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Thesis Format

Integrated Article


Doctor of Philosophy


Epidemiology and Biostatistics


Garg, Amit X


Upper urinary tract stones are a major determinant of pain and is suggested to accelerate disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). For these reasons, stones should be optimally managed in patients with ADPKD. However, the kidney distortions may make managing stones challenging in patients with ADPKD. Understanding of the epidemiology of upper urinary tract stones and stone intervention and the outcomes of stone interventions is limited. The aim of this thesis is to understand the epidemiology of upper urinary tract stones and stone interventions and consequences of stone management in patients with ADPKD.

To address this knowledge gap, we conducted two systematic reviews to understand the current knowledge on the prevalence and incidence of upper urinary tract stones, and the success and complication rate of the three common stone interventions (shockwave lithotripsy [SWL], ureteroscopy, and percutaneous nephrolithotomy [PCNL]) in patients with ADPKD. We conducted a chart review to validate International Classification of Diseases, 10th revision (ICD-10) codes related to ADPKD. We then conducted two cohort studies using ICES data to determine and compare the rate of stones and rate of stone intervention, and the complication rate of the most common stone intervention (ureteroscopy) in patients with ADPKD to patients without ADPKD with similar baseline health.

Chapter 2 showed that that there is poor consensus on how often patients with ADPKD develop or undergo intervention for upper urinary tract stones.

Chapter 3 showed that the efficacy and safety of stone interventions in patients with ADPKD remains uncertain.

Chapter 4 summarized the limitations of the existing literature based on the findings of the two systematic reviews.

Chapter 5 showed that majority of the patients with ICD-10 codes related to ADPKD truly have ADPKD according to strict clinical criteria.

Chapter 6 showed that patients with ADPKD presented to the hospital with upper urinary tract stones more, and that urologist were not managing stones in patients with ADPKD in a similar manner to comparable patients without ADPKD. It also showed that ureteroscopy is the most commonly performed stone intervention.

Chapter 7 showed ADPKD is associated with a statistically significant increase emergency department visits in selected patients with ADPKD who received ureteroscopy for upper urinary tract stones compared to patients without ADPKD.

Results can inform the use of ICD-10 codes to build ADPKD cohorts, inform clinical practice guidelines, and guide prognostication.

Summary for Lay Audience

Autosomal dominant polycystic kidney disease is a condition where the kidneys are filled with many cysts. Over time, the cysts grow in size and number and cause the kidneys to fail. Upper urinary tract stones are a major reason for pain and may cause kidneys to fail faster in these patients. For these reasons, stones should be managed well in patients with ADPKD. However, the kidney cysts in these patients may make this challenging. A thorough review of the literature shows that little is known about the rate of upper urinary tract stones and stone interventions, and the outcomes of ureteroscopy (a common procedure to treat upper urinary tract stones). The aim of this thesis was to fill this knowledge gap.

We did this by conducting large, follow-up studies using administrative databases. Our validation studies show that we can confidently use administrative codes to identify patients with ADPKD. This thesis confirms that hospital encounters with upper urinary tract stones are a manifestation of ADPKD. From the administrative data, urologists approach stones in ADPKD in a similar manner compared to patients without ADPKD, despite the distorted kidney anatomy potentially making stone interventions more challenging. Of all three commonly used interventions (SWL, ureteroscopy, and PCNL), ureteroscopy is the most common intervention used to manage stones in both patients with and without ADPKD. Our final thesis study shows that patients with ADPKD do not experience more ureteroscopic complications and hospital admission for any reason. However, they did experience more hospital presentation and emergency department visit for any reason compared to patients without ADPKD. This may be a consideration for patient counselling.

The knowledge gained from this thesis identifies knowledge gaps, and lays the foundation for future studies on ADPKD using healthcare administrative databases. It also clarifies the rate of hospital encounters with upper urinary tract stones and the rate of stone interventions, and provides the best evidence we have to date to inform clinical practice.

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