Renovascular hypertension in a patient with systemic lupus erythematosus and secondary antiphospholipid antibody syndrome.
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Angioplasty, Balloon↗
Biomedical subjects
A R Rosenkranz
Publications and source records attributed to A R Rosenkranz.
Cerebral vasculitis in a patient with hereditary complete C4 deficiency and systemic lupus erythematosus.
We describe the case of a female patient with hereditary complete C4 deficiency and systemic lupus erythematosus. She had suffered from lupus nephritis in early childhood. At the age of 23 years she developed severe lupus with skin disease and life-threatening cerebral vasculitis. Her cerebral disease was unresponsive to high-dose steroids, intravenous immunoglobulin, fresh frozen plasma and plasma exchange. Improvement was achieved with immunoadsorption in combination with mycophenolate mofetil. The patient made a complete recovery and is maintained in complete remission on mycophenolate and low-dose steroids.
Adult↗
Four consecutive renal transplantations in a patient with adenine phosphoribosyltransferase deficiency.
We report a patient with complete adenine phosphoribosyltransferase deficiency and urolithiasis, in whom 4 consecutive cadaveric renal transplantations were performed; 2,8-dihydroxyadenine crystal nephropathy recurred within weeks in the first and second graft when the patient was not treated with allopurinol immediately after transplantation. In the third graft, recurrence of disease could be prevented by immediate allopurinol treatment. This graft was lost due to chronic allograft nephropathy without significant crystal deposition. After a fourth transplantation, again without initial allopurinol, the disease recurred following an initial vascular rejection. Addition of allopurinol significantly improved renal function of the 2nd and 4th graft. This case indicates that outcome of renal transplantation in patients with adenine phosphoribosyltransferase deficiency critically depends on immediate postoperative pharmacotherapy with allopurinol, which is able to prevent 2,8-dihydroxyadenine nephropathy in the graft. Furthermore, rapid recurrence of disease without allopurinol seems to be triggered by delayed graft function and acute rejection.
Adenine Phosphoribosyltransferase↗
Variable parathyroid hormone(1-84)/carboxylterminal PTH ratios detected by 4 novel parathyroid hormone assays.
AIM: Parathyroidhormone (PTH) measurement is important in the evaluation of bone disease in patients with chronic renal failure. Large carboxyl-terminal PTH fragments (C-PTH) cross-react with second-generation PTH assays, lead to an overestimation of biologically active PTH, and are evaluated by a combination of second- and third-generation PTH assays. The aim of our study was to examine whether the use of 4 different PTH assays of putatively same specificity leads to comparable results detecting C-PTH fragments. SUBJECTS AND METHODS: In 70 chronic dialysis patients, total PTH and PTH(1-84) were measured in parallel by 4 novel PTH assays (Nichols Advantage Intact PTH and Bio-Intact PTH Chemiluminescence Assay, Nichols Institute Diagnostics, USA, DUO Total and CAP PTH IRMA, Scantibodies Laboratory, USA). The C-PTH concentration was quantitated by subtracting PTH(1-84) from total PTH. Consecutively, the PTH(1-84)/C-PTH ratio was calculated. RESULTS: Nichols Intact PTH and DUO Total PTH assays were highly correlated (r = 0.985), as well as Nichols Bio-Intact and DUO CAP assays (r = 0.984). However, total PTH values measured by the Nichols assay were 30% higher (median (range): 185 (9.9 - 2,332) versus 130 (2.3 - 1,271.1) pg/ml, p < 0.01). PTH(1-84) values, measured by the Nichols Bio-Intact PTH assay were 8% higher compared to the Scantibodies CAP assay (median (range): 79.6 (7.5 - 1,060.9) versus 73.7 (4.4 - 918.9) pg/ml, p = NS). Thirty-six patients had a ratio < 1 measured by the Nichols assays, whereas only 8 patients showed the same ratio when measured by the Scantibodies assays. In 28 patients (40%), contradictory PTH(1-84)/C-PTH ratios were found, showing a ratio < 1 when measured by the Nichols assays, but > 1 when the Scantibodies assays were used. CONCLUSION: In conclusion, our results suggest that the PTH(1-84)/C-PTH ratio cannot be equally used as a predictor of bone turnover when different PTH assays are used. Depending on those assays, differences in total PTH values mathematically lead to varying amounts of C-PTH fragments resulting in variable, even contradictory PTH(1-84)/C-PTH ratios.
Aged↗
Serum proteins modified by neutrophil-derived oxidants as mediators of neutrophil stimulation.
Reactive oxygen intermediates (ROI) released during inflammation may act as important mediators of neutrophil effector functions. The objective of this investigation was to evaluate the influence of ROI generation on neutrophil adhesion molecule regulation and degranulation. Induction of the neutrophil oxidative burst via Fcgamma receptor cross-linking was accompanied by up-regulation of neutrophil surface CD11b, CD35, and CD66b only in the presence of selected serum proteins, such as purified human C4, C5, or human serum albumin (HSA). Scavenging of ROI attenuated protein-dependent receptor regulations. Moreover, exogenous hydrogen peroxide was effective to increase neutrophil CD11b expression in a protein-dependent way. HSA exposed to neutrophil-derived ROI displayed signs of oxidative modification in terms of carbonyl formation. Such modified HSA transferred to resting neutrophils bound readily to the cell surface and effected receptor modulation as well as cellular spreading. In contrast, neither native HSA nor HSA protected against oxidation by the tocopherol analog Trolox exhibited agonistic properties. In conclusion, we demonstrate that neutrophil-derived ROI modify selected serum proteins, which, in turn, act as proinflammatory mediators of neutrophil stimulation.
Blood Proteins↗
Nonphlogistic clearance of late apoptotic neutrophils by macrophages: efficient phagocytosis independent of beta 2 integrins.
Neutrophils undergo constitutive death by apoptosis, leading to safe nonphlogistic phagocytosis and clearance by macrophages. Recent work has shown that before secondary necrosis, neutrophils exhibiting classical features of apoptosis can progress to a morphologically defined late apoptotic state. However, whether such neutrophils could be safely cleared was unknown. We now report that human late apoptotic neutrophils could be purified from cultured neutrophil populations undergoing constitutive death and were subsequently ingested by human monocyte-derived macrophages by serum-independent mechanisms that did not trigger the release of IL-8 or TNF-alpha. Such ingestion was specifically inhibited by Abs to thrombospondin-1 and the alpha(v)beta(3) vitronectin receptor. Murine bone marrow-derived macrophage phagocytosis of late and early apoptotic neutrophils occurred by similar mechanisms, proceeding with the same efficiency as that observed for wild-type controls when macrophages from [alpha(m)](-/-) or [beta(2)](-/-) mice were used. We conclude that specific nonphlogistic, beta(2) integrin-independent mechanisms involving thrombospondin-1 and alpha(v)beta(3) allow macrophages to ingest late apoptotic neutrophils without eliciting inflammatory cytokine secretion.
Animals↗
Complement-dependent acceleration of apoptosis in neutrophils by dialyzer membranes.
Recently, we have shown that cuprophan (CU) causes receptor modulation by a C5-dependent mechanism, which is activated by neutrophil-derived reactive oxygen intermediates. The objective of our study was to evaluate the contribution of dialyzer membranes to the induction of apoptosis in human neutrophils [polymorphonuclear cells (PMNs)]. PMNs harvested from healthy donors were incubated with hollow fibers from a biocompatible membrane polysulfone (PS) and a bioincompatible membrane CU, all in the presence of 25% human serum. After 4, 8, and 12 hours of incubation at 37 degrees C, apoptosis was quantitated by counting the numbers of cells showing features of apoptosis on cytospins by light microscopy and also by flow cytometry using propidium iodide nuclear staining. Compared with PMNs incubated with serum alone, cells cultured with fibers of PS demonstrated a higher percentage of apoptosis. Fibers from CU dialyzers led to a more pronounced induction of apoptosis in PMNs, which was significantly higher compared with PS. This effect was partly mediated by heat-sensitive serum products and depended on the presence of divalent cations. In contrast to the recently described C5-dependent pathway in PMN receptor modulation by CU, this effect seemed to depend on the presence of the complement factor C3. In conclusion, our results indicate that besides the well-known accelerated apoptosis of PMNs in uremia, both biocompatible and bioincompatible dialyzer material itself can accelerate apoptosis in human PMNs.
Apoptosis↗
[Hypertension and chronic renal insufficiency].
In the last ten years the incidence of patients with terminal renal insufficiency has been continuously rising. A decrease in numbers is expected through vigorous treatment of systolic and diastolic blood pressure. Any antihypertensive therapy--independent of the substance group used--decreasing blood pressure, will slow down the progression of renal insufficiency. Whenever possible, an angiotensin-converting enzyme inhibitor should be part of the treatment, since these drugs have been shown to be renoprotective beyond their antihypertensive effect in certain renal diseases. This review will discuss pathogenesis, treatment and the use of renoprotective drugs in hypertensive patients with chronic renal failure.
Angiotensin-Converting Enzyme Inhibitors↗
Multiple-dose pharmacokinetics of cefepime in long-term hemodialysis with high-flux membranes.
OBJECTIVE: Among uremic patients on hemodialysis, infectious complications leading to a high incidence of morbidity and mortality are a well-documented problem. In this multi-dose study, the safety, tolerance, and pharmacokinetics of cefepime during high-flux hemodialysis were investigated and an improved dosing schedule is presented. METHODS: Six long-term hemodialysis patients received 2 g cefepime i.v. at the end of hemodialysis three times per week. RESULTS: Trough levels of cefepime were 23.3 +/- 7.3 mg/l and peak serum concentrations 165.6 +/- 48.7 mg/l. After 3.5 h of high-flux hemodialysis, 72.2 +/- 6.4% of cefepime was eliminated. The intradialytic half-life was 1.6 +/- 0.29 h and the interdialytic half-life 22.0 +/- 2.14 h. CONCLUSION: A dosage of 2 g cefepime after each hemodialysis session achieved drug levels well above the minimal inhibitory concentration (MIC)90 for most of the target pathogens. Thus, the described dosing schedule is an efficient and cost saving antmicrobial therapy for severe infections in long-term hemodialysis patients with no residual renal function.
Adult↗
Recombinant tissue plasminogen activator is a useful alternative to heparin in priming quinton permcath.
Soft, cuffed, implantable central venous catheters such as the Quinton Permcath (Quinton Instrument Co, Seattle, WA) are increasingly used as permanent access in patients with end-stage renal disease. Their major limitations, besides infection, are thrombosis and inadequate blood flow. To prevent those complications, heparin is conventionally used for priming the Quinton Permcath between dialysis sessions. In this study, we compared recombinant tissue plasminogen activator (rTPA) with heparin for priming the Quinton Permcath in a prospective, randomized, crossover design. Twelve patients were randomly assigned to receive 2,000 IU of heparin or 2 mg of rTPA injected into each catheter lumen at the end of each dialysis session over a period of 4 months, followed by a switch to the other substance. Blood flow rate (flow), venous pressure (VP), and arterial pressure (AP) were monitored at each dialysis session hourly. Flow was significantly greater (P = 0.0001) with rTPA (mean +/- SD, 237.7 +/- 18.1 and 231.6 +/- 12.4 mL/min for the first and second 2 months, respectively) compared with heparin (208.5 +/- 10.1 and 206.9 +/- 14.2 mL/min for the first and second 2 months, respectively). VP was significantly less (P = 0.0001) with rTPA (135.4 +/- 8.2 and 140 +/- 15.2 mm Hg for the first and second 2 months, respectively) compared with heparin (160.5 +/- 16.1 and 159.2 +/- 20.7 mm Hg for the first and second 2 months, respectively). AP was significantly greater (P = 0.0002) with rTPA (-113.5 +/- 11.8 and -115.9 +/- 12.7 mm Hg for the first and second 2 months, respectively) compared with heparin (-136.5 +/- 23.3 and -134.7 +/- 25.8 mm Hg for the first and second 2 months, respectively). In addition, fewer complications (flow problems, clotting, and need for fibrinolysis) occurred in the rTPA period. These results show that rTPA is superior to heparin for priming the Quinton Permcath between hemodialysis sessions and can be used as a valuable alternative to conventional heparin in selected patients.
Aged↗
Regulatory interactions of alphabeta and gammadelta T cells in glomerulonephritis.
BACKGROUND: Several lines of evidence suggest that cellular immune mechanisms contribute to glomerulonephritis. METHODS: The roles of alphabeta and gammadelta T cells in the pathogenesis of glomerulonephritis were investigated in a model of nephrotoxic nephritis in mice deficient in either T-cell population [T-cell receptor (TCR)beta and TCRdelta knockout mice]. The model, induced by the injection of rabbit anti-mouse glomerular basement membrane antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. RESULTS: Mice deficient in either alphabeta or gammadelta T cells developed minimal proteinuria and glomerular lesions and had a significant reduction in macrophage accumulation compared with wild-type mice. In gammadelta T-cell-deficient mice, circulating levels and glomerular deposition of autologous IgG were comparable to wild-type levels, while alphabeta T-cell-deficient mice had no autologous IgG production. Autologous antibody production was not required for the development of glomerulonephritis since mice that lack IgG and B cells (micro-chain-/-) developed similar proteinuria to that observed in wild-type mice. CONCLUSIONS: These studies suggest a proinflammatory role for both alphabeta and gammadelta T cells in glomerular injury, independent of the humoral response. This is the first demonstration, to our knowledge, that both T-cell subsets contribute to the progression of a disease, and it suggests that complex regulatory interactions between alphabeta and gammadelta T cells play a role in glomerular injury.
Animals↗
Proteinuria in the transplanted patient.
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Disease Progression↗
Mechanisms of hypertension after renal transplantation.
Hypertension is extremely prevalent after renal transplantation, affecting up to 70% of all patients. An elevation in blood pressure is associated with an increased cardiovascular risk and may also contribute to chronic allograft failure. Renal transplantation provides interesting insights into the pathogenesis of hypertension. Experimental and human data show that the kidney is an essential organ for blood pressure regulation. In clinical practice a differential diagnosis that is based on excretory allograft function has proved useful.
Animals↗
Carl Ludwig Award 2000: experimental glomerulonephritis: the use of genetically deficient mice to elucidate the role of leukocytes and leukocyte adhesion receptors.
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Animals↗
P-selectin deficiency exacerbates experimental glomerulonephritis: a protective role for endothelial P-selectin in inflammation.
P-selectin is a leukocyte adhesion receptor present in endothelial cells and platelets. We examined the role of P-selectin in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) glomerulonephritis using P-selectin-deficient mice and chimeric mice expressing P-selectin only in platelets or endothelial cells. P-selectin-deficient mice exhibited more severe glomerular damage with increased interstitial mononuclear leukocytic infiltrates, and had significantly increased proteinuria and mortality when compared to wild-type mice. P-selectin on the endothelium was predominantly responsible for protection from the exacerbated disease, because chimeric mice with endothelial P-selectin, and not mice with platelet P-selectin, showed glomerular injury similar to that in wild-type animals. Levels of soluble circulating P-selectin were increased in nephritic wild-type mice and in chimeric mice with endothelial P-selectin, but not platelet P-selectin. Levels of soluble P-selectin, which has been shown to be anti-inflammatory in vitro, were inversely associated with the severity of disease. P-selectin was not expressed in the endothelium of the glomerulus or interstitium. Thus, the protective effect in wild-type mice may be accounted for, in part by soluble P-selectin shed by non-renal endothelial cells, although other endothelial P-selectin-dependent mechanisms cannot be ruled out.
Animals↗
Polymorphonuclear granulocyte stimulation by cellulose-based hemodialysis membranes.
Hemodialysis with cellulose-based membranes is associated with an array of adverse reactions, including leukopenia, pulmonary sequestration and dysfunction of leukocytes. Activation of the alternative pathway of complement due to direct contact of plasma with dialysis membrane is considered to be responsible for the induction of these side effects. In recent years, evidence has accumulated that other neutrophil effector functions such as reactive oxygen intermediate production play an important role as well. Here the importance of burst formation in cooperation with other inflammatory effector functions in the mechanisms of hemodialysis-related adverse effects will be discussed.
CD11 Antigens↗
Novel C5-dependent mechanism of neutrophil stimulation by bioincompatible dialyzer membranes.
The objective of the study was to evaluate the contribution of reactive oxygen intermediate formation for receptor modulation on neutrophils by the cellulosic dialyzer membrane cuprophan (CU). In patients dialyzed with CU, CD11b and CD66b upregulation on neutrophils (by 104.3 +/- 37.9% and 85.7 +/- 31.1%, respectively), and a downregulation of L-selectin (by 44.9 +/- 26.9%) was seen, whereas expression of CD11a remained unaltered. Hemodialysis with polysulfone did not bring about major changes in surface receptor expression. In vitro incubation of isolated neutrophils in the presence of serum with hollow fibers of CU or polysulfone showed similar results: Only CU resulted in upregulation of CD11b and CD66b expression (by 65.5 +/- 18.7% and 60.1 +/- 24%) and a decrease in CD62L expression (by 60.6 +/- 18.2%). In contrast to receptor alterations, generation of reactive oxygen intermediate by CU occurred in the absence of serum. Inhibition experiments with soluble complement receptor 1, which produced only partial inhibition of receptor up-/down-regulation, indicated the existence of also other than alternate complement-dependent mechanisms for neutrophil activation. By using C5-depleted serum instead of normal human serum, up-/down-regulation of CD11b, CD62L, and CD66b by CU was dramatically reduced, whereas C3-depleted serum did not produce that effect. C5-deficient serum repleted with purified C5, as well as purified C5 alone, was able to induce receptor modulation by CU comparable to normal human serum. L-Methionine, a specific inhibitor for the oxidative activation of C5, blocked the modulatory effect of CU in assays with purified C5 as well as with serum. As a result, in addition to the alternative pathway of complement, a C5-dependent mechanism probably activated by neutrophil-derived reactive oxygen intermediate leads to receptor modulation and subsequent generation of the well known side effects of bioincompatible dialyzer membranes.
Adult↗
Impaired mast cell development and innate immunity in Mac-1 (CD11b/CD18, CR3)-deficient mice.
Mac-1 (CD11b/CD18, CR3), a beta2 integrin expressed on leukocytes, is important in leukocyte migration. We demonstrate that Mac-1 is also expressed on peritoneal mast cells and LPS stimulated bone marrow-derived cultured mast cells, and that Mac-1-deficient mice, which lack this receptor, have significant reductions in the numbers of mast cells resident in the peritoneal cavity, peritoneal wall, and dorsal skin. The reduced numbers of mast cells in Mac-1-deficient mice may have important functional consequences, in that Mac-1-deficient mice exhibit significantly increased mortality after cecal ligation and puncture, a model of acute septic peritonitis in which host resistance has been shown to be dependent on both mast cells and complement. These findings demonstrate that Mac-1 is required for the expression of normal levels of mast cells in the peritoneal cavity, peritoneal wall, and certain areas of the skin, as well as for maintaining adequate mast cell-dependent host defense against bacterial infection.
Acute Disease↗