Captopril reduces interstitial renal fibrosis and preserves more normal renal tubules in neonatal dogs with partial urethral obstruction: a preliminary study

PURPOSE: Chronic renal damage due to tubulointerstitial fibrosis is one of several complications of posterior urethral valves in a significant number of children. As activation of the renin-angiotensin system plays an important role in this injury, we conducted this study to investigate whether administration of captopril reduced renal fibrosis in an experimental model using partial urethral obstruction (PUO) in neonatal dogs. MATERIAL AND METHODS: Experimental PUO was induced in all pups. These animals were then divided into two groups: in the first group (experimental), captopril 35 mg/kg/day, dissolved in drinking water, was administered for 6 weeks. The second group (positive control) did not receive any treatment. After 6 weeks all dogs underwent left nephrectomy. Volume fraction and absolute volume of the histological kidney parameters, i.e., normal glomerulus, normal tubule, vessels, degenerated glomerulus, degenerated tubule, fibrous tissue, were estimated using modern unbiased stereological methods. RESULTS: The absolute volume of interstitial fibrosis was lower in the experimental group (PUO with captopril treatment) (approximately 73%; p < 0.008) in comparison with positive control animals (PUO with no treatment). The mean absolute volume of normal tubules in the experimental group was more than the positive control group (approximately 33%, p < 0.008). The mean absolute volume of normal and degenerated glomerulus, vessels and degenerated tubule did not show a significant difference between the two groups. CONCLUSION: Administration of captopril decreases interstitial renal fibrosis and preserves renal tubules in neonatal dogs with PUO.     

Complete unilateral ureteral obstruction in the fetal lamb. Part II: Long-term outcomes of renal tissue development

PURPOSE: We analyzed the dynamics of the renal tissue response to experimental fetal urinary flow impairment concerning renal morphology, extracellular matrix composition, regulators of connective tissue degradation and PAX2 protein expression. MATERIALS AND METHODS: A total of 26 fetal lambs underwent surgical unilateral ureteral obstruction at 90 days of gestation and 14 twin matched animals served as controls. Kidneys were harvested 10, 20 and 40 days after the prior procedure in groups 1 to 3, respectively and in 1-month-old lambs (group 4). Morphological analysis was done using light microscopy. Picrosirius red staining was used to evaluate the area occupied by extracellular matrix components. Collagen I, III and IV, alpha-smooth muscle actin, MMP-1, 2 and 9, TIMP-1 and 2 and PAX2 protein were assessed using immunochemistry. RESULTS: All obstructed kidneys were hydronephrotic without dysplasia. Hypoplasia resulting from a decreased NGG was observed. The inflammatory response to obstruction was poor in fetal obstructed kidneys. From 10 days after obstruction interstitial fibrosis was noted and confirmed by an increase in picrosirius red staining. In obstructed kidneys immunochemistry showed an increase in collagen deposition beginning from the papillae and extending through the whole parenchyma. Aberrant interstitial collagen IV deposition was observed. The increase in alpha-smooth muscle actin staining was mainly localized in the blastema and interstitial cells in obstructed kidneys. MMP and TIMP immunostaining was mainly present in tubules throughout the whole nephrogenic period and persisted in mature kidneys. Beginning from 20 days after obstruction a progressive increase in MMP and TIMP expression was noted. This was associated with ectopic expression in the medullary tubules. PAX2 protein was highly expressed in the nephrogenic zone, decreasing progressively to being markedly decreased in control lamb kidneys. No difference was found in PAX2 expression during the fetal period when comparing unobstructed and obstructed kidneys, it but remained strongly expressed in the dilated collecting ducts of obstructed lambs. CONCLUSIONS: Complete unilateral ureteral obstruction performed in fetal lambs at 90 days of gestation led to pure hydronephrotic transformation, hypoplasia and a marked increase in connective tissue deposition. Inflammatory infiltrates and PAX2 dysregulation were not seen as having a decisive role in these modifications.     

Reduced number of glomeruli in kidneys with neonatally induced partial ureteropelvic obstruction in pigs

PURPOSE: We quantify the structural components of the nephron in adult pig kidneys with neonatally induced unilateral hydronephrosis in comparison with nonobstructed kidneys. MATERIALS AND METHODS: The study included 11 pigs with unilateral partial ureteropelvic obstruction induced 2 days after birth and 8 sham operated control pigs. Obstructed kidney glomerular filtration rate was significantly reduced at age 4 weeks but did not differ from control kidneys after 24 weeks. At age 24 weeks the kidneys were perfusion fixed, and the number and volume of glomeruli and tubular lengths were measured using stereological methods. RESULTS: Mean obstructed kidney volume did not differ from that of control kidneys. Mean number plus or minus standard deviation of glomeruli in the obstructed kidneys was reduced by 28% compared to that of control kidneys (502 +/- 163 x 103 versus 697 +/- 161 x 103, p = 0.02), whereas no difference in mean glomerular volume was observed. Mean length of the proximal or distal tubules did not differ between obstructed and control kidneys. Mean number or volume of glomeruli in nonobstructed kidneys contralateral to obstructed kidneys did not differ from that of control kidneys. The individual number of glomeruli in the obstructed kidneys was not associated with function of these kidneys. CONCLUSIONS: Neonatally induced unilateral partial ureteropelvic obstruction causes impaired nephrogenesis with a significant reduction in the number of nephrons, which is not reflected in measurements of kidney function in this model. The reduction in the number of glomeruli suggests that congenital unilateral obstruction impairs nephrogenesis.     

Renal pelvis volume during diuresis in children with hydronephrosis: implications for diagnosing obstruction with diuretic renography

PURPOSE: We measured the volume of the renal pelvis during diuretic renography (DR) in children with normal and hydronephrotic kidneys to determine if changes in pelvic volume could affect the accuracy of DR in diagnosing obstruction. MATERIALS AND METHODS: We studied 18 patients 1 month to 10 years old with unilateral hydronephrosis ultimately proved to be either obstructive or nonobstructive. Simultaneous DR and ultrasound were performed with patients supine using the gamma camera. Ultrasound measurements of the renal pelvis in 3 dimensions, obtained before and at intervals after diuretic injection, were used to calculate renal pelvic volume. The contralateral normal kidneys were used as controls. RESULTS: Between 15 and 60 minutes after diuretic injection the renal pelvis enlarged to a maximum volume in all hydronephrotic and normal kidneys and then gradually decreased in size. Mean average increase in volume for hydronephrotic kidneys ranged from 46% in obstructed kidneys to 88% in nonobstructed kidneys. Volume expansion caused dilution of isotope within the renal pelvis, which resulted in prolongation of elimination half-time (T1/2) in 42% of nonobstructed hydronephrotic kidneys sufficient to register an obstructed washout pattern. However, there were no differences in the initial pelvic volume or the rate or extent of increases or decreases in pelvic volume that would permit nonobstructed hydronephrotic kidneys to be distinguished from obstructed ones. CONCLUSIONS: The renal pelvis enlarges during diuresis in children with hydronephrosis. This enlargement causes dilution of isotope within the renal pelvis during DR, which prolonged the isotope washout rate or T1/2 sufficiently to produce an obstructed washout pattern in more than 40% of hydronephrotic kidneys that were ultimately proved to be nonobstructed. This misdiagnosis of obstruction is particularly likely to occur in children younger than 2 years because pelvic volume expansion is so exaggerated. Consequently, T1/2 appears to be particularly vulnerable to inaccuracy in diagnosing obstruction in this age group, and, therefore, it should not be relied on as an operative determinant.     

Pelviometry in the normal and the partially obstructed porcine kidney: recordings before and three weeks after application of ureteral obstruction

In 11 pigs a standardized proximal ureteric obstruction was applied. The effect of the obstruction was examined three weeks later. In both the normal and the obstructed systems the pressure-volume relationship was exponential. Mean pelvic capacity increased from 6.5 ml. to 44.1 ml. (p less than 0.002). Mean intrapelvic baseline pressure increased from 10.0 to 16.8 cm. H2O (p less than 0.02), and this parameter correlated positively to volume (rS = 0.79 - p less than 0.05). There was a slight decrease in the relative function of the obstructed kidney on renography (from 49% to 39% of the total renal function), but this was not significant. The decrease in function was correlated to the increase in capacity (rS = -0.69 - p less than 0.05). In this series renal deterioration occurred in the hydronephrotic kidneys, and at least in this model of acute ureteral obstruction there was no support for the theory that hydronephrotic transformation is a compensatory mechanism which protects the kidney when the upper urinary tract is obstructed.     

Reversible vasoconstriction in rats with congenital unilateral hydronephrosis

We studied the effects of inhibition of either prostaglandins or the role of prostanoids and the renin-angiotensin system on renal function in rats with congenital unilateral hydronephrosis. Wistar rats with congenital unilateral hydronephrosis were infused with normal saline (control), captopril dissolved in normal saline or indomethacin dissolved in a solution of sodium chloride and sodium carbonate. In the control group both glomerular filtration rate (GFR) and effective renal plasma flow were reduced in the right hydronephrotic kidney (RHK) compared with the normal left kidney. Indomethacin did not improve renal function in the RHK. Captopril significantly improved GFR in the RHK. These results support the conclusion that the renin-angiotensin system is an important mediator of reduced GFR in congenital unilateral hydronephrosis in rats.     

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction

BACKGROUND: The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS: Rat renal tubular epithelial cells (NRK-52E) were subjected to mechanical stretch, and apoptosis and cell size were analyzed by flow cytometry. Furthermore, we studied UUO in mice lacking the gene for inducible nitric oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptosis and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respectively. RESULTS: Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more apoptotic than unstretched cells. In UUO, the obstructed kidney of iNOS-/- mice exhibited more apoptotic renal tubules than the wild-type mice through 14 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more proliferative tubules compared with wild type. The obstructed kidney of wild-type mice exhibited higher total NOS activity until day 7 after UUO compared with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mice exhibited significantly lower iNOS activity and protein compared with the day 0 kidney. CONCLUSION: These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.     

Hydronephrotic obstructed kidney mimicking a congenital multicystic kidney: Case report with review of literature

Objective: To report a case of obstructed hydronephrotic kidney mimicking a multicystic kidney and to review the literature regarding differentiation of the hydronephrotic variant of multicystic kidney from the obstructed hydronephronic kidney. To suggest a possible algorithm in distinguishing them.Methods:We have reported a case of a 35-year-old male who presented with dull aching pain and a palpable right-sided cystic flank mass of several years duration. The initial workup suggested a nonfunctioning multicystic kidney while the operative findings and histopathology were suggestive of an obstructed hydroenphrotic kidney with pyelonephritic changes. We searched the literature using the key words hydronephrotic dysplastic kidney and multicystic kidney.Results:A detailed literature search did not reveal any such publication describing the differentiation of the hydronephrotic multicystic dysplastic kidney from the obstructed hydronephrotic kidney of pelviureteral obstruction. We reviewed the existing literature on this subject, on the basis of which, we have suggested a six-stepladder approach to distinguish such cases.Conclusion:By using the 6 step ladder protocol algorithm suggested by us one can attempt to distinguish the hydronephrotic variant of multicystic dysplastic kidney from the hydronephrotic kidney due to pelviureteral obstruction in patients presenting with a symptomatic cystic flank masses of renal origin. Differentiation between the two may be difficult at times due to the medial/central placement of cysts in the former. This is necessary since renal salvage may be possible in the latter while timely nephrectomy may be considered in the former to prevent against the hazards of leaving behind a dysplastic kidney in situ.     

多层螺旋CT（MSCT）灌注成像评价梗阻性积水肾肾功能的临床研究

目的：探讨多层螺旋CT（MSCT）灌注成像评价梗阻性积水肾肾功能的价值.方法：对36例单侧梗阻性重度肾积水、对侧肾显影正常的患者,按IVU结果分为显影组和不显影组,在梗阻解除前行MSCT灌注扫描,测量积水肾与对侧肾皮质的血流量（BF）、血容量（BV）值,并对两组间积水肾的BF和BV值进行比较.结果：36例中,显影组20例,MSCT检查显示积水肾皮质BF、BV值分别为（412.58±217.56）ml·100 g-1·min-1,（28.66±10.96）ml/100 g;不显影组16例,积水肾皮质BF、BV值分别为（185.24±189.30）ml·100g-1·min-1、（15.6±11.8）ml/100g.两组间积水肾肾皮质BF、BV值比较差异均有统计学意义（P＜0.01）,组内积水肾与对侧肾肾皮质BF、BV值差异显著（P＜0.01）,组间对侧肾肾皮质BF、BV值差异无显著性（P〉0.05）.结论：MSCT灌注成像较IVU能更准确地反映肾功能,在评价单侧梗阻性积水肾肾功能中具有一定价值.     

A case of congenital unilateral multicystic kidney with renal matrix calculi

A forty-two-year-old man was seen with right lumbar pain. Physical examination revealed a right flank mass. Conventional excretory urography showed lack of right renal function, whereas left kidney was visualized. Right nephrectomy was performed. A cluster of several different sized cysts was disclosed in the right renal region. The renal surface was smooth. The removed kidney weighed 1,150 g. The ureter was completely obstructed at the ureteropelvic junction. Cysts were filled with matrix calculi. Pathological examination showed dysplastic glomeruli and primitive tubules within loose embryonic mesenchyme between two cysts whose walls consisted of smooth muscle strands and connective tissue. The final diagnosis was a congenital unilateral multicystic kidney with renal matrix calculi. The multicystic kidney is the most common form of renal cystic disease in infancy. However, few cases in adults have been reported. The diagnostic approach, treatment and outcome of a congenital unilateral multicystic kidney are discussed.     

Experimental partial ureteric obstruction in newborn rats. VII. Are the long term effects on renal morphology avoided by release of the obstruction?

Partial obstruction of the left ureter was created in newborn rats. The obstruction was either permanent or was released after two or seven days. The effects were studied at the age of six weeks. The permanently obstructed kidneys characteristically exhibited considerable enlargement (X 18) of pelvic volume and prominent deformation of the papilla, frequently associated with moderate widening of collecting ducts and convoluted tubuli, and focal inflammatory and degenerative lesions. The weight difference between the hydronephrotic and the contralateral, intact kidney was significantly higher than in a sham operated group, although the combined kidney weight was unchanged, indicating a reduction on the obstructed side and a compensatory contralateral hypertrophy. In the group released after seven days, the pelvic volume had returned to normal; nevertheless the parenchymal weight pattern and the histological lesions were similar to those found in animals obstructed for six weeks. In the group released after two days, the pelvic volume had normalized, and the histological changes were less prominent than in animals obstructed for seven days or six weeks. Yet there was a significant difference in parenchymal weight between the hydronephrotic and the contralateral kidney, almost entirely caused by hypertrophy on the nonobstructed side. Thus, the ureteric obstruction must be released very early to avoid parenchymal weight reduction and curb the tissue lesions. On the other hand, the resulting parenchymal damage is moderate and does not seem to progress with time.     

Continuous infusion urography in unilateral hydronephrosis.

In cases of unilateral hydronephrosis the urine concentration of contrast medium, for example diatrizoate, depends on the remaining renal function, the rate of turnover in the obstructed renal pelvis and the function of the contralateral kidney. Contrast medium for a single injection or a short infusion time is rapidly excreted by the normal contraleteral kidney, without allowing high enough plasma levels long enough for sufficient urine concentrations in the hydronephrotic kidney. This excretion rate can be compensated for by continuous infusion urography for several hours with large doses of contrast medium (up to 1,250 ml. 30 per cent diatrizoate). This method was theoretically computerized, tested in animals experiments and clinically used in 11 patients. It can improve the diagnostic possibilites of excretory urography, especially in cases of unilateral obstruction, and can minimize the need for retrograde pyelography with its known complications.     

Renal functional outcome in unilateral hydronephrosis in newborn pigs

PURPOSE: We followed the course of neonatally induced, partial unilateral ureteral obstruction in pigs and established whether early function or morphological evaluation of the hydronephrotic kidney is predictive of outcome. MATERIALS AND METHODS: In 25 piglets unilateral partial ureteropelvic obstruction was induced 2 days after birth, while 11 underwent sham operation. Only obstructed kidneys with significant dilatation at 4 weeks were included for further study. Renal function was assessed on renography using (99m)technetium-diaminetriaminepentaacetic acid differential uptake. According to the plasma clearance of (99m)technetium-diaminetriaminepentaacetic acid the glomerular filtration rate was determined at ages 4, 12 and 24 weeks. Kidney morphology was studied in parallel by magnetic resonance imaging. RESULTS: A total of 12 obstructed kidneys with grade 3 or 4 hydronephrosis fulfilled study inclusion criteria. Of 6 kidneys with a functional share of 40% or greater at age 4 weeks 2 deteriorated to less than 40% at 24 weeks, while 4 of 6 with a share of less than 40% at age 4 weeks improved to greater than 40% at 24 weeks. The single kidney glomerular filtration rate at 4 weeks did not correlate with that at 12 or 24 weeks but the rate at 12 weeks correlated with that at 24 weeks (r2 = 0.8140, p <0.001). Neither relative volume of the obstructed kidney nor length of the contralateral nonobstructed kidney correlated with functional share of the obstructed kidney at any age. CONCLUSIONS: Early evaluation of kidney function or volume, or contralateral kidney length did not predict the outcome of neonatally induced unilateral hydronephrosis in pigs.     

Pathophysiology of hydronephrotic atrophy: the cause and role of active preglomerular vasoconstriction

Unilateral complete ureteral occlusion is followed by a decreased blood flow in the ipsilateral kidney, which is established within 1 week, after which a steady state of whole renal blood flow is observed. Active preglomerular vasoconstriction is assumed to be the main factor causing renal flow reduction in the hydronephrotic kidney, resulting in rapid decrease of the initial elevated pelvic pressure within 24 h. The assumption of active preglomerular vasoconstriction also explains the observation that blood flow reduction clearly precedes renal atrophy after ureteral ligation. Neither alpha-receptor blocking agents nor angiotensin II blockage, nor denervation, reversed flow reduction in the first hours or weeks after ureteral ligation. A thromboxane synthesis inhibitor (imidazole) did reverse flow reduction completely without affecting the contralateral renal blood flow, indicating that active vasoconstrictive is present. In respect to renal hydronephrotic atrophy, compartment analysis of the blood flow of the obstructed kidney demonstrates that vasoconstriction contributes to ischemic atrophy at least in the cortex of the hydronephrotic kidney. Vasoconstriction cannot be reversed by prostaglandin synthesis inhibition after renal atrophy is established, although the renal blood flow is still sensitive to other vasodilating drugs like dopamine. From our data we conclude that prostaglandin-mediated active preglomerular vasoconstriction is a main factor causing renal atrophy by ischemia.     

Long-term renal effects of unilateral ureteral obstruction and the role of endothelin

BACKGROUND: Angiotensin II (Ang II) and endothelin (ET) are involved in the alteration of renal function in unilateral ureteral obstruction (UUO). The renal response to Ang II following the reversal of a 24-hour UUO and the effect of ET blockade by bosentan during the time of obstruction were investigated. METHODS: Following blockade of the endogenous production of Ang II by captopril, the renal response to Ang II was studied in rats 15 to 18 days after a 24-hour UUO (N = 10) or a sham operation (N = 9) both with (N = 10) and without (N = 8) bosentan treatment in the periobstruction period. Similar studies were performed in another group (N = 9) two months following the reversal of obstruction. RESULTS: In the sham-operated group, Ang II reduced renal blood flow (RBF) by 42 +/- 9% (P < 0.01), glomerular filtration rate (GFR) by 30 +/- 8% (P < 0.01), urine volume (UV) by 44 +/- 9% (P < 0.001), and absolute (UNaV) and fractional sodium excretion (FENa) by 52 +/- 9% (P < 0.001) and 33 +/- 9% (P = 0.054), respectively. In the previously obstructed kidney, Ang II did not change RBF but increased GFR by 106 +/- 40% (P < 0.01), UV by 75 +/- 21% (P < 0.001), UNaV by 190 +/- 60% (P < 0.001), and FENa by 40 +/- 13% (P < 0.05). Bosentan treatment in the obstructed group prevented these Ang II-induced effects and did not have any effect on the sham-operated kidney. Two months following reversal of the obstruction, the response of the kidney was similar to that of the control kidney. CONCLUSION: Twenty-four-hour UUO results in a temporary abnormality in the renal response to Ang II, which is due, in part, to the actions of ET at the time of obstruction.     

Chronic ureteral obstruction in the rat suppresses renal tubular Bcl-2 and stimulates apoptosis

Unilateral ureteral obstruction (UUO) results in widespread tubular apoptosis in obstructed kidneys of both adults and neonates. The oncoprotein bcl-2 inhibits many forms of apoptosis, whereas the related protein bax promotes apoptosis. To evaluate the interaction of bcl-2, bax, and apoptosis in the renal response to UUO, adult and neonatal rats were subjected to UUO or sham operation, and kidneys were harvested 14 days later. Apoptotic cells were identified by the Tunel technique, and the distribution of bcl-2 and bax was determined by immunochemistry. In both adults and neonates, tubular and interstitial apoptosis was present in the obstructed kidney, but not in intact kidneys. In both adults and neonates, there was diffuse tubular bcl-2 and bax staining of sham-operated and intact kidneys. While bcl-2 was increased in scattered nonapoptotic tubules of the obstructed kidney, there was minimal staining of dilated apoptotic tubules. These results are consistent with the premise that bcl-2 normally suppresses renal tubular apoptosis. The distribution of bax staining in tubules of the obstructed kidney overlapped that of bcl-2. We conclude that chronic UUO inhibits bcl-2 expression in selected tubules of the obstructed kidney which contributes to activation of apoptosis and progressive renal damage in either neonatal or adult kidneys. Dysregulation of apoptosis may be a response to renal injury similar to that underlying the development of cystic kidney disease or renal dysplasia.     

Renal structural and functional repair in a mouse model of reversal of ureteral obstruction

The end point of immune and nonimmune renal injury typically involves glomerular and tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to renal fibrosis, less is known about the mechanisms that promote cellular repair and tissue remodeling. Described is a model of renal injury and repair after the reversal of unilateral ureteral obstruction (UUO) in male C57bl/6J mice. Male mice (20 to 25 g) underwent 10 d of UUO with or without 1, 2, 4, or 6 wk of reversal of UUO (R-UUO). UUO resulted in cortical tubular cell atrophy and tubular dilation in conjunction with an almost complete ablation of the outer medulla. This was associated with interstitial macrophage infiltration; increased hydroxyproline content; and upregulated type I, III, IV, and V collagen expression. The volume density of kidney occupied by renal tubules that exhibited a brush border was measured as an assessment of the degree of repair after R-UUO. After 6 wk of R-UUO, there was an increase in the area of kidney occupied by repaired tubules (83.7 +/- 5.9%), compared with 10 d UUO kidneys (32.6 +/- 7.3%). This coincided with reduced macrophage numbers, decreased hydroxyproline content, and reduced collagen accumulation and interstitial matrix expansion, compared with obstructed kidneys from UUO mice. GFR in the 6-wk R-UUO kidneys was restored to 43 to 88% of the GFR in the contralateral unobstructed kidneys. This study describes the regenerative potential of the kidney after the established interstitial matrix expansion and medullary ablation associated with UUO in the adult mouse.     

螺旋CT平扫测量肾实质体积和厚度评价慢性梗阻侧肾脏肾小球滤过率的价值

目的 探讨螺旋CT平扫测量肾实质体积和厚度判断梗阻侧肾小球滤过率(glomerular filtration rate,GFR)的价值,并比较2种肾实质形态学指标与梗阻侧GFR之间的关系.方法 利用螺旋CT平扫测量71例慢性单侧上尿路梗阻性疾病患者的肾实质体积和厚度.①肾实质体积测量:扫描双肾,逐层标示各横断面面积,结合扫描层厚计算肾实质体积,并计算梗阻侧肾实质体积占总的肾实质体积百分比(%CTvol).②肾实质厚度测量:选择包含肾脏集合系统的第一个和最后一个层面的内、外、后3个位置测量肾实质厚度,取平均值作为肾实质厚度,并计算梗阻侧肾实质厚度占总的肾实质厚度百分比(%CTt).采用99Tcm-DTPA肾动态显像技术,应用Gates法测定分肾及总的GFR值,计算梗阻侧肾GFR的百分比(%GFR),采用Pearson相关分析行%CTvol、%CTt与%GFR之间的相关分析.结果 71例患者%CTvol、%CTt与%GFR之间均有明显的相关性,r值分别为0.80(t=11.20,P＜0.05)和0.66(t=7.24,P＜0.05),直线回归方程分别为%GFR=0.05+0.80×%CTvol(F=125.48,P＜0.05)和%GFR=0.12+0.66×%CTt(F=52.36,P＜0.05).结论螺旋CT平扫测量肾实质体积和厚度可以作为临床上评价慢性梗阻侧肾GFR的方法,肾实质体积较肾实质厚度更准确.

Abstract：

Objective To evaluate the value of renal parenchymal volume and thickness by non-contrast spiral CT in evaluating the differential glomerular filtration rate (GFR) for chronic obstructed kidneys, and to compare the correlations between the two morphologic indices of renal parenchyma and the GFR for chronic obstructed kidneys. Methods Seventy-one patients who had a diagnosis of unilateral chronic upper urinary tract obstruction were included in this analysis. (1) The renal parenchymal volume was mea-sured by non-contrast spiral CT. Both kidneys were scanned by non-contrast spiral CT. The renal parenchymal area of each section was marked manually. Renal parenchymal volume was calculated as the sum of renal parenchymal area multiplied by the width of each section. The volume percentage of obstructed kidney (%CTvol) was also calculated. (2) Renal parenchymal thickness was measured on the first and last non-contrast CT image levels from the anterior, posterior and lateral locations of the kidney that clearly contained the collecting system. The mean of these measurements was defined as the renal parenchymal thickness. The differential renal parenchymal thickness of the obstructed kidney (%CTt) was defined as the percentage of the obstructed renal parenchymal thickness to the total renal parenchymal thickness for both kidneys. GFR was determined with 99Tcm-DTPA dynamic imaging system by Gates method. The differential GFR for obstructed kidney (%GFR) was the GFR percentage of obstructed kidney to the total GFR for both kidneys. The Pearson relation test was carried out between the %CTvol, %CTt and the %GFR respectively. Results %CTvol and %CTt correlated well with %GFR in chronic obstructed kidneys among the 71 test group patients. Pearson correlation coefficient r was 0.80 (t=11.20, P＜0.05) and 0.66 (t=7.24, P＜0.05), respectively. The linear correlation equation respectively was %GFR=0.05+0.80×%CTvol (F=125.48, P＜0.05) and %GFR=0.12+0.66×%CTt (F=52.36, P＜0.05). Conclusions Renal parenchymal volume and thickness by non-contrast spiral CT might be used as clinical practical parameters to evaluate the differential GFR for chronic obstructed kidneys. Renal parenchymal volume is more accurate than renal parenchymal thickness.     

Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction

Congenital obstructive nephropathy is a major cause of renal insufficiency in children. Osteopontin (OPN) is a phosphoprotein produced by the kidney that mediates cell adhesion and migration. We investigated the role of OPN in the renal response to unilateral ureteral obstruction (UUO) in neonatal mice. OPN null mutant (-/-) and wild-type (+/+) mice were subjected to sham operation or UUO within the first 2 days of life. At 7 and 21 days of age, fibroblasts (fibroblast-specific protein (FSP)-1), myofibroblasts (alpha-smooth muscle actin (SMA)), and macrophages (F4/80) were identified by immunohistochemical staining. Apoptotic cells were detected by terminal deoxy transferase uridine triphosphate nick end-labeling technique and interstitial collagen by Masson trichrome or picrosirius red stain. Compared to sham-operated or contralateral kidneys, obstructed kidneys showed increases in all parameters by 7 days, with further increases by 21 days. After 21 days UUO, there was an increase in tubular and interstitial apoptosis in OPN -/- mice as compared to +/+ animals (P<0.05). However, FSP-1- and alpha-SMA-positive cells and collagen in the obstructed kidney were decreased in OPN -/- compared to +/+ mice (P<0.05), whereas the interstitial macrophage population did not differ between groups. We conclude that OPN plays a significant role in the recruitment and activation of interstitial fibroblasts to myofibroblasts in the progression of interstitial fibrosis in the developing hydronephrotic kidney. However, OPN also suppresses apoptosis. Future approaches to limit the progression of obstructive nephropathy in the developing kidney will require targeting of specific renal compartments.