Peritoneal Dialysis Technique Survival: A Cohort Study.

RATIONALE & OBJECTIVE: Reasons for transfer from peritoneal dialysis (PD) to hemodialysis (HD) remain incompletely understood. Among incident and prevalent patients receiving PD, we evaluated the association between prior treatment with HD and PD technique survival. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults who initiated PD at a Dialysis Clinic, Inc. (DCI) outpatient facility between January 1, 2010 and September 30, 2019. EXPOSURES: The primary exposure of interest was timing of PD start, categorized as PD-first, PD-early, or PD-late. Other covariates included demographics, clinical characteristics, and routine laboratory results. OUTCOMES: Modality switch from PD to HD sustained for more than 90 days. ANALYTICAL APPROACH: Multivariable Fine-Gray models with competing risks and time-varying covariates, stratified at 9 months to account for lack of proportionality. RESULTS: Among 5224 patients who initiated PD at a DCI facility, 3174 initiated dialysis with PD ("PD-first"), 942 transitioned from HD to PD within 90 days ("PD-early"), and 1108 transitioned beyond 90 days ("PD-late"); 1472 (28%) subsequently transferred from PD to HD. PD-early and PD-late patients had higher risk of transfer to HD as compared to PD-first patients [adjusted hazard ratio (aHR) 1.51 (95% CI: 1.17-1.96) and 2.41 (1.94-3.00), respectively, in the first 9 months and aHR 1.16 (0.99-1.35) and 1.43 (1.24-1.65), respectively, after 9 months]. More peritonitis episodes, fewer home visits, lower serum albumin, lower residual kidney function, and lower peritoneal clearance calculated with weekly Kt/V were additional risk factors for PD-to-HD transfer. LIMITATIONS: Missing data on dialysis adequacy and residual kidney function, confounded by short PD technique survival. CONCLUSIONS: Initiating dialysis with PD is associated with greater PD technique survival, though many of those who initiate PD late in their dialysis course still experience substantial time on PD. Peritonitis, lower serum albumin, and lower Kt/V are risk factors for PD-to-HD transfer that may be amenable to intervention.

Dialysate Sodium Lowering in Maintenance Hemodialysis A Randomized Clinical Trial.

INTRODUCTION: Lowering dialysate sodium may improve volume and blood pressure control in maintenance hemodialysis patients. METHODS: We randomized 42 participants 2:1 to dialysate sodium 135 vs. 138 mEq/L for 6 months. This was followed by a 12 week extension in which sodium was increased to 140 mEq/L in low arm participants. The primary outcome was intradialytic hypotension (IDH). Secondary outcomes included dialysis disequilibrium symptoms, ER visits/hospitalizations, interdialytic weight gain, blood pressure (BP). Longitudinal changes across arms were analyzed using linear mixed regression. RESULTS: Treatment to dialysate sodium 135 vs. 138 mEq/L was not associated with a difference in a change in the rate of IDH (mean change (95%CI) 2.8 (0.8,9.5) vs. 2.7 (1.1, 6.2) events per 100 treatments per month; ratio of slopes 0.96(0.26,3.61) or ER visits/hospitalizations (7.3 (2.3, 12.4) vs. 6.7 (2.9, 10.6) events per 100 patient months; difference 0.6(-6.9,5.8). Symptom score was unchanged in the 135 mEq/L arm (0.7 (-1.4,2.7) and decreased in the 138 mEq/l arm (5.0,8.5,2.0); difference 6.0 (2.1,9.8)). Interdialytic weight gain declined in the 135 mEq/L arm and was unchanged in the 138 mEq/L arm,(-0.3(-0.5,0.0) vs. 0.3 (0.0, 0.6) kg over 6 months; difference (-0.6 (-0.1,-1.0) kg). In the extension phase, raising dialysate sodium from 135 to 140 mEq/L was associated with an increase in interdialytic weight gain (0.2 (0.1, 0.3) kg), predialysis BP (7.0 (4.8, 9.2)/ 3.9 (2.6, 5.1) mm Hg) and a reduction in IDH [OR 0.66 (0.45, 0.97)]. CONCLUSION: Use of a dialysate sodium of 135 as compared with 138 mEq/L was associated with a small reduction in interdialytic weight gain without impact on IDH or predialysis BP, but with an increase in symptoms. Raising dialysate sodium from 135 to 140mEq/L was associated with a reduction in IDH, a small increase in interdialytic weight gain and a marked increase in predialysis BP.

Serial SARS-CoV-2 Antibody Titers in Vaccinated Dialysis Patients: Prevalence of Unrecognized Infection and Duration of Seroresponse.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination. Exposures: Two and 3 doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months. Limitations: The assays used had upper limits. Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability. Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection.

Association of Longitudinal Urinary Metabolic Biomarkers With ADPKD Severity and Response to Metformin in TAME-PKD Clinical Trial Participants.

Introduction: Dysregulated cellular metabolism contributes to autosomal dominant polycystic kidney disease (ADPKD) pathogenesis. The Trial of Administration of Metformin in Polycystic Kidney Disease (TAME-PKD) tested the effects of metformin treatment over 2 years in adult ADPKD patients with mild-moderate disease severity. Metformin was found to be safe and tolerable with an insignificant trend toward reduced estimated glomerular filtration rate (eGFR) decline compared to placebo. Here we tested whether targeted urinary metabolic biomarkers measured in TAME-PKD participants correlated with disease progression, severity, and metformin treatment in cross-sectional and longitudinal analyses. Methods: Concentrations of total protein, targeted metabolites (lactate, pyruvate, and succinate), and glycolytic enzymes (pyruvate kinase-M2, lactate dehydrogenase-A, and pyruvate dehydrogenase kinase-1) were measured and normalized by creatinine or osmolality in urine specimens and compared with height-adjusted total kidney volume (htTKV) and eGFR at the different study timepoints. Results: In cross-sectional analyses utilizing placebo group data, urinary succinate normalized by creatinine negatively correlated with ln (htTKV), whereas protein excretion strongly positively correlated with ln (htTKV), and negatively correlated with eGFR. Significant time-varying negative associations occurred with eGFR and the lactate/pyruvate ratio and with urine protein normalized by osmolality, indicating correlations of these biomarkers with disease progression. In secondary analyses, urinary pyruvate normalized by osmolality was preserved in metformin-treated participants but declined in placebo over the 2-year study period with a significant between-arm difference, suggesting time-dependent urinary pyruvate changes may serve as a discriminator for metformin treatment effects in this study population. Conclusion: Proteinuria with enhanced glycolytic and reduced oxidative metabolic markers generally correlated with disease severity and risk of progression in the TAME-PKD study population.

Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse.

Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposures: Two and three doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: "Undiagnosed" SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥ 100 BAU/mL, not associated with receipt of vaccine or "diagnosed" SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥ 500 BAU/mL in the first month, with 23% maintaining a titer ≥ 500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥ 500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥ 500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.

SARS-CoV-2 Vaccine Effectiveness and Breakthrough Infections Among Patients Receiving Maintenance Dialysis.

RATIONALE & OBJECTIVE: SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19-related hospitalization or death in the dialysis population are unknown. STUDY DESIGN: Retrospective, observational study. SETTING & PARTICIPANTS: Adult patients without COVID-19 history receiving maintenance dialysis through a national dialysis provider and treated between February 1 and December 18, 2021, with follow-up through January 17, 2022. PREDICTOR: SARS-CoV-2 vaccination status. OUTCOMES: All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19. ANALYTICAL APPROACH: Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness. RESULTS: Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated, and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, and 891 (73%) occurred during the Delta variant-dominant period. Between the pre-Delta period and the Delta-dominant period, vaccine effectiveness rates against a severe COVID-19-related event (hospitalization or death) were 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike immunoglobulin G (IgG) assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and higher adjusted hazard ratios for infection and COVID-19-related hospitalization or death. LIMITATIONS: Observational design, residual biases, and confounding may exist. CONCLUSIONS: Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, a low anti-spike IgG level is associated with worse COVID-19-related outcomes.

Seroresponse to Inactivated and Recombinant Influenza Vaccines Among Maintenance Hemodialysis Patients.

RATIONALE & OBJECTIVE: High-dose influenza vaccine provides better protection against influenza infection in older adults than standard-dose vaccine. We compared vaccine seroresponse among hemodialysis patients over a period of 4 months after administration of high-dose trivalent inactivated (HD-IIV3), standard-dose quadrivalent inactivated (SD-IIV4), or quadrivalent recombinant quadrivalent (RIV4) influenza vaccine. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: Patients at 4 hemodialysis clinics who received influenza vaccine. EXPOSURE: Type of influenza vaccine. OUTCOME: Hemagglutination inhibition (HI) titers were measured at baseline and at 1, 2, 3, and 4 months after vaccination. The primary outcome was seroprotection rates at HI titers of at least 1:40 and at least 1:160 (antibody levels providing protection from infection in approximately 50% and 95% of immunocompetent individuals, respectively) at 1, 2, 3, and 4 months after vaccination. ANALYTICAL APPROACH: We calculated geometric mean titer as well as seroprotection and seroconversion rates. Adjusted generalized linear models with additional trend analyses were performed to evaluate the association between vaccine type and outcomes. RESULTS: 254 hemodialysis patients were vaccinated against influenza with HD-IIV3 (n = 141), SD-IIV4 (n = 36), or RIV4 (n = 77). A robust initial seroresponse to influenza A strains was observed after all 3 vaccines. Geometric mean titer and seroprotection (HI titer ≥1:160) rates against influenza A strains were higher and more sustained with HD-IIV3 than SD-IIV4 or RIV4. More than 80% of patients vaccinated with HD-IIV3 were seroprotected (HI titer ≥1:160) at month 4 (P < 0.001), whereas, among patients vaccinated with SD-IIV4 or RIV4, seroprotection rates were similar to those at baseline. Seroprotection rates were lower against B strains for all vaccines. LIMITATIONS: Because of the use of observational data, bias from unmeasured confounders may exist. Some age subgroups were small in number. Clinical outcome data were not available. CONCLUSIONS: Hemodialysis patients exhibited high seroprotection rates after all 3 influenza vaccines. The seroresponse waned more slowly with HD-IIV3 compared with SD-IIV4 and RIV4 vaccines.

Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG <1 Index or development of COVID-19). Cox regression adjusted for additional clinical characteristics. RESULTS: Among 1870 patients receiving maintenance dialysis, 1569 had no prior COVID-19. Patients without prior COVID-19 had declining titers over time. Among 443 recipients of BNT162b2 (Pfizer), median (interquartile range) anti-spike IgG titer declined from ≥20 (5.89 to ≥20) in month 1 after full vaccination to 1.96 (0.60-5.88) by month 6. Among 778 recipients of mRNA-1273 (Moderna), anti-spike IgG titer declined from ≥20 (interquartile range, ≥20 to ≥20) in month 1 to 7.99 (2.61 to ≥20) by month 6. The 348 recipients of Ad26.COV2.S (Janssen) had a lower titer response than recipients of an mRNA vaccine over all time periods. In time-to-event analyses, recipients of Ad26.COV2.S and mRNA-1273 had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first 2 months after full vaccination was associated with durability of the anti-spike IgG seroresponse; patients with anti-spike IgG titer 1-19.99 had a shorter time to loss of seroresponse compared with patients with anti-spike IgG titer ≥20 (hazard ratio, 15.5; 95% confidence interval, 11.7 to 20.7). CONCLUSIONS: Among patients receiving maintenance dialysis, vaccine-induced seroresponse wanes over time across vaccine types. Early titers after full vaccination are associated with the durability of seroresponse.

Pain and Obesity in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Analysis of the Halt Progression of Polycystic Kidney Disease (HALT-PKD) Studies.

RATIONALE & OBJECTIVE: Pain is a frequent complication of autosomal dominant polycystic kidney disease (ADPKD) and includes back and abdominal pain. We hypothesized that in adults with early- and late-stage ADPKD, overweight and obesity are independently associated with greater self-reported back, abdominal, and radicular pain at baseline and that weight loss would be associated with decreased pain over a follow-up period. STUDY DESIGN: Post hoc analysis of pooled data from 2 randomized trials. SETTING & PARTICIPANTS: Participants in the HALT-PKD study A or B. 867 individuals were included in a cross-sectional analysis. 4,248 observations from 871 participants were included in a longitudinal analysis. PREDICTOR: Overweight and obesity (cross-sectional); annual change in weight as a time-varying predictor (longitudinal). OUTCOME: Pain (Likert-scale responses; cross-sectional); annual change in pain (binary outcome of worsening pain or not worsening; longitudinal). ANALYTICAL APPROACH: Multivariable ordinal logistic regression (cross-sectional); generalized estimating equation analysis (longitudinal). RESULTS: Participants were aged 42±10 years and baseline estimated glomerular filtration rate was 71±26 mL/min/1.73 m2. Back, abdominal, and radicular pain were reported more frequently in individuals with increasing body mass index category (all P < 0.05 for trend). After multivariable adjustment, obesity was associated with increased odds of greater back and radicular pain, but not abdominal pain. Associations remained similar after further adjustment for baseline height-adjusted kidney and liver volume (study A only, n = 457); back pain: OR, 1.88 (95% CI, 1.15-3.08); and radicular pain: OR, 2.92 (95% CI, 1.45-5.91). Longitudinally (median follow-up, 5 years), weight loss (annual decrease in weight ≥ 4%) was associated with decreased adjusted odds of worsening back pain (OR, 0.87 [95% CI, 0.76-0.99]) compared with the reference group (stable weight). LIMITATIONS: Post hoc, associative analysis. CONCLUSIONS: In early- and late-stage ADPKD, obesity was associated with greater back and radicular pain independent of total kidney/liver volume. Mild weight loss was associated with favorable effects on back pain.

Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants.

BACKGROUND: Recent work suggests that dysregulated cellular metabolism may play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The TAME-PKD clinical trial is testing the safety, tolerability, and efficacy of metformin, a regulator of cell metabolism, in patients with ADPKD. This study investigates the cross-sectional association of urinary metabolic biomarkers with ADPKD severity among TAME-PKD trial participants at baseline. METHODS: Concentrations of total protein, targeted metabolites (lactate, pyruvate, succinate, and cAMP), and key glycolytic enzymes (pyruvate kinase M2 [PKM2], lactate dehydrogenase A [LDHA], and pyruvate dehydrogenase kinase 1 [PDK1]) were measured by ELISA, enzymatic assays, and immunoblotting in baseline urine specimens of 95 TAME-PKD participants. These analytes, normalized by urinary creatinine or osmolality to estimate excretion, were correlated with patients' baseline height-adjusted total kidney volumes (htTKVs) by MRI and eGFR. Additional analyses were performed, adjusting for participants' age and sex, using multivariable linear regression. RESULTS: Greater htTKV correlated with lower eGFR (r=-0.39; P=0.0001). Urinary protein excretion modestly correlated with eGFR (negatively) and htTKV (positively). Urinary cAMP normalized to creatinine positively correlated with eGFR. Among glycolytic enzymes, PKM2 and LDHA excretion positively correlated with htTKV, whereas PKM2 excretion negatively correlated with eGFR. These associations remained significant after adjustments for age and sex. Moreover, in adjusted models, succinate excretion was positively associated with eGFR, and protein excretion was more strongly associated with both eGFR and htTKV in patients <43 years old. CONCLUSIONS: Proteinuria correlated with ADPKD severity, and urinary excretion of PKM2 and LDHA correlated with ADPKD severity at baseline in the TAME-PKD study population. These findings are the first to provide evidence in human urine samples that upregulated glycolytic flux is a feature of ADPKD severity. Future analysis may reveal if metformin treatment affects both disease progression and the various urinary metabolic biomarkers in patients throughout the study.

Comparison of Dialysis Unit and Home Blood Pressures: An Observational Cohort Study.

RATIONALE & OBJECTIVE: Prior studies of patients receiving maintenance hemodialysis have shown that, on average, blood pressure (BP) measured predialysis is higher than BP measured at home. We hypothesized that a subset of hemodialysis patients has BP that is higher when measured at home than when measured predialysis and this subgroup of patients has a higher prevalence of left ventricular hypertrophy. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 97 hypertensive hemodialysis patients enrolled in the Blood Pressure in Dialysis Study (BID), a randomized trial of comparing target predialysis BP ≤140/90 to 155-165/90 mm Hg. EXPOSURE: Differences between predialysis and next-day home systolic BP measured ≥6 times over 1 year. OUTCOME: Left ventricular mass index (LVMI) by cardiac magnetic resonance imaging. ANALYTICAL APPROACH: A hierarchical clustering analysis divided patients into 3 clusters based on the average and variability of differences in systolic predialysis and home BP. Clusters were compared with respect to clinical factors and LVMI. RESULTS: Mean differences between predialysis and home systolic BP were 19.1 (95% CI, 17.0 to 21.1) mm Hg for cluster 1 ("home lower"), 3.7 (95% CI, 1.6 to 5.8) mm Hg for cluster 2 ("home and predialysis similar"), and -9.7 (95% CI, -12.0 to -7.4) mm Hg for cluster 3 ("home higher"). Systolic BP declined during dialysis in clusters 1 and 2 but increased in cluster 3. Interdialytic weight gains did not differ. After adjusting for sex and treatment arm, LVMI was higher in cluster 3 than in clusters 1 and 2: differences in means of 10.6 ± 4.96 (SE) g/m2 (P = 0.04) and 12.0 ± 5.08 g/m2 (P = 0.02), respectively. LIMITATIONS: Limited statistical power. CONCLUSIONS: Nearly one-third of participants had home BPs higher than predialysis BPs. These patients had LVMI higher than those with similar or lower BPs at home, indicating that their BP may have been undertreated.

Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.

COVID-19 Among US Dialysis Patients: Risk Factors and Outcomes From a National Dialysis Provider.

RATIONALE & OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 in this population. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients in clinics of a midsize national dialysis provider that had at least 1 patient who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from February to June 2020. PREDICTORS: Demographics, dialysis characteristics, residence in a congregated setting, comorbid conditions, measurements of frailty, and use of selected medications. OUTCOMES: COVID-19, defined as having a positive SARS-CoV-2 test result, and all-cause mortality among those with COVID-19. ANALYTICAL APPROACH: Logistic regression analyses conducted to identify clinical characteristics associated with COVID-19 and risk factors associated with mortality among patients following COVID-19. RESULTS: 438 of 7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 were 17-fold higher for those residing in a congregated setting (odds ratio [OR], 17.10 [95% CI, 13.51-21.54]). Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. LIMITATIONS: No distinction was detected between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. CONCLUSIONS: COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

Risks and Options With Gadolinium-Based Contrast Agents in Patients With CKD: A Review.

Gadolinium-based contrast agents (GBCAs) improve the diagnostic capabilities of magnetic resonance imaging. Although initially believed to be without major adverse effects, GBCA use in patients with severe chronic kidney disease (CKD) was demonstrated to cause nephrogenic systemic fibrosis (NSF). Restrictive policies of GBCA use in CKD and selective use of GBCAs that bind free gadolinium more strongly have resulted in the virtual elimination of NSF cases. Contemporary studies of the use of GBCAs with high binding affinity for free gadolinium in severe CKD demonstrate an absence of NSF. Despite these observations and the limitations of contemporary studies, physicians remain concerned about GBCA use in severe CKD. Concerns of GBCA use in severe CKD are magnified by recent observations demonstrating gadolinium deposition in brain and a possible systemic syndrome attributed to GBCAs. Radiologic advances have resulted in several new imaging modalities that can be used in the severe CKD population and that do not require GBCA administration. In this article, we critically review GBCA use in patients with severe CKD and provide recommendations regarding GBCA use in this population.