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Biomedical subjects

K M Koch

Publications and source records attributed to K M Koch.

At least 145 records · Page 8Linked to original sources
PubMed1992

Kidney transplantation in Alport's syndrome: long-term outcome and allograft anti-GBM nephritis.

Anti-glomerular basement membrane (anti-GBM) nephritis occurring in kidneys transplanted in patients with Alport's syndrome (AS) has been reported repeatedly. Therefore, we studied graft survival and course of renal function in all 30 AS patients grafted at Hannover Medical School and compared them with non-diabetic, age and sex matched patients, transplanted on the date closest to the transplantation of the AS patient. Serum creatinine, proteinuria, urinary sediment and anti-GBM antibodies were examined in all AS patients with functioning grafts. Cases of patient or graft loss in the AS group were analyzed retrospectively. One- and five-year patient survival was 100 and 91% in AS and 89 and 78% in controls (p > 0.05, respectively). One- and five-year first graft survival was 79 and 66% in both groups. Graft histology was available in 34 biopsies obtained from 21 kidneys in 15 AS patients. Anti-GBM nephritis was not detected in any of the biopsies. No graft was lost due to anti-GBM nephritis. Anti-GBM antibodies were detectable temporarily only in one AS patient. He also had linear IgG staining in his graft GBM, but no other signs of anti-GBM nephritis. We conclude that patient survival and graft survival in AS patients following kidney transplantation is not different from non-AS patients. Allograft anti-GBM nephritis is a rare complication in patients with Alport's syndrome.

Adult↗
PubMed1992

Glomerular hemodynamics of the clipped kidney: effects of captopril and diltiazem.

Glomerular hemodynamics of the clipped kidney in two kidney-one clip Goldblatt-hypertensive rats were studied by micropuncture techniques after administration of either captopril (20 mg/kg of b.wt./day p.o.) or diltiazem (3 mg/kg of b.wt./hr i.v.). Both drugs decreased mean arterial and poststenotic renal arterial pressure to comparable levels. Total kidney glomerular filtration rate was not significantly different in the three groups (0.78 +/- 0.09 in hypertensive controls, 0.62 +/- 0.11 after captopril and 0.74 +/- 0.07 ml/min/g of kidney weight after diltiazem). Glomerular capillary pressure fell significantly in both treated groups but was lower in captopril-treated animals (60 +/- 2 in hypertensive controls, 45 +/- 2 after captopril and 53 +/- 1 mm Hg after diltiazem, both P < .05 vs. hypertensive controls). Afferent arteriolar resistance was lowered in both treatment groups to the same extent, whereas only captopril decreased efferent arteriolar resistance. Single nephron filtration rate of cortical nephrons was not altered significantly by captopril due to a 96% increase in the ultrafiltration coefficient and a 58% rise in glomerular plasma flow, whereas diltiazem increased ultrafiltration coefficient by 62% but did not affect glomerular plasma flow. These studies indicate that, despite of decreased effective filtration pressure, glomerular filtration rate is well preserved after converting enzyme inhibition. Captopril and diltiazem have different effects on glomerular hemodynamics within the stenosed kidney.

Angiotensin II↗
PubMed1991

Cyclophosphamide pulse therapy in Wegener's granulomatosis.

Twenty-three patients with Wegener's granulomatosis, 15 with daily oral cyclophosphamide therapy and eight with intravenous cyclophosphamide pulse therapy, were studied retrospectively. All patients had involvement of the kidneys and systemic symptoms. Mean monthly cyclophosphamide dose was 1.0 g in the pulse group and 2.7 g in the daily treated group. In all patients remission could be achieved. During 207.5 months of daily oral therapy the following complications were observed: leukopenia, necessitating dose reduction in seven patients, severe infection in one patient, relapses in three patients. During 103 months of intravenous pulse therapy one patient developed leukopenia. No patient had a severe infection. Two relapses were seen. Our data suggest that cyclophosphamide pulse therapy is an effective treatment strategy in patients with Wegener's granulomatosis and kidney involvement. It offers the chance of bladder protection and marked total dose reduction, possibly decreasing the risk of malignancies.

Administration, Oral↗
PubMed1991

Hypertension as a possible complication of recombinant human erythropoietin therapy.

The analysis of the hemodynamics accompanying correction of renal anemia by rhEPO shows that--although they behave qualitatively as in nonuremic anemic patients--cardiac output and peripheral resistance may change inadequately and thereby cause a rise of blood pressure. The underlying mechanisms are not yet fully understood but to a great part may be related to preexisting pathology due to a history of longlasting hypertension. In some patients the development of hypertension may only represent a temporary phenomenon of hemodynamic dysregulation. To avoid cardiovascular complications the following should be considered: Patients with a history of hypertension, even if they are normotensive in the anemic state, are at a higher risk of developing hypertension during therapy with rhEPO. Hypertensive complications may be rare events when anemia is corrected slowly. In case of the development or aggravation of hypertension a reduction of the target hematocrit is indicated.

Anemia↗
PubMed1991

Clearance and synthesis rates of beta 2-microglobulin in patients undergoing hemodialysis and in normal subjects.

Retention of beta 2-microglobulin in patients undergoing hemodialysis is associated with a beta 2-microglobulin-derived amyloidosis. Removal of beta 2-microglobulin by renal replacement therapy has been proposed for the prevention of this amyloidosis. Currently, however, data on the beta 2-microglobulin synthesis rate in patients undergoing hemodialysis are scarce, and consequently it remains speculative how much removal would be necessary to counterbalance synthesis. The plasma kinetics of iodine 131-labeled beta 2-microglobulin were therefore examined in 11 patients with anuria who were undergoing long-term hemodialysis. Five healthy persons served as controls. Kinetic modeling of the plasma curves showed that the data fitted a two-pool model (r2 greater than 0.96) consisting of a rapid 2 to 4 hour distribution phase followed by a less steep curve, described by the plasma (metabolic) clearance (Clp). Synthetic rates were calculated from Clp and the beta 2-microglobulin steady state plasma concentration (plus beta 2-microglobulin removal during hemodialysis in the case of high flux hemodialysis). The results showed a significantly higher Clp in normal controls as compared with patients undergoing hemodialysis (65.5 +/- 12.8 ml/min (mean +/- SD) versus 3.4 +/- 0.7 ml/min). In contrast, the beta 2-microglobulin synthesis rate in the patient group (3.10 +/- 0.79 mg/kg/day) was not significantly different from that of normal controls (2.40 +/- 0.67 mg/kg/day), which was due to markedly elevated beta 2-microglobulin plasma concentrations in the patients (37.6 +/- 14.1 mg/L vs 1.92 +/- 0.27 mg/L). These findings suggest that the presence of end-stage renal disease does not have a significant impact on the beta 2-microglobulin generation rate. The degree of accumulation of beta 2-microglobulin in patients undergoing hemodialysis seems to depend on the loss of renal excretory function.

Hemofiltration↗
PubMed1990

Disseminated tuberculosis after renal transplantation. A report of two cases.

Disseminated mycobacterial infections occurred in two female renal graft recipients late after transplantation. In the first patient, initially presenting with fever, diagnosis was made at autopsy. Temporary defervescence following antibiotic therapy with ofloxacin possibly contributed to the fatal diagnostic delay. In the second case, body temperature was normal throughout the protracted course of the patient's illness. Her presenting symptom was rapidly increasing ascites, attributed initially to chronic liver disease. These cases demonstrate that tuberculosis remains a serious complication after renal transplantation, in particular due to its sometimes atypical clinical manifestations. Response to antibacterial therapy has to be critically evaluated in order to avoid fatal diagnostic delay.

Adult↗
PubMed1990

Transcription, not synthesis, of interleukin-1 and tumor necrosis factor by complement.

Stimulation of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) production was studied during in vitro hemodialysis (HD) of whole blood using cuprammonium (Cup) or polysulfone (PS) dialyzers. In the absence of LPS, circulation of whole blood for two hours through Cup or PS dialyzers was not sufficient to induce production of IL-1 beta or TNF alpha in peripheral blood mononuclear cells (PBMC) during subsequent 24 hour culture. However, compared to freshly isolated cells, post-HD PBMC were primed to produce more IL-1 beta and TNF alpha when subsequently stimulated with LPS. Despite the lack of spontaneous monokine synthesis after HD, we observed transcription of mRNA coding for IL-1 beta and TNF alpha after two hours of LPS-free HD. When compared to levels of mRNA induced by 5 ng/ml LPS (100%), Cup induced 27 +/- 6% whereas PS did not induce detectable transcription of IL-1 beta. In the case of TNF alpha mRNA, Cup induced 26 +/- 8% and PS 13 +/- 3%. Recombinant C5a induced mRNA for IL-1 beta in PBMC without detectable IL-1 beta protein synthesis. We conclude that transcription of mRNA for IL-1 beta and TNF alpha during HD is primarily caused by complement activation by Cup, but that LPS or other factors are required for translation of IL-1 beta and TNF alpha mRNA transcribed during HD.

Blotting, Northern↗
PubMed1990

Imaging of dialysis-related amyloid (AB-amyloid) deposits with 131I-beta 2-microglobulin.

The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

Amyloidosis↗
PubMed1990

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia.

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.

Adult↗
PubMed1990

Increase of C-reactive protein serum values following haemodialysis.

In this study serum C-reactive protein values were measured to prove the induction of an acute-phase response during the haemodialysis procedure in end-stage renal disease patients. C-reactive protein values were measured with a sensitive enzyme-linked immunosorbent assay to detect values below the detection limit of standard assays. Predialysis C-reactive protein serum values in 17 patients on regular haemodialysis with cuprophan dialysers were greater than those of 18 normal controls (P less than 0.001). In the same group of haemodialysis patients serum C-reactive protein values 24 h after haemodialysis were significantly greater than predialysis values (P less than 0.001). These results suggest that acute-phase proteins are induced during haemodialysis, probably due to cytokine release during the haemodialysis procedure.

Adult↗
PubMed1990

Role of excretory graft function for erythropoietin formation after renal transplantation.

To examine the role of renal excretory function for erythropoietin (EPO) formation we have determined the kinetics of plasma immunoreactive EPO (irEPO) in patients with end-stage renal disease undergoing renal allotransplantation (RTX). In 13 patients with immediate excretory graft function (imGF) and stable haemoglobin (Hb) concentrations (median Hb 9.5 g dl-1 and median irEPO 18 mU ml-1 before RTX) irEPO increased significantly on day 4 after RTX to a median value of 29 mU ml-1 and 2 days later reached a plateau of 34.4 +/- 3.3 mU ml-1 (mean +/- SD of daily median values during days 6-20). In patients with imGF having acute blood loss and subsequently receiving transfusions, irEPO responded in an inverse fashion to changes in Hb concentrations. In 12 patients with delayed graft function (dGF) (median Hb 8.8 g dl-1 and median irEPO 15 mU ml-1 before RTX) irEPO levels during the period of excretory failure remained either unchanged or displayed marked variations with peak values greatly exceeding those of patients with imGF. These variations were not related to changes in Hb concentrations and irEPO levels did not change following alterations in Hb concentrations. Upon recovery of excretory function irEPO approached the values found in patients with imGF. The results suggest that an intact excretory renal function is not a prerequisite for the capability to produce EPO, but correlates with the oxygen-dependent regulation of EPO formation.

Adolescent↗
PubMed1990

Skin microcirculation and regional peripheral resistance in patients with chronic renal anaemia treated with recombinant human erythropoietin.

Skin microcirculation and regional peripheral resistance were studied in 14 patients with renal anaemia during therapy with recombinant human erythropoietin. Haematocrit was raised from 20.0 to 31.3% after 10-12 weeks of treatment and remained stable over another period of 12 weeks. Antihypertensive treatment had to be intensified in five patients. Regional calf blood flow decreased significantly; accordingly, calculated peripheral vascular resistance was increased by more than 100%. However, transcutaneous oxygen pressure (37 degrees C and 44 degrees C) increased significantly. The pathological vasoconstrictor response of skin capillaries was not influenced. There were no significant differences of any parameter between the patients requiring reinforced antihypertensive therapy and those with stable blood pressure. In conclusion skin oxygenation may be improved by erythropoietin treatment to a large extent despite an increase in calculated total limb vascular resistance.

Adult↗