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Ann Transl Med 2018 Dec;6(24):467

Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

The 21 century is an exciting time to be in the field of metabolic medicine. As with many fields, one of the keys to anticipating the future is to understand the past. The term "inborn error of metabolism" was first coined in 1908 by Sir Archibald Garrod, in reference to four disorders (alkaptonuria, pentosuria, cystinuria and albinism). Read More

Urolithiasis 2019 Jan 25. Epub 2019 Jan 25.

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Guoxue Xiang#37, Chengdu, 610041, Sichuan, China.

Indian J Nephrol 2018 Nov-Dec;28(6):490

Department of Paediatrics, Al-Kindy College of Medicine, University of Baghdad, Baghdad, Iraq.

Pediatr Nephrol 2019 Jan 4. Epub 2019 Jan 4.

Department of Pediatrics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, N6A 5W9, Canada.

Background: The incidence of nephrolithiasis in children and adolescents is increasing and appears to double every 10 years. The most important role of the pediatric nephrologist is to diagnose and modify various metabolic and non-metabolic risk factors, as well as prevent long-term complications especially in the case of recurrent nephrolithiasis.

Objective: The purpose of this review is to summarize the existing literature on the etiology and management of pediatric nephrolithiasis. Read More

Urolithiasis 2019 Feb 18;47(1):91-98. Epub 2018 Dec 18.

Chair of Nephrology, Department of Translational Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.

In the last decades, proteomics has been largely applied to the Nephrology field, with the double aim to (1) elucidate the biological processes underlying renal diseases; (2) identify disease-specific biomarkers, predictor factors of therapeutic efficacy and prognostic factors of disease progression. Kidney stone disease, and in particular, inherited nephrolithiasis (INL) are not an exception. Given the multifactorial origin of these disorders, the combination of genomics and proteomics studies may complement each other, with the final objective to give a global and comprehensive mechanistic view. Read More

Compr Physiol 2018 Dec 13;9(1):343-373. Epub 2018 Dec 13.

Research School of Biology, The Australian National University, Canberra, ACT 2601, Australia.

The small intestine mediates the absorption of amino acids after ingestion of protein and sustains the supply of amino acids to all tissues. The small intestine is an important contributor to plasma amino acid homeostasis, while amino acid transport in the large intestine is more relevant for bacterial metabolites and fluid secretion. A number of rare inherited disorders have contributed to the identification of amino acid transporters in epithelial cells of the small intestine, in particular cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, and dicarboxylic aminoaciduria. Read More

J Pediatr Urol 2018 Nov 10. Epub 2018 Nov 10.

Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Hematuria, either macroscopic or microscopic, is an incidental finding of multiple nephrologic or urologic disorders. Disturbances of urine inhibitors or promotors have been suggested as the potential causes of isolated idiopathic hematuria in children and its recurrence. Meanwhile, appropriate treatment of these risk factors might improve secondary asymptomatic or macroscopic hematuria. Read More

Int Urol Nephrol 2018 Dec 5. Epub 2018 Dec 5.

Nephrology Division, New York University Langone Medical Center, New York, NY, USA.

Purpose: The purpose of the study was to assess the differences in the concentration and function of urinary proteins between patients with cystine stones (CYS) and healthy controls (HC). We postulated that CYS and HC groups would demonstrate different proteomic profiles.

Methods: A pilot study was performed comparing urinary proteomes of 10 patients with CYS and 10 age- and gender-matched HC, using liquid chromatography-mass spectrometry. Read More

Urolithiasis 2019 Feb 4;47(1):57-66. Epub 2018 Dec 4.

Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, 08854, USA.

Cystinuria, a genetic disorder of cystine transport, is characterized by excessive excretion of cystine in the urine and recurrent cystine stones in the kidneys and, to a lesser extent, in the bladder. Males generally are more severely affected than females. The disorder may lead to chronic kidney disease in many patients. Read More

Biomedicine (Taipei) 2018 Dec 26;8(4):26. Epub 2018 Nov 26.

Isfahan Kidney Transplantation Research Center, Department of Urology, Alzahra Research Centers, Isfahan University of Medical Science, Isfahan, Iran.

Background: Cystinuria as an autosomal recessive sickness is a relatively rare disease. Formation of cystine stones indicates cystinuria. Few studies are considered the cysteine crystal volume in management of cystinuria. Read More

Urolithiasis 2019 Feb 23;47(1):115-123. Epub 2018 Nov 23.

UOC Nefrologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Deciding whether to accept a donor with nephrolithiasis is a multifaceted task because of the challenge of finding enough suitable donors while at the same time ensuring the safety of both donors and recipients. Until not long ago, donors with a history of renal stones or with stones emerging during screening on imaging were not considered ideal, but recent guidelines have adopted less stringent criteria for potential donors at risk of stones. This review goes through the problems that need to be approached to arrive at a wise clinical decision, balancing the safety of donors and recipients with the need to expand the organ pool. Read More

J Cell Mol Med 2019 Feb 18;23(2):1593-1597. Epub 2018 Nov 18.

Endourology and Stone Disease Section, Division of Urology, University of Sao Paulo Medical School, Sao Paulo, Brazil.

The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome-Wide Human SNP 6. Read More

J Bone Miner Res 2018 Nov 5. Epub 2018 Nov 5.

Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Renal calcification (RCALC) resulting in nephrolithiasis and nephrocalcinosis, which affects ∼10% of adults by 70 years of age, involves environmental and genetic etiologies. Thus, nephrolithiasis and nephrocalcinosis occurs as an inherited disorder in ∼65% of patients, and may be associated with endocrine and metabolic disorders including: primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, and hyperoxaluria. Investigations of families with nephrolithiasis and nephrocalcinosis have identified some causative genes, but further progress is limited as large families are unavailable for genetic studies. Read More

Saudi J Kidney Dis Transpl 2018 Sep-Oct;29(5):1203-1206

Department of Pediatric Nephrology, Sheikh Khalifa Medical City, Abu Dhabi, UAE.

The incidence of urolithiasis in children has shown an increase in recent years which may be attributed to changing dietary patterns, sedentary lifestyles, and obesity. Among the various etiologies for renal stones in children, two rare entities worth mentioning are cystinuria and 2, 8-dihydroxyadenine (DHA) urolithiasis. Cystinuria is an inherited cause of nephrolithiasis which occurs due to impaired cystine reabsorption in the renal proximal tubule. Read More

ACS Chem Neurosci 2018 Nov 13. Epub 2018 Nov 13.

Department of Science, School of Technology , Pandit Deendayal Petroleum University , Gandhinagar , Gujarat 382007 , India.

We report for the very first time the discovery of amyloid-like self-assemblies formed by the nonaromatic single amino acids cysteine (Cys) and methionine (Met) under neutral aqueous conditions. The structure formation was assessed and characterized by various microscopic and spectroscopic techniques such as optical microscopy, phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The mechanism of self-assembly and the role of hydrogen bonding and thiol interactions of Cys and Met were assessed by Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and solid state NMR along with various control experiments. Read More

BMC Nephrol 2018 Oct 20;19(1):278. Epub 2018 Oct 20.

Institute of Human Genetics, University Hospital, Technical University RWTH Aachen, Pauwelsstr. 30, D-52074, Aachen, Germany.

Background: Cystinuria is caused by the defective renal reabsorption of cystine and dibasic amino acids, and results in cystine stone formation. So far, mutations in two genes have been identified as causative. The SLC3A1/rBAT gene encodes the heavy subunit of the heterodimeric rBAT-bAT transporter, whereas the light chain is encoded by the SLC7A9/ bAT gene. Read More

Arch Dis Child Educ Pract Ed 2018 Sep 15. Epub 2018 Sep 15.

Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

: A 12-year-old boy, with intermittent abdominal pain from 3 years of age, presented with increased frequency of right lower quadrant pain (at least three episodes per week over the past six months) and pain during micturition affecting school attendance. His family history included referred urolithiasis. An abdominal ultrasound performed 1 year before our visit showed a small stone of 4 mm in the right renal pelvis for which he did not receive any therapy. Read More

Biomed Chromatogr 2019 Feb 26;33(2):e4375. Epub 2018 Sep 26.

Department of Chemistry, Missouri University of Science and Technology, Rolla, MO, USA.

Tiopronin, formally 2-mercaptopropionylglycine (MPG), is currently prescribed to treat cystinuria and rheumatoid arthritis, and its antioxidant properties have led to its investigation as a treatment for cataracts, a condition in which oxidative stress is strongly implicated. To study its accumulation in the eye, a reliable, isocratic HPLC method was developed for the determination of MPG and its primary metabolite 2-mercaptopropionic acid (MPA) in plasma and relevant ocular tissues. This method utilizes pre-column derivatization and fluorescence detection. Read More

Clin Lab 2018 Jul;64(7):1145-1151

Background: Cystinuria is a rare inherited renal stone disease caused by mutations in the SLC3A1 and SLC7A9 genes. The Chinese cystinuria phenotype and genotype have rarely been reported in the literature.

Methods: For this research, the clinical features and genetic etiology were analyzed in seven children, and the clinical characteristics were summarized. Read More

Biomed Khim 2018 Aug;64(4):315-325

Institute of Molecular Medicine of the Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; Research Centre for Medical Genetics, Moscow, Russia.

Urolithiasis is a common urological problem. In most cases, this multifactorial pathology develops due to the combination of inherited low-penetrance gene variants and environment factors such as urinary tract infections and unbalanced diet. However, some cases are monogenic. Read More

Mol Biol Rep 2018 Oct 1;45(5):1165-1173. Epub 2018 Aug 1.

Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, P.O.Box: 81746-73461, Isfahan, Iran.

Cystinuria is an autosomal recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from renal tubule and small intestine. Mutations in two genes: SLC3A1, encoding the heavy chain rbAT of the renal cystine transport system and SLC7A9, the gene of its light chain b AT have a crucial role in the diseases. In our previous studies from Iranian populations with Cystinuria totally six and eleven novel mutations respectively identified in SLC3A1 and SLC7A9 genes. Read More

J Urol 2018 Dec 27;200(6):1285-1289. Epub 2018 Jul 27.

Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire; EDGE Consortium. Electronic address:

Purpose: Patients with cystinuria are often treated with medical alkalization and shock wave lithotripsy, although each treatment is hypothesized to increase the risk of calcium phosphate stones. We performed a multicenter retrospective review to evaluate whether stones of another composition develop in patients with cystinuria and with what frequency.

Materials And Methods: We retrospectively reviewed the records of a multi-institutional cohort of patients with cystinuria. Read More

J Bras Nefrol 2018 Jul-Sep;40(3):256-260. Epub 2018 Jun 21.

Mersin University Faculty of Medicine, Department of Pediatric Urology, Mersin, Turkey.

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. Read More

Metab Brain Dis 2018 Jun 24. Epub 2018 Jun 24.

2nd Medical Department with Cardiology and Intensive Care Medicine, Krankenanstalt Rudolfstiftung, Vienna, Austria.

Ann Cardiol Angeiol (Paris) 2018 Jun 19;67(3):219-221. Epub 2018 May 19.

Service d'endocrinologie-diabétologie-maladies métaboliques, l'institut du Thorax, CHU de Nantes, 44093 Nantes cedex 1, France. Electronic address:

A 31-year-old patient was followed for cystinuria, justifying CT scans. In 2006, a tissue mass of 3cm of the right adrenal gland, homogeneous, measured at 3.5cm in 2007 was noted. Read More

Angew Chem Int Ed Engl 2018 Jul 20;57(28):8421-8424. Epub 2018 Apr 20.

Department of Biological Chemistry and Molecular Modeling, IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain.

The study of molecular networks represents a conceptual revolution in chemistry. Building on previous knowledge and after understanding the rules of non-covalent interactions, the design of stimulus-responsive chemical systems is possible. Herein we report a new strategy, based on the reorganization of a dynamic chemical network that generates new fluorescent associations in the presence of cysteine or cystine. Read More

J Urol 2018 Apr 18;199(4):887-888. Epub 2018 Jan 18.

Metab Brain Dis 2018 08 7;33(4):1375-1379. Epub 2018 Apr 7.

Pediatric Hematology-Oncology Training and Research Hospital, Pediatric Genetic Unit, Ankara, Turkey.

Hypotonia-cystinuria syndrome is a very rare autosomal recessive contiguous gene deletion syndrome of PREPL and SLC3A1 at 2p21 with neuromuscular and neuroendocrinologic presentation. We report a two-year-six-month-old affected female infant and her five-month-old affected brother with a novel homozygous deletion in SLC3A1 and PREPL gene. Both of siblings had mild facial dysmorphism, hypotonia, feeding problems, failure to thrive, developmental delay. Read More

Bioorg Med Chem Lett 2018 05 10;28(8):1303-1308. Epub 2018 Mar 10.

Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, United States. Electronic address:

To overcome the chemical and metabolic stability issues of l-cystine dimethyl ester (CDME) and l-cystine methyl ester (CME), a series of l-cystine diamides with or without N-methylation was designed, synthesized, and evaluated for their inhibitory activity of l-cystine crystallization. l-Cystine diamides 2a-i without N-methylation were found to be potent inhibitors of l-cystine crystallization while N-methylation of l-cystine diamides resulted in derivatives 3b-i devoid of any inhibitory activity of l-cystine crystallization. Computational modeling indicates that N-methylation leads to significant decrease in binding of the l-cystine diamides to l-cystine crystal surface. Read More

Indian J Nephrol 2018 Jan-Feb;28(1):84-85

Medical Genetics, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.

J Urol 2018 Feb 8;199(2):336. Epub 2017 Nov 8.

J Zoo Wildl Med 2017 Dec;48(4):1102-1107

Cystinuria is a condition caused by defects in amino acid transport within the kidneys and small intestines. It has been reported in humans, dogs, domestic cats, ferrets, nondomestic canids, and nondomestic felids, including servals ( Leptailurus serval). Genetic mutations have been identified in dogs, humans, and domestic cats. Read More

Urol J 2017 01 23;15(1):11-15. Epub 2017 Jan 23.

Department of Urology, Ankara Training and Research Hospital, Ankara, Turkey.

Purpose: To investigate the effect of respiratory induced kidney mobility on success of shock wave lithotripsy (SWL) with an electrohydraulic lithotripter.

Materials And Methods: Between May 2013 and April 2015, 158 patients underwent SWL treatment for kidney stones with an electrohydraulic lithotripter. The exclusion criteria were presence of a known metabolic disease (such as cystinuria), non-opaque stones, need for focusing with ultrasonography, abnormal habitus, urinary tract abnormalities, and inability to tolerate SWL until the end of the procedure. Read More

Einstein (Sao Paulo) 2017 Oct-Dec;15(4):452-456. Epub 2017 Dec 18.

Centro Universitário Faculdade Assis Gurgacz, Cascavel, PR, Brazil.

Objective: To evaluate the prevalence of metabolic disorders associated with nephrolithiasis in a female population.

Methods: A retrospective study on 1,737 patients with evidence of recent formation of renal stones, being 54% females. The laboratory investigation consisted of at least two samples of blood and 24-hour urine to assess calcium, uric acid, citrate and creatinine levels, qualitative cystinuria, urinary pH following fasting and 12-hour water restriction, urine culture, serum creatinine and parathyroid hormone. Read More

Asian J Urol 2017 Jan 28;4(1):18-26. Epub 2016 Nov 28.

Smith Institute for Urology, Hofstra Northwell School of Medicine, Lake Success, NY, USA.

Over 1%-15% of the population worldwide is affected by nephrolithiasis, which remains the most common and costly disease that urologists manage today. Identification of at-risk individuals remains a theoretical and technological challenge. The search for monogenic causes of stone disease has been largely unfruitful and a technological challenge; however, several candidate genes have been implicated in the development of nephrolithiasis. Read More

Urol Nurs 2017 Mar-Apr;37(2):90-3

The diagnosis and treatment of patients with rare inherited metabolic disorders associated with recurrent and often obstructive kidney stones are important to the prevention of chronic kidney disease or end stage renal disease. Two case studies in this article describe the diagnosis and management of cystinuria, the most common rare kidney stone disorder. Read More

Urol Nurs 2017 Mar-Apr;37(2):81-9, 102

Kidney stones, especially those that present in childhood/adolescence, may be due to rare inherited disorders such as cystinuria. Early recognition and prompt treatment can help reduce or even prevent the serious long-term complications of these rare stone disorders. Read More

J Oral Maxillofac Surg 2018 May 22;76(5):1013-1015. Epub 2017 Nov 22.

Department Head, Aix Marseille University, Marseille, France; Surgery Department-Maxillofacial and Stomatology, Conception University Hospital, Marseille, France; and Laboratoire Parole et Langage, Aix-en-Provence, France.

Salivary gland lithiasis affects 1 to 2% of adults. The submandibular glands are concerned in 87% of cases. An association between kidney and salivary lithiases, although often mentioned, has rarely been observed. Read More

J Endourol 2018 02 3;32(2):148-153. Epub 2018 Jan 3.

1 Department of Urology, University of California , San Francisco, San Francisco, California.

Introduction: Cystinuria is a genetic disorder marked by elevated urinary cystine excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly similar contralateral renal anatomy, a subset of cystinuric patients consistently form stones in only one kidney. The aim of this study is to evaluate clinical outcomes in unilateral vs bilateral cystine stone formers. Read More

PLoS One 2017 22;12(11):e0188543. Epub 2017 Nov 22.

Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.

Background: A large and growing number of inherited genetic disease mutations are now known in the dog. Frequencies of these mutations are typically examined within the breed of discovery, possibly in related breeds, but nearly always in purebred dogs. No report to date has examined the frequencies of specific genetic disease mutations in a large population of mixed-breed dogs. Read More

J Urol 2017 Nov 9;198(5):975. Epub 2017 Aug 9.

J Urol 2018 Feb 12;199(2):495-499. Epub 2017 Sep 12.

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Jane and Charles Pak Center for Mineral Metabolism and Clinical Research, Dallas, Texas. Electronic address:

Purpose: An accurate urinary predictor of stone recurrence would be clinically advantageous for patients with cystinuria. A proprietary assay (Litholink, Chicago, Illinois) measures cystine capacity as a potentially more reliable estimate of stone forming propensity. The recommended capacity level to prevent stone formation, which is greater than 150 mg/l, has not been directly correlated with clinical stone activity. Read More

Minerva Urol Nefrol 2018 Feb 7;70(1):87-94. Epub 2017 Sep 7.

Department of Urology, University of Rome Tor Vergata, Rome, Italy.

Background: Nephrolithiasis is a common condition with several studies documenting an increased prevalence over the past four decades. EAU and AUA guidelines recommend 24-hour urine metabolic evaluation in high-risk stone formers. Aim of this study is to retrospectively evaluate the first three years of experience with LithoTest® (Biohealth Italia Srl, Turin, Italy) through the analysis of demographic, clinical and biochemical data collected from a large cohort of patients with kidney stones. Read More

Bio Protoc 2017 Jul;7(14)

Department of Urology, University of California, San Francisco, CA, USA.

Cystinuria is a rare genetic disorder characterized by recurrent, painful kidney stones, primarily composed of cystine, the dimer of the amino acid cysteine (Sumorok and Goldfarb, 2013). Using a mouse model of cystinuria, we have recently shown that administration of drugs that increase cystine solubility in the urine can be a novel therapeutic strategy for the clinical management of the disease (Zee ., 2017). Read More

J Pediatr Urol 2017 Aug 4;13(4):357.e1-357.e7. Epub 2017 Aug 4.

Division of Urology, The Hospital for Sick Children, Toronto, ON, Canada.

Introduction: Hypercalciuria, hypocitraturia and cystinuria are the most common underlying metabolic stone abnormalities in children. The present study compared stone growth patterns, stone burden, and the risk of stone-related surgery among these underlying metabolic conditions.

Methods: A retrospective cohort of 356 children with renal stones, followed from 2000 to 2015, was studied. Read More

Clin J Am Soc Nephrol 2017 Oct 22;12(10):1699-1708. Epub 2017 Aug 22.

Section of Nephrology, Department of Medicine, University of Chicago, Chicago, Illinois

Nephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Read More

BMC Genomics 2017 08 11;18(Suppl 5):550. Epub 2017 Aug 11.

School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, UK.

Background: Cystinuria is an inherited disease that results in the formation of cystine stones in the kidney, which can have serious health complications. Two genes (SLC7A9 and SLC3A1) that form an amino acid transporter are known to be responsible for the disease. Variants that cause the disease disrupt amino acid transport across the cell membrane, leading to the build-up of relatively insoluble cystine, resulting in formation of stones. Read More