Prevalence and correlates of sleep apnea among US Veterans with chronic kidney disease.

The prevalence and correlates of sleep apnea (SA) among Veterans with chronic kidney disease (CKD), a population at high risk of both SA and CKD, are unknown. We performed a cross-sectional analysis of 248 Veterans (18-89 years) selected only for presence of moderate to severe CKD. All participants underwent full, unattended polysomnography, measurement of renal function and a sleepiness questionnaire. Logistic regression with backward selection was used to identify predictors of prevalent SA (apnea-hypopnea index [AHI, ≥15 events/hr] and prevalent nocturnal hypoxia [NH, % of total sleep time spent at <90% oxygen saturation]). The mean age of our cohort was 73.2 ± 9.6 years, 95% were male, 78% were Caucasian and the mean body mass index (BMI) was 30.3 ± 4.8 kg/m2 . The prevalence of SA was 39%. There was no difference in daytime sleepiness among those with and without SA. In the final model, older age, higher BMI and diabetes mellitus (DM) were associated with higher odds of SA, after controlling for age, BMI, race and sex. Higher BMI, DM, unemployed/retired status, current smoking and higher serum bicarbonate level were associated with prevalent NH. To sum, SA was common among Veterans with moderate to severe CKD. Although some traditional risk factors for SA were associated with SA in this population, sleepiness did not correlate with SA. Further study is needed to validate our findings and understand how best to address the high burden of SA among Veterans with CKD.

Clock gene expression is altered in veterans with sleep apnea.

Clock gene dysregulation has been shown to underlie various sleep disorders and may lead to negative cardio-metabolic outcomes. However, the association between sleep apnea (SA) and core clock gene expression is unclear. We performed a cross-sectional analysis of 49 Veterans enrolled in a study of SA outcomes in veterans with chronic kidney disease, not selected for SA or sleep complaints. All participants underwent full polysomnography and next morning whole blood collection for clock gene expression. We defined SA as an apnea-hypopnea index ≥15 events/h; nocturnal hypoxemia(NH) was defined as ≥10% of total sleep time spent at <90% oxygen saturation. We used quantitative real-time PCR to compare the relative gene expression of clock genes between those with and without SA or NH. Clock genes studied were Bmal1, Ck1δ, Ck1ε, Clock, Cry1, Cry2, NPAS2, Per1, Per2, Per3, Rev-Erb-α, RORα, and Timeless. Our cohort was 90% male, mean age was 71 yr (SD 11), mean body mass index was 30 kg/m2 (SD 5); 41% had SA, and 27% had NH. Compared with those without SA, Per3 expression was reduced by 35% in SA ( P = 0.027). Compared with those without NH, NPAS2, Per1, and Rev-Erb-α expression was reduced in NH (50.4%, P = 0.027; 28.7%, P = 0.014; 31%, P = 0.040, respectively). There was no statistical difference in expression of the remaining clock genes by SA or NH status. Our findings suggest that SA or related NH and clock gene expression may be interrelated. Future study of 24 h clock gene expression in SA is needed to establish the role of clock gene regulation on the pathway between SA and cardio-metabolic outcomes.

Sleep Apnea and Kidney Function Trajectory: Results From a 20-Year Longitudinal Study of Healthy Middle-Aged Adults.

Study Objectives: To determine whether sleep apnea, defined by polysomnography, accelerates kidney function decline in generally healthy adults not selected for sleep apnea or kidney disease. Methods: We performed a retrospective cohort study in 855 participants from the Wisconsin Sleep Cohort Study, a large 20-year population-based study of sleep apnea, who had at least one polysomnogram and serial measurements of serum creatinine over time. Sleep apnea was defined as an apnea-hypopnea index ≥ 15 or positive airway pressure (PAP) use at baseline. We compared the slope of estimated glomerular filtration rate (eGFR) change and odds of rapid eGFR decline (>2.2 mL/minute/1.73 m2/year) for those with and without sleep apnea. Results: The mean follow-up was 13.9 ± 3.4 years. The cohort was 50.4 ± 7.6 years, 55% male, and 97% white. The mean eGFR was 89.3 ± 13.8 mL/minute/1.73 m2 and 11% had sleep apnea. Overall, the mean eGFR change was -0.88 ± 1.12 mL/minute/1.73 m2/year. Compared with those without sleep apnea, participants with sleep apnea had a 0.2 mL/minute/1.73 m2/year slower eGFR decline though this was not statistically significant (95% CI [-0.06-0.45], p = .134). When we excluded those on PAP therapy (n = 17), eGFR decline was even slower among those with sleep apnea (0.36 mL/minute/1.73 m2/year slower, 95% CI [0.08-063], p = .012). Those with sleep apnea had lower odds of rapid eGFR decline but this was not statistically significant, even after excluding PAP users. Conclusion: Among healthy middle-aged adults, the presence of sleep apnea at baseline did not accelerate kidney function decline compared with those without sleep apnea over time.

Renal Function and Death in Older Women: Which eGFR Formula Should We Use?

Background. The Berlin Initiative Study (BIS) eGFR equations were developed specifically for aged populations, but their predictive validity compared to standard formulae is unknown in older women. Methods. In a prospective study of 1289 community-dwelling older women (mean age 79.5 years), we compared the performance of the BIS1 SCr-based equation to the CKD-EPIcr and the BIS2 SCr- and Scysc-based equation to the CKD-EPIcr,cysc to predict cardiovascular and all-cause mortality. Results. Prevalence of specific eGFR category (i.e., ≥75, 60-74, 45-59, and <45) according to eGFR equation was 12.3%, 38.4%, 37.3%, and 12.0% for BIS1; 48.3%, 27.8%, 16.2%, and 7.8% for CKD-EPIcr; 14.1%, 38.6%, 37.6%, and 9.6% for BIS2; and 33.5%, 33.4%, 22.0%, and 11.1% for CKD-EPIcr,cysc, respectively. Over 9 ± 4 years, 667 (51.8%) women died. For each equation, women with eGFR <45 were at increased risk of mortality compared to eGFR ≥75 [adjusted HR (95% CI): BIS1, 1.5 (1.1-2.0); CKD-EPIcr, 1.7 (1.3-2.2); BIS2, 2.0 (1.4-2.8); CKD-EPIcr,cysc, 1.8 (1.4-2.3); p-trend <0.01]. Net reclassification analyses found no material difference in discriminant ability between the BIS and CKD-EPI equations. Results were similar for cardiovascular death. Conclusions. Compared to CKD-EPI, BIS equations identified a greater proportion of older women as having CKD but performed similarly to predict mortality risk. Thus, the BIS equations should not replace CKD-EPI equations to predict risk of death in older women.

Evaluating Region of Interest Measurement Strategies to Characterize Upper Urinary Tract Stones on Computerized Tomography.

PURPOSE: Computerized tomography imaging is regularly used to assess stone HU values as a surrogate for stone composition and fragility. Techniques for measuring HU values are unstandardized, leading to high variability. We investigated several region of interest measurement strategies to quantify this variability. MATERIALS AND METHODS: Patients from an institutional database who underwent preoperative computerized tomography, surgical stone extraction and stone composition analysis were identified. HU measurements were made of each patient stone using transverse/coronal slices in the abdominal/bone windows with 4 region of interest techniques, including 1) the maximum diameter region of interest, 2) the maximum diameter region of interest at all stone inclusive slices, 3) 2 equal-sized, nonoverlapping circular regions of interest and 4) 3 to 5 smaller nonoverlapping regions of interest randomly placed on the stone. Stones that were 80% or greater pure by composition were separately analyzed. RESULTS: A total of 172 patients were included in study. Mean ± SD stone size was 19.3 ± 15.6 mm. On subtype analysis 51 stones were calcium oxalate monohydrate, 9 were calcium oxalate dihydrate, 7 were calcium phosphate hydroxyapatite/brushite and 16 were uric acid. Mean HU values in the abdominal window for all stones identified by region of interest techniques 1 to 4 were 457 ± 253, 351 ± 210, 581 ± 363 and 587 ± 329, respectively. The distribution of means significantly differed across region of interest techniques, planes and windows when considering all stones together (p <0.0001), stones with greater than 80% calcium oxalate dihydrate (p = 0.0113) and greater than 80% calcium oxalate monohydrate (p <0.0001), and uric acid stones (p <0.0001). CONCLUSIONS: HU values obtained to assess stone density vary depending on window, plane and region of interest technique. We recommend that clinicians select a single region of interest measurement technique and use it consistently to minimize interinstitutional variability.

Association of Increased Urinary Albumin With Risk of Incident Clinical Fracture and Rate of Hip Bone Loss: the Osteoporotic Fractures in Men Study.

Prior studies suggest that increased urine albumin is associated with a heightened fracture risk in women, but results in men are unclear. We used data from Osteoporotic Fractures in Men (MrOS), a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of increased urine albumin with subsequent fractures and annualized rate of hip bone loss. We calculated albumin/creatinine ratio (ACR) from urine collected at the 2003-2005 visit. Subsequent clinical fractures were ascertained from triannual questionnaires and centrally adjudicated by review of radiographic reports. Total hip BMD was measured by DXA at the 2003-2005 visit and again an average of 3.5 years later. We estimated risk of incident clinical fracture using Cox proportional hazards models, and annualized BMD change using ANCOVA. Of 2982 men with calculable ACR, 9.4% had ACR ≥30 mg/g (albuminuria) and 1.0% had ACR ≥300 mg/g (macroalbuminuria). During a mean of 8.7 years of follow-up, 20.0% of men had an incident clinical fracture. In multivariate-adjusted models, neither higher ACR quintile (p for trend 0.75) nor albuminuria (HR versus no albuminuria, 0.89; 95% CI, 0.65 to 1.20) was associated with increased risk of incident clinical fracture. Increased urine albumin had a borderline significant, multivariate-adjusted, positive association with rate of total hip bone loss when modeled in ACR quintiles (p = 0.06), but not when modeled as albuminuria versus no albuminuria. Macroalbuminuria was associated with a higher rate of annualized hip bone loss compared to no albuminuria (-1.8% more annualized loss than in men with ACR <30 mg/g; p < 0.001), but the limited prevalence of macroalbuminuria precluded reliable estimates of its fracture associations. In these community-dwelling older men, we found no association between urine albumin levels and risk of incident clinical fracture, but found a borderline significant, positive association with rate of hip bone loss. © 2016 American Society for Bone and Mineral Research.

Estimated GFR and Mortality in Older Men: Are All eGFR Formulae Equal.

BACKGROUND: Recently, the first estimated glomerular filtration rate (eGFR) formula specifically developed for community-dwelling older adults, the Berlin Initiative Study Equation 2 (BIS2), was reported. To date, however, no study has examined the performance of the BIS2 to predict death in older adults as compared to equations used clinically and in research. METHODS: We prospectively followed 2,994 community-dwelling men (age 76.4 ± 5.6) enrolled in the MrOS Sleep Study. We calculated baseline eGFR from serum creatinine and cystatin-C using the BIS2, Chronic Kidney Disease Epidemiology (CKD-EPIcr,cysc), CKD-EPIcysc and CKD-EPIcr equations. Analyses included Cox-proportional hazards regression and net reclassification improvement (NRI) for the outcomes of all-cause and cardiovascular death. RESULTS: Follow-up time was 7.3 ± 1.9 years. By BIS2, 42 and 11% had eGFR <60 and <45, respectively, compared to CKD-EPIcr (23 and 6%), CKD-EPIcysc (36 and 13%) and CKD-EPIcr,cysc (28 and 8%). BIS2 eGFR <45 was associated with twofold higher rate of all-cause mortality when compared to eGFR ≥75 after multivariate adjustment (HR 2.1, 95% CI 1.5-2.8). Results were similar for CKD-EPIcr,cysc <45 (HR 2.1, 95% CI 1.6-2.7) and CKD-EPIcysc <45 (HR 2.1, 95% CI 1.7-2.7) and weaker for CKD-EPIcr <45 (HR 1.5, 95% CI 1.2-2.0). In NRI analyses, when compared to CKD-EPIcr,cysc, both BIS2 and CKD-EPIcr equations more often misclassified participants with respect to mortality. We found similar results for cardiovascular death. CONCLUSION: The BIS2 did not outperform and the CKD-EPIcr was inferior to the cystatin C-based CKD-EPI equations to predict death in this cohort of older men. Thus, the cystatin C-based CKD-EPI equations are the formulae of choice to predict death in community-dwelling older men.

Foods with added fiber lower serum creatinine levels in patients with chronic kidney disease.

OBJECTIVE: To determine the effect of foods with added fiber on blood urea nitrogen (BUN) and serum creatinine concentrations in patients with chronic kidney disease (CKD). DESIGN: Participants were enrolled in a 6-week single-blind crossover study. SETTING: Free living with partial dietary intervention. PATIENTS: Thirteen CKD patients with Modification of Diet in Renal Disease formula-based estimated glomerular filtration rate (eGFR) ≤50 mL/minute/1.73 m(2) at the time of screening (5 men, 8 women; mean age, 67.0 ± 14.8 years) completed the study. INTERVENTION: Patients consumed control foods (cereal, cookies, and bars) providing 1.6 g/day fiber daily for 2 weeks, followed by similar foods providing 23 g/day fiber daily for 4 weeks, incorporated into their usual diets. MAIN OUTCOME: The main outcome of the study was the determination of the impact of foods with added fiber on BUN and serum creatinine levels. RESULTS: Consuming foods with added fiber resulted in a 10.6% decrease in mean BUN concentration (13.8 ± 2.0 to 12.1 ± 1.8 mmol/L or 38.5 ± 5.6 to 34.0 ± 5.1 mg/dL; P < .05). Serum creatinine level decreased from a baseline value of 216 ± 26 to 201 ± 23 mmol/L (2.44 ± 0.30 to 2.27 ± 0.26 mg/dL; P < .05) after 2 weeks of fiber-containing food consumption, and remained significantly lower at 195 ± 23 mmol/L (2.21 ± 0.26 mg/dL) after 4 weeks of the intervention (P < .05). Calculated eGFR increased from a baseline value of 29.6 ± 3.5 to 31.4 ± 3.8 mL/minute/1.73 m(2) at the end of 2 weeks, and remained higher at 32.5 ± 3.6 mL/minute/1.73 m(2) after 4 weeks of fiber intervention (P < .05). CONCLUSION: We conclude that increasing fiber intake in CKD patients through the consumption of foods with added fiber may reduce serum creatinine levels and improve eGFR. Additional studies are warranted to confirm these findings and to determine whether the changes are due to direct effects on kidney function.

Sleep-disordered breathing and urinary albumin excretion in older men.

PURPOSE: Sleep-disordered breathing (SDB) may be deleterious to the cardiovascular system and other organs, including the kidney. Although older men are at increased risk for both kidney disease and SDB, it is unknown whether SDB is associated with higher urinary albumin excretion in this population. METHODS: We examined 507 community-dwelling men age ≥ 67 years (mean 76.0 ± 5.3) enrolled in the MrOS Sleep study who underwent overnight polysomnography and gave a spot urine sample. SDB severity was categorized using the respiratory disturbance index and percent total sleep time <90% oxygen saturation (%time O2<90). Urinary albumin excretion was expressed using the albumin-to-creatinine ratio (ACR). RESULTS: There was a graded association between respiratory disturbance index and ACR (age- and race-adjusted mean ACR = 9.35 mg/gCr for respiratory disturbance index ≥ 30 versus 6.72 mg/gCr for respiratory disturbance index < 5, p = 0.007). This association was attenuated after further adjustment for body mass index (BMI), hypertension and diabetes and no longer reached significance (p = 0.129). However, even after adjustment for age, race, BMI, hypertension, and diabetes, greater %time O2<90 was associated with higher ACR (10.35 mg/gCr for ≥10%time O2<90 versus 7.45 mg/gCr for <1%time O2<90, p = 0.046). CONCLUSION: SDB, measured by elevated respiratory disturbance index or nocturnal hypoxemia, was associated with higher ACR. The relationship between respiratory disturbance index and ACR was partially explained by higher BMI and greater prevalence of hypertension and diabetes among men with SDB. However, greater nocturnal hypoxemia was independently associated with higher ACR, suggesting that the hypoxia component of SDB may mediate any detrimental effect of SDB on the kidney.

Reduced renal function and sleep-disordered breathing in community-dwelling elderly men.

BACKGROUND: Sleep-disordered breathing (SDB) may increase the risk of cardiovascular disease (CVD) and death in chronic kidney disease (CKD). However, the association between mild reductions in renal function and SDB is uncertain. METHODS: We studied 508 community-dwelling men aged>or=67 years (mean 76.0+/-5.3) who were enrolled at the Minnesota site for the Minneapolis center of the Outcomes of Sleep Disorders in Older Men (MrOS) sleep study and had serum cystatin-C and creatinine measured coincident with overnight polysomnography. CKD was defined as estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m2 using Cockcroft-Gault (CG), modification of diet in renal disease (MDRD) and Mayo Clinic formulae. SDB was defined by a respiratory disturbance index (RDI)>or=15 events/h. RESULTS: Mean cystatin-C was 1.21+/-0.30 mg/L, and mean creatinine was 1.09+/-0.23 mg/dL. Median RDI was 7.0 events/h (range 0-73). Higher quartiles of cystatin-C were associated with higher mean RDI (p for trend=0.007). This association persisted after adjustment for age and race (p for trend=0.03), but not after adjustment for body mass index (BMI, p for trend=0.34). After adjusting for age, race, BMI, diabetes, hypertension, and CVD, CKD defined by the Mayo Clinic formula, but not CG or MDRD, was associated with a higher odds of SDB [odds ratio (OR) 1.95, 95% confidence interval (CI) 1.04-3.65, p=0.04]. CONCLUSIONS: Older men with reduced renal function as defined by higher cystatin-C concentration have higher average RDI. This effect is explained by higher BMI in men with higher cystatin-C. CKD defined by the Mayo Clinic formula is independently associated with twofold higher odds for SDB. Therefore, reduced renal function may be associated with SDB in older men.

Renal function and sleep-disordered breathing in older men.

BACKGROUND: Sleep-disordered breathing (SDB) is common in severe chronic kidney disease (CKD) and may contribute to morbidity and mortality in this population. However, the association between mild to moderate CKD and likelihood of SDB is uncertain. METHODS: We studied 2696 men >or=65 years (mean 73.0 +/- 5.5) enrolled in the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study who had serum creatinine (SCr) measured 3.4 years prior to overnight polysomnography (PSG). CKD was expressed as quartiles of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula. SDB was assessed using the respiratory disturbance index (RDI) with >or=4% oxygen desaturation. RESULTS: Mean SCr was 0.99 +/- 0.20 mg/dl; 14.8% had eGFR <60 ml/min/1.73 m(2). Median RDI was 7.4 events/hour (inter-quartile range 2.6-15.8). Lower eGFR was not associated with higher mean RDI in the unadjusted model (P for trend = 0.180). There was evidence of an interaction between eGFR and age for the prediction of RDI; an association between lower eGFR and higher RDI was evident only among men

Transplant tourism: Outcomes of United States residents who undergo kidney transplantation overseas.

BACKGROUND: Although international commerce in kidney transplantation is a reality, little is known about U.S. residents who travel abroad for kidney transplantation. METHODS: We retrospectively reviewed the clinical outcomes of patients who were evaluated at the University of Minnesota Medical Center or Hennepin County Medical Center, but then surreptitiously underwent kidney transplantation overseas. RESULTS: We identified 10 patients who underwent kidney transplantation outside the United States between September 16, 2002 and June 30, 2006 and then returned for care in our programs. Eight were transplanted in Pakistan (all Somali), one was transplanted in China (Chinese), and one was transplanted in Iran (Iranian). All but one had a living donor. Mean age was 36.8+/-12.5 years with median follow-up of 2.0 years (range 0.4-3.7). Three patients communicated their intent to travel abroad before transplantation. Induction immunosuppressive therapy (if any) was available in 3/10, and initial maintenance immunosuppression was known in 5/10. Complications were primarily infectious, with six potentially life-threatening infections in four patients. At last follow-up, mean serum creatinine was 1.13+/-0.34 mg/dL, acute rejection occurred in 2/10, 1/10 grafts failed due to acute rejection, and 9/10 patients were alive. CONCLUSIONS: Kidney function and graft survival were generally good after surreptitious overseas kidney transplantation. Major problems included incomplete perioperative information communicated to the posttransplant care facility and a high incidence of posttransplant infections. Longer follow-up and detailed cost analysis are needed to better understand the implications of the growing phenomenon of transplant tourism.