Immunology in medical practice. IV. Mechanisms in the development of primary nephropathies]

Humoral immunological reactions play a central part in the development of nephropathies. Immune complexes may form in the circulation and precipitate in the kidney, or form in the kidney by binding of antibodies from the circulation to antigens in the glomerular basement membrane. The localizations of immune complex deposition in the various compartments of the glomeruli determine the development of different forms of glomerulonephritis. Cellular immunological reactions play a part in the development of tubulo-interstitial nephritis and possibly also of minimal change nephropathy' and focal segmental glomerulosclerosis. The role of cellular immunological reactions in the development of most other nephropathies is less clear. Persistence of nephropathies leads to glomerulosclerosis and renal interstitial fibrosis. Ultimately, these cause loss of kidney function and necessitate haemodialysis.     

Prostaglandin-induced iris color darkening. An experimental model

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.     

Secretion of both IL-2 and IL-4 by tumor cells results in rejection and immunity

Chronic ischemia may cause end stage renal disease, especially in older patients with atherosclerotic renal artery stenosis. Examining the pathology of the ischemic kidney is a fundamental first step toward understanding the mechanisms of this injury. In experimental renal hypoperfusion, there is evidence of a mixture of adaptive responses, tubular and endothelial cell damage and repair events. These processes are reflected in a wide spectrum of morphological changes that include atrophy, focal necrosis, epithelial regeneration, apoptosis, inflammation, interstitial fibrosis, and thrombosis. The most severe damage is seen in the outer medulla, a region with marginal oxygenation even in normal circumstances. In the usual clinical case, the effects of aging, pre-existent hypertension, and the process of atherosclerosis further complicate the pathological picture. Lesions related to these factors include arteriosclerosis, athero-emboli, various types of glomerulosclerosis, and severe tubulointerstitial damage leading to "atubular glomeruli" and regional cortical scarring (nephrosclerosis). In this article, some mechanisms determining the varied and complex pathological findings that may be observed in individual cases are outlined.     

Gadolinium-based contrast and carbon dioxide angiography to evaluate renal transplants for vascular causes of renal insufficiency and accelerated hypertension

PURPOSE: To evaluate the utility and potential nephrotoxicity of gadolinium-based contrast angiography when used with carbon dioxide angiography in renal transplant patients with suspected vascular causes of renal insufficiency and/or accelerated hypertension. MATERIALS AND METHODS: Thirteen consecutive renal transplant patients with suspected vascular causes of renal insufficiency and/or accelerated hypertension were evaluated with gadolinium-based contrast and CO2 angiography with use of digital subtraction techniques. Stenotic lesions were treated with angioplasty with/or without stent placement. No iodinated contrast agents were used. Serum creatinine levels were obtained before and at 24 and 48 hours after the procedure. An increase in creatinine levels greater than 0.5 mg/dL (44 micromol/L) was considered significant. RESULTS: Nine patients were studied for renal insufficiency, two for accelerated hypertension, and two for both. All 13 studies were considered diagnostic. Significant stenoses were treated in four patients with angioplasty with or without stent placement. Two patients had progression of their renal insufficiency. One of these patients underwent biopsy and was found to have both acute and chronic rejection. The other patient underwent cardiac catheterization 2 days after a transplant renal artery angioplasty. In the remaining nine patients with renal insufficiency (creatinine range, 1.8-3.9 mg/dL [159-345 micromol/L]; mean, 2.7 mg/dL [239 micromol/L]), renal function improved or did not worsen. CONCLUSION: Based on this limited study, gadolinium-based contrast angiography appears to be a promising supplement to CO2 angiography for the diagnosis and treatment of vascular lesions in patients with renal transplant insufficiency and/or accelerated hypertension. Further study is necessary to determine safety, optimal gadolinium dosage, and imaging parameters.     

Hypertension and endstage renal disease

OBJECTIVE: To review current literature regarding the development of hypertensive renal disease, its epidemiology, and its pathophysiology. This review focuses on strategies to slow or halt the progression of endstage renal disease (ESRD) in hypertension, including the role of blood pressure control, different types of antihypertensive agents, early treatment, and dietary considerations. DATA SOURCES: Information was retrieved from searching the MEDLINE database for articles consisting of epidemiologic studies, clinical studies, and review articles pertaining to hypertension and ESRD. Information also was obtained from the US Renal Data System annual data reports. STUDY SELECTION: Emphasis was placed on clinical trials in the English language addressing issues in hypertension and ESRD. Clinical trials reporting relationships between blood pressure control and ESRD, as well as those comparing different antihypertensive agents, were evaluated. DATA EXTRACTION: The methodology and results from clinical trials were evaluated. Studies were assessed according to the measures of renal function used, baseline data collected, degree of blood pressure control, and antihypertensive therapy. DATA SYNTHESIS: Clinical trials including patients with essential hypertension, diabetes mellitus, and renal insufficiency of various etiologies were evaluated. The recommendations from these evaluations were based on study design and the types of populations used (i.e., blacks vs. whites, diabetics vs. nondiabetics). CONCLUSIONS: Blood pressure control is currently the most important strategy to slow or halt the progression of renal insufficiency in hypertensive individuals. Whether specific antihypertensives are renal protective is still controversial, but results from clinical trials are promising.     

Comparative clinical and biochemical analyses of two methods of pancreatic cannulation in pigs

Over the last 16 years the evolution of 24 pregnancies in 17 women with biopsy-proven glomerular disease was analyzed. The underlying renal histology was IgA nephropathy in 8 cases, lupus nephritis in 7, mesangiocapillary glomerulonephritis type I in 1, and focal segmental glomerulosclerosis in 1. All but 2 had normal renal function before conception and 3 were hypertensive. Fetal survival rate was 75%. There were 6 preterm deliveries (33.3%), 3 newborns small for gestational age (17%), 1 stillbirth, and 5 therapeutic abortions. The perinatal mortality was 5.5%. De novo hypertension occurred in 8 pregnancies (33.3%). In 11 pregnancies (46%) increased proteinuria was diagnosed and in 6 (25%) a decline in maternal renal function was recorded. Permanent impairment of renal function was seen in 2 women with renal insufficiency before conception. Maternal hypertension and renal function impairment were associated more frequently with obstetric complications. In conclusion, pregnancy is safe for normotensive mothers with glomerular diseases and normal renal function. Hypertension and impaired renal function at conception seem to carry increased risk for mothers and fetuses. Low-dose immunosuppressive treatment during pregnancy is not harmful for the fetus.     

The renal factor in the post-traumatic "fluid overload" syndrome

Hypervolemia with hypertension often occurs 36-72 hours following massive blood and fluid replacement for hypovolemic shock. This syndrome of "fluid overload" has been attributed to the rapid intravascular flux of previously sequestered fluid in patients with impaired diuresis. This hypothesis was tested in 35 injured patients who received a mean of 9.3 L of blood and 17.4 L of salt during resucitation. The renal parameters measured soon after resuscitation included: 1) renal clearance of inulin (GFR), para-amino hippurate (ERPF), milliosmoles, sodium, and free water; 2) inulin space, renal vascular resistance (RVR), O2 consumption, renin, renal blood flow (RBF), and response to furosemide. Eighteen patients developed hypertension, hypervolemia, and respiratory insufficiency. When compared to the 17 normovolemic, non-hypertensive patients, the 18 hypervolemic patients had significantly increased RVR, with a significant decrease in RBF despite an increase in plasma volume and cardiac output. Furosemide produced less diuresis and natriuresis in the hypertensive patients. The balance between hypovolemia and "fluid overload" seemed percarious in the hypertensive patients. Peripheral renin and catecholamine levels were normal in both groups. Patients with post-traumatic "fluid overload" appear to have a combination of hypervolemia, respiratory insufficiency, hypertension, increased cardiac output, decreased extracellular fluid space, and decreased renal perfusion. These findings suggest that decreased interstitial fluid space compliance rather than "fluid overload" is the underlying factor leading to respiratory insufficiency. The therapeutic aspects of these findings are discussed.     

Thrombotic lesions in primary plexogenic arteriopathy. Similar pathogenesis or complication?

In 78 patients with primary plexogenic arteriopathy (PPA), numbers of organized and recanalized thrombi were established in histologic slides of lung tissue and expressed per square centimeter of section. Three control groups of ten individuals each were used: normal, plexogenic arteriopathy secondary to ventricular septal defect, and hypoxic pulmonary hypertension. Thrombotic lesions were scarce in normal individuals but numerous in all three groups with pulmonary hypertension. There is also a positive correlation with age. Thrombotic lesions are absent or scarce in children but more common in adults, even in normal control subjects and particularly in pulmonary hypertension by whatever cause. In PPA there is likely to be a relation with the duration of illness but not with the stage of the disease. The complete pattern of plexogenic arteriopathy may develop in the absence of thrombotic lesions, which clearly are not essential for its pathogenesis. Rather than being part specifically of PPA, as sometimes suggested, thrombotic lesions complicate various types of hypertensive pulmonary vascular disease. Apparently the combination of sustained pulmonary hypertension and age, possibly through endothelial injury, may elicit thrombosis and its sequelae, which in turn may aggravate the pulmonary arterial pressure.     

Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure

Thin glomerular basement membrane (GBM) nephropathy, also called familial benign hematuria, is characterized by chronic hematuria and uniform thinning of the lamina densa of the glomerular basement membrane. It generally holds an excellent renal prognosis. Alport syndrome in early stages can also show attenuation of the GBM; conversely, renal insufficiency has been reported in familial benign hematuria. To discern early Alport syndrome from thin GBM nephropathy, we carried out a prospective epidemiological study in which 19 normotensive and non-azotemic adult patients with chronic microscopic (18 of 19) and macroscopic (1 of 19) hematuria and biopsy-proven thin GBM nephropathy were followed for a median of 12 years (range 9 to 15 years). Renal biopsies of thin GBM patients at entry showed an increased incidence of focal global glomerulosclerosis when compared to disease controls as IgA nephropathy (P = 0.047) and normal renal tissue (P = 0.0075). All renal biopsies showed the presence of the Goodpasture antigen when tested immunohistochemically. Presence of Alport syndrome was excluded clinically as none of the patients had complaints of hearing loss or abnormalities by audiography and ophthalmology. At the end of follow-up, the incidence of hypertension in thin GBM nephropathy (35%) exceeded that of healthy clinical controls (P = 0.048), and one hypertensive patient developed mild renal failure. In the normotensive patients, the glomerular filtration rate at follow-up as measured by inulin clearance was reduced in three out of seven; these were over 50 years of age. Although no family members were known to have renal disease at inclusion, within four families six elderly first degree relatives had developed unexplained renal insufficiency at the end of follow-up. Thus, thin GBM nephropathy predisposes to premature glomerular obsolescence, leading in time to increased incidences of hypertension and late onset renal insufficiency.     

Arterial hypertension in patients on chronic hemodialysis

Arterial hypertension is frequent among chronically dialyzed patients. The kidney obviously plays a major role in arterial blood pressure control. There is a large number of experimental data emphasizing different factors (in addition to renin important in renal hypertension prognosis) such as: sodium balance, angiotensin, etc [1-8]. Sympathetic activity disorders or lack of vasodilatory prostaglandins and quinine may also play a certain role. In uremic patients peripheral arteriolar resistance is increased, unlike normotensive uremic patients or those who prove to be normotensive upon clinical examinations [8, 11-15]. Hypertension occurs in approximately 80% of patients with chronic renal failure, producing a number of complications primarily affecting the CNS and systemic circulation [5-8, 10, 11, 13]. The study concerned patients on chronic dialysis, with a male to female ratio of 69.9%:32.1%. In most of them the underlying disease, which caused chronic renal failure, was glomerulonephritis (60.0%), then pyelonephritis (17.0%) and nephrosclerosis, nephrolithiasis, polycystic kidney and, finally, renal tumours. The effect of permanent haemodialysis during the first year of treatment, was efficacious on hypertension in 1704 (65.1%) patients; in 672 (25.7%) patients therapeutical effects were achieved by dialysis and antihypertensive drugs, while in 240 (9.2%) subjects there was no improvement. General observations suggest that two types of arterial hypertension persisted in patients with chronic renal failure: volume-dependent arterial hypertension which is more frequent (90-95%) among haemodialyzed patients and renin-dependent hypertension. Such findings are of utmost importance indicating that hypervolaemia is one of the major factors in the development of arterial hypertension in patients with chronic renal failure, with renin playing the secondary role. Salt-free diet should be used in the treatment of arterial hypertension for years, a well conducted haemodialysis is highly effective in the control of arterial hypertension among these patients. In our series of patients dialysed three times a week; normalization of blood pressure was faster with lower incidence of hypertensive crises during haemodialysis and with few complications. Water and sodium excess was reduced by frequent haemodialyses and sudden changes in electrolyte, hydrostatic and other metabolic effects were minimized. Increased values of plasma renin activity were observed in a small number of patients. Ultrafiltration is insufficient for normalization of blood pressure. Hypertensive crises were frequent in these patients. Their response to medicaments such as methyldopa, beta-adrenergic blockers or other antihypertensive drugs, was good. Severe changes in blood vessels, especially in fundus oculi blood vessels were frequent in these patients. The life of hypertensive glomerulonephritis patients was especially endangered (graphs 1-6). In addition to the mentioned factors arterial hypertension during haemodialysis may also be of cardiac origin, including increase in cardiac output due to arteriovenous anastomosis, disequilibrium syndrome, changes in osmotic gradient of both extra- and intracellular spaces with resultant arteriolar wall oedema, erythrocyte amount, hypoxia, composition of dialysis fluid (sodium concentration), plasma osmotic pressure, metabolic acidosis and other factors. More recently, natriuretic hormone has also been indentified as a cause of vascular refraction. Peripherial arteriolar resistance as a cause of arterial hypertension among uremic patients must not be forgotten, because the genesis of arterial hypertension in patients with chronic renal failure is multifactorial. The highest percentage refers to volume-dependent arterial hypertension, whereas the percentage of other aetiologic factors is lower. Haemodialysis enables the normalization of blood pressure in most of hypertensive patients.     

Changes in perfusion and blood flow distribution following normo- and hypothermic ischemia of the kidneys

Experimental examinations were performed in 22 dogs to find out the mechanism which leads to a permanent or a reversible damage of the renal parenchyma after normo- and hypothermic ischemia. For this reason the perfusion and the distribution were examined with 133Xe, the vascular changes by angiography, and the parenchymal function with 131I-Hippuran. After normothermic ischemia a short-term reactive hyperemia appeared, which however could not compensate the damage of the renal tubular cells and the resulting excretory insufficiency. After hypothermic ischemia the perfusion was reduced, probably as a consequence of a vasconstriction by cold, however, the function of the tubular cells remained intact, because of the protective mechanism of the hypothermia. The importance of these findings for the development of the so-called "shock-kidney" (acute tubular necrosis) and for the conservative renal surgery in hypothermia is discussed and the application of measures beneficial to perfusion, are suggested.     

Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients

BACKGROUND: Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases. METHODS AND RESULTS: In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective. CONCLUSIONS: Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of essential hypertension.     

Who contributes to the public health function?

OBJECTIVES: To describe patterns of hypertension history in patients with various types of end-stage renal disease (ESRD) and in persons with normal kidney function; and to identify risk factors for the diagnosis 'hypertensive ESRD'. DESIGN: A case-control study. SETTING: Population-based. PARTICIPANTS: Patients with ESRD due to hypertension (n = 214), diabetes (n = 239), other specified causes (n = 181), unknown causes (n = 82) and control subjects drawn from the general population (n = 361). MAIN OUTCOME MEASURES: Participants' history of hypertension. RESULTS: The prevalence of hypertension was 90% in ESRD patients and 27% in controls. Only 6% of patients with hypertensive ESRD had a history of malignant hypertension. Patients with hypertensive ESRD were more likely to have been hospitalized because of hypertension (36%) than were other ESRD patients (18%) or controls (5%). ESRD of any cause was more strongly associated with hypertension of > or = 25 years duration (odds ratio 51.0, compared with normal blood pressure) than it was with hypertension of shorter duration (15-25 years: odds ratio 31.8, 5-15 years: odds ratio 16.0, < 5 years: odds ratio 21.2). Among patients who had both hypertension and ESRD, the diagnosis of 'hypertensive ESRD' was associated independently with a long duration of hypertension, greater severity of hypertension, the absence of diabetes, black race, and limited education. CONCLUSIONS: Hypertension is common among patients with ESRD. The risk of ESRD from any cause increases progressively with the duration of hypertension, and with indicators of severe hypertension. This result supports the hypothesis that nonmalignant hypertension of long duration may cause renal insufficiency. The criteria used to diagnose hypertensive ESRD are consistent with pathophysiologic and epidemiologic evidence.     

Hypertension in diseases of the kidney. Pathogenesis and therapy

Renal disease is the cause of hypertension in about 5% of all hypertonics. Patients with renal hypertension are threatened by cardiovascular complications of hypertension even more frequently than patients with essential hypertension. Hypertension is moreover an important factor in the progression of renal insufficiency. In the pathogenesis of renal hypertension an important role is played by sodium and fluid retention and activation of the renin-angiotensin system. Progression of rental insufficiency can be retarded only by more strict control of hypertension than in patients with normal renal function. Optimal treatment is administration of angiotensin converting enzyme inhibitor which moreover in the majority of patients retards the progression of renal insufficiency more markedly than other antihypertensive drugs.     

Sonography of the kidneys and urinary tract in infancy

Sonography is the imaging method of choice in all diseases of the kidneys and urinary tract in infancy. The most important indications are all malformation syndromes, especially malformations of the urinary tract, urinary tract infections, space occupying lesions of the kidney, renal insufficiency, hematuria, arterial hypertension, abdominal pain and inherited kidney diseases.     

Protective effect of nicardipine treatment on renal microanatomical changes in spontaneously hypertensive rats

The effects of nicardipine administration on kidney morphology were studied in spontaneously hypertensive rats (SHR). Male 12-week-old SHR received an oral dose of 1 mg/Kg/day of nicardipine or vehicle for 8 weeks Age-matched Wistar-Kyoto rats were used as normotensive reference animals. At 20 weeks, the non treated SHR exhibited hypertension, albuminuria, decreased urinary sodium excretion and renal microanatomical changes. These changes were characterized by vascular alterations consisting in hypertrophy of the tunica media accompanied by a decrease of luminal surface. Glomerular changes consisting primarily in signs of glomerulosclerosis of varying degrees were noticeable in the kidneys of SHR. Treatment with nicardipine significantly reduced blood pressure and albuminuria and increased urinary sodium excretion. Moreover, hypertrophy of the tunica media and the luminal surface were decreased and increased respectively in nicardipine-treated SHR. The above results suggest that treatment with nicardipine reduces blood pressure in SHR and counteracts hypertension-dependent changes in the morphology of the kidney. The protective effect of the drug on hypertensive changes of renal microanatomy probably have functional relevance given of the influence of nicardipine treatment on albuminuria and urinary sodium excretion in SHR.     

The biological activity of human monoclonal IgG anti-D is reduced by beta-galactosidase treatment

In the present review, the possibilities of ergometric and pharmacological "intervention" with a view to improving the validity of scintirenography are reported. Exercise renography at present does not have a defined role in clinical routine. This procedure, however, gives additional information in hypertensive patients with respect to renal ischemia. Captopril scintirenography can be recommended as a screening test for renovascular hypertension. Furosemide-"intervention" differentiates between obstructive uropathy and dilatation of renal collecting system without obstruction. This is true especially in newborns with congenital abnormalities of the upper urinary tract, in order to stratify these young patients for surgical or conservative treatment.     

11-beta-hydroxysteroid dehydrogenase activity and gene expression in the hypertensive Bianchi-Milan rat

OBJECTIVE: 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD), by converting the active steroids cortisol and corticosterone to their inactive metabolites, regulates steroid exposure to the mineralocorticoid and glucocorticoid receptors. We explored the hypothesis that a defect in 11 beta-HSD could result in overstimulation of either the mineralocorticoid or glucocorticoid receptors with subsequent hypertension in an established animal model of hypertension, the Bianchi-Milan hypertensive (BMH) rat. DESIGN AND METHODS: Groups of BMH rats with established hypertension (42-46 days old) and prehypertensive rats (22 days old) were compared with age-matched normotensive control rats. Kidney and liver 11 beta-HSD and glucocorticoid receptor messenger RNA (mRNA) levels were assessed by Northern and dot-blot analyses, and 11 beta-HSD activity as percentage conversion of [3H]-corticosterone to [3H]11-dehydrocorticosterone by tissue homogenate. RESULTS: Hepatic 11 beta-HSD activity and gene expression were significantly reduced in the hypertensive BMH rat compared with its normotensive genetic control. 11 beta-HSD activity was also reduced in the prehypertensive BMH rat (aged 25 days) from hypertensive parents, excluding hypertension per se as the cause of the abnormality. Plasma corticosterone was higher in the hypertensive rats. There was no difference in renal 11 beta-HSD activity or gene expression between hypertensive and normotensive BMH rats, or in glucocorticoid receptor gene expression in the liver or kidney. CONCLUSIONS: Normal levels of renal 11 beta-HSD mRNA and activity are found in the BMH rat. However, the hypertensive BMH rat does demonstrate impaired hepatic 11 beta-HSD activity which occurs at a pretranslational level, although it is not clear how this relates to the pathogenesis of hypertension in this model.     

Hypertensive vascular disease as a cause of death in blacks versus whites: autopsy findings in 587 adults

Cardiovascular disease is the major cause of excess mortality among urban US blacks, but autopsy data comparing black-white differences in underlying pathological causes of cardiovascular death are lacking. We reviewed all 720 adult cases autopsied in 1991 in the New York City Medical Examiner's Office in which the coded cause of death was cardiovascular disease (International Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410, 411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases because race was missing or coded as other than black or white, gender was not coded, or there was an unusual circumstances of death or extreme obesity, 587 cases were available for analysis. There were 314 black and 273 white subjects. Black women were younger than white women at time of death (mean age, 54.7 versus 61.5 years; P<.001), whereas black and white men did not differ in mean age at death. Hypertensive vascular disease was the autopsy cause of death in 42% of blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart disease was the autopsy cause of death in 64% of white subjects but only 38% of blacks. These patterns were consistent in both sexes and after adjustment for age. Hypertensive vascular disease was far more common than atherosclerotic heart disease as the cause of death at autopsy among blacks compared with whites in New York City, whereas atherosclerotic heart disease was more common in whites. These findings suggest that ineffective control of hypertension is a major factor contributing to excess cardiovascular mortality among urban blacks.     

Therapy of focal and segmental glomerulosclerosis with methylprednisolone, cyclosporine A, and prednisone

Patients with steroid-resistant focal and segmental glomerulosclerosis (FSGS) have a poor prognosis but may benefit from high-dose methylprednisolone or cyclosporine A therapy. Ten patients were treated with a protocol of methylprednisolone infusions for 8 weeks followed by a combination of cyclosporine A and alternate-day prednisone for maintenance of remission for 2 weeks. Eight of ten patients remitted the nephrotic syndrome within 8 weeks of beginning treatment. One patient remitted edema but remained proteinuric, and one did not respond. After observation for 12-24 months, seven patients maintained remission with normal glomerular filtration rate. One non-responder had renal insufficiency and one patient had secondary non-response and end-stage renal disease. No patients developed hypertension. One patient had the diagnosis of Hodgkin disease made after 10 months of therapy. Follow-up renal biopsy in four patients showed no evidence of progressive interstitial disease. There were no other major side effects. Steroid-resistant FSGS may be successfully treated with the described protocol. Additional studies will be needed to determine if this approach prevents progression of renal disease.