Efficacy comparison of intravenous and subcutaneous recombinant human erythropoietin administration in hemodialysis patients.
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Biomedical subjects
Publications and source records attributed to E Ritz.
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We have used restriction fragment length polymorphism (RFLP) analysis to investigate the immunoglobulin constant heavy chain (IgCH) loci and the associated locus Dl4Sl, of Caucasoids from South East England and South-West. West Germany, Haplotypes were determined using probes to the Ig heavy chain switch loci S mu and S alpha 1, the IgC gamma 3 and IgC gamma 2 loci as well as the Dl4Sl locus which is 3' of the IgCH loci. The 6.3:1.7 kilobase (kb) Bst EII C gamma 3-C gamma 2 haplotype was the most prevalent in the population from South-East England (frequency 0.364), whilst the 2.3:3.7 kb C gamma 3-C gamma 2 haplotype was the major haplotype in the German population (frequency 0.400). With one exception, the major haplotypes of these two populations differed from the ones previously published for a Caucasoid population from California. This suggests that there may be a major ancestral IgCH haplotype which has been maintained in the population, whilst other haplotypes tend to be specific for a particular group of Caucasoids.
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Hypertension in type I diabetes appears to be causally related to nephropathy, whereas the relationship between hypertension and type II diabetes is more complex, hypertension being present in the absence of clinically overt nephropathy and even preceding the onset of diabetes. In the diabetic, hypertension is exquisitely sodium-sensitive. It is in diabetic nephropathy that the best evidence has been obtained that treatment of hypertension retards the progression of renal failure. Consensus is still lacking with respect to the point when antihypertensive treatment should be started and the target blood pressure that should be aimed at. Currently, there is no evidence in humans that converting enzyme inhibitors are superior to alternative antihypertensive agents in retarding progression, but tantalizing preliminary evidence on this has been reported in nondiabetic patients with renal failure.
A high dietary phosphate load relative to GFR is thought to explain, at least in part, diminished renal 1-alpha hydroxylase activity in early renal failure (RF). To assess the role of dietary phosphate/GFR ratio in more detail, we examined the response of 1,25(OH)2D3 concentration to a controlled isolated reduction of dietary phosphate intake for up to 10 days with no change of Ca, Na and energy intake. We studied 7 healthy controls (2 male, 5 female, median age 45 years) and 6 non-nephrotic patients with early renal failure (RF) (3 males, 3 females, median age 55 years; median Cin 60.5ml/min/1.73 m2; 41-69). During an initial 3-day period of controlled diet with usual phosphate intake no difference of UVPi (median 27.6 mmol/day, 18.9-43.8) was found between controls and RF. A diet with 15 mmol Pi/day (confirmed by duplicate meal analysis) significantly reduced median UVPi (controls: 27.7 to 11.9 mmol/d; RF 27.4 to 14.1 mmol/d) with no change of median UVCa. Median day to day variation of 1,25(OH)2D3 levels (by RIA) in controls was 15.4%. Lowering dietary phosphate intake did not significantly change median 1,25(OH)2D3 levels in controls (45.7 vs. 38.3 pg/ml) and patients with RF, respectively (23.5 vs. 19.1 pg/ml). No changes of intact iPTH values were found. The experiment had a 68% power to detect a 15% change and a 99% power to detect a 30% change at a significance level of p less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)
Using radioimmunological estimation of beta 2-microglobulin (beta 2M), significantly greater serum values were found in 36 dialysis patients (44.4 +/- 20.3 mg/l) in comparison to healthy probands (1.5 +/- 0.2 mg/l). A significant relation to the duration of dialysis, diuresis and serum aluminium and ferritin was found. The used dialysers MLW 1.3/1.8 m2 (regenerated cellulose membrane) did not eliminate beta 2M from the blood. Significantly greater beta 2M concentrations were observed in patients suffering from arthralgia and bone pain, but not in radiologically verified arthropathy and destructive spondylarthropathy. Post-mortem examinations of 13 patients on haemodialysis treatment for between 10 and 90 months revealed synovial beta 2M-derived (AB-)amyloid deposits in four patients at different joints, but not in radiologically suspect areas. The results suggest that independent of serum beta 2M, beta 2M-derived amyloidosis may occur in elderly patients on dialysis for less than 5 years. Several cases were completely asymptomatic.
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To examine and characterize the vascular renin--angiotensin system in low-renin models of renal hypertension with and without the presence of overt renal insufficiency, we studied the formation and metabolism of angiotensin in isolated perfused rat hindquarter preparations. Rats with 5/6 nephrectomy (5/6NX) and rats with one-kidney, one clip (1K1C) hypertension were compared to sham operated (sham) animals. Angiotensin peptides in plasma or perfusate were characterized by high-performance liquid chromatography and radioimmunoassay (RIA). Plasma angiotensin II was lower, and blood pressure was higher in both experimental groups, compared to sham animals. Plasma angiotensinogen, measured by both direct and indirect RIA, was increased in both experimental groups. The spontaneous release of angiotensin I and angiotensin II from perfused hindquarters did not differ between the groups. Angiotensin I conversion was not different in 5/6NX or 1K1C groups compared with controls. Furthermore, angiotensin conversion was completely inhibited by captopril (1 mumol/l) in all groups. Renin-induced angiotensin release was significantly increased in 5/6NX as compared with sham rats, whereas there was no difference in renin-induced angiotensin release between 1K1C and sham animals. Angiotensin II degradation was significantly attenuated in 5/6NX rats when compared with sham rats (27.6% versus 53.9%, respectively, P less than 0.05) but was unaltered in 1K1C rats. Thus, in chronic uremic hypertension, renin-induced angiotensin formation was increased in the face of decreased angiotensin II degradation. These data suggest that vascular angiotensin may contribute to the elevated blood pressure observed in chronic renal failure. In 1K1C rats, vascular angiotensin formation and metabolism was unchanged despite suppressed plasma angiotensin II.
Patient survival and renal outcome were followed in 25 patients with biopsy confirmed Wegener's granulomatosis and renal involvement. Fourteen out of 25 patients required dialysis on admission, 11/25 patients did not. All patients were treated with a novel protocol comprising methylprednisolone and cyclophosphamide. The median follow-up observation was 36 months (12-113 months). With the exception of 1 patient (who died from causes not related to Wegener's granulomatosis) all patients are alive. Among the patients initially requiring dialysis (n = 14) 4 are in terminal renal failure after 0, 7, 21 and 38 months respectively. In the nondialysis group (n = 11) only 1 patient subsequently required chronic dialysis 30 months after clinical admission. Renal failure was due to non-compliance with immunosuppressive therapy in at least 2 patients. Percentage of obsolescent glomeruli and the degree of tubulointerstitial lesions, but not active glomerular lesions (crescents, necroses) predicted renal outcome. The major cause of renal functional impairment was relapse of Wegener's granulomatosis usually within 2 years after clinical remission. Therefore prolonged treatment with cyclophosphamide for at least 2 years after clinical remission is recommended. Two patients with initially negative immunohistology had a second renal biopsy which revealed de novo appearance of mesangial IgA deposits.
Recently it has been recognized that even minor elevations of blood pressure contribute to progression of renal failure. Furthermore it has been documented that antihypertensive treatment retards progression of renal failure. Despite impressive experimental data firm clinical evidence, incontrovertible on biostatistical grounds, is not yet available to document that converting enzyme inhibitors (CEI) are superior to alternative antihypertensive agents with respect to halting progression. CEI undoubtedly reduce albuminuria, independent of their effect on systemic blood pressure, and this is related to alterations of glomerular permeability. Recent experimental data suggest that growth processes in damaged kidneys are an important aspect of progression. It is a fascinating perspective, but yet unproven, that CEI interfere with these processes.
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In radioimmunological estimation of beta 2-microglobulin (beta 2m) significant higher serum values were found in 36 dialysis patients (44.4 +/- 20.3 mg/l) in comparison with healthy probands (1.5 +/- 0.2 mg/l). A significant relation to the duration of dialysis, diuresis, symptoms of the musculo-skeletal system, but not to radiologic changes or bone biopsy findings could be seen. Post mortem examinations carried out in 21 dialysis patients revealed AB-amyloid deposits in synovial tissue of different joints (particularly shoulder and hip joint) or intervertebral discs in eight patients (age 48 to 73 years, dialysis duration less than four years) without correlation to serum beta 2m level or radiographically suspect areas. In the tissue of cervical spine or intervertebral discs of two patients suffering from destructive spondylarthropathy no amyloid could be detected. These results suggest that AB-amyloid may occur in elderly patients early in the course of hemodialysis and may be asymptomatic in most cases.
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