. Evidence for increased postprandial distal nephron calcium delivery in hypercalciuric stone-forming patients. Am J Physiol Renal Physiol 295: F1286 -F1294, 2008. First published August 20, 2008 doi:10.1152/ajprenal.90404.2008.-A main mechanism of idiopathic hypercalciuria (IH) in calcium stoneforming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using fourteen 1-h measurements of the clearances of sodium, calcium, and endogenous lithium during a three-meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normal subjects. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ, but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque. nephrolithiasis; tubule reabsorption; lithium clearance; hypercalciuria; proximal tubule IDIOPATHIC HYPERCALCIURIA (IH) is best described as a state of high urine calcium excretion commonly found in patients who form calcium renal stones and thought to play a causal role in such stones (22). Although gastrointestinal calcium absorption is above normal, offering an obvious mechanism for hypercalciuria, the kidney also participates. After eating common foods, patients with calcium stones and IH (IHSF) reduce their overall renal calcium reabsorption more than well-matched normal control subjects (23). This reduction permits high urine calcium losses despite unchanged serum calcium and calcium filtered load. Although serum parathyroid hormone decreases with meals, levels do so equally in IHSF patients and normal subjects, and therefore cannot be the main mechanism for the reduced tubule calcium reabsorption (23). Because the differential increase in urine calcium occurs without a corresponding difference of urine sodium between IHSF and normal, the cortical thick ascending limb of the loop of Henle was considered an attractive site of reduced calcium reabsorption (1) along with the distal convoluted tubule (8). Since filtered load of calcium did not differ between patients and normal subjects, hypercalciuria essentially arose from the change in tubule reabsorption.Which nephron sites participat...

OBJECTIVE To determine if the acute renal oxidative stress and inflammation after extracorporeal shock wave lithotripsy (ESWL), thought to be mediated by ischaemia, is most severe in the portion of the kidney within the focal zone of the lithotripter, and if these effects result primarily from ischaemic injury. MATERIALS AND METHODS Pigs (7–8‐weeks old) received either 2000 shock waves at 24 kV to the lower‐pole calyx of one kidney or unilateral renal ischaemia for 1 h. A third group (sham) received no treatment. Timed urine and blood samples were taken for analysis of lipid peroxidation and the inflammatory cytokines, tumour necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). At 4 h after treatment, kidneys were removed and samples of cortex and medulla were frozen for analysis of cytokines and heme oxygenase‐1 (HO‐1). RESULTS ESWL did not affect urinary excretion of malondialdehyde, but did elicit an eight‐fold induction of HO‐1 in the portion of the renal medulla within the focal zone of the lithotripter (F2), while remaining unchanged elsewhere in the treated kidney. There was no induction of HO‐1 in renal tissue after ischaemia‐reperfusion. Urinary excretion of TNF‐α increased from the lithotripsy‐treated kidney by 1 h after treatment, but was unaffected by ischaemia‐reperfusion. As with the HO‐1 response after lithotripsy, IL‐6 increased only in the renal medulla at F2. By contrast, ischaemia‐reperfusion increased IL‐6 in all samples from the treated kidney. CONCLUSION These findings show that the acute oxidative stress and inflammatory responses to ESWL are localized to the renal medulla at F2. Furthermore, the differing patterns of markers of injury for ESWL and ischaemia‐reperfusion suggest that ischaemia is not the principal cause of the injury response after ESWL.

Direct Numerical Simulation is performed of the forced Navier-Stokes equation in four spatial dimensions. Well equilibrated, long time runs at sufficient resolution were obtained to reliably measure spectral quantities, the velocity derivative skewness and the dimensionless dissipation rate. Comparisons to corresponding two and three dimensional results are made. Energy fluctuations are measured and show a clear reduction moving from three to four dimensions. The dynamics appear to show simplifications in four dimensions with a picture of increased forward energy transfer resulting in an extended inertial range with smaller Kolmogorov scale. This enhanced forwards transfer is linked to our finding of increased dissipative anomaly and velocity derivative skewness.

Objective To determine if the magnitude of the acute injury response to shock-wave lithotripsy (SWL) depends on the number of SWs delivered to the kidney, as SWL causes acute renal oxidative stress and inflammation which are most severe in the portion of the kidney within the focal zone of the lithotripter. Materials and Methods Pigs (7–8 weeks old) received 500, 1000 or 2000 SWs at 24 kV from a lithotripter to the lower pole calyx of one kidney. At 4 h after treatment the kidneys were removed, and samples of cortex and medulla were frozen for analysis of the cytokine, interleukin-6, and for the stress response protein, heme oxygenase-1 (HO-1). Urine samples taken before and after treatment were analysed for the inflammatory cytokine, tumour necrosis factor-α. For comparison, we included previously published cytokine data from pigs exposed to sham treatment. Results Treatment with either 1000 or 2000 SWs caused a significant induction of HO-1 in the renal medulla within the focal zone of the lithotripter (F2, 1000 SWs, P < 0.05; 2000 SWs, P < 0.001). Interleukin-6 was also significantly elevated in the renal medulla of the pigs that received either 1000 or 2000 SWs (P < 0.05 and <0.001, respectively). Linear dose–response modelling showed a significant correlation between the HO-1 and interleukin-6 responses with SW dose (P < 0.001). Urinary excretion of tumour necrosis factor-α from the lithotripsy-treated kidney increased only for pigs that received 2000 SWs (P < 0.05). Conclusion The magnitude of renal oxidative stress and inflammatory response in the medulla increased with the number of SWs. However, it is not known if the HO-1 response is beneficial or deleterious; determining that will inform us whether SWL-induced renal injury can be assessed by quantifying markers of oxidative stress and inflammation.

Abstract