The impact of surgical intervention on renal function in cystinuria / O impacto da intervenção cirúrgica sobre a função renal na cistinúria

ABSTRACT Introduction: Cystinuria is an autosomal recessive disorder due to intestinal and renal transport defects in cystine and dibasic amino acids, which result in recurrent urolithiasis and surgical interventions. This study aimed to assess the impact of surgical interventions on renal function by analyzing estimated glomerular filtration rates. Methods: Thirteen pediatric patients with cystinuria, who were followed-up in a single tertiary institution between 2004 and 2016, were included in the study. Medical records were reviewed to collect data on clinical presentation of patients, urine parameters, stone formation, medical treatment, surgical intervention, stone recurrence after surgical procedure, stone analysis, ultrasonography, 99m-technetium dimercaptosuccinic acid (99mTc-DMSA) radionuclide imaging results, and follow-up time. Creatinine clearances estimated by modified Schwartz (eGFR) formula before and after surgery were used to assess renal function and compared statistically. Results: Nine patients (69.2%) had renal scarring which were detected with 99mTc-DMSA radionuclide imaging. In ten patients (76.9%), open surgical intervention for stones were needed during follow-up. Significant difference was not detected between eGFR before and after surgical intervention (mean 92 versus 106, p = 0.36). Nine of the patients (69.2%) were stone free in the last ultrasonographic examination. Relapses of stone after surgery were seen in 66.6% of patients who underwent surgical intervention. Conclusions: Surgical interventions for urinary stones are commonly required in patients with cystinuria. Renal scarring is a prevalent finding in cystinuric patients. Surgical interventions have no negative impact on eGFR in patients with cystinuria according to the present study.

RESUMO Introdução: A cistinúria é um distúrbio autossômico recessivo causado por defeitos de transporte intestinal e renal da cistina e aminoácidos dibásicos que resultam em urolitíase recorrente e necessidade de intervenção cirúrgica. O presente estudo teve por objetivo avaliar o impacto das intervenções cirúrgicas sobre a função renal por meio da análise da taxa de filtração glomerular estimada. Métodos: Treze pacientes pediátricos com cistinúria acompanhados em uma instituição terciária entre 2004 e 2016 foram incluídos no estudo. Os prontuários médicos foram analisados e utilizados como fonte de dados sobre a apresentação clínica dos pacientes, parâmetros urinários, formação de cálculos, tratamento clínico, intervenção cirúrgica, recidiva de cálculos após procedimento cirúrgico, análise de cálculos, ultrassonografia, resultados de imagens com ácido dimercaptossuccínico marcado com tecnécio metaestável (99mTc-DMSA) e tempo de seguimento. A depuração de creatinina estimada pela fórmula modificada de Schwartz (TFGe) antes e após a cirurgia foi utilizada para avaliar e comparar estatisticamente os níveis de função renal. Resultados: Nove pacientes (69,2%) apresentaram cicatrizes renais detectadas por exame de imagem com 99mTc-DMSA. Dez pacientes (76,9%) necessitaram intervenção cirúrgica aberta por cálculo renal durante o seguimento. Não foram detectadas diferenças significativas entre os valores de TFGe anteriores e posteriores à intervenção cirúrgica (média de 92 vs. 106, p = 0,36). Nove pacientes (69,2%) não apresentaram cálculos no último exame ultrassonográfico. Recidivas de cálculos renais após cirurgia foram observadas em 66,6% dos pacientes submetidos a cirurgia. Conclusões: Intervenções cirúrgicas relativas a cálculos renais são frequentemente necessárias em pacientes com cistinúria. Cicatrizes renais são um achado prevalente em pacientes com cistinúria. De acordo com o presente estudo, cirurgia não afeta negativamente a TFGe de pacientes com cistinúria.

Reporte de un caso de Cistinuria: Uso de herramientas de diagnóstico a nivel nacional / Report of a case of cystinuria: Use of diagnostic tools at national level

La cistinuria es una enfermedad genética que se engloba dentro de alteraciones congénitas del transporte de aminoácidos con formación de cálculos en las vías urinarias, si bien es poco frecuente se caracteriza por su elevada recurrencia. En este trabajo presentamos el caso de una paciente de 34 años, con antecedentes de haber perdido un riñón por episodios anteriores de litiasis y con múltiples recidivas que es diagnosticada mediante la detección de cistina por espectroscopía infrarroja como componente único de 96 fragmentos de cálculos removidos mediante nefrolitotomía percutánea. La paciente fue evaluada laboratorialmente mediante el perfil metabólico y la cristaluria. Las indicaciones de tratamiento específicas incluyeron la administración de agentes alcalinizantes, régimen nutricional, y entrenamiento para control de pH urinario. Es importante señalar la agresividad de la litiasis de cistina con las consecuencias que puede tener la calidad de vida del paciente, y por tanto la importancia de contar con capacidades instaladas a nivel país para el diagnóstico y seguimiento de litiasis genéticas como la causada por la cistinuria(AU)

Cystinuria is a genetic disease that is included among congenital defects of renal amino acids transport that causes urinary stone formation. Although it is rare, it is characterized by its high recurrence. We present the case of a 34-year-old patient that lost one of her kidney because of recurrent episodes of lithiasis, and that was diagnosed by the detection of cystine with infrared spectroscopy as the sole component of 96 stone fragments removed by percutaneous nephrolithotomy. The patient was evaluated by metabolic profile and crystalluria. The specific treatment indications included the administration of alkalinizing agents, nutritional regimen, and training for personal measurement of urinary pH. This case highlights the aggressiveness of cystine stones with the consequences that may have on the quality of the patient life, and therefore the importance of having installed proper diagnostic capacities at national level to detect and monitor treatment efficacy in genetic lithiasis such as cystinuria(AU)

Genotype and Phenotype Analysis in Pediatric Patients with Cystinuria

Cystinuria is an inherited disorder characterized by defective renal reabsorption of cystine and dibasic amino acids leading to nephrolithiasis. This study was conducted to analyze the genotypes and phenotypes of pediatric patients with cystinuria. Eight children from Seoul National University Hospital and Asan Medical Center presenting with cystinuria from January 2003 to June 2016 were retrospectively analyzed. Mutational studies were performed by direct sequencing. Two of the 8 were male and 6 were female. The median ages at onset and diagnosis were 1.5 (range, 0.3–13.6) and 2.6 (range, 0.7–16.7) years, respectively. The median followed up was 7.7 (range, 3.4–14.0) years. Mutational analyses were performed in 7 patients and revealed biallelic SLC3A1 mutations (AA genotype) in 4 patients, a single heterozygous SLC3A1 mutation (A- genotype) in 1 patient, biallelic SLC7A9 mutations (BB genotype) in 1 patient, and a single heterozygous SLC7A9 mutation (B- genotype) in 1 patient. Two of the mutations were novel. No genotype-phenotype correlations were observed, except for earlier onset age in patients with non-AA genotypes than in patients with the AA genotype. All patients suffered from recurrent attacks of symptomatic nephrolithiasis, which lead to urologic interventions. At the last follow-up, 3 patients had a mild-to-moderate degree of renal dysfunction. This is the first study of genotypic and phenotypic analyses of patients with cystinuria in Korea.

Cuantificación de cistina en orina espontánea para la detección de cistinuria / Quantitation of urinary cystine for the detection of cystinuria / Determinagáo quantitativa de cistina urinaria para a detecgáo de cistinuria

La cistinuria es un error innato del metabolismo ocasionado por un defecto en el transporte renal de arginina, ornitina, lisina y cistina. La acumulación de este último aminoácido de baja solubilidad ocasiona episodios de urolitiasis característicos de la enfermedad. En el presente estudio se estandarizó un método espectrofotométrico confiable y de fácil ejecución para la determinación cuantitativa de cistina en orina espontánea. Se realizó el análisis en 184 muestras, correspondientes a 104 controles y 80 pacientes con urolitiasis. Con el objeto de validar el método y posteriormente establecer un rango de excreción normal en la población colombiana se evaluaron los siguientes parámetros: exactitud, precisión, linealidad y límite de detección. La técnica mostró coeficientes de variación intra e inter ensayos inferiores al 10% y una excelente linealidad, con un coeficiente r² entre concentraciones conocidas de cistina y absorbancia generada por el método de 0,998. Usando esta técnica se encontró un valor normal de excreción de 1,35 a 110,11 mg cistina/g creatinina. En cinco pacientes, de los 80 con nefrolitiasis, se hallaron valores elevados de cistina, compatibles con cistinuria. El método utilizado puede implementarse en cualquier laboratorio clínico para confirmar el diagnóstico de cistinuria e iniciar un tratamiento oportuno.

Cystinuria is an inborn error of metabolism, caused by a defect in renal tubular transport of the following aminoacids: arginine, ornithine, lysine and cystine. Accumulation of the latter poorly soluble aminoacid leads to the development of kidney stones, characteristic of the disease. In this study, an easy and dependable spectrophotometric method for the quantitative determination of urinary cystine was standardized. The analysis was performed on 184 samples from 104 controls and 80 patients with kidney stones. In order to validate the method and later establish a range of normal urinary cystine excretion in the Colombian population, the following parameters were evaluated: Accuracy, precision, linearity and lower limit of detection. The technique showed intra and intei assay coefficients of variation below 10%, and excellent linearity, with an R square (r²) coefficient between known cystine concentrations and absorbance generated by the method at 0.998. Using this technique, a normal urinary cystine excretion range of 1.35-110.11 mg cystine/g creatinine was found. Among the 80 patients with kidney stones, elevated urinary cystine levels were found in 5 of them, compatible with the presence of cystinuria. This method can be implemented in any clinical laboratory to confirm the diagnosis of cystinuria and provide opportune treatment.

A cistinúria é um erro inato do metabolismo, causado por um defeito no transporte tubular renal de ar-ginina, ornitina, lisina e cistina. A acumulagáo deste último aminoácido, pouco solúvel, provoca episodios de urolitíase, característicos da doenga. No presente estudo, foi padronizado um método espectrofotomé-trico confiável e de fácil execugáo para a determinagáo quantitativa de cistina em urina espontánea. A análise foi realizada em 184 amostras de 104 controles e 80 pacientes com urolitíase. A fim de validar o método e, posteriormente, estabelecer um intervalo de excregao normal na populagao colombiana, foram avaliados os seguintes parámetros: exatidáo, precisáo, linearidade e limite inferior de detecgáo. O método mostrou coeficientes de variagáo intra e inter ensaios inferiores a 10%, e excelente linearidade, com um coeficiente R quadrado (r²) entre concentragoes conhecidas de cistina e absorváncia gerada pelo método de 0,998. Com esta técnica, foi encontrado um valor normal de excregáo de 1,35-110,11 mg cistina/g de creatinina. Entre os 80 pacientes com urolitíase, foram encontrados níveis elevados de cistina em cinco deles, compatíveis com a presenga de cistinúria. Este método pode ser implementado em qualquer laboratorio clínico para confirmar o diagnóstico de cistinúria e proporcionar um tratamento oportuno.

Multimodal Treatments of Cystine Stones: An Observational, Retrospective Single-Center Analysis of 14 Cases

PURPOSE: To document the experiences of a single institution in evaluating the clinical courses and treatment outcomes of patients with cystine stones. MATERIALS AND METHODS: The clinical data of 14 patients with cystine stones who were treated at our institution from March 1994 to July 2012 were reviewed. These data included age at first visit, gender, family history, body mass index, presence of a single kidney, stone locations, stone burden, routine urinalysis, and culture. In addition, we also analyzed data on surgery, shock wave lithotripsy, medical treatment, stone recurrence or regrowth, and overall treatment success rates. RESULTS: The mean age of our patients at their first visit was 19.6+/-5.0 years, and eight patients were males. The median stone burden and mean urine pH before each surgery were 6.5 cm2 and 6.5+/-0.9, respectively. Two patients had a family history of cystine stones. Patients underwent surgery an average of 2.7 times. The median interval between surgeries was 27.3 months, and 1 open surgery, 12 percutaneous nephrolithotomies, and 25 ureterorenoscopies were performed. Potassium citrate or sodium bicarbonate was used in nine cases. D-Penicillamine was continuously used in three patients. Patients had an average incidence of 3.2 recurrences or regrowth of stones during the median follow-up period of 60.5 months. CONCLUSIONS: Patients with cystine stones have high recurrence or regrowth rates and relatively large stone burdens. Adequate treatment schedules must therefore be established in these cases to prevent possible deterioration of renal function.

A Case of Cystinuria with Multiple Renal Stones in an 8-month-old Girl

Cystinuria is an autosomal recessive disease characterized by impaired transport of cystine and dibasic amino acids in the proximal renal tubule, resulting in the formation of cystine stones. It is believed to account for about 1% of all kidney stones and up to 10% of pediatric stones. Here we report a case of cystinuria with multiple renal stones confirmed by genetic mutational analysis. An 8-month-old girl was admitted to AMC with persistent fever and multiple renal stones. A renal sonogram showed multiple stones at the right renal pelvis, right distal ureter, and left renal medullary portion. An approximately 1 cm renal stone was extracted spontaneously, and stone analysis revealed it to be composed entirely of cystine. Cystinuria was confirmed by increased urine dibasic amino acid levels, including cysteine, and genetic mutational analysis showed the patient to be a homozygote for the pathogenic c. 1820del (p.L607fs) of SLC3A1. Despite treatment with oral hydration and urinary alkalinization, and restricted intake of animal protein, the stones increased in size and number. The patient has since been treated with tiopronin.

Penicillamine-induced Elastosis Perforans Serpiginosa and Cutis Laxa in a Patient with Wilson's Disease

Elastosis perforans serpiginosa (EPS) is a rare reactive perforating dermatosis that is characterized by the transepidermal elimination of abnormal elastic fibers. Penicillamine, which is one of the clear triggers for EPS, is a heavy metal chelator that is primarily used for disorders such as cystinuria and Wilson's disease. It may cause alterations in the dermal elastic tissue such as pseudo-pseudoxanthoma elasticum, acquired cutis laxa, EPS and anetoderma. Herein we present a case of cutis laxa and EPS in a 34-year-old man who was previously on a long-term, high-dose of penicillamine for Wilson's disease. The combination of EPS and cutis laxa induced by penicillamine has rarely been reported and we report the first such case in Korea.

Non-Type I Cystinuria Associated with Mental retardation and Ataxia in a Korean Boy with a New Missence Mutation(G173R) in the SLC7A9 Gene

Cystinuria is an inherited renal and intestinal disease characterized by defective amino acids reabsorption and cystine urolithiasis. It is unusually associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9, have been identified in cystinuric patients. This report presents a 13-yr-old boy with cystinuria who manifested difficulty in walking, ataxia, and mental retardation. Somatosensory evoked potential of posterior tibial nerve stimulation showed the central conduction dysfunction through the posterior column of spinal cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and oral cystine loading test. We screened him and his family for gene mutation by direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new missence mutation G173R in SLC7A9 gene.

Urinary Lithiasis in Children : A Single Center Study

PURPOSE: Urinary lithiasis is uncommon in children, however, it may lead to chronic renal insufficiency and even end stage renal disease. The etiology of stone formation in children is largely unknown; although the most common causes are known to be associated with congenital anomalies of the genito-urinary(G-U) tract, urinary tract infections(UTI), and metabolic diseases. METHODS: A total of 73 children(male:female=42:31, mean age 6.6+/-5.3 years) presented with urinary lithiasis between Sep. 1998 and Jul. 2007 at Seoul National University Children's Hospital. The medical records were reviewed retrospectively. RESULTS: The most common presenting symptoms were gross hematuria(28/73, 38%) and flank or abdominal pain(23/73, 32%). The stones were located in the upper urinary tract in 48 patients(66%), in the bladder in 18(24%), and in both the bladder and upper urinary tract in 2 (3%). Congenital anomalies of the G-U tract with/without UTI were detected in 30 children (41%), hypercalciuria with/without hypercalcemia in 15(20%), and other metabolic diseases in 8(11%). In 17 patients(23%), no underlying cause of stone formation was detected. The majority of stones were infected stones(24/36, 67%), which were followed by calcium stones(8/36, 22%), uric acid stones(3/36, 8%), and cystine stones(1/36, 3%). Thirty-four patients(46%) underwent surgical procedures and/or extracorporeal shockwave lithotripsy for stone removal, and 13(18%) passed stones spontaneously with/without medical management. Stones recurred in 6 patients(8%): 4 with neurogenic bladder augmented by ileocystoplasty, 1 with cystinuria, and 1 with unknown etiology. CONCLUSION: The common causes of urinary lithiasis in children were congenital anomalies of the G-U tract with/without UTI and metabolic disorders including hypercalciuria/hypercalcemia. For the management of stones, minimally invasive procedures should be chosen on the basis of accompanying symptoms and the composition, locations and etiology of stones.

Successful treatment of homozygous cystinuria with captopril

Cystinuria is an autosomal recessive hereditary disorder associated with nephrolithiasis and its attendant complications. Traditional management using oral alkali, D-penicillamine, or mercaptopropionyglycine in an attempt to increase urinary cystine solubility is often unsuccessful due to intolerable side-effects. The aim of this study was to determine, if captopril could reduce urninary cystine excretion in homozygous cystinuric patients. Three cystinuric patients with a history of multiple cystine stones despite previous traditional therapy were treated with 150 mg captopril daily for 3 years after determination of their baseline 24-hour urine cystine excretion. Cystine excretion studies were repeated subsequently at 6-month intervals. The baseline 24-hour urine cystine excretion was within the expected limits for homozygous cystinuria in all patients [1072, 962 and 959 mg cystine per gm creatinine per 24 hours]. After institution of captopril treatment, all patients had a significant decrease in urinary cystine levels [374,313 and 451 mg cystine per gm creatinine per 24 hours]. No patient experienced recurrent nephrolithiasis or adverse drug effects. We conclude that captopril can significantly decrease urinary cystine excretion in patients with homozygous cystinuria. Captopril should be considered an alternative to traditional drug management of cystinuria

Successful Treatment of Homozygous Cystinuria with Captopril

Objective : Cystinuria is an autosomal recessive hereditary disorder associated with nephrolithiasis and its attendant complications. Traditional management using oral alkali; D-penicillamine; or mercaptopropionyglycine in an attempt to increase urinary cystine solubility is often unsuccessful due to intolerable side-effects. The aim of this study was to determine; if captopril could reduce urinary cystine excretion in homozygous cystinuric patients. Patients and methods : Three cystinuric patients with a history of multiple cystine stones despite previous traditional therapy were treated with 150 mg captopril daily for 3 years after determination of their baseline 24-hour urine cystine excretion. Cystine excretion studies were repeated subsequently at 6-month intervals. Results : The baseline 24-hour urine cystine excretion was within the expected limits for homozygous cystinuria in all patients (1072; 862 and 959 mg cystine per gm creatinine per 24 hours). After institution of captopril treatment; all patients had a significant decrease in urinary cystine levels (374; 313 and 451 mg cystine per gm creatinine per 24 hours). No patient experienced recurrent nephrolithiasis or adverse drug effects. Conclusion : We conclude that captopril can significantly decrease urinary cystine excretion in patients with homozygous cystinuria. Captopril should be considered an alternative to traditional drug management of cystinuria

Pediatric cystine calculi in west of Iran a study of 22 cases

Cystinuria is an autosomal recessive disorder which clinically presents as cystine calculi. In this study, we reviewed cystine calculi cases in the west of Iran to determine their common presentations and response to different therapeutic modalities. Between 1999 and 2005, we had 22 pediatric patients [11 boys and 11 girls] with cystine calculi. The demographic characteristics and clinical data of the patients as well as the treatment results were reviewed. The mean age of the patients was 34.20 ' 42.99 months [range, 4 to 156 months]. They were followed for a mean duration of 23 months [range, 3 to 70 months]. Thirteen patients [59.1%] had bilateral and 9 [41%] had unilateral kidney calculi. The sizes of the calculi were between 2 mm and 20 mm. Nine patients [41%] had renal atrophic changes and 1 [4.5%] had obstructive acute renal failure. Hydration and urinary alkalinization were administrated to all of the patients which yielded an excellent result in 54.5% and a poor response in 27.2%. Captopril started for 5 patients was effective only in 1. D-penicillamine had no favorable response. Extracorporeal shockwave lithotripsy was successful in 5 attempts and failed in 4. Surgical interventions were performed for 13 patients [59.1%] and 6 [27.2%] required more than 1 surgical operation. We recommend metabolic workup of childhood urolithiasis and appropriate medical management of its underlying disease. We also recommend minimally invasive urologic techniques including shockwave lithotripsy only when there are clear indications for nonmedical procedures

Physiological, Pharmacological and Toxicological Implications of Heterodimeric Amino Acid Transporters

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT (related to b0, +-amino acid transporter). Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters b0, +AT/BAT1 (b0, +-type amino acid transporter/b0, +-type amino acid transporter 1) and y+LAT1 (y+L-type amino acid transporter 1) result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

Cystine urinary lithiasis in Thailand: a report of five cases.

Cystine urinary stone is an autosomal recessive hereditary disease, frequently recurring and resisting fragmentation by Shockwave lithotripsy. As cases have never been reported before in Thailand, five cases of renal cystine stones at Ramathibodi Hospital were reported. Two were in the same family. In all cases the stones were removed by open surgery or percutaneous nephrolithotomy. Postoperatively, all the stones were analyzed by infrared spectroscopy for cystine. In two cases, cystine stones were also identified by scanning electron microscopy. Urine was analyzed for cystine by sodium cyanide-nitroprusside test, its concentration by spectrophotometry and cystine crystals were identified by the new crystal induction technique under light microscopy. By high-performance liquid chromatography (HPLC) test, urinary dibasic amino acids (ornithine, lysine, arginine) in these cases were also found to be significantly elevated. Clinical findings, diagnosis, treatment and prevention of cystine stones are reviewed.

Cystinuria: cause of recurrent renal stones in a 4-year-old girl.

This paper presents the case report of a 4-year and 6-month old girl with cystinuria. She clinically presented with recurrent radiopaque renal stones since the age of 3 years. She received 2 subsequent operations of pyelolithotomy combined with ureterolithotomy at the age of 3 years 6 months, and pyelolithotomy alone at the age of 5 years. She was initially diagnosed as having cystinuria by the presence of hexagonal plate crystals in her acidified urine and positive for the urinary cyanide-nitroprusside test. The diagnosis was confirmed by urinary amino acid analysis using quantitative ion-exchange chromatography which revealed increased amounts of cystine and dibasic amino acids of lysine and ornithine. In spite of maintaining a high fluid intake and alkalinizing urine by giving potassium citrate after the first operation, recurrent renal stones were found. Therefore, after the second operation, D-penicillamine was additionally introduced. During the 18-month follow-up, although there were recurrent renal stones, the rate of stone formation was slower. To the authors' knowledge, this is the first case report in Thailand.

Metabolic evaluation of children with recurrent nephrolithiasis

This study was conducted to define the underlying metabolic causes of recurrent renal stones in children at Alexandria, Egypt Out of 52 children with renal stones referred to Alexandria University Hospitals during the one year period of the study; 20 were recurrent [38.5%]. Their age ranged between one and 14 years. Mean age of onset was 3.5 +/- 3 years. Recurrence rate was one to three episodes over a mean period of 2.5 +/- 2 years. Before enrolment in the study, cases were subjected to one or more settings of stone surgery and/or ESWL. Thorough clinical, imaging and metabolic evaluation was done to all cases. Chemical analysis and infrared spectroscopy of all available stones were done. The results of the study revealed that stone recurrence was due to metabolic errors in 80% of the cases while the remaining 20% were idiopathic with no evidence of underlying metabolic diseases. Hypercalciuria was detected in 40% of cases. It was associated with distal renal tubular acidosis [RTA-l] in 62.5% and due to idiopathic renal leak [IH] in 37.5%. Cystinuria was present in 20% of cases, hyperuricosuria due to GSD-I in 10% and primary hyperoxaluria in another 10%. Hypocitraturia was found in 55% of cases. Hydronephrosis and recurrent UTIs were detected in 40% and 55% of cases respectively. All children with recurrent renal stones should undergo thorough metabolic evaluation to detect underlying etiology. Different etiological factors may coexist in the same patient; but underlying metabolic defects are the commonest in children with recurrent nephrolithiasis; [80%] in the current work. Early diagnosis and treatment of such metabolic errors will prevent or decrease the morbidity caused by recurrence, and will save these children from hazards of repeated stone surgery or ESWL

Relato de caso: ocorrência de doença de Crohn em uma paciente com cistinúria e retardo mental / Crohn's disease in a patient presenting with cystinuria and mental retardation

Uma mulher de 55 anos apresenta cistinúria, doença de Crohn e retardo mental. As manifestaçöes clínicas da doença de Crohn começaram aos 49 anos de idade. Um cálculo renal foi detectado aos 50 anos de idade e tratado com litotripsia extracorpórea. Cistinúria foi foi diagnosticada pelo encontro de cristais de cistina no sedimento urinário aos 55 anos de idade. O teste do nitroprussiato foi positivo. Na literatura, näo se encontram relatos da associaçäo dessas três entidades.(au)

A Case of Penicillamine Dermatopathy / 대한피부과학회지

Penicillamine dermatopathy refers to the characteristic hemorrhagic skin lesions found in persons receiving long-term penicillamine therapy for either Wilson's disease or cystinuria. These lesions are thought to develop as a result of faulty collagen and elastin synthesis. We described a 31-year-old woman with Wilson's disease who developed mild pruritic grouped matchhead-sized cream-colored papules on the dark reddish plaques on both knees and elbows.

Cistinúria - relato de caso e revisäo de literatura / Cystinuria - report of case and revision of literature

Cistinúria é uma doença genética autossômica recessiva, que na forma heterozigota leva a moderadas excreçöes dos aminoácidos cistina, lisina, arginina e ornitina na urina, e na forma homozigota leva à perda maciça dos quatro aminoácidos na urina e alto risco de formaçäo de cálculos renais. Descrevemos aqui o caso de uma criança, com história familiar de formaçäo de cálculos renais, que começou a eliminá-los aos 2 meses de idade, sendo diagnosticada e tratada 4 meses depois. Atualmente, com 4 anos de idade, apresenta funçäo renal normal, teve um episódio de infecçäo urinária e eliminou 10 cálculos após o início do tratamento. Foi submetida a procedimemto cirúrgico para retirada de um cálculo. Nos últimos 3 anos, sob tratamento, näo houve eliminaçäo ou evidência de formaçäo de cálculos renais.(au)