Robert Ross Quinn

Purpose of review: In this review, key considerations in the design, conduct, and analysis of observational studies in dialysis research are explored in a unique patient population for which interventional trials are challenging and limited. Recent findings: The use of target trial emulation is increasing and provides a conceptual framework for the design of observational studies. A target trial is a hypothetical trial that would be conducted to answer a research question. It requires investigators to ask a clinically relevant question and then specify eligibility criteria, the treatment strategies that will be compared, the follow-up period, outcomes of interest, and the causal contrast (intention-to-treat vs. per-protocol analysis). The protocol for an observational study is then created to mirror the target trial. In doing so, the question is clear, bias is reduced, and underlying assumptions are made transparent. Illustrative examples are used to highlight common pitfalls in dialysis research. Summary: In conclusion, randomized controlled trials are not always feasible or even the ideal approach for answering certain questions. However, observational studies are challenging and require careful planning and execution to ensure robust, unbiased results. Target trial emulation provides a blueprint to improve the quality of observational study design.

Background: An underappreciated complication of laparoscopic nephrectomy in male living kidney donors is testicular pain, swelling, and hydrocele development. A recent cohort study in Ontario, Canada, found that male donors had a higher rate of hydrocelectomy (7.7 vs. 0.1 events/1000 person-years) and scrotal ultrasounds (25.6 vs. 6.9 events/1000 person-years) than nondonors, when followed for a median of 9 years. Objective: To conduct a replication study in Alberta, Canada, examining the long-term risk of hydrocelectomy after laparoscopic living donor nephrectomy, comparing male donors to nondonors from the general population matched on baseline health indicators. Design: Population-based matched cohort study using linked healthcare databases. Setting: Alberta, Canada (April 1, 2002, to March 31, 2021). Patients: We matched 115 male kidney donors who underwent a laparoscopic nephrectomy with 1150 nondonors. The matching characteristics were age at cohort entry, date of cohort entry, rural residence, income, prior vasectomy, and prior inguinal hernia repair. Measure: ments: The primary outcome was a hydrocelectomy, and the secondary outcome was receipt of a scrotal ultrasound. Methods: Males were followed for a median of eight years, with a maximum follow-up of 19 years. Results: The rate of hydrocelectomy was higher in donors than in nondonors (3 of 115 [2.6%] vs. 1 of 1150 [0.1%]; 3.3 vs. 0.1 events/1000 person-years; P < 0.001). The rate of scrotal ultrasounds was also higher among donors than among nondonors (23.4 vs. 7.5 events/1000 person-years; P < 0.001). Limitations: A low event rate impeded a precise estimation of the risk of hydrocelectomy attributable to donation. Conclusions: In this population-based cohort study from Alberta, Canada, rates of hydrocelectomy and receipt of a scrotal ultrasound were significantly higher in males who underwent laparoscopic living donor nephrectomy than in male nondonors matched for age and other factors. Males considering living kidney donation should be informed of the risk of developing a symptomatic ipsilateral scrotal hydrocele in the years following laparoscopic nephrectomy.

Background: Fistulas are the preferred form of vascular access and historically, have been recommended by guidelines because they were associated with improved clinical outcomes and costs. However, there has never been a randomized comparison of catheters to fistulas and the evidence on which recommendations were based is observational with potential for bias. Methods: A pilot randomized controlled trial was conducted in 12 hemodialysis centers in Canada and Australia. Individuals aged 55 years and older who started hemodialysis using a tunneled or non-tunneled central venous catheter for vascular access were randomized to an attempt at fistula creation or continued use of a tunneled, central venous hemodialysis catheter. The primary outcome was feasibility, as measured by the proportion of eligible patients who consented to randomization and the proportion of patients randomized to the fistula group who underwent fistula placement within 90 days. Secondary outcomes included invasive access-related procedures, hospitalizations, access-related infections, tissue plasminogen activator usage, and death. Results: A total of 1287 patients were screened and 67 patients underwent randomization. A total of 25% of eligible patients agreed to randomization and 71% randomized to the fistula arm underwent fistula placement within 90 days. The most common reason patients declined to participate in the trial was that they preferred to continue to dialyze with their catheter. Patients randomized to fistulas had nominally more access-related interventions, hospitalizations, and bacteremia (the majority of which were catheter-related), while the catheter group experienced greater reliance on thrombolytic therapy. Conclusions: Findings from this trial suggest that conducting a definitive randomized trial of fistulas versus catheters is not feasible in the current climate. There was no signal of harm associated with randomization to the catheter strategy and most outcomes favored the catheter group. Patients exhibited strong preferences regarding choice of vascular access.

Peritoneal dialysis (PD) is being promoted worldwide, but nearly half of all patients who start PD will no longer be on therapy at two years, representing an important barrier to maximizing the safe and effective use of the therapy. Loss most commonly occurs due to HD transfer, death, or the receipt of a kidney transplant, but can also occur because patients recover kidney function, transfer to another dialysis program, or are lost to follow-up. Historically, the term “technique failure” has been used to describe loss from PD, but there has been no consistent definition, and as a consequence, it has been unclear whether the observed variability in the reported risk is related to differences in patient characteristics, practice patterns, or simply differences in the way it was defined, measured, analyzed, or reported. The International Society for Peritoneal Dialysis (ISPD) convened a working group to provide recommendations around key issues related to measuring time on PD therapy. These included standardizing definitions for causes of loss, as well as their measurement, analysis, and reporting. Key performance indicators were proposed for the purpose of benchmarking and to facilitate quality improvement and research. The target audience of this document includes physicians and other healthcare providers, dialysis programs, researchers, and national registries.

Home-based peritoneal dialysis (PD) is less resource-intensive than in-center hemodialysis. When provided with a choice, many patients prefer home-based therapies. The Starting Dialysis on Time, At Home on the Right Therapy (START) project was a quality improvement initiative aiming to increase PD use in Alberta, Canada. The START project provided site-specific audit and feedback reports on the processes of care for PD and increased the use of PD. In this current study, we conducted a retrospective cost analysis of the START project. We used the perspective of a publicly funded healthcare system to compare the costs before and after the START intervention. We used a decision analytic model stratifying the patient cohort by age (under and over 65 years) and estimated the impact of the START intervention on the overall cost of care at 1, 3, 5, and 10 years. Sensitivity analyses were performed. We found cost savings of $CAD 1.2 million, $CAD 1.9 million, $CAD 2.4 million, and $CAD 2.7 million for the START intervention at 1, 3, 5, and 10 years, respectively. Results were robust to a variety of sensitivity and scenario analyses. Even modest increases in PD utilization led to cost savings. We found that the implementation of a quality improvement initiative to increase PD resulted in substantial cost savings over time.

Key Points: The annual incidence of CKD is relatively low (approximately 2%) even in groups that are considered at higher risk, such as people with diabetes or hypertension. A substantial number of people are tested at least annually for CKD despite being at very low risk, such as those with an annual incidence of 0.02%. Considering age together with other risk factors for CKD to determine the frequency of testing may increase the diagnostic yield for incident CKD. Background: Guidelines recommend regular serum creatinine testing to detect CKD among people with diabetes or hypertension, but the ideal frequency of testing is unknown. We determined the diagnostic yield for incident CKD as defined by ≥2 measures of eGFR 60 ml/min per 1.73 m ² at baseline in Alberta, Canada. We assessed diagnostic yield overall and in categories defined by age, sex, comorbidity, albuminuria, or levels of a multivariable risk score for CKD. Results: Assuming annual testing, the number of tests needed (NTN) to detect one new CKD case was >67-fold higher among those younger than 50 years (2149, [95% confidence interval (CI), 2103 to 2196]) as compared with older than 70 years (32, [95% CI, 32 to 32]). NTN for annual testing was 50 (95% CI, 49 to 50) among people with diabetes, 57 (95% CI, 57 to 58) in those with hypertension, and 20 (95% CI, 20 to 21) among people with heart failure. When stratified by CKD risk score, the NTN for annual testing ranged from 7 (95% CI, 7 to 8) at a score of 9 (highest risk) to 5708 (95% CI, 5494 to 5930) at a score of 0 (lowest risk). Testing people with diabetes every 3 years instead of every year would delay the diagnosis of CKD by a mean of 1.5 years for 2, 12, and 32 per 1000 people with diabetes aged 70 years, respectively. Corresponding delays associated with testing people with hypertension every 3 years instead of every year would affect 2, 9, and 27 per 1000 people aged 70 years, respectively. If applied to all adult Albertans, these two changes in testing frequency would potentially avert more than 5.9 million laboratory assays over the next decade. Conclusions: Tailoring the frequency of serum creatinine testing according to age and the presence of other risk factors would decrease the NTN to detect cases of incident CKD.