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Biomedical subjects

R A Koene

Publications and source records attributed to R A Koene.

At least 163 records · Page 9Linked to original sources
PubMed1988

Prednisolone can increase glomerular permeability to proteins in nephrotic syndrome.

In patients with a nephrotic syndrome administration of prednisolone causes an increase of proteinuria. To elucidate the mechanism of this effect we have studied the acute proteinuric effect of prednisolone, 125 to 150 mg intravenously, in nine patients (7 M, 2F) with a nephrotic syndrome. Mean age (+/- SD) of the patients was 53 +/- 6 years, mean endogenous creatinine clearance 104 +/- 30 ml/min, and mean proteinuria 7.7 +/- 3.0 g/24 hr. After administration of prednisolone, urinary total protein excretion rose in all patients from a mean (+/- SEM) of 4.89 +/- 0.59 mg/min before to 9.09 +/- 0.99 mg/min at five hours after administration (P less than 0.01). Glomerular filtration rate (inulin clearance), effective renal plasma flow (PAH clearance), and filtration fraction did not change significantly. The increases of urinary excretion of albumin (median %: +92%), IgG (median %: +88%), and transferrin (median %: +76%) were comparable and correlated significantly. Urinary excretion of beta 2-microglobulin did not change significantly however. We conclude that intravenous administration of prednisolone to patients with a nephrotic syndrome causes an increase in urinary protein excretion rate which cannot be explained by changes in renal hemodynamics or tubular protein reabsorption, and which therefore must be the result of a change in glomerular permselectivity characteristics.

Capillary Permeability↗
PubMed1988

Antihypertensive effect of beta blockade in renal transplant recipients with or without host kidneys.

Host kidneys may contribute considerably to hypertension after renal transplantation. Their role in sustaining hypertension is more prominent if glomerulonephritis (GN) than if interstitial nephritis (IN) is the original renal disease. We compared the antihypertensive effect of beta-blockade in IN (n = 10) and GN (n = 19) hypertensive renal transplant recipients with host kidneys in situ with those who had undergone bilateral nephrectomy (BN, n = 10). Pretreatment blood pressures were comparable in BN, IN, and GN patients, being 165 +/- 6/108 +/- 3, 172 +/- 5/104 +/- 3, and 161 +/- 3/104 +/- 1, mmHg, respectively. Blood pressure did not change on beta-blockade in BN patients, whereas it decreased significantly more (P less than 0.001) in GN than in IN patients, changes of mean arterial pressure being -107 +/- 1.0, -14.9 +/- 1.3, and -6.8 +/- 1.6%, respectively. This failure to respond to beta-blockade in patients without host kidneys may be related to low activity of the renin-angiotensin system or to functional denervation of the grafted kidney. Further investigations of this phenomenon may clarify the mechanism of antihypertensive action of beta-blockade as well as the nature of hypertension after renal transplantation.

Adrenergic beta-Antagonists↗
PubMed1988

Diuretic and natriuretic effects of nifedipine in healthy persons.

1. We have studied the diuretic and natriuretic effects and the tubular site of action of nifedipine using free water clearance (CH2O) and lithium clearance. 2. We have compared the effects of nifedipine (10 mg p.o.) with those of placebo and of frusemide (40 mg p.o.) in seven healthy volunteers during maximal water diuresis. 3. Compared with placebo, nifedipine caused a significant rise in urinary flow rate and CH2O, paralleled by significant increases in fractional excretion of sodium and lithium. The rise in sodium excretion was not accompanied by an increase in potassium excretion. 4. Frusemide caused increases in sodium and lithium excretion, comparable with the effects seen after nifedipine. CH2O did not change however. 5. Our study demonstrates that nifedipine has a clear diuretic and natriuretic effect in healthy volunteers, which is predominantly established by interference with proximal tubular sodium reabsorption. Lithium clearance did not allow us to differentiate between nifedipine and frusemide effects, thus questioning the reliability of lithium as a marker of proximal tubular sodium reabsorption.

Adult↗
PubMed1988

Renal clearance of pancreatic and salivary amylase relative to creatinine clearance in patients with renal disease and proteinuria.

To study the charge-selective properties of the glomerular filter in renal disease, we measured the fractional clearance, relative to creatinine clearance (ECC), of the amylase isoenzymes pancreatic amylase and salivary amylase, which have identical size but different charge. In 63 healthy subjects the mean (and SD) fractional excretion of pancreatic amylase, 4.07% (1.24%), was fourfold that of salivary amylase: 1.02% (0.54%). For 29 patients with renal disease and proteinuria, the mean fractional excretion of pancreatic amylase was significantly lower, 3.31% (1.94%), and that of salivary amylase significantly higher, 2.06% (1.41%), than in controls. In these patients, fractional excretions of both these isoenzymes were negatively correlated with urinary excretion of beta 2-microglobulin and ECC. Evidently, differences in clearances of pancreatic and salivary amylase are a consequence of differences in charge-related glomerular filtration. The relative increase of salivary amylase clearance in patients with renal disease and proteinuria is most probably caused by a loss of the charge-selective properties of the glomerular basement membrane.

Adult↗
PubMed1988

Antiglomerular basement membrane nephritis in the mouse. Study on the role of complement in the heterologous phase.

The role of complement was examined in a model of antiglomerular basement membrane nephritis in the mouse, induced by intravenous injection of goat anti-mouse glomerular basement membrane serum, and characterized by early glomerular lesions and a dose-dependent albuminuria. We compared the reaction after injection of the antiserum in complement-normal B10.D2 new mice with that in congenic, congenitally C5-deficient B10.D2 old mice, and in both strains after C3 depletion by treatment with cobra venom factor. The dose-dependent albuminuria was not affected by the absence of complement activation. Also, deficiency of C3 and/or C5 had no inhibitory effect on the histologic glomerular lesions: it did not reduce the influx of polymorphonuclear granulocytes in the glomerular capillary vessels, nor prevented the eventual intravascular coagulation. We conclude that complement-independent mechanisms are involved in the development of the heterologous phase of antiglomerular basement membrane nephritis in the mouse.

Albuminuria↗
PubMed1988

Renal hemodynamic effects of a short-term high protein and low protein diet in patients with renal disease.

The renal hemodynamic effects of short-term protein loading and short term protein restriction were studied in patients with renal disease. Eleven patients adhered to a high protein diet (1.8 g/kg/day) and, subsequently, to a low protein diet (0.6 g/kg/day) for four weeks each. Renal hemodynamics were studied at the end of the respective dietary periods. Glomerular filtration rate (inulin clearance) did not change significantly (delta %: -1.5 +/- 5.4%; mean +/- s.e.m.), whereas endogenous creatinine clearance was lower on the low protein diet (delta %: -7.8 +/- 2.8%; p less than 0.02), suggesting an interference with the tubular secretion of creatinine. Effective renal plasma flow was significantly lower on the low protein diet (223.7 +/- 47.6 ml/min vs 282.1 +/- 67.1 ml/min; delta %: -15.4 +/- 4.9%; p less than 0.02). As a result, filtration fraction increased from 0.18 +/- 0.01 on the high protein diet to 0.22 +/- 0.02 on the low protein diet (p less than 0.01). The low protein diet caused a significant decrease in protein excretion from 4.0 +/- 0.9 g/24 h to 3.1 +/- 0.7 g/24 h (p less than 0.02). Our study demonstrates that renal hemodynamic responses to more sustained protein loading and protein restriction differ from the reported responses to acute protein loading. Different mechanisms may be involved. In this light it is doubtful if the renal hemodynamic response to acute protein loading can predict a beneficial effect of protein restriction.

Adult↗
PubMed1987

A new photometric method for the quantitation of Fc receptors for murine IgG1 on human monocytes and cell lines.

We have previously shown a polymorphism of human Fc receptors for mouse IgG1 using an EA rosette technique in which human erythrocytes sensitized with a murine IgG1 monoclonal antibody against glycophorin A acted as indicator cells. We now describe a method to quantitate this EA rosetting using the pseudoperoxidase activity present in erythrocytes. This photometric assay allows the sensitive quantitative determination of Fc receptor expression on human monocytes and cell lines. Not only the human Fc receptor for murine IgG1 can be studied in this way, but the method can also be applied to other Fc receptors. An important factor in this type of rosette assay appears to be the amount of negative charge present on the surface of the indicator erythrocytes. Using alcian blue as a probe, we found that this negative charge is higher on human erythrocytes than on sheep erythrocytes, which may contribute to a better signal-to-noise ratio. The method described facilitates the characterization of Fc receptors and permits the rapid screening of monoclonal anti-Fc receptor antibodies.

Absorption↗
PubMed1987

Effects of monoclonal anti-H-2Ld and anti-H-2Dd alloantibodies in the immunological enhancement of skin grafts and neonatal heart grafts in the mouse.

Three anti-H-2Ld and two anti-H-2Dd monoclonal alloantibodies were analyzed for their capacity to enhance skin graft and neonatal heart graft survival. Of two anti-H-2Ld antibodies with the same specificity but with different isotypes, IgG2a antibody 30-5-7S prolonged graft survival in a skin graft combination with an Ld difference, whereas IgM antibodies did not. A second IgG2a antibody, but with a specificity different from 30-5-7S, was ineffective on its own. However, when mixed with 30-5-7S, skin graft survival was augmented as compared with the prolongation by 30-5-7S alone. Enhancement by anti-H-2Ld antibodies was dependent on the extent of the H-2 graft barrier. It was abrogated on extension of the graft barrier to a D-end H-2 difference by using the B10.A----B10.BR combination. Also, anti-Dd antibodies, either alone or in combination with anti-Ld, were ineffective in this skin graft combination. By using the same graft combination but the less immunogenic neonatal heart graft model, anti-Ld antibodies were still ineffective, but both anti-Dd antibodies were able to enhance graft survival from 15 to 22 days. When mixed with anti-Ld antibody 30-5-7S, graft survival was augmented further to 30 days. These results indicate that two kinds of enhancing alloantibodies may be distinguished. One category interacts with immunodominant epitopes on H-2 molecules, but their effectiveness may be limited to a particular H-2 difference, because immunodominance may vary from one graft barrier to another. In the second category, antibodies are ineffective on their own but they are able to potentiate the effects of antibodies of the first kind. These allocations are relative, however, because they are dependent on the type of graft examined.

Animals↗
PubMed1987

Cyclosporin treatment with conversion after three months versus conventional immunosuppression in renal allograft recipients.

In a prospective randomised trial, 72 recipients of cadaver renal allografts received cyclosporin for 3 months followed by azathioprine and prednisone (cyclosporin group), and 71 received azathioprine and prednisone from the day of transplantation (conventional group). Graft survival was better in the cyclosporin group at 3 months and 1 year (93% and 80%) than in the conventional group (83% and 70%). This was not a significant difference. The incidence of acute rejection episodes in the first 3 months was significantly lower in the cyclosporin group (35% versus 77%, p less than 0.00001), as was the number of grafts lost because of immunological failure (1 versus 10, p less than 0.02). After conversion, renal function improved. Only 5 patients had acute rejection after conversion. These episodes were easily reversible in all cases and did not lead to graft loss. The numbers of grafts lost after conversion were similar in the two groups. Conversion of cyclosporin to azathioprine 3 months after renal transplantation is a safe procedure that obviates the long-term toxic effects of cyclosporin.

Acute Disease↗
PubMed1987

Mannitol as an indispensable constituent of an intraoperative hydration protocol for the prevention of acute renal failure after renal cadaveric transplantation.

With its incidence of about 40%, acute renal failure (ARF) is a major problem after cadaveric renal transplantation. We have previously shown that, with moderate hydration (2.5 L) of the recipient, together with rapid infusion of 250 ml of mannitol 20% just before clamp removal, the incidence of ARF decreased to below 10%. Administration of mannitol without hydration was not effective. In a prospective randomized trial we have now investigated whether hydration without mannitol is sufficient to prevent ARF. For this purpose patients were randomly allocated to treatment with moderate hydration with or without mannitol. Furthermore, in both treatment groups recipients were randomized to treatment with cyclosporine or azathioprine. The allocation method used guaranteed an even distribution for 10 important prognostic factors. In the cyclosporine group, the percentage of ARF was significantly lower in mannitol-treated (n = 32) than in glucose-treated patients (n = 32) (19% vs. 54%, P less than 0.01). In the azathioprine group the percentage of ARF was also lower in mannitol-treated (n = 33) than in glucose-treated patients (n = 34) (18% vs. 44%, P less than 0.05). Overall incidence of ARF in both groups was significantly lower in mannitol-treated patients (P less than 0.001). Thus, moderate hydration and administration of 250 ml mannitol 20% just before arterial clamp removal are both indispensable for optimal prevention of ARF after cadaveric renal transplantation.

Acute Kidney Injury↗
PubMed1987

Characterization of two Fc receptors for mouse immunoglobulins on human monocytes and cell lines.

We have previously reported a polymorphism in the mitogenic effect of murine (m) IgG1 anti-CD3 monoclonal antibodies. This polymorphism was genetically determined and could be attributed to polymorphism of the Fc receptor (FcR) for mIgG1 present on human monocytes. We have now extended these studies by quantitating FcR expression on monocytes and cell lines by a recently developed EA rosette assay, using the erythrocyte-associated pseudoperoxidase activity. The data show that the polymorphism of the monocyte FcR for mIgG1 is based on a quantitative rather than an absolute difference. Furthermore, this FcR is specific for mIgG1 and does not bind mIgG2a or mIgG2b nor, surprisingly, human IgG. The expression of this FcR on cell lines correlates with their accessory function in IgG1 anti-CD3-induced T cell proliferation. mIgG2a can inhibit the rosetting of monocytes with erythrocytes sensitized with human IgG. The FcR detected by this rosette technique can interact with all four human IgG subclasses but not with mIgG1 or mIgG2b. The expression of this type of FcR on human cell lines correlates well with their ability to support mIgG2a anti-CD3-induced mitogenesis. These direct measurements of FcR expression support the concept that human monocytes have two independent FcR with affinity for mouse IgG: one receptor specific for mIgG2a (which also binds human IgG), and a second specific for mIgG1.

Animals↗