More than 10% of the global human population is now afflicted with kidney stones, which are commonly associated with other significant health problems including diabetes, hypertension and obesity. Nearly 70% of these stones are primarily composed of calcium oxalate, a mineral previously assumed to be effectively insoluble within the kidney. This has limited currently available treatment options to painful passage and/or invasive surgical procedures. We analyze kidney stone thin sections with a combination of optical techniques, which include bright field, polarization, confocal and super-resolution nanometer-scale auto-fluorescence microscopy. Here we demonstrate using interdisciplinary geology and biology (geobiology) approaches that calcium oxalate stones undergo multiple events of dissolution as they crystallize and grow within the kidney. These observations open a fundamentally new paradigm for clinical approaches that include in vivo stone dissolution and identify high-frequency layering of organic matter and minerals as a template for biomineralization in natural and engineered settings.

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Background Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying in non-obese diabetic (NOD) mice. Our hypothesis was that hemin upregulation of HO1 would restore normal gastric emptying in humans with gastroparesis. Aims To compare effects of hemin and placebo infusions on HO1 activity and protein, gastric emptying, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. Methods In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41±5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, gastric emptying with 13C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. Results Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (P=.0002) and 7 (P=.008) and HO1 activity on day 3 (P=.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. Conclusions Hemin failed to sustain increased HO1 levels beyond a week and did not improve gastric emptying or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve gastric emptying.