Inflammatory Cytokines in the Papillary Tips and Urine of Nephrolithiasis Patients
| Autor: | Manoj Monga, Andrew Y. Sun, Benjamin Cohen, Bryan Hinck, Robert L. Fairchild, Karen Keslar |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Urology Biopsy 030232 urology & nephrology Inflammation Urine Nephrolithotomy Percutaneous Nephrolithiasis Proinflammatory cytokine Pathogenesis 03 medical and health sciences Kidney Calculi 0302 clinical medicine Medicine Humans Aged Kidney Medulla business.industry Middle Aged Prognosis Urine levels 030220 oncology & carcinogenesis Case-Control Studies Immunology Cytokines Female medicine.symptom business Biomarkers |
| Zdroj: | Journal of endourology. 32(3) |
| ISSN: | 1557-900X |
| Popis: | Intrarenal inflammation has been implicated in the pathogenesis of nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8, and CCL-2 in stone patients. However, no studies have assessed for inflammation in the renal papillae. We sought to characterize novel papillary tip and urinary biomarkers in stone patients.Ninety-two patients with nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary tip biopsies, kidney urine, and bladder urine were collected, as well as voided urine from eight healthy volunteers. Quantitative polymerase chain reaction was performed to measure inflammatory gene expression.Initial 84-gene polymerase chain reaction array revealed significant elevation of several cytokines in stone patients vs controls (fold change 2.3-694). Twenty-four genes were selected for final analysis. In 41 pairs of urine samples, levels of CCL5, CD40, FasL, RIPK2, SELE, TLR3, and IL-15 were significantly elevated in kidney vs bladder urine (p0.0001-0.04). In 23 triplets of samples, expression of these cytokines plus CCL2, CCL7, CCR2, CSF1, CXCL9, and CXCL10, was significantly greater in papillary tips vs urine samples (p0.001-0.05). Cytokine elevation was independent of maximum postoperative heart rate, respiratory rate, temperature, leukocyte count, urinary tract infection in the past year, presence or absence of antibiotics at the time of surgery, and stone composition (all p 0.05).Expression of CCL-2, CCL-5, CCL-7, CCR-2, CD40, CSF1, CXCL-9, CXCL-10, Fas-L, RIPK2, SELE, and TLR-3 is markedly elevated in the papillary tips, kidney urine, and bladder urine of nephrolithiasis patients. Cytokine elevation was independent of signs of systemic inflammation. These findings further support the role of inflammation in nephrolithiasis and imply that the inflammatory process likely begins at the renal papillae. These may represent novel biomarkers of stone disease, which may be useful in basic nephrolithiasis research, disease diagnosis, and prognosis. |
| Databáze: | OpenAIRE |
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