tiopronin
Regulatory sources consulted
Approved indications
- Prevention of cystine stones, with high fluid intake, alkali, and diet, in adults and patients aged 9 years or older with severe homozygous cystinuria not responding to those measures alone.
Contraindications
Absolute
- Hypersensitivity to tiopronin or components.
Clinical warnings
- Major warning · May cause proteinuria, nephrotic syndrome, or membranous nephropathy. Assess proteinuria before treatment and every 3–6 months; stop if proteinuria develops and monitor urinary protein and renal function. — FDA/DailyMed, set_id 02e24443-04c6-4b98-a395-49aec4a468de
- Major warning · Measure urinary cystine at 1 month and then every 3 months. Hypersensitivity with fever, rash, arthralgia, and lymphadenopathy may occur. — FDA/DailyMed, set_id 02e24443-04c6-4b98-a395-49aec4a468de
Drug interactions
- ModerateAlcohol
Mechanism: Alcohol accelerates tiopronin release from this delayed-release formulation.
Recommendation: Avoid alcohol from 2 hours before until 3 hours after each dose.
FDA/DailyMed, set_id 02e24443-04c6-4b98-a395-49aec4a468dehttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02e24443-04c6-4b98-a395-49aec4a468de
Adverse events
Common (≥1%)
Nausea or vomiting · Diarrhea or soft stools · Oral ulcers · Rash · Fatigue or fever · Arthralgia · Proteinuria
Rare but serious
Nephrotic syndrome · Membranous nephropathy · Severe hypersensitivity
Pregnancy and lactation
Published data have not identified a drug-associated fetal risk. Breastfeeding is not recommended because of serious reaction risk, including nephrotic syndrome, and possible suppression of milk production.
Recent literature (PubMed)
Drug-induced kidney diseases represent a wide range of diseases that are responsible for a significant proportion of all acute kidney injuries and chronic kidney diseases. In the present review, we focused on drug-induced glomerular diseases, more precisely podocytopathies - minimal change diseases (MCD), focal segmental glomerulosclerosis (FSGS) - and membranous nephropathies (MN), from a physiological and a pharmacological point of view. The glomerular filtration barrier is composed of podocytes that form foot processes tightly connected and directly in contact with the basal membrane and surrounding capillaries. The common clinical feature of these diseases is represented by the loss of the ability of the filtration barrier to retain large proteins, leading to massive proteinuria and nephrotic syndrome. Drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), D-penicillamine, tiopronin, trace elements, bisphosphonate, and interferons have been historically associated with the occurrence of MCD, FSGS, and MN. In the last ten years, the development of new anti-cancer agents, including tyrosine kinase inhibitors and immune checkpoint inhibitors, and research into their renal adverse effects highlighted these issues and have improved our comprehension of these diseases.
Cystinuria is the predominant hereditary factor leading to kidney stone formation in the pediatric population. The aim of this manuscript is to provide an overview of cystinuria in children. The authors performed a literature review on studies regarding cystinuria in children. A narrative synthesis for analysis of the studies was used. Cystine is a homodimeric amino acid formed by the disulfide bonding of two cysteine molecules. The problem with this autosomal recessive condition arises from a malfunction in the process of reabsorption. Cystine filtered from the renal glomerulus cannot be reabsorbed from the proximal tubules. Therefore, due to its extremely low solubility at normal urine pH, it precipitates and causes stone formation. Recurrent stone formation is the most prominent clinical presentation of cystinuria. The patients usually present with a renal colic episode with concomitant nausea and hematuria. The aim of medical treatment is to maintain the solubility of cystine in urine. The main strategies are to increase urine volume and urinary pH. Potassium citrate or potassium bicarbonate can be used to raise the pH of the urine to 7.5 to increase cystine solubility. If the treatment with alkalinization and higher urine output fails, cystine binding agents such as tiopronin and D-penicillamine can be added to the treatment. Surgical management of pediatric patients with cystine stones is similar to that in the adult population. However, cystine stones can be resistant to ESWL. Retrograde ureteroscopy with semirigid and flexible instruments is a good option for ureteral stones and also for renal stones less than 20 mm in diameter. The golden standard option for high-volume stones larger than 20 mm in diameter is percutaneous nephrolithotomy (PCNL). Cystinuria is the primary hereditary factor contributing to the formation of kidney stones throughout childhood. It is a genetic disorder that typically manifests as recurrent stone formations. The aim of the treatm
Neural epidermal growth factor-like 1 (NELL1) membranous nephropathy (MN) is notable for its segmental deposit distribution, IgG1 dominant deposits, and comparatively high rate of spontaneous remission. It has been associated with a variety of exposures and secondary conditions, specifically use of thiol-containing medications - including lipoic acid, bucillamine, and tiopronin - as well as traditional indigenous medications (TIM) particularly those with high mercury content, and non-steroid anti-inflammatory drugs (NSAIDs). Malignancies, graft vs. host disease (GVHD), infection, and autoimmune conditions have also been associated with NELL1 MN. Herein, we provide a detailed summary of the clinicopathologic features of NELL1 and associations with underlying conditions, with a focus on treatment and outcomes. Rare cases of dual NELL1 and phospholipase A2 receptor (PLA2R) positive MN are reviewed. Genome-wide association study of NELL1, role of NELL1 in other physiologic and pathologic processes, and connection between NELL1 MN and malignancy with relevance of NELL1 tumor staining are examined. Finally, relationships and potential disease mechanisms of thiol- and mercury- associated NELL1 MN are discussed.
Cystinuria is a rare genetic kidney stone disease, with no cure. Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria. Key electronic databases were searched for studies that described the clinical management of cystinuria with high diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels > 250 mg/L and patients being managed with urinary dilution, alkalinizing agents or other pharmacological agents. All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS). Two authors performed the quality assessment and excluded the studies with a low MINORS score. Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to > 3 L/day and urinary pH > 7.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence. Cystinur