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Biomedical subjects

R G Appel

Publications and source records attributed to R G Appel.

At least 19 recordsLinked to original sources

Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population.

BACKGROUND: A decline in renal function with age has been noted in some but not all individuals. The purpose of this study was to identify risk factors associated with a clinically significant increase in serum creatinine (of at least 0.3 mg/dL) in an older nondiabetic population. METHODS: A retrospective case-control study was performed analyzing data obtained from 4142 nondiabetic participants of the Cardiovascular Health Study Cohort, all at least 65 years of age, who had two measurements of serum creatinine performed at least three years apart. Cases were identified as participants who developed an increase in serum creatinine of at least 0.3 mg/dL, with controls including participants who did not sustain such an increase. RESULTS: There was an increase in the serum creatinine of at least 0.3 mg/dL in 2.8% of the population. In a multivariate "best-fit" model adjusted for gender, weight, black race, baseline serum creatinine, and age, the following factors were associated with an increase in serum creatinine: number of cigarettes smoked per day, systolic blood pressure, and maximum internal carotid artery intimal thickness. CONCLUSIONS: These data suggest that three very preventable or treatable conditions-hypertension, smoking, and prevalent vascular disease, which are associated with large and small vessel disease-are highly associated with clinically important changes in renal function in an older population.

Aged↗

IgA nephropathy and Reiter's syndrome. Report of two cases and review of the literature.

Immunoglobulin A (IgA) nephropathy is the commonest type of primary glomerulonephritis worldwide. It has previously been reported in association with the seronegative spondyloarthropathies (ankylosing spondylitis, Behcet's syndrome, psoriatic arthritis, Reiter's syndrome and the postenteritic arthritides). Since this condition was first described in 1968, 5 previous case reports of biopsy-proven IgA nephropathy associated with Reiter's syndrome have been published in the English-language literature. Here we report 2 more such cases, along with a review of the literature describing the association of IgA nephropathy and a number of other immune-complex-mediated glomerulonephritides with the seronegative spondyloarthropathies.

Adult↗

Genetic initiation of hypertensive and diabetic nephropathy.

The factors initiating the common etiologies of chronic renal failure remain elusive. This article reviews the evidence in support of a generalized genetic susceptibility to human end-stage renal disease, including kidney failure attributed to the systemic diseases of hypertension, diabetes mellitus, and glomerulonephritis. Molecular genetic techniques are powerful tools, assisting in the detection of the initiating factors in many complex diseases. In kidney disease, genetic methodologies complement the available anatomic, epidemiologic, and physiologic analyses. This article provides strategies to allow for the detection of human renal failure susceptibility genes. The identification of human renal failure genes would provide useful markers for disease susceptibility and speed the development of novel therapeutic strategies.

Animals↗

Clinical correlates of hypertensive end-stage renal disease.

Although there has been much discussion regarding the etiology of hypertensive renal disease, clinical characteristics of this condition have not been thoroughly studied. The purpose of this investigation was to identify clinical correlates of hypertensive end-stage renal disease (ESRD) in a population of patients older than 50 years and to compare these clinical findings with those in a group of ESRD patients with certain known disorders (established diagnoses). Data regarding demographics, cause of ESRD, educational level, presence of diabetes mellitus, angina, myocardial infarction, and peripheral vascular disease were obtained from the Southeastern Kidney Council for patients starting renal replacement therapy between January 1, 1990, and August 1, 1996. Clinical characteristics were compared for white and black patients. Demographic variables and comorbid conditions were compared between groups with general linear regression or logistic regression contrast techniques. A logistic regression model was formed with hypertensive ESRD or established diagnoses as the outcome variable and comorbid and socioeconomic variables as the independent variables. Hypertensive ESRD was diagnosed in 24% of white and 38% of black patients, while established diagnoses were present in 17% of white and 7% of black ESRD patients. The most common established diagnoses were polycystic kidney disease, specified glomerulonephritis, and nephrolithiasis or obstruction. In a logistic regression model, white patients were found more likely to be classified as having hypertensive ESRD if they were older, suffered from angina and other forms of atherosclerosis, smoked, and were less educated. White patients with hypertensive ESRD were more than 2.4 times as likely to suffer from angina as patients with established diagnoses. For black patients, the presence of peripheral vascular disease and female gender were associated with an increased chance of being diagnosed as having hypertensive ESRD. The results of this investigation show that there is a strong association between atherosclerosis and hypertensive ESRD in older white patients. In black patients, the association between atherosclerosis and hypertensive ESRD was also present, but not as strong. The unique association of hypertensive ESRD with atherosclerosis suggests that atherosclerosis is a risk factor for chronic renal failure and that a primary renal microvascular disorder may lead to both hypertension and progressive renal insufficiency.

Age Factors↗

Gallium-67-citrate scanning of renal parenchymal malacoplakia.

UNLABELLED: The purpose of this article is to review the potential role of nuclear medicine scanning, especially with 67Ga, in the presumptive diagnosis and clinical management of patients with renal parenchymal malacoplakia (RPMP), a rare disease associated with coliform bacterial infection of the kidney and characterized by chronic unresolving inflammatory infiltrates containing von Hansemann macrophages in the renal parenchyma. METHODS: Published cases of RPMP were collected from the archival literature by searching the MEDLINE database and by reviewing bibliographic references contained in articles on malacoplakia. Data on the clinical features and radiographic evaluation of patients with RPMP were extracted from the clinical case reports. RESULTS: Forty-three cases of RPMP published over the past 20 yr were identified. Ten of the 43 patients (23%) had 67Ga scanning as a component of their diagnostic evaluation. In all 10 patients, renal uptake of 67Ga was classified as intense. Two of those 10 patients had serial 67Ga scanning performed to assess response to antibiotic treatment; both patients exhibited decreased uptake or complete resolution of abnormal renal uptake over time, a finding also exhibited by our patient. CONCLUSION: Intense renal uptake of 67Ga, typically in the clinical setting of fever, progressive renal failure and nephromegaly, strongly supports a diagnosis of RPMP. In those patients receiving prolonged antimicrobial therapy for RPMP, resolution of abnormal 67Ga uptake over time may provide an objective endpoint for treatment.

Anti-Infective Agents↗

Renal artery repair in African-Americans.

PURPOSE: This retrospective review examines the results of atherosclerotic renal artery (RA) repair in consecutive hypertensive African-Americans treated at our center and compares these results with Caucasians treated during the same period. METHODS: From Jan. 1987 through Sep. 1996, a total of 485 patients underwent operative RA repair. Of these, 28 African-Americans and 370 Caucasians were managed for atherosclerotic renovascular disease. These cohorts were compared on the basis of preoperative blood pressure and renal function, extent of renal disease, extrarenal atherosclerosis, response to operation, and estimated survival. RESULTS: The African-American cohort included nine men and 19 women (mean age, 62 years) with hypertension (mean blood pressure, 204 +/- 31/109 +/- 20 mm Hg) for an average of 10.2 +/- 7.5 years. Ischemic nephropathy (serum creatinine level, > 1.3 mg/dl) was present in 82% (n = 23) of the African-American group. RA reconstructions were unilateral in nine patients and bilateral in 19 patients (including repair to two solitary kidneys), for a total of 45 RA reconstructions (30 RA bypass procedures; eight transrenal/transaortic RA endarterectomy procedures; two RA reimplantations; five nephrectomies). Nine patients underwent combined aortic procedures (four abdominal aortic aneurysm; five occlusive disease). There was one perioperative death in the African-American group as a result of sepsis and multiple organ failure. Among surgical survivors, 20 African-American patients (74%) had a beneficial hypertension response (7% cured, 67% improved). Mean estimated glomerular filtration rate improved significantly from 34 to 42 ml/min/1.73 m2 (p < 0.001). In the 23 patients with ischemic nephropathy, 13 (57%) demonstrated greater than 20% decrease in serum creatinine level. In comparison with the 370 Caucasians (191 men, 179 women), the African-American cohort had significantly more preoperative heart disease (congestive heart failure or left ventricular hypertrophy; 68% vs 46%; p = 0.03) and tended toward more severe renal dysfunction (mean serum creatinine level, 2.5 vs 2.1 mg/dl; p = 0.25). However, African-Americans demonstrated a beneficial blood pressure and renal function response after operation, similar to Caucasians. CONCLUSIONS: Our results indicate that the majority of selected African-Americans have a favorable blood pressure and renal function response to operative renal artery repair. This beneficial clinical response appears equivalent to the response observed in Caucasian patients and supports the search for RA disease in hypertensive African-Americans.

Adult↗

The link between hypertension and nephrosclerosis.

Nephrosclerosis is literally defined as hardening of the kidneys (Greek derivation: nephros, kidney; sklerosis, hardening). It is the result of scarring or replacement of the normal renal parenchyma by dense collagenous tissue. In practice, nephrosclerosis refers to diseases with predominant pathologic changes occurring in the preglomerular microvasculature and secondarily involving the glomeruli and interstitium. The relationship between mild to moderate hypertension and either nephrosclerosis or end-stage renal disease (ESRD) remains circumstantial, although these syndromes have long been associated in the medical literature. Nephrologists credit hypertension as the etiology of nephrosclerosis in 25% of patients initiating Medicare-supported renal replacement therapy, even though other processes may cause similar renal pathologic findings. Strikingly, serum creatinine values infrequently increase in patients with long-standing mild to moderate hypertension. Patients classified as having hypertensive ESRD typically present with advanced disease, making the processes that initiated the renal disease difficult to detect. Nephrologists are twice as likely to label an African-American patient as having hypertensive nephrosclerosis, compared with a white patient, when presented with identical clinical histories. This review proposes that many patients classified as having hypertensive nephrosclerosis actually have intrinsic renal parenchymal diseases, renal artery stenosis, unrecognized episodes of accelerated hypertension, or a primary renal microvascular disease. The familial clustering of ESRD attributed to hypertension in African-Americans and the identification of genes associated with renal injury in animals support the concept that inherited factors may predispose to renal failure. African-American families often have members with ESRD from disparate etiologies, including hypertensive ESRD. This suggests that common mechanisms, be they inherited or environmental, underlie the development of progressive renal failure in diverse forms of nephropathy. Identification of the mechanisms producing susceptibility to progressive renal disease would support the concept that mild to moderate elevations in blood pressure per se are uncommon causes of nephrosclerosis.

Animals↗

Surgical management of dialysis-dependent ischemic nephropathy.

PURPOSE: This retrospective review describes surgical management of dialysis-dependent ischemic nephropathy. METHODS: From February 1987 through September 1993, 340 patients underwent operative renal artery (RA) reconstruction at our center. A subgroup of 20 patients (6 women; 14 men; mean age 66 years) dependent on hemodialysis immediately before RA repair form the basis of this report. Glomerular filtration rates (EGFR) were estimated from at least three serum creatinine measurements obtained 26 weeks before and after operation. A linear regression model was used to estimate the mean rate of change of EGFR before and after RA repair. Comparative analysis of kidney status and change in EGFR were performed. The influence of function response on follow-up survival was determined by the product-limit method. RESULTS: Hemodialysis was discontinued in 16 of 20 patients (80%). For these 16 patients, postoperative EGFR ranged from 9.0 to 56.1 ml/min/1.73 m2 (mean 32.4 ml/min/1.73 m2). Two of 16 patients resumed hemodialysis 4 and 6 months after surgery. Discontinuation of dialysis was more likely after bilateral or complete RA repair (15 of 16 patients) versus unilateral repair (one of four patients; p = 0.01). Permanent discontinuation of dialysis was associated with a rapid preoperative rate of decline in EGFR (mean slope log(e) EGFR: -0.1393 +/- 0.0340 without dialysis; -0.0188 +/- 0.0464 with dialysis; p = 0.04, but NS after controlling for multiple comparisons). Immediate increase in EGFR after operation was inversely correlated with the severity of nephrosclerosis (rank correlation: -0.57; 95% confidence interval [-0.83, -0.10]). Follow-up death was associated with dialysis dependence; two deaths occurred among 14 patients not receiving dialysis, whereas five of six patients dependent on dialysis died (p < 0.01). CONCLUSION: Surgical correction of ischemic nephropathy can retrieve renal function in selected patients dependent on dialysis characterized by a rapid decline in preoperative EGFR in combination with global renal ischemia treated by complete or bilateral renal revascularization. After RA repair, discontinuation of dialysis may be associated with improved survival rates when compared with continued dialysis dependence.

Aged↗

Renovascular disease in older patients beginning renal replacement therapy.

Renovascular disease (RVD) in older patients can cause progressive renal insufficiency and even end-stage renal disease (ESRD). The frequency of this clinical problem is not well defined. Renal duplex sonography (RDS) correctly identifies the presence of RVD with an overall accuracy of approximately 95%. Therefore, the purpose of this study was to utilize RDS as a noninvasive tool to identify the presence of critical RVD (> or = 60% diameter-reducing stenosis or occlusion) in patients 50 years of age or older beginning renal replacement therapy. A total of 53 consecutive participating patients were prospectively interrogated. Complete interrogations occurred in 45 of the 53 patients (85%), and 92 of the 103 kidneys (89%). Critical RVD was noted in 10 of 45 patients (22%). RVD was bilateral in 5 patients, unilateral in 5 patients, and there were 4 renal artery occlusions noted. All patients with critical RVD were white (10 of 25 white patients or 40%). Total pack years of smoking as well as associated cardiovascular and cerebrovascular conditions were greater in those patients with critical RVD compared to those without. These results indicate that RDS remains technically feasible as renal blood flow and function decline. Unsuspected RVD possibly contributory to renal insufficiency exists in a significant number of primarily white patients 50 years of age or older beginning renal replacement therapy. These patients are generally smokers with a high frequency of associated extrarenal atherosclerosis The addition of RVD as a separate category of disease causing ESRD would improve U.S. Renal Data System ESRD classification. RVD should be recognized as a cause of ESRD.

Aged↗

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↗