Impact of Prior Abdominal Procedures on Peritoneal Dialysis Catheter Outcomes: Findings From the North American Peritoneal Dialysis Catheter Registry.

RATIONALE & OBJECTIVE: A history of prior abdominal procedures may influence the likelihood of referral for peritoneal dialysis (PD) catheter insertion. To guide clinical decision making in this population, this study examined the association between prior abdominal procedures and outcomes in patients undergoing PD catheter insertion. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults undergoing their first PD catheter insertion between November 1, 2011, and November 1, 2020, at 11 institutions in Canada and the United States participating in the International Society for Peritoneal Dialysis North American Catheter Registry. EXPOSURE: Prior abdominal procedure(s) defined as any procedure that enters the peritoneal cavity. OUTCOMES: The primary outcome was time to the first of (1) abandonment of the PD catheter or (2) interruption/termination of PD. Secondary outcomes were rates of emergency room visits, hospitalizations, and procedures. ANALYTICAL APPROACH: Cumulative incidence curves were used to describe the risk over time, and an adjusted Cox proportional hazards model was used to estimate the association between the exposure and primary outcome. Models for count data were used to estimate the associations between the exposure and secondary outcomes. RESULTS: Of 855 patients who met the inclusion criteria, 31% had a history of a prior abdominal procedure and 20% experienced at least 1 PD catheter-related complication that led to the primary outcome. Prior abdominal procedures were not associated with an increased risk of the primary outcome (adjusted HR, 1.12; 95% CI, 0.68-1.84). Upper-abdominal procedures were associated with a higher adjusted hazard of the primary outcome, but there was no dose-response relationship concerning the number of procedures. There was no association between prior abdominal procedures and other secondary outcomes. LIMITATIONS: Observational study and cohort limited to a sample of patients believed to be potential candidates for PD catheter insertion. CONCLUSION: A history of prior abdominal procedure(s) does not appear to influence catheter outcomes following PD catheter insertion. Such a history should not be a contraindication to PD. PLAIN-LANGUAGE SUMMARY: Peritoneal dialysis (PD) is a life-saving therapy for individuals with kidney failure that can be done at home. PD requires the placement of a tube, or catheter, into the abdomen to allow the exchange of dialysis fluid during treatment. There is concern that individuals who have undergone prior abdominal procedures and are referred for a catheter might have scarring that could affect catheter function. In some institutions, they might not even be offered PD therapy as an option. In this study, we found that a history of prior abdominal procedures did not increase the risk of PD catheter complications and should not dissuade patients from choosing PD or providers from recommending it.

The Association of Intra-Abdominal Adhesions with Peritoneal Dialysis Catheter-Related Complications.

BACKGROUND: This study investigated the association of intra-abdominal adhesions with the risk of peritoneal dialysis (PD) catheter complications. METHODS: Individuals undergoing laparoscopic PD catheter insertion were prospectively enrolled from eight centers in Canada and the United States. Patients were grouped based on the presence of adhesions observed during catheter insertion. The primary outcome was the composite of PD never starting, termination of PD, or the need for an invasive procedure caused by flow restriction or abdominal pain. RESULTS: Seven hundred and fifty-eight individuals were enrolled, of whom 201 (27%) had adhesions during laparoscopic PD catheter insertion. The risk of the primary outcome occurred in 35 (17%) in the adhesion group compared with 58 (10%) in the no adhesion group (adjusted HR, 1.64; 95% confidence interval [CI], 1.05 to 2.55) within 6 months of insertion. Lower abdominal or pelvic adhesions had an adjusted HR of 1.80 (95% CI, 1.09 to 2.98) compared with the no adhesion group. Invasive procedures were required in 26 (13%) and 47 (8%) of the adhesion and no adhesion groups, respectively (unadjusted HR, 1.60: 95% CI, 1.04 to 2.47) within 6 months of insertion. The adjusted odds ratio for adhesions for women was 1.65 (95% CI, 1.12 to 2.41), for body mass index per 5 kg/m 2 was 1.16 (95% CI, 1.003 to 1.34), and for prior abdominal surgery was 8.34 (95% CI, 5.5 to 12.34). Common abnormalities found during invasive procedures included PD catheter tip migration, occlusion of the lumen with fibrin, omental wrapping, adherence to the bowel, and the development of new adhesions. CONCLUSIONS: People with intra-abdominal adhesions undergoing PD catheter insertion were at higher risk for abdominal pain or flow restriction preventing PD from starting, PD termination, or requiring an invasive procedure. However, most patients, with or without adhesions, did not experience complications, and most complications did not lead to the termination of PD therapy.

Individuals heterozygous for ALG8 protein-truncating variants are at increased risk of a mild cystic kidney disease.

ALG8 protein-truncating variants (PTVs) have previously been described in patients with polycystic liver disease and in some cases cystic kidney disease. Given a lack of well-controlled studies, we determined whether individuals heterozygous for ALG8 PTVs are at increased risk of cystic kidney disease in a large, unselected health system-based observational cohort linked to electronic health records in Pennsylvania (Geisinger-Regeneron DiscovEHR MyCode study). Out of 174,172 patients, 236 were identified with ALG8 PTVs. Using ICD-based outcomes, patients with these variants were significantly at increased risk of having any kidney/liver cyst diagnosis (Odds Ratio 2.42, 95% confidence interval: 1.53-3.85), cystic kidney disease (3.03, 1.26-7.31), and nephrolithiasis (1.89, 1.96-2.97). To confirm this finding, blinded radiology review of computed tomography and magnetic resonance imaging studies was completed in a matched cohort of 52 thirty-plus year old ALG8 PTV heterozygotes and related non-heterozygotes. ALG8 PTV heterozygotes were significantly more likely to have cystic kidney disease, defined as four or more kidney cysts (57.7% vs. 7.7%), or bilateral kidney cysts (69.2% vs. 15.4%), but not one or more liver cyst (11.5% vs. 7.7%). In publicly available UK Biobank data, ALG8 PTV heterozygotes were at significantly increased risk of ICD code N28 (other disorders of kidney/ureter) (3.85% vs. 1.33%). ALG8 PTVs were not associated with chronic kidney disease or kidney failure in the MyCode study or the UK Biobank data. Thus, PTVs in ALG8 result in increased risk of a mild cystic kidney disease phenotype.

Exome Sequencing of a Clinical Population for Autosomal Dominant Polycystic Kidney Disease.

Importance: Most studies of autosomal dominant polycystic kidney disease (ADPKD) genetics have used kidney specialty cohorts, focusing on PKD1 and PKD2. These can lead to biased estimates of population prevalence of ADPKD-associated gene variants and their phenotypic expression. Objective: To determine the prevalence of ADPKD and contributions of PKD1, PKD2, and other genes related to cystic kidney disease in a large, unselected cohort. Design, Setting, and Participants: This retrospective observational study used an unselected health system-based cohort in central and northeast Pennsylvania with exome sequencing (enrolled from 2004 to 2020) and electronic health record data (up to October 2021). The genotype-first approach included the entire cohort and the phenotype-first approach focused on patients with ADPKD diagnosis codes, confirmed by chart and imaging review. Exposures: Loss-of-function (LOF) variants in PKD1, PKD2, and other genes associated with cystic kidney disease (ie, ALG8, ALG9, DNAJB11, GANAB, HNF1B, IFT140, SEC61B, PKHD1, PRKCSH, SEC63); likely pathogenic missense variants in PKD1 and PKD2. Main Outcomes and Measures: Genotype-first analysis: ADPKD diagnosis code (Q61.2, Q61.3, 753.13, 753.12); phenotype-first analysis: presence of a rare variant in PKD1, PKD2, or other genes associated with cystic kidney disease. Results: Of 174 172 patients (median age, 60 years; 60.6% female; 93% of European ancestry), 303 patients had ADPKD diagnosis codes, including 235 with sufficient chart review data for confirmation. In addition to PKD1 and PKD2, LOF variants in IFT140, GANAB, and HNF1B were associated with ADPKD diagnosis after correction for multiple comparisons. Among patients with LOF variants in PKD1, 66 of 68 (97%) had ADPKD; 43 of 43 patients (100%) with LOF variants in PKD2 had ADPKD. In contrast, only 24 of 77 patients (31.2%) with a PKD1 missense variant previously classified as "likely pathogenic" had ADPKD, suggesting misclassification or variable penetrance. Among patients with ADPKD diagnosis confirmed by chart review, 180 of 235 (76.6%) had a potential genetic cause, with the majority being rare variants in PKD1 (127 patients) or PKD2 (34 patients); 19 of 235 (8.1%) had variants in other genes associated with cystic kidney disease. Of these 235 patients with confirmed ADPKD, 150 (63.8%) had a family history of ADPKD. The yield for a genetic determinant of ADPKD was higher for those with a family history of ADPKD compared with those without family history (91.3% [137/150] vs 50.6% [43/85]; difference, 40.7% [95% CI, 29.2%-52.3%]; P < .001). Previously unreported PKD1, PKD2, and GANAB variants were identified with pedigree data suggesting pathogenicity, and several PKD1 missense variants previously reported as likely pathogenic appeared to be benign. Conclusions and Relevance: This study demonstrates substantial genetic and phenotypic variability in ADPKD among patients within a regional health system in the US.

A Simpler Machine Learning Model for Acute Kidney Injury Risk Stratification in Hospitalized Patients.

Background: Hospitalization-associated acute kidney injury (AKI), affecting one-in-five inpatients, is associated with increased mortality and major adverse cardiac/kidney endpoints. Early AKI risk stratification may enable closer monitoring and prevention. Given the complexity and resource utilization of existing machine learning models, we aimed to develop a simpler prediction model. Methods: Models were trained and validated to predict risk of AKI using electronic health record (EHR) data available at 24 h of inpatient admission. Input variables included demographics, laboratory values, medications, and comorbidities. Missing values were imputed using multiple imputation by chained equations. Results: 26,410 of 209,300 (12.6%) inpatients developed AKI during admission between 13 July 2012 and 11 July 2018. The area under the receiver operating characteristic curve (AUROC) was 0.86 for Random Forest and 0.85 for LASSO. Based on Youden's Index, a probability cutoff of >0.15 provided sensitivity and specificity of 0.80 and 0.79, respectively. AKI risk could be successfully predicted in 91% patients who required dialysis. The model predicted AKI an average of 2.3 days before it developed. Conclusions: The proposed simpler machine learning model utilizing data available at 24 h of admission is promising for early AKI risk stratification. It requires external validation and evaluation of effects of risk prediction on clinician behavior and patient outcomes.

Effect of age and rural residency on perceptions about SARS-CoV-2 pandemic and vaccination in kidney transplant recipients.

BACKGROUND: Transplant patients have poor outcomes in coronavirus-disease 2019 (COVID-19). The pandemic's effects on rural patients' overall care experience, attitudes to telemedicine, and vaccination are poorly understood. METHODS: We administered a cross-sectional survey to adult kidney transplant recipients in central Pennsylvania across four clinical sites between March 29, 2021 and June 2, 2021. We assessed the pandemic's impact on care access, telemedicine experience, attitudes toward preventive measures, vaccination, and variation by sociodemographic variables. RESULTS: Survey completion rate was 51% (303/594). Of these, 52.8% were rural residents. The most common impact was use of telemedicine (79.2%). Predominant barriers to telemedicine were lack of video devices (10.9%), perceived complexity (5.6%), and technical issues (5.3%). On a 0-10 Likert scale, the mean positive impression for telemedicine was 7.7; lower for patients with telephone-only versus video visits (7.0 vs. 8.2; p < .001), and age ≥60 years (7.4 vs. 8.1; p = .01) on univariate analyses. Time/travel savings were commonly identified (115/241, 47.7%) best parts of telemedicine and lack of personal connection (70/166, 42.2%) the worst. Only 68.9% had received any dose of COVID vaccination. The vaccinated group members were older (58.4 vs. 53.5 years; p = .007), and less likely rural (47.8% vs. 65.2%; p = .005). Common themes associated with vaccine hesitancy included concerns about safety (27/59, 46%), perceived lack of data (19/59, 32%), and distrust (17/59, 29%). At least one misconception about the vaccines or COVID-19 was quoted by 29% of vaccine-hesitant patients. CONCLUSIONS: Among respondents, the pandemic significantly impacted healthcare experience, especially in older patients in underserved communities. COVID-19 vaccination rate was relatively low, driven by misconceptions and lack of trust.

Vignette-Based Reflections to Inform Genetic Testing Policies in Living Kidney Donors.

Family history of kidney disease increases risk of end-stage kidney disease (ESKD) in donors. Pre-donation genetic testing is recommended in evaluation guidelines and regulatory policy. Collaborating across several institutions, we describe cases to illustrate the utility as well as practical issues in incorporating genetic testing in transplant protocols. Case 1 is from 2009, before pervasive genetic testing. A healthy 27-year-old Caucasian male had an uneventful donor evaluation for his mother, who had early onset ESKD of unclear cause. He participated in paired-exchange kidney donation, but developed progressive kidney disease and gout over the next 10 years. A uromodulin gene mutation (NM_003361.3(UMOD):c.377 G>A p.C126Y) was detected and kidney biopsy showed tubulointerstitial kidney disease. The patient subsequently required kidney transplantation himself. Case 2 was a 36-year-old African American female who had an uneventful kidney donor evaluation. She underwent gene panel-based testing to rule out ApolipoproteinL1 risk variants, for which was negative. Incidentally, a sickle-cell trait (NM_000518.5(HBB):c.20A>T p.Glu7Val) was noted, and she was declined for kidney donation. This led to significant patient anguish. Case 3 was a 26-year-old Caucasian female who underwent panel-based testing because the potential recipient, her cousin, carried a variant of uncertain significance in the hepatocyte nuclear factor-1-ß (HNF1B) gene. While the potential donor did not harbor this variant, she was found to have a likely pathogenic variant in complement factor I (NM_000204.4(CFI):c.1311dup:p.Asp438Argfs*8), precluding kidney donation. Our cases emphasize that while genetic testing can be invaluable in donor evaluation, transplant centers should utilize detailed informed consent, develop care pathways for secondary genetic findings, and share experience to develop best practices around genetic testing in donors.

Post-Discharge Mortality and Rehospitalization among Participants in a Comprehensive Acute Kidney Injury Rehabilitation Program.

Background: Hospitalization-associated AKI is common and is associated with markedly increased mortality and morbidity. This prospective cohort study examined the feasibility and association of an AKI rehabilitation program with postdischarge outcomes. Methods: Adult patients hospitalized from September 1, 2019 to February 29, 2020 in a large health system in Pennsylvania with stage 2-3 AKI who were alive and not on dialysis or hospice at discharge were evaluated for enrollment. The intervention included patient education, case manager services, and expedited nephrology appointments starting within 1-3 weeks of discharge. We examined the association between AKI rehabilitation program participation and risks of rehospitalization or mortality in logistic regression analyses adjusting for comorbidities, discharge disposition, and sociodemographic and kidney parameters. Sensitivity analysis was performed using propensity score matching. Results: Among the high-risk patients with AKI who were evaluated, 77 of 183 were suitable for inclusion. Out of these, 52 (68%) patients were enrolled and compared with 400 contemporary, nonparticipant survivors of stage 2/3 AKI. Crude postdischarge rates of rehospitalization or death were lower for participants versus nonparticipants at 30 days (15% versus 34%; P=0.01) and at 90 days (31% versus 51%; P=0.01). After multivariable adjustment, participation in the AKI rehabilitation program was associated with lower risk of rehospitalization or mortality at 30 days (OR, 0.41; 95% CI, 0.16 to 0.93), with similar findings at 90 days (OR, 0.52; 95% CI, 0.25 to 1.05). Due to small sample size, propensity-matched analyses were limited. The participants' rehospitalization or mortality was numerically lower but not statistically significant at 30 days (18% versus 31%; P=0.22) or at 90 days (47% versus 58%; P=0.4). Conclusions: The AKI rehabilitation program was feasible and potentially associated with improved 30-day rehospitalization or mortality. Our interventions present a roadmap to improve enrollment in future randomized trials.

Successful kidney transplantation from a hepatitis B surface antigen-positive donor to an antigen-negative recipient using a novel vaccination regimen.

Transplanting a kidney from a hepatitis B surface antigen (HBsAg)-positive donor to an HBsAg-negative recipient who is naturally immune has been successful in countries endemic for hepatitis B virus (HBV). However, in most of these cases, the donors were deceased. We present a report of a successful HBsAg-discordant kidney transplantation in the United States; in this case, a living donor kidney was transplanted to a vaccinated recipient. The wife of a 58-year-old HBsAg-negative man volunteered to donate a kidney to her husband. She had chronic hepatitis B but undetectable HBV DNA. She tested positive for HBsAg and antibody to hepatitis B core antigen, but hepatitis B e antigen was undetectable. The recipient failed to develop an antibody response to 3 doses of intramuscular recombinant HBV vaccine given in consecutive months. Immunity was induced by using biweekly intradermal vaccine. However, antibody titer tapered to <10 mIU/mL over 14 months. An intramuscular booster vaccine resulted in a prolonged anamnestic response, allowing for successful living unrelated donor transplantation. During the 10 years since transplantation, the patient has continued to have normal liver function, with undetectable HBsAg and HBV DNA. Antibody titers to HBsAg slowly decreased to 5.8 mIU/mL during the 10 years. Transplant function has been well preserved. This approach to inducing long-term immunity for transplantation merits further study in the United States.