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PubMed2004

Hypertension in HIV-1-infected patients and its impact on renal and cardiovascular integrity.

BACKGROUND: With increasing life spans of HIV-infected individuals under highly active antiretroviral therapy, long-term consequences of the chronic infection and antiretroviral treatment are becoming more prevalent. Data on prevalence and consequences of hypertension are limited, but recent studies suggest that HIV-infected individuals are at a higher risk of developing hypertension. METHODS: In this prospective study, HIV-1-infected patients from the Frankfurt AIDS Cohort Study (FACS) were followed for 1 year to determine the frequency of systemic hypertension and to assess the associated clinical and demographic factors. RESULTS: A total 214 HIV-1-infected patients, predominantly Caucasian males, participated in the study. Prevalence of systemic hypertension was 29%. The groups of hypertensive and normotensive individuals were comparable in terms of ethnic background and duration of infection. As in the general population, hypertensive subjects were older (49.1+/-11.1 vs 39.0+/-8.1 years; P<0.0001) and waist-to-hip ratio was higher than in normotensive individuals (0.99+/-0.07 vs 0.93+/-0.08; P<0.0001). Hypertension was associated with a much higher frequency of persistent proteinuria (41.1% vs 2.8%; P<0.001), coronary heart disease (16.1% vs 1.3%; P<0.0001) and myocardial infarction (8.1% vs 0.7%; P<0.005), whereas most cardiovascular risk factors were similar in both groups. CONCLUSIONS: Our data do not demonstrate any association between the presence of hypertension and antiretroviral therapy or immune status. However, hypertension seems to have a high impact on the existing risk for premature cardiovascular disease. Furthermore, overt proteinuria is frequent in HIV-1 infection with hypertension and might be due to hypertensive nephrosclerosis as well as yet undefined renal disease in these patients.

Adult↗

PubMed2004

Renal cell carcinoma co-existent with other renal disease: clinico-pathological features in pre-dialysis patients and those receiving dialysis or renal transplantation.

BACKGROUND: Patients on chronic dialysis are prone to developing acquired cystic kidney disease (ACKD), which may lead to the development of renal cell carcinoma (RCC). The risk factors for the development of RCC so far have not been determined in pre-dialysis patients with co-existent renal disease. The aim of this study was to evaluate the clinico-pathological features of RCC in pre-dialysis patients with associated renal diseases or in those undergoing chronic dialysis and renal transplantation. METHODS: We studied 32 kidneys from 31 patients with RCC and associated renal diseases. Of those, 18 kidneys were from 17 patients not on renal replacement therapy (RRT) when diagnosed with RCC; 14 patients received dialysis or dialysis followed by renal transplantation. Several clinico-pathological features were analysed and compared between the two groups. RESULTS: Overall, there was a preponderance of males (75%); nephrosclerosis was the predominant co-existent disease (31%). The median intervals from renal disease to RCC in the dialysis and transplanted groups were significantly longer than in the pre-dialysis group (15.8+/-1.1 vs 2.4+/-0.7 years, P<0.0001). In contrast to pre-dialysis RCC, the dialysis and transplant RCC groups had greater frequency of ACKD (100 vs 28%, P<0.0001), papillary type RCC (43 vs 11%, P<0.05) and multifocal tumours (43 vs 5%, P<0.05). At the end of the study, 71% of dialysis and transplanted patients and 72% of pre-dialysis patients were alive. CONCLUSIONS: ACKD develops in dialysis patients, as it does in those with renal disease prior to RRT. The duration of renal disease, rather than the dialysis procedure itself, appears to be the main determinant of ACKD and RCC. The RCC occurring in patients with ACKD and prolonged RRT is more frequently of the papillary type and multifocal than the RCC occurring in patients with no or few acquired cysts and a short history of renal disease. Long-term outcomes did not differ between the two groups.

Aged↗

PubMed2005

Influence of a pre-dialysis education programme (PDEP) on the mode of renal replacement therapy.

BACKGROUND: The distribution of renal replacement therapy (RRT) modalities among patients varies from country to country, and is often influenced by non-medical factors. In our department, patients progressing towards end-stage renal disease (ESRD) go through a structured Pre-Dialysis Education Programme (PDEP). The goals of the programme, based on both individualized information session(s) given by an experienced nurse to the patient and family and the use of in-house audio-visual tapes, are to inform on all modalities of RRT, in order to decrease anxiety and promote self-care RRT modalities. METHODS: To evaluate the influence of our PDEP on the choice of RRT modalities, we retrospectively reviewed the modalities chosen by all consecutive patients starting a first RRT in our institution between December 1994 and March 2000. RESULTS: Two hundred and forty-two patients started a first RRT during the study period. Fifty-seven patients, median age 66 (24-80) years, were directed towards in-centre haemodialysis (HD) for medical or psycho-social reasons (seven of whom were not involved in the PDEP); the remaining 185 patients, median age 53 (7-81) years, with no major medical complications, went through our PDEP. Eight of them (4%) received a pre-emptive renal transplantation. The therapeutic options of the other 177 patients were as follows: 75 (40%) patients, median age 65 (20-81) years opted for in-centre HD, while 102 patients opted for a self-care modality; 55 (31%) patients, median age 56 (7-77) years, chose peritoneal dialysis, 30 (16%) patients, median age 49 (21-68) years, chose to perform self-care HD in our satellite unit, and 17 (9%) patients, median age 46 (19-70) years, opted for home HD. Interestingly, in the whole cohort of patients, the cause of ESRD was associated with the RRT modality: the proportion of patients with chronic glomerulonephritis or chronic interstitial nephritis on self-care therapy was significantly higher than that of patients with nephrosclerosis, diabetic nephropathy or unknown cause of ESRD. CONCLUSION: In our centre offering all treatment RRT modalities, a high percentage of patients exposed to a structured PDEP start with a self-care RRT modality. This leaves in-centre HD for patients needing medical and nursing care, or for patients refusing to participate in their treatment. Additional large studies, preferably with a randomized design, should delineate the cost-benefit of such a PDEP on the final choice of a RRT modality.

Adult↗

PubMed1991

Hemopericardium following cerebral hemorrhage. Report of an autopsy case.

The simultaneous occurrence of cerebral hemorrhage and hemopericardium due to the rupture of a dissecting aneurysm has not been previously reported. We describe an autopsy case of a 45-year-old man with hypertension who died suddenly following both of these conditions. He had been treated for hypertension; the finding of arteriolar nephrosclerosis supported the existence of the disease. Because rupture of the aorta invariably causes a marked fall in blood pressure, the occurrence of cerebral hemorrhage following hemopericardium is highly unlikely. Thus, we presume that rupture of the aorta occurred after the cerebral hemorrhage.

Aortic Dissection↗

PubMed1984

The role of dietary protein in the progression and symptomatology of chronic renal failure.

Dietary factors may have substantial impact on the clinical manifestations and even the progression of chronic renal failure. Proper dietary management can prevent certain uremic complications, decrease azotemia, and may even prevent the loss of residual renal function. Recent studies indicate that dietary protein may accelerate the normal age-related deterioration of renal function in rats. The extensive ablation of functional renal mass in rats leads to hyperemia and hyperfiltration in remnant nephrons. Continued hyperfiltration theoretically results in glomerular damage, proteinuria, and ultimately glomerular sclerosis. Dietary protein restriction reduces the remnant nephron hyperfiltration and reduces the rate of glomerular sclerosis, at least in the rat. The role of dietary protein in the pathogenesis of human nephrosclerosis remains controversial. Though dietary factors may or may not affect the rate of progression of renal insufficiency, there is no doubt that proper dietary management can limit or forestall uremic symptoms and the need for dialysis. Diets containing about 0.5 gm protein/kg body weight/day usually maintain a neutral or slightly positive nitrogen balance, while lesser amounts usually result in malnutrition. When protein intake exceeds 0.5 gm/kg/day azotemia increases dramatically. The use of nitrogen-free keto- or hydroxy-analogues of amino acids promotes positive nitrogen balance while reducing azotemia in patients with near-end-stage renal disease.

Amino Acids↗

PubMed1988

Clinical experience with labetalol and enalapril in combination in patients with severe essential and renovascular hypertension.

Severe hypertension may be a difficult management issue, and it often requires therapy with multiple drugs at frequent dosing intervals. We report on the antihypertensive effects of the alpha-beta adrenergic blocking agent, labetalol, in combination with enalapril, a long-acting angiotensin-converting enzyme inhibitor, administered to 14 patients with severe hypertension (nine of whom had nephrosclerosis or renal artery stenosis) on other antihypertensive drug therapies. Blood pressure (BP), heart rate (HR), hematologic and blood chemistry values, and adverse side effects were monitored at 24 hours, 1 week, and 4 weeks of therapy. Rapid titration of the drugs was performed in the hospital in 10 patients; four were managed closely as outpatients. Following one month of combination therapy blood pressure decreased from 212 +/- 31/120 +/- 16 mm Hg at baseline to 155 +/- 19/86 +/- 12 mm Hg, and heart rate declined from 86 +/- 18 bpm to 70 +/- 16 bpm. Ten of the 14 patients (71%) maintained good BP control (BP less than 140/90 mm Hg) with no additional treatment. Serum potassium, creatinine, blood urea nitrogen concentrations, and hematologic parameters did not significantly change in 13 of 14 patients. Three patients developed symptomatic postural hypotension; in one patient this side effect resulted in discontinuation from the study. These data suggest that combination therapy with labetalol and enalapril is effective in lowering BP in patients with severe essential or renovascular hypertension. An additional advantage of this regimen is the twice-daily dosing interval, which may promote better long-term compliance.

Adolescent↗

PubMed1995

Case report: analgesic nephropathy: a soda and a powder.

Analgesic nephropathy has long been considered a potentially preventable cause of renal disease. Early reports were described in patients who consumed analgesics containing phenacetin. In recent data, the removal of phenacetin from analgesic preparations resulted in a reduction in analgesic-induced end stage renal disease in Europe and Australia. However, a reduction in the incidence of analgesic nephropathy has not occurred uniformly, suggesting that phenacetin is not the sole cause. Current data raise concerns regarding adverse renal effects of acetaminophen and nonsteroidal antiinflammatory drugs. Aspirin taken alone may be of least concern. The diagnosis of analgesic nephropathy is suggested in subjects with chronic renal failure, a history of daily consumption of analgesic preparations, small bumpy kidneys, and renal papillary necrosis or chronic interstitial nephritis. However, the spectrum of disease may be changing, because these agents also may increase the risk of cardiovascular disease and chronic renal disease due to nephrosclerosis, glomerulonephritis, and diabetes mellitus. Potential pathogenetic mechanisms in analgesic nephropathy include direct cellular injury induced by analgesics, prostaglandin inhibition with reduction or redistribution of renal blood flow, and interesting new concepts regarding the role of caffeine in increasing oxygen demand and reducing oxygen supply in the medulla. The primary goal of therapy is discontinuation of analgesic consumption. Because of the association between analgesic intake and uroepithelial tumors, surveillance of patients for neoplasm is suggested.

Analgesics↗

PubMed1994

Dysplastic tubular epithelium in "normal" kidney associated with renal cell carcinoma.

Intratubular epithelial dysplasia (IED) of the renal tubules has not been fully described in human renal cell carcinoma (RCC). This lesion has been found in male Syrian hamsters exposed to estrogens. One article reports IED in human kidney showing nephrosclerosis and RCC. We examined "normal" kidney tissue adjacent to 110 cases of RCC in an attempt to identify possible precursor lesions. There were 73 male and 37 female patients (M/F = 2:1). The ages ranged from 27 to 86 years (median 64 years). IED was identified in 30 cases. The lesions consisted of foci of crowded tubular epithelium with large, vesicular nuclei two to three times the size of nuclei of benign tubular cells with eosinophilic macronucleoli. The tubules were occasionally filled with dysplastic cells mimicking carcinoma in situ. The lesions were predominantly cortical and periglomerular. They either were subtle and focal or, less commonly, involved tubules diffusely. Eighteen of the 73 male patients (24%) had these lesions compared with 12 of 37 female patients (32%). They were more usually seen in the clear cell (21 of 66) and sarcomatoid (three of four) variants of RCC than in the oncocytic/granular cell (four of 25) or tubulopapillary (two of 14) variants. One case of collecting duct RCC showed no evidence of IED. Immunohistochemical assessment of 20 dysplastic and 20 nondysplastic lesions with their adjacent RCC for cytokeratin, vimentin, cathepsin-D, and epidermal growth factor receptors was inconclusive. Our findings suggest that IED associated with RCC might represent previously unrecognized precursor lesions along the spectrum ranging from dysplasia to frank carcinoma. The biological significance of these lesions, their preponderance in women, and the phenotypic and genotypic characteristics require further investigation.

Adult↗

PubMed1990

Renal uptake of Tl-201 in hypertensive patients undergoing myocardial perfusion imaging.

The detection of renovascular disease (RVD) has particular relevance in hypertensive patients (HP) who have symptoms of target organ damage. To evaluate the possibility of RVD in HP undergoing myocardial perfusion scintigraphy for chest pain symptoms, posterior renal images were obtained at 1-3 hours after Tl-201 injection. Analog and computer images were obtained for 5 minutes in 45 HP; 12 patients with no history of hypertension or renal disease served as normal controls. For qualitative analysis, images were coded and read by three observers as to symmetry of renal uptake. Differential renal uptake of Tl-201 (DRU) was quantitated on computer images. In normal controls, uptake was agreed on as symmetric. In HP, 6 patients had marked asymmetry of DRU and 4 had possibly significant asymmetry; 2 had decreased uptake in both kidneys suggesting bilateral RVD or nephrosclerosis. Objective correlation with DRU was obtained in 10 HP who had contrast angiography, confirming 4 cases of unilateral RVD and 2 of bilateral RVD. Thirteen patients also had renography with Tc-99m DTPA; differential renal function by this modality correlated well with DRU of Tl-201 (r = 0.98). Thus, DRU of Tl-201 can be used as a supplement to myocardial scintigraphy to identify HP who require further evaluation and treatment of RVD.

Adult↗

PubMed1993

Control of blood pressure and end-organ damage in maturing salt-loaded stroke-prone spontaneously hypertensive rats by oral angiotensin II receptor blockade.

OBJECTIVE: To study the effects of renin-angiotensin system blockade by a novel non-peptide angiotensin II receptor antagonist, losartan, on development of hypertension and acceleration of end-organ damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). DESIGN AND METHODS: One hundred and eighty-one male SHRSP were fed a 4% sodium diet from 6 to 18 weeks of age. Seventy-eight SHRSP were treated orally with losartan, 30 mg/kg per day. One hundred and three rats constituted untreated controls. Blood pressure, plasma renin activity (PRA), renal function and end-organ damage were monitored during the transition to malignant hypertension. RESULTS: Losartan prevented a blood pressure rise during the first 4 weeks of salt loading. Thereafter, blood pressure rose slowly in losartan-treated rats; however, at each time-point studied blood pressure was significantly lower in losartan-treated rats than in control rats. Losartan treatment increased PRA during the first 4 weeks, but this effect was not sustained. Thereafter, PRA decreased to control (week 0) levels. In contrast, 2 weeks after high-sodium feeding started, untreated SHRSP failed to suppress PRA appropriately; thereafter, PRA rose significantly. Losartan affected renal pathophysiology by blunting the decline in glomerular filtration rate, controlling proteinuria and preventing or delaying the appearance of malignant nephrosclerosis. Losartan treatment significantly increased survival and completely prevented cerebrovascular infarcts. CONCLUSIONS: The results indicate that angiotensin II blockade markedly reduces both hypertension and end-organ damage in chronically salt-loaded SHRSP and that the renin-angiotensin system may play an important role in the development of hypertensive cardiovascular disease in SHRSP.

Angiotensin II↗

PubMed1997

Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease.

Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. Eleven to 14% of end-stage renal disease (ESRD) cases are attributable to chronic IRD. A high percentage of patients entering ESRD programs are hypertensive. Many patients with a presumed diagnosis of hypertensive nephrosclerosis actually have undiagnosed ischemic nephropathy as the etiology of their ESRD. It is important for the clinician to identify IRD, because IRD is a potentially reversible cause of chronic renal failure in a hypertensive patient. Atherosclerotic renal artery disease is common among patients with coronary artery disease and aortic and peripheral vascular disease. Atherosclerotic renal artery disease is a progressive disorder, and its progression is associated with loss of renal mass and functioning. A decrease in glomerular filtration rate sufficient to cause an elevation of the serum creatinine concentration requires injury to both kidneys. Consequently, IRD can arise from one of two main clinical situations: bilateral hemodynamically significant renal artery stenosis leading to bilateral renal ischemia; and hemodynamically significant renal artery stenosis in a solitary functioning kidney, or in a kidney that is providing the majority of a patient's glomerular filtration. The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function, or a delay in progression to ESRD. There are six major clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed upon poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient. Noninvasive testing modalities that have been used recently include the angiotensin converting enzyme inhibitor renal scan, duplex Doppler sonography, magnetic resonance angiography, and the spiral computed tomography. Treatment methods include percutaneous transluminal angioplasty, endovascular stenting, and surgical revascularization. The results of treatment for preservation of renal function have been encouraging, with stabilization or improvement in renal function observed in a significant proportion of cases.

Humans↗

PubMed1997

The natriuretic effect of nifedipine gastrointestinal therapeutic system remains despite the presence of mild-to-moderate renal failure.

BACKGROUND: Calcium channel blockers facilitate the renal excretion of sodium and this effect is maintained during chronic administration of these drugs. However, it is unknown whether this natriuretic effect remains despite the presence of a decreased renal function. OBJECTIVE: To compare the natriuretic capacity of nifedipine gastrointestinal therapeutic system (GITS) and lisinopril in patients with mild-to-moderate chronic renal failure. METHODS: An open-label, randomized, comparative study was conducted to compare the natriuretic capacity of nifedipine GITS and lisinopril in the presence of mild-to-moderate renal failure (creatinine clearance 30-80 ml/min). After a wash-out period of 4 weeks an intravenous saline infusion (30 ml/kg of body weight of isotonic saline in 4 h) was performed and repeated after 4 weeks of active therapy. Two sex- and age-matched groups of hypertensive patients (n = 25) were included in the study. Renal failure was diagnosed as secondary to nephrosclerosis in all the patients. RESULTS: A significant increase in the renal capacity to excrete the sodium load was observed in patients receiving nifedipine GITS (n = 11) but not in those taking lisinopril (n = 13). Both drugs controlled blood pressure to a similar extent. No changes were observed in body weight, glomerular filtration rate and renal plasma flow (measured as inulin and paraaminohippurate clearances). A significant drop was observed in urinary albumin excretion after lisinopril, but not after nifedipine. Heart rate was higher in nifedipine group. CONCLUSION: The natriuretic capacity of nifedipine GITS remains despite the presence of mild-to-moderate chronic renal failure. Such an effect takes place in the absence of changes in renal hemodynamics, suggesting that it is caused by a direct tubular effect.

Administration, Oral↗

PubMed1999

Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats.

OBJECTIVE: The tissue renin-angiotensin system and extracellular matrix are involved in the cardiovascular hypertrophy and remodeling induced by hypertension. In this study, we examined the gene expression of the tissue renin-angiotensin system and fibronectin in inbred Dahl Iwai salt-sensitive and salt-resistant rats. MATERIALS AND METHODS: Eight pairs of 6-week-old male Dahl Iwai salt-sensitive and salt-resistant rats were fed either a low- or high-salt diet (0.3% or 8% NaCl, respectively) for 4 weeks. Activities of the circulating renin-angiotensin system were measured by radioimmunoassay and the gene expression of tissue angiotensinogen, the angiotensin II type 1 receptor (AT1) and fibronectin were analyzed by Northern blot analysis. RESULTS: Salt loading significantly increased blood pressure and produced cardiovascular hypertrophy and nephrosclerosis in the salt-sensitive rats. Activities of the circulating renin-angiotensin system were lower in salt-sensitive rats than in salt-resistant rats fed the low-salt diet, and salt loading lowered these activities in salt-resistant rats but not in salt-sensitive rats. In salt-resistant rats, salt loading increased renal, cardiac and aortic angiotensinogen, AT1 and fibronectin messenger (m)RNA expression except for aortic fibronectin mRNA expression. In contrast, in the salt-sensitive rats, salt loading stimulated the expression of cardiac fibronectin and aortic angiotensinogen, AT1 and fibronectin mRNAs. Furthermore, the cardiac and aortic fibronectin mRNA levels in salt-sensitive rats were higher than those in salt-resistant rats when both strains were fed the high-salt diet. CONCLUSIONS: These results demonstrate that the expression of tissue angiotensinogen, AT1 and fibronectin mRNAs is regulated differently in Dahl Iwai salt-sensitive and salt-resistant rats, and indicate that salt-mediated hypertension activates the cardiac fibronectin gene independently of the tissue renin-angiotensin system and stimulates the aortic fibronectin gene with activation of the tissue renin-angiotensin system.

Angiotensin I↗

PubMed2001

A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.

OBJECTIVE: To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in serum creatinine during the previous 2 years. METHODS: A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. RESULTS: Mean age of the group was 54 +/- 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4-6 mmHg lower. CONCLUSION: In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function. The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.

Adult↗

PubMed2004

Fasudil, a Rho-kinase inhibitor, attenuates glomerulosclerosis in Dahl salt-sensitive rats.

OBJECTIVE: The present study was designed to clarify whether the Rho-Rho-kinase pathway is involved in the process of hypertensive glomerulosclerosis and to assess the therapeutic effect of fasudil, a specific Rho-kinase inhibitor. METHOD AND RESULTS: Dahl salt-sensitive rats (DS) and Dahl salt-resistant rats (DR) were fed a high-salt diet at 6 weeks of age. Fasudil (30 mg/kg per day) was administered for 7 weeks to DS starting at the age of 11 weeks. After 7 weeks, untreated DS were characterized by decreased kidney function, increased proteinuria, abnormal morphological findings, increased adrenomedullin and atrial natriuretic peptide (ANP) levels, and increased renal messenger RNA expression of RhoB, Rho-kinasealpha, Rho-kinasebeta, collagen I and collagen III, and transforming growth factor-beta (TGF-beta) in the renal cortex compared with DR. Chronic fasudil treatment significantly improved renal function (serum creatinine, -26%; blood urea nitrogen, -41%; creatinine clearance, +42%), proteinuria (-24%) and histological findings (glomerular injury score, -49%; afferent arteriolar injury score, -17%) without changing blood pressure compared with untreated DS. Interestingly, long-term fasudil treatment decreased the plasma adrenomedullin (-25%) and ANP (-49%), but did not change the plasma renin or aldosterone. Furthermore, fasudil significantly decreased the messenger RNA expression of TGF-beta (-20%), collagen I (-23%), and collagen III (-24%) in the renal cortex. However, there were still significant differences in the aforementioned parameters between DR and fasudil-treated DS. CONCLUSION: These results suggest that the Rho-Rho-kinase pathway may be partly responsible for the pathogenesis of hypertensive glomerulosclerosis independently of blood pressure in DS, and that chronic inhibition of the Rho-Rho-kinase pathway may be a new strategy for treating hypertensive nephrosclerosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1984

Adaptation and decompensation of intrarenal small arteries in experimental hypertension.

In the presence of hypertension, the arterial and arteriolar vessel walls may undergo adaptive, destructive, and reparative changes. These different types of hypertensive alterations were studied simultaneously in the intrarenal vascular bed of two-kidney, one-clip hypertensive rats. After constriction of one renal artery, focal medial necrosis of the interlobular arteries developed in the untouched kidneys after the first 24 h. These earliest signs of vascular decompensation could be explained by short-lasting hypertensive episodes that were only detectable by continuous blood pressure recording in conscious animals. Two weeks after the experiment was started, owing to a widening of the media, a substantial increase in the wall-to-lumen ratio was observed in the interlobular arteries. At the same time, the frequency of focal medial necrosis began to fall significantly. Therefore we concluded that the structural vascular adaptation might be responsible for the disappearance of focal medial necrosis in spite of still rising blood pressure values. This assumption was confirmed by an additional experiment in previously chronically two-kidney, one-clip hypertensive rats: 24 h after removing the renal artery clip, a short, severely hypertensive period, induced by infusions of angiotensin II, caused hypertensive vascular lesions almost exclusively in the primarily clipped kidneys with a nonadapted vascular bed. Early intimal changes, which are known to lead to malignant nephrosclerosis, were not only absent in the beginning of two-kidney, one-clip hypertension, but also did not occur during the angiotensin-induced accelerated hypertension. Thus, even extremely high blood-pressure values per se may not be enough to initiate this crucial renal vascular disease.

Adaptation, Physiological↗

PubMed1999

The renin-angiotensin system and its receptors.

The renin-angiotensin system (RAS) plays an important role in blood pressure control and in water and salt homeostasis. It is involved in the pathophysiology of hypertension and structural alterations of the vasculature, kidney, and heart, including neointima formation, nephrosclerosis, postinfarction remodeling, and cardiac left ventricular hypertrophy (LVH). Recently, an increased knowledge of the effector peptides of the RAS, their receptors, and their respective functions has led to a new principle of treatment for hypertension: the inhibition of angiotensin (Ang) II via angiotensin-converting enzyme inhibitors or Ang II-receptor antagonists. In this review, the Ang receptors AT1 and AT2 and the potential roles of shorter angiotensin fragments, including Ang III(2-8), Ang IV(3-8), and Ang(1-7), are discussed.

Angiotensin II↗

PubMed1978

Frustrations in renal donation.

Extensive evaluation of a small series of potential renal donors has revealed an alarming rate of previously unsuspected disease precluding acceptability for renal donation. Of 19 patients considered for donation at the Medical University of South Carolina, 15 were unsuitable for medical reasons (diabetes mellitus, multiple sclerosis, sickle cell trait, hypertension, polycystic kidneys, duodenal ulcer, pulmonary disease), psychologic reasons, or changes on renal arteriography consistent with nephrosclerosis. The importance of a thorough donor evaluation including total patient awareness of the risks involved for both himself and the recipient and extensive psychologic testing is stressed. Even with strict criteria for renal donation, this high rejection rate is surprising.

Adolescent↗