Casey Jackson

Abstract Objective: To describe the clinical manifestations and treatment of hypermagnesemia and the potential drug errors that can lead to iatrogenic electrolyte toxicities. Summary: We report 2 cases of iatrogenic intravenous (IV) magnesium (Mg) overdose. Both cases developed extreme cardiovascular and neurologic symptoms consisting of vomiting, hypotension, bradycardia, flaccid paralysis, and severe mental depression. Diagnosis was made based upon serum ionized Mg levels (3.47 mmol/L; reference range: 0.43–0.58 mmol/L for Case #1; and 4.64 mmol/L; reference range: 0.42–0.55 mmol/L for Case #2). Each animal was treated with 0.9% NaCl for diuresis and IV calcium gluconate. Within 24 hours, the cardiovascular and neurologic status of both animals, as well as the serum Mg concentration, had normalized. Each animal was discharged with no complications. Both animals had been hospitalized for critical illness and had developed hypomagnesemia that was being treated with Mg sulfate infusions. The cause for the hypermagnesemia was due to miscalculations in treatment orders that led to erroneously administered Mg‐containing solutions. Confusing drug labels and varying units of measurement can lead to erroneous miscalculations, especially in critically ill patients that receive multiple IV infusions. New information provided: This is the first case report of iatrogenic Mg overdose in veterinary medicine. These 2 cases had a good clinical outcome with prompt recognition and supportive care.

We evaluated the ability of an antimicrobial and endotoxin-neutralizing agent, the recombinant amino terminal fragment of bactericidal permeability-increasing protein (rBPI21), to decrease plasma endotoxin concentration and severity of clinical signs of canine parvovirus and to improve survival. This randomized, double-blinded, placebo-controlled clinical trial included 40 client-owned dogs and 9 normal puppies from a closed research colony. Dogs weighing >5 kg (11 lb) with fecal antigen-confirmed parvovirus and clinical signs of vomiting and diarrhea were randomly assigned to receive placebo or rBPI21 infusion over 6 hours. Plasma endotoxin concentration was measured at 0, 3, and 6 hours of infusion. Owners chose continued medical care with either the Veterinary Hospital of the University of Pennsylvania Internal Medicine Service or a local veterinarian. Telephone follow-up was conducted at 14 days. Surviving dogs were reevaluated at >30 days (recovered group), at which time plasma samples for measurement of endotoxin concentration were obtained. Plasma endotoxin concentrations were significantly higher in dogs with parvovirus than in normal or recovered dogs. Despite 90% survival, the rBPI21 treatment did not have a significant effect on outcome, duration of hospitalization, or plasma endotoxin concentrations. Treatment in a tertiary care hospital, however, significantly improved survival but resulted in a significantly increased duration of hospitalization. Endotoxemia occurs in dogs with parvovirus enteritis, but rBPI21 is not associated with improved survival.

INTRODUCTION: Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood. METHODS: This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months. RESULTS: Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model. CONCLUSION: The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.

Introduction: Diabetic kidney disease is the most common cause of chronic end stage renal failure in the USA. Kidney biopsy is the gold standard diagnostic criteria; however, it is an invasive procedure; not everyone undergoes diagnostic biopsy. The relationship between histological and clinical parameters and prognosis in DKD is incompletely understood. TRIDENT, (Transformative research in diabetic nephropathy) plans to enroll 400 diabetic subjects undergoing clinically indicated renal biopsies and performs multi-omics characterization of subjects to identify pathways associated with kidney function decline. Genetic studies indicated that podocytes influence albuminuria and diabetic kidney disease development. We seek to understand whether podocyte and basement membrane changes correlate with kidney function, degree of albuminuria, and histopathologic features of diabetic nephropathy using electron microscopy and digital light microscopy. Methods: I performed quantitative characterization of podocyte foot process morphology using TRIDENT subject biopsies. Podocyte foot process width (FPW) was measured using electron micrographs in ImageJ and calculated: FPW = (π/4) × (ΣGBM length/Σfoot process). Results: In our cohort, the average FPW was 1.624μm, and the glomerular basement membrane (GBM) average thickness was 773.27μm. The average FPW and GBM thickness ranged from 519μm-4.806μm and 200μm-3230μm per patient, respectively. Using a Pearson’s correlation coefficient: GBM thickness positively correlates with RPS Class (.424240229), %interstitial fibrosis (.203720183), arteriolar hyalinosis (0.307801899), proteinuria (.639114291). Discussion: Podocyte features such as FPW and GBM thickness showed stronger correlation with proteinuria than other parameters. Some samples were collected in patients with advanced DKD; collecting samples earlier in the disease process may represent more accurate correlations between EM findings and disease severity. Overall podocyte structural changes strongly correlate with proteinuria, indicating the key role of podocytes in proteinuria.