Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10 mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury.

Objective: Celecoxib (CEL) is a nonsteroidal anti-inflammatory drug (NSAID) showing selective cycloxygenase-2 inhibition. While effective as a pain reducer, CEL exerts some negative influence on renal and gastrointestinal parameters. This study examined CEL pharmacodynamics and pharmacokinetics following drug reformulation as a poly(lactic-co-glycolic) acid nanoparticle (NP). Materials and Methods: Rats were administered either vehicle (VEH) (methylcellulose solution), blank NP, 40 mg/kg CEL in methylcellulose, or an equivalent NP dose (CEL-NP). Plasma and urine (over 12 hrs) samples were collected prior to and post-treatment. The mean percent change from baseline of urine flow rate along with electrolyte concentrations in plasma and urine were assessed based on 100 g body weight. Using tissues collected 24 hrs post-treatment, gastrointestinal inflammation was estimated through duodenal and gastric prostaglandin E2 (PGE2) and duodenal myeloperoxidase (MPO) levels; while kidney tissue was examined for dilatation and necrosis. CEL concentration was assayed in renal tissue and plasma utilizing high-performance liquid chromatography. Results: Although there were significant changes when comparing CEL and CEL-NP to VEH in plasma sodium concentration and potassium excretion rate, there was no significant variation between CEL and CEL-NP. There was a significant reduction of protective duodenal PGE2 in CEL compared to VEH (p = 0.0088) and CEL-NP (p = 0 .02). In the C EL-NP formulation, t1/2, Cmax, AUC0-∞, and Vd/F increased significantly when compared to CEL. Conclusions: At the observed dosage and duration, CEL-NP may not affect CEL-associated electrolyte parameters in either plasma or urine; however, it does provide increased systemic exposure while potentially alleviating some gastrointestinal outcomes related to inflammation.

Splenectomy has been reported to have a beneficial effect in treating Acute antibody-mediated rejection (ABMR). This reason for this often rapid and profound beneficial effect is not readily apparent from what is known about normal splenic immunoarchitecture. While the spleen is rich in mature B cells, it has not been noted to be a repository for direct antibody-secreting cells. We present a case of a Native American female who received a renal transplant and developed a severe episode of ABMR. The patient was initially refractory to both plasmapheresis and IVIG. The patient underwent an emergent splenectomy with almost immediate improvement in her renal function and a rapid drop in her DR51 antibodies. Immunohistochemical stains of the spleen demonstrated abundant clusters of CD138+ plasma cells (>10% CD138 cells as opposed to 1% CD138 cells as seen in traumatic controls). Though this is a single case, these findings offer a rationale for the rapid ameliorative effect of splenectomy in cases of antibody rejection. It is possible that the spleen during times of excessive antigenic stress may rapidly turn over B cells to active antibody-secreting cells or serve as a reservoir for these cells produced at other sites. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Background and Aim: Acute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large-scale, population-based, propensity-matched studies evaluating AKI's effect in this patient cohort. Methods: A retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI-related complications as mortality predictors were assessed using survey-weighted multivariable regression. We estimated AKI's independent effect by propensity-matching, post-stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment. Results: A total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02–3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79–1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P-trend < 0.001. Conclusion: Hospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients.

INTRODUCTION Apixaban has revolutionized anticoagulation in patients with atrial fibrillation in preventing strokes. Anticoagulant-induced nephropathy with warfarin is well known, but nephropathy with apixaban is a rare entity, and here we present a case of Apixaban-induced nephropathy. Case Description A 71-year-old patient with a medical history of persistent atrial fibrillation on apixaban, Ischemic cardiomyopathy, and chronic kidney disease stage (CKD) IIIa presented to the hospital with complaints of dyspnea and hemoptysis and tea-colored urine of three-day duration. On admission, the patient had acute kidney injury (AKI) on CKD, Methicillin sensitive Staphylococcus aureus (MSSA) bacteremia, and elevated international normalized ratio (INR) and apixaban were held. The hemoptysis worsened and prompted bronchoscopy revealing diffuse alveolar hemorrhage. The urinalysis showed gross hematuria with high red blood cell (RBC) count and 1+ proteinuria presumed secondary to MSSA associated glomerulonephritis. Evaluation for coagulopathy with serum mixing studies and autoimmune workup has been unremarkable. The patient's coagulopathy was considered secondary to decreased clearance of apixaban with AKI on CKD. However, the patient's kidney function continued to worsen, needing continuous renal replacement therapy and a kidney biopsy for a definitive diagnosis for his decline in kidney function. Kidney biopsy revealed IgA dominant infection associated glomerulitis with one out of hundred glomeruli with the crescent formation and signs of anticoagulant induced nephropathy with several intratubular RBC casts out of proportion to the degree of glomerular injury causing acute tubular damage. The patient's INR improved on dialysis. However, he continued to be oliguric before being terminally extubated. DISCUSSION With the increasing incidence of atrial fibrillation and the use of oral anticoagulants, it is vital to have anticoagulant induced as a differential in patients presenting with supra therapeutic INR and AKI. Apixaban-induced nephropathy is a subset of anticoagulant-induced nephropathy and an uncommon cause of the acute decline in kidney function needing dialysis. Prompt recognition and treatment will prevent further deterioration in kidney function and possible improvement.

C1q TNF-related protein-3 (CTRP3) is effective at preventing high-fat diet-induced fatty liver; Recent studies have shown that overexpression of C1q TNF-related protein-3 (CTRP3) in mice fed a high alcohol diet can protect the animal from developing fatty liver disease, and therefore may be a possible treatment for alcoholic fatty liver disease (ALD). However, the possible effects of overexpression of CTRP3 on other tissue has not been widely investigated. If overexpression of CTRP3 proves to be harmful to other tissues, its use as a treatment for ALD would come into question. This study utilized kidney tissue from mice that were fed a high fat diet for 13-14 weeks. The feeding started when the mice were 7 weeks old and continued for 9 weeks. The mice were divided into 4 categories: wild-type/low fat diet, wild-type/high fat diet, transgenic/low fat diet, and transgenic/high fat diet. The kidneys were harvested and fixed in 4% paraformaldehyde and subsequently paraffin embedded. Sections were cut at 4µ and stained using three different staining techniques: standard H&E, Periodic Acid Schiff (PAS), and Masson’s Trichrome Staining. These three methods were utilized to better visualize possible effects on the tissue, i.e. changes in connective tissue deposition or basement membrane thicknesses, etc. Light microscopic examination of the tissues to date has revealed abnormalities in some of the kidney tubules in the transgenic high fat diet group. These same abnormalities have not been observed in the other treatment groups. This study is still in its early stages and much more in-depth investigation is needed to determine which of the tubules of the nephron are affected, and what this effect is. If this study confirms that overexpression of CTRP3 coupled with a high fat diet is harmful to kidney tissues, the use of CTRP3 in the treatment of ALD would require careful monitoring of the patient’s diet.

During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.

No description available.

During the last ten years, several patients have presented to the Renal Unit of Groote Schuur Hospital with acute renal failure following the use of traditional (N'anga or Gqirha) medication. The history together with abnormal liver-function tests and renal failure was thought to be suggestive of a toxic aetiology. The specific toxin however remained unknown, until during the admission of one patient, a relative brought in the medication, analysis of which revealed a high concentration of potassium dichromate. Subsequently elevated levels of chromium were demonstrated by atomic absorption spectrometry in the blood and urine of this patient. Following this case there have been six further cases of acute renal failure resulting from use of dichromate containing traditional remedies. These remedies were obtained from a variety of sources including street-hawkers, herbal chemists, and traditional healers. Clinical and laboratory data relating to these seven patients will be presented.

Indiana University-Purdue University Indianapolis (IUPUI) / Chronic kidney disease (CKD) results in an increased fracture risk, partially due to elevations in parathyroid hormone (PTH) that lead to substantial bone loss. On its own, bone loss does not explain bone fragility in CKD, suggesting that changes in skeletal tissue (bone quality) may also be present. Understanding the factors that lead to fracture in these patients will have a substantial impact on patient care and could lead to a better understanding of how to reduce their fracture risk. Due to their suppression of PTH, calcitriol and its analogues are the current standard of care for bone disease in CKD. Yet, surprisingly little is known of their effects on bone. Agents effective in treating osteoporosis are not recommended in advanced CKD due to the lack of data regarding their efficacy and safety in these patients. The goals of the current study were to determine (1) the impact of CKD on bone quality, (2) the ability of calcitriol to improve skeletal parameters, and (3) the efficacy of various pharmacological interventions (calcium, bisphosphonates, anti-sclerostin antibody, and raloxifene) on bone mass, quality, and mechanical properties in CKD bone disease. Using a slowly progressive rat model of CKD, renal and mineral metabolism, bone morphology, bone quality, and bone mechanics (at several length scales) were assessed. Primarily due to elevated PTH, mechanical testing and tissue-level assessments revealed compromised bone quantity (high cortical porosity and low trabecular volume) and quality (high collagen cross-linking and low matrix bound water). Despite clinically relevant reductions in PTH, calcitriol treatment had no positive impact on skeletal properties. Most agents were only effective when PTH levels were normal. Raloxifene, however, led to greater whole bone and material toughness (the ability of bone to tolerate existing damage) despite modest PTH suppression. While the examination of bone quality in CKD is still in its infancy, these results indicate that enhancing bone quality with raloxifene may be an effective means to compensate for bone loss in CKD.