Citrate (CG-120) therapy in urolithiasis. 2. Effect on urinary and serum biochemistry

The long-term effects of citrate therapy (CG-120, 3 g/day or 4 g/day) were examined in 398 patients with upper urinary tract calculi. We studied the influence of citrate therapy on urinary and blood biochemistry in 353 of them. CG-120 caused a sustained increase in urinary citrate, urinary pH and potassium, but no substantial or significant changes in other urinary parameters (uric acid, phosphate, oxalate, sodium, chloride and urine volume). Although urinary calcium decreased significantly up to the 24th week, it did not change significantly there after and it tended to increase at the 54th week. Urinary creatinine excretion decreased after 34 weeks of administration, but this phenomenon could not be explained, because the level of blood urea nitrogen and serum creatinine was not elevated in any case before administration. There were no changes in the serum calcium, magnesium, phosphate, uric acid, sodium, potassium or chloride level.     

Comparative study of the effects of pyruvate and CG-120 in preventing experimental oxalate urolithiasis in rats

Male Wistar-strain rats which had been fed a calcium-oxalate lithogenic diet (a glycolate diet) developed urinary calculi in 4 weeks. Sodium pyruvate or CG-120 (a mixture of citrate salts) had been added to this diet to determine its effect in preventing lithogenicity. Rats in the group fed a pyruvate diet had, however, almost no stones in the urinary system. Rats in the CG-120 group showed results somewhat similar to those in the pyruvate group. Increased urinary citrate excretion was observed in both groups and could be implicated as the main inhibitory factor in stone formation. Therefore, it can be concluded that CG-120 exerts a beneficial effect close to that of pyruvate in preventing calculi formation and that both substances cause a high citrate excretion in urine.     

Clinical studies on recurrence of urolithiasis. (2) Hypercalciuria and recurrence of urolithiasis

According to the dynamics of the urinary calcium excretion mechanism, we have classified the patients with urolithiasis into 4 groups, namely group I (normocalciuria; urinary calcium excretion of 270 mg/day or less for male patients and 210 mg/day or less for female patients), group II (absorptive hypercalciuria; hypercalciuric with urinary calcium excretion of 200 mg/day or less under the low calcium diet), group III (renal hypercalciuria; hypercalciuric with urinary calcium excretion exceeds 200 mg/day even under a low calcium diet), and group IV (hyperparathyroidism; hypercalciuric patients as in group III with high serum calcium). Of the 97 stone formers, 77 were classified into group I, 9 into group II, 8 into group III and 3 into group IV. Both under the restricted diet and under the ambulatory free diet, urinary calcium excretion of groups II, III and IV was significantly higher than that of the group I patients. It was noteworthy, however, that some of the patients in group I excreted much calcium without restriction of their diet. Although no difference in excretion of oxalate, magnesium and phosphate was observed between the 4 groups, the patients in groups II, and III excreted more uric acid into their urine than group I patients. As for stone recurrence rate, no difference was noted between group I and group II, III or IV. Based on these findings, we conclude that hypercalciuria has no significant role in the stone forming mechanism. However, lowering of urinary calcium and other stone forming constituents is mandatory in preventing stone recurrence until the mechanism of stone formation is elucidated more precisely.     

ESWL治疗尿路结石的影响因素及疗效评价

目的：探讨进一步提高体外冲击波碎石术（ESWL）的疗效及减少并发症的方法。方法：回顾性总结10年来5140例ESWL治疗成功的经验及存在的问题。结果：ESWL前未作尿、血、肝功能及专科等常规检查可导致严重并发症；作低能及急诊ESWL治疗疗效满意。结论：要减少并发症，提高疗效，ESWL前常规检查不可忽视；肾盂肾盏的解剖结构、类型及患者健康等有关因素易影响结石排净率。     

The conservative therapy of urolithiasis (author's transl)]

Some common conservative treating methods of urolithiasis are critically discussed. Based on physico-chemical relationships of solubility and cristallisation of stone-forming compounds our own methods of conservative treatment of urolithiasis is presented.     

急性结石性胆囊炎行腹腔镜胆囊切除术120例临床经验与分析

目的 探讨急性结石性胆囊炎(acute calculous cholecystitis)行腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)的操作要点和临床价值.方法 回顾性分析扬州大学临床医学院2006年8月～2008年6月对120例急性结石性胆囊炎患者施行腹腔镜胆囊切除术.其中,胆囊与大网膜粘连72例,胆囊与横结肠粘连9例,胆囊与十二指肠粘连5例,胆囊颈部结石嵌顿68例,Mirizzi综合征2例.结果 120例手术均获成功,无中转开腹,术后无一例胆漏,平均手术时间(45.0±13.1)min.结论 急性结石性胆囊炎不是腹腔镜胆囊切除术的禁忌证.丰富的经验与娴熟的手术操作技术是该类手术成功的关键.它仍然体现创伤小、并发症少、恢复快的特点.     

Experimental and clinical studies on calcium urolithiasis: (I) Animal model for calcium oxalate urolithiasis using ethylene glycol and 1-alpha (OH) D3

As calcium oxalate stones are the most important component in urolithiasis, an experimental model has to be designed to clarify the pathogenesis and aid in their prevention. Hyperoxaluria as well as hypercalciuria were produced in rats by administering ethylene glycol (0.5%, in drinking water administered ad libitum) and 1-alpha (OH) D3 (0.5 micrograms/rat given every other day), respectively, for three to four weeks. Neither drug alone produced stones efficiently as did the combination regimen of these two compounds. The occurrence of stones was 77.3%, and with only a moderate degree of renal functional impairment. Biochemical and histological data were obtained using this model.     

Citrate therapy for polycystic kidney disease in rats

BACKGROUND: Few treatments are available to slow the progression to renal failure in autosomal dominant polycystic kidney disease (PKD). In an animal model of PKD, the male heterozygous Han:SPRD rat, intake of a solution of potassium citrate plus citric acid (KCitr) from age one to three months prevented a decline in glomerular filtration rate (GFR). The present study tested whether this beneficial effect is sustained and explored handling of citrate and ammonia in normal and cystic kidneys. METHODS: Rats were provided with tap water or citrate solutions to drink, and clearance and survival studies were performed. RESULTS: The GFRs of rats with PKD that consumed KCitr from one month of age were normal at six months of age, while those of their counterparts on water were about one third of normal. Long-term KCitr treatment extended the average life span of rats with PKD from 10 to 17 months. Compared with normal rats, water-drinking rats with PKD had higher plasma [citrate], renal cortical [citrate], and fractional excretion of citrate, and lower rates of renal citrate consumption, ammonia synthesis, and ammonia excretion. Cortical PNH3 was not elevated in cystic kidneys. Intake of Na3 citrate/citric acid solution or K3 citrate solution, but not ammonium citrate/citric acid solution, prevented a decline in GFR in three-month-old rats with PKD. CONCLUSIONS: Rats with PKD show abnormal renal handling of citrate and ammonia. Citrate salts that have an alkalinizing effect preserve GFR and extend survival.     

PGE(1) therapy for Martorell's ulcer

Martorell's ulcer is a type of ischaemic ulcer of the lower leg, defined by severe pain and female-to-male predominance. The aim of this article is to assess the therapeutic effectiveness of PGE(1), both in pain control and in the healing times of Martorell's ulcers for patients already undergoing antihypertensive treatment. Between January 2004 and December 2008, we recruited 10 patients with Martorell's ulcers. These patients were organized into two groups (A and B). Group A included six patients who underwent only antihypertensive treatment with calcium channel blockers or angiotensin converting enzyme inhibitors. Group B consisted of four patients who underwent continuous administration of PGE(1) through a single-day elastomer (120 μg/24 hours) for 7 days. In both groups, we observed a progressive reduction in the surface area of Martorell's ulcers until complete recovery, but there was a significant difference with regards to healing time. We also observed a significant improvement in symptomatic pain after only 2 days of PGE(1) therapy. It has now been proved that antihypertensive treatment leads to ulcers healing but, according to our experience, intravenous infusion of prostaglandins improves peripheral perfusion and symptomatic pain and decreases healing time.     

Inhibition by sodium-potassium citrate (CG-120) of calcium oxalate crystal growth on to kidney stone fragments obtained from extracorporeal shock wave lithotripsy

Retention of fragments within the kidney after extracorporeal shock wave lithotripsy (ESWL) continues to be a major shortcoming of this form of stone treatment. The aim of this study was to evaluate the ability of sodium-potassium citrate to inhibit calcium oxalate crystal nucleation and growth on to stone fragments remaining after ESWL. The continuous flow crystallisation technique was adapted to induce calcium oxalate crystal nucleation and growth on to the surface of fragmented kidney stones and the inhibitory effect of sodium-potassium citrate was assessed by scanning electron microscopy and by determining the relative increase in crystalline mass at final concentrations of 0, 2, 4, 6, 8, 10 mmol/l. Sodium-potassium citrate significantly inhibited the deposition of new crystalline calcium oxalate in a dose-dependent manner above 2 mmol/l; these findings were confirmed by scanning electron microscopy. It was concluded that sodium-potassium citrate may provide an effective means of preventing the formation of new kidney stones by the deposition of calcium oxalate on to residual stone fragments resulting from ESWL and that the technique used is an efficient means of testing the efficacy of therapeutic agents to prevent stone recurrence in patients treated with ESWL.