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Biomedical subjects

Elaine Worcester

Publications and source records attributed to Elaine Worcester.

5 recordsLinked to original sources

Pathophysiological correlates of two unique renal tubule lesions in rats with intestinal resection.

Rats with small bowel resection fed a high-oxalate diet develop extensive deposition of calcium oxalate (CaOx) and calcium phosphate crystals in the kidney after 4 mo. To explore the earliest sites of renal crystal deposition, rats received either small bowel resection or transection and were then fed either standard chow or a high-oxalate diet; perfusion-fixed renal tissue from five rats in each group was examined by light microscopy at 2, 4, 8, and 12 wk. Rats fed the high-oxalate diet developed birefringent microcrystals at the brush border of proximal tubule cells, with or without cell damage; the lesion was most common in rats with both resection and a high-oxalate diet (10/19 with the lesion) and was significantly correlated with urine oxalate excretion (P < 0.001). Rats with bowel resection fed normal chow had mild hyperoxaluria but high urine CaOx supersaturation; four of these rats developed birefringent crystal deposition with tubule plugging in inner medullary collecting ducts (IMCD). Two rats fed a high-oxalate diet also developed this lesion, which was correlated with CaOx supersaturation, but not oxalate excretion. Tissue was examined under oil immersion, and tiny birefringent crystals were noted on the apical surface of IMCD cells only in animals with IMCD crystal plugging. In one animal, IMCD crystals were both birefringent and nonbirefringent, suggesting a mix of CaOx and calcium phosphate. Overall, these animals demonstrate two distinct sites and mechanisms of renal crystal deposition and may help elucidate renal lesions seen in humans with enteric hyperoxaluria and stones.

Animals↗

Evidence against a contribution of conventional urine risk factors to de novo ESRD renal stones.

BACKGROUND: The authors measured urine and blood stone risk factors in African-American (AA) haemodialysis (HD) patients with new onset of stones during dialysis. METHODS: Patients with nephrolithiasis (NL) newly manifested during dialysis were matched by age, sex and urine output and dialysis duration to AA HD patients without history or symptoms of stones. Two 24 h urine and serum samples were collected and analysed for conventional stone risk factors. RESULTS: Three percent of the patients formed new stones while on HD; none had formed stones prior to end-stage renal disease. Newly onset NL patients had higher urine citrate and lower serum potassium levels than HD patients without stones. CONCLUSION: Usual stone risk factors did not correlate with new stones during dialysis.

Black or African American↗

Insights on the pathology of kidney stone formation.

The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and that its formation is conditioned by specific stone-forming pathophysiologies. To test this hypothesis, we performed intraoperative mapping studies with biopsies of papilla from the kidneys of 15 idiopathic calcium oxalate (CaOx) stone formers, four intestinal bypass for obesity patients and ten brushite stone formers, and obtained papillary specimens from four non-stone formers after nephrectomy. Both light and electron microscopic examination of tissue changes along with infrared and electron diffraction analyses of mineral composition were performed. Distinct patterns of mineral deposition and papillary pathology were discovered in each of the three different stone forming groups. CaOx stone formers had predictable sites of interstitial apatite crystals beginning at the thin loops of Henle and spreading to the urothelium. These plaque areas are termed Randall's plaque and are thought to serve as sites for stone attachment. The papilla and medullary tubules appeared normal. The intestinal bypass patients only had intraluminal sites of crystalline material in the medullary collecting ducts. The brushite stone formers had the most severe form of cortical and medullary changes with sites of Randall's plaque, and yellowish intraluminal deposits in medullary collecting ducts. All deposits were determined to be apatite. The metabolic and surgical pathologic finding in three distinct groups of stone formers clearly shows that "the histology of the renal papilla from a stone former is particular to the clinical setting". It is observations like these that we believe will provide the insights to allow the stone community to generate better clinical treatments for kidney stone disease, as we understand the pathogenesis of stone formation for each type of stone former.

Calcium Oxalate↗

Kidney stone disease.

About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.

Animals↗

Causes and consequences of kidney loss in patients with nephrolithiasis.

BACKGROUND: It is unknown whether stone formers may safely donate a kidney. Nephrectomy could accelerate stone formation, or loss of filtration with age. We contrast, here, the course of stone patients with two versus one kidney. METHODS: One hundred fifteen patients with a single functioning kidney were compared with 3151 patients with two kidneys. Cause of kidney loss was determined, along with stone types, rates of stone formation, urine stone risk factors, and creatinine clearance. RESULTS: Women were 49.6% of the patients with kidney loss, compared to 33.6% of ordinary stone formers. Obstruction, stone burden, and infection were the most common reasons for kidney loss. We found an increased number of struvite and calcium phosphate stones among single kidney patients. Before and during treatment, single kidney patients had fewer stones than ordinary stone formers. Creatinine clearance was lower in the single kidney patients; rate of loss of kidney function with age was higher among single kidney males versus two kidney males if all patients are considered. Among males >age 45 years, the difference disappears. Females with one and two kidneys lost function with age at equivalent rates. Compared with nonstone formers, male stone formers lose kidney function with age at an accelerated rate. CONCLUSION: Nephrectomy does not worsen stone disease. It may increase loss of renal function among younger males. The pattern of renal function loss with age differs between stone formers and nonstone formers.

Adult↗