Functional outcomes of sleep predict cardiovascular intermediary outcomes and all-cause mortality in patients on incident hemodialysis.

STUDY OBJECTIVES: Patients with end-stage kidney disease commonly experience sleep disturbances. Sleep disturbance has been inconsistently associated with mortality risk in patients on hemodialysis, but the burden of symptoms from sleep disturbances has emerged as a marker that may shed light on these discrepancies and guide treatment decisions. This study examines whether functional outcomes of sleep are associated with increased risk of intermediary cardiovascular outcomes or mortality among adults initiating hemodialysis. METHODS: In 228 participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which assesses functional outcomes of daytime sleepiness, was administered within 6 months of enrollment. Intermediary cardiovascular outcomes included QT correction (ms), heart rate variance (ms2), left ventricular mass index (g/m2), and left ventricular hypertrophy. The association of FOSQ-10 score with all-cause mortality was examined using proportional hazards regression. RESULTS: Mean age was 55 years, and median body mass index was 28 kg/m2 (interquartile range, 24, 33), with 70% of patients being African Americans. Median FOSQ-10 score was 19.7 (interquartile range, 17.1, 20.0). A 10% lower FOSQ-10 score was associated with increased mortality risk (hazard ratio, 1.09; 95% confidence interval, 1.01-1.18). Lower FOSQ-10 scores were associated with longer QT correction duration and lower heart rate variance but not left ventricular mass index or left ventricular mass index. CONCLUSIONS: In adults initiating dialysis, sleep-related functional impairment is common and is associated with intermediary cardiovascular disease measures and increased mortality risk. Future studies should assess the impact of screening for sleep disturbances in patients with end-stage kidney disease to identify individuals at increased risk for cardiovascular complications and death. CITATION: Fitzpatrick J, Kerns ES, Kim ED, et al. Functional outcomes of sleep predict cardiovascular intermediary outcomes and all-cause mortality in patients on incident hemodialysis. J Clin Sleep Med. 2021;17(8):1707-1715.

Prevalence and Risk Factors for CKD in the General Population of Southwestern Nicaragua.

BACKGROUND: Studies have described Mesoamerican nephropathy among agricultural workers of El Salvador and northwestern Nicaragua. Data on prevalence and risk factors for CKD beyond agricultural workers and in other regions in Nicaragua are sparse. METHODS: We recruited participants from 32 randomly selected communities in the Department of Rivas's ten municipalities in two phases. In phase 1, we screened participants using a field-based capillary creatinine measuring system and collected self-reported information on lifestyle and occupational, exposure, and health histories. Two years later, in phase 2, we enrolled 222 new participants, performing serum creatinine testing in these participants and confirmatory serum creatinine testing in phase 1 participants. RESULTS: We enrolled 1242 of 1397 adults (89%) living in 533 households (median age 41 years; 43% male). We confirmed CKD (eGFR<60 ml/min per 1.73 m2) in 53 of 1227 (4.3%) evaluable participants. In multivariable testing, risk factors for prevalent CKD included age (odds ratio [OR], 1.92; 95% confidence interval [95% CI], 1.89 to 1.96) and self-reported history of hypertension (OR, 1.95; 95% CI, 1.04 to 3.64), diabetes (OR, 2.88; 95% CI, 1.40 to 5.93), or current or past work in the sugarcane industry (OR 2.92; 95% CI, 1.36 to 6.27). CONCLUSIONS: Adjusted CKD prevalence was about 5% with repeat confirmatory testing in southwest Nicaragua, lower than in the northwest region. Risk factors included diabetes, hypertension, and current or prior work in the sugarcane industry but not in other forms of agricultural work. Formal CKD surveillance programs in Nicaragua are needed to assess the overall burden of CKD nationally, with a focus on agricultural workers.

Urgent-start peritoneal dialysis results in fewer procedures than hemodialysis.

BACKGROUND: Peritoneal dialysis (PD) is an underutilized modality for hospitalized patients with an urgent need to start renal replacement therapy in the USA. Most patients begin hemodialysis (HD) with a tunneled central venous catheter (CVC). METHODS: We examined the long-term burden of dialysis modality-related access procedures with urgent-start PD and urgent-start HD in a retrospective cohort of 73 adults. The number of access-related (mechanical and infection-related) procedures for each modality was compared in the first 30 days and cumulatively through the duration of follow-up. RESULTS: Fifty patients underwent CVC placement for HD and 23 patients underwent PD catheter placement for urgent-start dialysis. Patients were followed on average >1 year. The PD group was significantly younger, with less diabetes, with a higher pre-dialysis serum creatinine and more likely to have a planned dialysis access. The mean number of access-related procedures per patient in the two groups was not different at 30 days; however, when compared over the duration of follow-up, the number of access-related procedures was significantly higher in the HD group compared with the PD group (4.6 ± 3.9 versus 0.61 ± 0.84, P < 0.0001). This difference persisted when standardized to procedures per patient-month (0.37 ± 0.57 versus 0.081 ± 0.18, P = 0.019). Infection-related procedures were similar between groups. Findings were the same even after case-matching was performed for age and diabetes mellitus with 18 patients in each group. CONCLUSIONS: Urgent-start PD results in fewer invasive access procedures compared with urgent-start HD long term, and should be considered for urgent-start dialysis.

Obstructive Sleep Apnea Increases Sudden Cardiac Death in Incident Hemodialysis Patients.

BACKGROUND: Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown. METHODS: In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors. RESULTS: Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36-9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12-9.57]) and multiple cardiovascular risk factors. CONCLUSIONS: Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD.

Correction to: Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study.

The original version of this article unfortunately contained a mistake in the article title. The correct article title is "Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study".

Residual Renal Function and Obstructive Sleep Apnea in Peritoneal Dialysis: A Pilot Study.

PURPOSE: Obstructive sleep apnea is common in patients with end-stage renal disease, and there is increasing evidence that clinical factors specific to end-stage renal disease contribute pathophysiologically to obstructive sleep apnea. It is not known whether circumstances specific to dialysis modality, in this case peritoneal dialysis, affect obstructive sleep apnea. Our study aimed to investigate the prevalence of obstructive sleep apnea in the peritoneal dialysis population and the relevance of dialysis-specific measures and kidney function in assessing this bidirectional relationship. METHODS: Participants with end-stage renal disease who were treated with nocturnal automated peritoneal dialysis for at least 3 months were recruited from a hospital-based dialysis center. Laboratory measures of dialysis adequacy, peritoneal membrane transporter status, and residual renal function were gathered by chart review. Patients participated in a home sleep apnea test using a level III sleep apnea monitor. RESULTS: Of fifteen participants recruited, 33% had obstructive sleep apnea diagnosed by apnea-hypopnea index ≥ 5 events per hour of sleep. Renal creatinine clearance based upon 24-h urine collection was negatively correlated with apnea-hypopnea index (ρ = - 0.63, p = 0.012). There were no significant associations between anthropometric measures, intra-abdominal dwell volume, or peritoneal membrane transporter status and obstructive sleep apnea measures. CONCLUSIONS: The prevalence of obstructive sleep apnea and sleep disturbances is high in participants receiving peritoneal dialysis. Elevated apnea-hypopnea index is associated with lower residual renal function, whereas dialysis-specific measures such as intra-abdominal dwell volume and peritoneal membrane transporter status do not correlate with severity of obstructive sleep apnea.

Successful use of rituximab in glomerular basement membrane nephritis associated with HIV interstitial nephritis secondary to Castleman disease
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We report a case of glomerular basement membrane crescentic glomerulonephritis and multicentric Castleman disease-associated interstitial nephritis in a patient with human immunodeficiency virus (HIV) infection. The patient received corticosteroids, cyclophosphamide, and plasmapheresis, and within 3 weeks, there was worsening thrombocytopenia, anemia, and renal function requiring initiation of hemodialysis. He then received 8 weekly doses of rituximab, and there was steady improvement in renal function, such that he stopped dialysis within 6 weeks and has remained in disease remission at 1-year follow-up. This is the first case report of acute kidney injury caused by both antiglomerular basement membrane disease and multicentric Castleman disease, with a favorable response to rituximab.
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The Rivas Cohort Study: design and baseline characteristics of a Nicaraguan cohort.

BACKGROUND: A lack of advanced healthcare information systems and validated scientific cohorts in Nicaragua makes it difficult to estimate disease prevalences and other public health statistics. Although there is concern of an "epidemic" of chronic kidney disease (CKD) in this country, statistics regarding its magnitude are derived from only a small number of non-representative studies. Budgetary constraints and the logistical problems of maintaining a study cohort make longitudinal studies difficult. The Rivas Cohort was created to measure disease burden of CKD and other public health priorities in the Department of Rivas, Nicaragua. Using primarily volunteer research students and technologic innovation including GPS, digital photography and point of care biochemical analysis, the ability to establish a longitudinal chronic disease cohort is demonstrated. METHODS: Subjects were recruited from consecutive adjacent households in thirty-two randomly selected communities in the ten municipalities that comprise the Department of Rivas in southern Pacific coastal Nicaragua. The study was conducted in two phases. In the first phase, subjects were enrolled into the cohort and consented for future re-contact. In Phase II, conducted two years later, attempts were made to re-contact 400 of these subjects for additional data collection. Demographic, lifestyle, occupational, exposure and health data was collected for both phases of the study. Blood and urine testing and height, weight and blood pressure measurements were also performed. GPS coordinates of homes were recorded and maps of remote communities created. RESULTS: Of 1397 adults living in 533 households approached for participation a total of 1242 (89 %) were enrolled in the cohort. The median age is 41 years and 43 % are male, demographics in agreement with Nicaraguan census data for the Department of Rivas. During Phase II we attempted to re-contact 400 subjects for a follow-up study of CKD. It was possible to re-contact 84 % of these participants and of those re-contacted 95 % agreed to participate in the follow-up study. Of subjects that were not successfully re-contacted the majority had either moved (32) or were not at home (22) at the time of the study team visits. CONCLUSION: The Rivas Cohort Study enrolled a representative sample of 1242 adults living in the Department of Rivas, Nicaragua. The high re-contact and participation rates at two years suggests that the cohort is suitable for long-term studies and presents opportunities for investigations of disease prevalence, incidence, treatment and other public health matters. GPS coordinates and maps are available for future researchers who wish to use the cohort for additional studies.

Chronic kidney disease prevalence in Rivas, Nicaragua: use of a field device for creatinine measurement.

OBJECTIVE: An epidemic of chronic kidney disease (CKD) has been identified in Pacific coastal regions of Central America, and screening in the field in these low income countries remains logistically problematic. We tested the performance characteristics of a point of care creatinine analyzer compared to standardized serum creatinine measurements. METHODS: Measurements were conducted in 100 persons from a local health center (n=34) and hospital (n=66) in Rivas, Nicaragua using both a point-of-care analyzer (StatSensor Xpress, Nova Biomedical) and serum creatinine by Jaffe kinetic method with a Roche Cobas Integra 400 analyzer. Percent coefficient of variation, sensitivity and specificity of the StatSensor Xpress were determined. RESULTS: The average coefficient of variation (CV) was 1.28% for the serum creatinine and CV for the StatSensor Xpress analyzer was 6.8%. The median intra-individual creatinine results obtained with the StatSensor Xpress device were 0.32 mg/dL higher than those by serum creatinine by Jaffe kinetic method. The sensitivity and specificity of the StatSensor Xpress device for identifying subjects with abnormal creatinine (defined as >1.2 mg/dL) was 100% and 79%, respectively. CONCLUSIONS: Point of care testing for creatinine demonstrated acceptable repeatability, excellent sensitivity (100%) and modest specificity (79%). Using the point of care testing will allow for generalized screening in the field in low income countries; however, confirmation for elevated levels >1.2 mg/dL will require a second laboratory test confirmation.

Hourly oral sodium chloride for the rapid and predictable treatment of hyponatremia.

Hypertonic NaCl is first-line therapy for acute, severe and symptomatic hyponatremia; however, its use is often restricted to the intensive care unit (ICU). A 35-year-old female inpatient with an optic chiasm glioma and ventriculoperitoneal shunt for hydrocephalus developed acute hyponatremia (sodium 122 mEq/l) perhaps coinciding with haloperidol treatment. The sum of her urinary sodium and potassium concentrations was markedly hypertonic vis-à-vis plasma; it was inferred that serum sodium concentration would continue to fall even in the complete absence of fluid intake. Intravenous (i.v.) 3% NaCl was recommended; however, a city-wide public health emergency precluded her transfer to the ICU. She was treated with hourly oral NaCl tablets in a dose calculated to deliver the equivalent of 0.5 ml/kg/h of 3% NaCl with an objective of increasing the serum sodium concentration by 6 mEq/l. She experienced a graded and predictable increase in serum sodium concentration. A slight overshoot to 129 mEq/l was rapidly corrected with 0.25 l of D5W, and she stabilized at 127 mEq/l. We conclude that hourly oral NaCl, in conjunction with careful monitoring of the serum sodium concentration, may provide an attractive alternative to i.v. 3% NaCl for selected patients with severe hyponatremia.

Minimal change disease in pregnancy.

BACKGROUND: New onset minimal change disease (MCD) is rare in pregnancy with the potential for serious complications including acute kidney injury (AKI). CASE: A case of MCD was diagnosed at 19 weeks gestation by renal biopsy. Within one month of starting steroids, the patient experienced normalization of renal function and resolution of nephrotic syndrome, although hemodialysis was needed as a temporizing measure. CONCLUSION: The differential diagnosis for new onset proteinuria in pregnancy should include MCD. In selected cases, renal biopsy can be used to confirm diagnosis, and when indicated, hemodialysis should be instituted while awaiting a response to steroid therapy.

A reversible cause of 'end-stage renal disease': discrepant findings in serial duplex ultrasonograms in a suspected occlusion of a renal arterial bypass graft.

Duplex ultrasonography may be inaccurate due to a number of variables in operator and patient characteristics. We describe a 40-year-old woman who presented with acute kidney injury after prior complex abdominal aortic surgery that had left her with an essentially solitary functional kidney. On the basis of normal Doppler findings, she was started on dialysis. Owing to high clinical suspicion and a failure of renal function to return, a second Doppler study was performed 3 weeks after the first, revealing the characteristic tardus-parvus waveform of renal artery stenosis. The patient underwent urgent renal arterial angioplasty and stent placement. She experienced an immediate increase in urinary output, required no further dialysis, and the creatinine improved to 1.7 mg/dL (her prior renal baseline). The case illustrates an important complication of abdominal aortic aneurysm repair, draws attention to a potential source of error in the Doppler measurement, and underscores the limitations of duplex ultrasonography for excluding renal artery stenosis in the presence of high pretest probability.

Evolution of immunoglobulin deposition in C3-dominant membranoproliferative glomerulopathy.

BACKGROUND: Complement 3 glomerulopathy (C3GN) is a newly proposed subcategory of glomerular disease with features including membranoproliferative glomerulonephritis (MPGN), C3-dominant immunofluorescent staining without appreciable immunoglobulin deposition, and electron-dense deposits. Aberrations of alternative complement pathway (AP) have been found in many C3GN patients. CASE-DIAGNOSIS/TREATMENT: A 13-year-old boy presented with edema in association with an upper respiratory infection. Studies demonstrated nephrotic syndrome with hematuria and markedly low C3 and C4. Initial renal biopsy showed MPGN with strong C3 and immunoglobulin deposition. The patient partially responded to immunosuppression. Follow-up biopsies at 10 months and 3 years demonstrated MPGN with strong C3, with little to no immunoglobulin deposition. Based on this and elevated SC5b-9, treatment was changed to eculizumab with further decrease in proteinuria. CONCLUSIONS: Serial biopsies illustrated marked variability in immunoglobulin deposition in MPGN with persistently strong C3 deposition. Whether this evolution was related to the course of disease or to therapeutic intervention, the pathologic progression documented in this series of biopsies challenges the newly proposed subcategories of MPGN.