Acetazolamide (ACZ) is a relatively commonly used medication in critical illness, glaucoma and altitude sickness. ACZ is sometimes used in the intensive care unit to assist with the treatment of metabolic alkalosis in ventilated patients. This is a case report of a patient who received two doses of ACZ, one week apart, for metabolic alkalosis and subsequently developed renal colic and dysuria that progressed to hemorrhagic anuria and acute kidney injury. This is an incredibly rare side effect of ACZ therapy, and has been reported in a few case reports in the literature, but usually is associated with a longer duration of therapy. This case resolved entirely within 24 hours with aggressive fluid therapy. Clinicians using ACZ therapy for any reason should be aware of this rare but significant side effect.

Oil spills are well-known adverse anthropogenic events, as they can induce severe impacts on the environment and negative economic consequences. Still, much remains to be learned regarding the effects of crude oil exposure to aquatic organisms. The objectives of this dissertation were to fill some of those knowledge gaps by examining the effects of Deepwater Horizon (DWH) crude oil exposure on teleost kidney development and function. To this end, I analyzed how these effects translate into potential osmoregulatory impairments and investigated the interactive effects of ubiquitous natural factors, such as dissolved organic carbon (DOC) and ultraviolet (UV) light, on acute crude oil toxicity. Results demonstrated that acute early life stage (ELS) crude oil exposure induces developmental defects to the primordial kidney in teleost fish (i.e., the pronephros) as evident by alterations in: (1) transcriptional responses of key genes involved in pronephros development and function and (2) alterations in pronephros morphology. Crude oil-exposed zebrafish (Danio rerio) larvae presented defective pronephric function characterized by reduced renal clearance capacity and altered filtration selectivity, factors that likely contributed to the formation of edema. Latent osmoregulatory implications of crude oil exposure during ELS were observed in red drum (Sciaenops ocellatus) larvae, which manifested reduced survival in hypoosmotic waters, likely due to defective pronephros development and function. Finally, DOC-UV co-exposure slightly reduced acute crude oil photo-enhanced toxicity in red drum larvae. This dissertation provided novel information regarding crude oil toxicity that can be incorporated into environmental risk assessment and management for future oil spills.

Background and objectives: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic condition defined by an increase in cardiovascular calcifications and bone fragility. The condition is diagnosed by abnormal serum concentrations of calcium, phosphorus, parathyroid hormone and vitamin D. These biochemical abnormalities have been linked to abnormal bone metabolism as well as cardiovascular calcifications if left untreated. Phosphate binders are known to cause phosphate reduction through mechanisms involve the gastrointestinal route. Their relative effects remain uncertain. Controversy arises because of concerns related to systematic effects, tolerability, costs and impact on patient important outcomes. The objective of Chapters 2 and 3 was to explore the relative effectiveness of phosphate binders on patient-important outcomes and laboratory outcomes in patients with CKD-MBD using the frequentist and Bayesian approaches, respectively. The purpose of Chapter 4 was to critically appraise clinical practice guidelines addressing CKD-MBD. Methods and results Chapter 2: We performed network meta-analyses for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. non-calcium based phosphate binders (NCBPB) for all-cause mortality, cardiovascular mortality and hospitalization. Our results suggested higher mortality with calcium than either sevelamer in our network meta-analysis or NCBPB in our conventional meta-analysis. Conventional meta-analysis suggested no statistically difference in cardiovascular mortality between calcium and NCBPBs. Chapter 3: We performed Bayesian network meta-analyses to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. Moderate-quality evidence suggests superior effect of active treatment categories as compared to placebo for reducing serum phosphate. Our NMA results did not find statistically significant difference between active treatment categories in lowering serum phosphate. Chapter 4: We performed a systematic survey to critically appraise clinical practice guidelines addressing CKD-MBD. Most guidelines assessing CKD-MBD suffer from serious shortcomings using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE) criteria; a minority, however, fulfill the criteria. Limitations with respect to AGREE criteria do not, however, necessarily lead to inappropriate recommendations. Conclusion: Given the likely mortality reduction with sevelamer versus calcium, the results suggest that higher calcium levels associated with calcium based phosphate binders may contribute to the mortality differential. We found that most clinical practice guidelines related to CKD-MBD were not satisfactory with major problems with rigor, update and implementation. Recommendations were consistent and thus unassociated with guideline quality. In other instances, however, this may not be the case, and ensuring trustworthiness of guidelines will require adherence to methodological standards. / Thesis / Doctor of Philosophy (PhD)

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