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Renal disease in pregnancy.

Renal biopsy was obtained in 11 primiparous and 9 multiparous patients with severe pre-eclampsia. The large number of patients with renal disease allowed for single-case evaluation. Eclamptic convulsions and fetal deaths were observed in association with renal disease without foci of additional primary glomerular endotheliosis. The data indicate that pregnancy can exacerbate renal disease and allow for early diagnosis. Fluorescence angiography revealed changes in patients in whom the optic fundi were normal. Tissues of glomerulonephritis stained by immune fluorescence against immunoglobulins and on occasion against human fibrinogen. Primary endotheliosis and nephrosclerosis stained against fibrinogen only. There was no pattern of laboratory data to make the differential diagnosis between primary endotheliosis and various forms of renal disease. Fibrinogen breakdown products were inconsistently increased in contrast to fibrin monomer formation, which was increased regardless of the underlying morphology. It is our feeling that renal biopsy with subsequent pathologic classification is the only technique we have at present which provides relevant information on the effect of renal disease on pregnancy and vice versa.

Biopsy↗

Laparoscopic bilateral nephrectomy for renin-mediated hypertension.

Hypertension arising from retained native kidneys complicates the management of recipients of renal transplants. Reluctance to administer angiotensin-converting enzyme inhibitor (ACEI) drugs to patients taking cyclosporine has reopened the question of performing native nephrectomies for poorly controlled, renin-dependent hypertension. We report the first published cases of simultaneous bilateral laparoscopic nephrectomies in 2 patients: 1 in preparation for living-related donor transplantation and the other ten months following cadaver transplantation in a patient whose end-stage renal disease was from malignant nephrosclerosis. Both had very severe hypertension resistant to multiple drugs and both became normotensive with little or no antihypertensive medication following nephrectomies. A bilateral nephrectomy is currently feasible using a laparoscopic approach.

Adult↗

What effect does blood pressure control have on the progression toward renal failure?

Since hypertension is associated with nephrosclerosis and an increased progression toward end-stage renal failure, the therapeutic approach to the treatment of hypertension should aim to protect the kidney against damage or to halt the progression toward end-stage renal failure. It appears that compared with systolic and mean blood pressure, the level of diastolic blood pressure is particularly associated with renal damage. In the presence of kidney failure the choice of antihypertensive drug should be made according to pharmacokinetic and pharmacodynamic properties. From the pharmacokinetic point of view, drugs that are eliminated via the biliary route are preferable since no dosage adjustment is required, and those with a favorable trough to peak effect can achieve better blood pressure control by reducing blood pressure variability. Pharmacodynamic properties should include efficacy in lowering blood pressure, beneficial renal effects, and good tolerability. Hence, the dihydropyridine calcium antagonists, which are effective during volume repletion and which counteract vasoconstrictor mechanisms, seem to be particularly effective. There is some suggestion, but no definitive proof, that blood pressure should be lowered well below 140/90 mm Hg; to achieve this, combination therapy frequently must be used. The rationale for combining two or more antihypertensive drugs is based on the knowledge that this combination can exert an additive antihypertensive action while reducing side effects. The combination of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist may well fulfill these criteria since this combination could enhance both antihypertensive and renal hemodynamic effects in comparison to single-drug treatment and could reduce the side effects of both drugs.

Antihypertensive Agents↗

Essential hypertension: could the basic defect be in blood supply of vasomotor centre?

Various factors have been implicated in the pathogenesis of essential hypertension, although the exact cause of essential hypertension is still unknown. In this paper it is suggested that the basic pathology in essential hypertension may be an inherited defect in the blood supply of that part of reticular formation of rostral ventrolateral medulla which contains the pressor area. The posited defect is one in which the arterial branch supplying blood to the above-mentioned pressor area of vasomotor center arises from an artery which is stenosed. The other branches of this stenosed artery supply adjacent areas of medullary reticular formation concerned with other neurological functions. Due to this stenosis there is ischaemia of the pressor area resulting in increased systemic arterial pressure. During stress, the blood requirement of adjacent areas of the reticular formation (whose function is still not clearly defined) may increase, thus further decreasing blood flow to vasopressor area and increasing the cerebral ischaemic response. After a prolonged time, this increased blood pressure can cause hyaline arteriolar nephrosclerosis in kidney, which may participate in the maintenance of elevated systemic arterial pressure.

Adult↗

Tempol attenuates the development of hypertensive renal injury in Dahl salt-sensitive rats.

BACKGROUND: Dahl salt-sensitive (DS) rats given a high-salt diet develop renal lesions that are virtually identical to those in human hypertensive nephrosclerosis and are associated with increased oxidative stress. This study looks at the effects of a superoxide scavenger in preventing of hypertensive renal damage in high-salt-treated DS rats. METHODS: The DS rats (n = 5 per group) were treated with 0.3% NaCl diets (LS), 8% NaCl diets (HS), and 8% NaCl diets plus 10 mmol/L tempol in drinking water (HS+T) for 5 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method. As markers of renal damage, we measured serum creatinine, creatinine clearance, histopathologic indices, and transforming growth factor-beta1 (TGF-beta1; a mediator for renal fibrosis) expression. In addition, 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells and expression of heme oxygenase-1 (HO-1) were quantified as markers of oxidative stress. RESULTS: We found that a high-salt diet (8% NaCl) led to the development of hypertension, increased oxidative stress in the renal tissue (8-OHdG immunoreactive staining and HO-1 protein expression), increased renal histopathologic damage (arteriosclerosis index, matrix score, and interstitial volume) accompanied by accumulation of TGF-beta1, and decreased creatinine clearance in the DS rats. These adverse effects of salt were prevented by the tempol supplementation. CONCLUSIONS: Histopathologic and biochemical findings indicate that, in the DS rat, salt-induced hypertensive nephropathy is associated with increased oxidative stress. Superoxide mimetic tempol can reduce this detrimental effect of salt feeding through TGF-beta1 suppression and consequently prevent the development of hypertension and hypertensive nephropathy.

Animals↗

Tailored dialysis start may allow persistence of residual renal function after graft failure: a case report.

BACKGROUND: Restarting dialysis after kidney transplantation is a critical step with psychological and clinical implications. Maintenance of residual renal function a known factor affecting survival in chronic kidney disease, has so far not been investigated after a kidney transplantation. THE CASE: A 54-year-old woman who started dialysis in 1974 (first graft, 1975-1999) received a second "marginal" kidney graft in February 2001 (donor age, 65 years). Her chronic therapy was tacrolimus and steroids. She had a clinical history as follows: nadir creatinine level of 1.5 mg/dL, moderate-severe hypertension, progressive graft dysfunction, nonresponsiveness to addition of mycophenolate, tapering FK levels, and a rescue switch from tacrolimus to rapamycin. From October to December 2003, the creatinine level increased from 2-2.8 to 7 mg/dL. Biopsy specimen showed malignant and "benign" nephrosclerosis, posttransplantation glomerulopathy, and tacrolimus toxicity. Chronic dialysis was started (GFR <3 mL/min). Rapamycin was discontinued. Dialysis was tailored to reach an equivalent renal clearance of >15 mL/min (2 sessions/wk). Blood pressure control improved, nephrotoxic drugs were avoided, and fluid loss was minimized (maximum 500 mL/hr). By this policy, renal function progressively increased to GFR >10 mL/min in May 2004, allowing a once or twice weekly dialysis schedule, with good clinical balance, and obvious advantages for the quality of life. CONCLUSION: This long-term patient, who restarted dialysis with severely reduced renal function, regained sufficient renal function to allow once weekly dialysis. Thus, careful tailoring of dialysis sessions at the restart of dialysis may allow preservation of residual kidney function, at least in individuals for whom a subsequent graft is unlikely.

Female↗

Difficult vascular access in patients with end-stage renal failure.

BACKGROUND/AIM: End-stage renal failure patients requiring long-term hemodialysis need a durable vascular access. The arteriovenous fistula (AVF) with its long patency rate and low complication profile is usually the first choice for vascular access creation. However, when superficial veins are not suitable for AVF creation or all have been exhausted as a result of repeated AVF procedures, arteriovenous grafts (AVGs) using expanded polytetraflouroethylene (ePTFE) is an alternative. This study reviewed our experience in using PTFE AVGs for vascular access in patients requiring chronic hemodialysis. MATERIALS AND METHODS: In a prospective study, from September 2002 to October 2004, 21 PTFE AVGs were placed in 21 patients. We evaluated the complications and patency. RESULTS: There were 12 female and nine male patients of mean age 58+/-8.7 years (range=45 to 76 years). Nine patients (43%) had hypertensive nephrosclerosis, 6 (29%) diabetic, 2 (10%) glomerulonephritis, 3 (14%) systemic lupus erythematosis requiring long-term steroids, and 1 (4.7%) unknown cause. The patency rate at 24 months was 85.7%. Complications included graft thrombosis (three; 14.3%), wound infection (three; 14.3%) and graft infection (one; 4.8%). CONCLUSION: ePTFE AVGs offer reasonable patency and serviceability rates as a vascular access modality, but in view of their complication profile, the native vein arteriovenous fistula should continue to be the first choice for vascular access for patients requiring chronic hemodialysis.

Aged↗

Living kidney donors developing end-stage renal disease.

The incidence of end-stage kidney failure (ESRF) was analyzed among the cohort of 1112 living kidney donors who underwent nephrectomy from 1965 through 2005. It was found that at least six persons had developed ESRF at 14 to 27 years (median = 20 years), following donation. Five of six were men. Five were parents and one, a sibling. The diagnoses were nephrosclerosis (n = 4), postrenal failure (n = 1), and renal carcinoma (n = 1). One donor, aged 45 years, underwent kidney transplantation.

Cohort Studies↗

Complications associated with pulmonary resection in lung cancer patients on dialysis.

BACKGROUND: There are few studies available investigating the perioperative problems experienced by lung cancer patients on dialysis undergoing pulmonary resection. METHODS: A retrospective review of 7 patients on dialysis undergoing pulmonary resection for lung cancer was performed. RESULTS: The patient population consisted of 7 men, with a mean age of 59.9 years. The underlying kidney disease was glomerulonephritis in 5 patients and nephrosclerosis in 2. The mean levels of blood urea nitrogen and serum creatinine were 70.7 mg/dL and 9.4 mg/dL, respectively. Histologic diagnoses were adenocarcinoma in 2 patients and squamous cell carcinoma in 5. Standard lobectomy with lymph node dissection was performed in all cases. There was one operation related death due to pulmonary edema and subsequent development of pneumonia. There were two cases of sputum retention and four of hyperkalemia. One patient died of cerebral bleeding that occurred during dialysis 2 months postoperatively. CONCLUSIONS: In patients on dialysis who undergo pulmonary resection, there is a high incidence of pulmonary complications, in addition to hyperkalemia, hemodynamic instability, and a tendency for postoperative dialysis-associated bleeding.

Adenocarcinoma↗

The diagnostic and therapeutic uses of saralasin in renal transplant hypertension.

Saralasin was used as a functional test of the renin-angiotensin axis in 4 renal transplant patients with hypertension. Blood pressure was recorded by an automatic recording device and plasma renin activity was measured by radioimmunoassay of angiotensin I. A positive saralasin test suggested renin-mediated hypertension despite normal peripheral renin levels in a 40-year-old man whose original kidney disease was nephrosclerosis. Since the blood pressure was refractory to intravenous sodium nitroprusside saralasin was used for 14 hours to control blood pressure before and after arteriography in the patient. Removal of the native kidneys markedly ameliorated the hypertension. A 35-year-old woman with transplant hypertension was responsive to angiotensin blockade only during a period of abrupt worsening of blood pressure associated with an acute rejection episode. Finally, 2 patients with advanced chronic rejection responded to saralasin administration. These studies confirm that 1) angiotensin blockade is a useful tool in the diagnosis of renin-dependent hypertension even when plasma renin levels are not elevated, 2) saralasin can be used to control renin-dependent forms of hypertension that are refractory to intravenous sodium nitroprusside therapy and 3) transplant hypertension associated with acute and chronic rejection appears to be renin-dependent.

Adult↗

Obesity hypertension.

Obesity and hypertension are two major risk factors for the cardiovascular system. Whereas arterial hypertension increases afterload to the left ventricle, obesity produces an increase in stroke volume and increases preload. As a result of this double burden, the heart adapts with eccentric left ventricular hypertrophy. Contractility becomes impaired early in the course of obesity hypertension, and ventricular ectopy is observed. As a consequence, the obese hypertensive patient is at a high risk for congestive heart failure and sudden death. Despite the synergistic effects of obesity and hypertension on the heart, patients appear to be relatively protected from nephrosclerosis and coronary artery disease. These epidemiologic observations are supported by the pathophysiologic changes that take place in obesity hypertension. At any given level of arterial pressure, cardiac output and renal blood flow are elevated in obese hypertensive patients, whereas systemic and renal vascular resistance are decreased when compared to lean hypertensive patients. Because total peripheral resistance is considered the hemodynamic hallmark of arterial hypertension, systemic vascular complications may be less pronounced in obesity hypertension. Weight loss decreases preload, afterload to the left ventricle, and the sympathetic drive to the heart. Protecting the heart from these hypertrophic stimuli should be a major goal of preventive cardiology.

Heart Failure↗

Histologic parathyroid abnormalities in an autopsy series.

The parathyroid glands from 422 subjects without clinical, biochemical, or advanced histologic signs of renal disease were dissected at autopsy. The glands were evaluated histologically in relation to the subjects' age, sex, histologic renal features, other diseases, and medical therapy. Normal parathyroid glands generally had diffuse cellular arrangements, with variable fat cell content. Increased nodularity was observed, especially in enlarged parathyroid glands. Hyperplasia was present in 7 per cent and adenomas in 2.4 per cent. Hyperplastic glands were often nodular and asymmetric, and numbers of oxyphil cells were frequently increased. Some large nodules were histologically indistinguishable from adenomas. Serum calcium levels were elevated in subjects with adenomas or with hyperplastic glands containing large nodules. The findings seem to indicate that nodularity of the parathyroid tissue is a sign of abnormality and that adenomas may arise from such nodular hyperplasia. Hyperplasia and adenomas were more common in elderly subjects and in those with slight or moderate nephrosclerosis. Other diseases or medical therapy were not found to be correlated with parathyroid weight or histologic features.

Adolescent↗

Hyperplasia of renin-containing cells in a malignant pheochromocytoma: an immunohistochemical and semiquantitative study.

The renin-containing cells in the kidneys of a patient with malignant pheochromocytoma were investigated immunohistochemically. Elevated plasma renin and catecholamine levels were detected during the clinical course. Remarkable hyperplasia of renin-containing cells was observed in the afferent arterioles and interlobular arteries. Semiquantitative assessment was performed to compare this case with cases of renovascular hypertension, with one case of malignant nephrosclerosis, and with six cases without hypertension. The grade of hyperplasia of renin-containing cells in pheochromocytoma was similar to that in renovascular hypertension and was different from that observed in control cases. Histologic examination of the kidneys revealed neither stenosis of the renal arteries nor ischemic changes of glomeruli. Direct stimulation of renin-containing cells by catecholamines is suggested as the cause of the hyperplasia. This is the first morphologic demonstration of hyperplasia of renin-containing cells in pheochromocytoma.

Adult↗

Is vasopressin involved in the pathogenesis of malignant desoxycorticosterone hypertension in rats?

Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals. During the fourth to seventh week after the start of the experiment, malignant hypertension developed in most of the animals: body weight fell, reflecting volume depletion; serum osmolality and serum sodium and urea concentrations increased; in the kidneys malignant nephrosclerosis occurred. In such animals, plasma concentrations of arginine-vasopressin were increased ten-fold in comparison with control animals; intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood-pressure (B.P.) to normal or subnormal levels, while the injection of an angiotensin-I or angiotensin-II antibody did not affect B.P. In control animals none of the antibodies had an effect on B.P. It is concluded that in the pathogenesis of malignant D.O.C. hypertension vasopressin plays a role similar to that of renin-angiotensin in malignant renal hypertension.

Angiotensin II↗

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study.

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of the hemodialysis (HD) patients had an unknown etiology of their kidney disease. Diabetes, polycystic kidney disease (PKD), chronic pyelonephritis and nephrosclerosis (NS) were the most commonly documented diagnoses. Consanguinity was present in 26% of the total HD population. More consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their non-consanguineous counter-parts (45% versus 33%, P<0.02 and 42% versus 27%, P<0.01), respectively. Similarly, consanguineous polycystic patients were diagnosed and started earlier on dialysis when compared with the non-consanguineous population (34% versus 12%, P<0.05 and 28% versus 8%, P<0.05), respectively suggesting a different disease pattern. Furthermore, the risk for family history of kidney disease was noticeable in the non-consanguineous population and significantly higher among the consanguineous patients (12% versus 18%, P<0.04). Consanguinity-associated kidney diseases affected all religious communities, in particular the Muslim and the Druze (36 and 39%), respectively versus 17% of the Christian community. Certain geographical areas were more involved than others such as the North, South and the Bekaa with the highest percentage (40%) in the latter. Socio-economical level was not a contributing factor. We conclude that the documentation of the underlying etiology in end-stage renal diseases (ESRD) seems to be deficient. Furthermore, consanguinity is prevalent in the Lebanese dialysis patients population, in particular the Muslim and the Druze communities. Consanguinity-associated kidney diseases pattern seems to differ from that of the general HD population by disease diagnosis and initiation at a younger age and a significantly higher risk for familial renal disease. It is a cultural phenomenon prevalent predominantly in the rural areas. We recommend a multi-approach including educational, informative and probably legislative strategy in order to limit and hopefully discourage consanguineous marriages.

Adult↗

An autopsy study of Takayasu arteritis in India.

Autopsy findings of 10 patients with Takayasu arteritis (TA) are presented. These patients include six females and four males with a mean age of 22.6+/-10.2 years. Hypertension was the commonest mode of presentation. On autopsy, the vascular lesions in the aorta comprised of stenosis (eight), dilatation (six), aneurysm (two) and dissection of aorta involving its arch, thoracic and abdominal aorta (one). Abdominal aorta was the commonest site of involvement (nine patients) and renal artery was involved in six patients. Histologically, the three types of lesions were identified--active, fibrotic and combination of active and fibrotic lesions. Active inflammatory lesions in the arterial circuit were present despite a clinically chronic (silent) phase of the disease. Cardiac involvement included left ventricular hypertrophy (nine), right ventricular hypertrophy (four), biventricular hypertrophy (three), myocarditis (two) (rheumatic and Takayasu's myocarditis--one patient each) and involvement of coronary artery (one). The pulmonary artery was involved in two patients. Kidneys showed changes of malignant hypertension and benign nephrosclerosis in one patient each. Associated tuberculosis was present in four patients. The causes of mortality were congestive heart failure (four), chronic renal failure (two), intracranial bleed, aneurysmal rupture and pulmonary thromboembolism in one patient each. Thus, the major causes of morbidity and mortality in Indian patients with TA is due to severe uncontrolled hypertension and its effect on heart, kidney and brain. The disease appears to have a persistent activity for a prolonged period even when it appears to be clinically silent.

Adolescent↗

A review of the biological properties and clinical implications of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP), hypotensive and vasodilating peptides.

Adrenomedullin (AM), identified from pheochromocytoma and having 52 amino acids, elicits a long-lasting vasodilatation and diuresis. AM is mainly mediated by the intracellular adenylate cyclase coupled with cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) -cyclic guanosine monophosphate (cGMP) pathway through its specific receptor. The calcitonin receptor-like receptor (CLCR) and receptor-activity modifying protein (RAMP) 2 or RAMP3 models have been proposed as the candidate receptor. AM is produced mainly in cardiovascular tissues in response to stimuli such as shear stress and stretch, hormonal factors and cytokines. Recently established AM knockout mice lines revealed that AM is essential for development of vitelline vessels of embryo. Plasma AM levels elevate in cardiovascular diseases such as heart failure, hypertension and septic shock, where AM may play protective roles through its characteristic biological activities. Human AM gene delivery improves hypertension, renal function, cardiac hypertrophy and nephrosclerosis in the hypertensive rats. AM decreases cardiac preload and afterload and improves cardiac contractility and diuresis in patients with heart failure and hypertension. Advances in gene engineering and receptor studies may contribute to further understandings of biological implication and therapeutic availability of AM.

Adrenomedullin↗

Appointment attendance, pill counts, and achievement of goal blood pressure in the African American Study of Kidney Disease and Hypertension Pilot Study.

The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a 7-year clinical trial to assess the effect of two levels of blood pressure control based on mean arterial pressure (MAP) (low goal < or = 92 mm Hg or usual goal of 102-107 mm Hg) and three antihypertensive drug regimens (atenolol, amlodipine, or enalapril) as initial therapy in slowing the decline of renal function in African Americans with clinically diagnosed hypertensive nephrosclerosis. Ninety-four African American men and women between 18 and 70 years of age were randomized and followed for an average of 4.6 months. On average participants attended 87.5% of the scheduled monthly follow-up visits and achieved an acceptable level of medication adherence (80%-100% of prescribed doses by pill count) at 65.4% of those visits Blood pressure levels within goal were observed in 17.5% and 25.6% of the participants in the low- and usual MAP goal groups, respectively. Neither attendance nor medication adherence by pill count was associated with attainment of goal blood pressure. Although AASK Pilot Study participants maintained excellent attendance, their pill counts were lower than previously reported among clinical trial participants and goal blood pressure levels were difficult to achieve during the short period of follow-up.

Adult↗