Clinical application of the StatSensor and StatSensor Xpress point-of-care creatinine measurement devices in dogs.

BACKGROUND: Creatinine is a universally important blood parameter used to detect and monitor acute and chronic kidney disease. Reliable measurements at the bedside remain a challenge in human and veterinary medicine. Despite its potential, a trustworthy point-of-care creatinine biosensor has yet to be established. OBJECTIVES: We aimed to determine the precision and accuracy of the StatSensor (SS) and StatSensor Xpress (SSX) handheld creatinine measurement devices in dogs. METHODS: Paired creatinine samples from dogs with normal (creatinine ≤159 µmol/L), moderate (159-354 µmol/L), and marked (>354 µmol/L) azotemia were compared with a commercial enzymatic analyzer. Within-day precision and linearity studies were performed prior to method comparison studies. Method comparison was evaluated using Bland-Altman, concordance correlation coefficient, Deming, and Passing-Bablok regression analysis. RESULTS: Seventy-eight dogs were enrolled in the study, including 28 (35%), 25 (32%), and 26 (33%) with normal, moderate, and marked azotemia. Total error surpassed recommendations for all devices, and linearity deviated from identity for the SS1 and SS2. The concordance correlation coefficients of the SS1, SS2, SSXI, and SSX2, were 0.69, 0.59, 0.82, and 0.44, respectively. Bland-Altman analyses showed a high variation in the differences, and relationships showed high heteroskedasticity with negative systemic bias among high creatinine concentrations. CONCLUSIONS: Neither the SS and SSX are considered acceptable for clinical applications in dogs. Further research is indicated for the development of a reliable, cost-effective, point-of-care creatinine analyzer to improve the rapid detection and monitoring human and veterinary patients.

Clinicopathological characteristics of light chain proximal tubulopathy in Korean patients and the diagnostic usefulness of immunohistochemical staining for immunoglobulin light chain.

BACKGROUND: Light chain proximal tubulopathy (LCPT) is a rare paraproteinemic renal disease that has been mostly reported in Western patients. LCPT is characterized by the accumulation of immunoglobulin (Ig)-light chain (LC) in the proximal tubule. Immunohistochemical staining for Ig-LC has not been investigated in the context of LCPT. We reported the clinicopathological characteristics and Ig-LC immunoexpression of patients with LCPT for the first time in Korea. METHODS: We reviewed the clinicopathological findings of 5 Korean patients diagnosed with LCPT between 2016 and 2018. In addition, immunohistochemical staining for κ-LC and λ-LC was conducted on paraffin-embedded tissues. RESULTS: The median age was 63 years, and the male-to-female ratio was 3:2. The primary renal manifestations were either azotemia or tubular proteinuria. All patients were diagnosed with multiple myeloma with monoclonal κ-LC (#1-2) or λ-LC (#3-5) in the serum and urine. Kidney biopsies revealed diverse and subtle alterations of the proximal tubule, including crystallization, vacuolization, and/or swelling. Electron microscopy revealed crystals in patients #1-2 and non-crystalline particles within numerous/large/dysmorphic lysosomes in patients #3-5. Ig-LC restriction was demonstrated in the proximal tubule as κ-type in patients #1-2 and as λ-type in patients #3-5 by immunohistochemistry and immunofluorescence. Immunohistochemical staining showed diffuse positivity to κ- and λ-LC, although immunofluorescent staining for κ-LC was focal and weak. LCPT has diverse clinicopathological characteristics and subtle morphological alterations, which necessitate ancillary tests for diagnosis. CONCLUSIONS: We introduced immunohistochemical staining for Ig-LC as a useful tool for the diagnosis of LCPT, especially in the case of κ-type crystals.

[Azotemia in rabbits and rodents - an update]. / Azotämien bei Kaninchen und Nagern ­ ein Update.

An impaired elimination of urinary excreted substances and an increase of these substances in the blood (azotemia) can also occur in rabbits and rodents. In addition to renal diseases, prerenal and postrenal conditions can induce azotemia. A systematic evaluation of patients with azotemia is needed to find a diagnosis and to initiate an effective treatment. The article provides an overview of the diagnosis and therapy of common causes of azotemia in rabbits and rodents.

Renal azotemia and associated clinical and laboratory findings in dogs with Babesia rossi infection.

The occurrence of acute kidney injury in canine babesiosis is not well documented. Furthermore, interpretation of urine specific gravity (USG) to assess renal concentrating ability is hampered by the frequent presence of hemoglobinuria in this disease. This cross-sectional study aimed to test the hypothesis that renal azotemia (RA) is underdiagnosed according to current canine babesiosis literature by determining its occurrence at presentation, using urine osmolality instead of USG to measure urinary concentration. The second objective was to examine potential associations between the presence of RA and selected clinical and laboratory variables at presentation. Medical records available from 3 previously performed prospective data collections were reviewed retrospectively. Client-owned dogs that were diagnosed with babesiosis caused by Babesia rossi, were included if a complete blood count, biochemistry profile, and urinalysis was performed at admission. Urine osmolality was measured to identify dogs with RA. Differences between dogs with RA and dogs without RA were assessed by nonparametric statistics. One hundred and fifty-two dogs were included, of which 26 (17%) were azotemic at admission. The occurrence of RA was 14% (21/152), hence 81% (21/26) of all azotemic dogs were diagnosed with RA. In contrast, when diagnosis of RA was based on an admission USG < 1.030, only 23% (6/26) of the azotemic dogs would have been considered to have RA. Several signalment and clinicopathological findings were found to be associated with the presence of RA, including older age, and the presence of collapse, hypoglycemia, hyperphosphatemia, cerebral babesiosis, and acute respiratory distress syndrome. Lastly, survival at discharge was significantly lower in dogs diagnosed with RA at presentation. Our results clarified that RA is more common than previously reported in B. rossi. This study also demonstrated that USG determination is not a reliable method to evaluate renal concentrating ability in azotemic dogs with babesiosis. Thus, if available, urine osmolality should be part of the diagnostic work-up of dogs infected with B. rossi to avoid misclassification of dogs with RA as having prerenal azotemia. If urine osmolality cannot be measured, clinicians should realize that most azotemic dogs with B. rossi infection have RA.

Prognostic importance of plasma total magnesium in a cohort of cats with azotemic chronic kidney disease.

BACKGROUND: Hypomagnesemia is associated with increased mortality and renal function decline in humans with chronic kidney disease (CKD). Magnesium is furthermore inversely associated with fibroblast growth factor 23 (FGF23), an important prognostic factor in CKD in cats. However, the prognostic significance of plasma magnesium in cats with CKD is unknown. OBJECTIVES: To explore associations of plasma total magnesium concentration (tMg) with plasma FGF23 concentration, all-cause mortality, and disease progression in cats with azotemic CKD. ANIMALS: Records of 174 client-owned cats with IRIS stage 2-4 CKD. METHODS: Cohort study. Cats with azotemic CKD were identified from the records of two London-based first opinion practices (1999-2013). Possible associations of baseline plasma tMg with FGF23 concentration and risks of death and progression were explored using, respectively, linear, Cox, and logistic regression. RESULTS: Plasma tMg (reference interval, 1.73-2.57 mg/dL) was inversely associated with plasma FGF23 when controlling for plasma creatinine and phosphate concentrations (partial correlation coefficient, -0.50; P < .001). Hypomagnesemia was observed in 12% (20/174) of cats, and independently associated with increased risk of death (adjusted hazard ratio, 2.74; 95% confidence interval [CI], 1.35-5.55; P = .005). The unadjusted associations of hypermagnesemia (prevalence, 6%; 11/174 cats) with survival (hazard ratio, 2.88; 95% CI, 1.54-5.38; P = .001), and hypomagnesemia with progressive CKD (odds ratio, 17.7; 95% CI, 2.04-154; P = .009) lost significance in multivariable analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypomagnesemia was associated with higher plasma FGF23 concentrations and increased risk of death. Measurement of plasma tMg augments prognostic information in cats with CKD, but whether these observations are associations or causations warrants further investigation.

Azotemia and Proteinuria in Dogs Infected with Babesia gibsoni.

Babesiosis is a hemoprotozoal tick-borne disease that is commonly associated with thrombocytopenia and anemia; however, renal involvement has been documented in dogs. The purpose of this retrospective study was to document azotemia and proteinuria in dogs infected with Babesia sp. and to describe the response to antiprotozoal therapy. The electronic database of the North Carolina State University Vector Borne Disease Laboratory was searched to identify dogs who were diagnosed with babesiosis and to determine if they had proteinuria and/or azotemia. Dogs were excluded if they had coinfections or comorbidities known to cause glomerular injury. Of 35 dogs identified during the initial search, 5 were included; however, only 4 of these dogs had both pre- and posttreatment data. All five dogs were American pit bull terriers or American pit bull terrier-mixed breed dogs, were infected with Babesia gibsoni, and had hypoalbuminemia and proteinuria. Three dogs had azotemia. Responses to antiprotozoal treatment included normalization of (three) or increase in (one) serum albumin, resolution (one) or improvement (one) of azotemia, and reduction in proteinuria (two). Laboratory findings consistent with glomerular disease can be found in Babesia gibsoni-infected dogs, and treatment can lead to improvement of the azotemia and proteinuria.

Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism.

BACKGROUND: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism. OBJECTIVES: To investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats. ANIMALS: Two hundred and sixty-two hyperthyroid cats and 206 aged-matched, clinically normal cats. METHODS: Prospective study. We measured creatinine, urea nitrogen, SDMA, T4 , and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131 I) and classified 131 I-treated cats as azotemic or nonazotemic based on persistent, post-treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression. RESULTS: No hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4-8 months (median, 6 months) after 131 I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%. CONCLUSIONS AND CLINICAL IMPORTANCE: Finding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false-positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

Fatal proteinuric kidney disease in a 30-month-old German Fleckvieh heifer caused by unilateral focal segmental glomerulosclerosis subsequent to a non-functional counterpart kidney.

INTRODUCTION: A case of secondary focal segmental glomerulosclerosis (FSGS) in a heifer is presented. A 30-month-old female German Fleckvieh heifer showed deterioration of the general condition, a poor nutritional status, proteinuria, hypoalbuminemia, and renal azotemia. Pathologically, it was diagnosed with unilateral hydronephrosis, and contralateral renal fibrosis with numerous cysts. Histologically, the fibrotic kidney showed FSGS, hyaline reabsorption droplets in proximal tubular epithelial cells, interstitial fibrosis, and tubulointerstitial inflammation. Apart from that, thrombotic microangiopathy (TMA) was seen in few renal arteries and meningeal arterioles. Pathogenesis of FSGS secondary to unilateral renal parenchymal loss (hydronephrosis) and TMA is discussed.

Perspective on Clinical Application of Biomarkers in AKI.

Several biomarkers of renal injury have been identified but the utility of these biomarkers is largely confined to research studies, whereas widespread clinical applicability is limited. This is partly because the use of serum creatinine as the comparator has several limitations and restricts the full interpretation of biomarker performance. To highlight the potential for clinical application of biomarkers, the most pertinent biomarker data are summarized here, using clinically relevant scenarios in which biomarkers could assist with diagnostic and management dilemmas. The paradigms proposed in this review aim to enhance the clinical diagnosis, management, and prognosis of AKI through the combined use of available clinical markers and novel inflammatory, injury, and repair biomarkers.

Diagnosis, Treatment, and Prevention of Hemodialysis Emergencies.

Given the high comorbidity in patients on hemodialysis and the complexity of the dialysis treatment, it is remarkable how rarely a life-threatening complication occurs during dialysis. The low rate of dialysis emergencies can be attributed to numerous safety features in modern dialysis machines; meticulous treatment and testing of the dialysate solution to prevent exposure to trace elements, toxins, and pathogens; adherence to detailed treatment protocols; and extensive training of dialysis staff to handle medical emergencies. Most hemodialysis emergencies can be attributed to human error. A smaller number are due to rare idiosyncratic reactions. In this review, we highlight major emergencies that may occur during hemodialysis treatments, describe their pathogenesis, offer measures to minimize them, and provide specific interventions to prevent catastrophic consequences on the rare occasions when such emergencies arise. These emergencies include dialysis disequilibrium syndrome, venous air embolism, hemolysis, venous needle dislodgement, vascular access hemorrhage, major allergic reactions to the dialyzer or treatment medications, and disruption or contamination of the dialysis water system. Finally, we describe root cause analysis after a dialysis emergency has occurred to prevent a future recurrence.

Biomarkers in Acute Kidney Injury.

Acute kidney injury (AKI) is a common and often lethal complication that is also associated with severe morbidity in hospitalized patients. During the last decade, the standardization of AKI diagnostic criteria has helped to facilitate several large-scale investigations of biomarkers of AKI. These studies have led to the international clinical implementation of several biomarkers of renal injury. This review summarizes the results of many of these multicenter investigations and discusses the clinical utility and interpretation of several of these new clinical tests. The merits of combining biomarkers of kidney function is also discussed.

Serum cystatin C as a novel marker to differentiate pseudoazotemia in the setting of intraperitoneal urine extravasation.

Urinary ascites results in pseudoazotemia due to urinary creatinine reabsorption across the peritoneum. We report a case of a pyeloplasty complicated by urine extravasation, in which the diagnosis was aided by discrepant findings of an elevated serum creatinine level but a stable cystatin C level. Cystatin C is a marker of renal function but is not typically excreted into the urine and therefore can be used to differentiate pseudoazotemia from true azotemia and is a better marker of renal function in the setting of known urinary ascites. These findings are relevant for patients with potential traumatic or nontraumatic sources of urine extravasation.

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.

Azotemia protects the brain from osmotic demyelination on rapid correction of hyponatremia.

Osmotic demyelination syndrome (ODS) is a dreadful, irreversible and well-recognized clinical entity that classically occurs after rapid correction of hyponatremia. However, it has been observed that when hyponatremia is rapidly corrected in azotemic patients by hemodialysis (HD), patients do not necessarily develop ODS. We studied the effect of inadvertent rapid correction of hyponatremia with HD in patients with azotemia. Fifty-two azotemic patients, who underwent HD at the Sindh Institute of Urology and Transplantation, having pre-HD serum sodium level <125 mEq/L and post-HD serum sodium levels that increased by ≥12 mEq/L from their pre-dialysis level, were studied. Serum sodium was analyzed before and within 24 h after a HD session. HD was performed using bicarbonate solution, with the sodium concentration being 140 meq/L. The duration of the dialysis session was based on the discretion of the treating nephrologist. Patients were examined for any neurological symptoms or signs before and after HD and for up to two weeks. Magnetic resonance imaging was performed in required cases. None of the 52 patients with azotemia, despite inadvertent rapid correction of hyponatremia with HD, developed ODS. This study suggests that patients with azotemia do not develop ODS on rapid correction of hyponatremia by HD, which suggests a possible protective role of azotemia on the brain from osmotic demyelination. However, the mechanism by which azotemia protects the brain from demyelination in humans is largely hypothetical and further studies are needed to answer this question.

Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a protein that is used in human medicine as a real-time indicator of acute kidney injury (AKI). HYPOTHESIS: Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL-to-creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD). ANIMALS: 18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI. METHODS: Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single-injection plasma inulin clearance was performed in the healthy dogs. RESULTS: Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5-21.2), 22.0 ng/mL (7.7-62.3), and 48.3 ng/mL (5.7-469.0), respectively. UNCR was 2 × 10(-8) (0-46), 1,424 × 10(-8) (385-18,347), and 2,366 × 10(-8) (36-994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027). CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.

Congenital hypothyroidism and concurrent renal insufficiency in a kitten.

A 3-month-old male domestic short-hair kitten was presented with chronic constipation and disproportionate dwarfism. Radiographs of the long bones and spine revealed delayed epiphyseal ossification and epiphyseal dysgenesis. Diagnosis of congenital primary hypothyroidism was confirmed by low serum total thyroxine and high thyroid stimulating hormone concentrations. Appropriate supplementation of levothyroxine was instituted. The kitten subsequently developed mild renal azotaemia and renal proteinuria, possibly as a consequence of treatment or an unmasked congenital renal developmental abnormality. Early recognition, diagnosis and treatment are vital as alleviation of clinical signs may depend on the cat's age at the time of diagnosis.