| 1. |
- Fjellstedt, Erik, et al.
(author)
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A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria
- 2001
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In: Urological research. - : Springer Science and Business Media LLC. - 0300-5623 .- 1434-0879. ; 29:5, s. 295-302
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Journal article (peer-reviewed)abstract
- For many years, urine alkalinization has been one of the cornerstones in the treatment of homozygous cystinuria. Because of the relationship found between the excretion of urinary sodium and cystine, potassium citrate has emerged as the preferred sodium-free alkalizing agent. To evaluate the usefulness of potassium citrate for urine alkalization in cystinuric patients, sodium bicarbonate and potassium citrate were compared in 14 patients (10 on tiopronin treatment and four without treatment with sulfhydryl compounds). The study started with 1 week without the use of any alkalizing agents (Period 0) followed by 2 weeks with sodium bicarbonate (Period 1) and 2 weeks with potassium citrate (Period 2). Urinary pH, volume, excretion of sodium, potassium, citrate and free cystine, as well as the plasma potassium concentration, were recorded. Potassium citrate was shown to be effective as an alkalizing agent and, in this respect, not significantly different from sodium bicarbonate. Even though a normal diet was used, a significant increase in urinary sodium excretion was observed with sodium bicarbonate (Period 1). Urinary potassium and citrate excretion increased with potassium citrate (Period 2). A significant correlation was found between urinary sodium and cystine in the tiopronin-treated patients. No significant differences in cystine excretion were recorded in Periods 0, 1 and 2. Plasma potassium was significantly higher during Period 2, but only one patient developed a mild hyperkalemia (5.0 mmol/l). The use of potassium citrate for urine alkalization in homozygous cystinuria is effective and can be recommended in the absence of severe renal impairment.
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| 2. |
- Fjellstedt, Erik, et al.
(author)
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Cystine analyses of separate day and night urine as a basis for the management of patients with homozygous cystinuria
- 2001
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In: Urological research. - : Springer Science and Business Media LLC. - 0300-5623 .- 1434-0879. ; 29:5, s. 303-310
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Journal article (peer-reviewed)abstract
- Based on previous observations of the diurnal variation of urinary cystine excretion, the use of separate day and night urine collections was proposed. To improve the medical treatment of patients with cystinuria, this strategy was performed to guide the fluid intake and the administration of SH compounds (tiopronin, D-penicillamine,and MESNA).Twenty-six patients (19 treated with SH compounds and seven with alkalinization and hydration only) were followed during two 3.5-year periods. During Period 1, 24-h urine was collected and during Period 2, separate day and night urine was collected.There were 56 episodes of high urinary cystine supersaturation (>1,200 µmol/l) during Period 2, 47% of which would have evaded detection with 24-h urine analysis. In comparison with Period 1, the urinary cystine concentration was lower (P<0.05), and the urinary volume was higher (P<0.05) during Period 2. Patients treated with tiopronin had reduced cystine excretion (P<0.05) and at the end of Period 2, an increased dose of tiopronin, reflecting a more aggressive treatment. Furthermore, a reduced number of stone episodes and need of active stone removal (P<0.05) was noted in the whole group of patients. Analyses of separate day and night urine samples can be used advantageously to reveal episodes of high supersaturation with cystine not detected in 24-h urine samples. Such a procedure might be useful for optimizing the treatment of patients with cystinuria.
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| 3. |
- Fjellstedt, Erik, et al.
(author)
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Urinary excretion of total cystine and the dibasic amino acids arginine, lysine and ornithine in relation to genetic findings in patients with cystinuria treated with sulfhydryl compounds
- 2003
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In: Urological research. - : Springer Science and Business Media LLC. - 0300-5623 .- 1434-0879. ; 31:6, s. 417-425
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Journal article (peer-reviewed)abstract
- Advances in molecular genetics have brought a deeper understanding of cystinuria. This autosomal recessive disease, which is caused by a defective tubular reabsorption of cystine and the three dibasic amino acids arginine, lysine and ornithine, results in a lifelong risk of renal stone formation because of the low solubility of cystine in urine. Mutations detected within the two genes known to be associated with cystinuria, SLC3A1 (related to type I) and SLC7A9 (related to non-type I), cannot, however, in all cases explain the disease. Inasmuch as a high urinary concentration of cystine is the basis of stone formation in these patients, our aim was to measure urinary total cystine, arginine, lysine and ornithine, in patients currently lacking a full genetic explanation for their disease. Thirty-three patients with cystinuria who were on long-term treatment with tiopronin or D-penicillamine were divided into two groups. Group 1 comprised eight patients who carried mutation in one of the SLC3A1 alleles and two patients who completely lacked mutations both in the SLC3A1 and the SLC7A9 genes, that is genetic findings discordant with the increased urinary excretion of cystine and the dibasic amino acids in these patients. Group 2 comprised 23 patients homozygous for mutations within SLC3A1, that is genetic findings in accordance with the excretion pattern of classic type I cystinuria. When the two groups were compared, Group 1 had a significantly higher total urinary excretion of cystine (p<0.01) as well as of arginine, lysine and ornithine (p<0.05) than Group 2. Also, when the two patients without mutations were excluded from the calculations, there still was a significant difference in the urinary excretion of total cystine (p<0.05). This suggests that the two patients without any detected mutations in the two known cystine transport genes also contributed to the difference. These unexpected findings indicate that an additional gene or genes participate in the urinary cystine reabsorption in the cystinuric patients who currently are without a full genetic explanation for their disease.
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| 4. |
- Harnevik, Lotta, et al.
(author)
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Identification of 12 novel mutations in the SLC3A1 gene in Swedish cystinuria patients
- 2001
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 18:6, s. 516-525
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Journal article (peer-reviewed)abstract
- Cystinuria is an autosomal recessive disorder that affects luminal transport of cystine and dibasic amino acids in the kidneys and the small intestine. Three subtypes of cystinuria can be defined biochemically, and the classical form (type I) has been associated with mutations in the amino acid transporter gene SLC3A1. The mutations detected in SLC3A1 tend to be population specific and have not been previously investigated in Sweden. We have screened the entire coding sequence and the intron/exon boundaries of the SLC3A1 gene in 53 cystinuria patients by means of single strand conformation polymorphism (SSCP) and DNA sequencing. We identified 12 novel mutations (a 2 bp deletion, one splice site mutation, and 10 missense mutations) and detected another three mutations that were previously reported. Five polymorphisms were also identified, four of which were formerly described. The most frequent mutation in this study was the previously reported M467T and it was also detected in the normal population with an allelic frequency of 0.5%. Thirty-seven patients were homozygous for mutations in the SLC3A1 gene and another seven were heterozygous which implies that other genes may be involved in cystinuria. Future investigation of the non-type I cystinuria gene SLC7A9 may complement our results but recent studies also suggest the presence of other potential disease genes.
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| 5. |
- Jendle-Bengten, Cecilia, et al.
(author)
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Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate
- 2000
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In: Scandinavian Journal of Urology and Nephrology. - 0036-5599 .- 1651-2065. ; 34:1, s. 36-41
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Journal article (peer-reviewed)abstract
- We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75-5 g of sodium potassium citrate (SPC, 14-18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period t(T)) than during a period of the same length immediately before treatment (period t(B)), but greater than the number formed during a corresponding period immediately after the diagnosis (period t(A)). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period t(T) than that during periods t(A) and t(B), but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups T(R) and T(NR), but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group T(R). When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75-5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment.
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