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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 109 records · Page 6Linked to original sources
PubMed2000

Counteracting progression of renal disease: A look into the future.

It is the very nature of research, including medical research, that truly novel results are not predictable. Nevertheless, some predictions concerning the understanding and management of progression of renal disease are plausible. It is very likely that in the future, exploding health budgets will force authorities and nephrologists to more effectively apply existing knowledge in this field to patients with early renal disease, particularly diabetics. We hope that this optimistic note is justified, although experience admittedly indicates that it is very much against human nature to behave rationally. With the powerful methodological tools available today, it is safe to predict that insight into the mechanisms underlying progression will also increase. Although pharmacological blockade of the renin-angiotensin system has been one of the great success stories of the past two decades, in many patients, progression is seen despite administration of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. Fortunately, additional targets for intervention, such as endothelin-1, inflammatory cascades, chemokines, etc., are on the horizon. A particularly fertile target for prevention of progression will be kidney grafts, since it has become increasingly clear that factors unrelated to allo-immunity play an important role in chronic allograft nephropathy.

Disease Progression↗
PubMed2000

Microvascular disease--the Cinderella of uraemic heart disease.

It has been known for a long time that atherosclerosis, particularly plaques in the epicardiac coronary conduit arteries, are more frequent in patients with chronic renal failure than in non-uraemic patients. It has been only recently, however, that modification of post-stenotic remodelling of cardiac arteries as well as abnormalities of the arterioles and the capillaries in the myocardium of uraemic animals and uraemic patients have been recognized and analysed. These lesions can be dissociated from changes in blood pressure and may be an important cause contributing to reduced ischaemia tolerance and cardiac malfunction (pump failure, arrhythmia) thus predisposing to cardiac death. Recent insights into angiogenesis, particularly adaptive angiogenesis in response to hypoxia, may potentially provide novel approaches to the understanding and management of cardiac microangiopathy in renal failure.

Animals↗
PubMed2000

Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure.

BACKGROUND: An excessive rate of cardiac death is a well-known feature of renal failure. Coronary heart disease is frequent and the possibility has been raised that the natural history of the coronary plaque is different in uraemic patients. We assessed the morphology of coronary arteries in patients with end-stage renal failure and compared them with coronary arteries of matched non-uraemic control patients. METHODS: Fifty-four cases were identified at autopsy who met the inclusion criteria: cases, end-stage renal disease (n=27); controls, non-renal patients with coronary artery disease (n=27). At autopsy all three coronary arteries were prepared at corresponding sites for investigations: (i) qualitative analysis (after Stary), (ii) quantitative measurements of intima and media thickness (by planimetry), (iii) immunohistochemical analysis of the coronary plaques and (iv) X-ray diffraction of selected calcified plaques. RESULTS: Qualitative analysis of the coronary arteries showed significantly more calcified plaques of coronary arteries in patients with end-stage renal failure. Plaques of non-uraemic patients were mostly fibroatheromatous. Media thickness of coronary arteries was significantly higher in uraemic patients (187+/-53 microm vs 135+/-29 microm in controls) and intima thickness tended to be higher (158+/-38 microm vs 142+/-31 microm) but this difference was not statistically significant. Plaque area (4.09+/-1. 50 mm(2) vs 4.39+/-0.88 mm(2)) was comparable in both groups. Lumen area, however, was significantly lower in end-stage renal patients. Immunohistochemical analysis of the cellular infiltrate in coronary arteries showed no major differences in these advanced plaques of uraemic and non-uraemic subjects. CONCLUSION: Coronary plaques in patients with end-stage renal failure are characterized by increased media thickness and marked calcification. In contrast to the previous opinion the most marked difference compared to non-uraemic controls does not concern the size, but the composition of the plaque. Deposition of calcium within the plaques may contribute to the high complication rate in uraemic patients.

Aged↗
PubMed2000

The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group.

BACKGROUND: Diabetic nephropathy is the most common cause of end-stage renal disease in the developed world. Angiotensin-converting enzyme inhibitors have been demonstrated to be renoprotective in type I diabetes and are now the standard of care for both hypertensive and non-hypertensive type I diabetic patients with any level of proteinuria. The role of blockade of the renin-angiotensin system in type II diabetic patients is not defined. The Collaborative Study Group has initiated the Irbesartan Type II Diabetic Nephropathy Trial (IDNT), studying the effect of the angiotensin II receptor antagonist irbesartan on progression of renal disease and mortality in type II diabetic patients with overt nephropathy and hypertension. Here we report the study design and baseline patient characteristics. METHODS: To qualify, hypertensive type II patients, age 30-70 years, must have a 24 h urinary protein excretion of >900 mg and a serum creatinine 90-265 micromol/l (1.0-3. 0 mg/dl) in women and 110-265 micromol/l (1.2-3.0 mg/dl) in men. Three treatment arms include irbesartan, placebo and amlodipine, with every attempt made to achieve similar blood pressure levels in all treatment arms. A total of 1650 patients will be enrolled utilizing approximately 225 clinics worldwide. The primary outcome measure is time to event to the composite end-point of doubling of serum creatinine, end-stage renal disease or death. The secondary outcome measure is time to composite end-point of fatal or non-fatal cardiovascular events. The average length of patient follow-up is expected to be approximately 36 months. RESULTS: The baseline characteristics of the study subjects are: age 59+/-8 years, duration of diabetes 15+/-9 years, height 168+/-11 cm (5 ft 6 in), weight 87+/-19 kg (192 lb), body mass index 31+/-7 kg/m(2), blood pressure 156+/-18 mmHg/85+/-11 mmHg, serum creatinine 150+/-53 micromol/l (1.7+/-0.6 mg/dl), creatinine clearance 66+/-34 ml/min and 24 h urine protein 4.0+/-3.5 g/day.

Adult↗
PubMed2000

G(-699)/C polymorphism in the bradykinin-1 receptor gene in patients with renal failure.

BACKGROUND: Bradykinin is thought to have protective effects on the progression of renal failure. Of particular interest, it has been reported that one polymorphism in the promoter region of the human kinin B1-receptor gene which is associated with higher activity, is less frequently found in patients with end-stage renal failure. The present study was performed to independently confirm these results. DESIGN: Cross-sectional study on 376 healthy controls, 262 non-diabetic dialysis patients and 175 patients with type 1 diabetes >/=10 years and microalbuminuria (of whom 21 were dialysis-dependent) and 334 patients with type 2 diabetes >/=10 years and nephropathy (of whom 61 were dialysis-dependent). METHODS: Genotyping was performed by polymerase chain reaction, followed by restriction enzyme analysis. RESULTS: All groups were in Hardy Weinberg equilibrium. The study showed no significant difference in the frequency of the C-allele between controls (0.093) and non-diabetic dialysis patients (0.095). No significant difference in C-allele frequency was observed between controls and patients with type 1 diabetes and microalbuminuria (0.092) or patients with type 2 diabetes and nephropathy (0.099). CONCLUSION: In large cohorts of patients with non-diabetic end-stage renal disease and diabetic renal disease with and without end-stage renal failure, no change in the frequency of the C-699 allele of the B-1-receptor gene was found.

Adult↗
PubMed2000

Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF), a recently cloned member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent neurotrophic factor in vitro and in vivo. GDNF is essential for nephrogenesis and the highest expression of GDNF is found in the developing kidney. Increased plasma GDNF levels have recently been documented in patients with chronic renal failure; the source and role of this increase, however, remain unclear. No data are available about the expression of GDNF in human adult kidney or human adult mesangial cell (HMC) cultures. We hypothesized that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor in the pathogenesis of glomerulosclerosis. METHODS: To address this hypothesis, we first investigated (by RT-PCR) the expression of GDNF mRNA and the mRNAs of the GDNF receptors Ret and GFRalpha-1 in (i) adult human renal cortex and medulla and (ii) in HMC in culture. The results were compared to the expression of these molecules in different developmental stages of the rat kidney. We found that both GDNF and its receptors were expressed in human adult kidney and HMC. Since this finding implicates a role for GDNF beyond nephrogenesis, i.e. in renal physiology/pathophysiology, we investigated the effect of GDNF on HMC growth, i.e. (i) cellular protein synthesis as an index of hypertrophy ([(3)H]methionine incorporation), (ii) DNA synthesis ([(3)H]thymidine incorporation) and cell proliferation (cell numbers) as indices of hyperplasia, and (iii) extracellular matrix synthesis, i.e. collagenous and non-collagenous extracellular proteins ([(3)H]proline incorporation into the collagenase-sensitive and -insensitive fraction). HMC cultures were used as a surrogate model for the development of glomerulosclerosis. RESULTS: GDNF induced a biphasic growth stimulatory effect in HMC with stimulation at the lowest concentration used (2 ng/ml) but had no effect at higher concentrations (20 and 50 ng/ml). In contrast, cellular protein synthesis and extracellular matrix synthesis were significantly and dose-dependently increased by GDNF. CONCLUSIONS: These results suggest that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor for mesangial cells and might thus be a player in the pathogenesis of glomerulosclerosis.

Aging↗