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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 55 records · Page 3Linked to original sources
PubMed2002

Consequences of late referral in diabetic renal disease.

The incidence of patients with end-stage renal disease and type 2 diabetes has increased tremendously over the past few decades. Unfortunately, many patients with diabetes are referred late to nephrologists. Currently, between a quarter and a third of European patients are referred to a nephrologist less than one month prior to the initiation of renal replacement therapy. The causes of late referral can be categorised into physician-related factors, patient-related factors, and factors related to the disease itself, such as the lack of a good general indicator of renal function. The consequences of late referral include poorer status upon referral, higher rates of hospitalisation and higher costs, and even increased mortality. Several interventions can be undertaken to improve the referral of patients with renal disease and diabetes, including improved medical education, better communication between GPs and nephrologists, adoption of a team approach between nephrologists, diabetologists and GPs, improved patient information, development of guidelines, and financial incentives to encourage earlier referral of these patients.

Diabetes Mellitus, Type 2↗
PubMed2001

[Incidence and clinical characteristics of renal insufficiency in diabetic patients].

BACKGROUND: In all Western countries there is a dramatic increase of diabetic patients who need renal replacement therapy. Very different figures for incidence and prevalence have been reported. There is a strong suspicion that the epidemiological dimension of the problem has been underestimated in many of the statistics. METHODS: In a retrospective analysis we assessed all patients admitted to the Department Internal Medicine Heidelberg from January 1(st) 1998 - December 31(st), 2000 for renal replacement therapy, i. e. hemodialysis or CAPD, because of acute or chronic renal failure. We counted the number of known diabetic patients (i) with signs of classical diabetic nephropathy (enlarged kidneys, proteinuria > 1g/24h +/- retinopathy), (ii) with atypical renal changes (contracted kidneys, proteinuria < 1 g/24 h) and (iii) diabetic patients with (coincident) primary chronic renal disease as well as (iv) the proportion of patients in whom the diagnosis of diabetes had been unknown when uremia had supervened. RESULTS: Dialysis treatment was started in 568 patients for acute (ARF; n = 341) or chronic (CRF; n = 227) renal failure. 95/341 (28 %) patients with ARF had diabetes. ARF occured in no less than 12/95 (13 %) of the diabetic patients after cardiological intervention. Diabetes was present in 111/227 patients with CRF (7 type 1, 104 type 2); in 12/111 patients the diagnosis of diabetes was established only after admission. Only 67/111 of the diabetic patients (60 %) had classical signs of diabetic nephropathy, in 14/111 (13 %) patients the classical signs of diabetic nephropathy were absent and in 30/111 (27 %) non-diabetic primary chronic renal disease was present. CONCLUSION: The study illustrates the importance of diabetes for the epidemiology of renal failure. A sizeable proportion of patients with acute renal failure have diabetes, typically patients with pre-existing nephropathy in whom this complication supervenes during diagnosis and treatment of late diabetic complications. In diabetic patients with chronic renal failure the presentation is frequently atypical and non-diabetic primary renal disease is present more frequently than expected by chance. In a sizeable proportion of patients diabetes had not been diagnosed by the time chronic renal failure occurred.

Acute Kidney Injury↗
PubMed2001

Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.

BACKGROUND: It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. METHODS: We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. RESULTS: The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. CONCLUSIONS: The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.

Adult↗
PubMed2001

Retinoids inhibit the actions of angiotensin II on vascular smooth muscle cells.

Retinoids are derivatives of vitamin A and powerful inhibitors of cell proliferation and inflammation. Angiotensin II (Ang II) contributes to vascular lesions by promoting cell growth of vascular smooth muscle cells (VSMCs). Therefore, we examined whether retinoids interfere with the proproliferative actions of Ang II in VSMCs via AT(1) receptor-dependent or activator protein-1 (AP-1)-dependent mechanisms. VSMCs express retinoid receptor proteins, ie, retinoic acid receptor (RAR) alpha and retinoid X receptor (RXR) alpha. Long-term exposure to 1 micromol/L all-trans retinoic acid (RA) dose-dependently inhibited Ang II-induced cell proliferation (P<0.005) as well as DNA and protein synthesis (P<0.001). All-trans RA blocked Ang II stimulation of transforming growth factor-beta(1) mRNA (P<0.005). All-trans RA inhibition of vascular VSMC growth was mediated both via RAR- and RXR-dependent pathways, as shown by receptor-specific synthetic retinoids. Transfection experiments revealed that inhibition of AP-1-dependent gene transcription is one mechanism by which all-trans RA inhibits Ang II action. RARalpha cotransfection enhanced the anti-AP-1 effects of all-trans RA dose-dependently. AP-1 activity was similarly inhibited by cotransfection with either RARalpha or RXRalpha. Ang II-induced gene expression of c-fos was abrogated by all-trans RA treatment (P<0.005). In VSMCs, all-trans RA downregulated AT(1) receptor mRNA (P<0.01) and reduced B(max) (P<0.001). All-trans RA repressed Ang II-stimulated AT(1) receptor promoter activity. The all-trans RA inhibitory effect was abolished when the AP-1 consensus site on the AT(1) receptor promoter was deleted. Our findings demonstrate that retinoids are potent inhibitors of the actions of Ang II on VSMCs. The findings support the notion that retinoids may interfere with proliferative vascular disease.

Alitretinoin↗
PubMed2001

Advanced glycation endproducts (AGEs) as uremic toxins.

Products of non-enzymatic glycation accumulate both in diabetic and non-diabetic patients with renal failure. The increase in concentration is presumably due to increased generation, secondary to oxidative stress and due to decreased (renal) elimination; whether accumulation of AGEs of dietary origin plays a role is currently under investigation. AGE's have been related to progression of diabetic (and possibly also non-diabetic) renal disease and to a number of complications of the uremic syndrome. These comprise beta-2-microglobulin-derived dialysis-related amyloidosis, dyslipidemia, vascular dysfunction and accelerated atherogenesis. A specific case is AGE related damage to the peritoneal membrane in CAPD patients. Removal of AGE by dialysis is negligible and even high flux dialysis eliminates only a quantitatively limited amount of AGE. In contrast, a rapid decrease of AGE concentrations in plasma is noted after renal transplantation. Dietary AGEs may contribute significantly to the total AGE load of the body, particularly in uremia.

Diabetic Nephropathies↗
PubMed2001

Hypertension after renal transplantation.

With current immunosuppression, elevated blood pressure is found in almost 90% of renal graft recipients. Major causes of this are impairment of renal function (secondary to chronic allograft nephropathy or less frequently recurrence of primary renal disease), the use of calcineurin inhibitors as immunosuppressants, uncontrolled renin secretion by the shrunken kidneys of the recipient, stenosing lesions of the transplant artery (or the upstream arteries of the recipient), polycythemia, and genetic predisposition to hypertension of the graft donor. Even minor degrees of blood pressure elevation have a significant impact on survival of the recipient and on graft survival, presumably by amplifying vascular injury to the graft. In this respect, elevation of systolic blood pressure and an abnormal circadian blood pressure profile are of particular relevance. In contrast to previous opinion, angiotensin converting enzyme inhibitors are indicated in treatment, but given the causal role of sodium retention and graft vasoconstriction, diuretics and calcium channel blockers remain mainstays of antihypertensive treatment in the renal allograft recipient.

Antihypertensive Agents↗
PubMed2001

Chronic renal transplantation: a model for the hyperhomocysteinemia of renal insufficiency.

Renal transplant recipients (RTR) are considered representative of patients with chronic renal insufficiency (CRI) in general with respect to both reduced, progressively declining renal function, and increased risk for cardiovascular disease (CVD). In accord with this argument, we hypothesized that total (t) plasma concentrations of the putatively atherothrombotic amino acid homocysteine (Hcy) would be equivalent in RTR and CRI patients with comparable renal function. We determined plasma tHcy, folate, pyridoxal 5'-phosphate, and B12 concentrations, in addition to serum creatinine and albumin concentrations, in 86 chronic, stable RTR, and 238 patients with CRI. Within comparable ranges of serum creatinine (i.e. RTR=0.6-4.2 mg/dl; CRI=0.7-4.1 mg/dl), tHcy concentrations did not differ between the two groups (RTR=15.0 micromol/l; CRI=14.9 micromol/l, P=0.899). ANCOVA revealed that renal function, gauged as a simple creatinine measurement, was the major independent determinant of plasma tHcy concentrations, accounting for approximately 80-90% of the total variability in tHcy predicted by the full model (i.e. full model R(2)) containing, in addition to creatinine, the seven other potential explanatory variables. If controlled trials confirm that tHcy-lowering treatment reduces CVD events rates in RTR, these results should be applicable to CRI patients in general.

Adult↗
PubMed2001

Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate.

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.

Adult↗
PubMed2001

Renal function: the Cinderella of cardiovascular risk profile.

The presence of an altered renal function in essential hypertension, advanced heart failure (HF) and after a myocardial infarction (MI) is associated with higher cardiovascular morbidity and mortality. Indices of altered renal function (e.g., microalbuminuria, increased serum creatinine concentrations, decrease in estimated creatinine clearance or overt proteinuria) are independent predictors of cardiovascular morbidity and mortality in any of the three clinical situations. These parameters should then be routinely evaluated in clinical practice. These facts have several therapeutic implications. First, although there is no evidence-based information on the level of blood pressure that confers optimal renal protection, levels substantially lower than past recommendations are advisable. Second, hypertensive kidney damage should be prevented by early treatment of hypertensive patients, particularly those with microalbuminuria. Finally, to avoid further aggravation of high cardiovascular risk, antihypertensive agents devoid of unwanted metabolic side effects should be used for the treatment of hypertensive vascular damage. In HF, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker seem to be the most renoprotective. Renal outcome is also improved by ACE inhibition after an MI. Finally, renal and cardiovascular outcome seem to run in parallel in all these situations.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Blood pressure in diabetic nephropathy--current controversies.

Hypertension has been recognized as an early and constant feature of diabetic nephropathy, but recent studies also suggest that a genetic predisposition to hypertension is an important risk factor for diabetic nephropathy. Antihypertensive treatment attenuates progression in diabetic nephropathy, but there is increasing evidence that very early treatment and very low target blood pressures should be implemented. There is also evidence for local activation of the renin system in the kidney as a result of hyperglycaemia. Apart from blood pressure, proteinuria should be monitored and dosing of ACE inhibitors should be guided, also by reduction of protein excretion.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Isotretinoin alleviates renal damage in rat chronic glomerulonephritis.

BACKGROUND: Retinoids, derivatives of vitamin A, have strong anti-inflammatory and antiproliferative properties. We previously demonstrated that the pan-agonists all-transretinoic acid (RA) and isotretinoin (13-cis RA) alleviate renal damage in rat acute glomerulonephritis (GN) induced by anti-Thy-1.1 mAb OX-7. METHODS: The present study examined the effects of low dose and high dose treatment with isotretinoin in the chronic glomerulonephritis model, Thy-GN. Thy-GN was induced by a single intravenous injection of monoclonal antibody (mAb) 1-22-3 in uninephrectomized Wistar rats (N = 7 to 10 per group). Control and nephritic groups were treated with vehicle (veh), low dose isotretinoin (2 mg/kg body wt), or high dose isotretinoin (10 mg/kg body wt). The experiment was terminated 60 days after induction of Thy-GN. RESULTS: In animals with Thy-GN, isotretinoin abrogated the increase in blood pressure and significantly reduced albuminuria. Glomerulosclerosis index, glomerular and interstitial cell counts, as well as the area of the interstitial space were significantly lower in nephritic rats treated with low and high dose isotretinoin compared to vehicle-treated nephritic controls. Treatment with isotretinoin also significantly reduced the number of glomerular and interstitial macrophages. The increase of transforming growth factor (TGF)-beta1, TGF receptor II and prepro-endothelin-1 gene expression in vehicle-treated nephritic rats was significantly attenuated by isotretinoin. CONCLUSIONS: Treatment with isotretinoin significantly reduces glomerular and interstitial damage in rats with chronic glomerulonephritis as indicated by different functional and histological markers. Retinoids may provide a novel therapeutic option for the treatment of glomerulonephritis.

Albuminuria↗
PubMed2001

Glomerulosclerosis and progression: effect of subantihypertensive doses of alpha and beta blockers.

BACKGROUND: Uremia is characterized by inadequately increased sympathetic activity. Sympathetic overactivity is involved in the genesis of hypertension in uremia, but its potential role on progression has not been well investigated. To address this issue, the effect of subantihypertensive doses of an alpha blocker and a beta blocker, and their combination on renal morphology and on albuminuria were investigated in the model of the subtotally nephrectomized rat. METHODS: Male Sprague-Dawley rats were subjected to surgical ablation (SNX) or sham operation (sham). Three days after surgery groups were treated either with phenoxybenzamine (PBZ, 5 mg/kg body weight/day), metoprolol (MET, 150 mg/kg body weight/day) or their combination (PBZ 2.5 mg/kg body weight/day + MET, 50 mg/kg body weight/day). Renal morphology was evaluated after 12 weeks by quantitative histology, immunohistochemistry, and electron microscopy. Urine albumin excretion and kidney endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) mRNA expression were assessed. RESULTS: Systolic blood pressure was significantly higher in all SNX groups compared with sham-operated controls with no difference in the SNX groups. The number of glomeruli per left kidney was reduced from 30,904 +/- 3212 to 17,480 +/- 2341 by SNX (-43.5%). Mean glomerular volume increased from 2.63 +/- 0.7 in untreated sham operated to 4.11 +/- 0.48 microm 3 x 10(6) in untreated SNX (56.3%). The glomerulosclerosis index did not change in SNX + PBZ rats, but was significantly lower in SNX + MET (0.56 +/- 0.14) and particularly SNX + PBZ + MET rats (0.49 +/- 0.11) than in untreated SNX (0.74 +/- 0.24). Glomerular capillary length density (LV) as a sensitive index of capillary obliteration was significantly lower in SNX and almost normalized in the three intervention groups. The same was true for the mean podocyte number per glomerulus. Glomerular ultrastructure in SNX was largely preserved by all treatments. The albumin excretion rate was significantly higher in untreated SNX than in sham; it was significantly lower in all treated SNX groups. CONCLUSION: The beneficial effect of non-hypotensive doses of alpha and beta blockers and their combination on renal morphology and albuminuria in the model of renal ablation argue for a blood pressure-independent role of sympathetic overactivity in the genesis of progression. In addition, the beneficial effect of adrenergic receptor blockade indicates that a substantial part is not mediated by sympathetic cotransmitters such as adenosine 5'-triphosphate (ATP) and neuropeptide Y (NPY).

Adrenergic alpha-Antagonists↗
PubMed2001

Complement components as uremic toxins and their potential role as mediators of microinflammation.

Cardiovascular disease is the major cause of death in end-stage renal disease (ESRD) patients. There is growing evidence that atherogenesis is an inflammatory rather than a purely degenerative process leading to a state of microinflammation. This raises the issue of whether treatment modalities of ESRD contribute to the microinflammatory state. One potential candidate in this context is the complement system. Here we consider three potential pathways linking complement activation to progression of atherosclerosis: (1) complement activation on artificial surfaces depends on their physicochemical characteristics, the effect of which is amplified because of the accumulation of complement factor D; (2) the exposure of ESRD patients to endotoxin creates a microinflammatory state, and this may amplify complement-induced damage; exposure to endotoxin may result from frequent infections because of the impairment of host-defense mechanisms or from transfer of bacterial contaminants across dialysis membranes into the blood stream; and (3) direct transduction of proinflammatory signals from blood-material interactions to the vascular system. We conclude that the complement system is an important candidate system in the genesis of microinflammation and accelerated atherogenesis in ESRD. We advance the hypothesis that the generation of proinflammatory signals, in which the complement system appears to be involved--both through systemic and local activation--plays a role in the development of late complications of uremia, including coronary heart disease. This hypothesis provides a rationale to maximize the biocompatibility of the dialysis procedure, that is, selection of nonactivating materials, use of ultrapure dialysis fluid, and--still theoretical--high-flux dialysis to remove factor D.

Acute-Phase Reaction↗