Nonsteroidal Anti-inflammatory Drugs Treatment Research Articles

A randomized pilot study of acupuncture treatment for primary dysmenorrhea

ObjectiveTo compare the therapeutic effect of acupuncture and non-steroidal anti-inflammatory drug (NSAID) therapy in primary dysmenorrhea patients. Study designThirty-five young women with a diagnosis of primary dysmenorrhea were recruited for the study. Their dysmenorrhea severity was rated by visual analog scale (VAS) immediately prior to entry into the study. They were randomly divided into two groups; and the following month they were given NSAID (group 1, n=24) or acupuncture treatment (group 2, n=11). Pain was rated again using VAS during menstruation in both groups. ResultsAfter one month's treatment, pain scores were significantly lower in both groups (p<0.05). Mean pain scores decreased by 52.2% and 69.5% in the NSAID and acupuncture groups, respectively. ConclusionAcupuncture was as effective as NSAID therapy for patients with primary dysmenorrhea. Since this was a pilot study with a small sample size and short follow-up period, larger studies are needed to clarify the effect of acupuncture in the treatment of primary dysmenorrhea.

Differential stem- and progenitor-cell trafficking by prostaglandin E2

SUMMARYTo maintain lifelong production of blood cells, hematopoietic stem cells (HSC) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSC (LT-HSC) reside in several, perhaps overlapping, niches that produce regulatory molecules/signals necessary for homeostasis and increased output following stress/injury 1–5. Despite significant advances in specific cellular or molecular mechanisms governing HSC/niche interactions, little is understood about regulatory function within the intact mammalian hematopoietic niche. Recently, we and others described a positive regulatory role for Prostaglandin E2 (PGE2) on HSC function ex vivo 6,7. While exploring the role of endogenous PGE2 we unexpectedly observed hematopoietic egress after nonsteroidal anti-inflammatory drug (NSAID) treatment. Surprisingly, this was independent of the SDF-1/CXCR4 axis. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin (OPN). Hematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in higher species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced EP4 receptor signaling. These results not only uncover unique regulatory roles for EP4 signaling in HSC retention in the niche but also define a rapidly translatable strategy to therapeutically enhance transplantation.

Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Turnover: An Evidence-Based Review

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for acute and chronic pain control and treatment of inflammation, osteoarthritis and rheumatoid arthritis. NSAIDs have been shown to inhibit bone healing in animal studies due to the inhibition of prostaglandin synthesis. However, little evidence exists regarding the effect of NSAID exposure on human bone metabolism. This systematic review summarizes the current literature of randomized controlled trials (RCTs) investigating NSAIDs with bone remodeling-related outcomes in humans. After performing computerized searches in the most widely indexed databases, study selection, data abstraction and risk of bias assessment were conducted in duplicate. The results were controversial regarding the association of NSAID with bone formation or resorption. Increased bone mineral density following NSAID exposure was reported by some studies. Based on the levels of biochemical markers, no effect was seen on bone formation, while some evidence was found for a decreased rate of bone resorption in NSAID patients. Trials investigating the effects of NSAID treatment on bone metabolism outcomes of human patients are limited. Further research is required to confirm or refute the findings of this systematic review.

Lame broiler chickens respond to non-steroidal anti-inflammatory drugs with objective changes in gait function: A controlled clinical trial

Leg health of intensively reared broiler chickens is a significant problem, yet little is known regarding the nature of lameness-associated pain. Kinematic changes in gait have been reported in naturally lame broilers following subcutaneous non-steroidal anti-inflammatory drug (NSAID) administration, compared to a placebo group. In the current study, an extensive range of gait parameters were defined using a commercial motion-capturing system to record three-dimensional temporospatial information from walking broilers pre- and post-treatment. Data analysis, performed using multi-level models, revealed gait modifications in broilers receiving NSAID, but not in those receiving saline. The effect of walking velocity was accounted for retrospectively.An increase in velocity following NSAID treatment (carprofen: P<0.001; meloxicam: P=0.044) indicated improved walking ability. For several measures, the polarity of the treatment effect depended upon walking speed. At slow speeds certain parameters become more like those of non-lame broilers, which may have been indicative of improved stability: stride length and duration (both NSAIDs), transverse back displacement (meloxicam), and vertical leg displacement (carprofen). However, these same parameters also revealed that NSAID treatment caused imbalance at faster speeds, which may have signified an excessive dosage. Although doses employed were not conclusively effective, evidence was provided that factors besides body conformation influenced mobility in the test cohort. The study showed that the model would be useful in future studies to increase our understanding of pain associated with specific lameness types in broiler chickens.

Effects of Combined Treatment with Aspirin and Diclofenac or Indomethacin on the Gastric Mucosa of the Rat : Reduced Damage by Proton Pump Inhibitors

Objectives: To investigate the gastric mucosal injury caused by the combined treatment of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) and to identify the optimum methods to avoid such injury. Methods: Sixty albino Wistar rats of 200-250gm were used in this study. The animals were divided into 8 groups. Group I served as control and received the vehicle of the used drugs (aspirin, diclofenac and indomethacin). Groups II, III, and IV received single daily dose of aspirin (4mg/kg body weight), diclofenac (2mg/kg. body weight) and indomethacin (2mg/kg body weight) respectively. Group V received aspirin and diclofenac and Group VI received aspirin and indomethacin as above. Group VII and VIII received omeprazole (2mg/kg body weight) one hour befor ingestion of aspirin and diclofenac or aspirin and indomethacin as above. At the end of treatment, lesions in the stomach were evaluated macroscopically and microscopically. Results: Macroscopic analysis showed that treatment with aspirin, diclofenac and indomethacin separately induced multiple gastric mucosal lesions which were larger and deeper following the combined treatment of aspirin and either diclofenac or indomethacin. Microscopically the lesions include increased mucous production, oedema, congestion, necrosis and hemorrhage of the fundic mucosa. After the administration of omeprazole (proton pump inhibitor) most of the mucosal lesions show evidence of partial healing. Conclusion: Combined treatment with aspirin and diclofenac or indomethacin produced larger and deeper gastric fundic mucosal lesion than aspirin treatment alone. Omeprazole ingestion added to the above drugs significantly healed lesions compared to the control group by 75% and 70% (p=0.05).

Chest Pain: The Only Symptom of Gastric Ulcer

A 51-year-old woman presented with a 3-month history of left-sided chest pain. The pain was colicky, without associated tenderness, and involved the T5-8 thoracic dermatomes. We suspected referred pain from peptic ulcer, and upper gastrointestinal endoscopy revealed multiple ulcers in the middle-third of the gastric lesser curvature. As the patient was on non-steroidal anti-inflammatory drug (NSAID) treatment for tension headaches, NSAID-induced peptic ulcer was diagnosed. Proton-pump inhibitor (PPI) treatment resulted in prompt pain relief. There are few reports of chest pain as the sole presenting symptom of peptic ulcer. Nevertheless, although rare, peptic ulcer should also be considered in the differential diagnosis of chest pain.

Coexistence of Ankylosing Spondylitis and Klinefelter's Syndrome

Ankylosing spondylitis is a chronic inflammatory disease characterized by inflammatory lower back pain and morning stiffness and accompanied by spine and sacroiliac joint involvement. Klinefelter's syndrome is a genetic condition that only affects males. Affected males have an extra X chromosome. This paper reports a 30-years-old male on followup with the diagnosis of Klinefelters syndrome. The patient admitted with complaints of inflammatory lower back, and neck pain and morning stiffness and was diagnosed with ankylosing spondylitis. Nonsteroidal anti-inflammatory drug and salazopyrine treatment resulted in significant regression in his complaints.

Kinesiology Tape Compared to NSAIDS in the Treatment of Rotator Cuff Impingement

Objectives:To determine if kinesiology tape is as effective as nonsteroidal anti-inflammatory drugs (NSAIDS) when used as an adjunctive therapy to exercise at reducing pain and improving function in patients with rotator cuff impingement.Methods:A prospective, single-blind, randomized control trial was conducted. One hundred patients (average age: 48 ± 12.3, 61 males, 39 females) with a diagnosis of subacromial impingement syndrome were recruited and randomly assigned to one of three treatment groups: taping and exercise (n=33), NSAIDs and exercise (n=29), or exercise only (n=38). All patients completed a two-week (four sessions) exercise program guided by a registered physiotherapist. The physiotherapist applied the kinesiology tape to the patients in the taping and exercise group who wore the tape full time for an average of 3.5 days. Patients were assessed pre and post treatment by a research assistant who was blinded to each patient’s assigned treatment group. Patients were provided with a usage diary to record their compliance with the treatment protocol. Shoulder pain and function were assessed using a Numeric Pain Rating Scale, the Simple Shoulder Test (SST), and the Constant Score.Results:A significant improvement in pain with arm elevation, SST, and Constant Scores was observed in all the groups: taping and exercise group (1.2±2.5, 1.6±2.2, 7.8±8.1, respectively; p<0.05), NSAIDs and exercise group (2.1±2.4, 1.5±2.7, 11.0±11.7; respectively; p<0.05), and the exercise only group (1.3±2.6, 1.4±2.2, 6.3±10.9, respectively; p<0.05). A significant improvement in activities of daily living and functional arm level was observed in the taping and exercise group (0.8±1.2, 1.6±2.2 respectively; p<0.05) and the NSAIDS and exercise group (1.0±1.6, 0.8±2.0 respectively; p<0.05). Between-group differences were not statistically significant. Although all treatment groups showed a slight trend toward increased strength, the results were not significant. Patients were more compliant with the kinesiology tape (100%) than the NSAIDS treatment regime (84%). 88.5% of participants reported on average less than 2/10 discomfort with the tape.Conclusion:Kinesiology tape is as effective as NSAIDs as an adjuvant therapy to exercise at reducing shoulder pain and improving function in patients with subacromial impingement. Patients demonstrated increased compliance with the addition of kinesiology tape to an exercise program as compared to NSAIDS. Kinesiology tape appears to be well-tolerated and may prove to be a safer alternative to NSAIDs in the conservative treatment of shoulder impingement pain and dysfunction.

Abstract P3-08-03: Urinary levels of prostaglandin E2 metabolite and postmenopausal breast cancer

Abstract Estrogens are considered a key player in the mammary carcinogenesis. In postmenopausal women, peripheral aromatization of androgens is the predominant source of estrogens. Given that prostaglandin E2 (PGE2) is a potent activator of aromatase expression, we hypothesized that endogenous level of PGE2 would influence estrogen bioavailability and subsequent breast cancer risk in postmenopausal women. In addition, because PGE2 synthesis is suppressed by treatment of non-steroidal anti-inflammatory drugs (NSAIDs) via inhibition of cyclooxygenase enzyme activity, we further hypothesized that regular use of NSAIDs may modify the association between PGE2 and postmenopausal breast cancer risk. We carried out a case-cohort analysis within the NIEHS Sister Study, a prospective cohort study of 50,884 women. Postmenopausal women who were aged 50 or older and did not report current use of hormones were eligible for the present analysis (N = 11,338). Urinary levels of a major PGE2 metabolite (PGE-M), which is generally accepted as the most accurate index of endogenous PGE2 formation, were quantified using liquid chromatography/tandem mass spectrometry in 302 incident breast cancer cases and 305 subcohort members who were randomly selected by frequency matching for age among cases. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Prentice's pseudo-likelihood approach with Barlow's weighting scheme. Several factors were associated with higher levels of urinary PGE-M in the multivariable analysis, including current smoking, obesity, high caloric intake from saturated fat and surgical menopause. No associations were observed for dietary intake of omega 3 fatty acids, use of vitamin supplements and physical activity. Overall, there was no association between urinary PGE-M and postmenopausal breast cancer risk. After including the interaction terms between NSAID use and urinary levels of PGE-M in the model, however, high levels of urinary PGE-M were associated with an increased risk of breast cancer in postmenopausal women who did not regularly use NSAIDs (likelihood ratio test p &amp;lt;0.01). Taking into account use of NSAIDs 1 day prior to urine collection did not change results. NSAID use may modify the conversion of androgens to estrogen and thereby lower breast cancer risk. Expected data on estrogen and estrogen metabolites will help us better understand these findings. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-03.

Ongoing treatment with non-steroidal anti-inflammatory drugs at time of admission is associated with poorer prognosis in patients with first-time acute myocardial infarction

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with increased cardiovascular morbidity and mortality. The purpose of this study was to examine the effect of ongoing NSAID treatment at time of admission for myocardial infarction (MI) on prognosis. All patients admitted with first-time MI in 1997-2006 were included by use of individual-level linkage of nationwide registries. By claimed prescription of NSAIDs, availability of tablets was estimated within 14 days prior to inclusion and defined ongoing use. Risk of death within 30 days and risk of death or MI within 1 year was analyzed by logistic regression and Cox proportional-hazard models, respectively. A total of 97,458 patients were included (mean age 69.9 [SD 13.2] years and 62% males); the 30 day and 1 year mortality rates were 18.1% and 27.7%, respectively. Ongoing NSAID treatment was identified in 12,156 (12.5%) patients and 30-day mortality was significantly increased in patients receiving rofecoxib (odds ratio [OR] 1.43; 95% confidence interval [CI] 1.22-1.68) and celecoxib (OR 1.23; CI 1.03-1.47) relative to no use of NSAIDs. Correspondingly, the 1-year rate of death or recurrent MI was significantly increased in patients receiving rofecoxib (hazard ratio [HR] 1.15; CI 1.04-1.27), celecoxib (HR 1.13; CI 1.01-1.26), diclofenac (HR 1.12; CI 1.04-1.20) or any NSAID use (HR 1.05; CI 1.02-1.09). No association was found for naproxen or ibuprofen. Ongoing treatment with NSAIDs and in particular the cyclooxygenase-2-selective inhibitors rofecoxib, celecoxib, and diclofenac is associated with worsened prognosis in patients admitted with first-time MI.

Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor

Nerve growth factor (NGF) is critical for the development and maintenance of sympathetic and sensory neurons in the developing nervous system, including nociceptors. In the adult nervous system, NGF is known to produce significant pain signals by binding to the TrkA and p75NTR receptors. Several pathological pain disorders are associated with nerve growth factor dysregulation, including neuropathic pain, osteoarthritic pain, and hyperalgesia. Currently, clinical management of these pathologies has relied on the use of opioid and non-steroidal anti-inflammatory drugs (NSAID). However, several chronic pain conditions demonstrate insensitivity to NSAID treatment or the development of detrimental opioid-related side effects, including addiction. As NGF plays an important role in pain generation; antibodies, small molecules and peptides have been designed to antagonize NGF. In this review, we discuss the structural biology of NGF ligand/receptor interaction, and we review current biological and pharmacological strategies to modulate NGF-related pathologies.

Zerebrale Rundherde unter TNF-α-Blocker-Therapie bei vorbestehender Sarkoidose und Sakroiliitis

This article reports the case of a 55-year-old man who presented with aphasia caused by intracerebral lesions and had a history of pulmonary sarcoidosis. Due to nonsteroidal anti-inflammatory drug-resistant spondyloarthritis TNF-alpha inhibitor treatment was started after a negative tuberculosis screening. Subsequently the patient developed pulmonary tuberculosis and cerebral tuberculoma reactivated by the TNF-alpha inhibitor therapy accompanied by pulmonary sarcoidosis with sacroiliitis and oligoarthritis. This case report emphasises the risk of atypical tuberculosis infections under TNF-alpha inhibitors despite negative results of tuberculosis screening.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Treatment Satisfaction after Switching to Another Therapy in Spanish Orthopaedic Clinic Outpatients with Knee or Hip Osteoarthritis Previously Refractory to Paracetamol

Hip and knee osteoarthritis is highly prevalent in the elderly, and the incidence is estimated to increase in the coming decades. Prior to surgery, symptomatic treatment, starting with non-pharmacological therapies, should be prescribed. Paracetamol (acetaminophen) is the recommended first pharmacological treatment for osteoarthritis. If paracetamol is ineffective, non-steroidal anti-inflammatory drug (NSAID) treatment is indicated. The superiority of NSAIDs over paracetamol has been demonstrated in several studies. Furthermore, the assessment of patient satisfaction could be an adequate indicator of the quality of care given and is likely related to the evolution of the condition and the therapeutic regimen. The objective of this study was to assess the satisfaction of patients diagnosed with hip and/or knee osteoarthritis who had been previously treated with paracetamol and switched to NSAID treatment due to a lack of effectiveness by paracetamol. An observational, prospective, multicentre and comparative study was conducted in 2009 among patients diagnosed with hip and knee OA who visited outpatient orthopaedic clinics. The evaluation of treatment effectiveness was carried out using a patient-based visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The satisfaction regarding change of treatment due to a lack of effectiveness and/or the presence of adverse effects was evaluated using the osteoARthritis Treatment Satisfaction (ARTS) questionnaire. A total of 2437 patients were evaluated (knee OA: 1438 [59%]; hip OA: 621 [25.5%]; knee and hip OA: 124 [5.1%]; and without OA location registered: 254 [10.4%]). The study findings showed an increase in patient satisfaction after abandoning the use of paracetamol to treat OA. Statistically significant increases in both overall satisfaction mean (from 57.7 [SD 13.5] to 71.3 [SD 12.0]) and in each of the four domains of the ARTS questionnaire were observed (p < 0.0001 in all cases). According to the WOMAC and a VAS, treatment effectiveness increased significantly after 3 months (p < 0.0001) and significant correlations with satisfaction were observed (r = -0.32 and r = -0.29, respectively; p < 0.0001). The mean (SD) change in global satisfaction in patients treated with NSAIDs was 14.9 (15.5) versus 7.2 (14.4) for patients treated with non-NSAIDs (p < 0.0001). Patients taking NSAID treatment showed substantially more improvement over those taking non-NSAID treatment. NSAIDs relieve pain due to OA in paracetamol-resistant patients and improve treatment effectiveness and patient satisfaction with treatment. Furthermore, paracetamol-refractory subjects under conventional medical treatment with NSAIDs experienced the drug as more effective and also tended to be more satisfied with treatment than those treated with non-NSAIDs.

Does Concomitant Use of NSAIDs Reduce the Effectiveness of Antidepressants?

Does Concomitant Use of NSAIDs Reduce the Effectiveness of Antidepressants?

Postoperative use of non-steroidal anti-inflammatory drugs in patients with anastomotic leakage requiring reoperation after colorectal resection: cohort study based on prospective data

Objectives To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.Design Cohort study based on data from a prospective clinical...

Safety and Efficacy of On-demand Versus Continuous Use of Nonsteroidal Antiinflammatory Drugs in Patients with Inflammatory Arthritis: A Systematic Literature Review

To systematically review the efficacy and safety of on-demand versus continuous use of nonsteroidal antiinflammatory drugs (NSAID) in patients with inflammatory arthritis and to assess if longterm continuous treatment with NSAID in comparison with NSAID treatment on-demand reduces radiographic progression. A systematic literature review was performed in Medline, Embase, the Cochrane Library, and American College of Rheumatology/European League Against Rheumatism 2008-2009 meeting abstracts as part of the multinational 3e (Evidence, Expertise, Exchange) Initiative for generating practical recommendations about Pain Management by Pharmacotherapy in Inflammatory Arthritis. Articles fulfilling predefined inclusion criteria were reviewed and quality appraisal was performed. The search yielded a total of 1410 articles from Medline and Embase, 73 from Cochrane Central, and 3 meeting abstracts. After review, only one study fulfilled the defined inclusion criteria, which indicated that longterm continuous treatment with NSAID versus NSAID treatment on-demand reduced radiographic progression in patients with ankylosing spondylitis. Secondary measured endpoints were disease activity measures including pain and the frequency of observed adverse events in both groups. Relevant adverse events tended to occur more frequently in the continuous treatment group with odds ratios of 2.79 for hypertension, 1.67 for abdominal pain, 1.35 for diarrhea, 0.95 for dyspepsia, and 3.2 for depression. None of these differences were statistically significant, with the exception of depression, which could not be explained. Based on a single study, there does not seem to be a statistical difference in efficacy between the on-demand versus continuous use of NSAID in the context of ankylosing spondylitis. There were no studies in patients with rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis. Research is needed to study the risk-benefit ratio of continuous versus on-demand use of NSAID.

Antiinflammatory Treatment Ameliorates HPA Stress Axis Dysfunction in a Mouse Model of Stress Sensitivity

Dysregulated stress responsivity is a hallmark of neuropsychiatric disease. The regulation of stress activation and recovery involves tight coordination between neuronal and glial networks. At a certain threshold of sensitivity, stress exposure can evoke a neuroimmune response. Astrocytes are potential mediators of these effects because they are able to respond to neuroimmune effector molecules and regulate neuronal activity. Mice deficient in corticotropin-releasing factor receptor-2 display increased stress sensitivity and are therefore a useful model in which to examine the intersection of neuroimmune activation and stress pathway dysregulation. We hypothesized that a component of elevated stress reactivity may involve an engagement of neuroimmune effectors, including astrocytes. Therefore, we hypothesized that this phenotype may be rescued by concomitant nonsteroidal antiinflammatory drug (NSAID) treatment. To examine this, mice exposed to chronic stress were treated with NSAID in their drinking water, and changes in hypothalamic-pituitary-adrenal stress axis function were examined. As a correlate of altered astrocyte function, levels of glial fibrillary acidic protein were measured. Supportive of our hypothesis, NSAID treatment rescued the hypothalamic-pituitary-adrenal stress axis dysfunction in stress-sensitive corticotropin-releasing factor receptor-2(-/-) mice and also reversed the stress-induced increase in glial fibrillary acidic protein in stress-regulating brain regions including the paraventricular nucleus of the hypothalamus, ventral hippocampus, and prefrontal cortex. These findings support the local involvement of astrocytes in the exacerbation of stress pathway dysregulation. The specificity of these effects in a stress-sensitive genotype highlights the importance of utilizing a model of stress dysregulation in the examination of factors that may translate to neuropsychiatric disease.

Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C

The enteric epithelium must absorb nutrients and water and act as a barrier to the entry of luminal material into the body; this barrier function is a key component of innate immunity. Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy occurs via inhibition of prostaglandin synthesis and perturbed epithelial mitochondrial activity. Here, the direct effect of NSAIDs [indomethacin, piroxicam (cyclooxygenase 1 and 2 inhibitors), and SC-560 (a cyclooxygenase 1 inhibitor)] on the barrier function of human T84 epithelial cell line monolayers was assessed by transepithelial electrical resistance (TER) and internalization and translocation of a commensal Escherichia coli. Exposure to E. coli in the presence and absence of drugs for 16 h reduced TER; however, monolayers cotreated with E. coli and indomethacin, but not piroxicam or SC-560, displayed significant increases in internalization and translocation of the bacteria. This was accompanied by increased reactive oxygen species (ROS) production, which was also increased in epithelia treated with E. coli only. Colocalization revealed upregulation of superoxide synthesis by mitochondria in epithelia treated with E. coli + indomethacin. Addition of antioxidants (vitamin C or a green tea polyphenol, epigallocathechin gallate) quenched the ROS and prevented the increase in E. coli internalization and translocation evoked by indomethacin, but not the drop in TER. Evidence of increased apoptosis was not observed in this model. The data implicate epithelial-derived ROS in indomethacin-induced barrier dysfunction and show that a portion of the bacteria likely cross the epithelium via a transcellular pathway. We speculate that addition of antioxidants as dietary supplements to NSAID treatment regimens would reduce the magnitude of decreased barrier function, specifically the transepithelial passage of bacteria.

Indomethacin Reduces Glomerular and Tubular Damage Markers but Not Renal Inflammation in Chronic Kidney Disease Patients: A Post-Hoc Analysis

Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs) may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal) side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12) with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP)), patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID). Healthy subjects (n = 10) screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38–513] vs NSAID 38[17–218] mg/24 h, p<0.01; IgG4: 50[16–68] vs 10[1–38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55–404] vs 50[28–110] ug/24 h, p = 0.03; KIM-1: 9[5]–[14] vs 5[2]–[9] ug/24 h, p = 0.01). Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal inflammation markers. Future studies should address whether the short term glomerulo- and tubulo-protective effects as observed outweigh the possible side-effects of NSAID treatment on the long term.