Usefulness of serum amyloid A for the diagnosis of pyelonephritis in cats: A prospective evaluation.

BACKGROUND: The diagnosis of pyelonephritis in cats is challenging and development of a noninvasive and accurate biomarker is needed. HYPOTHESES: Serum amyloid A (SAA) is increased in cats with pyelonephritis, but not in cats with other urinary tract diseases. ANIMALS: A cohort of 125 cats (149 observations). METHODS: This was a prospective study. Group 1 included cats with a diagnosis of pyelonephritis either confirmed by bacterial culture of pelvic urine (Group 1a) or presumed (1b). Group 2 included cats for which pyelonephritis was ruled out (with certainty: Group 2a or judged unlikely: Group 2b). SAA concentration was compared between groups, and accuracy of SAA for the diagnosis of pyelonephritis was calculated using a Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Median SAA concentration was significantly higher in Group 1a (86.8 mg/L [73.3; 161.5]; n = 8) than in Group 2a (4 mg/L [1.8; 5.6], n = 19; P < .001) and in Group 2b (5.4 mg/L [3.1; 9.7], n = 113; P < .001). It was also significantly higher in Group 1b (98.8 mg/L [83.1; 147.3]; n = 9) than in Group 2b (P < .001) and Group 2a (P < .001). Optimal diagnostic cut-off for SAA concentration was 51.3 mg/L. yielding a sensitivity of 88% (95% confidence interval: [64%; 99%]) and a specificity of 94% (95% confidence interval: [88%; 97%]). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of SAA could be used to rule out pyelonephritis in the case of low suspicion of the disease. Increased SAA concentration is suggestive of pyelonephritis despite a lack of specificity.

Acute pyelonephritis in cats is frequently caused by Escherichia coli resistant to potentiated penicillins but has a better prognosis than other causes of acute kidney injury.

OBJECTIVE: To describe the clinical findings, microbiological data, treatment, and outcome of a population of cats with suspected acute pyelonephritis (APN). ANIMALS: 32 client-owned cats. CLINICAL PRESENTATION AND PROCEDURES: Retrospective case series from 2 veterinary teaching hospitals between January 1, 2014, and December 31, 2020. Cats were included if they had a positive bacterial urine culture and a clinical diagnosis of acute kidney injury. RESULTS: Older female cats with underlying chronic kidney disease have a higher probability to develop bacterial culture-positive acute kidney injury or APN. Escherichia coli was the most commonly cultured bacterial species, and E coli isolates with susceptibility testing were resistant to amoxicillin-clavulanate but susceptible to fluoroquinolones or third-generation cephalosporins. Of the 20 cats with available follow-up information in the medical record, 14 were alive at 3 months after hospital discharge. Markers of renal function including creatinine (P = .008), BUN (P = .005), and phosphorus (P < .001) at the time of presentation were all higher in nonsurvivors compared with survivors. CLINICAL RELEVANCE: The survival rate with feline APN is higher than previous reports of acute kidney injury when all etiologies are considered. Nonsurvivors had more pronounced azotemia upon initial presentation. Amoxicillin-clavulanate was a poor empirical antimicrobial in this cohort based on the microbiological data.

Pyelonephritic end-stage kidney and ureterocutaneous fistula in a Shetland pony.

A 12-y-old Shetland Pony was presented with a mucus-secreting fistula in the right paralumbar fossa. Surgery was performed to unravel the origin of the fistula. The horse died under anesthesia and was forwarded to autopsy. The right kidney was markedly atrophic and fibrotic, consistent with unilateral end-stage kidney. The right ureter was markedly thickened, but with luminal continuity leading into the urinary bladder where a partial obstruction caused by nodular para-ureteral fat necrosis was evident. The lumen of the cutaneous fistula was continuous with the right ureter; therefore, we diagnosed the lesion as a ureterocutaneous fistula. Anomalies of the ureter are uncommon, and ureterocutaneous fistula formation in equids has not been reported previously to our knowledge.

Do post-surgical multiresistant urinary infections occur in horses? Case of unilateral pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria as a complication of cystotomy.

Pyelonephritis is a serious condition that is rarely described in horses. In contrast, urinary tract infections are common in humans and small animals, and multi-drug-resistant urinary infections are an emerging threat. In this report, we describe a horse with unilateral pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria belonging to the Enterobacter cloacae complex. [Correction added on 9 August 2023, after first online publication: The preceding sentence was corrected.] An 11-year-old Swedish warmblood gelding was diagnosed with a cystolith and a cystotomy through an open left para-inguinal approach was performed. Seven days after surgery the horse presented with pyrexia, dullness and colic. Diagnostic testing and renal transabdominal ultrasonography confirmed the presence of a right-sided pyelonephritis. Culture and antimicrobial susceptibility testing revealed a pure growth of extended-spectrum beta-lactamases-producing E. cloacae complex bacteria with resistance against beta-lactams, aminoglycoside and trimethoprim-sulphonamide classes. Treatment included prolonged oral antimicrobials according to susceptibility testing results (enrofloxacin), judicious use of non-steroidal anti-inflammatory drugs, fluid therapy and gastric ulcer prophylaxis. The horse recovered successfully and is currently in good health (follow-up of 5 years). Once the infection resolved, unilateral renal scarring occurred. Multidrug-resistant upper-urinary infections occur in horses and should be considered in a post-surgical patient that develops fever. Early diagnosis, urine bacterial culturing and antimicrobial susceptibility testing were crucial in this case to successful management.

Genomic analysis of a multidrug methicillin-resistant staphylococcus epidermidis recovered from the urine of a guinea pig (Cavia porcellus) with suspected pyelonephritis.

Staphylococcus epidermidis is an emerging pathogen causing infant pyelonephritis. There is a lack of genomic data on Staphylococcus epidermidis as the etiology of pyelonephritis and its resistant determinants. In this study, we have conducted a genomic and microbiologic investigation of an S. epidermidis recovered from the urine of a guinea pig with suspected pyelonephritis in Brazil. The genome was sequenced using the Illumina MiSeq platform and de novo assembled using SPades. Resistome, virulome, and plasmidome were in silico predicted using bioinformatics tools. Data analysis revealed that S. epidermidis USP-LZB-G06 belonged to sequence type ST332. Strikingly, a broad resistome (antibiotics, hazardous heavy metals, and biocides) was predicted, including the presence of the clinically relevant mecA, blaZ, and qacA efflux pump genes. SNP-based analysis revealed that strain USP-LZB-G06 was clustered along mecA positive S. epidermidis strains of ST332 isolated between 2008 and 2016 from humans in Australia and the United States of America. Our results indicate that the detection of this microorganism should be considered as a urinary tract infection agent in exotic pets, particularly guinea pigs. In addition, there is an urgent need to update veterinarians regarding the detection and therapeutic management of these microorganisms.

Urinary microRNAome in healthy cats and cats with pyelonephritis or other urological conditions.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level. miRNAs have been found in urine and have shown diagnostic potential in human nephropathies. Here, we aimed to characterize, for the first time, the feline urinary miRNAome and explore the use of urinary miRNA profiles as non-invasive biomarkers for feline pyelonephritis (PN). Thirty-eight cats were included in a prospective case-control study and classified in five groups: healthy Control cats (n = 11), cats with PN (n = 10), cats with subclinical bacteriuria or cystitis (SB/C, n = 5), cats with ureteral obstruction (n = 7) and cats with chronic kidney disease (n = 5). By small RNA sequencing we identified 212 miRNAs in cat urine, including annotated (n = 137) and putative novel (n = 75) miRNAs. The 15 most highly abundant urinary miRNAs accounted for nearly 71% of all detected miRNAs, most of which were previously identified in feline kidney. Ninety-nine differentially abundant (DA) miRNAs were identified when comparing Control cats to cats with urological conditions and 102 DA miRNAs when comparing PN to other urological conditions. Tissue clustering analysis revealed that the majority of urine samples clustered close to kidney, which confirm the likely cellular origin of the secreted urinary miRNAs. Relevant DA miRNAs were verified by quantitative real-time PCR (qPCR). Eighteen miRNAs discriminated Control cats from cats with a urological condition. Of those, seven miRNAs were DA by both RNAseq and qPCR methods between Control and PN cats (miR-125b-5p, miR-27a-3p, miR-21-5p, miR-27b-3p, miR-125a-5p, miR-17-5p and miR-23a-3p) or DA between Control and SB/C cats (miR-125b-5p). Six additional miRNAs (miR-30b-5p, miR-30c, miR-30e-5p, miR-27a-3p, miR-27b-39 and miR-222) relevant for discriminating PN from other urological conditions were identified by qPCR alone (n = 4) or by both methods (n = 2) (P<0.05). This panel of 13 miRNAs has potential as non-invasive urinary biomarkers for diagnostic of PN and other urological conditions in cats.

A multicenter study of antimicrobial prescriptions for cats diagnosed with bacterial urinary tract disease.

OBJECTIVES: The aim of this study was to evaluate initial antimicrobial therapy in cats diagnosed with upper or lower bacterial urinary tract infections at veterinary practices in the USA and Canada. METHODS: Electronic medical records from a veterinary practice corporation with clinics in the USA and Canada were queried between 2 January 2016 and 3 December 2018. Feline patient visits with a diagnosis field entry of urinary tract infection, cystitis and pyelonephritis, as well as variation of those names and more colloquial diagnoses such as kidney and bladder infection, and where an antimicrobial was prescribed, were retrieved. RESULTS: Prescription data for 5724 visits were identified. Sporadic cystitis was the most common diagnosis (n = 5051 [88%]), with 491 (8.6%) cats diagnosed with pyelonephritis and 182 (3.2%) with chronic or recurrent cystitis. Cefovecin was the most commonly prescribed antimicrobial for all conditions, followed by amoxicillin-clavulanic acid. Significant differences in antimicrobial drug class prescribing were noted between practice types and countries, and over the 3-year study period. For sporadic cystitis, prescription of amoxicillin-clavulanic acid increased significantly and cefovecin decreased between 2016 and 2018, and 2017 and 2018, while fluoroquinolone use increased between 2017 and 2018. CONCLUSIONS AND RELEVANCE: The results indicate targets for intervention and some encouraging trends. Understanding how antimicrobials are used is a key component of antimicrobial stewardship and is required to establish benchmarks, identify areas for improvement, aid in the development of interventions and evaluate the impact of interventions or other changes.

Evaluation of antimicrobial prescriptions in dogs with suspected bacterial urinary tract disease.

BACKGROUND: Antimicrobials are commonly used to treat urinary tract disease in dogs. Understanding antimicrobial use is a critical component of antimicrobial stewardship efforts. HYPOTHESIS/OBJECTIVES: To evaluate antimicrobial prescriptions for dogs diagnosed with acute cystitis, recurrent cystitis, and pyelonephritis. ANIMALS: Dogs prescribed antimicrobials for urinary tract disease at veterinary practices in the United States and Canada. MATERIALS AND METHODS: A retrospective review of antimicrobial prescriptions was performed. RESULTS: The main clinical concerns were sporadic bacterial cystitis (n = 6582), recurrent cystitis (n = 428), and pyelonephritis (n = 326). Amoxicillin/clavulanic acid (2702, 41%), cefpodoxime (1024, 16%), and amoxicillin (874, 13%) were most commonly prescribed for sporadic bacterial cystitis. The median prescribed duration was 12 days (range, 3-60 days; interquartile range [IQR], 4 days). Shorter durations were used in 2018 (median, 10 days; IQR, 4 days) compared to both 2016 and 2017 (both median, 14 days; IQR, 4 days; P ≤ .0002). Amoxicillin/clavulanic acid (146, 33%), marbofloxacin (95, 21%), and cefpodoxime (65, 14%) were most commonly used for recurrent cystitis; median duration of 14 days (range, 3-77 days; IQR, 10.5 days). Amoxicillin/clavulanic acid (86, 26%), marbofloxacin (56, 17%), and enrofloxacin (36, 11%) were most commonly prescribed for pyelonephritis; however, 93 (29%) dogs received drug combinations. The median duration of treatment was 14 days (range, 3-77 days; IQR, 11 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Decreases in duration and increased use of recommended first-line antimicrobials were encouraging. Common drug choices and durations should still be targets for antimicrobial stewardship programs that aim to optimize antimicrobial use, concurrently maximizing patient benefits while minimizing antimicrobial use and use of higher tier antimicrobials.

Pyelonephritis and Cystic Endometrial Hyperplasia in a Captive Sunda Pangolin (Manis javanica).

The Sunda pangolin (Manis javanica) is one of the most trafficked animal species globally, and is listed as Critically Endangered by the IUCN. There is limited information on reproductive biology or pathology of this species. We now document the clinical and pathological features of pyelonephritis and cystic endometrial hyperplasia in one of these animals. Ultrasonographic examination revealed pathological changes in the kidneys and uterus. On histopathological examination, there was marked interstitial infiltration of macrophages, neutrophils and lymphocytes in kidney tissue, fibrinonecrotic ureteritis and mild endometrial hyperplasia. This first report of these urogenital lesions in this species will be valuable for the conduct of health and reproductive assessments of the Sunda pangolin, which inform conservation and ex-situ management of this species.

First report of urinary tract infection caused by Comamonas kerstersii in a goat.

BACKGROUND: Comamonas kerstersii is rarely associated with infections in humans and has never been reported in animals until now. CASE PRESENTATION: Herein, we describe a case of urinary tract infection caused by C. kerstersii in a young goat. A seven-month-old male goat showed lethargy, generalised weakness and anorexia and in the last hours before its death, severe depression, slight abdominal distention, ruminal stasis, and sternal recumbency. Grossly, multifocal haemorrhages in different organs and tissues, subcutaneous oedema and hydrocele, serous fluid with scattered fibrin deposition on the serosa of the abdominal organs and severe pyelonephritis with multifocal renal infarction were detected. Histopathological examination confirmed severe chronic active pyelonephritis with renal infarcts, multi-organ vasculitis and thrombosis suggestive of an infectious diseases of bacterial origin. The bacterium was identified using routine methods, matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS), and sequencing of the gyrB gene. CONCLUSIONS: To the best of our knowledge, this is the first report of C. kerstersii infection in animals (goat). Our findings support the possibility of C. kerstersii isolation from extraintestinal sites and suggest this organism as a possible cause of urinary tract infection.

Acute on chronic kidney disease in cats: Etiology, clinical and clinicopathologic findings, prognostic markers, and outcome.

BACKGROUND: Chronic kidney disease (CKD) and acute decompensation of CKD (ACKD) are common in cats. OBJECTIVES: To characterize the etiology, clinical and clinicopathologic findings, and the short- and long-term prognosis of feline ACKD. ANIMALS: One hundred cats with ACKD. METHODS: Retrospective study, search of medical records for cats with ACKD. RESULTS: Common clinical signs included anorexia (85%), lethargy (60%), weight loss (39%), and vomiting (27%). Suspected etiologies included ureteral obstruction (11%), renal ischemia (9%), pyelonephritis (8%), others (6%), or unknown (66%). Hospitalization duration was longer in survivors versus nonsurvivors (median = 7 days, range = 2-26 versus median = 3 days, range = 2-20, respectively, P < .001). The survival rate to discharge was 58%. Age, serum creatinine, urea, and phosphorous concentrations were higher and venous blood pH was lower in nonsurvivors. However, only serum phosphorus remained associated with the short-term outcome in the multivariable model (P = .02; 95% confidence interval = 1.03-1.39). Survivors had a median survival time of 66 days after discharge. Serum creatinine concentrations at presentation as well as at discharge were associated with long-term survival (P < .002 for both). CONCLUSIONS: The short-term prognosis of ACKD is comparable to acute kidney injury, while the long-term prognosis is guarded.

Stability and profiling of urinary microRNAs in healthy cats and cats with pyelonephritis or other urological conditions.

BACKGROUND: Specific biomarkers of pyelonephritis (PN) in cats are lacking. MicroRNAs (miRNAs) have diagnostic potential in human nephropathies. OBJECTIVES: To investigate the presence/stability of miRNAs in whole urine of cats and the discriminatory potential of selected urinary miRNAs for PN in cats. ANIMALS: Twelve healthy cats, 5 cats with PN, and 13 cats with chronic kidney disease (n = 5), subclinical bacteriuria (n = 3), and ureteral obstructions (n = 5) recruited from 2 companion animal hospitals. METHODS: Prospective case-control study. Expression profiles of 24 miRNAs were performed by quantitative PCR (qPCR). Effect of storage temperature (4°C [24 hours], -20°C, and -80°C) was determined for a subset of miRNAs in healthy cats. RESULTS: Urinary miR-4286, miR-30c, miR-204, miR4454, miR-21, miR-16, miR-191, and miR-30a were detected. For the majority of miRNAs tested, storage at 4°C and -20°C resulted in significantly lower miRNA yield compared to storage at -80°C (mean log2fold changes across miRNAs from -0.5 ± 0.4 SD to -1.20 ± 0.4 SD (4°C versus -80°C) and from -0.7 ± 0.2 SD to -1.20 ± 0.3 SD (-20°C versus -80°C)). Cats with PN had significantly upregulated miR-16 with a mean log2fold change of 1.0 ± 0.4 SD, compared with controls (-0.1 ± 0.2, P = .01) and other urological conditions (0.6 ± 0.3, P = .04). CONCLUSIONS: Upregulation of miR16 might be PN-specific, pathogen-specific (Escherichia coli), or both.

Bilateral Pyelonephritis in a Cat with Multiple Urinary Malformations Including Ureteral Pseudodiverticulosis.

Ureteral pseudodiverticulosis is an unusual acquired abnormality in humans and dogs. This report describes the first feline case of ureteral pseudodiverticulosis, associated with right retrocaval ureter and malposition of the uretero-vesical junctions, in the context of pyelonephritis. The coexistence of pseudodiverticulosis with other urinary abnormalities suggested that this lesion should be considered in other patients with urinary pathology.

Pyelonephritis caused by Mannheimia varigena in a Holstein calf.

A 7-day-old calf died following development of mild respiratory symptoms. Postmortem examination revealed the kidneys were inflamed, and Gram-negative bacteria was detected in the kidneys, supporting the diagnosis of suppurative pyelonephritis. Mannheimia varigena antigen was found in the lesions and the cytoplasm of macrophages and neutrophils in the renal cortex. The Gram-negative bacilli from the kidney were identified as M. varigena by sequencing the 16S rDNA. Although M. varigena is known to cause bovine respiratory disease syndrome, shipping fever, and meningitis, it was unknown that it could also cause suppurative pyelonephritis. Our study provides the first evidence of suppurative pyelonephritis caused by M. varigena in cattle and information that would improve our understanding, diagnosis, and treatment for M. varigena infections.

Hydronephrosis in a dairy calf: A diagnosis delayed by a clinician's Bayesian brain reasoning.

A 3-week-old female dairy calf was presented because of severe weakness and diarrhea. Physical examination and ultrasound findings lead to a tentative diagnosis of intestinal obstruction, although serum biochemistry suggested a primary renal disorder. Reassessment of ultrasound images allowed diagnosis of hydronephrosis that had been misdiagnosed probably because of the clinician's biased Bayesian reasoning. Pyelonephritis without renal failure was diagnosed 2.5 months later. The calf was euthanized and the diagnoses were confirmed.

Une hydronéphrose rénale chez un veau laitier : quand le raisonnement Bayesien du clinicien rend le diagnostic plus difficile. Une génisse âgée de 3 semaines est présenté pour faiblesse générale et diarrhée. L'examen clinique et les images échographiques de l'abdomen sont compatibles avec une obstruction intestinale. Mais les résultats d'analyse biochimique montrent une anomalie rénale. Un examen échographique supplémentaire est compatible avec un diagnostic d'hydronéphrose. Le diagnostic d'hydronéphrose n'avait pas été fait à la première visite probablement suite au raisonnement Bayesien du clinicien. Le veau est revu 2,5 mois plus tard. L'échographie de l'abdomen, les analyses urinaire et sanguine montrent une pyélonéphrite sans insuffisance rénale. Le veau est euthanasié et l'autopsie montre l'hydronéphrose et pyélonéphrite bilatérale.(Traduit par les auteurs).

Outbreak of Opportunistic Ascending Pyelonephritis with Numerous Yeast after Experimental Humanization Surgery in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ and NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ Immunodeficient Mice.

Unexpected mortality occurred in a group of 12 NOD.Cg-NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) and 12 NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ (NRG) immunodeficient mice. At 10 d after routine bone marrow-liver-thymus humanization surgery, 9 mice were found dead without observation of initiating clinical signs; 1 d later (day 11), 3 additional mice showed signs of morbidity, including severe hunching, lateral recumbency, slow movement, shallow respiration, and decreased response to external stimulus. All remaining mice rapidly decompensated and were found dead or were euthanized within 4 d after the first death. Histopathology revealed severe ascending pyelonephritis with numerous yeast. Cultures in some mice were positive for Enterococcus faecalis or Staphylococcus xylosus, 2 bacteria considered commensals in rodents. In addition, Candida albicans was cultured from some animals. Further investigation revealed that a restraining device used for tail vein injections was the likely fomite harboring Candida organisms. These findings indicate that ascending pyelonephritis, with Candida as the etiologic agent, can cause significant mortality in NSG and NRG immunodeficient mice.

Metastatic thymoma in the liver of a dog.

A 12-y-old neutered male Portuguese Water dog was presented because of a 1-y history of persistent hyporexia, diarrhea, and recurrent pyelonephritis. Abdominal ultrasound revealed hepatic nodules and diffuse splenomegaly, and radiographs revealed a mediastinal mass. Fine-needle aspirates of the liver, spleen, and mediastinal mass were suspicious for lymphoma. Flow cytometry identified small T cells that co-expressed CD4 and CD8 at all sites, most suspicious for thymoma, but lymphoma could not be ruled out. PCR for antigen receptor rearrangements analysis identified polyclonal amplification of the T-cell receptor genes, more consistent with thymoma than lymphoma. Histopathology of the liver and thymic mass confirmed thymoma with hepatic metastasis.

Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease.

OBJECTIVE To determine the prevalence of bacteriuria (ie, a positive microbial culture result for ≥ 1 urine sample) in dogs with chronic kidney disease (CKD) and characterize findings of subclinical bacteriuria (SBU), bacterial cystitis, or pyelonephritis in these patients. DESIGN Retrospective, observational study. ANIMALS 182 dogs. PROCEDURES Medical records from January 2010 through July 2015 were reviewed to identify dogs with CKD that underwent urinalysis and urine microbial culture. Signalment, clinicopathologic data, stage of CKD according to previously published guidelines, results of urinalysis and urine culture, and abdominal ultrasonographic findings were recorded. Dogs with positive urine culture results were categorized as having SBU, bacterial cystitis, or pyelonephritis on the basis of these data. Prevalence of bacteriuria was calculated. Associations between CKD stage, presence of bacteriuria, and diagnosis category were analyzed statistically. RESULTS 33 of 182 (18.1%) dogs (40/235 [17.0%] urine samples) had positive culture results. All dogs received antimicrobials on the basis of culture and susceptibility test findings. Most positive culture results (18/40 [45%] samples) were found for dogs with SBU, followed by dogs with pyelonephritis (16/40 [40%]) and cystitis (6/40 [15%]). Escherichia coli was the most frequently observed isolate (29/40 [73%] cultures from 25/33 dogs). The CKD stage was not associated with presence of bacteriuria or diagnosis category. CONCLUSIONS AND CLINICAL RELEVANCE The prevalence of positive urine culture results in dogs with CKD was lower than that reported for dogs with some systemic diseases that may predispose to infection. Prospective research is needed to assess the clinical importance of SBU in dogs with CKD.