Gut microbiota promoting propionic acid production accompanies caloric restriction-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for 7 days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during caloric restriction-induced weight loss (adjusted p < 0.05). Repeated measures correlation revealed the relative abundances of Prevotella 9 copri (correlation coefficient = 0.532, 95% CI (0.275, 0.717), p = 0.0002) significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during caloric restriction-induced weight loss.

Gut microbiota promoting propionic acid production accompanies diet-induced intentional weight loss in cats.

Rodent models and human clinical studies have shown gut microbiota-derived short-chain fatty acids (SCFAs) play roles in obesity and insulin resistance. These roles have been minimally explored in cats, where in the USA an estimated 60% of cats are overweight or obese. Overweight/obese research cats (n = 7) were transitioned from a maintenance diet to a reduced calorie diet fed ad libitum for seven days, then calories were restricted to achieve 1-2% weight loss per week for an additional 77 days. Cats then received their original maintenance diet again for 14 days. Significant intentional weight loss was noted after calorie restriction (adjusted p < 0.0001). 16S rRNA gene amplicon sequencing and targeted SCFA metabolomics were performed on fecal samples. Fecal microbial community structure significantly differed between the four study phases (PERMANOVA p = 0.011). Fecal propionic acid was significantly higher during diet-induced weight loss (adjusted p < 0.05). Spearman correlation revealed the relative abundances of Prevotella 9 copri (ρ = 0.6385, p = 0.0006) and Blautia caecimuris (ρ = 0.5269, p = 0.0068) were significantly correlated with propionic acid composition. Like humans, obese cats experienced an altered microbial community structure and function, favoring propionic acid production, during diet-induced weight loss.

Consistency of faecal scoring using two canine faecal scoring systems.

OBJECTIVE: To determine the agreement of canine faecal scoring between individuals with different levels of experience using two available faecal scoring systems. MATERIALS AND METHODS: Naturally-voided, undisturbed bowel movements from 126 dogs were evaluated by veterinarians (n = 3) and members of the lay public (n = 126) within 15 minutes of defecation. Each participant was provided a copy of the Purina and Waltham faecal scoring charts in order to characterise the faeces. Agreement between veterinarians and lay people was assessed with kappa statistics, Bland-Altman analysis and visualised with Bland-Altman plots. RESULTS: Variable levels of consistency were observed in assessing faecal form among individuals with varying degrees of experience. Fair to substantial agreement existed between individual veterinarians scoring the same bowel movement (kappa statistic ranging from 0.40 to 0.77 on the Purina Scale and 0.54 to 0.61 on the Waltham Scale), while the agreement scores between the veterinarian and the lay public was fair (kappa statistic of 0.38 on the Purina Scale and 0.34 on the Waltham Scale). Disagreement in faecal scores occurred more frequently with lay people versus veterinarians. CLINICAL SIGNIFICANCE: The consistency of faecal scoring improved based on the level of experience with the highest agreement consistently noted between veterinarians. In all comparisons, there was inconsistency in faecal scoring which might have implications for veterinarians managing diarrhoeic canine patients. Further studies are needed to better investigate how faecal scoring can be optimised for use in clinical and research settings.

Clostridioides difficile carriage in animals and the associated changes in the host fecal microbiota.

The relationship between the gut microbiota and Clostridioides difficile, and its role in the severity of C. difficile infection in humans is an area of active research. Intestinal carriage of toxigenic and non-toxigenic C. difficile strains, with and without clinical signs, is reported in animals, however few studies have looked at the risk factors associated with C. difficile carriage and the role of the host gut microbiota. Here, we isolated and characterized C. difficile strains from different animal species (predominantly canines (dogs), felines (cats), and equines (horses)) that were brought in for tertiary care at North Carolina State University Veterinary Hospital. C. difficile strains were characterized by toxin gene profiling, fluorescent PCR ribotyping, and antimicrobial susceptibility testing. 16S rRNA gene sequencing was done on animal feces to investigate the relationship between the presence of C. difficile and the gut microbiota in different hosts. Here, we show that C. difficile was recovered from 20.9% of samples (42/201), which included 33 canines, 2 felines, and 7 equines. Over 69% (29/42) of the isolates were toxigenic and belonged to 14 different ribotypes including ones known to cause CDI in humans. The presence of C. difficile results in a shift in the fecal microbial community structure in both canines and equines. Commensal Clostridium hiranonis was negatively associated with C. difficile in canines. Further experimentation showed a clear antagonistic relationship between the two strains in vitro, suggesting that commensal Clostridia might play a role in colonization resistance against C. difficile in different hosts.

CXCR4 expression mediates glioma cell invasiveness.

Glioblastoma multiforme is a highly invasive tumor bearing a dismal prognosis. Experimental strategies that focus on the specific biological cues governing the invasive capacity of these tumors may hold significant therapeutic promise. In this context, we describe the in vitro and in vivo association of the cell surface chemokine receptor, CXCR4, with the development of an invasive phenotype in malignant glioblastoma. We demonstrate that invasive populations of glioma cells overexpress CXCR4 at the message and protein levels, and that this expression ranges from 25- to 89-fold higher than that found in noninvasive tumor cells. Furthermore, neutralization of CXCR4 significantly impairs the in vitro invasive capacity of malignant glial cells. In addition, glioma cells secrete CXCL12 and demonstrate robust invasive capacity toward a CXCL12 gradient in vitro. These findings underscore the importance of CXCR4 as a potential therapeutic target for the treatment of invasive glioblastoma.

HIV-associated nephropathy: case study and review of the literature.

Human immunodeficiency virus type 1 (HIV-1)-seropositive patients are at risk for the development of a variety of acute and chronic renal diseases. The most common cause of chronic renal failure in HIV-1-seropositive patients is HIV-associated nephropathy (HIVAN). HIVAN occurs almost exclusively in black patients and the majority of published cases are of patients who present with acquired immunodeficiency syndrome (AIDS). This disease is currently the third leading cause of end-stage renal disease in blacks aged 20-64. Because HIV-1-seropositive patients may develop a wide variety of acute and chronic renal diseases, definitive diagnosis requires renal biopsy. Emerging data suggest a direct role of HIV-1 infection of kidney cells in the pathogenesis of HIVAN. There have been no well-controlled clinical trials in the treatment of HIVAN. The therapeutic agents with the most promise are angiotensin-converting enzyme inhibitors and antiretroviral medications. Long-term renal prognosis may be changing in the setting of improved aggressive antiretroviral therapy. Patient survival is determined primarily by the stage of HIV-1 infection. In this article, we present the case history of a patient who developed HIVAN. We then review the current literature concerning the epidemiology, differential diagnosis, etiology, and treatment of HIVAN.

Treatment of HIV-associated nephropathy.

HIV-Associated Nephropathy (HIVAN) is the most common cause of chronic renal disease in HIV-1 infected patients. The disease occurs predominantly in blacks between the ages of 20 and 64. In this population it is currently the third leading cause of end-stage renal disease. The majority of patients with HIVAN have an AIDS-defining condition when the kidney disease is diagnosed. Without treatment they progress to end-stage renal disease within weeks to months. Patients with HIVAN should be treated with highly active antiretroviral therapy (HAART). Treatment should prolong survival and may improve or stabilize kidney function. Steroids have short-term benefits but long-term benefits have not been shown. Converting enzyme inhibitors (CEI) seem to stabilize kidney function and appear to be most effective when administered early in the course of HIVAN. A randomized controlled trial comparing HAART therapy to HAART and CEI should be performed.

HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection.

BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) can be the initial presentation of HIV-1 infection. As a result, many have assumed that HIVAN can occur at any point in the infection. This issue has important implications for appropriate therapy and, perhaps, for pathogenesis. Since the development of new case definitions for acquired immunodeficiency syndrome (AIDS) and better tools to assess infection, the relationship of HIVAN to the time of AIDS infection has not been addressed. In this study, we reassessed the stage of infection at the time of HIVAN diagnosis in 10 patients, and we reviewed all previously published cases applying the new case definitions to assess stage of infection. METHODS: HIVAN was confirmed by kidney biopsy in HIV seropositive patients with azotemia and/or proteinuria. CD4+ cell count and plasma HIV-1 RNA copy number were measured. We also reviewed all published cases of HIVAN to determine if AIDS-defining conditions, by current Centers for Disease Control definitions, were present in patients with biopsy-proven HIVAN. RESULTS: Twenty HIV-1 seropositive patients with proteinuria and an elevated creatinine concentration were biopsied. HIVAN was the single most common cause of renal disease. CD4+ cell count was below 200/mm3 in all patients with HIVAN, fulfilling Centers for Disease Control criteria for an AIDS-defining condition. HIV-1 plasma RNA was detectable in all patients with HIVAN. In reviewing previous reports, an AIDS-defining condition was present in virtually all patients with HIVAN. CONCLUSION: HIVAN develops late, not early, in the course of HIV-1 infection following the development of AIDS. This likely accounts for the poor prognosis noted in previous publications and has implications for pathogenesis. In addition, given the detectable viral RNA levels, highly active antiretroviral therapy is indicated in HIVAN. Highly active antiretroviral therapy may improve survival as well as alter the natural history of HIVAN.

The human immunodeficiency virus (HIV) epidemic and HIV-associated nephropathy.

Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN), the single most common cause of end-stage renal failure in seropositive patients, has increased in incidence by 30% each year since 1991. Occurring almost exclusively in blacks, HIVAN became the third leading cause of ESRD in blacks, ages 20 to 64, in 1995. During that year, the absolute number of new acquired immune deficiency syndrome (AIDS) cases declined for the first time since the epidemic began. The decrease occurred predominantly in white males, whereas in blacks with heterosexual exposures for risk factors, the incidence actually increased. Also in 1995, the number of AIDS-related deaths declined for the first time. If these trends continue, we can expect a continued increase in the number of blacks living with AIDS. We estimate that 1% to 4% will develop renal failure from HIVAN. The incidence of HIVAN can be expected to increase unless new approaches are successful in preventing the spread of HIV-1 in all segments of the population or in treating the renal complications of HIV-1 infection.

Percutaneous renal biopsy complicated by renal capsular artery pseudoaneurysm.

We report a case of renal capsular artery pseudoaneurysm caused by percutaneous renal biopsy. The injury was diagnosed and treated with arteriography and transarterial embolization. Because the arterial injury was extraparenchymal, the clinical manifestations of blood loss were flank pain and decreasing hematocrit without hematuria. Injury to renal capsular arteries during percutaneous renal biopsy is a rare possibility because of their small size.

Are we missing an epidemic of HIV-associated nephropathy?

HIV-associated nephropathy is infrequently cited as a common cause of ESRD. It is likely, however, that by the end of the decade, HIV-associated nephropathy will be the third leading cause of ESRD in African Americans between the ages of 20 and 64. Underreporting for reasons of confidentiality and a failure to track this specific diagnostic category nationally may account for the nephrology community's inattention. As a result of this community's failure to define this issue, national agencies are poorly prepared to recognize and anticipate the changing demographics of the AIDS epidemic as it affects the practice of nephrology. The study presented here concluded: that a national registry should be created to track the incidence of HIV-associated nephropathy as a cause of ESRD; that renal biopsies should be routinely performed to confirm the clinical diagnosis of HIV-associated nephropathy; that anonymous serological screening of all patients and health care providers in dialysis units be reconsidered in order to maintain vigilance for potential unit outbreaks; that the National Institutes of Health and the Office of AIDS Research be better appraised of the importance of this issue by the nephrology community; and that special attention be directed toward the underlying cause(s) of HIV-associated nephropathy and the cofactor(s) that determine the predilection of this disease in blacks.

Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure.

In diabetes and ageing, glucose-derived advanced glycosylation endproducts (AGEs) cross-link proteins and cause vascular tissue damage. Elimination of circulating low-molecular weight AGE-modified molecules (LMW-AGEs) by the kidney is impaired in diabetic patients with end-stage renal disease, a group subject to accelerated atherosclerosis. We determined the effectiveness of current renal replacement treatments on elimination of serum LMW-AGEs in diabetic and non-diabetic patients with end-stage renal disease. Although diabetic patients receiving high-flux haemodialysis achieved 33% lower steady-state serum LMW-AGE than did those in conventional haemodialysis (p < 0.005), LMW-AGE concentrations remained 3.5-6 fold above normal, whether high-flux dialysis, conventional haemodialysis, or chronic ambulatory peritoneal dialysis were used. High-flux haemodialysis markedly reduced AGE during each treatment session (47.9% in the diabetic, p < 0.001 and 60.6% in the non-diabetic group, p < 0.001) but concentrations returned to pre-treatment range within 3 hours. In contrast, normal LMW-AGE concentrations were maintained in patients with functioning renal transplants. We found that LMW-AGEs with an apparent molecular weight of 2000-6000 circulate and retain strong inherent chemical reactivity--when exposed to collagen in vitro, up to 77% attached covalently to form AGE-collagen, and the AGE-crosslink inhibitor aminoguanidine completely inhibited this reaction. The results suggest that LMW-AGEs comprise a set of chemically-reactive molecules that are refractory to removal by current dialysis treatments. Through covalent reattachment onto vascular matrix or serum components, LMW-AGEs may exacerbate vascular pathology associated with end-stage renal disease.

Glomerular hemodynamics in cyclosporine nephrotoxicity following uninephrectomy.

Experiments were performed to determine the cause of the reduced glomerular filtration rate (GFR) in cyclosporine nephrotoxicity during compensatory renal growth. Sprague-Dawley rats were uninephrectomized and given daily injections of cyclosporine (30 mg/kg, i.m.) or vehicle (olive oil), and studied 7 or 14 days later. In cyclosporine treated rats GFR was lower seven days (1.34 +/- 0.10 vs. 1.68 +/- 0.07 ml/min) and 14 days (1.19 +/- 0.08 vs. 1.58 +/- 0.04, P less than 0.025) following uninephrectomy. Arterial blood pressure, cardiac output and renal blood flow (RBF) were not different in cyclosporine and control rats. Kidney mass increased to the same extent in cyclosporine and control rats. Micropuncture of the glomerular microcirculation in similarly prepared Munich-Wistar rats demonstrated low whole kidney GFR (1.10 +/- 0.07 vs. 1.55 +/- 0.13 ml/min, P less than 0.01), and single nephron GFR (31.07 +/- 2.27 vs. 42.36 +/- 2.47 nl/min, P less than 0.005) in cyclosporine treated rats as compared to controls. Single nephron plasma flow, afferent and efferent arteriolar resistance, the transglomerular hydrostatic pressure gradient, and arterial blood pressure were the same in both groups. The glomerular capillary ultrafiltration coefficient (Kf) was lower in cyclosporine treated rats compared to controls [0.039 +/- 0.002 vs. 0.075 +/- 0.013 nl/(sec.mm Hg), P less than 0.025]. We conclude that in this model of cyclosporine nephrotoxicity the low GFR is caused solely by a reduction in Kf, and that cyclosporine can reduce GFR without causing renal vasoconstriction.

Reduced renal blood flow in early cisplatin-induced acute renal failure in the rat.

Studies were designed to determine the cause of the reduced glomerular filtration rate (GFR) in early cisplatin-induced acute renal failure. Rats were studied 72 h following a single intraperitoneal injection of cisplatin (5 mg/kg) or vehicle (0.9% NaCl). Whole kidney GFR and blood flow were lower in cisplatin-treated animals than in controls (0.30 +/- 0.06 vs. 1.17 +/- 0.06 ml X min-1 X g kidney wt-1 and 5.30 +/- 0.62 vs. 8.25 +/- 0.43 ml X min-1 X g kidney wt-1, respectively; P less than 0.001), as were superficial nephron GFR and stop-flow pressure (20.2 +/- 2.1 vs. 34.5 +/- 2.0 nl X min-1 X g kidney wt-1 and 29.0 +/- 1.9 vs. 39.8 +/- 1.3 mmHg, respectively; P less than 0.001). After volume expansion, renal plasma flow increased in control rats, whereas whole kidney and single nephron GFR did not change. In experimental animals, whole kidney filtration rate rose to 0.58 +/- 0.07 ml X min-1 X g kidney wt-1, single nephron filtration rate increased to 29.9 +/- 3.5 nl X min-1 X g kidney wt-1 (P less than 0.005), and renal plasma flow increased to 5.62 +/- 0.60 ml X min-1 X g kidney wt-1 (P less than 0.05). Intratubular hydrostatic pressure was not different in the two groups before or after volume expansion. The results of these studies show that the reduced GFR in early cisplatin-induced renal failure is due, in part, to reversible changes in renal blood flow and renal vascular resistance.