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- Eriksson, Per, et al.
(author)
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Improved outcome in Wegener's granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts
- 2009
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 496-506
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Journal article (peer-reviewed)abstract
- Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. The nephrology and rheumatology clinics at Linkoping University Hospital, Sweden. All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n = 32, old cohort) and after (n = 63, recent cohort) December 31, 1996. The two cohorts differed regarding the proportion of WG (75% vs. 56%, P = 0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 mu mol L-1 (16% dialysis-dependent) vs. 192 mu mol L-1 (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.
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- Lindell, Åke
(author)
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Clinical studies on cystinuria : With special reference to treatment with tiopronin
- 1996
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Doctoral thesis (other academic/artistic)abstract
- Cystinuria is an inherited disorder of the renal tubular transport of cystine and the dibasic amino acids across cell membranes. Defective renal tubular reabsorption causes a greatly increased urinary excretion of thepoorly soluble cystine, which in turn results in the formation of renal stones. Because of the life-long tendency for stone formation the patients are highly susceptible to complications of renal stone disease. Urinary supersaturation of cystine can be counteracted by reducing the urinary concentration (increased fluid intake, chemical modification with a sulfhydryl compound) or by increasing its solubility (urinary alkalinization). Long-tenn treatment with the sulfhydryl compound tiopronin (2-mercaptopropionylglycine) was evaluated in 31 patients with homozygous cystinuria (Papers I, II, IV). The patients were followed over an average of 7.8 years and the treatment was monitored by regular measurements of cystine in 24-hour urine samples by ionexch: mge chromatography, and by X-ray examinations. In 40 cystimnic patients total and split kidney function were investigated by gamma camera renography and measurement of glomerular filtration rate (GFR), mainly51CR-EDTA-clearance (Paper Ill). The diurnal variations in urinary cystine excretion was studied in 8 patients (Paper VI), and the effect of a low sodium intake in 13 (Paper V). A urinary free cystine concentration below the assumed level of saturation of 1200 J..Lmol/1 in 24h urine samples was achieved in 90% of patients treated with tiopronin. The required doses varied from 500 to 3000 mg!day which illustrates the necessity for individualization of treatment by regular measurements of the urinary cystine concentration. Increasing doses of tiopronin resulted in an unexpected decrease in the urinary excretion of the soluble tiopronin-cysteine mixed disulphide suggesting an influence on the general metabolism of cystine and cysteine. The rate of new stone· formation wa<> reduced by 60% and the need for active stone removal by 72%. Stone fonnation was eliminated in two thirds of the patients. In the remaining third there was some formation ofrenal stones in spite of acceptable concentrations of cystine in 24h samples. This shows that also the therapeutic level of urinary cystine has to be individually adjusted in some patients. Measurements of cystine in6h samples in patients without tiopronin treatment revealed considerable variations with peak concentration exceeding the corresponding 24h concentration by as mUch as 91%. Fractionated urine sampling may therefore be a tool for further adjustment of therapy. Treatment with tiopronin was well tolerated by the majority of patients, and the finding of clinically reversible membranous glomerulonephritis in 3 patients does not disqualify the drug from further use. Thirty per cent of 40 patients had light to moderate impainnent of renal function. Only 28% had an entirely normal renal function with both GFR and renography within nonnallimits, but there was no case with severe renal impairment. A renographic comparison between the pre-treatment and treatment periods suggested that the stone-preventing treatment based on monitoring of urinary cystine concentration resulted in preservation of renal function. Restriction of sodium intake resulted in a decrease in urinary cystine excretion in patients without tiopronin treatment, whereas the effect was significantly less in patients with tiopronin. In the patients without tiopronin the sodium delivery conveyed by sodium bicarbonate treatment neutralized the increased solubility of cystine obtained by its alkalinizing effect. The excretion of the disulphide between tiopronin and cysteine wasalso sodium dependent suggesting an active tubular reabsorption of this compound.
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