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Normal calcium oxalate crystal growth inhibition in severe calcium oxalate nephrolithiasis.

Urine from mammalian kidneys is regularly supersaturated with respect to calcium oxalate monohydrate, the most common solid phase in human nephrolithiasis, and also inhibits the nucleation, growth, and aggregation of calcium oxalate crystals. Nephrolithiasis is often associated with increased supersaturation, and it is assumed that this increase overbalances the inhibition effects, causing stones. However, some patients form stones in the absence of increased supersaturation, and in those patients, one might assume that reduced inhibition is the cause of their stones. This hypothesis was tested in 25 patients who formed at least ten stones each, yet lacked the usual metabolic abnormalities that increase supersaturation. Compared with 25 age- and sex-matched control subjects, urine supersaturation among the patients was not increased; this is an expected result of this study's selection criteria. Compared with the same age- and sex-matched control subjects, urine from the patients showed no evidence for reduced inhibition of calcium oxalate crystal growth, so low inhibition of growth did not contribute to pathogenesis of stones in our highly selected study population, despite their otherwise unexplained and active stone formation. These results do not support the hypothesis that growth inhibition defects are a cause of stone disease.

Calcium Oxalate↗

Anomalous phospholipid n-6 polyunsaturated fatty acid composition in idiopathic calcium nephrolithiasis.

Anomalies in the erythrocyte transport of anions and cations have been described in idiopathic calcium oxalate nephrolithiasis and seem to play a pathogenetic role in this disease. In consideration of the hypothesis that the complex array of ion flux cell abnormalities is an epiphenomenon of an anomaly in the composition of cell membranes, this study investigated cell-membrane lipid composition. In idiopathic calcium oxalate renal stone formers, in which ion transport abnormalities were present, and in healthy control subjects, plasma and erythrocyte membrane lipid composition, the erythrocyte oxalate exchange, and Na/K/2Cl cotransport activity were evaluated. Furthermore, in stone formers, the effect of a 30-day fish-oil diet supplementation on plasma lipids, erythrocyte oxalate exchange, oxaluria, and calciuria was investigated. The effect of archidonic acid released by phospholipase A2 on anion-carrier phosphorylation and activity in erythrocytes was evaluated as well. Patients had a lower content of linoleic and higher concentration of archidonic acids in both plasma and erythrocyte membrane phospholipids, and an increased archidonic/linoleic acid ratio. The archidonic acid level correlated with the erythrocyte oxalate exchange and sodium cotransport activity. Fish-oil supplementation lowered calcium and oxalate urine excretion, and normalized the erythrocyte oxalate exchange. Phospholipase A2 increased the erythrocyte anion-carrier protein phosphorylation and the oxalate exchange. This study shows that idiopathic calcium nephrolithiasis in the patient group reported here is characterized by a systemic defect in phospholipid archidonic acid levels that might provide an answer to the link between genetic background, dietary habits, and renal lithiasis.

Adult↗

Two cases of renal hypouricemia with nephrolithiasis.

We treated two cases of renal hypouricemia with nephrolithiasis. The serum uric acid level of the first patient was 1.5 mg/dl, and the ratio of uric acid clearance to creatinine clearance (CUA/Ccr) was 75.7%. In the benzbromarone (BZB) suppression test, CUA/Ccr was increased from 60.4% to 130.0%, but was not decreased in response to the pyrazinamide (PZA) suppression test. This patient was considered to have a presecretory reabsorptive urate transportation defect. His condition was also associated with IgA nephropathy. The serum uric acid level in the second patient was 1.0 mg/dl and CUA/Ccr was 56.0%. Neither PZA nor BZB had a significant effect on CUA/Ccr. He was considered to have a subtotal uric acid transportation defect. Both patients were incidentally found to have nephrolithiasis. The second patient had abnormal maximum tubular secretory capacity for para-aminohippurate (PAH) (TmPAH), and was found to have two kinds of proximal tubular abnormalities related to uric acid and PAH.

Adult↗

Heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG) and bikunin are up-regulated during calcium oxalate nephrolithiasis in rat kidney.

We reported that expression of both HSPG and of bikunin are increased in calcium oxalate (CaOx) nephrolithic rat kidneys (lida et al., J. Am. Soc. Nephrol. 1999, Urol. Res. 1997). However, these findings were obtained from separate experiments. The present study evaluates whether levels of HSPG and bikunin expression differ in the rat kidney during calcium oxalate nephrolithiasis. Twenty-four male Wistar rats weighing 200-250 g were assigned to one of four groups (n = 6 each group) and administered with 0.5% ethylene glycol daily and 0.5 microgram of 1 alpha-OH-D3 every other day to induce CaOx nephrolithiasis. Animals were sacrificed 1 or 2 weeks later and both kidneys were excised. The cortex was separated from the medulla and papillary tips in the right kidney, then stored in liquid nitrogen for quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR). The left kidney was fixed in 10% buffered formalin for histochemical studies. We assessed the variable gene expression of both HSPG and bikunin by QC-RT-PCR. Immunohistochemical analyses of left kidney tissue samples determined the localization of HSPG and bikunin. Normal rats serving as controls (n = 6 each) were also sacrificed and processed in the same manner as the experimental groups. QC-RT-PCR confirmed that HSPG and bikunin mRNA expression is significantly increased in nephrolithic kidneys (p < 0.05; Mann-Whitney test), and that medulla and papillary tips tended to express more mRNA of both. Immunohistochemical studies revealed that the production of HS and bikunin was increased in both the distal and proximal tubules of nephrolithic kidneys. These findings suggest that the increased expression of both HSPG and bikunin play an important role during calcium oxalate stone formation. In addition, this phenomenon might be associated with the progression of urothelial damage.

Animals↗

Postpartum anuria caused by silent bilateral nephrolithiasis.

A case of remarkable silent anuria caused by bilateral nephrolithiasis in the post-partum period is reported. The anuria was not associated with any kind of pain and the diagnosis was not revealed until three days postpartum when an intravenous pyelography was carried out. Differential diagnosis and management of nephrolithiasis are discussed. Ultrasound scanning is recommended as a routine procedure for all patients with signs and symptoms of renal dysfunction during pregnancy.

Adult↗

Nephrolithiasis: how it happens and what to do about it.

Nephrolithiasis is caused by several biochemical mechanisms, identification of which allows specific therapy that may prevent recurrences. In patients with their first kidney stone, careful evaluation is needed to identify those at highest risk for recurrence. Extensive evaluation of this subgroup should lead to proper diagnosis and management of nephrolithiasis, resulting in lower morbidity for these patients.

Acute Disease↗

Oxypurinol nephrolithiasis in regional enteritis secondary to allopurinol therapy.

A patient with regional enteritis and recurrent uric acid nephrolithiasis was treated with allopurinol. While on 600 mg of allopurinol daily, she began to pass many small, soft, yellow stones. Analysis of the stones by liquid chromatographic and gas chromatograph/mass spectrometric techniques revealed that their major constituent was oxypurinol, a metabolite of allopurinol. Metabolic studies of the patient indicated that increasing doses of allopurinol were associated with increases in xanthine and oxypurinol excretion, while uric acid excretion was not reduced. This case illustrates a complication of high-dose allopurinol therapy in the treatment of uric acid nephrolithiasis.

Adult↗

Evidence justifying a high fluid intake in treatment of nephrolithiasis.

We quantitatively assessed the effect of urinary dilution on the crystallization of calcium salts. Urinary dilution was achieved in vitro (1 to 2 L/d) by addition of water to urine from six patients with renal stones and two normal subjects, and in vivo (1.023 to 2.383 L/d) by an increased ingestion of distilled water in four patients with nephrolithiasis and three normal subjects. Both forms of urinary dilution significantly reduced the urinary activity product ratio (state of saturation) of calcium phosphate (brushite), calcium oxalate, and monosodium urate. Moreover, the formation product ratio (limit of metastability or minimum supersaturation needed to elicit spontaneous nucleation) of calcium oxalate significantly increased, although that for brushite did not change significantly. Thus, there was a reduced propensity for crystallization of calcium salts. The results provide objective evidence for the beneficial role of an increased fluid intake in the management of nephrolithiasis.

Calcium Oxalate↗

Bilateral uric acid nephrolithiasis and ureteral hypertrophy in a free-ranging river otter (Lontra canadensis).

We report the first case of uric acid nephrolithiasis in a free-ranging river otter (Lontra canadensis). A 7 yr old male river otter collected from the Skagit River of western Washington (USA) had bilateral nephrolithiasis and severely enlarged ureters (one of 305 examined [0.33%]). The uroliths were 97% uric acid and 3% protein. Microscopic changes in the kidney were confined to expansion of renal calyces, minor loss of medullary tissue, and multifocal atrophy of the cortical tubules. No inflammation was observed in either kidney or the ureters. The ureters were enlarged due to marked hypertrophy of smooth muscle plus dilation of the lumen. Fusion of the major calyces into a single ureteral lumen was several cm distal to that of two adult male otters used as histopathologic control specimens. This case report is part of a large contaminant study of river otters collected from Oregon and Washington. It is important to understand diseases and lesions of the otter as part of our overall evaluation of this population.

Animals↗

Role of sex hormones in experimental calcium oxalate nephrolithiasis.

It is unclear why men have a higher incidence of calcium oxalate nephrolithiasis than women. This study examined the role of sex hormones on urinary oxalate excretion and kidney stone formation in an experimental model of urolithiasis. Adult male and female Sprague Dawley rats with different sex hormone modulations were given 0.75% ethylene glycol for 2 wk to induce hyperoxaluria and kidney calcium oxalate crystal deposition. The study groups were: intact male and female rats; castrated male and female rats; intact male or female rats with opposite sex hormone implants; and castrated male and female rats with either testosterone or estradiol implants. Overall, a significant negative correlation between urinary oxalate and plasma estradiol/testosterone ratio was found. None of the estradiol-implanted rats, whether male or female, intact or castrated, developed kidney crystal deposits. The three groups of testosterone-implanted rats had a 43 to 88% rate of kidney calcium oxalate crystal deposition. These results indicate that androgens increase and estrogens decrease urinary oxalate excretion, plasma oxalate concentration, and kidney calcium oxalate crystal deposition. These findings may partly explain why nephrolithiasis is a predominantly male disease.

Animals↗

Prevention of recurrent nephrolithiasis.

The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones.

Consensus Development Conferences, NIH as Topic↗

Genetic and dietary factors in idiopathic calcium nephrolithiasis. What do we have, what do we need?

Nephrolithiasis is a complex, multifactorial disease resulting from an interaction between environmental and genetic factors, even if the actual contributions of these factors to stone disease are not yet quantifiable. The lack of convincing findings on genetic factors and genes responsible for nephrolithiasis is due to our still inadequate understanding of the pathogenesis. The hypothesis of an anomaly in cell membrane lipid composition might conceivably be the defect which links genetic and dietary factors and renal stone disease.

Animals↗

Nephrolithiasis associated with autosomal dominant polycystic kidney disease: contemporary urological management.

PURPOSE: We evaluate the role of contemporary urological intervention in patients with nephrolithiasis associated with autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: Intervention for upper tract stones associated with autosomal dominant polycystic kidney disease was performed in 5 women and 2 men 29 to 65 years old (mean age 47). Indications for intervention consisted of flank pain in 6 patients and/or hematuria in 2. A total of 12 procedures (mean 1.7 per patient) were performed, including shock wave lithotripsy in 6 patients, percutaneous nephrolithotomy in 2, retrograde endoscopy or manipulation in 3 and extended pyelonephrolithotomy in 1. RESULTS: All patients were rendered stone-free or had only residual "dust." Hospital stay for 5 patients was 1 night or less and there were no complications. Renal function for each patient was stable or improved as measured by serum creatinine. CONCLUSIONS: Most patients with autosomal dominant polycystic kidney disease who require intervention for nephrolithiasis can be safely and effectively treated with essentially any or all contemporary, minimally invasive techniques. The choice of intervention can be based primarily on size and location of the upper tract stones rather than the associated presence of polycystic kidneys.

Adult↗

[Metaphylaxis of nephrolithiasis].

Etiological factors and pathogenetic mechanisms were studied in 538 patients with nephrolithiasis. By composition of uroliths and salts, all the patients were divided into groups by types of urolithiasis (oxalate, urate, phosphate, cystic and mixed). After elimination of the uroliths using different methods, metaphylaxis of nephrolithiasis was conducted in all the patients. It varied with type of lithogenesis, etiology and pathogenesis. Antirecurrence therapy included diet with restriction of lithogenic substances, endogenic reduction of lithogenic metabolites and measures to decrease and block crystallization and lithogenesis. The treatment has diminished the incidence of recurrences from 32.3 to 9.6% (total), from 14.4 to 5.3% (in oxalate type), 47.2 to 16.9% (in phosphate type), 39.7 to 6.7% (in urate type), 40.5 to 17.7% (in mixed type).

Adult↗

[Surgical treatment of complicated forms of coral-like nephrolithiasis].

The paper presents the results of operative treatment of complicated coral nephrolithiasis in 22 patients. Organ-saving operations were made in exacerbation of pyelonephritis with pyoseptic intoxication, severe renal failure with hyperazotemia. Partial nephrolithotomy (semisectional), sectional nephrolithotomy, resection of the kidney and coral calculus and calicolithotomy were made in 10, 1, 5 and 1 patients, respectively. As a rule, nephrolithotomy was completed with renal drainage by nephrostomy. After resection of a renal segment nephrostomy was not necessary. Postoperative complications did not occur. These occur only in 2 patients with bilateral coral calculi after nephrolithotomy and pyelolithotomy (urinary fistulas). To correct them, nephrostomy was made. One lethal outcome was caused by cardiovascular failure. The above surgery led to normalization of nitrogen-eliminating function of the operated kidney, elimination of intoxication and improvement of the patient's condition. Efficiency of the above operations recommends allows to recommend them for treatment of severe coral nephrolithiasis.

Adult↗

Urinary citrate excretion in idiopathic nephrolithiasis.

OBJECTIVE: To determine urinary citrate excretion in children with nephrolithiasis and normal controls. DESIGN: Prospective. SETTING: Tertiary care center in New Delhi. METHODS: This study was done on 50 children, below the age of 12 years, with idiopathic urinary calculi and 150 age and weight matched controls. The children were divided into 3 groups: Group 1 (1-4 years), Group 2 (5-8 years) and Group 3 (9-12 years). Urinary citrate was estimated in a 24-hour urine sample using colorimetric method. The stones removed from these children were also analysed. RESULTS: There was a preponderance of urinary stones in males; the highest incidence being in Group 1. Excretion of citrate in 24-hour urine sample was significantly lower in patients compared to controls, for males in all age groups and for females in Group 3. However, there was no statistically significant difference in the urinary citrate value between males and females in a given age group for either controls or patients. The urinary citrate excretion increased with age in patients and controls, but the levels in patients were lower. Depending upon the constituents, four types of stones were identified, calcium phosphate, calcium oxalate, uric acid and magnesium ammonium phosphate. Nine stones had at least more than one major constituent. Hypocitraturia was detected in 43 percent cases. The incidence was 76 percent for calcium phosphate, 87 percent for calcium oxalate, 40 percent for uric acid stones and 50 percent for magnesium ammonium phosphate. CONCLUSION: This study shows that low urinary citrate is associated with urinary stones in children, especially in endemic areas, in the absence of obvious etiological factors. Urinary citrate excretion should be determined in all children with nephrolithiasis.

Case-Control Studies↗

Hyperoxaluria, nephrolithiasis, nephrocalcinosis and renal failure after massive resection of the small intestine: report of a case.

Hyperoxaluria is frequently seen in patients with inflammatory bowel disease, or after resection of the ileum. It is assumed to be responsible for the development of nephrolithiasis, nephrocalcinosis (oxalate nephrosis) and progressive renal impairment in these patients. Steatorrhea may aggravate the severity of hyperoxaluria. A 60-year-old male underwent massive resection of the jejunum and ileum 10 years prior to admission, due to strangulation of the small bowel, with occlusion of the superior mesenteric artery. He remained well except for steatorrhea which developed two-and-a-half years prior to admission, when microhematuria, proteinuria and oxaluria developed progressively. Since that time, the nephrolithiasis, nephrocalcinosis and renal failure have continued to worsen despite therapy with oxalate restriction and oxalate-binding agents. A renal biopsy, performed late in the clinical course, showed severe changes in the renal parenchyma. The decline in renal function proved irreversible. The unusual metabolic consequences of massive resection of the small intestine and their mechanisms are discussed.

Humans↗

[Telelithotripsy in the treatment of staghorn nephrolithiasis in children using the URAT-P lithotriptor].

The paper presents the results of telelithotripsy monotherapy for 34 staghorn stones in 32 nephrolithiasis children carried out at the RSFSR Research Institute of Urology, Moscow. Commonest manifestations of the disease were leukocyturia (87.5% of cases) and Proteus bacteriuria (31.8% of cases). Basing on roentgenological findings, the stones were classified into 3 groups: initial (K1), incomplete (K2) and complete (K3). All the children underwent treatment on Soviet lithotriptor "URAT-P" under a delicate regime using different techniques of disintegration which started from the periphery and advanced to the pelvic part of the calculus. No pretreatment drainage of the pelvicaliceal system was performed. The intended staged disintegration of the stones was achieved in 94.2% of cases at 2.4 sessions, on the average, and overall number of impulses 1973.1 per each stone. At discharge 76.4% of the children were free of the main mass of the stone dust. Acute pyelonephritis which appeared the most frequent postoperative complication developed in 7.8% of the patients one of which required open nephrostomy and one percutaneous puncture nephrostomy. Other cases were treated by specific antimicrobial therapy. Complete series of investigations in the postoperative period did not reveal any intra- or pararenal hematomas. Radioisotopic renography revealed improvement in renal function in 62% of cases in early postoperative follow-up. Thus, 93.8% of children with stag-horn stones were spared of traumatic operative intervention or invasive manipulations. This makes the method of telelithotripsy a valuable therapeutic tool in childhood staghorn nephrolithiasis.

Adolescent↗