Value of renal cortical thickness as a predictor of renal function impairment in chronic renal disease patients

Objective: To determine the presence of linear relationship between renal cortical thickness, bipolar length, and parenchymal thickness in chronic kidney disease patients presenting with different estimated glomerular filtration rates (GFRs) and to assess the reproducibility of these measurements using ultrasonography. Materials and Methods: Ultrasonography was performed in 54 chronic renal failure patients. The scans were performed by two independent and blinded radiologists. The estimated GFR was calculated using the Cockcroft-Gault equation. Interobserver agreement was calculated and a linear correlation coefficient (r) was determined in order to establish the relationship between the different renal measurements and estimated GFR. Results: The correlation between GFR and measurements of renal cortical thickness, bipolar length, and parenchymal thickness was, respectively, moderate (r = 0.478; p < 0.001), poor (r = 0.380; p = 0.004), and poor (r = 0.277; p = 0.116). The interobserver agreement was considered excellent (0.754) for measurements of cortical thickness and bipolar length (0.833), and satisfactory for parenchymal thickness (0.523). Conclusion: The interobserver reproducibility for renal measurements obtained was good. A moderate correlation was observed between estimated GFR and cortical thickness, but bipolar length and parenchymal thickness were poorly correlated.

Osmoregulatory defect in adult mice associated with deficient prenatal expression of six2

Suboptimal kidney development resulting from a genetic deficit in nephron number can have lifelong consequences that may lead to cardiorenal complications upon exposure to secondary insults in later life. To determine whether the inherited reduced renal reserve compromises the ability to handle osmotic stress in the adult animal, we challenged the heterozygous 3H1 Brachyrrhine ( Br/+) mouse, which displays heritable renal hypoplasia associated with reduced embryonic six2 expression, to a solution of 2% NaCl for 5 days or to fluid restriction for 48 h. Blood chemistry, fluid intake, and physiological parameters, including renal measurements, were determined. Systemic hypertonicity by prolonged salt loading led to significant increases in plasma osmolality and plasma Na+, along with polydipsia and polyuria, with a significant urine-concentrating defect that was resistant to DDAVP treatment in the adult Br/+ mouse compared with wild-type littermates. The Br/+ mouse also developed a significant increase in blood urea nitrogen at baseline that was further elevated when 2% NaCl was given. Fluid restriction for 48 h further enhanced plasma osmolality and plasma Na+ responses, although the Br/+ mouse was evidently able to produce a small amount of concentrated urine at this time. Hypothalamic c-Fos expression was appropriately activated in the Br/+ mouse in response to both osmotic challenges, indicating an intact central neuroendocrine pathway that was not affected by the lack of congenital six2 expression. Collectively, our results demonstrate impaired osmoregulatory mechanisms consistent with chronic renal failure in the Br/+ mouse and indicate that six2 haploinsufficiency has a direct effect on postnatal fluid and electrolyte handling associated with fluid imbalance.

Effects of physiological hyperinsulinemia on systemic, renal, and hepatic substrate metabolism

To determine the effect of physiological hyperinsulinemia on renal and hepatic substrate metabolism, we assessed systemic and renal glucose release and uptake, systemic and renal gluconeogenesis from glutamine, and certain aspects of systemic and renal glutamine and free fatty acid (FFA) metabolism. These were assessed under basal postabsorptive conditions and during 4-h hyperinsulinemic euglycemic clamp experiments in nine normal volunteers using a combination of isotopic techniques and renal balance measurements. Hepatic glucose release (HGR) and glutamine gluconeogenesis were calculated as the difference between systemic and renal measurements. Infusion of insulin suppressed systemic glucose release and glutamine gluconeogenesis by ∼50% during the last hour of the insulin infusion ( P < 0.001). Renal glucose release and glutamine gluconeogenesis decreased from 2.3 ± 0.4 to 0.9 ± 0.2 ( P < 0.002) and from 0.52 ± 0.07 to 0.14 ± 0.03 μmol ⋅ kg−1 ⋅ min−1( P < 0.001), respectively. HGR and glutamine gluconeogenesis decreased from 8.7 ± 0.4 to 4.5 ± 0.5 ( P < 0.001) and from 0.35 ± 0.02 to 0.27 ± 0.03 μmol ⋅ kg−1 ⋅ min−1( P < 0.002), respectively. Renal glucose uptake (RGU) increased from 1.61 ± 0.19 to 2.18 ± 0.25 μmol ⋅ kg−1 ⋅ min−1( P = 0.029) but accounted for only ∼5% of systemic glucose disposal (40.6 ± 4.3 μmol ⋅ kg−1 ⋅ min−1). Both systemic and renal FFA clearance increased approximately fourfold ( P < 0.001 for both). Nevertheless, renal FFA uptake decreased ( P = 0.024) and was inversely correlated with RGU ( r = −0.582, P = 0.011). Finally, insulin increased systemic glutamine release ( P = 0.007), uptake ( P < 0.005), and clearance ( P < 0.001) but left renal glutamine uptake and release unaffected ( P > 0.4 for both).