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Determination of protein-bound urinary gamma-carboxyglutamic acid in calcium nephrolithiasis.

Nephrocalcin is a urinary gamma-carboxyglutamic acid (Gla) containing protein that may be a physiological inhibitor of calcium oxalate nephrolithiasis. Nephrocalcin isolated from urine of stone formers seems to be abnormal in lacking Gla that is required for inhibitory activity. In order to study this hypothesis, we compared the protein-bound urinary Gla contents in 32 calcium oxalate stone formers and in 24 controls. Protein-bound Gla was resolved by reversed-phase high-performance liquid chromatography after elimination of free Gla, alkaline hydrolysis and precolumn derivatization with o-phthalaldehyde and mercaptoethanol. Protein-bound urinary Gla concentrations were similar in stone formers (0.83 +/- 0.38 mumol/l, mean +/- SD) and controls (0.81 +/- 0.27) and were less than 5% of free urinary Gla. However, excretion rates of free and protein-bound Gla (nmol/min) were higher in stone formers (P = 0.006 and P = 0.002). Positive correlations (P = 0.000) were observed between free and protein-bound Gla both in controls and in stone formers. These results do not support the hypothesis of a lacking Gla nephrocalcin in stone formers.

1-Carboxyglutamic Acid↗

Nephrolithiasis and urine ion changes in ulcerative colitis patients undergoing colectomy and endorectal ileal pullthrough.

Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (t1), after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 +/- 101 cc (mean +/- SE) at t1 to 715 +/- 101 cc at t2 and then increased to 1278 +/- 421 cc at t3 (significant, with P less than 0.01 by t test). Urinary excretions of Mg2+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2+ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones.

Adolescent↗

Ureteropelvic junction obstruction in nephrolithiasis. An etiologic factor.

Obstruction is rarely accepted as the sole cause of calculi. We have reviewed 106 cases of nephrolithiasis for which surgery was performed at the St. Luke's Hospital Center during the past ten years. In 17 of these cases, obstruction of the ureteropelvic junction was demonstrated, an incidence of 16 per cent. We propose the theory that too frequently the responsible ureteropelvic junction obstruction goes undetected when a "routine" pyelolithotomy or nephrolithotomy is performed.

Adolescent↗

Vascular polyps of ureter associated with megacalycosis and nephrolithiasis.

Multiple benign vascular polyps of the ureter are rare, and the associated congenital megacalycosis and nephrolithiasis are very uncommon. Herein we report a case with vascular polyps of the right ureteropelvic junction dissociated with extensive hydronephrosis which was considered to be megacalycosis. Clinical features and treatment modalities are reviewed.

Adolescent↗

Role of linear tomography in evaluation of patients with nephrolithiasis.

One hundred twenty-four consecutive patients with suspected or known nephrolithiasis were referred for evaluation by linear tomography. Renal calculi were detected in 98 patients (79%). Linear tomography revealed more renal calculi than did preliminary KUB films in 46 patients (37%), although in only 10 cases (8%) was the tomogram positive if the KUB was negative. Exact quantification of the numbers and locations of renal stones is important in patients to be managed metabolically, and in those being evaluated in advance of or following percutaneous or extracorporeal lithotripsy.

Humans↗

Study of potassium citrate treatment of crystalluric nephrolithiasis.

Patients with crystalluric nephrolithiasis were treated orally with aqueous potassium citrate solution three times a day with a large quantity of water. After administration of potassium citrate, citric acid (P < 0.001) and potassium (P < 0.001) excretion was significantly increased. Increase in protein (P < 0.05) and uric acid (P < 0.05) excretion in urine revealed their association with the crystallization process. Crystals were absent in 12 (71%) out of 17 patients. Calcium excretion in urine was significantly decreased (P < 0.05). A decrease of calcium ions availability to oxalate ions to form calcium oxalate crystals may result in the prevention of calcium oxalate stone formation.

Adult↗

[Epidemiology of nephrolithiasis in France].

Nephrolithiasis is a frequent disease that affects about 10% of people in western countries. The prevalence of calcium oxalate stones has been constantly increasing during the past fifty years in France as well as in other industrialized countries. Stone composition varies depending to gender and age of patients and also underlines the role of other risk factors and associated pathologies such as body mass index and diabetes mellitus. The decrease in struvite frequency in female patients is the result of a significantly improved diagnostic and treatment of urinary tract infections by urea-splitting bacteria. In contrast, the increasing occurrence of weddellite calculi in stone forming women aged more than 50 years could be the consequence of post-menopausal therapy. A high prevalence of uric acid was found in overweight and obese stone formers and in diabetic ones as well. Another important finding was the increased occurrence with time of calcium oxalate stones formed from papillary Randall's plaques, especially in young patients. Nutritional risk factors for stone disease are well known: they include excessive consumption of animal proteins, sodium chloride and rapidly absorbed glucides, and insufficient dietary intake of fruits and potassium-rich vegetables, which provide an alkaline load. As a consequence, an excessive production of hydrogen ions may induce several urinary disorders including low urine pH, high urine calcium and uric acid excretion and low urine citrate excretion. Excess in calorie intake, high chocolate consumption inducing hyperoxaluria and low water intake are other factors, which favour excessive urine concentration of solutes. Restoring the dietary balance is the first advice to prevent stone recurrence. However, the striking increase of some types of calculi, such as calcium oxalate stones developed from Randall's plaque, should alert to peculiar lithogenetic risk factors and suggests that specific advices should be given to prevent stone formation.

Calcium Oxalate↗

Emergence of Talanin protein associated with human uric acid nephrolithiasis in the Hominidae lineage.

Recently, we identified a susceptibility locus for human uric acid nephrolithiasis (UAN) on 10q21-q22 and demonstrated that a novel gene (ZNF365) included in this region produces through alternative splicing several transcripts coding for four protein isoforms. Mutation analysis showed that one of them (Talanin) is associated with UAN. We examined the evolutionary conservation of ZNF365 gene through a comparative genomic approach. Searching for mouse homologs of ZNF365 transcripts, we identified a highly conserved mouse ortholog of ZNF365A transcript, expressed specifically in brain. We did not found a mouse homolog for ZNF365D transcript encoding the Talanin protein, even if we were able to identify the corresponding genomic region in mouse and rat not yet organized in canonical gene structure suggesting that ZNF365D was originated after the branching of hominoid from rodent lineage. In mouse and in most mammals, a functional uricase degrades the uric acid to allantoin, but uricase activity was lost during the Miocene epoch in hominoids. Searching for the presence of Talanin in Primates, we found a canonical intron-exon structure with several stop codons preventing protein production in Old World and New World monkeys. In humans, we observe expression and we have evidence that ZNF365D transcript produces a functional protein. It seems therefore that ZNF365D transcript emerged during primate evolution from a noncoding genomic sequence that evolved in a standard gene structure and assumed its role in parallel with the disappearance of uricase, probably against a disadvantageous excessive hyperuricemia.

Alternative Splicing↗

Nephrolithiasis and hydronephrosis in an HIV-infected man receiving tenofovir.

The use of tenofovir as part of a HAART regimen has been widely used in HIV-multi-experienced-patients because of its favourable resistance profile. Tenofovir is mainly eliminated by the kidneys and renal toxicity should be carefully monitored. We describe here the case of an HIV-infected patient, without a prior history of renal failure who developed nephrolithiasis and hydronephrosis after starting a tenofovir-containing HAART regimen.

Adenine↗

Nephrolithiasis: acute management and prevention.

The primary care physician has a responsibility not only to recognize and treat acute stone passage but to ensure that the patient with recurrent stones has metabolic evaluation and appropriate preventive care. Renal colic is typically severe, radiates to the groin, is associated with hematuria, and may cause ileus. About 90% of stones that cause renal colic pass spontaneously. The patient with acute renal colic should be treated with fluids and analgesics and should strain the urine to recover stone for analysis. Highgrade obstruction or failure of oral analgesics to relieve pain may require hospitalization; a urinary tract infection in the setting of an obstruction is a urologic emergency requiring immediate drainage, usually with a ureteral stent. Several approaches are available when stones do not pass spontaneously, including extracorporeal shock wave lithotripsy, percutaneous lithotripsy, and ureteroscopic laser lithotripsy. Calcium stone disease has a lifetime prevalence of 10% in men and causes significant morbidity. Renal failure is unusual. Stone types include calcium oxalate, uric acid, struvite, and cystine. Stone analysis is particularly important when a noncalcareous constituent is identified. The majority of patients with nephrolithiasis will have recurrence, so prevention is a high priority. High fluid intake is a mainstay of prevention. Metabolic evaluation will indicate other appropriate preventive measures, which may include dietary salt and protein restriction, and use of thiazide diuretics, neutral phosphate, potassium citrate, allopurinol, and magnesium salts. Dietary calcium restriction may worsen oxaluria and negative calcium balance (osteoporosis).

Acute Disease↗

Nephrocalcinosis and nephrolithiasis in infants with congestive heart failure treated with furosemide.

Nephrocalcinosis and nephrolithiasis developed in five children after furosemide therapy for congestive heart failure. In four children renal calcifications were detected by ultrasonography and in one by autopsy. Discontinuation of the loop diuretic in three children resulted in resolution of the calcifications in two of the patients. Residual renal morbidity included reduced creatinine clearance, microscopic hematuria, and hypercalciuria. The phenomenon of renal calcifications associated with furosemide treatment is more frequent than previously recognized.

Female↗

Management of lower pole nephrolithiasis: a critical analysis.

The results of extracorporeal shock wave lithotripsy (ESWL*) and percutaneous nephrostolithotomy for the treatment of lower pole nephrolithiasis were examined in 32 consecutive patients undergoing percutaneous nephrostolithotomy at the Methodist Hospital of Indiana and through meta-analysis of publications providing adequate stratification of treatment results. Of 101 cases managed with percutaneous nephrostolithotomy 91 (90%) were stone-free, a result significantly better than that achieved with ESWL (1,733 of 2,927 stone-free, 59%). Stone-free rates with percutaneous nephrostolithotomy were independent of stone burden, whereas stone-free rates with ESWL were inversely correlated to the stone burden treated. The morbidity of patients undergoing percutaneous nephrostolithotomy at our hospital was minimal, with a mean hospital stay of 4.7 +/- 2.8 days. No blood transfusions were required. All patients became stone-free. The percentage of urolithiasis patients with lower pole calculi is increasing. Because of the significantly greater efficacy of percutaneous nephrostolithotomy for lower pole calculi, particularly stones larger than 10 mm. in diameter, further consideration should be given to an initial approach with percutaneous nephrostolithotomy.

Adult↗

Hot occupation and nephrolithiasis.

We investigated the prevalence of stone disease and urinary stone risk factors in machinists chronically exposed to a hot environment and massive sweating, without interference of nephrotoxic metals or other lithogenic compounds. The study was performed at a glass plant and exposure to heat stress was estimated by the Wet Bulb Globe Temperature climatic index. The prevalence of nephrolithiasis on the entire population of the machinists was 8.5% (20 of 236), while the prevalence on the controls working in normal temperature was 2.4% (4 of 165) (p = 0.03). A high incidence (38.8%) of uric acid stones was present in the workers exposed to heat stress. Among the urinary stone risk indexes determined for 3 days during the 8-hour work shift on a randomly selected sample of 21 workers exposed and 21 workers not exposed to heat stress without any evidence of stone disease significant differences were found in uric acid concentration (722 +/- 195 versus 482 +/- 184 mg./l., p < 0.001), specific gravity (1,026 +/- 4 versus 1,021 +/- 6, p < 0.005) and pH (5.31 +/- 0.28 versus 5.64 +/- 0.54, p < 0.02), respectively. Thus, high uric acid relative supersaturation was present during occupation in hot temperatures (8.67 +/- 3.49) compared to occupation in normal temperatures (4.15 +/- 2.7) (p < 0.001). This study confirms that chronic dehydration represents a real lithogenic risk factor, mainly for uric acid stones, and adequate fluid intake is recommended during hot occupations.

Adult↗

Randomized double-blind study of potassium citrate in idiopathic hypocitraturic calcium nephrolithiasis.

In an attempt to document the efficacy of potassium citrate in stone formation, 57 patients with active lithiasis (2 or more stones during the preceding 2 years) and hypocitraturia were randomly allocated into 2 groups, with 1 group taking 30 to 60 mEq. potassium citrate daily in wax matrix tablet formation and the other group receiving placebo. In 18 patients receiving potassium citrate for 3 years stone formation significantly declined after treatment from 1.2 +/- 0.6 to 0.1 +/- 0.2 per patient year (p < 0.0001), in 13 patients (72%) the disease was in remission and all patients showed a reduced stone formation rate individually. In contrast, 20 patients taking placebo medication for 3 years showed no significant change in stone formation rate (1.1 +/- 0.4 to 1.1 +/- 0.3 per patient year) and in only 4 patients (20%) was the disease in remission. The stone formation rate during potassium citrate treatment was significantly lower than during the placebo treatment (0.1 +/- 0.2 versus 1.1 +/- 0.3 per patient year, p < 0.001). Potassium citrate therapy caused a significant increase in urinary citrate, pH and potassium, whereas placebo did not. Adverse reactions to potassium citrate were mild causing only 2 patients in the potassium citrate group and 1 in the placebo group to withdraw from the study. In summary, our randomized trial showed the efficacy of potassium citrate in preventing new stone formation in idiopathic hypocitraturic calcium nephrolithiasis.

Adult↗

The metabolic evaluation of patients with recurrent nephrolithiasis: a review of comprehensive and simplified approaches.

The advent of percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy has definitely altered the way in which symptomatic renal calculi are approached. However, these new techniques should not affect the need for appropriate diagnostic evaluation and institution of medical treatment for the prevention of recurrent nephrolithiasis. A diagnostic evaluation should identify underlying physiological and environmental defects responsible for stone formation, as well as identify specific medical disorders that cause recurrent stone formation. With this information one then can construct an appropriate treatment program that will prevent the occurrence of additional calculi. Comprehensive metabolic protocols have evolved from tedious inpatient procedures to more convenient outpatient tests that can be performed in approximately 2 weeks. In addition, the advent of automated urinalysis packages has allowed many physicians access to reliable, sophisticated technology. Further dissemination of these simplified metabolic protocols will enable more accurate diagnosis of recurrent stone disease and, hopefully, permit the institution of appropriate medical therapy by a wider group of treating physicians.

Calcium↗

Medical management of nephrolithiasis in Dallas: update 1987.

With available medical treatment programs a remission of stone disease could be achieved in more than 80 per cent of the patients and a decrease in individual stone formation rate obtained in greater than 90 per cent. The need for stone removal may be reduced dramatically by an effective prophylactic program. There is some evidence that certain stones (even calcareous types) may undergo dissolution in vivo with appropriate therapy. Moreover, properly applied medical treatments may be capable of overcoming nonrenal manifestations as well as preventing new stone formation. Thus, the potential development of bone disease in patients with renal tubular acidosis may be averted by potassium citrate therapy. Despite these advantages it is clear that the medical treatment approach cannot provide total control of the disease. Stone disease generally presents with a surgical problem related to an already formed stone before medical diagnosis and selective treatment may be applied. Some patients, albeit a minority, are recalcitrant to medical treatment no matter how heroic. A satisfactory response to medical treatment requires continued compliance by the patient to the recommended treatment program and a commitment by the physician to provide long-term followup care. There is no cure, only prophylaxis. The increasing ease and decreasing cost of new approaches to stone removal, particularly with the advent of second generation extracorporeal lithotripsy, will undoubtedly cast a continuing uncertainty on the need for medical diagnosis and treatment. Several factors might influence the choice between surgical and medical approaches. One factor is the severity of stone disease. Patients with repeated episodes of stone formation might be more likely to adopt preventive therapy, whereas those with infrequent stone episodes may elect simply to have them removed upon their occurrence without medical treatment between episodes. Also, the possibility that lithotripsy may cause long-term hazards (for example development of hypertension) must be clarified. Another factor is the occurrence of extrarenal manifestations. In patients suffering from systemic disorders in which nephrolithiasis is only 1 manifestation (for example distal renal tubular acidosis) a medical approach may be justified exclusive of effects on stone formation. Finally, one must consider the relative practicality and cost between stone removal and a medical approach. It is likely that improvements and reductions in costs will occur with both approaches. It is hoped that urologists and internists work jointly to find an appropriate balance between the 2 approaches.(ABSTRACT TRUNCATED AT 400 WORDS)

Chlorothiazide↗

Use of potassium citrate as potassium supplement during thiazide therapy of calcium nephrolithiasis.

The effectiveness of potassium citrate as a potassium supplement was compared to that of potassium chloride in 13 patients with calcium nephrolithiasis treated with thiazide. Thiazide treatment alone reduced serum potassium, urinary calcium and citrate without affecting urinary pH. Urinary saturation of calcium oxalate and brushite decreased but not as much as the decrement in urinary calcium because of reduced citrate-calcium complexation. Potassium chloride supplementation averted thiazide-induced hypokalemia and hypocitraturia without influencing hypocalciuric action of thiazide or urinary pH. The decline in urinary saturation of calcium salts paralleled the decrement in urinary calcium. Potassium citrate supplementation also kept urinary calcium low and corrected hypokalemia. Moreover, it increased urinary pH and citrate above levels in other phases. Thus, the ability of thiazide to lower the urinary saturation of calcium oxalate was accentuated by potassium citrate supplementation but not by potassium chloride supplementation, probably owing to increased citrate complexation of calcium. Moreover, the potassium citrate therapy was more effective than potassium chloride supplementation in reducing the propensity for the spontaneous precipitation of calcium oxalate in urine. In conclusion, potassium citrate supplementation may be superior to potassium chloride supplementation in patients receiving thiazide in whom stones form.

Adult↗

Paecilomyces pyelonephritis complicating nephrolithiasis and review of Paecilomyces infections.

We report a case of Paecilomyces variotii isolated from the renal pelvis at ureterolithotomy. The patient presented with nephrolithiasis, acute flank pain, fever and pyuria, which resolved postoperatively. Paecilomyces has infected the cornea, prosthetic lens implants, lacrimal sac, maxillary sinuses, prosthetic mitral and aortic valves, skin and a ventriculoperitoneal shunt.

Humans↗