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H Kreis

Publications and source records attributed to H Kreis.

At least 163 records · Page 9Linked to original sources
PubMed1986

Role of antibodies directed against tubular basement membranes in human renal transplantation.

Direct immunofluorescence studies of graft biopsies from 662 renal transplant recipients demonstrated linear IgG deposition along tubular basement membranes (TBM) in 18 cases. In ten of them, circulating anti-TBM antibodies, whose detectable levels varied from 1/4 to 1/100, were demonstrated by indirect immunofluorescence on normal human kidneys. These antibodies reacted with every human kidney tested and in two cases, it could be demonstrated that they recognized the TBM of the patient's own end-stage kidney. Hence, they reacted as autoantibodies. Circulating anti-TBM antibodies were detected within the first 6 months after transplantation, remained present for an average of 3 months, and never recurred once they had disappeared. Serial biopsies demonstrated the loss of IgG linear fixation on TBM. Neither tubular nor interstitial injury was significantly associated with the presence of anti-TBM antibodies, and the transplant survival was not different in these patients who developed anti-TBM antibodies compared to our entire population of transplant biopsies.

Actuarial Analysis↗
PubMed1986

Prophylactic use of OKT3 monoclonal antibody in cadaver kidney recipients. Utilization of OKT3 as the sole immunosuppressive agent.

We describe the first clinical trial of OKT3, a monoclonal anti-T-cell antibody, for prevention of kidney transplant rejection. 13 patients receiving a first cadaveric kidney transplant were randomly assigned to conventional treatment with azathioprine and high-dose steroids (7 patients) or to treatment with daily injection of OKT3 alone (6 patients). The first OKT3 injection resulted in a dramatic decrease in T3+, T4+, and T8+ cells, while patients simultaneously experienced fever, chills, and diarrhea. These symptoms did not recur with subsequent injections. All six OKT3-treated patients had a rejection necessitating introduction of steroids 12.8 +/- 2.9 days after surgery. Rejection was related to appearance of anti-OKT3 antibodies leading to disappearance of detectable OKT3 in the serum. Modulating (T3-, T4+ or T3-, T8+) cells were observed in all patients but were functionally inactive. As no rejection was observed before day 9 posttransplant, despite the lack of additional immunosuppressive agents, we conclude that OKT3 is a powerful, well-tolerated immunosuppressive agent. However, it is highly immunogenic and anti-OKT3 antibodies lead to loss of clinical effectiveness in this protocol. The use of OKT3 alone for prevention of kidney graft rejection cannot be recommended until a method for reducing the effects of anti-OKT3 immunization is developed.

Acute Disease↗
PubMed1986

Linear glomerular IgG fixation in renal allografts: incidence and significance in Alport's syndrome.

Twelve of 767 renal allograft recipients developed linear fixation of IgG along the glomerular basement membrane (GBM) by direct immunofluorescence technique. This was associated with linear fixation along the tubular basement membrane in 7 of them. Circulating anti-GBM antibodies were not detected by indirect immunofluorescence or radioimmunoassay in any patient whereas anti-TBM antibodies were found in 2 of 4 with linear TBM fixation. Among the 12 patients with linear GBM fixation, 5 had Alport's syndrome; the 7 others had various renal diseases, excluding anti-GBM nephritis. Among the 767 patients, 34 had Alport's syndrome or variants (i.e., 4.5%). The incidence of linear GBM fixation is much higher in Alport's syndrome than in other renal diseases. Linear GBM fixation was not clearly related to anti-GBM antibodies and was not accompanied by significant deterioration of graft function. These findings may be relevant, however, to the missing GBM antigen in Alport's syndrome.

Adult↗
PubMed1986

[Destruction of the allograft].

Allograft rejection is an immunological process which appears as a two-step phenomenon: during the first step, alloantigens are recognized as foreign, or "non-self", and production of "killer agents" is initiated. During the second step, the target organ is invaded by these killer agents and destroyed. Recognition, attack and destruction of the target are the different phases of rejection step II, and its clinical and/or pathological expression is generally referred to as a rejection episode. There is only one mechanism leading to the destruction of the allograft. However, its clinical or pathological expression can vary according to its severity and to the predominance of one of the effector agents (antibody or cytotoxic cell). Although permanent, the rejection process usually progresses in a wave motion; first waves are sharp and severe, but with time they become smoother and less severe. Rejection episodes are, therefore, generally described as hyperacute, acute and chronic. Endothelial cells of the allograft arteries are the main target although all the various histological structures of the graft can be injured. Immuno-suppressive agents as well as good histocompatibility can drastically modify both the course of rejection and its expression.

Acute Disease↗
PubMed1985

Comparison of several atherogenicity indices by the analysis of serum lipoprotein composition in patients with chronic renal failure with or without haemodialysis, and in renal transplant patients.

We investigated serum lipoproteins in uraemic and kidney transplant patients, and compared the results with those from normal persons. In uraemic patients, with or without haemodialysis, and in kidney transplant patients, the ratio of HDL-cholesterol to total cholesterol minus HDL-cholesterol, the ratio of HDL-phospholipids to total phospholipids minus HDL-phospholipids, and the ratio of apolipoprotein A to apolipoprotein B are all decreased, though to different extents, when compared with healthy control subjects. Furthermore, important differences exist in the relative HDL composition between the 3 patient groups and healthy control subjects. Thus, the ratio of apolipoprotein A/HDL-cholesterol and that of HDL-cholesterol/HDL-phospholipids are significantly altered in uraemic haemodialyzed patients, while the ratio of apolipoprotein A/HDL-phospholipids is normal. By contrast, the 3 ratios are normal in uraemic undialyzed patients, and the 2 ratios, apolipoprotein A/HDL-cholesterol and apolipoprotein A/HDL-phospholipids are normal in renal transplant patients. The last ratio, HDL-cholesterol/HDL-phospholipids, is increased in this group of patients. Thus, it appears that HDL-cholesterol, HDL-phospholipids, and total apolipoprotein A represent different aspects of the same lipoprotein. The determination of all three parameters could lead to a different approach in the evaluation of the so-called cardiovascular risk, at least for uraemic patients and renal transplant patients.

Arteriosclerosis↗
PubMed1985

[Urologic complications in adult kidney recipients].

In this article, the authors study the complications following all the kidney transplantations performed in their hospital between 1969 and 1980. During this period, 580 patients underwent 637 transplantations, including 120 (19%) with urological complications: urinary fistulae (49%), stenoses (28%), vesicorenal refluxes (13%), and calculi (10%). The postoperative mortality rate was 2.7%. Some patients presented with two or more complications. The circumstances of the discovery of the sequelae and the treatment prescribed are described in each case and a comparative study is made with other transplantation centers.

Adult↗
PubMed1984

Unusually restricted anti-isotype human immune response to OKT3 monoclonal antibody.

The unusual anti-mouse immunoglobulin (Ig) sensitization of a renal allograft recipient who was treated prophylactically with the anti-T cell monoclonal antibody OKT3 (IgG2a) is reported. Whereas in most patients, the injection of OKT3 (5 mg/day, i.v. for 13 days) induces the rapid appearance of neutralizing anti-OKT3 antibodies, the patient reported here did not show the signs of conventional anti-OKT3 sensitization. High levels of circulating OKT3 persisted and no OKT3+ lymphocytes reappeared during the whole treatment period. Moreover, no IgG or IgM anti-OKT3 antibodies were detected at any time, using a specific enzyme-linked immunosorbent assay. However, an atypical anti-isotype response was evidenced in this subject whose Ig were shown by indirect fluorescence to bind to normal T cells coated with OKT3 or with other anti-T cell murine monoclonal antibodies carrying the IgG2a isotype (no reactivity was observed with IgG1 or IgG2b molecules). The patient's Ig did not bind to normal T cells coated with F(ab')2 fragments of OKT3 and did not inhibit the binding of OKT3 to its target antigen indicating that they reacted with the Fc fragment of the OKT3 molecule. Additionally, and probably explained by this unusual anti-OKT3 response, the patient's Ig were shown to inhibit the phytohemagglutinin-induced proliferation of normal lymphocytes, to bind under selected in vitro conditions to normal T cells and lastly to enhance the antigenic modulation induced in vitro by OKT3 on its membrane receptor.

Antibodies, Monoclonal↗
PubMed1984

Nonsteroid antiinflammatory agents as a substitute treatment for steroids in ATGAM-treated cadaver kidney recipients.

A nonsteroid antiinflammatory agent (Ibuprofen) was used in a controlled randomized study to determine its ability to replace steroids in the prophylaxis of cadaveric kidney rejection. Thirty-three cadaver kidney recipients were randomly assigned either to a control group (16 patients) receiving azathioprine, high doses of prednisolone, and antithymocyte globulin (ATGAM) for three months, or to an experimental group (17 patients) receiving azathioprine and ATGAM according to the same protocol, ibuprofen instead of steroids. The frequency of rejection was higher in the experimental group (2.18 episodes per patient) than in the control group (1.44 episodes per patient). Nevertheless, in the experimental group 5 patients had no early rejection episode, 60% of early rejections were totally reversible without steroids, and 3 patients never received steroids at all during the first year and had normal renal function and biopsies. Steroids had to be introduced in the treatment of 14 patients, but after an average period of 32.5 days after surgery OKT3+ cell level was higher in the experimental group than in the control group, but similar to the OKT3+ cell level of patients receiving conventional therapy without ATGAM. Whatever the type of treatment, an increase in the OKT4+/OKT8+ ratio was associated in most cases with increased serum creatinine values. Conversely, a decreased OKT4+/OKT8+ ratio associated with renal failure was found in cases showing biological evidence of cytomegalovirus infection.

Adult↗
PubMed1983

Pyridoxal 5'-phosphate deficiency in uremic undialyzed, hemodialyzed, and non-uremic kidney transplant patients.

In this study, we have investigated plasma pyridoxal 5'-phosphate (PLP) concentrations in undialyzed and dialyzed uremic patients and in kidney transplant subjects, using an enzymatic technique with thermal deproteinization to liberate PLP from plasma proteins. The specificity of the reaction indicates no interference with pyridoxal and only 3% interference with pyridoxamine phosphate. In 17 hemodialyzed patients, a deficiency of about 50% of plasma PLP concentration is found as compared to 25 healthy subjects (22.2 +/- 2.47 vs. 48.8 +/- 3.00 nmol . l-1), as mean +/- SEM). In seven undialyzed uremic patients with end-stage renal failure, the plasma PLP concentration is also decreased (29.3 +/- 1.74 nmol . l-1). The absence of PLP in plasma ultrafiltrates demonstrates that no loss of PLP occurs due to hemodialysis. The daily oral supplementation with 250-750 mg pyridoxal induces a supraphysiological increase in plasma PLP concentration in hemodialyzed as well as in undialyzed patients. In 116 non-uremic kidney transplant subjects, the mean plasma PLP concentration was 33.8 +/- 3.50 nmol . l-1). In 65% of these patients, a marked deficit (below 20 nmol . l-1) was observed. In conclusion, uremic patients have a deficient vitamin B6 state. Its correction with pyridoxal to restore physiological plasma PLP concentration necessitates oral supplementation with lower doses that those widely used at present. In kidney transplant patients a similar plasma PLP deficiency is observed in the absence of chronic renal failure.

Adult↗
PubMed1983

Interest in and limitations of monoclonal anti-T-cell antibodies for the follow-up of renal transplant patients.

The OKT series of anti-T-cell monoclonals has been used on 442 occasions in 41 renal allograft recipients in a 6-12 month follow-up study. Standard immunosuppressive therapy (including antithymocyte globulin in 26 patients) tended to decrease the helper-inducer/suppressor-cytotoxic cell ratio (OKT4/OKT8). Conversely, 71% of 35 renal failure episodes were associated with increased OKT4/OKT8 ratios. Twenty-three percent of renal failure episodes were associated with dramatically decreased OKT4/OKT8 ratios. At least half of these cases could be explained by a cytomegalovirus infection. In fact, similar infections were found in 6 out of 17 patients with low OKT4/OKT8 values in the absence of renal failure. These results prompt us to use anti-T cell monoclonals for the diagnosis of rejection because only nine episodes of transient increase in the OKT4/OKT8 ratio were observed in the absence of rejection. The interest of this new method for the immunological follow-up of transplanted patients is, however, limited by the difficulty in interpreting a significant percentage of tests because of (1) the presence of doubly labeled cells (OKT4+OKT8+) or the significant discrepancy between the number of OKT3+ cells and total cells labeled with OKT4 and/or OKT8 antibodies; (2) gross lymphocytopenia--most often observed in patients receiving antithymocyte globulins plus steroids; and (3) the clinically unexplained shifts in the T cell subset ratios mentioned above.

Antibodies, Monoclonal↗