphate and magnesium concentration.In pure (=100 per cent) CaOx and uric acid lithiasis serum uric acid and creatinine are higher than in controls, urine pH and calcium clearance in some groups are different too. Clearances of magnesium, uric acid, phosphate, sodium are within normal limits in urolithiasis. When expressing the propensity to form stones in terms of activity products, then only uric acid lithiasis deviates substantially from normal. All other stone types differ only slightly or not at all from each other and controls respectively.It is concluded that 1) in our geographic region the various stone types prevail in different age periods; 2) there are distinct alterations of parameters of mineral metabolism in urolithiasis; 3) measuring urine clearances may lead to assume falsely normal mean urine excretion of stone forming constituents.     

Calcium oxalate calculi found attached to the renal papilla: Preliminary evidence for early mechanisms in stone formation

BACKGROUND: Calculi are commonly found attached to the renal papilla in calcium oxalate (CaOx) stone formers, but the mechanisms by which stones form in this manner are not well established. MATERIALS AND METHODS: Data are presented from three attached stones collected from different patients. Stone morphology and composition were determined using micro computed tomography (CT) and infrared microspectrometry. RESULTS: One of the stones was composed of CaOx with a peripheral region of apatite, such as might have come from a Randall's plaque. Another stone was covered with large CaOx crystals but contained at least two layers of apatite, with no apatite regions exposed at the surface. The third stone contained CaOx with inclusions of apatite and more apatite on its surface, along with a substantial volume of poorly mineralized material that could not be identified. CONCLUSIONS: The complexity of these stones and their differing morphologies do not by themselves allow inference of the mechanism of stone formation. Future work will require the careful documentation of attached stones on the papilla, as well as study of the papilla after the stone has been removed, before it can be determined whether such diverse CaOx stones originate from the same or different underlying etiologies.     

Clinical patterns of paediatric urolithiasis

A series of 270 paediatric stone patients was studied retrospectively according to the clinical pattern of urolithiasis (age and sex, stone location, stone analysis, recurrence rate) and aetiology of stone disease (infection, anatomical, metabolic or idiopathic). Infection stones occurred earliest and more commonly in males and were usually upper tract struvite calculi related to Proteus infection. Anatomical stones were most commonly associated with pelviureteric junction (PUJ) obstruction and had a high recurrence rate, despite surgical correction of obstruction. Idiopathic stones most resembled those found in adult urolithiasis by virtue of occurring latest, being sited in the ureter more often and being more frequently composed of calcium oxalate. Metabolic stones were most frequently calcium phosphate or cystine and virtually all were renal. They comprised the smallest group but had the highest recurrence rate.     

复杂性肾结石化学成分分析(附84例报告)

目的 :分析复杂性肾结石化学成分特点 ,为预防其复发提供依据。方法 :对 84例在我院行微经皮肾镜取石术的复杂性肾结石患者 (纳入标准为鹿角形结石、单肾或双肾多发性结石且最大结石直径 >2 .5cm)进行结石化学成分分析 ,同时收集相关临床资料。结果 :80例 (95 .2 % )为含钙混合性结石和感染结石 ,其中草酸钙加磷酸钙 30例 (35 .7% ) ;草酸钙加尿酸 14例 (16 .7% ) ;草酸钙加磷酸钙加尿酸 10例 (11.9% ) ,草酸钙加磷酸钙加胱氮酸 1例 ;含钙结石并发感染结石 14例 (16 .7% ) ;感染结石 11例 (13.1% )。 4例 (4 .8% )为单一成分。结论 :体积较大的复杂性肾结石成分复杂 ,生长过程中常多种病因参与 ,应加强其病因诊断和针对多种病因采用积极的预防性治疗     

232例湖北地区泌尿系结石红外光谱成分分析

目的：分析湖北地区泌尿系结石化学成分的构成,为本地区结石的防治提供依据。方法：采用结石红外光谱自动分析系统对2011年11月～2012年8月期间收集到的湖北地区泌尿系结石232例进行成分分析。结果：232例结石中,各成分的检出率为：一水草酸钙（COM）85．34％,二水草酸钙（COD）62．93％,碳酸磷灰石（CA）24．14％,无水尿酸（UA）12．93％,二水磷酸氢钙（PH）4．31％,磷酸铵镁（MAP）6．90％,黄嘌呤1．29％,胱氨酸（CYS）1．29％,方解石0．86％,尿酸铵（AU）0．86％。含草酸钙成分结石86．21％,含磷酸钙成分结石28．45％,含磷酸铵镁成分结石6．90％,含尿酸成分结石13．79％,含胱氨酸成分结石1．29％。混合成分结石181例（78．02％）,尿路结石发病男性多于女性,男女比例为3．14：1。结论：湖北地区泌尿系结石以混合性结石为主,COM检出率最高,其次为COD。结石成分分析对于结石的防治有重要意义。     

Thiazides reduce brushite, but not calcium oxalate, supersaturation, and stone formation in genetic hypercalciuric stone-forming rats

Over 59 generations, a strain of rats has been inbred to maximize urine calcium excretion. The rats now excrete eight to 10 times as much calcium as controls. These rats uniformly form calcium phosphate (apatite) kidney stones and have been termed genetic hypercalciuric stone-forming (GHS) rats. The addition of a common amino acid and oxalate precursor, hydroxyproline, to the diet of the GHS rats leads to formation of calcium oxalate (CaOx) kidney stones. Hydroxyproline-supplemented GHS rats were used to test the hypothesis that the thiazide diuretic chlorthalidone would decrease urine calcium excretion, supersaturation, and perhaps stone formation. All GHS rats received a fixed amount of a standard 1.2% calcium diet with 5% trans-4-hydroxy-l-proline (hydroxyproline) so that the rats would exclusively form CaOx stones. Half of the rats had chlorthalidone (Thz; 4 to 5 mg/kg per d) added to their diets. Urine was collected weekly, and at the conclusion of the study, the kidneys, ureters, and bladders were radiographed for the presence of stones. Compared with control, the addition of Thz led to a significant reduction of urine calcium and phosphorus excretion, whereas urine oxalate excretion increased. Supersaturation with respect to the calcium hydrogen phosphate fell, whereas supersaturation with respect to CaOx was unchanged. Rats that were fed Thz had fewer stones. As calcium phosphate seems to be the preferred initial solid phase in patients with CaOx kidney stones, the reduction in supersaturation with respect to the calcium phosphate solid phase may be the mechanism by which thiazides reduce CaOx stone formation.