Evaluation of the clinical outcome of hypercalcemia of malignancy and concurrent azotemia in dogs with lymphoma.

BACKGROUND: Hypercalcemia of malignancy (HM) secondary to lymphoma in dogs has the potential to cause renal injury. HYPOTHESIS/OBJECTIVES: Characterize outcomes related to acute kidney injury (AKI) secondary to HM. We hypothesized that dogs do suffer AKI regardless of HM severity at the time of lymphoma diagnosis or relapse. ANIMALS: Retrospective study. Twenty-nine dogs with lymphoma, HM, and azotemia (International Renal Interest Society [IRIS] grade II or higher AKI) that underwent chemotherapy were identified at 2 veterinary institutions. METHODS: Logistic regression and descriptive statistical analysis were performed to evaluate data for potential prognostic factors. RESULTS: After initiating treatment, resolution of hypercalcemia and azotemia occurred in 100% (29/29) and 79.3% (23/29) of dogs, respectively. Resolution of azotemia was influenced by serum creatinine concentration (odds ratio [OR], 0.148; Confidence interval [CI], 0.03-0.734; P = .02) and total hypercalcemia (OR, 0.36; CI, 0.14-0.93; P = .04) at diagnosis, whereas blood urea nitrogen concentration, IRIS grade, sex, and whether or not dogs were hospitalized were not significant factors. At data analysis, 13.8% (4/29) of dogs were alive or lost to follow-up. Of those dead, 4 dogs (15%) had renal disease at the time of death, 2/4 having concurrent lymphoma progression. CONCLUSIONS AND CLINICAL IMPORTANCE: Although AKI may be of clinical concern in dogs with HM secondary to lymphoma at diagnosis, death secondary to renal impairment appears to be infrequent.

IL-6 mediates the hepatic acute phase response after prerenal azotemia in a clinically defined murine model.

Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.

Treatment of portal vein thrombosis using vascular access port implantation in a Dalmatian dog: A case report.

Background: Portal vein thrombosis is a disease with potentially deleterious outcomes including portal vein hypertension and intestinal infarction. The factors contributing is various; however, dogs with with acute portal vein thrombosis or multiple thromboses are less likely to survive. Therefore, acute development of portal hypertension has a requires an immediate treatment. Case Description: A 10-year-old Dalmatian was referred for syncope and azotemia, hyperammonemia. After each examinations including computed tomography scan, we diagnosed with acute portal vein thrombosis with unknown cause. A portal vein port was inserted to prevent and control the portal vein thrombus. The port was placed in abdomen subcutaneously after the position of the catheter were stabilized. Low-molecular-weight heparin was injected from the port to manage thrombosis after the operation. This case responded well to this treatment. Syncope and azotemia, hyperammonemia resolved and no relapse of thrombosis was found 6 months after the operation. Conclusion: Implantable vascular access port is a drug delivery system with the advantage of dealing with treatment-resistant acute portal vein thrombosis.

Retrospective Analysis of Mortality Cases in Advanced and Metastatic Solid Tumors With Concurrent Prerenal Azotemia.

BACKGROUND/AIM: A retrospective study of cases with metastatic or advanced solid tumors complicated with AKI (acute kidney injury) with prerenal azotemia. PATIENTS AND METHODS: Criteria included: (1) advanced or metastatic solid tumors that led to mortality; (2) prerenal azotemia identified upon renal function evaluation and (3) BUN to Cr ratio (BCR)≥15. We also compared the outcomes of patients with BCR>20 with those of patients with BCR=15-20. RESULTS: A total of 218 patients with solid tumors were enrolled. One hundred and forty (64%) and 78 (36%) patients had BCR>20 and 15-20, respectively. Before AKI occurrence, 136 (62%) had thromboembolic complications and 96 (44%) paraneoplastic syndromes. Median survival time was 1 week in all patients. Median survival time was statistically different between the groups with BCR15-20 and BCR>20 (p<0.005, log-rank test). CONCLUSION: Cancer patients with concurrent AKI and prerenal azotemia carry a very poor prognosis.

Pernicious azotaemia? A case series of subacute combined degeneration of the cord secondary to nitrous oxide abuse.

Nitrous oxide abuse is a rare cause of vitamin B12 deficiency and consequent subacute combined degeneration of the spinal cord. Worldwide and Australian statistics indicate that recreational use of nitrous oxide is increasing. We report four cases of females aged 18-24 years presenting with clinical symptoms of subacute combined degeneration of the spinal cord. MRI during admission demonstrated the classic findings of T2 hyperintensity, predominantly within the dorsal columns of the spinal cord, with variable involvement of the lateral corticospinal tracts. These cases highlight the ready availability of nitrous oxide and the fact that heavy prolonged recreational use is occurring in the community. It is important that clinicians in emergency and community settings are alerted to this unusual cause of subacute combined degeneration of the spinal cord because early aggressive vitamin B12 replacement together with behavioural change can reverse this disabling neurological syndrome.

Induced pluripotent stem cell-derived endothelial progenitor cells attenuate ischemic acute kidney injury and cardiac dysfunction.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which is associated with high morbidity and mortality. AKI is a serious and costly medical condition. Effective therapy for AKI is an unmet clinical need, and molecular mechanisms underlying the interactions between an injured kidney and distant organs remain unclear. Therefore, novel therapeutic strategies should be developed. METHODS: We directed the differentiation of human induced pluripotent stem (iPS) cells into endothelial progenitor cells (iEPCs), which were then applied for treating mouse AKI. The mouse model of AKI was induced by I/R injury. RESULTS: We discovered that intravenously infused iEPCs were recruited to the injured kidney, expressed the mature endothelial cell marker CD31, and replaced injured endothelial cells. Moreover, infused iEPCs produced abundant proangiogenic proteins, which entered into circulation. In AKI mice, blood urea nitrogen and plasma creatinine levels increased 2 days after I/R injury and reduced after the infusion of iEPCs. Tubular injury, cell apoptosis, and peritubular capillary rarefaction in injured kidneys were attenuated accordingly. In the AKI mice, iEPC therapy also ameliorated apoptosis of cardiomyocytes and cardiac dysfunction, as indicated by echocardiography. The therapy also ameliorated an increase in serum brain natriuretic peptide. Regarding the relevant mechanisms, indoxyl sulfate and interleukin-1ß synergistically induced apoptosis of cardiomyocytes. Systemic iEPC therapy downregulated the proapoptotic protein caspase-3 and upregulated the anti-apoptotic protein Bcl-2 in the hearts of the AKI mice, possibly through the reduction of indoxyl sulfate and interleukin-1ß. CONCLUSIONS: Therapy using human iPS cell-derived iEPCs provided a protective effect against ischemic AKI and remote cardiac dysfunction through the repair of endothelial cells and the attenuation of cardiomyocyte apoptosis.

Detection and seroprevalence of morbillivirus and other paramyxoviruses in geriatric cats with and without evidence of azotemic chronic kidney disease.

BACKGROUND: Feline morbillivirus (FeMV) is associated with the presence of tubulo-interstitial nephritis (TIN) in cats, however the seroprevalence of FeMV in the UK and the association between the presence of FeMV and renal azotemia is unknown HYPOTHESIS/OBJECTIVES: To identify whether paramyxoviruses are present in urine samples of geriatric cats and to develop an assay to assess FeMV seroprevalence. To investigate the relationship between both urinary paramyxovirus (including FeMV) excretion and FeMV seroprevalence and azotemic chronic kidney disease (CKD). ANIMALS: Seventy-nine cats (40 for FeMV detection; 72 for seroprevalence). METHODS: Retrospective cross-sectional, case control study. Viral RNA was extracted from urine for RT-PCR. PCR products were sequenced for virus identification and comparison. The FeMV N protein gene was cloned and partially purified for use as an antigen to screen cat sera for anti-FeMV antibodies by Western Blot. RESULTS: Feline morbillivirus RNA from five distinct morbilliviruses were identified. Detection was not significantly different between azotemic CKD (1/16) and nonazotemic groups (4/24; P = .36). Three distinct, non-FeMV paramyxoviruses were present in the nonazotemic group but their absence from the azotemic group was not statistically significant (P = .15). 6/14 (43%) azotemic cats and 40/55 (73%) nonazotemic cats were seropositive (P = .06). CONCLUSIONS AND CLINICAL IMPORTANCE: Feline morbillivirus was detected in cats in the UK for the First time. However, there was no association between virus prevalence or seropositivity and azotemic CKD. These data do not support the hypothesis that FeMV infection is associated with the development of azotemic CKD in cats in the UK.

Survival analysis to evaluate associations between periodontal disease and the risk of development of chronic azotemic kidney disease in cats evaluated at primary care veterinary hospitals.

OBJECTIVE To examine potential associations between periodontal disease (PD) and the risk of development of chronic azotemic kidney disease (CKD) among cats and determine whether the risk of CKD increases with severity of PD. DESIGN Retrospective cohort study. ANIMALS 169, 242 cats. PROCEDURES Cats were evaluated ≥ 3 times at any of 829 hospitals from January 1, 2002, through June 30, 2013. Cats with an initial diagnosis of PD of any stage (n = 56,414) were frequency matched with cats that had no history or evidence of PD (112,828) by age and year of study entry. Data on signalment, PD, and other conditions potentially related to CKD were extracted from electronic medical records. Cox proportional hazards modeling was used to estimate the association of PD with CKD after controlling for covariates. RESULTS PD was associated with increased risk of CKD; risk was highest for cats with stage 3 or 4 PD. Risk of CKD increased with age. Purebred cats had greater risk of CKD than mixed-breed cats. General anesthesia within the year before study exit and diagnosis of cystitis at any point prior to study exit (including prior to study entry) were each associated with increased CKD risk. Diagnosis of diabetes mellitus or hepatic lipidosis at any point prior to study exit was associated with decreased CKD risk. CONCLUSIONS AND CLINICAL RELEVANCE The findings supported the benefit of maintaining good oral health and can be useful to veterinarians for educating owners on the importance of preventing PD in cats.

Fish gall bladder consumption presenting as acute renal failure.

A forty two year old male was admitted with history of anuria and breathlessness following consumption of raw rohu fish gall bladder. He had azotemia and required hemodialysis. His renal failure improved over a period of about four weeks. Incidences have been reported from South East Asian countries associating consumption of raw rohu fish gall bladder with acute renal failure.

HYPERCALCEMIA AND METASTATIC MINERALIZATION INVOLVING FOOTPADS IN ROCK HYRAXES (PROCAVIA CAPENSIS).

Three rock hyraxes (Procavia capensis) maintained in a zoological collection had chronic hypercalcemia and azotemia. In addition, all animals displayed signs of lameness due to footpad lesions that were histologically characterized as marked metastatic mineralization with granulomatous inflammation, reminiscent of calcinosis circumscripta. Although the animals were managed with aggressive fluid therapy, calciuresis, and dietary modification, all were eventually humanely euthanized due to the severity of their footpad lesions and/or progression of renal disease. Metastatic mineralization was also noted in other soft tissues among the three cases, including the stomach, colon, lung, vascular wall, ovary, and kidney. Varying degrees of interstitial nephritis were confirmed on postmortem examination, and in the absence of other causes for hypercalcemia, metastatic mineralization was presumably the consequence renal dysfunction. The renal pathway is the primary mode of calcium excretion in the rock hyrax. In renal dysfunction, hypercalcemia may develop secondary to decreased calcium excretion. Footpad mineralization is an uncommon sequel to renal dysfunction in domestic animals but has not been reported in rock hyraxes. A retrospective review of mortality data in this collection revealed a notable prevalence of renal lesions, including two additional animals with metastatic mineralization and renal dysfunction. Expanding knowledge of renal diseases will further guide preventative and clinical measures, including screening for metastatic mineralization and therapeutic trials for management of hypercalcemia and calcium mineral deposition in the footpads and other soft tissues.

Hyperaldosteronism and its association with hypotension and azotaemia in canine babesiosis.

BACKGROUND: The previous work on canine babesiosis revealed hypokalaemia and increased fractional excretion of potassium in infected dogs suggesting a role for aldosterone in the loss of potassium via the kidneys in affected dogs. Moreover, hypotension, which is one of the complications of canine babesiosis leading to renal failure, may induce secondary hyperaldosteronism. ANIMALS AND METHODS: In this study, the serum aldosterone concentration was determined in 14 dogs infected with Babesia canis. The Mann-Whitney U test was used to compare serum aldosterone concentration and blood pressure between these dogs and 10 healthy dogs. Spearman's rank correlations between serum aldosterone concentration and blood pressure and between serum aldosterone and urea and creatinine concentrations were calculated. RESULTS: Increased concentrations of aldosterone above reference intervals were observed in only 4 out of the 14 dogs. The results showed significantly (p < 0.05) higher serum aldosterone concentrations and lower blood pressures in infected dogs in comparison to healthy dogs, and significantly negative correlations between aldosterone concentration and systolic arterial pressure (r = -0.63), diastolic arterial pressure (r = -0.67) and mean arterial pressure (r = -0.65). Serum aldosterone concentration was also significantly correlated with serum urea concentration (r = 0.72), serum creatinine concentration (r = 0.69) and serum potassium concentration (r = -0.57). CONCLUSION: The results of this study show hyperaldosteronism in some cases of canine babesiosis as a possible response to hypotension. However, both the hypotension and severe azotaemia observed in dogs infected with B. canis and associated hyperaldosteronaemia suggest that this response is insufficient.

Hyponatraemic encephalopathy in azotaemic neonatal foals: four cases.

CASE SERIES: Four neonatal foals were presented, over a 2-year period, (2011-2012) with aimlessly walking, head pressing, 'chewing gum' seizures and ataxia. The neurological lesion was consistent with increased intracranial pressure in all cases. All foals had severe hyponatraemia and azotaemia identified on biochemistry. Hyponatraemia was transient in 3/4 cases, with the foal in the final case requiring long-term sodium supplementation. Three foals survived to hospital discharge; one was euthanased because of anuric renal failure and one of the surviving foals was euthanased with septic osteomyelitis 2 weeks after initial discharge. CONCLUSION: Correction of the sodium deficit resulted in resolution of the neurological signs in these foals; however, azotaemia was slow to resolve, suggesting acute renal failure.

Acute kidney injury during pregnancy.

Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

Renal dysfunction in end-stage liver disease and post-liver transplant.

Renal dysfunction is a frequent complication in patients with end-stage liver disease awaiting orthotopic liver transplantation and in the post-liver transplant period. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, other causes of acute kidney injury in this population include prerenal azotemia and acute tubular necrosis. Renal injury in a patient with cirrhosis is associated with a poor prognosis.

Kyasanur Forest disease virus infection in mice is associated with higher morbidity and mortality than infection with the closely related Alkhurma hemorrhagic fever virus.

BACKGROUND: Kyasanur Forest disease virus (KFDV) and Alkhurma hemorrhagic fever virus (AHFV) are closely related members of the Flavivirus genus and are important causes of human disease in India and the Arabian Peninsula, respectively. Despite high genetic similarity, the viruses have distinctly different host ranges and ecologies. Human cases of KFDV or AHFV develop a spectrum of disease syndromes ranging from liver pathology to neurologic disease. Case reports suggest KFDV is more commonly associated with hepatic and gastrointestinal manifestations whereas AHFV is more commonly associated with neurologic disease. METHODOLOGY/PRINCIPAL FINDINGS: Inoculation of three immunocompetent laboratory mouse strains revealed that KFDV was consistently more lethal than AHFV. In subsequent studies utilizing C57BL/6J mice, we demonstrated that KFDV infection was associated with higher viral loads and significantly higher mortality. KFDV-infected mice rapidly developed more severe disease than AHFV-infected mice, as evidenced by significant abnormalities on clinical chemistry panels and more severe pathology in the brain and gastrointestinal tract. CONCLUSIONS/SIGNIFICANCE: Infections of C57BL/6J mice with KFDV or AHFV resulted in clinical disease syndromes that closely approximate the diseases seen in human cases. Despite high genetic similarity, there were clear differences in survival, viral kinetics, clinical chemistry data and histology. These results suggest that distinct mouse models for AHFV and KFDV are necessary in order to gain a better understanding of the unique pathogenesis of each virus, as well as to provide platforms for testing promising vaccines and therapeutics.

[Nutrition of patients with stomach acid-dependent pathology and inflammatory diseases of the urogenital system].

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Pulmonary abnormalities in dogs with renal azotemia.

BACKGROUND: Clinical signs associated with respiratory tract disease are regularly encountered in people with kidney failure, and have been anecdotally reported in dogs. OBJECTIVES: To compare clinical signs indicative of pulmonary disease, clinicopathologic findings, radiographic abnormalities, and histologic findings in dogs with acute kidney injury (AKI) or International Renal Interest Society Stage 3 or 4 chronic kidney disease (CKD) to nonazotemic dogs. To determine associations between abnormalities indicative of pulmonary disease and outcome in azotemic dogs. ANIMALS: One hundred sixty-seven pet dogs (54 AKI dogs, 50 CKD dogs, 63 nonazotemic control dogs diagnosed with intracranial disease). METHODS: Retrospective cohort study comparing signalment, clinical signs, clinicopathologic variables, prevalence, and severity of pulmonary radiographic patterns, histopathologic findings, and survival times in AKI, CKD, and control dogs. RESULTS: Clinical signs of pulmonary disease were significantly more common in AKI dogs. Prevalence of an alveolar lung pattern was greater in AKI and CKD dogs. Alveolar mineralization was the most common pulmonary histologic lesion in AKI dogs (6 of 8 dogs), with concurrent alveolar concretions or mineralization of pulmonary vessels or bronchioles noted in 1 dog each; mineralization of lung tissues was not noted in control dogs. Neither clinical signs nor presence of an alveolar pattern were associated with likelihood of survival to discharge or median number of days from discharge until death. CONCLUSIONS AND CLINICAL IMPORTANCE: Abnormalities indicative of pulmonary disease are more common in azotemic dogs than in control dogs; however, prognosis is not associated with presence of clinical or radiographic pulmonary dysfunction.