Recent Advances in the Therapy of Cystinuria

Lotz, Myron; Potts, John T.; Bartter, Frederic C.

doi:10.1093/milmed/130.8.768

Cited by 7 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of any sign of allergic reaction in the other nine patients treated with N-acetyl-penicfllamine is of interest in view of the incidence of hyperssitivity in cystinuric patients treated with D-penicillamine. Out of a total of 32 patients in four reported series, 13 (41%) developed morbilliform rashes, fever, upper respiratory tract symptoms, or other clear evidence of an allergic reaction (Crawhall et al, 1964;Lotz, Potts, and Bartter, 1965a;McDonald and Henneman, 1965;MacDonald and Fellers, 1966). D-Penicillamine therapy has been associated with impairment of renal function (Goldberg et al, 1963) and with the onset of the nephrotic syndrome (Fellers and Shahidi, 1959;Sternlieb and Scheinberg, 1964).…”

Section: Discussionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

“…It is likely that the other undesirable side-effects are related to molecular configuration involving the participation of two or more of the reactive groups. The known actions of D-penicillamine in decreasing free urinary cystine in cystinuria involve only the sulphydryl group necessary to form a mixed disulphide with cysteine (Eldjarn and Hambraeus, 1964;Bartter et al, 1965).…”

mentioning

confidence: 99%

See 2 more Smart Citations

New Agent in the Treatment of Cystinuria: N-acetyl-D-penicillamine

Stokes¹,

Potts²,

Lotz³

et al. 1968

BMJ

View full text Add to dashboard Cite

Treatment of cystinuria with D-penicille, introduced by Crawhall, Scowen, and Watts (1963), has dramatically reduced morbidity due to cystine urolithiasis in selected patients, both by preventing new stone formation (Crawhall, Scowen, and Watts, 1964; Bartter, Lotz, Thier, Rosenberg, and Potts, 1965;MacDonald and Fellers, 1966) and by dissolving stones lodged in the renal pelvis (Lotz and Bartter, 1965;McDonald and Henneman, 1965). These effects were apparently based on formation of the more soluble mixed disulphide, penicillaminecysteine, in place of cystine. However, the administration of D-penicillamine involves a definite risk of complications, such as reactions resembling serum sickness, skin rash, nephrotic syndrome, agranulocytosis, impairment of taste sensation, and iron depletion. In addition, D-penicillamilne inactivates pyridoxal-5-phosphate and gives rise to biochemical changes typical of pyridoxine deficiency in experimental animals (Asatoor, 1964) and in man (Jaffe, Altman, and Merryman, 1964). It also affects collagen metabolism, producing inhibition of wound-healing in normal rats (Nimni and Bavetta, 1965) and in patients after long-term treatment for Wilson's disease or cystinuria (Scheinberg, 1964;Harris and Sjoerdsma, 1966).All three of the reactive sites of the D-penicillamine molecule -the a-amino group, the sulphydryl group, and the terminal carboxyl group-are required for maximal metal-chelating activity (Aposhian, 1961); interference with pyridoxal phosphate involves at least two, the a-amino and the sulphydryl (du Vigneaud, Kuchinskas, and Horvath, 1957 Henry, Sobel, and Chiamori (1958), respectively. In six patients urinary excretion of kynurenine during 24 hours after a 2-g. oral load of L-tryptophan was determined by the method of Tompsett (1959). N-acetyl-penicillamine, 2 to 4 g./day by mouth in equally divided six-hourly doses, was administered for a period of five days to five weeks. Haematological, liverfunction, and tryptophan-loading tests were repeated at weekly intervals; serum copper, ceruloplasmin, and inulin and P.A.H.clearances were determined on one or more occasions; and the 24-hour urinary output of free cystine, N-acetylpenicillamine-cysteine mixed disulphide and cysteine-homocysteine mixed disulphide was measured daily or at intervals. Similar studies were also carried out in eight patients during a course of D-penicillamine 2 to 4 g./day.The procedures for collecting 24-hour urine specimens, for determining renal clearances, and for measuring cystine and mixed disulphides in urine and plasma were as described elsewhere (Stokes, Potts, Lotz, and Bartter, 1966a, 1968), except for a modification of the automatic amino-acid analyser system necessary for the determination of homocysteine-cysteine; elution at 550 C. with 0.2 M sodium citrate pH 3.5 buffer (68 ml./hour) was followed after 30 minutes by 0.2 M citrate pH 4.1 buffer containing 2.3% benzyl alcohol and 5% propanol. ResultsCharacteristics of N-acetyl-D-penicillamine and N-acetyl-D-penicillamine-cysteine N-ace...

show abstract

Section: Discussionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

New Agent in the Treatment of Cystinuria: N-acetyl-D-penicillamine

Stokes¹,

Potts²,

Lotz³

et al. 1968

BMJ

View full text Add to dashboard Cite

show abstract

“…Further work was reported by the same group in 1964 and soon confirmed by other workers (Lotz and Potts, 1964;King and Boyce, 1965). Within a few years dissolution of stones had also been reported in cystinuric patients taking penicillamine (McDonald and Henneman, 1965;Lotz et al, 1965;Crawhall et al, 1967;Frimpter, 1968). L(--)penicillamine and DL(--)penicillamine should not be used since L(--)penicillamine is more toxic than the D(--)penicillamine due to its effect on pyridoxine metabolism (Gibbs and Watts, 1969).…”

Section: Cysteine -Homocysteine Disulphidementioning

confidence: 99%

Cystinuria and its treatment: 25 years experience at St. Bartholomew's hospital

Stephens

1989

J of Inher Metab Disea

View full text Add to dashboard Cite

Cystinuria is an inherited condition affecting the active transport of the diamino acids cystine, ornithine, lysine and arginine across the renal tubule and the small intestine. The only clinical effect is the production of urinary tract stones and if these can be prevented the affected individuals can lead a normal life. In many people cystine stones can be dissolved and new stone formation prevented by a high fluid intake, but if this does not succeed regular treatment with penicillamine will do so. Although many side-effects have been described with penicillamine treatment it is rare for them to be severe enough to prevent its use in patients with cystinuria. Since the clinical effects of cystinuria can be prevented by either a high fluid intake or by penicillamine it is important to make the diagnosis in affected individuals as soon as possible and cystinuria should therefore be considered in all people (regardless of age) who form urinary stones.

show abstract

“…DENT and SENIOR (1955) have pointed out that daily protein intake would have to be restricted to 20 g, if the urinary cystine output is to be lowered by one third. This view has been supported by LoTZ et al (1965) and by KOLB et al (1967), although ZINNEMANN and JONES (1966) think so harsh a restriction unnecessary. An intake as low as this barely escapes the risk of malnutrition, even in adults.…”

Section: The Treatment Of Cystine Calculimentioning

confidence: 99%