Advanced Image-Guided Percutaneous Technique Versus Advanced Laparoscopic Surgical Technique for Peritoneal Dialysis Catheter Placement.

Rationale & Objective: Timely placement of a functional peritoneal dialysis (PD) catheter is crucial to long-term PD success. Advanced image-guided percutaneous and advanced laparoscopic techniques both represent best practice catheter placement options. Advanced image-guided percutaneous is a minimally invasive procedure that does not require general anesthesia. Study Design: Retrospective cohort study comparing time from referral to procedure, complication rate, and 1-year catheter survival between placement techniques. Setting & Participants: Patients who had advanced laparoscopic or advanced image-guided percutaneous PD catheter placement from January 1, 2011 to December 31, 2013 in an integrated Northern California health care delivery system. Exposure: PD catheter placement using advanced laparoscopic or advanced image-guided percutaneous techniques. Outcomes: One-year PD catheter survival; major, minor, and infectious complications; time from referral to PD catheter placement; and procedure time. Analytical Approach: Wilcoxon rank sum tests to compare referral and procedure times; χ2/Fisher exact tests to compare complications; and modified least-squares regression to compare adjusted 1-year catheter survival between PD placement techniques. Results: We identified 191 and 238 PD catheters placed through advanced image-guided percutaneous and advanced laparoscopic techniques, respectively. Adjusted 1-year PD catheter survival was 80% (95% CI, 74%-87%) using advanced image-guided percutaneous technique vs 91% (87%-96%) using advanced laparoscopic technique (P = 0.01). Major complications were <1% in both groups. Minor and infectious complications were 45.6% and 38.7% in advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P = 0.01). Median days from referral to procedure were 12 and 33 for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Median procedure time was 30 and 44.5 minutes for patients undergoing advanced image-guided percutaneous and advanced laparoscopic techniques, respectively (P < 0.001). Limitations: Retrospective study with practice preference influenced by timing, local expertise, and resources. Conclusions: Both advanced image-guided percutaneous and advanced laparoscopic techniques reported rare major complications and demonstrated excellent (advanced laparoscopic) and acceptable (advanced image-guided percutaneous) 1-year PD catheter survival. For patients referred for PD catheter placement at centers where advanced laparoscopic resources or expertise remain limited, the advanced image-guided percutaneous technique can provide a complementary and timely option to support the utilization of PD. Plain-Language Summary: Peritoneal dialysis is a preferred dialysis modality for many patients. However, the lack of available skilled surgeons can limit the placement of the peritoneal dialysis catheter in a timely manner. In the past decade, interventional radiology has developed expertise in placing peritoneal dialysis catheters. Using data from an integrated health care system, we compared the outcome of peritoneal dialysis catheters placed using laparoscopic surgery and interventional radiology techniques. Our results showed excellent 1-year patency of peritoneal dialysis catheters placed using laparoscopic surgery, whereas interventional radiology placement of catheters had lower but acceptable 1-year patency survival, based on best practice guideline criteria. Hence, interventional radiology placement of peritoneal dialysis catheters may be a viable alternative when laparoscopic surgery is not available or feasible.

Associations between vitamin C intake and serum uric acid in US adults: Findings from National Health and Nutrition Examination Survey 2011-2016.

BACKGROUNDS: Dietary factors has been found to influence serum uric acid (SUA) levels. We further explored the associations between dietary and supplemental vitamin C intake and SUA in a large population-based study. METHODS: The cross-sectional study included 6308 participants (3146 males and 3162 females) aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 in the United States. The dietary vitamin C was log-transformed for statistical analysis. Hyperuricemia was defined as SUA concentrations >420 umol/L in males or >360 umol/L in females. The associations of dietary vitamin C and supplemental vitamin C with SUA levels and hyperuricemia risk were evaluated using weighted linear regression models and weighted multivariate logistic regression models, and a subgroup analysis stratified by gender was also conducted. RESULTS: In this large-scale database study, there was a negative association between dietary vitamin C (log transformed) and SUA levels in US adults (ß = -7.27, 95% CI: -11.58, -2.97). The inverse relationship existed among males but not females (P for interaction = 0.02). There was inverse correlation between dietary vitamin C (log transformed) and hyperuricemia risk (OR = 0.68, 95% CI: 0.57, 0.81), especially in males compared to females determined through an interaction test (P = 0.04). There were no associations between supplemental vitamin C and SUA levels (ß = 1.00 (95% CI: -4.44, 6.44) or hyperuricemia risk (OR = 0.98 (95% CI: 0.78, 1.24). High-dosage supplemental vitamin C (>300 mg) and hyperuricemia risk were not associated (OR = 1.04, 95% CI: 0.69, 1.56). CONCLUSIONS: This study demonstrated that there were negative associations between dietary vitamin C and SUA levels and hyperuricemia risk among US adults. The inverse correlations between dietary vitamin C and hyperuricemia risk were more significant in males compared to females. There were no associations between supplemental vitamin C and SUA levels or hyperuricemia risk.

Urgent Start Peritoneal Dialysis: A Population-Based Cohort Study.

Rationale & Objective: It is a common practice to start patients in urgent need of dialysis on hemodialysis via a central venous catheter. Because central venous catheter use is associated with increased risk of infections, hospitalizations, and mortality, urgent start peritoneal dialysis (PD) increasingly represents a viable alternative. This study aimed to examine clinical outcomes, complications, mortality, and modality retention in patients who initiated urgent start PD. Study Design: Retrospective cohort study. Setting and Participants: Eighty-four adult members of a large integrated health care system who initiated urgent start PD between January 1, 2011, and December 31, 2014. Exposure: Urgent start PD. Outcomes: Retention rates at 30, 90, and 365 days; time to the development of noninfectious and infectious complications, modality failure, and all-cause mortality. Analytical Approach: Cumulative incidence of all-cause mortality was estimated using the Kaplan-Meier method. Retention rates for PD were computed using binomial proportions. Results: Occurrence of major complications was less than 5%. Catheter malfunction occurred in 6% of cases; of those, catheter patency could be established in 80%. Infectious complications occurred in 20% of patients who initiated PD and included peritonitis and exit site infections. At 365 days after initiation, the cumulative incidence of all-cause mortality was 9.7% (95% CI, 4.7%-19.4%). PD retention rates were 98.8%, 91.3%, and 80.0% at 30 days, 90 days, and 1 year, respectively. Limitations: Retrospective cohort design, a well-matched comparable group of urgent start hemodialysis patients could not be identified, small number of patients in a single integrated health care system, uncertain or limited generalizability of findings to other health care systems. Conclusions: At 1 year after initiation, patients who initiated urgent start PD had high survival and modality retention rates. In unplanned initiation of dialysis, urgent start PD is a viable and sustainable option and should be considered in selected patients to optimize care.

Population-based identification and temporal trend of children with primary nephrotic syndrome: The Kaiser Permanente nephrotic syndrome study.

INTRODUCTION: Limited population-based data exist about children with primary nephrotic syndrome (NS). METHODS: We identified a cohort of children with primary NS receiving care in Kaiser Permanente Northern California, an integrated healthcare delivery system caring for >750,000 children. We identified all children <18 years between 1996 and 2012 who had nephrotic range proteinuria (urine ACR>3500 mg/g, urine PCR>3.5 mg/mg, 24-hour urine protein>3500 mg or urine dipstick>300 mg/dL) in laboratory databases or a diagnosis of NS in electronic health records. Nephrologists reviewed health records for clinical presentation and laboratory and biopsy results to confirm primary NS. RESULTS: Among 365 cases of confirmed NS, 179 had confirmed primary NS attributed to presumed minimal change disease (MCD) (72%), focal segmental glomerulosclerosis (FSGS) (23%) or membranous nephropathy (MN) (5%). The overall incidence of primary NS was 1.47 (95% Confidence Interval:1.27-1.70) per 100,000 person-years. Biopsy data were available in 40% of cases. Median age for patients with primary NS was 6.9 (interquartile range:3.7 to 12.9) years, 43% were female and 26% were white, 13% black, 17% Asian/Pacific Islander, and 32% Hispanic. CONCLUSION: This population-based identification of children with primary NS leveraging electronic health records can provide a unique approach and platform for describing the natural history of NS and identifying determinants of outcomes in children with primary NS.

Timing of AKI after urgent percutaneous coronary intervention and clinical outcomes: a high-dimensional propensity score analysis.

INTRODUCTION: Acute kidney injury is a common complication of percutaneous coronary intervention and has been associated with an increased risk of death and progressive chronic kidney disease. However, whether the timing of acute kidney injury after urgent percutaneous coronary intervention could be used to improve patient risk stratification is not known. METHODS: We conducted a retrospective cohort study in adults surviving an urgent percutaneous coronary intervention between 2008 and 2013 within Kaiser Permanente Northern California, a large integrated healthcare delivery system, to evaluate the impact of acute kidney injury during hospitalization at 12 (±6), 24 (±6) and 48 (±6) hours after urgent percutaneous coronary intervention and subsequent risks of adverse outcomes within the first year after discharge. We used multivariable Cox proportional hazards models with adjustment for a high-dimensional propensity score for developing acute kidney injury after percutaneous coronary intervention to examine the associations between acute kidney injury timing and all-cause death and worsening chronic kidney disease. RESULTS: Among 7250 eligible adults undergoing urgent percutaneous coronary intervention, 306 (4.2%) had acute kidney injury at one or more of the examined time periods after percutaneous coronary intervention. After adjustment, acute kidney injury at 12 (±6) hours was independently associated with higher risks of death (adjusted hazard ratio [aHR] 3.55, 95% confidence interval [CI] 2.19-5.75) and worsening kidney function (aHR 2.40, 95% CI:1.24-4.63). Similar results were observed for acute kidney injury at 24 (±6) hours and death (aHR 3.90, 95% CI:2.29-6.66) and worsening chronic kidney disease (aHR 4.77, 95% CI:2.46-9.23). Acute kidney injury at 48 (±6) hours was associated with excess mortality (aHR 1.97, 95% CI:1.19-3.26) but was not significantly associated with worsening kidney function (aHR 0.91, 95% CI:0.42-1.98). CONCLUSIONS: Timing of acute kidney injury after urgent percutaneous coronary intervention may be differentially associated with subsequent risk of worsening kidney function but not death.

Primary Nephrotic Syndrome and Risks of ESKD, Cardiovascular Events, and Death: The Kaiser Permanente Nephrotic Syndrome Study.

BACKGROUND: Little population-based data exist about adults with primary nephrotic syndrome. METHODS: To evaluate kidney, cardiovascular, and mortality outcomes in adults with primary nephrotic syndrome, we identified adults within an integrated health care delivery system (Kaiser Permanente Northern California) with nephrotic-range proteinuria or diagnosed nephrotic syndrome between 1996 and 2012. Nephrologists reviewed medical records for clinical presentation, laboratory findings, and biopsy results to confirm primary nephrotic syndrome and assigned etiology. We identified a 1:100 time-matched cohort of adults without diabetes, diagnosed nephrotic syndrome, or proteinuria as controls to compare rates of ESKD, cardiovascular outcomes, and death through 2014, using multivariable Cox regression. RESULTS: We confirmed 907 patients with primary nephrotic syndrome (655 definite and 252 presumed patients with FSGS [40%], membranous nephropathy [40%], and minimal change disease [20%]). Mean age was 49 years; 43% were women. Adults with primary nephrotic syndrome had higher adjusted rates of ESKD (adjusted hazard ratio [aHR], 19.63; 95% confidence interval [95% CI], 12.76 to 30.20), acute coronary syndrome (aHR, 2.58; 95% CI, 1.89 to 3.52), heart failure (aHR, 3.01; 95% CI, 2.16 to 4.19), ischemic stroke (aHR, 1.80; 95% CI, 1.06 to 3.05), venous thromboembolism (aHR, 2.56; 95% CI, 1.35 to 4.85), and death (aHR, 1.34; 95% CI, 1.09 to 1.64) versus controls. Excess ESKD risk was significantly higher for FSGS and membranous nephropathy than for presumed minimal change disease. The three etiologies of primary nephrotic syndrome did not differ significantly in terms of cardiovascular outcomes and death. CONCLUSIONS: Adults with primary nephrotic syndrome experience higher adjusted rates of ESKD, cardiovascular outcomes, and death, with significant variation by underlying etiology in the risk for developing ESKD.

Implication of Trends in Timing of Dialysis Initiation for Incidence of End-stage Kidney Disease.

Importance: In the last 2 decades, there have been notable changes in the level of estimated glomerular filtration rate (eGFR) at which patients initiate long-term dialysis in the US and around the world. How changes over time in the likelihood of dialysis initiation at any given eGFR level in at-risk patients are associated with the population burden of end-stage kidney disease (ESKD) has not been not well defined. Objective: To examine temporal trends in long-term dialysis initiation by level of eGFR and to quantify how these patterns are associated with the number of patients with ESKD. Design, Setting, and Participants: Retrospective cohort study analyzing data obtained from a large, integrated health care delivery system in Northern California from 2001 to 2018 in successive 3-year intervals. Included individuals, ranging in number from as few as 983 122 (2001-2003) to as many as 1 844 317 (2016-2018), were adult members with 1 or more outpatient serum creatinine levels determined in the prior year. Main Outcomes and Measures: One-year risk of initiating long-term dialysis stratified by eGFR levels. Multivariable logistic regression was performed to assess temporal trends in each 3-year cohort with adjustment for age, sex, race, and diabetes status. The potential change in dialysis initiation in the final cohort (2016-2018) was estimated using the relative difference between the standardized risks in the initial cohort (2001-2003) and the final cohort. Results: In the initial 3-year cohort, the mean (SD) age was 55.4 (16.3) years, 55.0% were women, and the prevalence of diabetes was 14.9%. These characteristics, as well as the distribution of index eGFR, were stable across the study period. The likelihood of receiving dialysis at eGFR levels of 10 to 24 mL/min/1.73 m2 generally increased over time. For example, the 1-year odds of initiating dialysis increased for every 3-year interval by 5.2% (adjusted odds ratio, 1.052; 95% CI, 1.004-1.102) among adults with an index eGFR of 20 to 24 mL/min/1.73 m2, by 6.6% (adjusted odds ratio, 1.066; 95% CI, 1.007-1.130) among adults with an eGFR of 16 to 17 mL/min/1.73 m2, and by 5.3% (adjusted odds ratio, 1.053; 95% CI, 1.008-1.100) among adults with an eGFR of 10 to 13 mL/min/1.73 m2, adjusting for age, sex, race, and diabetes. The incidence of new cases of ESKD was estimated to have potentially been 16% (95% CI, 13%-18%) lower if there were no changes in system-level practice patterns or other factors besides timing of initiating long-term dialysis from the initial 3-year interval (2001-2003) to the final interval (2016-2018) assessed in this study. Conclusions and Relevance: The present results underscore the importance the timing of initiating long-term dialysis has on the size of the population of individuals with ESKD.

Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI.

BACKGROUND AND OBJECTIVES: How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders. RESULTS: Forty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12). CONCLUSIONS: In this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.

Trends Associated With Large-scale Expansion of Peritoneal Dialysis Within an Integrated Care Delivery Model.

IMPORTANCE: Despite favorable national trends in the incidence of end-stage renal disease (ESRD) from 2008 to 2011, ESRD incidence has been increasing recently, and less than 10% of patients with ESRD start renal replacement therapy with peritoneal dialysis (PD) in the United States. Given known and potential advantages of PD over hemodialysis, the Kaiser Permanente Northern California integrated health care delivery system implemented a program to expand use of PD. OBJECTIVES: To describe the system-level approach to expansion of PD use and temporal trends in initiation and persistence of PD and its associated mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adult members of a large integrated health care delivery system in Northern California who initiated chronic dialysis therapy from January 1, 2008, through December 31, 2018. Data were analyzed from March 1, 2018, through May 31, 2019. EXPOSURE: From 2008 to 2018, Kaiser Permanente Northern California implemented a multidisciplinary, system-wide approach to increase use of PD that included patient and caregiver education, education and support tools for health care professionals, streamlined system-level processes, monitoring, and continuous quality improvement. MAIN OUTCOMES AND MEASURES: Temporal trends in the proportion of patients starting chronic dialysis with PD vs hemodialysis compared with national trends. Secondary outcomes included persistence of PD at 1 year in those initiating it and standardized 1-year mortality rates in those initiating PD or hemodialysis. RESULTS: Among 13 500 eligible health plan members in the study population (7840 men [58.1%] and 5660 women [41.9%]; mean [SD] age, 64.3 [14.4] years), initiation of PD increased from 165 of 1089 all new dialysis patients (15.2%) in 2008 to 486 of 1438 (33.8%) in 2018, which was substantially higher than national trends (6.1% in 2008 and 9.7% in 2016). Among the 2974 patients who initiated PD from 2008 to 2017, 2387 (80.3%) continued PD at 1 year after initiation, with a significant increase in age-, sex-, and race-standardized rates from 2008 (69.1%) to 2017 (84.2%). Age-, sex-, and race-standardized 1-year mortality for patients receiving PD and hemodialysis did not change significantly across this 10-year period (17.3% to 15.5% for hemodialysis, P = 0.89 for trend; and 5.5% to 7.3% for PD, P = 0.12 for trend). CONCLUSIONS AND RELEVANCE: This study suggests that large-scale expansion of PD is feasible using a multidisciplinary, integrated, coordinated care approach; we believe these findings represent a national opportunity to improve outcomes for patients with advanced kidney disease.

Elevated BP after AKI.

The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP--defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit--during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization.

Effects of sodium thiosulfate on vascular calcification in end-stage renal disease: a pilot study of feasibility, safety and efficacy.

BACKGROUND AND OBJECTIVES: Vascular calcification is a major contributor to morbidity and mortality in hemodialysis. The objective of this pilot study was to determine the feasibility, safety and efficacy of sodium thiosulfate (STS) in the progression of vascular calcification in hemodialysis patients. METHODS: Chronic hemodialysis patients underwent a battery of cardiovascular tests. Those with coronary artery calcium (Agatston scores >50) received intravenous STS after each dialysis for 5 months (n = 22) and the tests were repeated. Changes in MDCT-determined calcification were assessed as the mean annualized rate of change in 3 vascular beds (coronary, thoracic and carotid arteries) and in L1-L2 vertebral bone density. RESULTS: Although individual analyses showed coronary artery calcification progression in 14/22 subjects, there was no progression in the mean annualized rate of change of vascular calcification in the entire group. The L1-L2 vertebral bone density showed no changes. There were no correlations between rates of progression of vascular calcification and phosphorus, fetuin or C-reactive protein levels. Changes in coronary artery calcification scores correlated with those of the thoracic aorta. CONCLUSION: STS treatment is feasible, appears safe and may decrease the rate of progression of vascular calcification in hemodialysis patients. A large, randomized, controlled trial is warranted.