Postnatal maturation of the rabbit cortical collecting duct

The mature, fully differentiated cortical collecting duct plays a major role in the final renal regulation of Na⁺, K⁺ and H⁺ transport. To characterize the growth of this segment, we measured the outer diameter and the dry weight of cortical collecting ducts isolated from newborn, 1-month-old, and adult rabbits. During the 1st month of life no significant changes were observed; however, there was a 60% increase in both parameters after the 4th week of life. Growth-related accretion of K⁺ was demonstrated by showing tubular K⁺ content to increase by 60% with maturation. Concomitant with the increase in tubular size, total cell number per millimeter of tubular length rose by 30%. Approximately 50% of the observed increment in tubular size could be accounted for by cell hyperplasia, with the remaining increase resulting from cell hypertrophy. Hypertrophy of principal cells was confirmed by scanning electron microscopy, which demonstrated a doubling of the circumferential width without any change in longitudinal length. Hyperplasia was confirmed, using a fluorescent chromatin stain, by our finding of a mitotic frequency of 3/1000 cells in the neonatal mid-cortical collecting duct; the observed number of mitoses was 10-fold higher at the most cortical end (ampulla). The number of intercalated cells per millimeter of tubule length, identified by bright green fluorescence after cortical collecting ducts were stained with 6-carboxyfluorescein diacetate, was found to double during maturation, the increase being significant only after the 4th postnatal week. We conclude that maturation of the mid-cortical collecting duct results from both cellular hyperplasia and hypertrophy. It is unlikely that this segment plays a major role in regulating Na⁺, K⁺, and H⁺ transport in the neonatal kidney.     

Water transport in the immature rabbit collecting duct

 Immature animals have limited ability to concentrate the urine. This is in part the result of end-organ resistance to arginine vasopressin (AVP). To characterize this response, we measured water absorption in microperfused cortical collecting ducts (iCCD) and outer medullary CD (iOMCD) derived from 2- to 12-day-old rabbits. The roles of adenosine 3′,5′-cyclic monophosphate (cAMP) and prostaglandins were investigated. Baseline osmotic water permeability (L_p, 10⁻⁷ cm/atm per s) in the iCCD (20.3±2.4) and iOMCD (19.7±5.6) was not different from mature CCD (mCCD) (14.6±3.1). After AVP, L_p in the iCCD (46.7±10.0) was significantly lower than in the mCCD (114.3±21.8). Neither stimulation with cAMP (85.6±51.3) nor inhibition of endogenous prostaglandin production with indomethacin (57.6±29.8) abolished the blunted response to AVP in the iCCD. We conclude that AVP-stimulated water transport in the iCCD is impaired. The disruption in AVP response is, at least in part, localized distal to cAMP, and is not mediated by prostaglandins. Received: 29 December 1997 / Revised: 13 April 1998 / Accepted: 14 April 1998     

Cation channels of the rabbit outer medullary collecting duct.

The outer medullary collecting duct (OMCD) produces high rates of proton secretion, and previous data show a significant role for an H+,K+-ATPase in luminal acidification. This mechanism of acidification requires proton secretion to occur in exchange for potassium absorption. Because net transport of potassium is small in the OMCD, pathways for potassium secretion would appear essential to explain the contribution of an H+,K+-ATPase under potassium-replete conditions. A significant issue is whether a potassium exit pathway (i.e., cation channel) is present at the apical and/or the basolateral membrane. In this report, using patch-clamp techniques to examine single channel conductances from the native rabbit OMCD, we show that the apical membrane has potassium permeable cation channels.     

Mechanism of iodide transport in the rabbit cortical collecting duct

Background Pendrin, an anion exchanger known to participate in iodide transport in the apical membrane of follicular cells of the thyroid gland, has recently been shown to exist in the apical membrane of the β- and γ-intercalated (β/γ-IC) cells of the cortical collecting duct (CCD). We examined mechanisms of iodide transport in the CCD. Methods Rabbit CCD was perfused in vitro, and lumen-to-bath flux coefficients for both ¹²⁵I⁻ (K_{I (lb)}) and ³⁶Cl⁻ (K_{Cl (lb)}) were measured simultaneously. The intracellular pH (pHi) of β/γ-IC cells in the perfused CCD was measured by microscopic fluorometory, by loading 2′,7′-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein tetraacetoxy methylester (BCECF-AM), a fluorescent marker for pHi. The effects on pHi of the replacement of NaCl with Na cyclamate, NaI, or NaBr in the lumen or bath were observed. Results K_{I (lb)} was comparable to or slightly higher than K_{Cl (lb)}. Both iodide and chloride in the lumen caused self- and cross-inhibitions to both fluxes. The addition of 5-nitro-2-(-3-phenylpropylamino)-benzoate (NPPB), a Cl⁻ channel inhibitor, to the bath significantly reduced K_{Cl (lb)}, but not K_{I (lb)}. Replacement of luminal fluid NaCl with Na cyclamate, NaI, or NaBr caused alkalization of pHi, no change in pHi, and slight acidification of pHi, respectively. Replacement of bath NaCl with Na cyclamate, NaI, or NaBr caused alkalization, alkalization, and acidification of pHi, respectively. Luminal NaI prevented the acidification of pHi caused by bath Na cyclamate. Conclusions The data are consistent with the model that iodide is transported via the Cl⁻/HCO₃⁻ exchanger in the apical membrane of β/γ-IC cells and exits the basolateral membrane via an electroneutral transporter that is distinct from the Cl⁻ channel. We could not, however, identify which type of β/γ-IC cell was mainly responsible.     

Generation of pH gradient across the rabbit collecting duct segments perfused in vitro

Ability of pH gradient generation was examined in three segments of rabbit collecting duct, cortical collecting duct (CCD), outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD). These segments were perfused in vitro, and the steady-state luminal pH in stop-flow condition (pHs) and the electrochemical potential difference of H+ (EH) were determined using double-barreled liquid membrane pH microelectrode punctured into the lumen. In CCD, pHs was 7.71 +/- 0.08 in normal rabbits, 7.72 +/- 0.08 in DOCA-treated rabbits and 7.27 +/- 0.05 in starved rabbits, while peritubular fluid was kept at pH 7.5 EH (positive value means H+ accumulation in the lumen above electrochemical equilibrium) was -15.3 +/- 5.2, -31.3 +/- 3.7 and 10.3 +/- 3.1 mV, respectively. Peritubular acidification (peritubular pH 6.8) by reducing HCO3-concentration decreased pHs, but increased its negativity of EH in all groups. In OMCD pHs was 6.57 +/- 0.08 in normal, 6.58 +/- 0.11 in DOCA-treated and 6.47 +/- 0.12 in starved animals. EH was 54.5 +/- 4.6, 57.7 +/- 6.8 and 64.2 +/- 6.9 mV, respectively. Peritubular acidification lowered pHs further, 5.51 +/- 0.07, 5.67 +/- 0.16 and 5.41 +/- 0.19, respectively. EH was enhanced in all groups. In IMCD pHs was 7.36 +/- 0.04 with EH being 6.8 +/- 2.9 mV, and peritubular acidification did not generate pH gradient. These data suggest that the generation of a steep acid pH gradient is mainly due to OMCD. Luminal alkalinization predominated in CCD except in starved rabbits. IMCD did not generate appreciable pH gradient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successive lectin-binding changes within the collecting duct during post-natal development of the rabbit kidney

Histological sections of neonatal rabbit kidney of various ages were analysed to study the ontogeny of the collecting duct system. In addition, the sections were incubated with fluorescent wheat germ (WGA) and peanut agglutinin (PNA) to investigate the terminal differentiation of collecting duct cells. With both lectins we found different binding behaviours in the three segments of the collecting duct anlagen, the ampullary bud, the ampullary neck and the collecting duct. During the observed steps in development the lectin-binding pattern in the collecting duct and the ampullary neck appeared unchanged. In the collecting duct most cells reacted with WGA and only a few with PNA, while in the ampullary neck all cells bound both WGA and PNA. In the ampullary bud, however, the lectin-binding pattern changed between unlabelled and completely labelled stages with both lectins. The results indicate that both intercalated and principal cells originate from a common precursor cell.     

Bellini duct (collecting duct) carcinoma of the kidney

Carcinoma of the collecting ducts, or Bellini carcinoma, is a rare renal tumour and, unlike most renal cell carcinomas, it derives from distal tubules. It displays highly aggressive behaviour and has a poor prognosis. In this study, the authors present three cases which they observed over the past three years.     

Cortically located collecting duct carcinoma

Collecting duct carcinoma is a rare, highly aggressive, renal tumor arising from the distal collecting ducts. Various histologic patterns can be found in the same tumor but most demonstrate duct-like or papillary architecture surrounded by desmoplastic stroma. Grossly, these tumors are typically located in the medullary portion of the kidney near the region of the pelvis without extensive hemorrhage. It has a tendency to affect young patients and present at more advanced stages with a poorer prognosis. We describe a case of collecting duct carcinoma with histologic and immunohistochemical findings in a cortically located tumor.     

Organization of collecting duct intercalated cells

Our understanding of the mechanisms by which the collecting duct transports HCO3 continues to evolve rapidly. The models put forth in Figure 1, though esthetically pleasing by virtue of their simplicity, will undoubtedly require modification as the above areas and others continue to be explored. It should be noted that a large percentage of the citations in this review emanate from colleagues of Dr. Donald Seldin who have been or currently are nephrologists at Southwestern Medical School in Dallas. The length of this list is testimony to the large number of investigators in the field of renal acid-base research who have been intellectually stimulated by their contact with Dr. Seldin.     

The role of the collecting duct in urinary concentration

In summary, the three major segments of the collecting duct subserve three different functions in the urinary concentrating mechanism. The main function of the cortical collecting tubule is to raise the fractional solute contribution and absolute concentration of urea in fluid that it delivers to the outer medullary collecting duct. The function of the outer medullary collecting duct is to raise further the absolute intraluminal urea concentration. Finally, the inner medullary collecting duct has two major functions in urinary concentration: first, it adds net urea to the papillary interstitium, and second, it allows the generation of maximally concentrated urine due to osmotic water equilibration. Indeed, the urine osmolality can rise to levels higher than the papillary interstitial osmolality as a consequence of inequalities of the reflection coefficients of urea and sodium chloride.     

肾集合管癌8例临床病理分析

目的探究肾集合管癌的临床及病理特征。方法回顾性研究我院收治的8例肾集合管癌患者的临床、病理资料并进行随访。结果 8例患者均施行肾根治性切除术,术中见肿瘤直径5~12cm。肿瘤主要位于肾髓质,呈侵袭性生长,以腺管或腺管乳头状结构为主,部分表现为片状生长,间质内含较多淋巴细胞,并伴有集合管上皮的异型增生。免疫组化显示肿瘤细胞均表达CK7、CK19、上皮膜抗原(EMA)、34βE12、PNA,UEA-1、vimentin呈部分阳性表达,而HMB45和S-100为阴性。随访患者中4例患者发生转移,2例死于肾癌转移,2例带瘤生存。平均生存时间为12.8个月。结论肾集合管癌较罕见,恶性程度高,侵袭性强,预后差。根治性手术为主要治疗手段,术后靶向治疗可能改善患者预后,但仍需临床试验进一步验证。