A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs). CASE PRESENTATION: We present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea. CONCLUSIONS: This case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

[The relationship between urinary albumin excretion and serum uric acid in general population].

OBJECTIVE: To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. METHODS: The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. RESULTS: (1) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9%, 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37.2% vs 13.7%, P < 0.01). (2) The participants were divided according to the quartiles (25%, 50%, 75%) of serum uric acid level, and the frequencies of albuminuria in males were 13.2%, 13.9%, 17.2% and 25.4%, while those in females were 8.4%, 6.2%, 9.6% and 24.8%. (3) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR = 2.31, 95%CI 1.15-4.68; P = 0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. CONCLUSIONS: The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.

[Analyzing urinary proteome patterns of metabolic syndrome patients with early renal injury by magnet bead separation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry].

OBJECTIVE: To determine the potential urinary biomarkers of metabolic syndrome (MS) with early renal injury and establish diagnostic models by magnetic bead-based separation and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). METHODS: Participants were selected from the epidemiologic study on MS and renal involvement among residents in Pinggu district, Beijing. Eight-hour overnight urine samples were fractionated by means of magnetic bead-based weak cation exchange chromatography and subsequently analyzed with MALDI-TOF-MS. Wilcoxon test and random forests were used to screen differential protein peaks of MS patients with early renal injury, then combined with genetic algorithm and support vector machine, respectively, to establish diagnostic models. RESULTS: Totally 54 cases of MS without renal injury and 46 cases of MS with early renal injury were enrolled. Totally twenty protein peaks were up-regulated in the urine of MS patients with early renal injury by Wilcoxon test (P < 0.05); random forests algorithm revealed twelve protein peaks up-regulated in the urine of MS patients with early renal injury (importance value of mean decrease in accuracy > 0.005). Genetic algorithm based model showed 82.6% sensitivity, 84.3% specificity, and 83.5% accuracy by a 10-fold cross-validation in identifying MS patients with early renal injury; correspondingly, the support vector machine based model reported 89.2% sensitivity, 81.1% specificity and 85.5% accuracy. Four protein peaks were included in two diagnostic models with mass-to-charge ratios of 2756.98, 3019.11, 9077.04, and 10 054.26. CONCLUSIONS: The urinary proteome patterns of MS with early renal injury were successfully established with magnetic bead-based separation and MALDI-TOF-MS technology. A series of urinary differential expressing protein peaks were identified with bioinformatics tools. Diagnostic models combining cluster of protein peaks are capable of differentiating MS patients with early renal injury from those without renal injury. The different urine protein excretion patterns revealed in this study provide urinary candidate biomarkers of MS patients with early renal injury for future identification and biological roles investigation.