A longitudinal study on the acceptance and effects of a therapeutic renal food in pet dogs with IRIS-Stage 1 chronic kidney disease.

Currently, nutritional management is recommended when serum creatinine (Cr) exceeds 1.4 mg/dl in dogs with IRIS-Stage 2 chronic kidney disease (CKD) to slow progressive loss of kidney function, reduce clinical and biochemical consequences of CKD, and maintain adequate nutrition. It is unknown if dietary interventions benefit non-azotemic dogs at earlier stages. A prospective 12-month feeding trial was performed in client-owned dogs with IRIS-Stage 1 CKD (n = 36; 20 had persistently dilute urine with urine specific gravity (USG) <1.020 without identifiable non-renal cause; six had persistent proteinuria of renal origin with urine protein creatinine (UPC) ratio >0.5; 10 had both). Ease of transition to therapeutic renal food and effects on renal biomarkers and quality of life attributes were assessed. Dogs were transitioned over 1 week from grocery-branded foods to renal food. At 0, 3, 6, 9, and 12-months a questionnaire to assess owner's perception of their pet's acceptance of renal food and quality of life was completed. Renal biomarkers, including serum Cr, blood urea nitrogen (BUN), and symmetric dimethylarginine (SDMA), and USG and UPC ratio were measured. Of 36 dogs initially enrolled, 35 (97%) dogs were transitioned to therapeutic renal food. Dogs moderately or extremely liked the food 88% of the time, ate most or all of the food 84% of the time, and were moderately or extremely enthusiastic while eating 76% of the time. All renal biomarkers (Cr, BUN, and SDMA) were decreased (p ≤ .05) from baseline at 3-months, and remained decreased from baseline at 12-months in dogs completing the study (n = 20). Proteinuria was reduced in 12 of 16 dogs (p = .045) with proteinuria. Owners reported improvement in overall health and quality of life attributes, and hair and coat quality (all p < .01). In summary, dogs with IRIS-Stage 1 CKD readily transition to renal food. Decreasing serum biomarker concentrations and reduction in proteinuria suggest stabilized kidney function.

Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.

Association of caspase-9 and RUNX3 with inflammatory bowel disease.

Previous linkage studies have identified a region at 1p36 as the susceptibility locus (IBD7) of inflammatory bowel disease (IBD). The objective of this study was to investigate whether polymorphisms of caspase-9 (CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. We studied 555 Crohn's disease (CD) and 651 ulcerative colitis (UC) patients recruited from a single UK center. A total of 964 healthy Caucasian subjects were recruited as controls from general practitioner well person clinics in Oxfordshire. Fourteen single nucleotide polymorphisms (SNPs) of CASP9 and 11 SNPs of RUNX3 were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (homogenous MassEXTEND, hME, Sequenom™, Sequenom Inc., San Diego, CA). Linkage disequilibrium (LD) and haplotype association analysis were performed using 2ld and phase v2.0 software. No association of individual SNPs of CASP9 or RUNX3 with UC or CD was identified. The rs1052571 of CASP9 was associated with severe UC [P = 0.0034, odds ratio (OR) = 1.957, 95% confidence interval (CI) = 1.240-3.088]. Significant haplotype associations between CASP9 and IBD were identified, while no association of RUNX3 haplotypes with either UC or CD was found. Our findings suggested that CASP9 gene might be another IBD susceptibility gene.

In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope.

Celiac disease (CD) is an increasingly diagnosed enteropathy (prevalence, 1:200-1:300) that is induced by dietary exposure to wheat gliadins (as well as related proteins in rye and barley) and is strongly associated with HLA-DQ2 (alpha1*0501, beta1*0201), which is present in over 90% of CD patients. Because a variety of gliadin peptides have been identified as epitopes for gliadin-specific T-cell clones and as bioactive sequences in feeding studies and in ex vivo CD intestinal biopsy challenge, it has been unclear whether a 'dominant' T-cell epitope is associated with CD. Here, we used fresh peripheral blood lymphocytes from individual subjects undergoing short-term antigen challenge and tissue transglutaminase-treated, overlapping synthetic peptides spanning A-gliadin to demonstrate a transient, disease-specific, DQ2-restricted, CD4 T-cell response to a single dominant epitope. Optimal gamma interferon release in an ELISPOT assay was elicited by a 17-amino-acid peptide corresponding to the partially deamidated peptide of A-gliadin amino acids 57-73 (Q65E). Consistent with earlier reports indicating that host tissue transglutaminase modification of gliadin enhances gliadin-specific CD T-cell responses, tissue transglutaminase specifically deamidated Q65 in the peptide of A-gliadin amino acids 56-75. Discovery of this dominant epitope may allow development of antigen-specific immunotherapy for CD.

The genetics of NOD-like receptors in Crohn's disease.

The first Crohn's disease (CD) susceptibility gene identified was CARD15, which is a member of the emerging NOD-like receptor (NLR) family. These function as intracellular cystosolic pattern recognition receptors (PRRs) and play a central role in the innate immune response. We studied other members of the NLR family using a gene-wide haplotype tagging approach in a well-characterised collection of 547 CD patients and 465 controls. Four single nucleotide polymorphisms (SNPs) in NLRP3 had P values < 0.05 and are in high linkage disequilibrium (LD) with each other (r(2) > 0.90 for all four SNPs). rs4925648 and rs10925019 were the most strongly associated with CD susceptibility (P = 0.001, odds ratio (OR) 1.62, 95% CI 1.2-2.18; and P = 6.5 x 10(-4), OR 1.65, 95% CI 1.23-2.19, respectively). rs1363758 located in NLRP11 was associated with CD susceptibility [P = 0.002 (1.64, 1.19-2.25)], which was weakly confirmed in an independent case-cohort collection on joint analysis [P = 0.05, (1.28, 1-1.64)]. On sub-phenotype analysis, an interesting association between NLRP1 and skin extra-intestinal manifestations and colonic, inflammatory CD was identified. None of these results was replicated in the Wellcome Trust Case Control Consortium study and therefore need replication in a further large cohort.

Dose-titration effects of fish oil in osteoarthritic dogs.

BACKGROUND: Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). OBJECTIVE: Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. ANIMALS: One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. METHODS: Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. RESULTS: Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. CONCLUSIONS AND CLINICAL IMPORTANCE: Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.

"Can I Live": Black American Adolescent Boys' Reports of Police Abuse and the Role of Religiosity on Mental Health.

State sanctioned violence aimed at Black individuals and communities is an issue that has pervaded American history and society since before the establishment of the United States. For Black males, anticipating and preparing for involuntary police contact, unfortunately, is an inevitable part of life. The purpose of this study is to examine the impact of reports of police abuse on mental health and perceived racial out-group perceptions and the protective role of religiosity among a nationally representative sample of Black American adolescent boys (Mage = 14.98). Linear multiple regression was used to determine the interactive effects of subjective religiosity and reported police abuse on Black American adolescent boys. Higher reports of subjective religiosity were associated with lower depressive symptomatology. Reports of police abuse were associated with lower public regard beliefs (belief that society views Black Americans less favorably). Results highlight the impact experiencing police abuse has on Black adolescent boys and we conclude with implications, areas for future research and intervention points.

Confirmation of the novel association at the BTNL2 locus with ulcerative colitis.

Linkage in families and association in population case-control investigations have clearly shown that genes within the major histocompatibility complex region on chromosome 6p are relevant to the susceptibility and pathogenesis of ulcerative colitis (UC) and Crohn's disease. However, identifying the causative variants by fine mapping has not been conclusive. In this study using 58 single nucleotide polymorphisms (SNPs) with 616 UC cases, there was significant association with SNP rs2294881 of the (butyrophilin-like 2) BTNL2 gene with odds ratio (OR) = 2.80, confidence interval (CI) = 1.62-4.84 and P = 5.69 x 10(-4) (P(Bonferroni) = 3.3 x 10(-2)) and replication of SNP rs9268480. The missense SNP rs2076523 (K196E) showed novel association with a subset of UC cases with colectomy (n = 126), OR = 0.25, CI = 0.11-0.58 and P = 4.42 x 10(-4) (P(Bonferroni) = 2.56 x 10(-2)). These three associated variants within the BTNL2 gene were neither in linkage disequilibrium with each other nor correlated with the SNPs tagging the human leukocyte antigen (HLA)-DRB1*1502 and HLA-DRB1*0301 alleles.

Development, evaluation, and peer verification of a rapid real-time PCR method for the detection of animal material.

Four real-time PCR assays that can be used with U.S.- and European Union-rendered materials to detect three ruminant species (bovine, caprine, and ovine) and a select set of avians (chicken, goose, and turkey) were developed. This method was evaluated against stringent acceptance criteria previously developed by the U.S. Food and Drug Administration, Center for Veterinary Medicine's Office of Research. Acceptance criteria for determining success used a statistical approach requiring a 90% probability of achieving the correct response, within a 95% confidence interval. A minimum detection level of 0.1% meat and bone meal (MBM) was required, consistent with the sensitivity of the validated PCR-based method currently used by the U.S. Food and Drug Administration as an aid in enforcement of the Agency's feed ban. PCR primer specificity was determined by using a panel of DNA samples derived from 16 different animal species. The method is able to detect 0.1% rendered material in complete feed in less than 1.5 h of total assay time, a significant improvement over the current method, which requires 7 to 8 h for completion. The real-time assay for the detection of animal material passed stringent acceptance criteria for sensitivity, selectivity, and specificity. The method also passed ruggedness, real-time platform, and second analyst trials. Two external laboratories participating in a peer-verification trial demonstrated 100% specificity in identifying bovine MBM, ovine MBM, or caprine meat meal, while exhibiting a 0.6% rate of false positives. These results demonstrated that this method was capable of being used by other laboratories.

Upper limb motor function in young adults with spina bifida and hydrocephalus.

OBJECTIVE: The objective of the study was to measure upper limb motor function in young adults with spina bifida meningomyelocele (SBM) and typically developing age peers. METHOD: Participants were 26 young adults with SBM, with a Verbal or Performance IQ score of at least 70 on the Wechsler scales, and 27 age- and gender-matched controls. Four upper limb motor function tasks were performed under four different visual and cognitive challenge conditions. Motor independence was assessed by questionnaire. RESULTS: Fewer SBM than control participants obtained perfect posture and rebound scores. The SBM group performed less accurately and was more disrupted by cognitive challenge than controls on limb dysmetria tasks. The SBM group was slower than controls on the diadochokinesis task. Adaptive motor independence was related to one upper limb motor task, arm posture, and upper rather than lower spinal lesions were associated with less motor independence. CONCLUSIONS: Young adults with SBM have significant limitations in upper limb function and are more disrupted by some challenges while performing upper limb motor tasks. Within the group of young adults with SBM, upper spinal lesions compromise motor independence more than lower spinal lesions.

Emergence of inflammatory bowel disease 'beyond the West': do prosperity and improved hygiene have a role?

Inflammatory bowel disease (IBD) is increasing in many countries 'beyond the West'. This increase may be due to an increased rate of diagnosis but might also represent a true increase in incidence. Economic development, leading to improved hygiene and other changes in lifestyle, may play a role in the increase in IBD. However, the marked difference in prevalence between ethnic groups suggests that the genetic background of populations may also be relevant and supports the current hypothesis that IBD represents an interaction between environmental factors and a genetically susceptible host. Investigating the early stages of IBD as it emerges in new populations may provide new clues to its pathophysiology.

Potential use of DNA barcodes in regulatory science: applications of the Regulatory Fish Encyclopedia.

The use of a DNA-based identification system (DNA barcoding) founded on the mitochondrial gene cytochrome c oxidase subunit I (COI) was investigated for updating the U.S. Food and Drug Administration Regulatory Fish Encyclopedia (RFE; http://www.cfsan.fda.gov/-frf/rfe0.html). The RFE is a compilation of data used to identify fish species. It was compiled to help regulators identify species substitution that could result in potential adverse health consequences or could be a source of economic fraud. For each of many aquatic species commonly sold in the United States, the RFE includes high-resolution photographs of whole fish and their marketed product forms and species-specific biochemical patterns for authenticated fish species. These patterns currently include data from isoelectric focusing studies. In this article, we describe the generation of DNA barcodes for 172 individual authenticated fish representing 72 species from 27 families contained in the RFE. These barcode sequences can be used as an additional identification resource. In a blind study, 60 unknown fish muscle samples were barcoded, and the results were compared with the RFE barcode reference library. All 60 samples were correctly identified to species based on the barcoding data. Our study indicates that DNA barcoding can be a powerful tool for species identification and has broad potential applications.

Computational toxicology methods in public health practice.

ABSTRACT Hazard identification and health risk assessment traditionally rely on results of experimental testing in laboratory animals. It is a lengthy and expensive process, which at the end still involves large uncertainty because the sensitivity of animals is unequal to the sensitivity of humans. The Agency for Toxic Substances and Disease Registry (ATSDR) Computational Toxicology and Method Development Laboratory develops and applies advanced computational models that augment the traditional toxicological approach with multilevel cross-extrapolation techniques. On the one hand, these techniques help to reduce the uncertainty associated with experimental testing, and on the other, they encompass yet untested chemicals, which otherwise would be left out of public health assessment. Computational models also improve understanding of the mode of action of toxic agents, and fundamental mechanisms by which they may cause injury to the people. The improved knowledge is incorporated in scientific health guidance documents of the Agency, including the Toxicological Profiles, which are used as the basis for scientifically defensible public health assessments.

Infliximab for the treatment of ulcerative colitis: outcomes in Oxford from 2000 to 2006.

BACKGROUND: Infliximab has been shown to be of benefit in the treatment of ulcerative colitis but long-term colectomy rates remain unknown. AIMS: To review the rate of colectomy after infliximab for ulcerative colitis and to identify factors that might predict the need for colectomy. METHODS: We conducted a retrospective cohort study of patients with active ulcerative colitis treated with infliximab between 2000 and 2006. The primary outcome was colectomy-free survival. Disease and treatment characteristics and complications were documented. RESULTS: Thirty patients were treated with infliximab for refractory ulcerative colitis. Sixteen (53%) came to colectomy a median of 140 days after their first infusion (range 4-607). There was no difference in colectomy between those receiving infliximab for acute severe ulcerative colitis failing intravenous steroids (8/14) and out-patients with steroid-refractory ulcerative colitis (8/16). Only 17% (5/30) achieved a steroid-free remission after a median follow-up of 13 months (range 2-72). Univariate analysis showed that a younger age at diagnosis of colitis was significantly associated with an increased rate of colectomy (27.5 years vs. 38.7 years, P = 0.016). CONCLUSION: Over half the patients studied came to colectomy. Of those avoiding colectomy, only five (17%) sustained a steroid-free remission.

Assessment of two enzyme-linked immunosorbent assay tests marketed for detection of ruminant proteins in finished feed.

The performance characteristics of two enzyme-linked immunosorbent assay (ELISA) test kits, ELISA Technologies' MELISA-Tek test and Tepnel BioSystems' BioKit for (Cooked) Species Identification test, designed to detect ruminant proteins in animal feed, were evaluated. The test kits were evaluated by using acceptance criteria developed by the U.S. Food and Drug Administration's Center for Veterinary Medicine Office of Research for evaluating selectivity, sensitivity, ruggedness, and specificity. The acceptance criteria for determining success used a statistical approach requiring a 90% probability of achieving the correct response within a 95% confidence interval. In practice, this measure requires the test to achieve the correct response 58 times for every 60 samples evaluated, or a 96.7% accuracy rate. A minimum detection level of 0.1% bovine meat and bone meal (BMBM) was required, consistent with the sensitivity of the analytical methods presently used by the U.S. Food and Drug Administration. Selectivity was assessed by testing 60 dairy feed samples that contained no added animal proteins; sensitivity was determined by evaluating 60 samples (per level of fortification) of this same feed that contained 0.025, 0.05, 0.1, 0.25, 0.5, 1, or 2% BMBM. The MELISA-Tek test passed the acceptance set-point criteria for selectivity assessment but failed the sensitivity assessment at all levels except at the 2% level. The MELISA-Tek test came close to passing at the 1% level, detecting true-positive findings at a rate of 93%, but failed at lower levels, in spite of the label claim of 0.5% sensitivity. The BioKit for (Cooked) Species Identification test detected only 2 of 17 samples fortified at the 2% BMBM level and failed to detect any other BMBM-fortified samples. The results of this evaluation indicate that neither test is adequate for regulatory use.

The Birmingham Interlocking Pelvic Osteotomy for acetabular dysplasia: 13- to 21-year survival outcomes.

AIMS: The aim of this study was to evaluate the long-term clinical and radiographic outcomes of the Birmingham Interlocking Pelvic Osteotomy (BIPO). PATIENTS AND METHODS: In this prospective study, we report the mid- to long-term clinical outcomes of the first 100 consecutive patients (116 hips; 88 in women, 28 in men) undergoing BIPO, reflecting the surgeon's learning curve. Failure was defined as conversion to hip arthroplasty. The mean age at operation was 31 years (7 to 57). Three patients (three hips) were lost to follow-up. RESULTS: Survivorship was 76% at ten years and 57% at a mean of 17 years. Younger patients (< 20 years) had the best survivorship (20 hips at risk; 90% at 17 years; 95% confidence interval 65 to 97). Post-operative complications occurred after 12 operations (10.4%) over the duration of the study. Increasing patient age and hip arthritis grade were primary determinants of surgical failure. CONCLUSION: BIPO provides good to excellent survivorship in appropriately selected patients, with a relatively low rate of complications. Our results are comparable with other established methods of periacetabular osteotomy (PAO), such as the Bernese PAO, even during the surgeon's initial learning curve. Cite this article: Bone Joint J 2017;99-B:724-31.

Review article: interactions between genotype and response to therapy in inflammatory bowel diseases.

BACKGROUND: More than half of the patients with inflammatory bowel diseases are candidates for immunosuppressive therapy. However, even the most effective drugs used in inflammatory bowel disease are only successful in about two-thirds of patients. Adverse events limit their use in a further substantial proportion of patients. Recent research has focussed on the possibility of predicting a drugs' efficacy and/or toxicity by identifying polymorphic variants in the genes encoding enzymes involved in metabolic pathways. AIM: To highlight recent advances and limitations in the field of pharmacogenetics in inflammatory bowel disease. RESULTS: Recent pharmacogenetic studies have mainly focussed on immunosuppressive agents including corticosteroids, azathioprine, methotrexate and infliximab. Several polymorphic genes encoding enzymes involved in the metabolism of these drugs have been identified including the inosine triphosphate pyrophosphatase in thiopurine therapy, the methylene tetrahydrofolate reductase in methotrexate therapy and polymorphisms in apoptosis genes in infliximab therapy. However, at the present time, genotyping for the variants of the thiopurine methyltransferase gene, an enzyme important for the metabolism of the thiopurine drugs, is the only useful test in clinical practice. CONCLUSIONS: Although the field of pharmacogenetics in inflammatory bowel disease is promising most new targets have so far failed to translate into clinical practice. Future pharmaceutical trials should include pharmacogenetic research to test appropriate candidate genes in a prospective manner.

Reducing transfer times for coronary angiography in patients with acute coronary syndromes: one solution to a national problem.

BACKGROUND: Patients with acute coronary syndrome (ACS) are at high risk of further cardiac events and benefit from early intervention, as reflected by international guidelines recommending early transfer to interventional centres. The current average waiting time of up to 21 days contravenes evidence based early intervention, creates geographical inequity of access, wastes bed days, and is unsatisfactory for patients. METHODS: A regional transfer unit (RTU) was created to expatriate access of ACS patients referred from other centres to the revascularisation service. By redesigning the care pathway patients arriving on the RTU undergo angiography within 24 hours, and then leave the RTU the following day, allowing other ACS patients to be treated. RESULTS: During the first six months of the RTU, the mean waiting time from referral to procedure decreased from 20 (SD 15) days (range 0-51) to 8 (SD 3) days (range 0-21) for 365 patients transferred from a district general hospital. Ninety seven per cent of patients underwent angiography within 24 hours, 61% having undergone percutaneous coronary intervention at the same sitting, and 78% were discharged home within 24 hours. CONCLUSIONS: Delivering standards laid out in the National Service Framework, reducing inequalities of care across the region, and facilitating evidence based strategies of care represents a challenging and complex issue. For high risk patients suffering ACS who need early invasive investigation, a coordinated network wide approach together with the creation of an RTU resulted in a 62% reduction in waiting times for no extra resources. Further improvements can be expected through increased capacity of this verified strategy.

Nutritional Interventions that Slow the Age-Associated Decline in Renal Function in a Canine Geriatric Model for Elderly Humans.

OBJECTIVE: To determine the effects of feeding traditional and renal protective foods (RPF) supplemented with functional food bioactives on glomerular filtration rate (GFR), lean body percent (LB%), and selected circulating biomarker and metabolite concentrations in a geriatric dog model. DESIGN: Randomized block design and cross-sectional study. SETTING: Hill's Pet Nutrition, Inc. dog colony. PARTICIPANTS: Eighty-one geriatric dogs (mean age, 10.4; range, 7.9-14.2 years) and 30 mature-adult dogs (mean age, 5.0; range, 3.3-6.9 years). INTERVENTION: Geriatric dogs were fed one of three foods (n = 27 per group) for 6 months: a traditional RPF (control) that was energy dense and mildly protein-restricted, or control food supplemented with increasing amounts of functional food bioactives: fish oil, lipoic acid, fruits and vegetables, and higher quality protein sources [functional foods one (FF1) and two (FF2)]. Geriatric dogs were compared before and after the feeding trial with mature adult dogs. MEASUREMENTS: Renal function was assessed by GFR, LB% was determined by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites were measured in blood. RESULTS: Before the feeding trial, GFR (+28.2%), LB% (+18.6%), and serum total protein (+10.0%) were higher in mature versus healthy geriatric dogs (all P<0.001). Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%. Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) symmetric dimethylarginine (SDMA) concentrations (-14.3%). Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%). CONCLUSION: Supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein.

Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease.

BACKGROUND: Serum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval. OBJECTIVES: To report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr. ANIMALS: CKD dogs (n = 19) included those persistently azotemic for ≥3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20). METHODS: Retrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography-mass spectrometry in dogs with necropsy confirmed CKD. RESULTS: Serum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2-27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = -0.80) and serum Cr (r = -0.89) concentrations were significantly related to glomerular filtration rate (both P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Using serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease.