Impact of urinary calcium excretion on kidney, bone, and cardiovascular systems in patients with bone biopsy proven osteoporosis: a longitudinal long-term follow-up study.

The impact of urine calcium on kidney, bone, and cardiovascular systems in osteoporosis is not well-known. In this 7-year-follow-up study, high urine calcium did not affect kidney function but increased risk of kidney stones, while low urine calcium increased cardiovascular diseases. Maintaining normal urine calcium is beneficial for bone health. PURPOSE: Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients' health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis. METHODS: Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients' outcomes. RESULTS: Study included 230 patients with mean follow-up of 7.2 ± 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 ± 19 ml/min/1.73 m2. Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD). CONCLUSION: UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD.

Evidence of geoelectrical resistivity values on groundwater conditions in Wadi El Natrun and its vicinities, West Delta, Egypt (cases studies).

Recently, Wadi El Natrun and its surroundings have witnessed intensive investments in land reclamation, including the arbitrary drilling of hundreds of groundwater wells. Currently, serious hydrogeological and environmental problems have been addressed, such as groundwater quality degradation and water head drop. Electrical resistivity measurements were performed at six locations across the study area to assess its ability to reveal the heterogeneous subsurface stratigraphic and hydrogeological setting of groundwater aquifer(s). The geoelectrical results successfully reflect the current vulnerable hydrogeological setting of the study sites. The current study highlights the current practice in which farmers rely on isolated 1-dimensional vertical electrical sounding (1D VES), which is not the only exploration tool for such electrically conductive stratigraphic succession. One of the main findings is addressing the advantage of applying 2-dimensional electrical resistivity imaging (2D ERI), where it offers a more robust view of both vertical and lateral variation of the investigated subsurface section (Case 3). On the other hand, the Geographic Information System (GIS) could mirror the present groundwater potentiality status, where both GIS analysis and resistivity results coincide, and where the good potentiality zone is restricted to the west and southwest directions of the study area (area of interest (aoi)), where the resistivity values of water bearing are relatively high and lie on the main drainage (Cases 2, 5, and 6). On the contrary, poor potentiality zones are deemed because of their proximity to tiny attributers, and are characterized by low resistivity values (Cases 1, 3 & 4), Finally, the current research study demonstrates the significance of combining morphometrical analysis with geophysics techniques for such environmental problems, where groundwater is primarily controlled by geomorphological features and geological conditions, including lithology and geological structures.

Upregulation of epidermal growth factor and its receptor in the kidneys of rats with streptozotocin-induced diabetes.

We have studied the acute changes (up to 30 days) in the expression of epidermal growth factor (EGF) and its receptor (EGFr) in the kidneys of adult male Wistar rats made diabetic by a single intravenous injection of streptozotocin (55 mg/kg) using a combination of immunocytochemical staining and in situ hybridization histochemistry. In the absence of insulin treatment, diabetic rats displayed renal growth (hypertrophy and hyperplasia). It was accompanied by an increase in immunostainable EGF within the thick ascending limb (TAL) of the loops of Henle which was apparent within 24 h of the onset of diabetes, reached a peak by day 7 and persisted to the end of the experimental period (day 30). In situ hybridization histochemistry revealed that these changes were preceded by a rapid rise in EGF mRNA in the cells of the TAL, which was highest after 1 day but declined to control levels by day 7. Increased immunostainable EGFr was evident in both the proximal and TAL and in the cortical collecting ducts from day 1. Staining of the proximal tubules declined rapidly after day 1 but that of the TAL and collecting ducts persisted until day 7 and declined thereafter. These results are discussed in light of the role of EGF in the hypertrophy and repair of the diabetic kidney.

Subtotal nephrectomy: a mosaic of growth factors.

We have studied the distribution of immunoreactive growth factors, by an avidin-biotin-peroxidase technique, throughout the course of progressive renal scarring in rats submitted to extensive renal ablation. Groups of rats (n = 6) were sacrificed at Days 7, 15, 21, 30, 90 and 150 following subtotal nephrectomy (SNx) by ligation and resection of the renal poles. During the early stages, when compensatory renal growth took place, increased renal immunostaining for insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) was detected within the collecting ducts and distal tubules, respectively. As renal scarring became established by Days 90 and 150, these two growth factors were detected within the cells of damaged and vacuolated distal tubules. By contrast, a progressive increase immunostain for platelet-derived growth factor (PDGF)-AB was apparent within the glomeruli from Day 15 onward preceding the onset of glomerulosclerosis. A third staining pattern was apparent by Day 15 for transforming growth factor-beta (TGF-beta) and by Day 30 for IGF-I consisting of a perivascular and interstitial distribution coinciding with adventitial expansion and tubulo-interstitial fibrosis, respectively. A mosaic of growth factors is expressed within the kidneys of rats submitted to extensive renal ablation.

Experimental diabetic renal growth: role of growth hormone and insulin-like growth factor-I.

We have compared the kidneys of two inbred strains of rats (Lewis and Lewis-Dwarf) 7 days after the induction of diabetes mellitus with streptozotocin, in order to examine the influence of a selective growth hormone (GH) deficiency on diabetic renal growth and insulin-like growth factor-I (IGF-I) content of the kidneys. Insulin-like growth factor-I (IGF-I) content of the kidneys. Insulin-like growth factor-I was measured by radioimmunoassay and its distribution within the kidney by immunohistochemical staining. We detected a significant increase in both the wet weight (32.9 +/- 5.3%, P = 0.0085) and dry weight (16.3 +/- 6.3%, P = 0.046) of the kidneys of diabetic Lewis rats but dwarf rats, selectively deficient in GH, did not show a significant increase in either parameter. Extractable IGF-I increased within the kidneys of diabetic rats of both strains but to a lesser extent in the dwarf rats (+105 +/- 28% and +65 +/- 21% respectively, P < 0.01). In diabetic Lewis rats a positive correlation was noted between the severity of glycaemia and kidney IGF-I content (r = 0.604, P < 0.05) but no such correlation was noted in dwarf rats. Inulin-like growth factor-I immunostaining increased in diabetic rats of both strains, mainly within cells of the thick ascending limb of the loop of Henle including damaged and vacuolated cells. However, morphometric analysis of the staining showed that it was significantly less widespread in the diabetic dwarf rats (P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-like growth factor-I and experimental diabetic kidney disease.

Insulin-like growth factor-I (IGF-I) has been implicated in the pathogenesis of experimental diabetic renal growth. In this study, we have examined the serial changes of renal IGF-I, by radioimmunoassay (RIA) and immunohistochemistry, in rats made diabetic by a single intravenous injection of streptozotocin (STZ; 55 mg/kg). The kidney IGF-I content, as determined by RIA, increased within 48 h of the induction of diabetes mellitus, peaked on day 4 and returned to normal levels by day 30. Renal IGF-I correlated positively with the severity of hyperglycaemia on day 7 (r = 0.685, p < 0.001). Immunostaining showed IGF-I to be located within the cortical collecting ducts of normal rats. In diabetic rats, IGF-I also appeared within the cells of the thick ascending limbs of the loops of Henle, in particular those undergoing cytoplasmic vacuolation. The changes in immunoreactive IGF-I assessed stereologically were consistent with the amounts of extractable IGF-I. They were not observed in normoglycaemic, STZ-injected, rats treated with high-dose insulin. This study suggests that IGF-I is involved in diabetic tubular injury and growth.