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Biomedical subjects

Elaine M Worcester

Publications and source records attributed to Elaine M Worcester.

15 recordsLinked to original sources
PubMed2007

Evidence that postprandial reduction of renal calcium reabsorption mediates hypercalciuria of patients with calcium nephrolithiasis.

Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The increased urinary calcium arises from increased intestinal absorption of calcium, but it is unclear whether increased filtered load or decreased renal tubular reabsorption of calcium is the main mechanism for the increased renal excretion. To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1 day. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, and calories. Fasting and fed, ultrafiltrable calcium levels, and filtered load of calcium did not differ between N and IHSF. Urine calcium rose with meals, and fractional reabsorption fell in all subjects, but the change was significantly higher in IHSF. The changes in calcium excretion were independent of sodium excretion. Serum parathyroid hormone levels did not differ between N and IHSF, and they could not account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and phosphorus levels in IHSF were below N throughout the day, and tubule phosphate reabsorption was lower in IHSF than N after meals. The primary mechanism by which kidneys ferry absorbed calcium into the urine after meals is via reduced tubule calcium reabsorption, and IHSF differ from N in the magnitude of the response. Parathyroid hormone is not likely to be a sufficient explanation for this difference.

Adult↗
PubMed2006

Renal function in patients with nephrolithiasis.

PURPOSE: We describe kidney function, as measured by creatinine clearance in stone formers, and classified by type of stone formed and systemic etiologies of stone formation. MATERIALS AND METHODS: The mean of 3 pretreatment 24-hour creatinine clearance measurements in each of 1,856 stone formers and creatinine clearance in 153 normal individuals were used. Clearance was adjusted for patient sex, age and body weight using general linear modeling. RESULTS: As a group, all stone formers had decreased clearance adjusted for age, sex and body weight compared to that in normal individuals. Although clearance was particularly low in cystine and struvite stone formers, they were below normal in even common CaOx stone formers. CONCLUSIONS: As a rule, patients with kidney stones do not have normal kidney function. In clinical management all efforts must be made to minimize renal injury, balancing the risks of obstruction from stones against those of urological procedures.

Creatinine↗
PubMed2006

Endoscopic evidence of calculus attachment to Randall's plaque.

PURPOSE: It has been proposed that calcium oxalate calculi begin as small stones attached to the renal papillae at sites of Randall's plaque. However, no study has investigated the prevalence of attached stones in calcium oxalate stone formers or the relationship between stone attachment site and Randall's plaque. In this study we used endoscopic examination of renal papillae in stone formers undergoing percutaneous nephrolithotomy to investigate both issues. MATERIALS AND METHODS: Idiopathic calcium oxalate stone formers undergoing PNL for stone removal were enrolled in this study. Multiple papillae were examined and images were recorded by digital video. The presence or absence of papillary plaque and attached stones was noted, as was the site of stone attachment. RESULTS: In 23 patients, 24 kidneys and 172 renal papillae were examined. All kidneys were found to have papillary plaque and 11 of the patients had attached stones. Most papillae (91%) contained plaque. CONCLUSIONS: The prevalence of attached stones in calcium oxalate stone formers (48%) is greater than that previously reported for the general population. Attachment appears to be on Randall's plaque. The high prevalence of attached stones and the appearance of the attachment site are consistent with a mechanism of calcium oxalate stone formation in which stones begin as plaque overgrowth.

Calcium Oxalate↗
PubMed2006

Reduced renal function and benefits of treatment in cystinuria vs other forms of nephrolithiasis.

UNLABELLED: A significant study from the USA compares cystine stone formers and routine stone formers; the former group had a higher requirement for therapeutic procedures, but this was less if they took chelating agents, although remaining higher than in the latter group. Other interesting findings are also presented. OBJECTIVE: First, to compare two types of stone formers (SF), those with cystinuria and those without, for effects of treatments for stones, as cystinuria leads to recurrent stones that are difficult to fragment with shock-wave lithotripsy, and there is disagreement about the efficacy of current treatments. Second, to compare these two groups with respect to blood pressure (BP) and renal function, as cystine stones may be associated with more morbidity than are routine stones. PATIENTS AND METHODS: Fifty-two cystinuric patients (cystine SF) entering our programme since 1970 were compared with 3215 SF without cystinuria (routine SF), of whom 114 had a single functioning kidney (routine SF + nephrectomy). All patients had three 24-h urine and blood samples taken to determine the risk of stones before their first clinic visit; these studies were repeated after therapy was initiated, and at regular intervals to monitor therapy. Cystine was measured in the urine samples of the cystine SF. All stone-related procedures were recorded, and BP measured at clinic visits. Creatinine clearances (CCr) were calculated from each set of serum and urine values. Cystine supersaturation (SS) was directly measured in 16 urine samples collected before treatment and 13 afterward. RESULTS: Patients were treated with increased fluid intake, potassium alkali and chelating agents such as alpha-mercapto-propionyl-glycine, as needed. The mean (sd) CCr, corrected for age and gender, was significantly lower at entry in cystine SF than in routine SF, at 91 (6) vs 160 (1) L/day, respectively (P < 0.001), and remained so at the last CCr. Neither systolic nor diastolic BP, similarly corrected, differed between the groups, but cystine SF had significantly more procedures, corrected for time at risk, before treatment than did routine SF, at 4.0 (0.4) vs 1.86 (0.06), respectively (P < 0.001); time-adjusted procedures decreased significantly in both groups during treatment, but remained higher in cystine SF, at 0.88 (0.14) vs 0.23 (0.02), respectively, (P < 0.001). Urine volume and pH were significantly higher in cystine SF than in routine SF, both before and during treatment. Cystine SS decreased during treatment, consistent with the increase in urine volume and decline in procedure rates during treatment. CONCLUSION: Cystine SF have significantly higher procedure rates than routine SF, but procedure rates decline during therapy, although they remain higher than in routine SF. The lower CCr in cystinurics suggests that treatment to prevent stone recurrence and the need for procedures is particularly important, and emphasizes the need for a close follow-up. Use of cystine SS measurements may allow closer monitoring of the effect of treatment on the risk of stone recurrence.

Adult↗
PubMed2005

A new animal model of hyperoxaluria and nephrolithiasis in rats with small bowel resection.

An association between small bowel resection and stone disease has been noted, which is primarily due to increased gut oxalate absorption and resulting excretion by the kidney. In order to better understand the factors affecting both oxalate absorption and renal excretion, and the resulting renal lesions, we have developed a rodent model of small bowel resection and hyperoxaluria. Using this model, we have studied the renal histology in animals with hyperoxaluria over time spans from 2 weeks to 7 months. The initial lesion appears to be crystal formation along the brush border of the proximal tubule, with eventual crystal deposition in collecting ducts and papillary interstitium, and eventual tubule obstruction, interstitial inflammation and fibrosis. Crystal formation appears to dissociate from urinary supersaturation. We hypothesize that oxalate transporters in the proximal tubule may increase local saturations, leading to crystal formation at this site initially. Further studies are required to better characterize the causes and consequences of hyperoxaluria in this animal model.

Animals↗
PubMed2005

Nephrolithiasis and nephrocalcinosis in rats with small bowel resection.

Intestinal resection (IR) may lead to hyperoxaluria and nephrolithiasis. A rat model of IR was developed, in which kidney stones form. We describe the urine chemistries and histopathologic features. Rats underwent resection of 40-45 cm of distal ileum (n=16) or sham resection (SR) (n=8), and were then fed a 1% Na oxalate, 0.02% Ca diet. After 1 week on the diet, 24 h urine samples were obtained for stone chemistries. At 4-7 months after surgery, kidneys were examined grossly and by light microscopy. The extent and location of crystallization was assessed by polarized light. Histochemistry and infrared spectroscopy were used to determine crystal composition. IR rats had higher urine oxalate excretion (P<0.01) and concentration (P<0.001) than SR rats, and lower urine citrate excretion; only IR rats formed kidney stones (12/15 surviving rats). Tissue calcification was found only in kidneys from IR rats, located in the cortex (83% of kidneys), medulla (73%) and papillary tip (47%). Crystals, composed of CaOx, apatite, and calcium carbonate, filled collecting duct lumens, and were associated with tubular obstruction, and interstitial inflammation. Crystals in the papillary interstitium incited inflammation with tubular destruction and development of progressive papillary erosion. This new rat model of nephrolithiasis and nephrocalcinosis resembles the pattern of urinary abnormalities and tissue calcification that may be seen in humans with small bowel resection. The model allows further studies of the mechanisms of renal crystal formation, and possible therapeutic interventions.

Animals↗
PubMed2005

Nephrolithiasis and increased blood pressure among females with high body mass index.

BACKGROUND: We hypothesized that one reason for the heterogeneity in previously reported links between kidney stones and blood pressure (BP) was the differential effects of nephrolithiasis among subgroups of individuals. In particular, we hypothesized that the association between stone history and BP may vary with respect to sex and body size. METHODS: Data from the Third National Health and Nutrition Examination Survey were used to estimate the association between history of stone disease and odds of prior diagnosis of hypertension and mean difference in systolic BP, diastolic BP, and pulse pressure. Nine hundred nineteen persons with a history of stones and 19,120 persons without stones were available for analysis. RESULTS: In women, it was estimated that stone formers (SFs) experienced a 69% increase in odds of self-reported hypertension (95% confidence interval [CI], 1.33 to 2.17; P < 0.001). No significant difference was found in men. The estimated difference in mean systolic and diastolic BP comparing SFs with non-SFs increased with body mass index in both sexes, but was more pronounced in women. Mean systolic BPs in women SFs in quintiles 4 and 5 of body mass index were 7.62 mm Hg (95% CI, 1.04 to 14.2; P = 0.024) and 4.36 mm Hg (95% CI, 0.30 to 8.42; P = 0.036) greater than those in similar women non-SFs, respectively. CONCLUSION: Our findings not only support the link between kidney stone disease and BP, but also suggest that overweight women SFs may be at significantly increased risk for hypertension.

Adolescent↗
PubMed2005

Apatite plaque particles in inner medulla of kidneys of calcium oxalate stone formers: osteopontin localization.

BACKGROUND: We have previously shown that interstitial plaque particles appear first in the basement membranes of thin loops of Henle and then in the interstitial space. However, it is not known if the plaque in the basement membrane of thin loops of Henle is of the same or different form than the interstitial plaque. Thus our purpose here is to detail the structure of the interstitial and membrane-bound plaque and explore the relationship of plaque apatite to osteopontin, a well-known crystal-associated urine protein. METHODS: Deep papillary biopsy tissue was studied from all 15 calcium oxalate stone formers and four nonforming subjects that we previously reported on [Evan et al, J Clin Ivest, 2003]. Routine light and transmission electron microscopy (TEM) as well as light microscopy and TEM immunohistochemical localization of osteopontin antibody were performed on all 19 subjects. RESULTS: In the basement membrane, plaque particles are individual and appear laminated with alternating light regions of crystal and electron-dense organic layers. In the interstitium, individual particles are not abundant but are instead aggregated to form regions of attached particles and in some regions what appears to be a fusion or syncytium in which crystal islands float in an organic sea. By light microscopy immunohistochemistry, osteopontin was localized to cells of the loops of Henle and collecting ducts as well as on sites of plaque. By immunoelectron microscopy, osteopontin immunogold label was found mainly on the surfaces of apatite crystal phase, at the junction of the crystal/organic layers. A similar immunogold labeling pattern was seen in the particles forming the syncytial islands of interstitial plaque. CONCLUSION: If indeed we accept the hypothesis that apatite plaque may be an anchored site on which calcium oxalate stones form and grow, the present work makes clear that it is unlikely that the surface of plaque presented to the final urine will be apatite crystal per se. However, our findings clearly show osteopontin is one of the crystal-associated urine proteins involved in the formation of the organic layers of the plaque particles.

Apatites↗
PubMed2005

Crystal-associated nephropathy in patients with brushite nephrolithiasis.

BACKGROUND: We have biopsied the renal cortex and papillae of patients who form brushite renal stones asking if this unusual stone type is associated with specific tissue changes. We contrasted these with biopsies of 15 calcium oxalate stone formers, three stone formers with intestinal bypass, and four normal subjects. METHODS: We studied all ten brushite stone formers treated with percutaneous nephrolithotomy (PNL) during the past 3 years using digital video imaging of renal papillae, and obtained cortical and papillary biopsies. Biopsies were analyzed by light and electron microscopy, microinfrared spectroscopy, and electron diffraction. RESULTS: Apatite crystals plugged scattered terminal collecting ducts whose cells were injured or dead, and surrounding interstitium inflamed and fibrotic. White papillary deposits of interstitial apatite particles, so called Randall's plaque, were also present. Glomerular changes and cortical tubular atrophy and interstitial fibrosis were moderate to severe. CONCLUSION: Brushite stone formers combine the interstitial plaque of calcium oxalate stone formers with the collecting duct apatite plugs found in stone formers with intestinal bypass. Collecting duct injury and interstitial fibrosis are severe. Prominent cortical fibrosis, tubule atrophy, and glomerular pathology seem secondary to the collecting duct plugging. We believe crystallization obstructs and destroys terminal collecting duct segments thereby damaging nephrons, perhaps via intranephronal obstruction, and producing a hitherto unrecognized renal disease.

Adolescent↗
PubMed2005

Decreased renal function among adults with a history of nephrolithiasis: a study of NHANES III.

BACKGROUND: Although intuitively appealing, the hypothesis that nephrolithiasis is associated with decreased renal function has not thoroughly been investigated. Because the prevalence of nephrolithiasis and chronic renal disease in westernized societies has risen over the past three decades, we sought to determine if persons with a history of kidney stones have lower renal function relative to nonstone formers. METHODS: We used data from the Third National Health and Nutrition Examination Survey (NHANES III) to compare estimated glomerular filtration rate (GFR) between persons over age 30 with and without a history of kidney stones. In total, 876 persons with a history of stones, and 14,129 persons without stones were available for analysis. RESULTS: We observed that the association between history of stones and estimated GFR depends on body mass index (BMI) (P= 0.004). After adjustment for potential confounding factors, mean estimated GFR in stone formers with a BMI >/=27 kg/m(2) was 3.4 mL/min/1.73 m(2) lower than that of similar nonstone formers (95% CI -5.8, -1.1) (P= 0.005). No difference was found among persons with a BMI <27 kg/m(2). The probability of an overweight stone former having an estimated GFR between 30 and 59 mL/min/1.73 m(2) relative to a GFR above 90 mL/min/1.73 m(2) was nearly twice that of a similar nonstone former [relative risk ratio (RRR) = 1.87, 95% CI 1.06, 3.30]. CONCLUSION: Among overweight persons, nephrolithiasis may not merely be a disease of stones, but may also reduce kidney function. Further work in alternate study samples is needed to validate this finding and determine the mechanisms responsible.

Adult↗
PubMed2004

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.

Age Distribution↗
PubMed2003

Urine stone risk factors in nephrolithiasis patients with and without bowel disease.

BACKGROUND: The prevalence of nephrolithiasis among patients with bowel disease is higher than in the general population. We examined urine stone risk factors and clinical characteristics of these patients, contrasted with a large group of stone forming patients without systemic disease. METHODS: A total of 180 patients with bowel disease were compared with a group of 2048 nephrolithiasis patients with calcium or uric acid stones and without systemic diseases. Bowel diseases included inflammatory bowel disease with and without bowel resections, bowel resections from cancer or trauma, and bypass procedures for obesity or hypercholesterolemia. Urine stone risk factors, stone rates, stone compositions, and creatinine clearance were measured. RESULTS: Compared to ordinary stone forming patients, bowel patients formed stones higher in rate of recurrence and in uric acid content. Uric acid content was highest when colon surgery had occurred. Urine volumes were low among all bowel patients except those with a bypass. Average creatinine clearance values were low among all bowel patients. Urine oxalate excretion was modestly elevated after small bowel resection, but very high with bypass. Supersaturations were increased mainly by low urine volume and-for uric acid-low pH. Patients with no surgery were indistinguishable from routine stone formers. CONCLUSIONS: Low urine volume and pH are the main stone-forming abnormalities in bowel disease patients. Hyperoxaluria is extreme after bypass, but only modest after small bowel surgery. In the absence of surgery, bowel disease patients with stones cannot be distinguished from common stone formers by comprehensive stone risk measurements.

Calcium Oxalate↗
PubMed2002

Stones from bowel disease.

Kidney stones are increased in patients with bowel disease, particularly those who have had resection of part of their gastrointestinal tract. These stones are usually CaOx, but there is a marked increase in the tendency to form uric acid stones, as well, particularly in patients with colon resection. These patients all share a tendency to chronic volume contraction due to loss of water and salt in diarrheal stool, which leads to decreased urine volumes. They also have decreased absorption, and therefore diminished urinary excretion, of citrate and magnesium, which normally act as inhibitors of CaOx crystallization. Patients with colon resection and ileostomy form uric acid stones, as loss of bicarbonate in the ileostomy effluent leads to formation of an acid urine. This, coupled with low urine volume, decreases the solubility of uric acid, causing crystallization and stone formation. Prevention of stones requires treatment with alkalinizing agents to raise urine pH to about 6.5, and attempts to increase urine volume, which increases the solubility of uric acid and prevents crystallization. Patients with small bowel resection may develop steatorrhea; if the colon is present, they are at risk of hyperoxaluria due to increased permeability of the colon to oxalate in the presence of fatty acids, and increased concentrations of free oxalate in the bowel lumen due to fatty acid binding of luminal calcium. EH leads to supersaturation of urine with respect to CaOx, in conjunction with low volume, hypocitraturia and hypomagnesuria. Therapy involves a low-fat, low-oxalate diet, attempts to increase urine volume, and agents such as calcium given to bind oxalate in the gut lumen. Correction of hypocitraturia and hypomagnesuria are also helpful.

Calcium Oxalate↗
PubMed2001

Effects of urinary macromolecules on hydroxyapatite crystal formation.

Particle size analysis was combined with titration data obtained in constant-composition, hydroxyapatite (HA)-seeded, crystal growth assays. With addition of large amounts of HA (250 microg), titration rates were linear, new crystal formation was minimal, and aggregation effects could be detected. With addition of small amounts of HA (62.5 microg), nucleation of new HA was observed. The effects of urinary macromolecules, i.e., osteopontin (OPN), recombinant glutathione-S-transferase-OPN (G-OPN), Tamm-Horsfall protein, chondroitin sulfate, human serum albumin, mixed urinary macromolecules from a stone-former (SFU1), mixed urinary macromolecules from a normal individual (NU1), and polyaspartic acid (PA), were examined in this system. Crystal growth inhibition, as measured by the slope of linear titration curves in this system, was observed with PA, G-OPN, OPN, SFU1, and NU1. All of the macromolecules tested inhibited aggregation, including Tamm-Horsfall protein, which did not inhibit growth. As reflected by the ratio of the final number of particles to the initial number in the 62.5-microg seed addition, the macromolecules that were most effective in inhibiting growth, i.e., OPN, G-OPN, PA, SFU1, and NU1, actually increased secondary nucleation. Recombinant G-OPN demonstrated less inhibitory activity than did OPN isolated from cell culture. Chondroitin sulfate and human serum albumin exhibited no significant effects on the various components of HA crystallization under these conditions. SFU1 and NU1 slowed growth and increased secondary nucleation to similar degrees, and neither exhibited any measurable effect on aggregation. Therefore, crystal surface sites that participate in nucleation, growth, and aggregation processes are affected independently by macromolecules, presumably because of differences in their structural features. These results illustrate the utility of combining these techniques to provide a much greater understanding of crystallization behavior than that possible with either analysis alone.

Crystallization↗