Acute kidney injury from presumptive intramural ureteral hemorrhage secondary to diphacinone rodenticide exposure in a dog.

OBJECTIVE: To describe the clinical features and outcome of a dog with anticoagulant rodenticide (diphacinone) exposure, which was subsequently diagnosed with a coagulopathy characterized by hemoperitoneum, and presumptive ureteral wall hemorrhage contributing to acute kidney injury (AKI). CASE SUMMARY: A 4-year-old, female neutered Australian Cattle Dog was evaluated for an acute onset of lethargy, decreased appetite, and a mild right thoracic limb lameness. Radiographs and point of care ultrasound demonstrated retroperitoneal and peritoneal effusion. Diagnostic abdominocentesis confirmed hemorrhagic effusion. Complete blood count, biochemistry, and coagulation profile showed a regenerative anemia (PCV 32%), thrombocytopenia (platelets 96 × 109 /L [96 × 103 /µl]), azotemia (BUN 38.9 mmol/L [109 mg/dl], creatinine 512.8 µmol/L [5.8 mg/dl]), and coagulopathy (prothrombin time >100 s, activated partial thromboplastin time >42.3 s). The client reported access to anticoagulant rodenticide up to 72 hours prior to presentation. Ultrasonographic examination revealed bilateral pyelectasia and hydroureter with thickened distal ureteral walls at the level of the ureteral-vesicular junctions. The ultrasonographic conclusion was presumptive intramural ureteral hemorrhage resulting in ureteral obstruction. The patient was diagnosed with AKI with likely prerenal, renal, and postrenal components. Treatment included vitamin K and frozen plasma transfusion. The patient recovered fully and was discharged 3 days after presentation. Two days after discharge, the patient had improvement in azotemia (BUN 10.7 mmol/L [30 mg/dl], creatinine 176.6 µmol/L [2.0 mg/dl]). Gas chromatography-mass spectrometry confirmed presence of diphacinone in the blood. Repeat ultrasound and biochemistry 60 and 210 days, respectively, after discharge showed resolution of ureteral wall thickening, hydroureter, pyelectasia, and recovery of kidney parameters. NEW OR UNIQUE INFORMATION: Although nephropathies secondary to anticoagulant therapy have been described in people, the authors believe this is the first report of diphacinone anticoagulant rodenticide exposure contributing to an AKI secondary to obstruction from ureteral wall hemorrhage in the veterinary literature.

Does intravenous contrast medium administration result in altered renal biomarkers? A study in clinically stable cats with and without azotemia.

OBJECTIVES: The aim of this study was to determine the prevalence of post-contrast acute kidney injury or comparable side effects on kidney function in cats receiving the non-ionic, iodinated agent ioversol and/or paramagnetic agent gadoteric acid. METHODS: Fifty-two animals were divided into four groups on the basis of contrast medium administration for imaging: ioversol (n = 27), gadoteric acid (n = 12), dual contrast media (n = 4) or control, which received an infusion of isotone intravenous fluids only during anaesthesia (n = 9). Blood and urine samples were obtained three times after contrast administration and compared with values obtained prior to administration of the contrast medium. Creatinine (<1.60 mg/dl), symmetric dimethylarginine (SDMA; ⩽14 µg/dl), urine protein:creatinine ratio (UPC; <0.2) and critical differences for creatinine (<0.3 mg/dl) and SDMA (<5.98 µg/dl) were measured. RESULTS: No significant short-term effects on mean creatinine, SDMA and UPC measurements were seen. Borderline proteinuria (UPC, 0.2-0.4) was detected in 11.4% of cases after contrast media administration. A UPC of more than 0.2 in five cases indicated that contrast media may affect kidney function, leading to (transient) proteinuria. CONCLUSIONS AND RELEVANCE: This study found no side effect on renal function following the administration of ioversol or gadoteric acid, provided patients were adequately hydrated. However, the clinical relevance of proteinuria in some cats needs to be evaluated in future studies.

Effectiveness of N-Acetylcysteine in the Treatment of Renal Deterioration Caused by Long-Term Exposure to Bisphenol A.

Human health hazards caused by bisphenol A (BPA), a precursor for epoxy resins and polycarbonate-based plastics, are well documented and are closely associated with mitochondrial impairment and oxidative imbalance. This study aimed to assess the therapeutic efficacy of N-acetylcysteine (NAC) on renal deterioration caused by long-term BPA exposure and examine the signaling transduction pathway involved. Male Wistar rats were given vehicle or BPA orally for 12 weeks then the BPA-treated group was subdivided to receive vehicle or NAC concurrently with BPA for a further 4 weeks, while the vehicle-treated normal control group continued to receive vehicle through to the end of experiment. Proteinuria, azotemia, glomerular filtration reduction and histopathological abnormalities caused by chronic BPA exposure were significantly reduced following NAC therapy. NAC also diminished nitric oxide and lipid peroxidation but enhanced renal glutathione levels, and counteracted BPA-induced mitochondrial swelling, increased mitochondrial reactive oxygen species production, and the loss of mitochondrial membrane potential. The benefit of NAC was related to the modulation of signaling proteins in the AMPK-SIRT3-SOD2 axis. The present study shows the potential of NAC to restore mitochondrial integrity and oxidative balance after long-term BPA exposure, and suggests that NAC therapy is an effective approach to tackle renal deterioration in this condition.

Urine kidney safety biomarkers improve understanding of indirect intra-renal injury potential in dogs with a drug-induced prerenal azotemia.

Drug-induced kidney injury (DIKI) is a frequent occurrence in nonclinical drug development. It is well established that novel urine kidney safety biomarkers will outperform urea nitrogen (BUN) and serum creatinine (sCr) for monitoring direct drug injury to the kidney across numerous compounds spanning diverse mechanisms and efforts are underway for a formal regulatory clinical qualification. However, it remains unclear how these novel biomarkers will perform under prerenal azotemia when BUN and sCr are elevated but no intra-renal injury is suspected. This lack of knowledge is largely due to the dearth of such nonclinical animal models. We report here that treatment of dogs with a potent antihypertensive compound MK-5478 at a suprapharmacologic dose for up to 9 days results in the development of prerenal azotemia and, in some dogs, kidney toxicity through the dual sustained effects of MK-5478 as a nitric oxide donor and an angiotensin II receptor blocker (ARB). While conventional serum biomarkers BUN, and often sCr as well, were highly elevated in these dogs with or without kidney damage, urine kidney biomarkers clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) showed increases only in dogs with kidney histopathologic changes following the sustained period of prerenal azotemia. Urine albumin (ALB) and total protein also tracked with kidney lesions but with less sensitivity. Thus, we present evidence for the first time that urine kidney safety biomarkers used together with BUN and sCr can distinguish intra-renal injury among dogs with prerenal azotemia while the conventional serum biomarkers alone are ambiguous, either being interpreted as false positives of kidney injury, or dismissed under circumstances as benign without appreciation for a threshold of impending injury.

Severe hypernatremia and transient azotemia in a cat following inadvertent intravenous administration of a commercial polyethylene glycol solution.

OBJECTIVE: To describe the clinical signs, clinicopathologic abnormalities, treatment, and outcome after IV administration of polyethylene glycol 3350 (PEG3350) in a cat. CASE SUMMARY: A cat was inadvertently administered 6 g/kg of PEG3350 in electrolyte solution, IV, resulting in severe hypernatremia (203 mmol/L), diffuse encephalopathy, hemolysis, and moderate azotemia. The hemolysis and acute kidney injury observed immediately following PEG3350 administration resolved with supportive care. Administration of IV and oral electrolyte-free water slowly corrected the hypernatremia and the neurologic signs subsequently improved. Complete resolution of clinical signs was documented one month following hospital discharge. The PEG3350 concentrations in serum, plasma, and urine samples confirmed toxic exposure to PEG3350. Efficacy of treatment was evident by decreasing concentrations of PEG3350 in serum after the first 24 hours of treatment. Renal elimination of PEG3350 was significant and PEG3350 was still detected in the urine 17 days after exposure. NEW INFORMATION PROVIDED: This is the first report to describe the clinical signs and clinicopathologic abnormalities in a cat intoxicated with IV PEG3350. Potential pathophysiologic mechanisms are discussed, and the successful supportive medical treatment is outlined.

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats.

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg-1 and was most commonly administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%) and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in 21.8% of cats, and was lower than previously reported in dogs. The results of this study showed that treatment of cats with toceranib is well-tolerated and toxicity is uncommon. Additional studies to define a more structured dosing schedule and to evaluate the efficacy of toceranib in the treatment of feline cancers are needed.

Presumed masitinib-induced nephrotic syndrome and azotemia in a dog.

Masitinib mesylate is a tyrosine-kinase inhibitor approved for the treatment of nonresectable or recurrent, Grade 2 or 3 mast cell tumors in dogs. This report describes nephrotic syndrome and acute kidney injury attributed to masitinib and illustrates the need for regular monitoring of serum creatinine concentration, urinalysis, and urine protein:creatinine ratio during its use.

Présomption de syndrome néphrotique et d'azotémie induits par le masitinib chez un chien. Le mésylate de masitinib est un inhibiteur de la tyrosine-kinase homologué pour le traitement des mastocytes non résécables ou récurrents de grade 2 ou 3 chez les chiens. Ce rapport décrit le syndrome néphrotique et une blessure aiguë au rein attribués au masitinib et illustre le besoin d'une surveillance régulière de la concentration sérique de créatinine, des analyses d'urine et du ratio protéine:créatinine urinaire durant son utilisation.(Traduit par Isabelle Vallières).

A Case of Salicylate Intoxication Complicated by Coagulopathy, Pulmonary Edema, and Pancreatitis.

The large availability of salicylic acid products makes them an often encountered source of poisoning in the emergency department. Even though in most cases the prognosis is good, with a low incidence of long-term morbidity and mortality, complications do occur, and some of those can be life threatening. We present an unusual case of salicylate intoxication in an adolescent in which several uncommon complications (severe coagulopathy, pulmonary edema, and pancreatitis) conjoined together. We review the literature and discuss the complications pathogenesis and differential diagnosis. We suggest that these potentially life-threatening complications be acknowledged, investigated, and rapidly treated.

[Retrospective study on the effects of a whey protein concentrate on body composition in 262 sarcopenic tube fed patients]. / Studio retrospettivo sugli effetti di un concentrato di proteine del siero del latte sulla composizione corporea di 262 pazienti in nutrizione enterale affetti da sarcopenia.

AIM: As pointed in ESPEN guidelines on the use of bioelectrical impedance analysis (BIA), "body cell mass (BCM) is the protein rich compartment which is affected in catabolic states, and loss of BCM is associated with poor clinical outcome". Whey proteins are known to improve lean mass in many conditions. We retrospectively evaluated the effects of a WP concentrate with high cysteine content (WPHCC) on BCM of 262 sarcopenic tube fed patients (pts). METHODS: Two hundred sixty-two sarcopenic tube fed pts (130 males, mean age 68,1±15,6 years) were given daily supplemental WPHCC (0.7±0.2 g/kg body weight) after their usual feeding formula, with the aim to improve their BCM. Each patient received a multifrequency impedance test before and after the beginning of WPHCC supplementation (mean follow-up: 4.2±2.8 months). Fifty percent of patients were affected by neurodegenerative diseases, 36% by cancer, 14% by other conditions. RESULTS: BCM, body weight and fat mass significantly improved (P<0.01) after treatment. No severe side effects were recorded. A slight increase in blood urea was observed. CONCLUSION: In our population WPHCC have been safe and effective in improving BCM. WPHCC could be useful to improve BCM in sarcopenic tube fed pts, although renal function should be monitored.

Antitumor effects of deracoxib treatment in 26 dogs with transitional cell carcinoma of the urinary bladder.

OBJECTIVE-To evaluate the antitumor activity and toxic effects of deracoxib, a selective cyclooxygenase-2 inhibitor, in dogs with transitional cell carcinoma (TCC) of the urinary bladder. DESIGN-Clinical trial. Animals-26 client-owned dogs with naturally occurring, histologically confirmed, measurableTCC of the urinary bladder. PROCEDURES-Dogs were treated PO with deracoxib at a dosage of 3 mg/kg/d (1.36 mg/lb/d) as a single-agent treatment for TCC. Tumor response was assessed via radiography, abdominal ultrasonography, and ultrasonographic mapping of urinary bladder masses. Toxic effects of deracoxib administration in dogs were assessed through clinical observations and hematologic and biochemical analyses. RESULTS-Of 24 dogs for which tumor response was assessed, 4 (17%) had partial remission, 17 (71%) had stable disease, and 3 (13%) had progressive disease; initial response could not be assessed in 2 of 26 dogs. The median survival time was 323 days. Median time to progressive disease was 133 days. Renal, hepatic, and gastrointestinal abnormalities attributed to deracoxib administration were noted in 4% (1/26), 4% (1/26), and 19% (5/26) of dogs, respectively. CONCLUSIONS AND CLINICAL RELEVANCE-Results indicated that deracoxib was generally well tolerated by dogs and had antitumor activity against TCC.

Acute oxalate intoxication associated to ingestion of eshnan (Seidlitzia rosmarinus) in sheep.

An outbreak of acute oxalate intoxication in a sheep flock was associated to Seidlitzia rosmarinus (Chenopodiaceae) with a mortality rate of about 19%. Affected sheep showed marked azotemia and hypocalcemia. Post-mortem findings included congestion and hemorrhage in visceral organs, ruminitis frequently associated with precipitation of birefringent calcium oxalate crystals, and acute nephrosis with numerous birefringent calcium oxalate crystals in renal tubules. This is the first report of oxalate poisoning due to ingestion of S. rosmarinus in sheep.

Prospective evaluation of tissue plasminogen activator in 11 cats with arterial thromboembolism.

The purpose of this study was to evaluate the clinical response and side effects of tissue plasminogen activator (tPA) for the treatment of feline arterial thromboembolism (ATE). Previous reports of conservative and thrombolytic therapy were used to provide a historical control group of cats with ATE. The study was terminated due to a high frequency of adverse outcomes. tPA was administered to 11 cats with clinical signs of ATE for a median duration of 4.0 h (range 2-12h) prior to treatment. Pulses were restored in 40% of limbs within 4h and 53% within 24h. Motor function was restored to 33% of limbs within 24h. Adverse effects were seen in 11/11 cats following administration of tPA including azotemia (n=5), neurological signs (n=5), cardiac arrhythmias (n=5), hyperkalemia (n=4), acidosis (n=2) and sudden death in one cat. Ultimately, three cats (27%) were discharged alive from the hospital. While signs compatible with thrombolysis were noted in many cats following tPA administration, a high rate of side effects and low rate of hospital discharge were noted in this study.

Azotemia associated with use of lenalidomide in plasma cell dyscrasias.

Azotemia associated with the use of lenalidomide, a new and effective therapy for multiple myeloma, has not been reported in patients with multiple myeloma. We describe five patients with plasma cell dyscrasias and renal insufficiency (AL amyloidosis, monoclonal gammopathy of undetermined significance with Fanconi syndrome, and multiple myeloma) treated with lenalidomide and dexamethasone who developed progressive azotemia. Onset of azotemia after initiation of lenalidomide was variable (2 weeks to several months) and was irreversible in four patients. Four patients required hemodialysis after exposure to lenalidomide; two previously were untreated for their plasma cell dyscrasia. The mechanism of azotemia is unknown, but the combination of potentially nephrotoxic paraproteins and lenalidomide, which is immunomodulatory and anti-angiogenic, may underlie this process. We conclude that azotemia is an uncommon, but serious, potential complication of lenalidomide therapy in plasma cell dyscrasias with associated renal insufficiency. We advise careful monitoring of renal function after initiation of lenalidomide in this setting.

Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients.

INTRODUCTION: Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients. PATIENTS: Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with >25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr. RESULTS: 100 Caucasians, M:F=52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9+/-9 (7-47) to 39.2+/-15.4 (17-89) ml/min/1.73 m(2) BSA, 26.5 (3-46) months after stopping AB (P=0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibitor use/abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine -2.1+/-0.6 versus 1.5+/-0.4 mg/dL, P=0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44-83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB. CONCLUSIONS: Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study.

Late onset azotemia from RAAS blockade in CKD patients with normal renal arteries and no precipitating risk factors.

Despite proven renoprotection from RAAS blockade and its increased application since the early 1990s, we have experienced an increasing CKD/ESRD epidemic, especially among U.S. diabetics. Consequently, some concerns regarding iatrogenic azotemia from RAAS blockade have surfaced. We hypothesized that susceptible CKD patients with normal renal arteries on conventional angiography, including MRA, but who have microvascular arteriolar narrowing in the renal circulation - mimicking large vessel renal artery stenosis, even without precipitating risk factors - could experience worsening azotemia after periods of time exceeding three months on stable doses of RAAS blockade. Between September 2002 and February 2005, as part of a larger prospective study of renal failure in CKD patients on RAAS blockade, we studied five patients with >25% higher serum creatinine and normal MRA without precipitating factors. RAAS blockade was discontinued. eGFR by MDRD was monitored. Five Caucasians (M:F = 1:4; age 68 years) were enrolled and followed-up at 29.6 months. The duration of RAAS blockade at enrollment was 34.6 months. The baseline eGFR had decreased from 28.4 +/- 7.1 to 17.0 +/- 7.4 ml/min/1.73 m(2) BSA (p < 0.001) at enrollment. One required temporary hemodialysis; no deaths occurred. eGFR increased from 17.0 +/- 7.4 to 24.6 +/- 9.5 ml/min/1.73 m(2) BSA (p = 0.009), 29.6 (20-43) months after stopping the RAAS blockade. We conclude that worsening azotemia occurs in susceptible CKD patients on stable doses of RAAS blockade after long periods of time, despite normal renal arteries without precipitating risk factors. We submit that microvascular renal arteriolar narrowing is the pathophysiologic mechanism. These observations call for further study.

An investigation of predictors of renal insufficiency following treatment of hyperthyroidism in cats.

To determine if routine pre-treatment clinical data can be used to predict the development of overt renal insufficiency following treatment of feline hyperthyroidism, we studied retrospectively all non-azotemic cats undergoing treatment for hyperthyroidism at our hospital. Medical records were reviewed for signalment, clinical signs, and serum biochemical, hematologic and urinalysis parameters before and after treatment for hyperthyroidism. Two groups - cats that developed post-treatment renal insufficiency, and those that did not - were compared. No significant differences could be detected between the groups with respect to the parameters measured. Our study suggests that the results of routine pre-treatment clinical data cannot be used to reliably predict renal function after treatment for hyperthyroidism, validating the necessity of a methimazole trial prior to definitive therapy. The widely held belief that cats with pre-treatment urine specific gravity>1.035 are at less risk for development of renal azotemia after treatment of hyperthyroidism seems unwarranted.

Microalbuminuria is not associated with cisplatin-induced azotemia in dogs.

BACKGROUND: Cisplatin is an effective antineoplastic agent but its use is limited by renal toxicity. Microalbuminuria is a marker of renal damage and might be an indicator of cisplatin-induced azotemia. NULL HYPOTHESIS: Microalbuminuria is not associated with azotemia in dogs treated with cisplatin. ANIMALS: This study used 32 client-owned dogs. METHODS: This was a prospective observational study in which cancer-bearing dogs were treated with cisplatin chemotherapy. Cisplatin-induced azotemia was defined as an increase of serum creatinine concentration above the reference range. Serum creatinine concentration, other routine tests of renal function, and microalbuminuria were measured after each cisplatin treatment. Variables potentially associated with azotemia were compared by use of Fisher's exact test and Wilcoxon's rank-sum test. RESULTS: Cisplatin-induced azotemia occurred in 10 (31%) dogs after 1-5 treatments. At each of the first 3 treatments, the proportions of dogs with microalbuminuria were similar between dogs with and without azotemia. CONCLUSIONS AND CLINICAL IMPORTANCE: Microalbuminuria measured after each treatment was not associated with azotemia through the first 3 treatments. Testing for microalbuminuria as a marker for cisplatin-induced renal damage is insensitive and not recommended.