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Biomedical subjects

E Ritz

Publications and source records attributed to E Ritz.

At least 199 records · Page 11Linked to original sources
PubMed1998

Left ventricular hypertrophy in renal failure.

In patients with terminal renal failure, left ventricular hypertrophy (LVH) is extremely common. It is found in approximately 60 to 80% of patients starting renal replacement therapy. The main causes of LVH are increased preload from hypervolemia and increased afterload from increased peripheral resistance, giving rise to a mixture of eccentric and concentric hypertrophy, but other factors (high cardiac output from anemia and arteriovenous (A-V) fistula, altered compliance of central arteries, and activation of local systems such as renin and endothelin) also play a role. The clinical importance of LVH derives from the fact that LVH is a predictor of cardiac death in dialyzed patients independent of blood pressure. LVH is accompanied by microvascular disease and by marked interstitial fibrosis (more than seen in non-renal patients with similar degrees of hypertension). Recent findings suggest that LV remodeling starts early and is seen even in normotensive patients with glomerulonephritis when GFR is still normal. The strategies to reduce LVH include reduction of hypervolemia, (near) normalization of hemoglobin and lowering of blood pressure, particularly by administration of angiotensin converting enzyme inhibitors.

Humans↗
PubMed1998

Comparing outcomes in renal replacement therapy: how should we correct for case mix?

The need to evaluate the effectiveness of clinical practice to justify expensive therapy in the face of financial constraints in all areas of health care delivery makes it necessary to identify groups of patients who are likely to benefit most from treatment. Various risk stratification methods have been used for analyzing survival probabilities for patients receiving renal replacement therapy. Complicated risk stratification methods produce large numbers of risk groups of small sizes, which makes comparison between individual centers difficult. We compared three simple methods of risk stratification, that divided patients into low-, medium-, and high-risk groups, in a cohort of 1,407 patients who commenced renal replacement therapy in five European countries during a 7-year period. Method 1 considered age (>55 years) and diabetes alone; method 2 used a higher age limit (>70 years) and comorbid illnesses, including those other than diabetes; and method 3 used only the number of comorbidities (none, 1, or > or =2) for stratification. Kaplan-Meier survival curves were constructed for comparison between risk groups and Cox's regression model used to assess strength of relationship with mortality. Although patient survival was significantly different between the low-, medium-, and high-risk groups using all three methods, Cox's regression analysis showed that method 2 provided the greatest discrimination between risk groups. In predicting mortality, method 2 (based on comorbidities and age) showed the highest sensitivity and specificity (84% and 80%, respectively) compared with method 1 (80% and 74%) and method 3 (64% and 82%). Validation of this approach in other populations in a prospective study is required before this method, which takes into account the influences of both age and comorbidity for risk stratification, can be used for comparing survival data and for presenting results of renal replacement therapy.

Adolescent↗
PubMed1998

In situ upregulation of IL-10 reflects the activity of human glomerulonephritides.

A reciprocal regulation between the expression of tumor necrosis factor (TNF)-alpha and interleukin (IL)-10, demonstrated in monocytes and mesangial cells, provides a rationale for new therapeutic approaches in glomerulonephritis (GN). Administration of IL-10 to mice with antibody-mediated GN attenuated the severity of glomerular lesions. Recently, however, it has been shown that the genetically determined predominance of Th1 or Th2 cytokines results in different glomerular responses to the same planted antigen, but in an equally severe impairment of renal function. We looked for the expression of IL-10 and TNF-alpha in 111 renal biopsy specimens with proliferative and nonproliferative forms of GN and in 10 control kidneys, by means of immunocytochemistry, in situ hybridization, or reverse-transcriptase polymerase chain reaction (RT-PCR). Six patients had acute endocapillary GN (AGN), 10 patients had pauci-immune GN due to microscopic polyangiitis (MP), 48 patients had immunoglobulin-A (IgA)-GN, 18 patients had idiopathic membranous GN (IMGN), 12 patients had minimal change disease (MCD), and 13 patients had focal segmental glomerulosclerosis (FSGS) and four other forms of GN. Antibodies against monocytes (CD14) and macrophages (CD68) were applied to attribute the expression of TNF-alpha and IL-10 to resident renal or infiltrating cells. We show that mRNAs for TNF-alpha and IL-10 are detected by RT-PCR and in situ hybridization in the normal kidney. A constitutive expression of TNF-alpha protein is observed in mesangial cells, smooth muscle cells in renal arteries, and in the interstitium. A trace immunoreactivity for IL-10 is restricted to arterial smooth muscle cells, distal tubular epithelial cells, and some interstitial cells. Upregulation of both cytokines is found in glomerular diseases. The expression of TNF-alpha increases in mesangial areas in MCD, IMGN stages I/II, and IgA-GN with minor glomerular abnormalities, that is, under conditions with a generally well-preserved glomerular structure. Conversely, marked glomerular proliferation in IgA-GN and, particularly, acute vascular lesions in MP, are accompanied by a significant upregulation of IL-10 (at the mRNA and protein level). Patients with nephrotic-range proteinuria show a significant increase in tubulointerstitial expression of IL-10, whereas the immunoreactivity for TNF-alpha reflects the extent of interstitial fibrosis. Thus, our results confirm previous suggestions that proinflammatory and antiinflammatory cytokines are produced in situ by resident renal cells and contribute to the natural course of human GN.

Adult↗
PubMed1998

Reduced insulin-mediated glucose uptake by euglycemic clamp in offspring of patients with type 2 diabetes.

Family studies point to an important genetic element in the genesis of type 2 diabetes. A variety of metabolic abnormalities have been documented in offspring of patients with type 2 diabetes. It has not been shown, however, at what age reduced insulin sensitivity is demonstrable using the sensitive the euglycemic clamp technique. To address this issue we screened 425 consecutive type 2 diabetic patients and examined all available (n = 48) normotensive, normoglycemic, non-smoking offspring (mean age 31.4+/-0.9 years) and compared them to 22 healthy offspring of non-diabetic parents (controls). The two groups were of similar age and BMI. Measurements in offspring and controls included baseline IRI, tissue glucose uptake (TGU, using euglycemic hyperinsulinemic clamp technique), and 24 hour ambulatory blood pressure (ABP). TGU was significantly (p < 0.001) lower in offspring of diabetic parents (338.8+/-19.9 (mol/kg/min) when compared to controls (516.6+/-22.2 micromol/kg/min). 24 h systolic ABP was significantly higher (p < 0.02) in propositi compared to controls (121.2+/-2.2 mm Hg and 113.8+/-1.7 mm Hg, respectively). No difference in triglycerides concentration was found. A borderline negative correlation was observed, however, between triglyceride levels and TGU (R = -0.48, p < 0.001). TGU was not related to the presence or absence of diabetic nephropathy in the parents. We conclude: Insulin resistance and various facets of the metabolic syndrome are demonstrable even at age 30 years in young non-obese, normotensive offspring of patients with type 2 diabetes. These disturbances are not related to the presence of microvascular complications in parents.

Adult↗
PubMed1998

The sympathetic nervous system and the kidney: its importance in renal diseases.

There is a two-way relation between the sympathetic nerve system and the kidney. On the one hand the sympathetic nerve system affects renal function, i.e. renal hemodynamics, renin secretion and tubular sodium transport. On the other hand the kidney is the source of activating afferent signals, presumably via stimulation of chemoreceptors and baroreceptors. This concept is supported by clinical observations in endstage and pre-endstage renal disease, where sympathetic overactivity is present. It has been shown to depend on the presence of the diseased kidney and is abolished by bilateral nephrectomy. Experimentally, interruption of afferent nerve traffic by dorsal rhizotomy partially prevents hypertension in renal damage models. Imidazoline-preferring binding sites are found in the kidney. In the rat, natriuresis is elicited by injection of moxonidine into the renal artery. In humans, there is no definite evidence for a natriuretic effect, but some observations point in this direction. In renal disease, the issue arises whether sympathetic overactivity contributes to progression of renal failure. Indirect evidence in this direction could be the marked acceleration of progression by smoking, a state of known sympathetic overactivity. In experimental models of renal damage, treatment with moxonidine in antihypertensive doses markedly attenuated development of glomerulosclerosis. Preliminary observations show that even non-antihypertensive doses of moxonidine interfere with the development of glomerulosclerosis. Sympathicolytic agents are obviously rational in the antihypertensive therapy of the renal patient, because uraemia is a state of sympathetic overactivity and because blood pressure-independent effects of sympathetic activation on progression are likely.

Animals↗
PubMed1998

The renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure is not dependent on enhanced kinin activity.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been shown to ameliorate the progression of glomerulosclerosis both in experimental models of uraemia and in patients with renal failure. It has not been documented, however, whether this is due to a decrease in angiotensin II generation or is a consequence of elevated local level of bradykinin. METHODS: Morphometric investigation of renal tissue was performed in 5/6 nephrectomized (SNx) rats, i.e. untreated or treated with the ACE inhibitor ramipril (SNx-RAM), the B2 kinin receptor antagonist HOE 140 (SNx-HOE), or a combination of both (SNx-RAM + HOE) over 8 weeks. A further group of SNx received delayed treatment with ramipril from week 5 onward (SNx-RAMD). In addition, a sham-operated (SHAM) control group was studied. RESULTS: Systolic blood pressure was significantly lower in both SNx-RAM and SNx-RAM + HOE groups compared to (untreated) SNx. The glomerulosclerosis index (GSI) was substantially higher in the (untreated) SNx group (0.24 +/- 0.04) vs SHAM (0.02 +/- 0.01). A significantly higher GSI was found in the SNx-HOE group (0.45 +/- 0.08) as compared to (untreated) SNx. However, in the SNx-RAM, SNx-RAM + HOE, and SNx-RAMD groups, the GSI was lowered to a similar extent (0.1 +/- 0.02, 0.09 +/- 0.02, and 0.07 +/- 0.01 respectively). In addition, a concomitant attenuation of tubulointerstitial damage was noted in all the above groups. CONCLUSION: Increased kinin activity does not appear to play a major role in the renoprotective effect of ACE inhibitors in the remnant kidney model.

Angiotensin Receptor Antagonists↗
PubMed1998

Audit of antihypertensive treatment in patients with renal failure.

BACKGROUND: Recently, intensified antihypertensive treatment has been recommended for patients with proteinuric renal disease, and a target blood pressure of 125/75 mmHg has been proposed. METHODS: In a retrospective crossectional study, all consecutive patients with renal disease and reduced GFR seen in the renal outpatient clinic Heidelberg during a specified time period were analysed. Physicians administered antihypertensive agents according to their clinical judgment aware of recent recommendations, but without structured guidelines. The aims of the study were: (i) to monitor achieved blood pressure (clinic measurement, self measurement, ambulatory BP measurement); (ii) to monitor the number of antihypertensive medications required; and (iii) to analyse the factors which determine achieved blood pressure and the number of antihypertensive agents required. RESULTS: There were 201 non-transplanted patients, median age 60 years (range 20-86), 131 male, 70 female, median S-creatinine 2.33 mg/dl (1.4-10.9). Fifty-two of the patients had diabetes, 41 GN, 18 ADPKD, 17 vasculitis, seven reflux nephropathy, three analgesic nephropathy and 63 other or unknown renal diseases. When the patients had originally been referred to the renal clinic, median clinic BP had been 160 mmHg systolic (104-260) and 95 mmHg diastolic (65-160). Under nephrological care, achieved clinic systolic (140; 90-190) and diastolic BP values (85; 45-130) were significantly (P<0.0001) lower. Achieved BP was slightly (r=0.23, P<0.05) correlated with age, was not significantly different between genders, and was not correlated to proteinuria, serum creatinine, renal disease or BMI. Average self measured BP values were not different from systolic and diastolic clinic BP values. Ambulatory BP values, however, were significantly (P<0.0001) lower, e.g. daytime systolic BP 133 mmHg (107-171), diastolic 82 mmHg (65-97). A night-time decrease of BP > or = 15% was seen in 18/25 patients only. The median number of antihypertensive classes required was 3 (range 1-7) in non-diabetic and 3.5 (1-7) in diabetic patients, respectively. The number of antihypertensive classes was independent of serum creatinine, BMI or proteinuria, but was significantly (P<0.01) higher in males (4; 1-7) than in females (3; 1-6) and correlated to age (r=27, P<0.01). CONCLUSIONS: The study (i) illustrates the difficulty to achieve recommended target BP in patients with renal failure, (ii) shows remarkably little white coat effect on clinic blood pressure, (iii) illustrates the value of ambulatory blood pressure measurement and (iv) documents the importance of multidrug antihypertensive treatment in patients with renal failure.

Adult↗
PubMed1998

Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases.

BACKGROUND: Ultrasound-guided renal biopsy with an automated spring-loaded biopsy device has become the standard method for kidney biopsy. Information on the success rate and safety of the routine use of this procedure from large series is not available. Such information is of interest for cost benefit considerations and for medicolegal purposes. We performed an audit of this procedure. SUBJECTS AND METHODS: From January 1993 to June 1997, 1090 percutaneous renal biopsies were performed in the renal units of Heidelberg (n = 557) and Karlsruhe (n = 533) using a spring-loaded biopsy device (Biopty; Radiplast AB, Uppsala, Sweden). After intensive local disinfection, biopsies were performed under local anaesthesia and direct visualization by ultrasound (Sonolayer SSH-140 A, Toshiba Inc., Japan). A puncturing adaptor was used (model UAGV 009 A, Toshiba, Japan). Of the 1090 biopsies 114 (10.4%) were performed on renal allografts and 976 (89.6%) on orthotopic kidneys. Biopsies were performed only if patients were strictly normotensive (<140/90 mmHg) and had normal coagulation parameters (PT, PTT, factor VIII, thrombocyte count, and bleeding time). All patients had been advised not to take aspirin or non-steroidal antiinflammatory agents for at least 5 days prior biopsy. We analysed (1) yield of diagnostically useful material, and (2) frequency of postbiopsy complications (e.g. macrohaematuria, haematoma, infections, and AV fistula). RESULTS: Except for one case requiring interventional radiology because of persisting blood loss and three cases requiring blood transfusions, no serious complications were seen in the 1090 consecutive renal biopsies, e.g. death, loss of kidney, life-threatening haemorrhage, or persisting haemodynamically relevant AV fistulae. The frequency of minor haematoma with an extension >2 x 2 cm, but no significant decrease of haemoglobin, was 2.2% (25/1090). Self-limited mild macrohaematuria occurred in 0.8% (9/1090). The incidence of small, haemodynamically irrelevant AV fistulae detected by Doppler ultrasound was 9% (48/533). Sufficient tissue for reliable histopathological diagnosis was obtained in almost all cases (1077/1090 = 98.8%). The median number of glomeruli per biopsy sample was 9 (range 1-37). CONCLUSION: If contraindications, especially high blood pressure and abnormal haemostasis, are respected, ultrasound-guided percutaneous renal biopsy with an automated biopsy device is safe. Skilled operators obtain satisfactory amounts of kidney tissue in almost all cases.

Adolescent↗
PubMed1998

A polymorphism in the gene for the atrial natriuretic peptide and diabetic nephropathy. Diabetic Nephropathy Study Group.

BACKGROUND: Atrial natriuretic peptide is involved in blood pressure regulation via its vasodilating and natriuretic actions. Since diabetic nephropathy and hypertension are closely related, ANP is a reasonable candidate gene for diabetic nephropathy (DN). METHODS: We genotyped 410 patients with type I diabetes (without DN n = 307; with DN n = 103) and 658 patients with type II diabetes (without DN n = 464; with DN n = 194). In the patients the duration of diabetes was at least 10 years. Diabetic nephropathy was defined as urinary albumin excretion of > or = 30 mg/24 h. The HpaII polymorphism in intron 2 of the ANP gene was determined using PCR amplification followed by restriction digest. Alleles were separated on agarose gels stained with ethidium bromide. RESULTS: We compared genotype distribution and allele frequencies between patients with and without nephropathy. No significant difference was observed either in type I (allele frequency without DN H1, 0.02/H2, 0.98 vs with DN H1, 0.05/H2, 0.95; P = 0.132) or in type II diabetes (allele frequency without DN H1, 0.04/H2, 0.96 vs with DN H1, 0.05/H2, 0.95; P = 0.551). CONCLUSIONS: The polymorphism in the gene for the atrial natriuretic peptide does not seem to play a major role in the development of diabetic nephropathy in either type I or in type II diabetes.

Adult↗
PubMed1998

Cardiac remodelling in experimental renal failure--an immunohistochemical study.

BACKGROUND: In view of the high rate of cardiac death in renal failure, the factors involved in the genesis of structural changes in the heart are of obvious interest. The present study addresses the issue whether growth factors known to be involved in cardiac remodelling are abnormally expressed in rats with renal failure. METHODS: Sprague Dawley rats were subjected to binephrectomy (2 days) or subtotal nephrectomy (8 weeks). Controls were sham-operated rats and rats with Goldblatt hypertension. Cardiac expression of proliferating cellular nuclear antigen (PCNA), of growth factors and of their receptors (PDGF, TGF-beta, VEGF) was investigated immunohistochemically. In addition, cardiac PDGF-and TGF-beta mRNA were assessed using quantitative RT-PCR. RESULTS: Eight weeks after subtotal nephrectomy (SNX) significantly increased expression of PCNA and PDGF was found in the cardiac interstitium and of PCNA and VEGF in the walls of intramyocardial arteries. In addition, PCNA-positive cardiomyocytes were noted in SNX. Similar changes were not seen in the hearts of hypertensive controls, i.e. rats with renovascular hypertension, despite slightly higher blood pressure and more pronounced left ventricular hypertrophy (LVH). While significant changes of cardiac PDGF- and TGF-beta mRNA expression could not be documented in the whole-heart homogenates 8 weeks after subtotal nephrectomy, 2 days after bilateral nephrectomy PDGF mRNA was significantly increased and TGF-beta mRNA decreased. CONCLUSION: The observations demonstrate (i) specific activation of cardiac interstitial cells after SNX, (ii) activation of postmitotic cardiomyocytes, possibly predisposing to apoptosis, (iii) increased expression of PDGF in the cardiac interstitium and in the wall of intramyocardial arteries, (iv) increased expression of VEGF associated with hypertrophy of arterial smooth muscle cells. These results were not explained by elevated blood pressure or LVH, respectively.

Acute Kidney Injury↗
PubMed1998

Does the vitamin D receptor genotype predict bone mineral loss in haemodialysed patients?

BACKGROUND: It has been suggested that the vitamin D receptor (VDR) gene BsmI-polymorphism is a genetic determinant of bone metabolism. DESIGN: To test this hypothesis, the relationship between VDR genotypes, bone mineral density (baseline and after 18 months) and parameters of calcium metabolism and bone turnover were investigated prospectively in 88 haemodialysed patients not receiving active vitamin D metabolites. METHODS: Whole body, lumbar spine and femoral neck bone mineral density (BMD) were assessed by dual energy X-ray absorptiometry (DEXA). In addition calcium, phosphorus, 25(OH)D3, 1,25(OH)2D3, osteocalcin serum concentrations, alkaline phosphatase activity and intact 1,84 PTH levels were measured. RESULTS: VDR genotype BB, Bb and bb were found in 27, 49 and 24% of patients. Initial BMD (g/cm2) of whole body, lumbar spine and femoral neck did not differ between genotypes (whole body: BB 1.055 +/- 0.120, Bb 1.082 +/- 0.102, bb 1.128 +/- 0.120; lumbar spine: BB 1.075 +/- 0.199, Bb 1.079 +/- 0.185, bb 1.099 +/- 0.170; femoral neck: BB 0.808 +/- 0.160, Bb 0.862 +/- 0.127, bb 0.842 +/- 0.125; mean +/- SD), but the decrease of whole body and femoral neck BMD during 18 months was significantly (P < 0.02) different between the genotype groups (whole body: BB -0.048 +/- 0.028, Bb -0.031 +/- 0.029, bb -0.024 +/- 0.023; femoral neck BB -0.044 +/- 0.069, Bb -0.032 +/- 0.081, bb -0.012 +/- 0.029 g/cm2). CONCLUSION: This preliminary study suggests faster mineral loss in BB genotype of VDR in haemodialysed patients.

Adolescent↗
PubMed1998

Effects of testosterone on glomerular growth after uninephrectomy.

BACKGROUND: Renal functional prognosis is consistently more adverse in male individuals with renal disease. Male animals develop more marked proteinuria and glomerulosclerosis in several models of renal damage. Renal and glomerular growth are important permissive factors for progression of renal failure. PURPOSE OF THE STUDY: To investigate the influence of testosterone on renal and glomerular growth. DESIGN: Renal compensatory growth after uninephrectomy (UNX) was chosen as a model of renal growth. The effect of testosterone was assessed in control male, in orchidectomized (OX) male, and in ovariectomized (OV) female SD rats. Observation time was 10 months. MEASUREMENTS: Albuminuria by nephelometry; glomerular diameter, glomerular tuft area, renal zonal analysis by quantitative stereology. Testosterone and dihydroxytestosterone by gas chromatography and RIA. RESULTS: In sham-operated male rats, testosterone administration did not change the (left) kidney:body-weight ratio after uninephrectomy. In contrast, in OX male rats, testosterone administration caused a significant increase in kidney:body-weight ratio and in albuminuria. In these animals, glomerular diameter and outer stripe width were significantly lower in OX rats than in sham-operated controls. Glomerular volume and outer stripe width in OX animals were significantly higher after uninephrectomy (UNX) and were further increased in OX-UNX animals by administration of testosterone. Similar effects on glomerular diameter, cortical width (single) kidney:body-weight ratio were seen when OV female rats were treated with testosterone. CONCLUSION: After gonadal ablation, administration of testosterone amplifies compensatory glomerular and tubular growth in uninephrectomized male and female rats, i.e. testosterone is a permissive factor. Stimulation of glomerular growth may favour development of glomerulosclerosis.

Adaptation, Physiological↗