Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

Characterization and control of proton-ATPase along the nephron.

International audienceSince it is now well established that the Na-H exchanger accounts for only part of tubular proton secretion, we attempted to characterize the molecular processes responsible for the remaining moiety. In particular, we evaluated the possible roles of proton pumps in urinary acidification. For this purpose, we characterized ATPase activities associated with the electrogenic H pump, on the one hand, and with H-K-ATPase, on the other. In order to circumvent the axial heterogeneity of nephron, this study was carried out on microdissected segments of nephron. The present report summarized experiments which aimed: (1) at characterizing H-ATPase and H-K-ATPase on kinetic and pharmacologic bases in the successive segments of mammalian nephrons; (2) at evaluating the ionic transport mediated by these two ATPases; and (3) at determining the factors which control the activity of these pumps

Effect of metabolic acidosis and alkalosis on NEM-sensitive ATPase in rat nephron segments

International audienceAn N-ethylmaleimide (NEM)-sensitive adenosinetriphosphatase (ATPase) displaying the kinetic and pharmacological properties of an electrogenic proton pump has been described in the different segments of rat nephron, where it mediates part of the active tubular proton secretion. This study was therefore designed to evaluate whether changes in urinary acidification observed during metabolic acidosis or alkalosis were associated with alterations of the activity of tubular NEM-sensitive ATPase, and if so, to localize the nephron segments responsible for these changes. Within 1 wk after the onset of ammonium chloride treatment, rats developed a metabolic acidosis, and NEM-sensitive ATPase activity was markedly increased in the medullary thick ascending limb of Henle's loop and outer medullary collecting tubule, and slightly increased in the cortical collecting tubule. Conversely, treatment with sodium bicarbonate induced a metabolic alkalosis that was accompanied by decreased NEM-sensitive ATPase activity in medullary thick ascending limb and outer medullary collecting tubule. NEM-sensitive ATPase activity was not altered in any other nephron segment tested in alkalotic and acidotic rats, i.e., the proximal tubule and the cortical thick ascending limb of Henle's loop. Changes qualitatively similar were observed as soon as 3 h after the onset of NaHCO3 or NH4Cl-loading. In the medullary collecting tubule, alterations of NEM-sensitive ATPase activity are in part due to hyperaldosteronism observed in both acidotic and alkalotic rats.(ABSTRACT TRUNCATED AT 250 WORDS

Difference in the Na affinity of Na(+)-K(+)-ATPase along the rabbit nephron: modulation by K

International audienceThe sensitivity of Na(+)-K(+)-ATPase to Na was determined in single segments of rabbit nephron isolated by microdissection. In the cortical collecting tubule (CCT), Na(+)-K(+)-ATPase was threefold more sensitive to Na (apparent K0.5 approximately 3 mM) than in proximal convoluted tubule and cortical thick ascending limb (apparent K0.5 approximately 10 mM). Furthermore, increasing K concentration from 5 to greater than 100 mM markedly reduced the affinity of the pump for Na in all three nephron segments. In fact, the main shift in Na affinity occurred when K changed from 100 to 120 mM; in the CCT, increasing K concentration from 100 to 120 mM while maintaining Na concentration at 10 mM reduced Na(+)-K(+)-ATPase activity by greater than 35%. These findings confirm that, in kidney cells as in other cells, intracellular Na limits the rate of Na(+)-K(+)-ATPase. Thus any alteration of intracellular Na concentration modifies the pump activity in a way that contributes to the restoration of intracellular Na homeostasis. This adaptive property is particularly efficient in the collecting tubule in which the apparent K0.5 of the pump for Na is close to normal intracellular Na concentration. Furthermore, changes in intracellular K concentration, which usually accompany those of Na so as to maintain the total cation concentration constant, potentiate the regulatory role of Na through modifications of its affinity for the pump

Renal proton adenosine triphosphatases.

International audienc

K(+)-ATPase-mediated Rb+ transport in rat collecting tubule: modulation during K+ deprivation

International audienceTo evaluate the involvement of K(+)-ATPase activity in K+ transport in the terminal segments of the rat nephron, we searched for the existence of a component of Rb+ uptake into microdissected segments of collecting tubule associated with the activity of this ATPase. Results indicated that K(+)-ATPase is stimulated by K+ and by Rb+ in a similar fashion and that it is specifically inhibited by the imidazopyridine Sch 28080 (apparent affinity approximately 5 x 10(-7) M). In both cortical and outer medullary collecting tubules (CCT and MCT) of normal rats, 10(-4) M Sch 28080 significantly inhibited the initial rate of Rb+ uptake. Sch 28080-sensitive Rb+ uptake in these two nephron segments was not altered by ouabain, as K(+)-ATPase activity. Finally, both K(+)-ATPase activity and Sch 28080-sensitive Rb+ uptake were increased by similar factors in the CCT and MCT of rats fed a K(+)-depleted diet for 3 days. In these two nephron segments, the apparent stoichiometry of K(+)-ATPase was 1 Rb+:1 ATP. These results demonstrate that K(+)-ATPase reflects the activity of a K+ pump that is pharmacologically similar to the gastric H(+)-K+ pump