ABSTRACT
BACKGROUND: The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis. METHODS: A literature review was conducted to identify genes that are monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) database was used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a phenotypic profile of a gene (PPG) such that one PPG encompasses all related disease phenotypes for a specific gene. The total number of PPGs involving each phenotype category was measured, and the median phenotype category was determined. Phenotype categories were classified as overrepresented or underrepresented if the number of PPGs involving them was higher or lower than the median, respectively. Chi-square test was conducted to determine whether the number of PPGs affecting a given category significantly deviated from the median. RESULTS: Fifty-five genes were identified as monogenic causes of nephrolithiasis. A total of six significantly overrepresented and three significantly underrepresented phenotype categories were identified (p < 0.05). Four phenotypic categories (growth, neurological, skeletal, and abdomen/gastrointestinal) are significantly overrepresented after Bonferroni correction for multiple comparisons (p < 0.002). Among all phenotypes, impaired growth is the most common manifestation. CONCLUSION: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.
Subject(s)
Kidney Calculi , Nephrolithiasis , Humans , Nephrolithiasis/epidemiology , Kidney Calculi/complications , Phenotype , KidneyABSTRACT
Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.