Faculty Bibliography

Background: Urine chemistry is a determinant of stone formation in cystinuria. We previously showed that positive cystine capacity (CysCap), a measure of higher cystine solubility, led to fewer stone events. We queried the RKSC Cystinuria Registry to determine urinary and medication variables associated with positive (CysCap+), rather than negative (CysCap-) values.
Method(s): This is the 1st report from the Cystinuria Registry, with data on 300 people with cystinuria (142 males, 158 females; age at enrollment 38 +/- 17 years). 112 participants had 306 determinations of CysCap, measured by Litholink (Chicago, IL). In this cross-sectional study we compared variables associated with CysCap+ vs CysCap-.
Result(s): Lower urine Na (r=0.48; Fig 1A) and creatinine (r=0.62, not shown) were associated with lower 24h urine cystine (UC; P<0.001). Increasing CysCap values were seen with increasing urine pH (rs=0.45, Fig 1B), volume (rs=0.44) and decreasing UC (rs=-0.44 Fig 1C; all P<0.001). Dividing Cyscap determinations into CysCap+ and CysCapgroups (Table), only higher urine volume and greater daily citrate doses were different. Relatively few participants were taking citrate or tiopronin.
Conclusion(s): Higher urine pH and volume and lower UC were associated with less lithogenic urine; lower UC was seen with less Na and creatinine. Higher volume and citrate doses distinguished patients with less lithogenic urine. Many patients with cystinuria may be undertreated and would benefit from better dietary adherence. (Table Presented)

Accurate assessment of blood volume (BV) may be helpful for prescribing hemodialysis (HD) and for reducing complications related to hypovolemia and volume overload. Monitoring changes in relative BV (RBV) using hematocrit, e.g., Crit-Line Monitor (CLM-III), an indirect method, cannot be used to determine absolute BV. We report the first study of BV measurement for assessing volume status in HD patients using the indicator dilutional method. Ten adult HD patients were enrolled in this prospective observational study. BV measurement was performed before and after HD using BV analysis (BVA)-100 (Daxor Corporation, New York, NY, USA). BVA-100 calculates BV using radiolabeled albumin (Iodine-131) followed by serial measures of the radioisotope. Fluid loss from the extravascular space was calculated by subtracting the change in BV from total weight loss. Intradialytic changes in RBV were measured by CLM-III. Eight out of 10 cases had significant hypervolemia, two cases were normovolemic. The range of BV variation from predicted normal was 156 to 1990 mL. Significant inter-individual differences in extravascular space fluid loss ranged from 54% to 99% of total weight loss. Spearman correlation showed a good correlation in the measurement of RBV by BVA-100 and CLM-III in 8 out of 10 patients (r(2) = 0.64). BV measurement using BVA-100 is useful to determine absolute BV as well as changes in BV and correlates reasonably well with CLM-III measurements. Individual refilling ability can be determined as well. This may prove useful in prescribing and monitoring ultrafiltration rates, establishment of optimal BV in HD patients and reducing morbidity and mortality associated with chronic HD.

Cystinuria is a genetic cause of recurrent kidney stones which may be more recurrent and larger than more common non-cystine stones. They may have a greater impact on health-related quality of life (HRQoL). We measured this impact by surveying HRQoL in patients with stones, comparing non-cystine stone formers (NCSF) to cystine stone formers (CYSF) and both groups to normative values of the US population. We used SF-36v2 via an internet instrument. CYSF patients were recruited via cystinuria-related websites, two patient advocacy groups, and an active endourology practice. NCSF patients were recruited from the same practice and by email. Total n surveyed with scorable data: 214 CYSF and 81 NCSF. The participants included 128 men and 161 women. The group of CYSF were significantly younger (39 vs. 54 years) and suffered longer from kidney stones (255 vs. 136 months). CYSF patients had significantly more episodes of stones than NCSF patients in the last year (N = 108 CYSF, N = 20 NCSF). More frequent stones in the last year and mental comorbidities most often predicted worse scores in the individual HRQoL domains. However, cystine stone composition was a significant predictor of worse scores only for role emotional. Better scores in all SF-36 domains were associated with greater time since the last kidney stone event. Although kidney stones are often transient, kidney stone formers, regardless of stone composition, have a worse HRQoL than the standard US population, which has a normative score of 50, such as general health (41.2 +/- 12.8), bodily pain (46.5 +/- 11.8) and mental health (45.1 +/- 12.6). CYSF are more frequent and severe stone formers compared with NCSF with a resulting greater, direct impact on the HRQoL of CYSF patients. Whether preventive strategies for cystinuria are being properly utilized by practitioners, and which strategies are most effective, should be established.

BACKGROUND: Obstructive sleep apnea is commonly associated with metabolic changes and obesity, and changes in body weight by either medical or surgical approaches have been considered to affect the severity of sleep apnea and appetite-controlling hormones. This prospective study evaluated the effect of weight loss induced by laparoscopic adjustable gastric banding (LAGB) surgery on respiratory disturbance during sleep, oxygen saturation levels, sleep architecture, and leptin and ghrelin levels. METHODS: Participants were patients at a university-based medical center surgical weight loss program. All participants with a body mass index > 30 kg/m(2) undergoing LAGB surgery for weight reduction were offered the opportunity to participate in the study. Procedures included overnight polysomnography followed by fasting hormone levels at baseline and 12 months postoperatively. RESULTS: Thirty subjects (10 men, 20 women) of mean age 44.0 +/- 12.5 years were recruited. At 12 months postoperatively, mean excess weight loss was 44.4% +/- 14%. The apnea-hypopnea index decreased from 34.2 +/- 35 to 19.0 +/- 21.7 events per hour (P < 0.0001), while leptin levels decreased from 24.5 +/- 17.42 pg/mL to 11.6 +/- 10.6 pg/mL (P = 0.02). Ghrelin levels did not change substantially. Nadir oxygen saturation levels increased from 81% to 84% at 12 months (P = 0.03). Mean oxygen saturation improved and was positively correlated with ghrelin levels at both time points (r = 0.39, P = 0.07, and r = 0.60, P = 0.01). CONCLUSION: LAGB surgery was associated with 44.4% excess weight loss at 12 months, accompanied by a 33.7% improvement in apnea-hypopnea index as well as a reduction in leptin levels by 31.7% in this group. An association between ghrelin and mean oxygen saturation was seen and deserves further investigation.

PURPOSE: Cheyne-Stokes respiration during sleep is associated with increased mortality in heart failure. The magnitude of oxidative stress is a marker of disease severity and a valuable predictor of mortality in heart failure. Increased oxidative stress associated with periodic breathing during Cheyne-Stokes respiration may mediate increased mortality in these patients. We hypothesized that the presence of Cheyne-Stokes respiration is associated with oxidative stress by increasing the formation of reactive oxygen species in patients with heart failure. METHODS AND RESULTS: Twenty-three patients with heart failure [left ventricular ejection fraction 30.2 +/- 9% (mean +/- standard deviation)] and 11 healthy controls underwent nocturnal polysomnography. Subjects with obstructive sleep apnea were excluded. The majority (88%) of patients with heart failure had Cheyne-Stokes respiration during sleep. The intensity of oxidative stress in neutrophils was greater in patients with heart failure (4,218 +/- 1,706 mean fluorescence intensity/cell vs. 1,003 +/- 348 for controls, p < 0.001) and correlated with the duration of Cheyne-Stokes respiration. Oxidative stress was negatively correlated with SaO(2) nadir during sleep (r = -0.43, p = 0.039). The duration of Cheyne-Stokes respiration predicted severity of oxidative stress in patients with heart failure (beta = 483 mean fluorescence intensity/cell, p < 0.02). CONCLUSIONS: Levels of oxidative stress are increased in patients with heart failure and Cheyne-Stokes respiration during sleep compared with healthy controls. The duration of Cheyne-Stokes respiration predicts the magnitude of oxidative stress in heart failure. Increased oxidative stress may mediate increased mortality associated with Cheyne-Stokes respiration in patients with heart failure

BACKGROUND: Urinary oxalate excretion is an important contributor to calcium oxalate stone formation. Methods of reducing oxalate excretion are not wholly satisfactory, and no controlled trials using them have been performed to prevent stone recurrence. Some lactic acid bacteria can degrade oxalate in vitro. This study sought to reduce urinary oxalate excretion in calcium stone formers with idiopathic hyperoxaluria. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A randomized, double-blind, placebo-controlled trial was performed of Oxadrop, a mix of four lactic acid bacterium species. This preparation previously reduced oxalate excretion in stone formers with idiopathic and enteric hyperoxaluria. Patients were selected from two stone prevention clinics. Twenty people with calcium stones and idiopathic hyperoxaluria (>40 mg/d) were enrolled and randomly assigned 1:1 in placebo and active preparation arms. Both groups took 3.6 g of granulate each day: Either placebo or the experimental preparation. Participants performed two consecutive 24-h urine collections at baseline, at 28 d of therapy, and at 56 d, after being off the preparation for 4 wk. Diet was replicated at each point. RESULTS: There was no effect of the study preparation: Mean 24-h urinary oxalate excretion in placebo-treated patients was 73.9 mg at baseline and 72.7 mg after treatment, whereas the Oxadrop-treated patients had 59.1 mg at baseline and 55.4 mg after treatment. The preparation was well tolerated; three participants on active treatment experienced mild constipation. CONCLUSIONS: In this randomized, placebo-controlled trial, Oxadrop did not reduce urinary oxalate excretion in participants with idiopathic hyperoxaluria

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Its possible association with obstructive sleep apnea is a major cause of concern for clinicians. As the prevalence of both COPD and sleep apnea continues to rise, further investigation of this interaction is needed. In addition, COPD patients are at risk for hypoventilation during sleep due to the underlying respiratory dysfunction. In this study, 13 COPD subjects and 13 non-COPD control subjects were compared for the presence and severity of obstructive sleep apnea and nocturnal hypoventilation. All 26 subjects had presented to a sleep clinic and showed no signs of daytime hypoxemia. After matching for BMI and age, COPD subjects had a similar prevalence of sleep apnea with a lower degree of severity compared to the control subjects. However, less severe events, such as RERA, occurred at similar rates between the two groups. There was no significant difference between groups in the magnitude of oxyhemoglobin desaturation during sleep. Interestingly, severity and presence of nocturnal hypoxemia correlated with that of sleep apnea in the control group, but not in the COPD subjects. In conclusion, COPD without daytime hypoxemia was not a risk factor for sleep apnea or nocturnal hypoventilation in this study