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Biomedical subjects

K M Koch

Publications and source records attributed to K M Koch.

At least 109 records · Page 6Linked to original sources
PubMed1995

Beta 2-microglobulin amyloidosis: why and how to look for it.

Thirty years after the introduction of chronic dialysis into clinical practice, amyloidosis based on the precursor molecule beta 2-microglobulin (beta 2m-A) has emerged as an important complication of end-stage renal disease in patients on renal replacement therapies other than transplantation. For the individual patient, diagnosis of beta 2m-A is important to exclude other treatable causes of the symptoms, initiate symptomatic treatment, prevent possible life-threatening complications, and assign a high priority for transplantation. For the ESRD population as a whole, early specific diagnosis should help to assess the influence of various therapeutic modes on the development and course of beta 2m-A and to guide further the optimization of renal replacement therapy. Besides, sophisticated diagnostic techniques may yield valuable information on underlying pathogenetic mechanisms of beta 2m-A. Morphology, including immunohistochemistry, as the most definitive and specific diagnostic proof must rely on invasive procedures to obtain the appropriate material from clinically affected sites. Clinical assessment and imaging techniques such as x-ray and joint sonography suffer from non-specificity. Scintigraphic imaging of beta 2m-A after injection of radiolabelled beta 2-microglobulin is a non-invasive, specific, and highly sensitive way of diagnosis. Further refinement and more widespread use of this method can be expected to enhance the understanding of beta 2m-A pathogenesis and promote therapeutic and preventive efforts against this complication.

Amyloidosis↗
PubMed1995

Treatment of renal anemia by erythropoietin substitution. The effects on the cardiovascular system.

Recombinant human erythropoietin (r-HuEPO) effectively corrects the anemia of end stage renal disease (ESRD). Development or aggravation of hypertension has been the most commonly reported side-effect of r-HuEPO treatment. Placebo controlled trials have shown incidence rates ranging from 16-21%. Renal failure itself obviously is a prerequisite in the pathogenesis of r-HuEPO-induced hypertension, since it was never observed in anemic patients without renal disease. Increased whole blood viscosity and/or reduced hypoxic vasodilatation due to the rise in hematocrit may play a role in the development of hypertension at high concentrations of hematocrit. However, at hematocrit levels around 30% additional hypertensinogenic effects of r-HuEPO treatment seem likely. Endothelin and prostanoids are possible mediators of this effect. Left ventricular hypertrophy (concentric and eccentric), which can be due to hypertension and anemia, is commonly observed in ESRD patients and has been shown to be a predictor of cardiac morbidity and mortality in these patients. Following correction of anemia with r-HuEPO measures of left ventricular hypertrophy decrease by about 18% within a year. Normalization, though, is generally not achieved and in patients with r-HuEPO induced hypertension the increase of blood pressure may oppose the beneficial effects of r-HuEPO treatment on cardiac hypertrophy.

Anemia↗
PubMed1994

Plasma levels of tumor necrosis factor (TNF) and soluble TNF receptors in kidney transplant recipients.

Tumor necrosis factor-alpha is elevated in plasma during kidney transplant rejection. However, the measurement and biological activity of TNF alpha is influenced by inhibitory soluble TNF receptors. We therefore determined plasma levels of TNF alpha and the 2 soluble TNF receptors, the 55-kDa TNF receptor (TNF-sR55) and the 75-kDa TNF receptor (TNF-sR75), by immunoassays in 25 patients before and daily after kidney transplantation. Plasma samples were retrospectively assigned to 3 groups: (1) patients with well-functioning grafts (n = 14); (2) patients with biopsy-proven graft rejections (n = 7 patients with 10 rejections); and (3) patients with episodes of CsA nephrotoxicity (n = 4 patients with 9 samples). On the day of biopsy-proven graft rejection, TNF alpha increased from 8.6 +/- 0.9 pg/ml to 14.8 +/- 3.5 pg/ml (P < 0.02), TNF-sR55 from 6.6 +/- 1.3 ng/ml to 9.0 +/- 1.2 ng/ml (NS), and TNF-sR75 from 10.3 +/- 1.0 ng/ml to 15.3 +/- 2.0 ng/ml (P < 0.01). During episodes of CsA toxicity, TNF alpha levels did not change, TNF-sR55 increased from 5.2 +/- 0.5 ng/ml to 10.5 +/- 0.5 ng/ml (P < 0.01), and TNF-sR75 increased from 10.2 +/- 0.8 ng/ml to 17.5 +/- 0.9 ng/ml (P < 0.01). There was a strong correlation between serum creatinine and plasma TNF-sR55 (r = 0.7, P < 0.001) and TNF-sR75 (r = 0.7, P < 0.001), but not with TNF alpha. Therefore, levels of TNF-sR55 and TNF-sR75 were corrected for serum creatinine. An index expressing TNF alpha over actively released soluble receptors (index = TNF alpha/(corr.TNF-sR55 + corr.TNF-sR75)) detected rejection episodes with a sensitivity of 70-80% and a specificity of 89%. We conclude that the measurement of plasma TNF alpha in combination with its soluble receptors is superior to isolated TNF alpha determinations in discriminating acute graft rejection from episodes of CsA toxicity in kidney transplant recipients.

Adult↗
PubMed1994

[Lumbar spondylodiscitis caused by Salmonella enteritidis].

A 19-year-old boy developed paravertebral muscular pain in the lumbar region after an episode of extremely arduous sporting activity, with fever followed by meningism. The cerebrospinal fluid showed a reactive pleocytosis. Initially, no acute inflammatory changes were present on serum and blood analysis, although the erythrocyte sedimentation rate was moderately increased to 25/60 mm. Pyrexia of up to 38.5 degrees C developed 6 days after admission. Because Borrelia IgM and IgG titres were positive, the diagnosis was at first thought to be atypical borreliosis and the patient was treated with antibiotics. However, after a further episode of fever. Salmonella antibody titres, which had initially been normal, rose to 1: 3200 (Salmonella typhi O and H antigens) and 1: 12800 (Salmonella enteritidis, H antigen). At this stage, the erythrocyte sedimentation rate rose to 86/120 mm and the C-reactive protein to 77 mg/dl. The white cell count remained normal throughout. Blood cultures grew Salmonella enteritidis. Abnormalities on bone scintigraphy were confirmed by CT and MRI scans, showing spondylodiscitis of lumbar vertebrae 1 and 2 with limited osteolysis. The lesion resolved completely on 6 week's treatment with ciprofloxacin (200 mg twice a day intravenously) and conservative supportive treatment. Spondylodiscitis is an uncommon complication of salmonellosis and may occur long after the diarrhoea. Cross reactions with Borrelia flagellin antigens may lead to the wrong diagnosis being made.

Adult↗
PubMed1994

Low-dose prednisolone/chlorambucil therapy in patients with severe membranous glomerulonephritis.

Because of the high rate of spontaneous remission, treatment of membranous nephropathy with prednisolone and chlorambucil is still controversial. The aim of this study was to give this therapy only to those patients at risk of developing renal insufficiency and to test the efficacy of a low-dose therapeutic regimen. Seventeen patients with more than 10 g protein excretion per day (mean 16.9) and/or a deterioration in renal function (mean serum creatinine, 162 mumol/l) were included. Serum total protein, serum lipids, proteinuria, serum creatinine, and blood pressure were measured, along with the diuretic and antihypertensive medication. The observation time before the start of treatment was 27 +/- 27 months. Steroids were given during months 1, 3, and 5 (methylprednisolone 3 x 500 mg intravenously) prednisolone 0.5 mg/kgBW daily per os for 1 week, then tapered by 0.1 mg/kg BW/week for 1 month). Chlorambucil was given during months 2, 4, and 6 at a dose of 0.12 mg/kgBW daily. At the end of treatment proteinuria had significantly decreased (mean of all patients, 7.8 +/- 1.4 g/d) in all patients. Six months after the end of treatment proteinuria was significantly lower than at baseline in 14 of 17 patients. Hypoproteinemia and hyperlipidemia had improved; diuretic and antihypertensive medication were reduced. Elevated serum creatinine decreased in 7 of 9 patients (pretreatment, 227 +/- 39 mumol/l; 6 months, 176 +/- 28 mumol/l). Nonresponders with respect to serum creatinine responded with respect to proteinuria. Regarding adverse effects, two patients complained of dyspepsia while taking steroids; during chlorambucil treatment two patients experienced nausea and lack of appetite, and one developed leukopenia (1600/microliters).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial.

Intermittent bolus administration of calcitriol--i.e., 1,25-dihydroxycholecalciferol or 1,25-(OH)2D3--is highly efficacious in dialysis patients. In experimental studies, intermittent administration of calcitriol is superior to continuous administration in suppressing preproparathyroid hormone (PTH) mRNA and circulating PTH concentrations. In a randomized, prospective, open multicenter trial 45 dialysis patients with elevated 1,84-iPTH (> or = 20 pmol/l, normal 1-6 pmol/l) levels were randomly allocated to daily administration of 0.75 microgram calcitriol (continuous) or twice weekly administration (intermittent); the two protocols provided an identical total weekly doses of 5.25 micrograms calcitriol. Patients were dialyzed with a dialysate Ca concentration of 1.75 mmol/l and had oral CaCO3 or Ca acetate. 1,84-iPTH (immunoradiometric assay) and serum Ca and Pi levels were measured weekly. At the beginning of the study, the median 1,84-iPTH value was 37 pmol/l (range 20-115) in the intermittent versus 36 pmol/l (range 21-72) in the continuous calcitriol group. After 2 weeks, the median 1,84-iPTH level was 18.5 pmol/l (range 1.4-106) versus 18 pmol/l (range 1.2-48). After 12 weeks, 11 of 21 of the patients in the intermittent and 18 of 24 patients in the continuous group had reached the treatment goal, i.e., 1,84-iPTH < or = 10 pmol/l without hypercalcemia or hyperphosphatemia. There were seven episodes of hypercalcemia (> 2.7 mmol/l) in the intermittent versus two in the continuous group; the mean peak Ca level was 2.8 mmol/l (range 2.76-3.0) versus 2.9 mmol/l (range 2.74-3.06). There were 21 versus 17 episodes, respectively, of hyperphosphatemia (> 2.2 mmol/l).

Administration, Oral↗
PubMed1994

Interstitial nephritis associated with 5-aminosalicylic acid.

A patient with severe Crohn's disease was treated with 5-aminosalicylic acid (5-ASA). Following initiation of treatment, serum creatinine increased slowly from 105 to 530 mumol/l (creatinine clearance 16 ml/min). The diagnosis of an interstitial nephritis was made based on normal urinary findings and the renal biopsy histology of interstitial mononuclear infiltrates and normal glomeruli, 5-ASA was discontinued and serum creatinine decreased to 245 mumol/l (creatinine clearance 40 ml/min) during the following 3 months. Partial reversibility of renal failure following discontinuation of 5-ASA and the absence of other drugs possibly causing interstitial nephritis suggest a causal relationship between 5-ASA and interstitial nephritis.

Adult↗
PubMed1994

The effect of ultrafiltered dialysate on the cellular content of interleukin-1 receptor antagonist in patients on chronic hemodialysis.

We investigated the effect of dialysate ultrafiltration on the content of IL-1 receptor antagonist (IL-1Ra) in mononuclear cells (PBMC) as a marker of the inflammatory response. 11 patients on Cuprophan dialyzers were randomly assigned to treatment with standard bicarbonate dialysate first and then to ultrafiltered dialysate or the reverse order in a crossover design. In each treatment period (at least 4 weeks) weekly separations of PBMC were performed before the start of dialysis. Cellular content of IL-1Ra was determined in PBMC that were frozen immediately after separation; all values of IL-1Ra in each treatment period were averaged. The dialysate contained a median of 148 (range, 61-400) colony-forming units without dialysate filter; no bacterial growth was detected in ultrafiltered dialysate. The median endotoxin content was 80 pg/ml in nonfiltered dialysate; endotoxin was below 5 pg/ml in all ultrafiltered dialysate samples. Cellular content of IL-1Ra decreased in all but 1 patient with the use of ultrafiltered dialysate (mean +/- SEM: 1,467 +/- 113 pg/ml without dialysate filter vs. 1,166 +/- 104 pg/ml with filter, p = 0.016). The present study demonstrates that the bacterial contamination of the dialysate induces a systemic inflammatory response in hemodialysis patients.

Bacteria↗
PubMed1994

On the specificity of assays to detect circulating immunoglobulin A-fibronectin complexes: implications for the study of serologic phenomena in patients with immunoglobulin A nephropathy.

Immunoglobulin A (IgA)-fibronectin complexes have been proposed as specific serologic markers of IgA nephropathy. They have been detected by the use of ELISA composed of an immobilized antifibronectin antibody (or albumin as a negative control) and an enzyme-conjugated anti-IgA antibody (antifibronectin capture assay). By the use of this type of assay, plasma samples from 32 normal controls, 38 IgA nephropathy patients, and 81 patients with other types of glomerulonephritis were analyzed. Extinction values in IgA nephropathy patients were higher (P = 0.06) than in patients with other glomerulonephritis types and significantly higher than in normals. Markedly lower values were obtained when the plates were coated with albumin. However, when the antifibronectin antibody was replaced by normal IgG or F(ab')2 fragments, almost identical extinctions were measured. The use of different antifibronectin antibodies, IgG, ELISA plates, or blocking regimens did not modify these results. Extinction values could not be suppressed by the addition of exogenous fibronectin. Similar extinctions were observed when plasma samples were replaced by physiologic concentrations of fibronectin-free IgA. Extinction values measured in the plasma samples correlated significantly with IgA concentrations in plasma as analyzed by nephelometry. A collagen binding assay, a second type of assay used to measure IgA-fibronectin complexes, also allowed the detection of fibronectin-free IgA, and again, extinctions measured in plasma could not be suppressed by exogenous fibronectin. In conclusion, both antifibronectin capture ELISA and collagen binding assays do not specifically detect only IgA-fibronectin complexes, but also total plasma IgA, which is frequently, but nonspecifically, elevated in IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Effect of cyclosporin on kidney proteolytic enzymes in men and rats.

Cyclosporin (CsA) induces autophagolysosomes in proximal tubules. A major lysosomal function is degradation of cell proteins. Cathepsin B and L are marker enzymes for the activity of lysosomal protein degradation. Therefore we measured cathepsin activities in microdissected proximal tubule segments and urine from rats treated with CsA, 30 mg/24 h by gavage for 42 days. Cathepsin activity was increased in proximal tubule by 117% and in 24-h urine by 37% compared to controls. Unchanged values of serum cathepsin activity and of proteinuria excluded increased glomerular filtration or decreased tubular absorption as major source of urine cathepsins. Therefore urine cathepsin excretion reflected tubular cathepsin activity. Urine cathepsin excretion was also measured in patients without renal disease treated with CsA for multiple sclerosis (MS). It was increased by 59% in patients with CsA serum values > 120 ng/ml compared to MS patients without CsA or with serum CsA < 120 ng/ml. Urine cathepsin excretion increased linearly with serum CsA (P < 0.001). The data suggest that cathepsin activity is increased in proximal tubules of CsA-treated patients. Hence CsA may stimulate protein degradation in proximal tubules of men and rats.

Adult↗
PubMed1993

[Cyclophosphamide bolus therapy in lupus nephritis].

A pilot study of 21 patients (17 women; 4 men; mean age 35 [18-59] years), randomized into two groups, was undertaken to test how many cycles of intravenous pulse cyclophosphamide administration were required in lupus nephritis to achieve remission. It was planned that patients randomized to group A should be treated for 3 months, those in group B for over 12 months. In the first cycle the cyclophosphamide dosage was 500 mg/m2, in the subsequent cycles, 4 weeks apart, it was raised by 250 mg/m2 to a maximum of 1,000 mg/m2, if the WBC count was over 2,000/microliters. Three women in group B gave up treatment prematurely after 5-8 cycles, because a remission had occurred. In group A only one patient went into remission after only three cycles. Of the total of 18 patients in both groups whose data could be evaluated, 15 achieved remission after an average of 7.3 cycles and a cumulative total cyclophosphamide dosage of 9.3 g. The disease progressed in two patients, one died. No recurrence has so far been observed after a follow-up period of 1-41 months. Three patients had infections and two had developed leukopenia as side effects. Pulse cyclophosphamide has thus been shown to be an effective treatment in lupus nephritis, but it must be continued for more than 3 months.

Adolescent↗
PubMed1993

[Clinical experiences with nocturnal intermittent peritoneal dialysis].

Nocturnal intermittent peritoneal dialysis (NIPD) was performed in 56 patients (37 men, 19 women; mean age 44 [18-77] years, 18 of them diabetics). The NIPD protocol laid down 6-10 automatic changes of 1.5-2.3 1 dialysate (mean glucose concentration: 1.9%) each night. Clinical and biochemical tests were performed three times, at least 4 weeks apart (the first one after 2 months of stable NIPD). 36 of the 52 patients under the age of 60 were working. Mean hospital stay (excluding catheter implantation and training) was 5 days yearly. Mean peritonitis rate was one episode every 54 months. Because of technical problems a change from peritoneal to haemodialysis became necessary in four patients. Clinical and biochemical findings were: creatinine 877 +/- 269 mumol/l, urea 20 +/- 5.2 mmol/l, potassium 4.5 +/- 0.6 mmol/l, calcium 2.3 +/- 0.2 mmol/l, phosphate 1.7 +/- 0.5 mmol/l, total protein 69 +/- 7 g/l, cholesterol 6.8 +/- 1.7 mmol/l, and triglycerides 2.6 +/- 1.4 mmol/l. These data show that NIPD is an effective method of dialysis which--in comparison with other techniques--has several advantages. Peritonitis and technical failure are rare.

Adult↗