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Biomedical subjects

A Bohle

Publications and source records attributed to A Bohle.

At least 19 recordsLinked to original sources

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury

The pathogenesis of chronic renal insufficiency in renal vasculopathies.

Comparative clinical and morphological investigations on the pathogenesis of chronic renal insufficiency in various types of renal vasculopathy revealed the following: 1) Compensated benign nephrosclerosis, with hyalinosis of the walls of the afferent vessels, does not lead to renal insufficiency, since relatively few glomeruli, mostly subcapsular, become obliterated in this disease. 2) In decompensated benign nephrosclerosis, in which not only the afferent vessels but also the glomeruli and the cortical interstitium are involved, there is a significant positive correlation between the relative width of the renal cortical interstitium and the serum creatinine concentration and a significant negative correlation between the relative volume of the postglomerular capillaries and the serum creatinine concentration, as in the primary glomerulopathies. 3) In primary malignant nephrosclerosis, which is always accompanied by haemolytic-uraemic syndrome, the relative width of the cortical interstitium is not related to the serum creatinine concentration. Chronic renal insufficiency develops in this disease as a result of a fall in glomerular filtration rate to inadequate levels due to impairment of renal perfusion by stenotic changes in the preglomerular vessels. 4) In secondary malignant nephrosclerosis, which is never accompanied by haemolytic-uraemic syndrome, there is, as in the primary glomerulopathies, a significant positive correlation between the relative width of the renal cortical interstitium and the serum creatinine concentration and a significant negative correlation between the relative capillary volume and the serum creatinine concentration. 5) In decompensated benign nephrosclerosis the severity of the renal insufficiency depends largely on the degree of obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterioles

[Acute noninflammatory renal failure. New pathogenetic aspects in light of findings obtained in autopsy and biopsy of kidneys].

Thorough studies of kidney specimens obtained at autopsy or by renal biopsy revealed, that in noninflammatory acute renal failure oliguria/anuria is caused by increased activation o the renal renin-angiotensin system and increased generation of adenosine. At the polyuric phase moderately increased adenosine in kidney tissue seems to be the main factor responsible for decreased glomerular filtration.

Acute Kidney Injury

Pathogenesis of chronic renal failure in primary glomerulopathies.

Comparative analysis of renal biopsy findings and clinical status in patients with different types of glomerulopathy (primary glomerulonephritis, 1747; diabetic glomerulosclerosis, 488; renal AA and AL amyloidosis, 225) was undertaken to investigate the pathogenesis of chronic renal failure in these diseases. Morphometric, cytological and electron-microscopic investigations were undertaken and yielded the following results: 1. Disease of the renal corpuscles alone, even if it is very severe, does not lead to renal insufficiency or even elevation of the serum creatinine concentration. 2. Chronic renal insufficiency develops only in those cases of glomerulopathy in which the postglomerular capillaries in the renal cortex exhibit chronic inflammation that causes such severe narrowing of these vessels as to impair glomerular perfusion. 3. The passage of basement membrane material from the glomerular capillaries into the primary urine may play a critical role in the pathogenesis of some forms of chronic renal failure, since this material can be reabsorbed by the tubules and is probably presented as an autoantigen to intraepithelial T lymphocytes by proximal tubular epithelial cells that express distinct HLA class II antigens and ICAM-1. 4. The presentation of these autoantigens to intraepithelial T lymphocytes leads in genetically predisposed individuals to an autoimmune response with a consequent marked increase in numbers of T lymphocytes and an increase in macrophages/monocytes, fibroblasts/fibrocytes and plasma cells, and increased production of extracellular matrix by fibroblasts/fibrocytes. 5. The increase in extracellular matrix leads to obliteration of the postglomerular capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Capillaries

The long-term prognosis of the primary glomerulonephritides. A morphological and clinical analysis of 1747 cases.

Long-term studies of all types of primary glomerulonephritis (GN) taking into consideration the major morphological and clinical findings revealed the following: 1) Endocapillary GN, post-streptococcal type has a very good prognosis when only glomerulitis is present. The prognosis is significantly worse if either interstitial inflammation with fibrosis or nephrotic syndrome (NS) is present at the time of the biopsy. 2) The prognosis of the various types of mesangioproliferative GN (IgA nephritis, non-IgA nephritis, and immunohistologically negative GN) is very good if there is only glomerulitis. The prognosis is worse for all three types when the renal cortical interstitium exhibits inflammation with fibrosis at the time of the biopsy, and is worst of all when both interstitial fibrosis (IF) and the signs of acute renal failure (ARF) are present. Of this group, the type in which there are negative immunohistological findings exhibits the best prognosis. No difference in prognosis is found between IgA nephritis and non-IgA nephritis. 3) Minimal changes GN with NS has a very good prognosis when the interstitium is not involved. The presence of interstitial inflammation and fibrosis worsens the prognosis significantly. 4) Focal sclerosing GN has a much poorer prognosis than minimal changes GN with NS, even when there is glomerulitis only (5- and 10-year renal survival rates (RSRs) of 90% and 67%, respectively). If interstitial inflammation and fibrosis are present, the prognosis is significantly worse (5- and 10-year RSRs of 84% and 55%, respectively). The prognosis is worst when both ARF and IF are present at the time of the biopsy (5- and 10-year RSRs of 56% and 46%, respectively). From the clinical side, the prognosis is significantly worse if, at the time of the biopsy, NS is present or the serum creatinine concentration is elevated to more than 1.3 mg%. 5) Chronic membranous GN has a better prognosis than focal sclerosing GN if glomerulitis only is present (5-year RSR, 88%; 10-year RSR, 77%). If the renal cortical interstitium is also involved (in the form of IF), the prognosis is significantly worse (5-year RSR, 65%; 10-year RSR, 38%). The prognosis in this disease, too, is worst when both ARF and IF are present at the time of the biopsy (5-year RSR, 38%; 10-year RSR, 25%). 6) Membranoproliferative GN has a worse prognosis than any of the types of GN so far mentioned (5-year RSR, 51%; 10-year RSR, 32%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.

Adult

The consequences for renal function of widening of the interstitium and changes in the tubular epithelium of the renal cortex and outer medulla in various renal diseases.

The following parameters were measured in 63 renal biopsy specimens, most of which exhibited mesangioproliferative glomerulonephritis: the relative area of the interstitium and the area of the capillaries in the cortex and outer stripe of the outer medulla, and the area of the epithelium of the proximal tubules and of the ascending limbs of Henle's loop. The percentage of hyalinized glomeruli was also determined. Investigation of correlations between these values and parameters of renal function revealed the following: 1) The serum creatinine concentration increases and the endogenous creatinine clearance decreases significantly as the interstitium of both the cortex and the outer stripe of the outer medulla increases in width. 2) The urine osmolality decreases significantly as the epithelial areas of the proximal tubules and ascending limbs of Henle's loop decrease, and as the serum creatinine concentration rises and the areas of the interstitium increase. 3) No significant correlation exists between the percentage of hyalinized glomeruli and the urine osmolality. 4) The total area of the intertubular capillaries in the cortex decreases significantly as the interstitium in this area increases in width and as the serum creatinine concentration increases. 5) Compensatory hypertrophy of individual nephrons, as proposed by Bricker's hypothesis, was found only where more than 90% of the glomeruli were hyalinized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis.

Investigation of renal biopsy specimens from 488 patients with diabetic glomerulosclerosis (DGS) of varying severity revealed the following: 1) The severity of DGS increases with the duration of the diabetes. 2) As the severity of DGS increases, it is complicated with increasing frequency by exudative changes, which correspond in detail to hyperperfusion lesions described in the literature. 3) As the severity of DGS increases, the severity of arteriolosclerosis and the incidence of nephrotic syndrome increase significantly. 4) The 5- and 10-year renal survival rates are highest for those diabetic patients in whom the tubules and renal cortical interstitium are of normal appearance. These survival rates are diminished if any of the following are present at the time of biopsy: a) interstitial fibrosis; b) hyperperfusion lesions; c) nephrotic syndrome; d) elevation of the serum creatinine concentration to more than 1.3 mg%. 5) No significant correlation was found between renal survival rate and age, sex, or type of diabetes. 6) The inflammation of the renal interstitium seen in diabetes does not differ from that seen in chronic glomerulonephritis. Monocytes, macrophages, T lymphocytes, fibroblasts and fibrocytes play the major role in this inflammation. This inflammatory process is considered to represent not pyelonephritis, but rather an auto-immune process. In other words, it is proposed that the diabetic kidney fails not only as a result of non-specific glomerular lesions (hyperperfusion lesions) but also because of non-specific tubulointerstitial changes, whereas diabetic glomerulosclerosis alone does not lead to chronic renal failure.

Adult

Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis.

Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.

Adult

Hyperperfusion injury in IgA nephropathy.

The authors have found morphological alterations identical with hyperfiltration glomerular injury in the renal biopsies of 23 out of 100 patients with IgA nephropathy. In 15 of them the lesions were similar to the different stages of segmental glomerular hyalinosis and sclerosis with deposition of IgM and C3. At the time of renal biopsy, the serum creatinine of all except 8 patients was normal (maximally 170 mumol/1), only 13 had hypertension, and all except 2 were proteinuric. During the follow-up period (mean +/- 2Sd = 138 +/- 76 months) all of them became hypertensive. In 10 patients end-stage renal failure developed, and in another 10, serum creatinine also became elevated (range 124 - 504 mumol/1). On the basis of these data the development of focal segmental hyalinosis and sclerosis should be interpreted as a bad prognostic sign in IgA nephropathy.

Adult

Hyperperfusion injury in IgA nephropathy.

The authors have found morphological alterations identical with hyperfiltration glomerular injury in the renal biopsies of 23 out of 100 patients with IgA nephropathy. In 15 of them the lesions were similar to the different stages of segmental glomerular hyalinosis and sclerosis with deposition of IgM and C3. At the time of renal biopsy, the serum creatinine of all except 8 patients was normal (maximally 170 mumol/1), only 13 had hypertension, and all except 2 were proteinuric. During the follow-up period (mean +/- 2Sd = 138 +/- 76 months) all of them became hypertensive. In 10 patients end-stage renal failure developed, and in another 10, serum creatinine also became elevated (range 124 - 504 mumol/1). On the basis of these data the development of focal segmental hyalinosis and sclerosis should be interpreted as a bad prognostic sign in IgA nephropathy.

Adult

The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis.

Morphometric investigation of the structures of the cortex in kidneys exhibiting various types of glomerulopathy revealed the following: 1. In various types of glomerulonephritis, diabetic glomerulosclerosis, and glomerular amyloidosis there are significant correlations between the severity of fibrosis of the renal cortical interstitium and tubular atrophy resulting from chronic interstitial inflammation, and the serum creatinine concentration, creatinine clearance, inulin clearance and PAH clearance. 2. As illustrated with the example of membranoproliferative glomerulonephritis type I, if glomerulopathy alone is present, there is no elevation of the serum creatinine concentration, even if the glomerular inflammatory changes are severe; neither are severe renal amyloidosis that is confined to the glomeruli and severe isolated diabetic glomerulosclerosis associated with elevation of the serum creatinine concentration. 3. There is a significant negative correlation between the severity of interstitial fibrosis resulting from chronic inflammation and the total number and cross-sectional area of the intertubular capillaries; i.e., the total cross-sectional area and number of capillaries per unit area decrease as the fibrosis of the cortical interstitium increases. 4. Cases of glomerulonephritis in which there is accompanying fibrosis of the renal cortical interstitium have a significantly worse long-term prognosis than those in which there is only severe glomerulitis. 5. Obliteration of the post-glomerular capillaries leads to an increase in the cross-sectional area of the glomerular capillary convolution, the morphological equivalent of an increase in intraglomerular pressure. 6. The cause of the disease of the renal cortical interstitium that may accompany the various types of glomerulonephritis is not known. It is considered possible, as a working hypothesis, that this inflammation represents a T-cell stimulated autoimmune process in which fibroblast proliferation occurs, leading to an increase in numbers of fibrocytes in the renal cortical interstitium and thus to increased production of collagen.

Creatinine

Association of glomerular and interstitial mononuclear leukocytes with different forms of glomerulonephritis.

Immunophenotyping of mononuclear leukocytes was performed in renal tissue obtained from 69 patients with different forms of glomerulonephritis (GN) and from ten donors' kidneys for transplantation used as controls. A panel of monoclonal antibodies was used in the immunoperoxidase technique on frozen sections to define B- and T-lymphocyte subpopulations, NK cells and monocytes/macrophages, as well as the expression of HLA class II antigens-DQ, -DR and -DP. Quantification of labelled leukocytes revealed a significant increase of CD4+ and CD8+ T-cells in glomeruli of rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis and even of focal gomerulosclerosis. The number of glomerular monocytes/macrophages was significantly increased only in rapidly progressive glomerulonephritis, whereas in membranoproliferative glomerulonephritis it was decreased. No differences to normal tissue were detected in glomeruli for all other types of inflammatory cells. Interstitial cells were mostly T-lymphocytes in all forms of glomerulonephritis. In all groups the CD4+/CD8+ ratio was somewhat greater than 1 and even about 2 in rapidly progressive glomerulonephritis. Only in particular case was this ratio inversed. High expression of HLA class II antigens was observed on interstitial mononuclear leukocytes, as a sign of their activation. The excess of HLA-DQ-positive cells over the sum of CD14+ and CD20+ cells provides evidence not only for presence of activated T-lymphocytes but perhaps also for accumulation of renal dendritic cells in the interstitium in glomerulonephritis associated with interstitial infiltration.

Antibodies, Monoclonal

IgA nephritis: on the importance of morphological and clinical parameters in the long-term prognosis of 239 patients.

This study is concerned with the correlation between tubulointerstitial changes (interstitial fibrosis, acute renal failure, and interstitial fibrosis with acute renal failure), glomerular changes (focal and segmental lesions, hyperperfusion lesions), vascular changes, clinical data at the time of biopsy (serum creatinine concentration, creatinine clearance, hematuria, proteinuria, and hypertension) and first symptoms (hematuria, proteinuria and hypertension) and the kidney survival rate in 239 patients with IgA nephritis without nephrotic syndrome. The morphological and clinical parameters were subjected to multivariate analysis in order to examine their significance with regard to the prognosis. The interstitial fibrosis was proven to be the most important morphological parameter, and the most important clinical parameters were the serum creatinine concentration and the creatinine clearance.

Acute Kidney Injury

Acute renal failure in man: new aspects concerning pathogenesis. A morphometric study.

The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.

ADP-Ribosylation Factor 6