Endothelin-1 expression in scleroderma renal crisis

The objective of the study was to investigate the role of endothelin-1 in the pathogenesis of scleroderma renal crisis in patients with systemic sclerosis. We used immunohistochemical analysis with anti-endothelin-1 and anti-von Willebrand factor antibodies in comparing kidney biopsies from patients with systemic sclerosis and scleroderma renal crisis (n = 14); from normal kidneys (n = 5); and from patients with typical hemolytic uremic syndrome and thrombotic microangiopathy (n = 5), antiphospholipid syndrome (n = 6), diabetic nephropathy (n = 5), minimal change disease with cyclosporine toxicity (n = 5), or nephroangiosclerosis (n = 5). Kidney biopsies from all systemic sclerosis patients presented specific lesions: glomerular lesions with thickened capillary walls (n = 6, 42.8%), mesangiolysis (n = 3, 21.4%), fibrin thrombi (n = 3, 21.4%), hypertrophy of juxtaglomerular apparatus (n = 5, 35.7%), arteriolar lesions showing mucinous intimal thickening and lumen mucoid occlusions (n = 13, 92.8%), proliferation of intimal cells (ie, "onion-skin" lesions; n = 13, 92.8%), fibrinoid necrosis (n = 3, 21.4%), and fibrin thrombosis (n = 4, 28.6%). Chronic lesions in large arteries showed modifications such as fibrous intimal thickening (n = 13, 92.8%). The pattern of endothelial staining for endothelin-1 in both glomeruli and arteriolar lesions appears to be specific for scleroderma renal crisis. Glomerular endothelin-1 staining without arteriolar staining was seen in hemolytic uremic syndrome; and isolated arteriolar staining (without glomerular staining) was seen in a number of conditions including antiphospholipid nephropathy, cyclosporine toxicity, and diabetic nephropathy. Endothelin-1 is overexpressed in glomeruli and arterioles of patients with scleroderma renal crisis, which suggests that endothelin-1 might be a therapeutic target in this condition.     

Depolarization pattern of ventricular epicardium in two-kidney one-clip hypertensive rats

The present study is the first attempt to examine the effect of left ventricular hypertrophy (LVH) on the excitation pattern of the ventricular epicardium in experimental hypertensive rats. The left renal artery was clipped in Wistar rats (n = 8; 6-8 months old; weight, 174-295 g) to produce two-kidney one-clip (2K1C) hypertension. After 4 weeks, blood pressure was measured, and epicardial potential mapping was performed under sinus rhythm from 64 unipolar electrodes regularly distributed over the ventricular epicardium. Systolic blood pressure was approximately 40% higher in the rats with a clipped renal artery (162 +/- 14 mmHg, mean +/- s.d.) than in the normotensive rats (115 +/- 3 mmHg). LVH (approximately 23% increase in the ratio of the left ventricular weight to the body weight, P < 0.05) was observed in the 2K1C hypertensive rats. The depolarization pattern of the ventricular epicardium in the normotensive rats was similar to that in the rats with 2K1C hypertensive LVH. The duration of ventricular epicardial activation was shown to increase (approximately 35%, P < 0.05) in the hypertensive rats as compared to the normotensive animals. This study provides an explanation for alterations of the body surface potential distribution in hypertensive patients with LVH.     

Renal ACE2 expression in human kidney disease

Angiotensin-converting enzyme 2 (ACE2) is a recently discovered homologue of angiotensin-converting enzyme (ACE) that is thought to counterbalance ACE. ACE2 cleaves angiotensin I and angiotensin II into the inactive angiotensin 1-9, and the vasodilator and anti-proliferative angiotensin 1-7, respectively. ACE2 is known to be present in human kidney, but no data on renal disease are available to date. Renal biopsies from 58 patients with diverse primary and secondary renal diseases were studied (hypertensive nephropathy n = 5, IgA glomerulopathy n = 8, minimal change nephropathy n = 7, diabetic nephropathy n = 8, focal glomerulosclerosis n = 5, vasculitis n = 7, and membranous glomerulopathy n = 18) in addition to 17 renal transplants and 18 samples from normal renal tissue. Immunohistochemical staining for ACE2 was scored semi-quantitatively. In control kidneys, ACE2 was present in tubular and glomerular epithelium and in vascular smooth muscle cells and the endothelium of interlobular arteries. In all primary and secondary renal diseases, and renal transplants, neo-expression of ACE2 was found in glomerular and peritubular capillary endothelium. There were no differences between the various renal disorders, or between acute and chronic rejection and control transplants. ACE inhibitor treatment did not alter ACE2 expression. In primary and secondary renal disease, and in transplanted kidneys, neo-expression of ACE2 occurs in glomerular and peritubular capillary endothelium. Further studies should elucidate the possible protective mechanisms involved in the de novo expression of ACE2 in renal disease.     

Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension

Red-cell lithium-sodium countertransport is increased in patients with essential hypertension. It has been proposed that sodium-hydrogen ion exchange in the brush border of the renal proximal tubules is analogous to red-cell countertransport. To investigate the rate of sodium reabsorption by the proximal renal tubules in hypertension, we measured lithium clearance (a measure of proximal tubular reabsorption of sodium), as well as red-cell countertransport, in 14 patients with untreated essential hypertension and in 31 controls. As a group, the hypertensive patients had a higher average (+/- SEM) rate of red-cell countertransport (0.378 +/- 0.030 mmol of lithium per liter of cells per hour, P less than 0.01) and a lower renal fractional lithium clearance (13.96 +/- 0.69 percent, P less than 0.01) than normotensive subjects (0.317 +/- 0.015 mmol of lithium per liter of cells per hour and 17.75 +/- 0.81 percent, respectively). Within the normotensive group, subjects with hypertension in at least one first-degree relative had significantly lower fractional lithium clearances than subjects with no hypertensive relatives (15.37 +/- 0.84 percent vs. 19.06 +/- 1.07 percent, P less than 0.05). We conclude that hypertensive patients have heightened proximal tubular reabsorption of sodium and that red-cell countertransport is a marker of the renal abnormality. Enhanced proximal tubular sodium reabsorption may precede the development of essential hypertension.     

Platelet magnesium depletion in normotensive and hypertensive obese subjects: the role of salt-regulating hormones and catecholamines.

We measured plasma and platelet magnesium concentrations, plasma epinephrine and norepinephrine, and plasma aldosterone and renin concentrations in normotensive (NT-Ob, n = 19, BMI 35.7 +/- 7.4 kg/m2, WHR 0.92 +/- 0.05) and hypertensive (HT-Ob, n = 11, BMI 35.2 +/- 3.6 kg/m2, WHR 0.93 +/- 0.07) obese subjects, and in a group of age- and sex-matched lean controls (n = 14, BMI 23.1 +/- 1.8 kg/m2, WHR 0.79 +/- 0.05). Plasma aldosterone and renin concentrations were significantly higher in obese subjects with respect to controls. Moreover, plasma norepinephrine and epinephrine levels were significantly increased in obese subjects, and plasma norepinephrine was higher in HT-Ob when compared to NT-Ob group. Platelet magnesium concentrations were significantly reduced in both normotensive and hypertensive obese subjects with respect to controls (controls 2.65 +/- 0.35 mumol/10(8) cells, NT-Ob 2.02 +/- 0.19 mumol/10(8) cells--p < 0.001, HT-Ob 1.98 +/- 0.18 mumol/10(8) cells--p < 0.001), while a slightly significant decrease in plasma magnesium levels was only detectable in HT-Ob group. Urinary magnesium and magnesium fractional excretion were significantly increased in hypertensive obeses. Pearson's correlation analysis, separately performed in each group of subjects, showed that plasma aldosterone, renin, epinephrine, norepinephrine and magnesium fractional excretion were negatively correlated to platelet magnesium levels in NT-Ob and HT-Ob groups, but not in lean controls. The multiple linear regression analysis performed in the whole group of obese subjects considering platelet magnesium as a dependent variable showed that platelet magnesium decrease together with the increase in plasma epinephrine (p = 0.046) and norepinephrine (p = 0.020), also after adjusting for age, sex, BMI, WHR, HOMA IR and diagnosis of hypertension. Furthermore, platelet magnesium showed a trend for negative association (p < 0.1) to plasma aldosterone and magnesium fractional excretion in multivariate analysis. The impairment in platelet magnesium handling observed in normotensive and hypertensive obese patients seems to be associated to a rise in renin-angiotensin-aldosterone and sympathetic systems activity. Our results suggest that platelet magnesium depletion, together with disturbances of salt-regulating hormones and catecholamines, may be involved in the pathophysiology of cardiovascular complications from obesity.     

Consequences of renal morphologic damage induced by inhibition of converting enzyme in rat renovascular hypertension

The consequences of morphologic changes in the kidney distal to a stenosis induced by chronic administration of a converting enzyme inhibitor were determined after induction of experimental renovascular hypertension in rats. The relationship between changes in morphology in the clipped kidney and diuresis, creatinine, and mortality was studied by converting a two-kidney, one-clip model into a one-kidney, one-clip model after 1 month of converting enzyme inhibition. The right renal artery was constricted with a clip of 0.2 mm diameter to increase blood pressure, the left kidney was left untouched. After 1 month, systolic blood pressure had increased to 173 +/- 27 mm Hg in the clipped animals (n = 47) compared with 139 +/- 8 mm Hg in sham-operated animals (n = 15; group 1). An inhibitor of angiotensin-converting enzyme, MK421 (2 mg/kg, po), or an equivalent volume of vehicle was then administered daily for 1 month. After treatment with the converting enzyme inhibitor, blood pressure (148 +/- 28 mm Hg) was virtually identical with that of a sham-operated, vehicle-treated control group (145 +/- 16 mm Hg, n = 15), and was significantly lower than that of untreated hypertensive rats (186 +/- 30 mm Hg, n = 17) (group 2). The weight of the left kidney was increased in the untreated hypertensive animals as compared with sham-operated controls (1260 +/- 168 mg for group 2 versus 1075 +/- 100 mg for group 1). After treatment with MK421, the weight of the contralateral kidney (1472 +/- 190 mg) was further increased. After 1 month of treatment with MK421 or vehicle, the unclipped left kidney was removed from all animals. The treated animals were then randomly divided into two groups: one in which treatment with MK421 was stopped (treated/untreated, n = 24; group 3) and a second in which the treatment was continued (treated/treated, n = 23; group 4). The ability of the rats to excrete a water load of 15 ml was then examined 12 hours after removal of the unclipped left kidney. In the two groups of treated rats, the urinary excretion of the water load was decreased and frequency of oliguria was increased as compared with controls and hypertensive untreated rats. Survival rates were affected by the treatment: 3 deaths occurred in the hypertensive untreated group 2, 10 in the treated/untreated group 3, and 12 in the treated/treated group 4. The majority of these deaths could be attributed to renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)     

The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease

BACKGROUND. A high incidence of hypertension (50 to 75 percent) occurs early in the course of autosomal dominant polycystic kidney disease. Cyst enlargement, causing bilateral renal ischemia and subsequent release of renin, is proposed as the cause of this form of hypertension. METHODS. To investigate this hypothesis, we measured plasma renin activity and aldosterone concentrations during short-term and long-term converting-enzyme inhibition in 14 patients with hypertension due to polycystic kidney disease, 9 patients with essential hypertension, 11 normotensive patients with polycystic kidney disease, and 13 normal subjects. The groups were comparable with respect to age, sex, body-surface area, degree of hypertension, sodium excretion, and renal function. RESULTS. During the short-term study, the mean (+/- SE) plasma renin activity was significantly higher in the hypertensive patients with polycystic kidney disease than in the patients with essential hypertension, in the supine (0.36 +/- 0.06 vs. 0.22 +/- 0.06 ng per liter.second, P = 0.05) and upright positions (1.03 +/- 0.14 vs. 0.61 +/- 0.08 ng per liter.second, P less than 0.03) and after converting-enzyme inhibition (1.97 +/- 0.28 vs. 0.67 +/- 0.17 ng per liter.second, P less than 0.0006). The mean arterial pressures measured in the supine and upright positions and the plasma aldosterone concentrations measured in the upright position were significantly higher in the normotensive patients with polycystic kidney disease than in the normal subjects. After six weeks of converting-enzyme inhibition, renal plasma flow increased (P less than 0.005), and both renal vascular resistance (P less than 0.007) and the filtration fraction (P less than 0.02) decreased significantly in the hypertensive patients with polycystic kidney disease but not in the patients with essential hypertension. CONCLUSIONS. The renin-angiotensin-aldosterone system is stimulated significantly more in hypertensive patients with polycystic kidney disease than in comparable patients with essential hypertension. The increased renin release, perhaps due to renal ischemia caused by cyst expansion, probably contributes to the early development of hypertension in polycystic kidney disease.     

Renal hemodynamics and the renin-angiotensin-aldosterone system in normotensive subjects with hypertensive and normotensive parents

BACKGROUND AND METHODS. The kidney is important in blood-pressure regulation, but its role in the development of essential hypertension is still subject to debate. We compared renal hemodynamics, measured in terms of the clearance of para-aminohippuric acid and inulin, and the characteristics of the renin-angiotensin-aldosterone system in three groups of normotensive subjects at different degrees of risk for hypertension: 41 subjects with two normotensive parents, 52 with one normotensive and one hypertensive parent, and 61 with two hypertensive parents. The subjects ranged in age from 7 to 32 years. RESULTS. The mean renal blood flow was lower in the subjects with two hypertensive parents than in those with two normotensive parents (mean difference [+/- SE], 198 +/- 61 ml per minute per 1.73 m2 of body-surface area; P = 0.002). Moreover, both the filtration fraction and renal vascular resistance were higher in the subjects with two hypertensive parents (filtration fraction: mean difference, 3.0 +/- 1.1 percentage points; P = 0.006; renal vascular resistance: mean difference, 2.7 +/- 0.8 mm Hg per deciliter per minute per 1.73 m2; P = 0.006). The subjects with two hypertensive parents had lower plasma concentrations of renin (mean difference, 3.3 +/- 1.6 mU per liter; P = 0.03) and aldosterone (mean difference, 111 +/- 36 pmol per liter; P = 0.003) than those with two normotensive parents. The differences could not be explained by the small differences in blood pressure between the groups. The values in the subjects with one hypertensive and one normotensive parent fell between those for the other two groups. CONCLUSIONS. Renal vasoconstriction is increased and renin and aldosterone secretion is decreased in young persons at risk for hypertension. These findings support the hypothesis that alterations in renal hemodynamics occur at an early stage in the development of familial hypertension.     

On glomerular structural alterations in type-1 diabetes

Glomerular structural modifications were measured in kidney biopsies from two follow-up studies in type-1 diabetic patients with microalbuminuria and in kidney donors. Stereologic methods were used to obtain data on glomerular composition and absolute quantities per glomerulus to supplement data on diabetic glomerulopathy previously published. Diabetic patients at baseline (n=37) showed significant changes compared with controls (n=11). The volume fraction of tuft/glomerulus was increased, the proportion of capillary surface facing peripheral basement membrane was decreased (0.72+/-0.04 vs 0.77+/-0.03, P=0.0008), the ratio of mesangial surfaces, urinary/capillary, was decreased (0.67+/-0.17 vs 1.11+/-0.28, P<10(-4)), and the average capillary diameter was increased (8.9+/-0.9 microm vs 7.5+/-1.0 microm, P=0.0002). The total volume of mesangial extracellular material per glomerulus was increased (P=0.01), whereas glomerular volume was not significantly different from controls. Follow-up biopsies after antihypertensive treatment with ACE-inhibitor (n=7) or beta-blocker (n=6; 36-48 months) and after intensive insulin treatment (n=7; 24-33 months) showed no change. In a conventionally treated group (n=9), the glomerular volume, the volume of extracellular material/glomerulus, and the capillary length increased. The mean capillary diameter did not correlate with the glomerular volume. In conclusion, the development of diabetic glomerulopathy entails structural modifications of the glomerular tuft. Antihypertensive and intensified insulin treatment seem to slow the progression of ultrastructural changes.     

造影剂肾病发病机制中炎症反应的探讨*

  目的：通过观察肿瘤坏死因子α（TNF-α）与核因子κB（NF-κB）在造影剂肾病(CIN)模型大鼠肾组织中的表达,初步探讨CIN发病中是否存在炎症反应机制。方法：将96只雄性SD大鼠随机分成2组：模型组（n=48）和对照组（n=48）,分别从尾静脉注射碘造影剂和生理盐水10 mL/kg。在注射后6 h、12 h、24 h、48 h、72 h、5 d、10 d和15 d各处死6只大鼠,留取血液和肾组织,采用HE染色法观察肾脏病理变化,免疫组化和RT-PCR法分别检测肾损伤分子1（KIM-1）、NF-κB、TNF-α蛋白和mRNA表达情况,并进行相关性分析。结果：（1）对照组血清肌酐（SCr）和血尿素氮（BUN）各时点变化不大（P＞0.05）,模型组各时点（除15 d外）SCr和BUN水平明显高于对照组（P＜0.05）;（2）对照组各时点肾小管无明显损伤,病理评分无显著差异（P＞0.05）。模型组的肾小管损伤评分显著高于同一时点的对照组（P＜0.05）;（3）各因子在造膜后6 h后开始大量表达,KIM-1蛋白及mRNA在24 h达高峰,NF-κB、TNF-α蛋白及mRNA在48 h达高峰,且与对照组对应时点（除15 d外）比较均有显著差异（P＜0.05）;（4）模型组肾小管损伤评分与NF-κB、TNF-α蛋白及mRNA表达呈正相关（r=0.843、0.758、0.743和0.707,P＜0.05）;模型组肾组织的NF-κB、TNF-α蛋白及mRNA表达与KIM-1蛋白及mRNA表达呈正相关（r=0.863、0.807、0.839和0.855,均P＜0.05）。结论：NF-κB和TNF-α在CIN大鼠肾脏中的表达上调,其表达水平与肾小管损伤程度相关。CIN的发生发展中存在炎症反应机制。     

新疆哈萨克族隔离群醛固酮合成酶基因多态性与原发性高血压的关联性

目的探讨哈萨克族人群醛固酮合成酶基因CYP11B2T(-344)C多态性与原发性高血压的关联性。方法用聚合酶链反应、限制性内切酶方法检测了新疆巴里坤县哈萨克族186例原发性高血压患者和168名正常人群CYP11B2基因T(-344)C多态性。结果哈萨克族正常人群及高血压患者的CYP11B2基因T(-344)C多态CC、CT、TT基因型频率分布分别为0.12、0.61、0.27和0.20、0.50、0.30,C和T等位基因分布频率分别为0.43、0.57和0.45、0.55,符合Hardy-Weinberg平衡。群体相关分析结果表明CYP11B2基因的C及T等位基因分布在高血压病组及正常人群差异无显著性(χ2=0.380,P=0.537);基因型频率之间差异无显著性(χ2=4.838,P=0.089)。然而女性高血压组CC基因型频率较正常人群高(χ2=6.104,P<0.05)。结论CYP11B2基因T(-344)C多态性可能与新疆巴里坤哈萨克族女性高血压有关。     

Bioelectric impedance in the estimation of hemodynamic and fluid status in dialysis patients

In order to estimate the hemodynamic and fluid changes, "dry body weight" and intradialytic stability, electric bioimpedance cardiography was performed in 37 dialysis patients during dialysis procedure, i.e. before, at 2 h and after dialysis. The following parameters were estimated: systemic vascular resistance index-fl. Ohm/m2 (SVRI), mean arterial pressure-Torr (MAP), thoracic fluid conductivity/Ohm (TFC), cardiac index-L/min/m2 (CI), left cardiac work index-kg m/m2 (LCWI) and ejection fraction % (EF). Results were compared with changes in total body water estimated by the urea kinetic model (UKM). The patients were divided into three groups: normotensive (n = 12), hypertensive (n = 15) and hypotensive (n = 10). EF was increased in all the three groups, but only in hypotensives this change was significant (from 40.5 +/- 9.1 to 50.2 +/- 5.41, p < 0.01). The changes in other hemodynamic parameters (CI, LCWI, SVRI) did not reach statistical significance. TFC decreased significantly in all the three groups: normotensive from 0.056 +/- 0.009 to 0.048 +/- 0.009 (p < 0.001), hypotensive from 0.043 +/- 0.009 to 0.035 +/- 0.058 (p < 0.001) and hypertensive from 0.054 +/- 0.016 to 0.045 +/- 0.014 (p < 0.001). These changes were accompanied by a significant decrease in total body water (TBW): from 34.05 +/- 4.19 to 32.72 +/- 4.51 in the hypotensive group, from 34.06 +/- 7.18 to 32.91 +/- 7.27 in the normotensive group, and from 38.92 +/- 7.06 to 37.59 +/- 7.04 in the hypertensive group. The technique was found to be simple, noninvasive and helpful for the estimation of individual hemodynamic changes during dialysis procedure.     

Comparison of chloride concentration and osmolality in proximal tubular fluid, peritubular capillary plasma and systemic plasma in the rat.

1. Chloride concentration and osmolalities were compared in consecutively collected samples of proximal tubular fluid, peritubular capillary plasma and systemic plasma. 2. Mean chloride concentrations (m-mole/l) were 141.3+/-2.6 in tubular fluid, 114.8+/-1.7 in peritubular capillary plasma and 119.4+/-1.8 in systemic plasma. 3. Mean osmolalities (m-osmole/kg H2O) were 297+/-2.2 in tubular fluid, 293+/-2.4 in peritubular capillary plasma and 299+/-1.8 in systemic plasma. 4. These differences are discussed in relation to the anatomical and functional organization of the peritubular capillaries and renal tubules.     

Goldblatt hypertension and operant thermoregulation in shaved, sialoadenectomized rats

The thermobehavioral consequences of angiotensinogenic two-kidney (2K) and sodium-volume dependent one-kidney (1K) forms of Goldblatt (one-clip) renovascular hypertension were assessed in shaved, sialoadenectomized rats. The 2K group (n = 8) underwent unilateral renal artery stenosis with the contralateral kidney left intact; whereas the Sham-Operation (Sham-Op) Control group (n = 7) received only a laparotomy. The 1K group (n = 8) underwent unilateral renal artery stenosis with contralateral nephrectomy, and the Uninephrectomy Control group (n = 6) was only unilaterally nephrectomized. Shaping and testing was conducted in a convective thermal controller that permitted the experimenters to control, through continuously reinforced bar-pressing, the ambient temperature during exposure to warm (37 degrees C) or cold (17 degrees C) temperatures. Testing at each temperature occurred over two 6-hr sessions with an interpolated 48-hr rest period. Both 2K and 1K hypertensive rats exhibited longer durations of heat escape than their appropriate normotensive controls across both testing sessions. No differences were detected in response frequency, duration of cold escape responding, or body temperature. The results suggest that either the increased vascular resistance or the neuroendocrine-sympathetic disorder linked to the pathogenesis of Goldblatt renovascular hypertension may promote heat retention or lower heat tolerance.     

Remission of essential hypertension after renal transplantation

Six patients in whom "essential hypertension" led to nephrosclerosis and kidney failure received kidney transplants from normotensive donors. After an average follow-up of 4.5 years, all were normotensive and had evidence of reversal of hypertensive damage to the heart and retinal vessels. These six patients, all of whom were black, and six control subjects matched for age, sex, and race were admitted to the General Clinical Research Center for 11 days for observation of their blood pressure and their responses to salt deprivation and salt loading. Mean arterial pressure (+/- S.E.M.) among the patients who had previously had essential hypertension was similar to that of the normal controls (92 +/- 1.9 vs. 94 +/- 3.9; P not significant), and both groups had similar responses to salt deprivation and salt loading. Thus, essential hypertension in human beings is shown to be similar to the hypertension seen in spontaneously hypertensive rats in that both can be corrected by transplantation of a kidney from a normotensive donor. This observation supports the concept of the primary of the kidney in causing essential hypertension.     

Transport and metabolism of octanoate by the perfused rat kidney.

These studies were done to determine the capacity of the perfused rat kidney to metabolize and transport the medium-chain fatty acid, octanoate (C8). Use of C8, which is water soluble, facilitated the study of transport, since protein, normally needed to transport long-chain fatty acids in solution, could be omitted from the perfusate. Using a filtering kidney it was found that total metabolism and incorporation of [1-14C]octanoate occurred at a rate of 3.9 +/- 0.3 micromol-g wet wt-1-20 min-1 when the perfusate octanoate was 2.8 mM, and reabsorptive uptake occurred at the rate of 7.5 +/- 1.3 micromol-g wet wt-1-20 min-1 at the same octanoate concentration. Use of a nonfiltering kidney (10% dextran perfusate) allowed quantitation of peritubular octanoate uptake. This peritubular uptake showed saturation above 0.7 mM perfusate octanoate with an apparent transport maximum (Tmax) at 2.1 micromol-g wet wt-1-20 min-1. Many previous experiments have linked renal fatty acid transport with that of the organic anion transport system. The apparent peritubular Tmax observed for octanoate suggests carrier-mediated transport. However, this transport did not appear to be inhibited by other organic acids such as probenecid (1--2 mM) and p-aminohippurate (1--2 mM).     

Long-term control of hypertension in dialysis patients by low dose atenolol

Hypertension in dialysis patients is considered a major factor in cardiovascular mortality. We investigated long-term efficacy of intermittent atenolol (AT) administration in 10 (7M/3F) hypertensive dialysis patients, age 60.5 (38-72), on dialysis for 56.5 months (8-156) thrice per week (10.5-13.5 h/w) (A). A similar group of 11 normotensive patients served as controls (B). Hypertension was defined as BP> 140/90 (day) and >120/80 mmHg (night) by a 44-h ambulatory BP monitoring (ABPM) after the mid-week session. Dialysis ultrafiltration, hematology, biochemistry were similar in A and B. Atenolol was started on an alternate day, 37.5 mg/w and increased as needed. After 34 days (6-80) and a dose of 68.75 (37.5-450) mg/w, BP dropped (ABPM: MAP 104+/-11.5 to 95.6+/-10.4 mmHg, P=0.0025) similar to controls and daytime HR dropped: 84.6+/-9.2 to 69.3+/-8.2, P=0.0008 and at night: 79.5+/-7.6 to 68.6+/-8.6 b/1' becoming lower than in B: 83+/-10.8/69.3+/-8.2, P=0.009 and 80.5+/-11.7/68.6+/-8.6 b/1' (P=0. 02). Six months later ABPM in A as well as echocardiography in A and B remained unchanged. Moderate, volume independent hypertension in stable dialysis patients is easily controlled during the interdialytic period by small intermittent atenolol doses.     

Impairment and recovery of the clipped kidney in two kidney, one clip hypertensive rats during and after antihypertensive therapy

Earlier experiments have shown that in sodium depleted hypertensive rats with bilaterally constricted renal arteries the arterial pressure normalized after blockade of the renin-angiotensin system; simultaneously acute renal failure occurred. In hypertensive rats with unilateral renal artery stenosis an impaired excretory function of the clipped kidney can be expected, but may not be detectable by conventional tests of renal function. Male Wistar rats with chronic two kidney, one clip hypertension were fed a low sodium diet. After 7 days the rats were treated with vehicle, with the vasodilator dihydralazine, or with the angiotension converting enzyme inhibitor MK 421 for 2 weeks. During the 14-day treatment period a continuous blood pressure reduction was achieved in dihydralazine and MK 421 treated rats. Overall excretory kidney function (plasma creatinine concentration) was well maintained in all three groups until the end of the antihypertensive drug treatment. At the end of drug therapy mean glomerular filtration rates of the left clipped kidneys were significantly lower in both treated groups compared to hypertensive controls, and mean glomerular filtration rate of the left clipped kidneys of dihydralazine treated rats was significantly higher than in MK 421 treated rats: controls (N = 6) 1.03 +/- 0.03, dihydralazine-group (N = 10) 0.28 +/- 0.07, MK 421-group (N = 9) 0.03 +/- 0.01 ml/min. Renal blood flows were comparable in both treated groups. Only the left kidneys of rats treated with MK 421 showed a prominent tubular atrophy. Seven days after declipping of the left renal artery and right nephrectomy a considerable restitution of the tubular structure had occurred in the MK 421-group. The recovery of tubular epithelial cells was paralleled by a rise in glomerular filtration rate: MK 421 group (N = 7) 1.25 +/- 0.08 ml/min. Thus, the clipped kidney in two kidney, one clip hypertensive rats showed functional and morphological signs of impairment when systemic arterial pressure was reduced to the normal range. The alterations of the clipped kidney were most pronounced in rats with renin-angiotensin system-blockade.     

C4d/CD34 double-immunofluorescence staining of renal allograft biopsies for assessing peritubular capillary C4d positivity

Immunofluorescence detection of the complement split product C4d along peritubular capillaries in renal allograft biopsies is the mainstay for the diagnosis of antibody-mediated rejection. The extent of peritubular capillary C4d positivity may have significant clinical ramifications; however, peritubular capillary density in the renal cortex is often difficult to assess with single-channel immunofluorescence. In this study, we report a C4d/CD34 double-immunofluorescence staining protocol for renal allograft frozen sections that allows rapid and sensitive detection of C4d positivity, as well as improved accuracy in estimating the C4d-positive fraction of peritubular capillaries. In addition, this method aids in determining whether C4d-positive structures correspond to peritubular capillaries or whether they represent common mimics of peritubular capillaries such as tubular basement membranes. C4d/CD34 double immunofluorescence provides rapid, convenient, and low-cost implementation for laboratories currently utilizing single-channel C4d immunofluorescence.     

Systemic hypertension after kidney transplantation: associated risk factors and influence on graft survival

Systemic hypertension after kidney transplant (HAPT) has been associated with a reduction in graft survival and increased morbidity and mortality of kidney transplant recipients. With the use of calcinuerin inhibitors, prevalence of HAPT has increased to 60-80%. The purpose of this study was to document the prevalence of HAPT in kidney transplant recipients attending the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" associated risk factors and the effect of hypertension in long term graft survival. We retrospectively reviewed the clinical charts of all the patients that underwent kidney transplant from 1984 to 1994. The following risk factors were studied: age, gender, cause of renal failure, presence of hypertension before kidney transplant, histocompatibility, acute rejection episodes, chronic rejection, serum creatinine values and use of cyclosporine. We divided subjects in two groups: normotensive (NT) and hypertensive (HT). HAPT included 3140/90 mmHg blood pressure level observed at least during two consecutive evaluations or the use of antihypertensive medication. We analyzed 215 grafts from 205 patients (10 patients had two kidney transplants); mean age at transplant of 30 +/- 9 years, 131 subjects were female and 84 male. One hundred and eighty eight patients (88%) displayed pretransplant hypertension. The mean follow up was 56+/-32 months. In the postransplant period 152 (71%) were HT and 63 (29%) NT. The HT group had significantly higher blood pressure and serum creatinine values than the NT group (P < 0.001), in spite of an adequate blood pressure control in 65% of the patients from the HT group. The NT group displayed a higher graft survival than the HT group; 60 +/- 30 months vs. 51 +/- 32 months respectively (p<0.01). Multivariate analysis did not show any risk factors independently associated with the development of HAPT. The prevalence of HAPT in our series is similar to the one reported in the literature. During the postransplant period there was a reduction of hypertensive patients (88% pretransplant vs. 71% postransplant). HAPT is a significant risk factor associated with long term survival of the graft.