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Biomedical subjects

E Honkanen

Publications and source records attributed to E Honkanen.

At least 37 records · Page 2Linked to original sources

Urinary transforming growth factor-beta 1 in membranous glomerulonephritis.

BACKGROUND: Human idiopathic membranous glomerulonephritis (MGN) has a highly variable clinical course and factors determining its outcome are poorly known. Since transforming growth factor-beta 1 (TGF-beta 1) has an essential role in renal fibrogenesis, we studied the possibility to use urinary excretion of TGF-beta 1 in the assessment of progression of the disease in patients with MGN. METHODS: Urinary TGF-beta 1 was determined in 41 patients with MGN, 25 healthy subjects, six non-proteinuric renal transplant patients, 10 patients with IgA glomerulonephritis, and seven proteinuric patients (with non-progressive diseases) using a novel, double antibody enzyme immunoassay. The results were compared with renal morphology and clinical indices of activity of MGN over 12 months. RESULTS: The median urinary TGF-beta 1 excretion (pg/mg creatinine) was significantly higher (1730; range 60-16,970) in MGN patients than in the healthy controls (300; 30-1330; P < 0.0001). In renal allograft recipients the excretion was 840 (250-3440; P < 0.0001 vs healthy controls), in IgA GN it was 1130 (30-4910; P = 0.039), and in proteinuric patients it was 39 (29-165; P = NS). In MGN but not in the proteinuric controls or renal allograft recipients, urinary TGF-beta 1 correlated with urinary albumin excretion (r = 0.86, P < 0.0001) but no correlation with renal function or the duration of the disease was found. Urinary TGF-beta 1 at renal biopsy correlated with interstitial cellular inflammation and its excretion 1 year before the biopsy correlated with indices of sclerosis/fibrosis. Immunosuppressive therapy significantly decreased urinary TGF-beta 1 from 2800 (1610-16,960) to 840 (170-1600) pg/mg creatinine (P = 0.028). Patients with persistent nephrotic syndrome and/or declining renal function had a higher initial TGF-beta 1 excretion (median 3680; 1830-7420 pg/mg creatinine) than those entering partial or complete remission (1060; 60-1960; P = 0.003) within 12 months from sampling.

Adult↗

Peritoneal dialysis access: prospective randomized comparison of single-cuff and double-cuff straight Tenckhoff catheters.

BACKGROUND: A prerequisite to the technical success of chronic peritoneal dialysis is a functioning peritoneal catheter. The option of using Tenckhoff catheters with single or double Dacron cuffs has been available for almost 3 decades, but still there is no consensus as to which is the preferable type. METHOD: Sixty consecutive patients requiring a catheter for CAPD were randomized to receive either a straight deep single-cuff Tenckhoff catheter or a double-cuff Tenckhoff catheter. The catheters were surgically inserted. RESULTS: There were no early failures. Two subcutaneous cuff extrusions were treated with shaving of the cuff. In the long term, eight patients in both groups required transfer to haemodialysis (5 and 3 prolonged peritonitis, 1 and 0 exit-site infection, 2 and 5 unable to cope or inadequacy of dialysis). There was no significant difference in the probability of developing first episode of peritonitis or exit site infection between the groups. Overall probability of catheter survival was 95.5 and 96.7% at 1 year, 82.7 and 79.9% at 2 in the two groups respectively. CONCLUSIONS: There was no significant difference between catheters with single or double cuffs with respect to catheter survival, episodes of peritonitis and exit-site infections.

Adult↗

Urinary excretion of TGF-beta 1, PDGF-BB and fibronectin in insulin-dependent diabetes mellitus patients.

We studied the urinary excretion of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor-BB (PDGF) and fibronectin (FN) in 104 patients (52 normoalbuminuric, 24 microalbuminuric, and 28 with overt diabetic nephropathy) with insulin-dependent diabetes mellitus (IDDM) of a long duration and in 30 non-diabetic controls. IDDM patients had higher urinary excretion of TGF-beta 1, PDGF and FN compared to controls. Urinary excretion of TGF-beta 1 and PDGF was elevated in all IDDM subgroups, while FN excretion was significantly increased only in patients with macroalbuminuria. Urinary excretion of TGF-beta 1 and FN did not differ between normoalbuminuric IDDM patients with long duration of diabetes, a group at low risk of ever developing diabetic nephropathy, and IDDM patients with incipient or overt diabetic nephropathy. Excretion of PDGF was significantly higher in patients with micro- and macroalbuminuria compared to normoalbuminuric patients, but there was a considerable overlap between the groups. In conclusion, although longitudinal follow-up studies are needed to further clarify the issue, our results in long-standing IDDM do not support a hypothesis of urinary excretion of TGF-beta 1, PDGF or FN to predict development of diabetic nephropathy.

Adult↗

Urinary excretion of protectin (CD59), complement SC5b-9 and cytokines in membranous glomerulonephritis.

Protectin (CD59) is a low molecular weight glycophosphoinositol-anchored inhibitor of the membrane attack complex of complement (MAC) that is present, for example, on the membranes of endothelial cells and on epithelial cells of glomeruli and distal tubuli. To examine for the possibility that CD59 becomes detached from cell surfaces following cell injury, this study evaluated renal excretion of CD59 in patients with idiopathic membranous glomerulonephritis (MGN; N = 21), diabetic nephropathy (DNP; N = 15) and in healthy control subjects (N = 13). CD59 in human urine was quantitated by a competitive solid-phase radioimmunoassay having approximately 13 kDa soluble urinary CD59 as a standard. Immunofluorescence microscopy demonstrated a decreased expression of CD59 in the glomeruli of MGN patients. Using a Triton X-114 phase separation method 91 to 97% of urinary CD59 was found to be in a soluble form without anchor-associated phospholipid. The mean (+/- SEM) level of urinary CD59 was 5.6 +/- 0.2 micrograms/ml in MGN patients, 3.7 +/- 0.4 micrograms/ml in healthy controls (P < 0.001) and 2.6 +/- 0.1 in DNP patients (P < 0.001). When related to urinary creatinine (UCr) the corresponding values were 11.9 +/- 5.6, 4.8 +/- 0.3 (P = 0.021) and 4.4 +/- 0.2 (P < 0.002), respectively. The amount of CD59 in urine correlated with the urinary excretion of soluble terminal complement complexes, SC5b-9 (r = 0.594, P < 0.006) in MGN patients. The excretion of CD59 also correlated with the excretion of the inflammatory mediator IL-1 beta (r = 0.671, P = 0.001) but not with TNF-alpha (r = 0.314, P = 0.178). No correlation of CD59 excretion was observed with duration of the disease level of proteinuria, serum albumin concentration or serum creatinine level. Based on these findings we speculate that the increased excretion of CD59 into urine in MGN patients is due to complement activation and inflammation induced shedding of CD59 from glomerular cells.

Adult↗

Urinary alpha 1- and beta 2-microglobulin in light chain proteinuria.

Thirteen patients with light chain (LC) proteinuria (11 with multiple myeloma and two with monoclonal gammopathy of undetermined significance) were followed up for one to 3.5 (median 2.5) years and studied for urinary excretion of LCs, alpha 1-microglobulin (alpha 1 M), beta 2-microglobulin (beta 2M), albumin, and serum creatinine concentration at intervals of 6 +/- 2 months. At the beginning of the follow-up, urinary alpha 1M excretion correlated with that of beta 2M (r = 0.81, p = 0.0007) and LCs (0.69, p = 0.0084), and with the serum creatinine level (r = 0.56, p = 0.047). During the follow-up period, renal function remained stable in eight patients despite high or fluctuating LC excretion. In seven of them, urinary alpha 1M was repeatedly below 150 mg/24 h and in one it transiently exceeded that level. The remaining five patients had an unstable renal function (deterioration in four, improvement in one) although their urinary LC and albumin excretion during the study period was comparable to those in patients with stable renal function. In the five patients with unstable renal function, high (> 150 mg/24 h) urinary alpha 1M excretion was associated with a rise in the serum creatinine level. alpha 1M excretion was thus found to be a useful indicator of renal damage caused by LCs.

Aged↗

Urinary excretion of cytokines and complement SC5b-9 in idiopathic membranous glomerulonephritis.

Idiopathic membranous glomerulonephritis (iMGN) has previously been shown to be associated with urinary excretion of terminal complement complexes while increased urinary levels of cytokines have been reported in mesangial proliferative glomerulonephritis. In the present cross-sectional study urinary excretion of IL-1 beta, TNF-alpha, IL-6, and soluble C5b-9 (SC5b-9) was examined for 23 patients with iMGN, 16 patients with diabetic nephropathy (DNP), and 17 healthy subjects. IL-1 beta excretion (pg/mg crea) was significantly higher in iMGN patients (375, range 162-11,000) than in DNP patients (39, range 22-59, P < 0.001) or healthy controls (151, range 23-481, P < 0.001). TNF-alpha excretion rate (pg/mg crea) was clearly higher (38, range 21-700) in iMGN patients than in DNP patients (14, range 8-52, P < 0.001) or healthy subjects (11, range 7-26, P < 0.001). Median IL-6 excretion (pg/mg crea) was only marginally higher in iMGN patients (73, range 0-850) than in healthy subjects (64, range 3-158, P = 0.02) but significantly higher than in DNP patients (29, range 17-47, P < 0.001). No significant correlation with corresponding serum values was observed for urinary IL-6 or TNF-alpha excretion. Urinary IL-1 beta and TNF-alpha correlated with decreased renal function. Five of 23 patients showed progression of iMGN over a follow-up of 6 months. The excretion of all cytokines, TNF-alpha in particular, was significantly higher in patients with a progressive disease than in the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term survival in idiopathic membranous glomerulonephritis: can the course be clinically predicted?

72 adult patients with idiopathic membranous glomerulonephritis (iMGN), 92% having proteinuria 3 g/24 h or more, were studied for the clinical evolution of the disease and factors which might be involved in the development of chronic renal insufficiency (CRI). At 10 years, 46% were in complete or partial remission, 4% had the nephrotic syndrome (NS), 26% had some degree of CRI, and 24% were dead or started on dialysis. The actuarial patient and kidney survival rates were 80% and 64%, respectively at 10 years. Patient survival rate was not affected by gender, age (after adjustment for age- and sex-matched population) or the severity of NS at diagnosis. 20 patients showed CRI and apart from the more frequent (p < 0.05) presence of CRI at diagnosis, no clinical features discriminated them from those having intact renal function. Furthermore, no clinical factors at diagnosis predicted the final renal function among the 72 patients. However, it appeared that the evolution of clinical status of iMGN was rapid CRI appearing 1.4 (median, range from 0 to 15.1) years after the diagnosis. At one and two years, renal function correlated significantly (r = 0.54, p < 0.0001 at two years) with the final renal function. What is more, the type of the evolution of proteinuria over the first two years gave valuable information on the eventual deterioration of renal function. Patients having stable non-nephrotic grade proteinuria and those in whom NS disappeared, had excellent renal outcome while those in particular showing an increased severity of NS had poor prognosis in terms of renal survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Hepatitis C antibodies in dialysis patients and patients with leukaemia.

The prevalence of hepatitis C antibodies (anti-HCV) among multitransfused patients was studied and compared with predicted values obtained from a post-transfusion hepatitis study and from data on the prevalence of anti-HCV among blood donors. The prevalence of hepatitis B core antibodies (anti-HBc) was also studied to determine the routes of transmission of hepatitis C virus. The patients consisted of 65 dialysis patients (57 on haemodialysis and 8 on continuous ambulatory peritoneal dialysis) and 71 leukaemia patients in long-term remission [49 with acute myeloid leukaemia (AML) and 22 with acute lymphatic leukaemia (ALL)]. The presence of anti-HCV was investigated using a second generation enzyme-linked immunosorbent assay. Reactive samples were confirmed by a second generation recombinant immunoblot assay. Anti-HBc was studied in the 65 dialysis patients and in 40 of the leukaemia patients. Three (4.6%) of the 65 dialysis patients and 12 (24.5%) of the 49 AML patients were anti-HCV positive whereas all of the ALL patients were seronegative. The total number of blood units transfused to 134 patients (data on two dialysis patients were not available) was 18,148, out of which 17,575 units had been transfused prior to the initiation of anti-HCV screening of blood donors. On the basis of the anti-HCV prevalence among blood donors and the incidence of post-transfusion hepatitis, the predicted number of seropositive patients was 11 and 18, respectively. Five of the 65 dialysis patients were anti-HBc positive, compared with only one of the 40 leukaemia patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Alpha-1-antitrypsin, CRP and interleukin-6 in ANCA-positive vasculitis.

Alfa-1-antitrypsin (a-1-AT), C-reactive protein (CRP) and interleukin-6 (IL-6) serum levels were measured during different phases of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. Correlation between ANCA and these variables was observed. Both a-1-AT and CRP fluctuations indicated changes in activity that could not always be detected by ANCA. On the other hand, these acute phase proteins were also less specific. IL-6 was not as sensitive as CRP and a-1-AT, a clearly increased mean value was observed only in patients with high ANCA titers.

Antibodies, Antineutrophil Cytoplasmic↗

Individualized use of hemodialysis and peritoneal dialysis.

Over the past few years it has better been realized how individual the needs for the effectiveness ("dose") of dialytic therapy are and which treatment related factors affect the morbidity and mortality of dialysis patients. Although the role of urea, a marker of small molecular weight uremic toxins, has been challenged, most studies have been based on kinetics of urea during and between dialyses. The dose of dialysis affects also the nutritional status and a special role for "middle" molecules as anorectic factors has been suggested. This article gives an in-depth view of some factors which affect the needs for the effectiveness of dialytic therapy, a summary of the goals of the treatment, and some practical guidelines how to reach them.

Dietary Proteins↗

Outcome of patients with secondary amyloidosis in dialysis treatment.

Between the years 1974 and 1987, 37 patients with secondary amyloidosis entered dialysis treatment at our department. All had amyloidosis secondary to chronic arthritic disease (35) or to other chronic inflammatory causes (2). Only two patients were maintained on CAPD throughout follow-up; 12 patients (32%) received a kidney transplant. Survival in dialysis at 1 year was 82%, at 2 years 46%, and at 3 years 37%. Survival of amyloidosis patients transplanted at the Finnish transplant centre within the same period was worse at 1 year, but better at 2 and 3 years, 70%, 62%, and 62% respectively, but the difference was not significant. Populations are not compatible, since patients were selected for transplantation. Infection was a common cause of death, 7/18 (39%) deaths; cardiac deaths were less common, only two myocardial infarctions and one cardiac arrhythmia (17%). Symptoms of cardiac amyloid infiltration indicated a poor prognosis, although it did not necessarily predict death of a cardiac cause. Cardiac infiltration of amyloid was more common in autopsy than previously reported (10 of 13 patients), probably indicating longer duration of amyloidosis in patients treated with renal replacement therapy. Patients who died within follow-up had a shorter interval between the start of primary disease and the development of amyloidosis than those who survived, 11.8 versus 17.7 years (P = 0.041), and also a slightly shorter period between diagnosis of amyloidosis and start of dialysis, 3.0 versus 4.4 years (P = 0.129). This indicates that the rate of progression of amyloidosis determines the development of disease-associated complications, and fast progression may predict serious outcome.

Adult↗

CAPD with low calcium dialysate and calcium carbonate: results of a 24-week study.

Twelve patients (median age 44.5 years) on CAPD, who had previously used a dialysate calcium concentration of 1.75 mmol/l (for a median time of 11.5 months) were started on a low calcium dialysate (LCD) with a calcium concentration of 1.25 mmol/l and followed up for 24 weeks. During the first eight weeks, no changes in the doses of oral phosphate binders were made and serum ionized calcium decreased from 1.30 +/- 0.02 (mean +/- SE) mmol/l to 1.17 +/- 0.02 (p < 0.0001) and serum PTH (1-84) rose from 68 (median, range 16-397) ng/l to 147 (70-449, p = 0.005). After week 8, increasing doses of calcium carbonate were used to achieve target calcium levels of 1.20-1.30 mmol/l. No aluminum-containing binders were used. Calcium carbonate doses were increased from 2.3 (median, range 0.75-12) g/d to 6.8 (3.8-15.0, p = 0.0004) and serum phosphorus concentrations decreased from 2.00 mmol/l (median, range 1.25-2.67) at 8 weeks to 1.61 (1.18-2.39) at 24 weeks (p = 0.023). Serum intact PTH(1-84) values remained elevated despite the gradually increasing serum calcium concentrations. Hypercalcemia was recorded in 20/36 (56%) of blood samples during a period of four weeks before the start of LCD, and such episodes were observed in 15/89 (17%) of samples (p < 0.001) on LCD during the period when calcium carbonate doses were increased. It is concluded that on LCD 1) the number of episodes of hypercalcemia was markedly reduced, 2) higher calcium carbonate doses could be used, and thus 3) the control of serum phosphorus improved.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Serum hyaluronic acid and procollagen III amino terminal propeptide in chronic renal failure.

Elevated serum concentrations of hyaluronic acid (HA) and procollagen III amino terminal propeptide (PIIINP) have been found in various diseases characterized by altered metabolism of collagen. In the present study, their serum levels were measured in 105 renal patients and 22 normal controls. Median HA concentrations were 23 micrograms/l in controls, 47 micrograms/l in patients with chronic renal failure (CRF, not on dialysis; p less than 0.001), 75 micrograms/l on CAPD (p less than 0.001) vs. controls, p = 0.045 vs. CRF), and 167 micrograms/l on hemodialysis (p less than 0.001 vs. controls, CRF, and CAPD), respectively. The values correlated positively with age but not with renal function or the type of renal disease. In hemodialysis patients, HA correlated with the duration of renal replacement therapy and serum beta 2-microglobulin but not with serum alkaline phosphatase or C-terminal parathormone. Serum HA did not change significantly during hemodialysis treatment and was independent of the type of dialyzer membrane material. Median PIIINP values were 2.7 micrograms/l in controls, 4.4 micrograms/l in patients with CRF (p less than 0.001), 6.9 micrograms/l on CAPD (p less than 0.001 vs. controls, p = 0.022 vs. CRF), and 8.6 micrograms/l on hemodialysis (p = 0.001 vs. controls, NS vs. CRF or CAPD). Values correlated with HA only in patients on CAPD but they did not correlate with age, renal function or duration of renal replacement therapy. It is concluded that renal failure, especially long-term dialysis treatment, is associated with elevated serum concentrations of HA and--to a minor degree--PIINP. Thus, they may be a sign of altered connective tissue metabolism in patients on long-term dialysis.

Age Factors↗

Acute-phase proteins during hemodialysis: correlations with serum interleukin-1 beta levels and different dialysis membranes.

The effects of hemodialysis (HD) on the levels of serum amyloid A (SAA), C-reactive protein (CRP) and interleukin-1 beta (IL-1 beta) were studied in 8 patients. Bicarbonate dialysate was used exclusively, and three different membranes, Cuprophan (CU), cellulose acetate (CA), and polymethylmetachrylate (PMMA) were compared. The SAA levels increased significantly with each membrane. With CU, they rose from 4.0 +/- 2.0 (mg/l, mean +/- SEM) to 9.6 +/- 2.8 at 60 min and to 15.0 +/- 4.9 at 240 min. The values with CA were 3.8 +/- 2.1, 15.3 +/- 5.6, and 23.8 +/- 3.9; and with PMMA 2.4 +/- 1.3, 12.1 +/- 5.6, and 12.1 +/- 5.9, respectively. The alterations of SAA neither correlated with the weight loss nor the increase of serum albumin during dialysis. The CRP values showed insignificant changes. The IL-1 beta levels rose with CU from 87 +/-18 (ng/l) to 155 +/- 33 at 60 min and to 172 +/- 47 at 240 min. With CA, the values were 67 +/- 14, 198 +/- 46, and 121 +/- 23, and with PMMA 63 +/- 13, 246 +/- 93, and 211 +/- 86, respectively. These results did not correlate with the effects of the membranes on complement activation. It is concluded that the release of cytokines during HD apparently leads to a rapid synthesis of acute-phase proteins as a sign of inflammation. Thus, SAA may be used as one indicator of the biocompatibility of HD treatment.

Adult↗