Acquired Fanconi syndrome in mixed cryoglobulinemia patients: a single-center case series.

PURPOSE: Cryoglobulinemia is a pathological condition characterized by the presence of cryoglobulins in the blood, with cryoglobulinemic glomerulonephritis being the most frequent form of renal involvement. Fanconi syndrome presents as a generalized dysfunction of the proximal tubule, characterized by the presence of polyuria, phosphaturia, glycosuria, proteinuria, proximal renal tubular acidosis, and osteomalacia. We aimed to present five cases co-occurring with Fanconi syndrome and cryoglobulinemia. METHODS: We retrospectively summarized the cases of five patients with Fanconi syndrome and cryoglobulinemia at Peking Union Medical College Hospital from January 2012 to June 2022. The clinical features, diagnosis, treatment, and prognosis were systematically analyzed. RESULTS: All five patients exhibited typical features of Fanconi syndrome, and cryoglobulinemia was concurrently detected in all cases. These patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, and IgM constitutes the predominant monoclonal component in cryoglobulins. In addition to supplemental treatment, timely immunosuppressive therapy may potentially benefit the long-term renal prognosis of patients with this condition. CONCLUSION: Our findings highlight the rare co-occurrence of Fanconi syndrome and cryoglobulinemia in clinical practice. Despite the lack of causal evidence, the coexistence of Fanconi syndrome and tubulointerstitial injury is also noteworthy in patients with cryoglobulinemia, underscoring the importance of thorough evaluation and tailored management in patients presenting with overlapping renal manifestations. Key Points • Patients with mixed cryoglobulinemia can clinically present with tubulointerstitial injury, specifically manifesting as Fanconi syndrome. • In addition to typical symptoms of Fanconi syndrome, these patients also exhibit positive anti-nuclear antibody spectrum and hyperglobulinemia, while IgM constitutes the monoclonal component in cryoglobulins. • Timely immunosuppressive therapy may improve long-term renal prognosis in these patients.

7-hydroxycoumarin-ß-D-glucuronide protects against cisplatin-induced acute kidney injury via inhibiting p38 MAPK-mediated apoptosis in mice.

AIMS: Cisplatin is a widely-used drug in the clinical treatment of tumors, but kidney nephrotoxicity is one of the reasons that limits its widespread use. We previously found that 7-hydroxycoumarin-ß-D-glucuronide (7-HCG) was one of metabolites of skimmin and highly enriched in the kidneys and maintained a high blood concentration in skimmin-treated rats. Therefore, we investigated whether 7-HCG has a protective effect on cisplatin-induced acute kidney injury. MATERIALS AND METHODS: Male C57BL/6 mice were continuously administered 7-HCG for five days, and on the third day, an intraperitoneal injection of cisplatin was given to induce acute kidney injury. After 72 h, the mice were sacrificed for analysis. Serum and renal tissue were collected for renal function evaluation. RNA sequencing was used to explore mechanism, and further validated by western blot and immunohistochemistry. In addition, pharmacokinetic study of oral 7-HCG administration was performed to examine how much 7-hydroxycoumarin (7-HC) was metabolized and 7-HC possible effect on renal protection. KEY FINDINGS: 7-HCG significantly reduced serum BUN and SCR levels, and alleviated pathological damage in renal tissue, and reduced the renal index. RNA sequencing revealed that 7-HCG could reverse p38 MAPK regulation and apoptosis. By western blotting, it was found that 7-HCG could reduce renal injury by reducing p-p38, p-ERK, p-JNK, cleaved-caspase3 and Bax. The immunohistochemical results of cleaved-caspase3 were consistent with western blotting. 7-HCG also significantly reduced the production of ROS in kidney tissue. Pharmacokinetic experiments have shown that 7-HCG in the blood increased rapidly and was eliminated slowly, with an average t1/2ß of 18.3 h. And the concentration of 7-HCG in the target organ kidney was about 4 times higher than that in blood. SIGNIFICANCE: Our findings indicate that 7-HCG could exert its protective effect against cisplatin-induced acute kidney injury by inhibiting apoptosis via p38 MAPK regulation and elucidates its pharmacokinetics.

Amino acid environment affinity model based on graph attention network.

Proteins are engines involved in almost all functions of life. They have specific spatial structures formed by twisting and folding of one or more polypeptide chains composed of amino acids. Protein sites are protein structure microenvironments that can be identified by three-dimensional locations and local neighborhoods in which the structure or function exists. Understanding the amino acid environment affinity is essential for additional protein structural or functional studies, such as mutation analysis and functional site detection. In this study, an amino acid environment affinity model based on the graph attention network was developed. Initially, we constructed a protein graph according to the distance between amino acid pairs. Then, we extracted a set of structural features for each node. Finally, the protein graph and the associated node feature set were set to input the graph attention network model and to obtain the amino acid affinities. Numerical results show that our proposed method significantly outperforms a recent 3DCNN-based method by almost 30%.

Serum Adiponectin Levels Are Positively Associated With Diabetic Peripheral Neuropathy in Chinese Patients With Type 2 Diabetes.

Objective: To investigate the association between serum adiponectin levels and diabetic peripheral neuropathy (DPN) in Chinese type 2 diabetes (T2D) patients. Design and Methods: Two hundred nineteen T2D patients aged 40-79 years were divided into two groups according to whether they had DPN. The systemic levels of five biomarkers were measured using a human adipokine multiplexed bead-based immunoassay. Diabetic peripheral neuropathy diagnostic criteria included both common DPN symptoms and neurological screening tests. Results: Most features of DPN (n=98) and non-DPN patients (n=121) are similar, but the DPN patients were slightly older, had longer diabetes duration, higher hemoglobin (Hb) A1c, lower estimated glomerular filtration rates (eGFR), less exercise, and used lipid-lowering drugs more often. Serum adiponectin levels of DPN patients were higher than that of non-DPN patients (8.13 vs. 9.63 mg/ml, P = 0.004). Serum adiponectin levels were positively associated with DPN after adjusting for age, gender, body mass index, hypertension, HbA1c, alcohol intake, smoking status, physical activity, log-transformed low density lipoprotein cholesterol, lipid-lowering drug usage, eGFR, and diabetes duration {odds ratio (OR) 1.72 [95% confidence interval (CI) 1.02-2.89], P = 0.041}. The OR refers to a doubling in biomarkers. Conclusions: Serum adiponectin levels were higher in DPN patients compared to non­DPN patients in this Chinese T2D population. Serum adiponectin levels were positively associated with DPN presence, independent of multiple confounders.

Clinical features of 30 patients with cryoglobulinemia.

OBJECTIVE: To summarize the clinical features of cryoglobulinemia. METHOD: We retrospectively analyzed the clinical data of 30 patients admitted to Peking Union Medical College Hospital from January 2003 to March 2013 due to cryoglobulinemia. RESULTS: The average age was(53.8±11.9)years in these 30 patients(12 men and 18 women),among whom 22 patient(73.3%)developed infectious diseases including hepatitis B(n=11)and hepatitis C(n=11);in addition,3 hepatitis B patients and 1 hepatitis C patient also had malignancies. Four patients(13.3%)were accompanied with malignant lymphocytic proliferation diseases,and three(10.0%)with connective tissue diseases. The cause of disease was unclear in 5 patients(16.7%). The clinical manifestations varied due to the primary diseases;notably,20 patients(66.7%)had an onset of purpura rash,22(73.3%)and 19(63.3%)were accompanied with hypertension and chronic renal insufficiency,respectively. The severity of renal involvement was relevant with the increase of C reactive protein,erythrocytes,sedimentation rate,and IgM and the decrease of complements. Treatment should be directed at the primary diseases. Glucocorticoid and immunosuppressants were good choices for relieving renal involvement. Elderly, type 1 cryoglobulinemia,and poor renal function were associated with the poor prognosis. CONCLUSIONS: Cryoglobulinemia is mainly seen in middle and elderly patients. It can often affect multiple systems,in particular the kidney. Inflammatory markers,IgM,and complements is related with the disease severity. Age,primary disease,and renal function are related with prognosis.

Transitional cell carcinoma associated with aristolochic acid nephropathy: most common cancer in chronic hemodialysis patients in China.

BACKGROUND: The research of cancer in patients on hemodialysis (HD) in China has not been reported. The aim of this study was to investigate the clinical and histological features and outcomes of cancer in Chinese HD patients. METHODS: The study subjects were 49 cancer patients (1.4%) out of 3448 end stage renal disease (ESRD) patients maintained on HD at China-Japan Friendship Hospital from October 1997 to July 2011. RESULTS: Urinary tract cancer (74%) was the most common followed by gastrointestinal tract cancer (12%), breast cancer (6%), lung cancer (4%), thyroid cancer (2%), and hematologic cancer (2%). Thirty-three patients (67%) had urinary tract transitional cell carcinoma (TCC) and 29 of them had aristolochic acid nephropathy (AAN) as underlying disease. Death occurred in eight patients out of 49, and the survival rate of HD patients with cancer was similar to those without cancer (P = 0.120). CONCLUSION: The urinary tract TCC is the most common cancer in HD patients with AAN in one of the centers of northern China.