Reversible membranous glomerulonephritis associated with ketoprofen

An 87-year-old woman presented with the nephrotic syndrome 12 months after administration of ketoprofen, 100 mg daily for osteoarthritis. Clinical course and laboratory data were consistent with drug-induced nephropathy. Kidney biopsy showed membranous glomerulonephritis. Evolution was favorable with resolution of proteinuria after drug withdrawal and steroid administration. A review of the literature on nephrotic syndrome associated with NSAID reveals membranous glomerulonephritis to be an unusual complication.     

Increased remission of early stage membranous nephropathy on long-term treatment with corticosteroid.

Sixty-five patients with primary membranous nephropathy were examined in order to assess the effects of long-term treatment with corticosteroid. The observation period varied from 8 to 279 months (average, 95 months). The patients were treated with corticosteroid alone or with combinations of corticosteroid and immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAID) and/or dipyridamole. At 6 months after treatment, only 14% of the patients had achieved complete remission. At 24 months after treatment, 46% of the patients showed complete remission. The rate of clinical remission, i.e. complete and incomplete remission, was markedly increased in stage I and II patients with membranous nephropathy by Ehrenreich and Churg's classification but not in stage III patients. The actuarial survival curve indicated that 84% of the patients were alive at 10 years after onset. These data suggest that active treatment with corticosteroid is beneficial for patients with primary membranous nephropathy.     

Renal involvement in patients with rheumatoid arthritis

In rheumatoid arthritis (RA) kidney is commonly affected organ with clinical presentation characterised by proteinuria (often nephrotic range) and microhematuria followed by chronic renal failure. This condition is well recognized as a rheumatoid nephropathy (rheumatoid glomerulonephritis), which is mediated by an immunological inflammation and by nephrotoxic effects of numerous drugs usually used in rheumatoid arthiritis treatment, such as NSAID, DMARD. In the patohistological examination various kinds of associated renal lesions could be seen. The most often are amyloidosis, glomerulonephritis, interstitial nephritis. In this study, we presented 15 patients, 10 women and 5 men, mean age of 60.2 with average rheumatoid arthritis duration of 19.4 years and signs of rheumatoid nephropathy. In all patients renal biopsy was performed with frequency of histopathological findings as follows: amyloidosis in 5 patients, IgA nephropathy in 3 patients, FSGS in 3 patients, mesangial proliferative glomerulonephritis in 3 patients, minimal change disease, pauci-immune glomerulonephritis and thin membrane disease in 1 patient. In all patients (except patient with thin membrane nephropathy) we started immunossuppresive therapy with glucocorticoids in combination with cyclophosphamide or cyclosporin or azatioprine. In conclusion, in all patients with rheumatoid arthritis, parameters of renal function should be monitored and in the case of patologic results, renal biopsy should be be performed. In the treatment of RA patients with related renal disorder, suspected causal drug should be removed from the treatment and specific immunosuppressive therapy initiated.     

Successful relatively low-dose corticosteroid therapy for diclofenac-induced acute interstitial nephritis with severe renal failure

We report a case of nephrotic syndrome and acute renal failure that developed in a 73-year-old woman after six months of treatment with the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Renal biopsy revealed interstitial nephritis and minimal change nephropathy. Despite discontinuation of treatment with diclofenac, she subsequently became anuric and required hemodialysis for progressive azotemia. Since her anuria was persistent, treatment with prednisone at a dose of 30 mg/day was started. With progressive increase in urine output after the initiation of corticosteroid treatment, a constant decrease in serum creatinine was observed along with improvement of creatinine clearance. In addition, the increased urinary excretion of beta2-microglobulin (beta2MG) and N-acetyl-beta-D-glucosaminidase (NAG) on admission was also improved during the treatment. Our findings suggest that corticosteroid treatment should be reserved for patients with the protracted deterioration of renal function even after discontinuation of offending trigger agents.     

Non-steroidal anti-inflammatory drug-associated nephrotoxicity in Bartter syndrome

We have followed four patients with Bartter syndrome for a mean of 25.4 years (range 21.5–28.8 years) after diagnosis. All patients received non-steroidal anti-inflammatory drugs (NSAID). In all patients, various degrees of renal dysfunction were noted to be temporally associated with NSAID therapy. In two patients, renal dysfunction resolved after discontinuing NSAID therapy, while maintaining other chronic medications such as potassium-sparing diuretics. Renal dysfunction persisted after NSAID withdrawal in two patients. We report these cases as a warning that NSAID should be considered an important cause of either reversible or irreversible renal dysfunction in Bartter syndrome. Received December 2, 1997; received in revised form May 27, 1998; accepted May 29, 1998     

Transcutaneous electrical nerve stimulation for pain management in patients with uncomplicated minor rib fractures.

OBJECTIVE: Few non-surgical conditions are more painful than rib fractures. There are a few methods for pain relief in patients with minor rib fractures. METHODS: We used a non-steroidal anti-inflammatory drug (NSAID, Naproxen sodium) and transcutaneous electrical nerve stimulator (TENS) to control pain of the patients with uncomplicated minor rib fractures. One hundred consecutive patients admitted to Kartal Education and Research Hospital Emergency Service, were randomized into four groups. The patients were assigned to one of the following pain treatments: NSAID, TENS, NSAID plus inactive TENS or placebo. The patients used NSAIDs and placebo four times a day and TENS twice a day for 3 days. All patients were asked to assess their pain level with a scoring system on days 0, 1 and 3. RESULTS: The most effective treatment was TENS on days 1 and 3 (P<0.05). Although NSAID and NSAID plus inactive TENS controlled pain better than placebo on day 1 (P<0.05), this superiority did not continue to day 3 (P>0.05). There was no difference between NSAID and NSAID plus inactive TENS in controlling pain on either days 1 or 3. CONCLUSION: We conclude that TENS was more effective than NSAID or placebo in patients with uncomplicated minor rib fractures, because of its prominent and admirable efficacy in reduction of pain.     

Non-steroidal anti-inflammatory drugs and amyotrophic lateral sclerosis: Results from five prospective cohort studies

Animal and pathological studies suggest that inflammation may contribute to amyotrophic lateral sclerosis (ALS) pathology and that non-steroidal anti-inflammatory drugs (NSAIDs) might be protective. However, there are no prospective data on the relation between NSAID use and ALS risk in humans. The relation between NSAID use and ALS risk was explored in five large prospective cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health - AARP Diet and Health Study). Detailed NSAID information was sought from 780,000 participants, 708 of whom developed ALS during follow-up. Cox proportional hazards models were used within each cohort and cohort-specific estimates were pooled with random effects models. Results showed that neither non-aspirin NSAID use, nor aspirin use was associated with ALS risk overall. The multivariable, pooled relative risk was 0.96 (95% CI 0.76-1.22) among non-aspirin NSAID users compared with non-users. Duration of NSAID use in years and frequency of NSAID use were not associated with ALS risk overall. In conclusion, the results do not support an overall effect of NSAIDs on ALS risk, but because NSAIDs have heterogeneous effects, a role of individual compounds cannot be excluded.     

Comparing the Anti-Inflammatory Effects of Corticotherapy and Non-steroid Anti-Inflammatory Drugs in Infertile Patients with Infectious Aetiology

To compare the anti-inflammatory effectiveness of corticotherapy and non-steroid anti-inflammatory drugs (NSAID), we examined 126 infertile men with infectious aetiology. Seventy-seven patients were on corticotherapy and antibiotherapy (thirty-eight patients on high-dose and thirty-nine patients on low-dose corticotherapy). Forty-nine patients had antibiotherapy and NSAID. According to our results in both the high- and low-dose groups sperm motility significantly improved, but in the high dose group more side effects were reported. In order to overcome the effects of infections on male infertility, we prefer corticotherapy instead of NSAID because it is more effective than NSAID.     

Nonsteroid anti-inflammatory drugs and the risk of peptic ulcers after gastric bypass and sleeve gastrectomy

BackgroundPharmacologic pain treatment is common among bariatric patients. Nonsteroid anti-inflammatory drugs (NSAID) are not recommended after Roux-en-Y gastric bypass (RYGB) because of the increased risk of marginal ulceration, but the connection with NSAID is not unambiguous.ObjectivesExamine the association between NSAID exposure and peptic ulcers after primary laparoscopic RYGB and sleeve gastrectomy (SG) respectively.SettingUniversity Hospital, Sweden.MethodsCross-matched data from 3 national registers were used in this retrospective, population-based cohort study of all primary laparoscopic RYGB and SG in Sweden within the period from 2010–2015. NSAID exposure was analyzed with individual data of dispensed daily defined doses (DDD) of NSAID after surgery. Multivariate logistic regression estimated the association between NSAID exposure and peptic ulcers, expressed as odds ratios with 95% confidence intervals adjusted for confounding.ResultsOf the 41,380 patients (37,913 RYGB, 3467 SG), 1.8% were diagnosed with peptic ulcers after surgery (RYGB 1.9%, SG .2%). In total, 60% of the patients had been prescribed NSAID during a follow-up period of 4.1 (1.0–7.0) years in median. The adjusted risk odds ratios for NSAID exposure were 1.10 (.88–1.38), 1.43 (1.16–1.76), and 1.52 (1.25–1.84) for >0–30 DDD, >30–100 DDD, and >100 DDD, respectively. In subanalysis, the association was similar for RYGB alone, whereas no association was found for SG.ConclusionThe results of the present study support the notion that continuous NSAID use of ≥30 days is a significant risk factor for the development of peptic ulcers after RYGB, whereas temporary use (<30 days) is not. No association between NSAID exposure and the development of peptic ulcers after SG was identified.     

Low‐intensity pulsed ultrasound and nonsteroidal anti‐inflammatory drugs have opposing effects during stress fracture repair

Low‐intensity pulsed ultrasound (LIPUS) and nonsteroidal anti‐inflammatory drugs (NSAIDs) were used to treat stress fracture. Bilateral stress fractures were induced in the ulnas of 48 adult rats. Animals were divided into two groups (NSAID and VEH), and treated 5 days per week with celecoxib (5 mg/kg) mixed in a vehicle solution of polyethylene glycol and saline (NSAID) or vehicle alone (VEH). One‐to‐three hours following drug administration, all animals were treated with unilateral active‐LIPUS and contralateral inactive‐LIPUS. Equal numbers of ulnas from each drug group were histologically evaluated at 2, 4, and 8 weeks following induction of stress fracture. Neither LIPUS nor NSAID influenced bone resorption, but each had significant and opposite effects on intracortical bone formation rate. These effects indicate that LIPUS may be used to facilitate stress fracture repair whereas NSAID may delay tissue level repair of stress fractures. There was no interaction between LIPUS and NSAID, indicating that the beneficial LIPUS effect was not mediated by the cyclooxygenase‐2 pathway. LIPUS accelerated stress fracture healing, whereas the NSAID delayed repair. When used in combination, the beneficial LIPUS effect was not impaired by the detrimental NSAID effect. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1559–1567, 2007     

The efficacy of oral nonsteroidal anti-inflammatory medication (NSAID) in the treatment of plantar fasciitis: a randomized, prospective, placebo-controlled study

BACKGROUND: Plantar fasciitis frequently responds to a broad range of conservative therapies, and there is no single universally accepted way of treating this condition. Modalities commonly used include rest, ice massage, stretching of the Achilles tendon and plantar fascia, nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroid injections, foot padding, taping, shoe modifications (steel shank and anterior rocker bottom), arch supports, heel cups, custom foot orthoses, night splints, ultrasound, and casting. To our knowledge, no prospective, randomized, placebo controlled double-blind study has evaluated the efficacy of oral NSAIDs in the treatment of plantar fasciitis. METHODS: Twenty-nine patients with the diagnosis of plantar fasciitis were treated with a conservative regimen that included heel-cord stretching, viscoelastic heel cups, and night splinting. They were randomly assigned to either a placebo group or an NSAID group. In the NSAID group, celecoxib was added to the treatment regimen. RESULTS: Pain and disability mean scores improved significantly over time in both groups, although there was no statistical significance between the placebo and NSAID groups at 1, 2, or 6 months. There was a trend towards improved pain relief and disability in the NSAID group, especially in the interval between the 2 and 6-month followup. Pain improved from baseline to 6 months by a factor of 5.2 and disability by 3.8 in the NSAID group compared to 3.6 and 3.5, respectively, in the placebo group. Even though at baseline the pain and disability scores were higher in the NSAID group, the final pain and disability scores were subjectively lower in the NSAID group than in the placebo group (1.43 for pain and 1.16 for disability in the NSAID group, compared to 1.86 and 1.49, respectively, in the placebo group). CONCLUSIONS: These results provide some evidence that the use of an NSAID may increase pain relief and decrease disability in patients with plantar fasciitis when used with a conservative treatment regimen.     

Is there still a role for standard nonsteroidal antirheumatic agents?

Although beneficial and widely used, nonsteroidal anti-inflammatory drugs (NSAID) are asociated with serious gastrointestinal (GI) side effects including ulceration, hemorrhage, and perforation with annual incidence of 2-4%. Prevention of NSAID-induced gastroduodenal ulcerations with proton pump inhibitors (IPP) is recommended in patients wit greater risk for serious GI complications. It is reasonable to expect that specific inhibitors of COX-2 drugs will be used in 20-30% of patients when NSAID are needed. That still leaves great importance on conventional NSAID. If an NSAID is indicated, it should be given at the lowest effective dose with regard to specific indication.     

Should non-steroidal anti-inflammatory drugs be used continuously in ankylosing spondylitis?

ObjectiveThe 2010 update of ASAS/EULAR recommendations for managing ankylosing spondylitis (AS) specify that continuous non-steroidal anti-inflammatory drug (NSAID) treatment should be preferred in patients with persistently active, symptomatic disease. Here, our objective was to assess whether continuous NSAID therapy improves disease control and influences radiographic progression compared to on-demand therapy. We also assessed the safety profiles of both regimens.MethodsWe performed a review by searching the PubMed and Embase databases using two MeSH term combinations to compare continuous and on-demand NSAID therapy in terms of disease control, radiographic progression, and safety.ResultsThe only study evaluating the impact of continuous NSAID therapy on disease control showed no significant difference with on-demand therapy. In four studies, continuous treatment was associated with slower radiographic progression, as assessed in three studies using the modified Stoke Ankylosing Spondylitis Spinal Score (m-SASSS). Three studies compared the safety of continuous and on-demand celecoxib, two in osteoarthritis and one in AS, and found no significant differences regarding the usual side effects of Cox-2 inhibitors.ConclusionsSeveral studies showed slower radiographic progression with continuous NSAID therapy in AS. No studies demonstrated superiority of continuous NSAID therapy regarding symptom control. Continuous NSAID therapy (at least with Cox-2 inhibitors) does not modify safety compared to on-demand therapy.     

Cyclooxygenase inhibitors

DISTINCT EFFECTS: Since the discovery of the two isoforms of COX, the therapeutic effects of nonsteroidal antiinflammatory drugs (NSAID) can be distinguished from their adverse effects linked to the inhibition of the constitutional form via selective inhibition of the inducible form. Non-selective NSAID that inhibit both COX isoforms are difficult to use for long-term regimens. NSAID AND CANCER PREVENTION: Epidemiology studies and animal and in vitro studies have demonstrated that regular use of NSAID reduced the incidence of colorectal cancer and certain precancer lesions. PROMISING PERSPECTIVES: COX-2 specific inhibitors, for example cerecoxib or rofecoxib, are potentially interesting for human therapy for chemoprevention of epithelial cancer or as medical treatment, alone or in combination with other anticancer treatments.     

NSAID Exposure and Risk of Nonunion: A Meta-Analysis of Case–Control and Cohort Studies

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain control. However, concerns regarding the potential deleterious effects of NSAIDs on bone healing have compelled many physicians to avoid NSAIDs in patients with healing fractures, osteotomies, and fusions. We systematically reviewed and analyzed the best clinical evidence regarding the effects of NSAID exposure on bone healing. Medline, Embase, and Cochrane electronic databases were searched for prospective and retrospective clinical studies of fracture, osteotomy, and fusion studies of patients with NSAID exposure and nonunion as an outcome. Study quality was assessed using the Newcastle–Ottawa Scale. Data on study design, patient characteristics, and risk estimates were extracted. Pooled effect estimates were calculated. Subanalyses were performed by bone type and by NSAID dose, duration, and route of administration. In the initial analysis of 11 cohort and case-control studies, the pooled odds ratio for nonunion with NSAID exposure was 3.0 (95% confidence interval 1.6–5.6). A significant association between lower-quality studies and higher reported odds ratios for nonunion was observed. When only higher-quality studies were considered, seven spine fusion studies were analyzed, and no statistically significant association between NSAID exposure and nonunion was identified (odds ratio = 2.2, 95% confidence interval 0.8–6.3). There was no increased risk of nonunion with NSAID exposure when only the highest-quality studies were assessed. Randomized controlled trials assessing NSAID exposure in fracture, fusion, and osteotomy populations are warranted to confirm or refute the findings of this meta-analysis of observational studies.     

Treatment of arthroses in the elderly patient

BACKGROUND: Elderly subjects with osteoarthritis are treated with analgesic drugs, non-steroidal antiinflammatory drugs (NSAID) and intra-articular corticosteroid injections as well as symptomatic slow acting drugs in osteoarthritis (Sy-SADOA). BASIC REGIMENS: Initial treatment for osteoarthritis pain should be paracetamol, followed by NSAID if necessary, especially in the elderly, because of their adverse effects. EFFICACY: Sy-SADOA are effective on pain and function with a persistent effect, allowing the reduction of analgesic and NSAID dosage.     

The role of viscosupplementation with hylan G-F 20 (Synvisc®) in the treatment of osteoarthritis of the knee: a Canadian multicenter trial comparing hylan G-F 20 alone, hylan G-F 20 with non-steroidal anti-inflammatory drugs (NSAIDs) and NSAIDs alone

To determine the safety and efficacy of viscosupplementation with hylan G-F 20, a cross-linked hyaluronan preparation, used either alone or in combination with continuous non-steroidal anti-inflammatory drug (NSAID) therapy, a randomized, controlled, multicenter clinical trial, assessed by a blinded assessor, was conducted in 102 patients with osteoarthritis (OA) of the knee. All patients were on continuous NSAID therapy for at least 30 days prior to entering the study. Patients were randomized into three parallel groups: (1) NSAID continuation plus three control arthrocenteses at weekly intervals; (2) NSAID discontinuation but with three weekly intra-articular injections of hylan G-F 20; and (3) NSAID continuation plus three injections, one every week, intra-articular injections of hylan G-F 20. Outcome measures of pain and joint function were evaluated by both the patients and an evaluator at baseline and weeks 1, 2, 3, 7 and 12, with a follow-up telephone evaluation at 26 weeks. At 12 weeks all groups showed statistically significant improvements from baseline, but did not differ from each other. A statistical test for equivalence, the q-statistic, demonstrated that viscosupplementation with hylan G-F 20 was at least as good or better than continuous NSAID therapy for all outcome measurements except activity restriction. At 26 weeks both groups receiving hylan G-F 20 were significantly better than the group receiving NSAIDs alone. A transient local reaction was observed in three patients after hylan G-F 20 injection; only one patient withdrew from the study as a result and all recovered without any sequela.Hylan G-F 20 is a safe and effective treatment for OA of the knee and can be used either as a replacement for or an adjunct to NSAID therapy.     

Are there any differences in the cardiovascular tolerance between classical NSAIDs and coxibs?

Three placebo-controlled studies have demonstrated deleterious cardiovascular (CV) effects of rofecoxib, celecoxib, and pare/valdecoxib. It remains to be determined whether this CV toxicity is specific to coxibs, or shared with all non-steroidal anti-inflammatory drugs (NSAID). Seven meta-analyses show that, in comparison with non-specific NSAIDs, the risk of thrombotic CV accident is increased with rofecoxib and celecoxib, but not with valdecoxib or lumiracoxib. Concerning the risk of thrombotic CV accident, seven of the ten observational studies which have evaluated the risk, have found an increased risk for the non-specific NSAID in comparison with non-exposed subjects,. The seven observational studies, which evaluated the risk of coxibs, have all found an increased risk with rofecoxib, and two with celecoxib. Three studies out of six have shown an increase of risk with rofecoxib and one study out of five with celecoxib. Two of the three studies, which have compared rofecoxib with celecoxib, have found an increased risk with rofecoxib. Concerning the risk of arterial hypertension, oedemas or congestive cardiac insufficiency, a meta-analysis and a randomised trial have shown a deleterious effect of rofecoxib in comparison with celecoxib and non-specific NSAID. Two studies have shown a deleterious effect of the non-selective NSAID and three a deleterious effect of rofecoxib in comparison with non-exposed subjects. Three studies have demonstrated a deleterious effect of rofecoxib in comparison with non-specific NSAID. No study has shown any deleterious effect of celecoxib in comparison with subjects non-exposed or exposed to non-specific NSAID. These studies suggest that all the NSAID, specific or not, increase the CV and renal risk. This risk seems variable from a compound to another one and must be evaluated, for each patient, according to the susceptibility and associated risk factors. While waiting for other long-term controlled studies, the available data show the existence of a risk of CV secondary effect linked to the class of NSAID, specific (coxibs) or not.