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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 235 records · Page 13Linked to original sources
PubMed1998

Genetic abnormalities in parathyroid nodules of uremic patients.

The molecular pathway of autonomous growth of the parathyroid glands in uremic patients is poorly understood. We have analyzed 71 parathyroid lesions from 24 patients with refractory hyperparathyroidism for allelic loss at chromosomes 1, 3, 6, 9, 11, 12, 13, 15, and 17 and at the X chromosome. Microsatellite analysis was performed using 24 highly polymorphic markers. Deletions at chromosomes 1, 3, 6, 11, 12, and 13 and at the X chromosome were detected in only 10 of 67 nodules (15%). No allelic loss of the p16 and p53 tumor suppressor genes or the extracellular calcium receptor gene was found. The X-chromosome inactivation assay revealed a monoclonal pattern in 58% of hyperplastic nodules in females. Our results indicate monoclonal growth in the majority of hyperplastic nodules and suggest that some of these lesions might be considered precursors for adenoma development.

Female↗
PubMed1998

Does essential hypertension cause progressive renal disease?

In the distant past, terminal renal failure occurred mainly as a result of malignant hypertension. The introduction of effective antihypertensive therapy has made malignant hypertension rare, and researchers have stopped focusing on the kidney's role in their hypertension research. However, recent long-term observational studies have documented an impressive relationship between hypertension and impaired renal function in patients without primary chronic renal disease; elderly and African American individuals with hypertension have the worst prognoses. The hallmark of hypertensive renal injury is thought to be a progressive increase in intrarenal vascular resistance, which may precede changes in renal structure. Because we lack evidence from renal biopsy studies, it is unclear whether an increase in albumin (protein) excretion correlates with these disturbances of renal function and structure. Nevertheless, because urinary excretion of albumin in patients with essential hypertension is related to the risk of cardiovascular complications, its measurement provides important clinical information.

Albuminuria↗
PubMed1998

Optimizing antihypertensive therapy in patients with diabetic nephropathy.

The number of cases of diabetic nephropathy is increasing, especially among patients with non-insulin-dependent diabetes mellitus (NIDDM). It is difficult to prevent the occurrence or progression of NIDDM, and current levels of treatment are below standard. According to one study, actuarial 5-year survival rates are only about 38% for patients with insulin-dependent diabetes mellitus and 9% for those with NIDDM receiving renal replacement therapy. Because cardiovascular diseases are responsible for more than half of these deaths, hypertension, as a major contributing factor to cardiac death, is a crucial component in the therapy for such patients. It is well established that lowering blood pressure is an important preventive measure to be taken in patients with diabetic nephropathy; blockade of the renin-angiotensin system offers benefits beyond lowering blood pressure in type I diabetic nephropathy. Two major trials are currently underway to determine the effects of angiotensin II receptor antagonists on nephropathy in patients with NIDDM. The Irbesartan Diabetic Nephropathy Trial (IDNT) has already enrolled approximately 85% of the proposed 1650 NIDDM patients to be randomly assigned to placebo, irbesartan or amlodipine. Baseline characteristics of the initial cohort are presented. In light of the well-documented case for blockade of the renin-angiotensin system in diabetes, the potentially superior blockade afforded by angiotensin II receptor antagonists, and the superior tolerability of these agents, trials such as the IDNT take on special importance for the treatment of diabetic patients. From these data may come the justification for the belief that angiotensin II receptor antagonists impart greater benefits in the treatment of diabetes than merely their well-documented role in lowering blood pressure.

Angiotensin Receptor Antagonists↗
PubMed1997

[Nephropathy and hypertension in type II diabetes].

BACKGROUND: In Germany nephropathy in patients with type II diabetes has become the most frequent single cause of uremia requiring renal replacement therapy. This calls for effective measures of prevention. DIABETIC NEPHROPATHY AND HYPERTENSION: In patients with established diabetic nephropathy, hypertension is the most important pathogenetic factor which is susceptible to therapeutic intervention. Some pathogenetic mechanisms are discussed which impact on antihypertensive therapy. Interaction between hypertension and diabetic nephropathy is analyzed. CONCLUSION: Diabetic nephropathy in patients with type II diabetes has become the most frequent cause of endstage renal failure in Germany. Preventive measures, i. e. near normal glycemia and particularly antihypertensive treatment, have been proven to interfere with progression of renal failure in diabetic nephropathy. Early recognition is possible by testing for urinary albumin (microalbuminuria). In patients with diabetic nephropathy, blood pressure should be lowered to values well within the range of normotension by dietary salt restriction and antihypertensive drug therapy.

Combined Modality Therapy↗
PubMed1997

The Heidelberg classification of renal cell tumours.

This paper presents the conclusions of a workshop entitled 'Impact of Molecular Genetics on the Classification of Renal Cell Tumours', which was held in Heidelberg in October 1996. The focus on 'renal cell tumours' excludes any discussion of Wilms' tumour and its variants, or of tumours metastatic to the kidneys. The proposed classification subdivides renal cell tumours into benign and malignant parenchymal neoplasms and, where possible, limits each subcategory to the most commonly documented genetic abnormalities. Benign tumours are subclassified into metanephric adenoma and adenofibroma, papillary renal cell adenoma, and renal oncocytoma. Malignant tumours are subclassified into common or conventional renal cell carcinoma; papillary renal cell carcinoma; chromophobe renal cell carcinoma; collecting duct carcinoma, with medullary carcinoma of the kidney; and renal cell carcinoma, unclassified. This classification is based on current genetic knowledge, correlates with recognizable histological findings, and is applicable to routine diagnostic practice.

Humans↗
PubMed1997

Rats with moderate renal failure show capillary deficit in heart but not skeletal muscle.

In previous studies on experimental renal failure, hypertrophy of cardiomyocytes, diminished capillarization, and increased intercapillary distances had been observed, abnormalities that will expose the heart to reduced ischemia tolerance. It has not been established, however, whether such structural alterations are unique for the heart (eg, as a consequence of left ventricular hypertrophy) or are demonstrable in other tissues as well. Clarification of this point is important to test hypotheses on some potential mechanisms for cardiac undercapillarization. To address this issue further, we compared capillary length density (by stereologic techniques) in perfusion-fixed skeletal muscle (m. psoas) and hearts of subtotally nephrectomized (SNX) rats with moderate renal failure to those in sham-operated pair-fed controls. The duration of renal failure was 8 weeks. SNX rats had significantly higher mean systolic blood pressure (128 mm Hg v 109 mm Hg), serum creatinine, and urea levels. Despite pair feeding, the mean body weight was significantly lower in the SNX rats (409 g v 471 g), but the left ventricular weight to body weight ratio tended to be higher than in the sham-operated controls (2.39 mg/g v 2.13 mg/g). In the heart, myocyte mean cross-sectional area (675 +/- 112 microm2 v 545 +/- 111 microm2) and volume density of nonvascular interstitial tissue (3.47 +/- 1.04 v 1.33 +/- 0.22) were significantly higher in the SNX rats than in the controls. In parallel, myocardial capillary length density was significantly reduced after subtotal nephrectomy (3,036 +/- 535 mm/mm3 v 3,916 +/- 615 mm/mm3). In contrast, in skeletal muscle, myocyte cross-sectional area (3,109 +/- 783 microm2 v 3,042 +/- 639 microm2), capillary length density (718 +/- 248 mm/mm3 v 717 +/- 184 mm/mm3), and three-dimensional capillary fiber ratio (2.10 +/- 0.26 v 2.13 +/- 0.4) were similar in SNX and control rats. These data document a selective defect of capillarization in the heart of animals with moderate renal failure, pointing to tissue-specific abnormalities of cardiac capillarogenesis.

Animals↗
PubMed1997

Demonstration of the proliferation marker Ki-67 in renal biopsies: correlation to clinical findings.

Assessment of cell proliferation in renal biopsy samples is a potentially promising analytical tool to evaluate disease activity. So far no information is available on the correlation between proliferative activity in different anatomic compartments of the kidney and clinical symptoms. To elucidate this issue, we examined renal biopsy specimens from 20 patients with systemic vasculitis (15 Wegener's granulomatosis, five microscopic polyangiitis), 20 patients with immunoglobulin (Ig) A nephropathy (IgAN), 13 patients with minimal-change disease (MCD), 11 patients with tubulointerstitial nephritis, and five patients with diabetes mellitus. The streptavidin-biotin-peroxidase complex technique was applied to autoclave-pretreated, formalin-fixed, paraffin-embedded tissue sections to label different cell types with the antibody MIB1 directed against the Ki-67 antigen. Proliferation index (PI) was estimated as the number of positively stained nuclei per glomerular cross-section or per square millimeter section area. The interstitial cells were discriminated by additional staining of Ki-67-processed samples with specific immune markers. In patients with vasculitis, PI was considerably elevated in the extracapillary glomerular compartment (0.86), in proximal tubules (6.24), and in the interstitium (8.62). High proliferative activity was also noted in interstitium (3.98) and proximal tubules (1.35) of patients with IgAN. Of particular interest was the increased interstitial proliferative activity (15.0) in diabetic patients. Resident renal cells, but not infiltrating cells, seemed to constitute the majority of the proliferating cell population in the interstitium. In systemic vasculitis, clinical disease activity was significantly correlated to endocapillary (r(s) = 0.58), extracapillary (r(s) = 0.67), proximal tubular (r(s) = 0.67), and interstitial PI (r(s) = 0.61). By multiple linear regression analysis, proximal tubular PI was correlated to the presence of hematuria (beta = 0.72) and to interstitial fibrosis score (beta = 0.59). Interstitial PI was independently correlated to antineutrophil cytoplasmic antibodies (ANCA) titer (beta = 0.7) and interstitial fibrosis score (beta = 0.55), and it was the only one PI correlated to serum creatinine concentration (beta = 0.53). The independent association between interstitial PI and serum creatinine (beta = 0.64) was also found in IgAN. Proximal tubular PI was correlated to interstitial fibrosis score (beta = 0.59) and proteinuria (beta = 0.54). In MCD, high PI values were noted in proximal tubular cells (1.42) but not in glomeruli and the interstitium. In conclusion, assessment of proliferation activity by immunohistology provides additional information beyond conventional pathological techniques to evaluate disease activity and prognosis in renal biopsies.

Adult↗
PubMed1997

Pathogenesis and course of renal disease in IDDM/NIDDM: differences and similarities.

In the past the opinion prevailed that renal prognosis was less adverse in non-insulin-dependent diabetes mellitus (NIDDM) as compared with insulin-dependent diabetes mellitus (IDDM). This notion has to be revised in the light of recent evidence, based on epidemiologic data of NIDDM patients reaching endstage renal failure and a comparison of the cumulative prevalence of proteinuria and renal failure, respectively, in NIDDM as compared with IDDM. It has also been established that initial renal hemodynamic changes are quite comparable in NIDDM and in IDDM. It follows that past complacency about the renal sequelae of NIDDM is no longer justified and that preventive measures to interfere with the development of diabetic nephropathy are similarly important in NIDDM and IDDM.

Diabetes Mellitus, Type 1↗
PubMed1997

Cardiac disease in chronic uremia: pathophysiology.

In chronic uremia, apart from frequent coronary lesions, further abnormalities of the heart recently reported include (1) left ventricular hypertrophy, not completely explained by hypertension, (2) interstitial myocardial fibrosis, for which parathyroid hormone is a permissive factor, (3) reduced myocardial perfusion reserve, secondary to functional and structural changes of intramyocardial arteries and to reduced capillary density, (4) abnormalities of myocardial metabolism, which act in concert with restriction of blood flow by microvascular abnormalities to reduce ischemic tolerance. Such metabolic abnormalities include diminished responsiveness to beta-adrenergic stimulation, abnormal control of intracellular calcium concentration, impaired maintenance of energy-rich nucleotide concentrations under conditions of ischemia, impaired insulin-mediated glucose uptake, and abnormalities of myocardial oxidative metabolism.

Animals↗
PubMed1997

Renal function in the elderly: impact of hypertension and cardiac function.

In senescence renal function is thought to decline markedly even in the absence of renal disease. It has also been proposed that the changes in renal function with age are not uniform and that confounding factors such as hypertension or atherosclerosis may play a role. We performed a comprehensive study to compare several aspects of renal function in four groups: (i) young healthy normotensive subjects (N = 24; 13 males; mean age 26 +/- 3 years); (ii) elderly healthy normotensive subjects (elderly NT; N = 29; 13 males; 68 +/- 7 years); (iii) elderly treated and untreated hypertensive patients (elderly HT; N = 25; 13 males; 70 +/- 6 years); and (iv) elderly patients with compensated mild to moderate heart failure (elderly HF; N = 14; 6 males; 69 +/- 6 years). Compared to young subjects mean GFR (C(In)) and ERPF (C(PAH)) were significantly lower in the elderly, despite similar mean plasma creatinine levels (young, 121 +/- 11, 650 +/- 85 ml/min/1.73 m2; elderly NT, 103 +/- 11, 486 +/- 102; elderly HT, 103 +/- 13, 427 +/- 55; elderly HF, 92 +/- 14, 377 +/- 103). Nevertheless, GFR was within the normal range in the majority of elderly NT and HT, but not in elderly HF. ERPF was significantly lower in elderly HT as compared with elderly NT, and still lower in elderly HF. Mean renovascular resistance and filtration fraction were significantly higher in the elderly, particularly in elderly HT and HF as compared with the young. Mean fractional excretion of Na+ was similar in all groups studied, but the lithium clearance was significantly lower in the elderly, suggesting a greater proximal and less distal sodium reabsorption in senescence. In the elderly, mean PTH concentration and urinary excretion of pyridoline cross-links were significantly higher and mean 25-(OH)D3, calcitriol and phosphate concentrations significantly lower; the correlation between PTH and GFR was significant (r = -0.432, P < 0.001). The results document that the decrease in renal hemodynamics with senescence is less marked than suggested by some studies using less stringent methodology and inclusion criteria. Comorbid conditions confound renal function in the elderly. Age-associated changes in renal hemodynamics are accompanied by significant alterations of renal hormones and of renal sodium handling.

Adult↗
PubMed1997

Nephropathy of type II diabetes: evidence for hereditary factors?

Family studies point to an important genetic element in the genesis of diabetic nephropathy, but it is not known whether renal abnormalities are present prior to the onset of diabetes. To address this issue we examined all consecutive patients suffering from type II diabetes with a duration of more than 10 years who attended a diabetes outpatient clinic. Ninety-four patients had nephropathy, 307 did not. All offspring who were phenotypically normal (no hypertension, normal oral glucose tolerance, non-smoking) and agreed to participate were examined, 26 from nephropathic and 30 from non-nephropathic diabetic parents. They were compared with 30 offspring matched for age, gender and BMI from non-diabetic parents as controls. We measured urinary albumin excretion under baseline conditions and at several time points after ingestion of 300 g cooked beef and submaximal treadmill exercise, respectively. In addition, casual blood pressure, ambulatory blood pressure, urinary albumin and urinary alpha-1-microglobulin were measured. Primary renal disease was excluded by clinical examination. Under baseline conditions, median urinary albumin excretion rate (AER; microgram/min) was significantly (P < 0.005) higher in offspring of nephropathic type II diabetic patients (7.8; range 1.04 to 19.5) than in the offspring of non-nephropathic type II diabetic patients (4.8; 0.36 to 17.5) and controls (4.4; 0.16 to 18.4). Submaximal treadmill exercise caused a greater proportional increase of AER in offspring of nephropathic type II diabetics (median 16-fold) than in offspring of non-nephropathic diabetic patients (6.3-fold) or controls (4.8-fold). In offspring of nephropathic diabetic patients casual and particularly ambulatory systolic blood pressures were significantly higher, but AER was not correlated with blood pressure. In summary, higher values, albeit within the normal range, for baseline and postexercise albuminuria were noted in phenotypically normal offspring of parents with type II diabetes and nephropathy. The observation suggests that changes in transglomerular albumin traffic are demonstrable prior to the onset of diabetes and diabetic nephropathy in subjects with a potential genetic predisposition to these conditions.

Adult↗
PubMed1997

Parathyroid hormone prevents 1,25 (OH)2D3 induced down-regulation of the vitamin D receptor in growth plate chondrocytes in vitro.

1,25(OH)2D3 has an antiproliferative effect on growth plate chondrocytes when given in high doses, whereas low doses stimulate chondrocyte proliferation. In the present in vitro study we investigated the effects of parathyroid hormone (PTH) when given concomitantly with 1,25(OH)2D3 on cell proliferation and vitamin D receptor (VDR) regulation. Freshly isolated rat tibial chondrocytes were grown in monolayer cultures or in agarose stabilized suspension cultures (10% charcoal-treated FCS). VDR expression was determined by RT-PCR generating a 297 bp fragment and by binding assays (Scatchard analysis) with [3H]-1,25(OH)2D3. Cell proliferation was measured by [3H]-thymidine incorporation, growth curves in monolayer cultures and by colony formation in agarose-stabilized suspension cultures. Optimal concentration of 1,25(OH)2D3 (10(-12) M) and of PTH fragments [bPTH(1-34) or hPTH(28-48), 10(-10)M] showed additive effects on DNA synthesis of and colony formation by growth plate chondrocytes. This may be explained in part by an up-regulation of VDR by PTH: PTH increased both mRNA expression of VDR and binding capacity. 1,25(OH)2D3 (10(-12) M) induced an up-regulation of the VDR within 24 hours followed by a down-regulation after incubation for more than 24 hours. PTH fragments added concomitantly prevented the down-regulation seen with 1,25(OH)2D3. These findings provide evidence that PTH is a growth promoting hormone that also modulates the effects of 1,25(OH)2D3 by regulating the VDR status of 1,25(OH)2D3 target cells.

Animals↗
PubMed1997

Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides.

To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed. Antibodies against antigens expressed on podocytes (PP-44), endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic glomerular and/or blood-derived infiltrating cells. Our results demonstrate that IL-1 RII is constitutively expressed on endothelial cells, and its expression can be induced in proximal tubular cells and in the interstitium. In diseased glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages of the disease and is not only accompanied by a marked reactivity for IL-1 RI, but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with marked glomerular proliferation and/or sclerosis, a reduced expression of the PP-44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related peptides are noted. These results suggest that intrinsic glomerular production of IL-1 may be of relevance for the protection of glomeruli from continuing injury.

Acute Disease↗