Shveta S. Motwani

Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea

BACKGROUND In both healthy male subjects and men with heart failure, the severity of obstructive sleep apnea (OSA) is related to the amount of fluid displaced from their legs into the neck overnight. Whether overnight rostral fluid shift contributes to the pathogenesis of OSA in patients with end-stage renal disease (ESRD) is unknown. We hypothesized that the change in neck circumference (NC) and severity of OSA are related to the extent of overnight change in leg fluid volume (LFV) in patients with ESRD. METHODS We studied 26 patients with ESRD (14 men) on conventional hemodialysis. All subjects underwent polysomnography. LFV was measured by bioelectric impedance at bedtime and repeated in the next morning on awakening. RESULTS Our cohorts overall apnea-hypopnea index was 22.8±26.8 episodes/h of sleep. Their overnight change in LFV was -243±278 mL. The change in LFV correlated with apnea-hypopnea time (AHT) (P=0.001) and NC (P=0.0016). Other independent factors associated with AHT included age (P=0.005), baseline neck (P=0.0002), sitting time (P=0.008) and male gender. Stepwise multiple regression analysis revealed that age, change in LFV and male gender remained independent related to AHT. CONCLUSIONS Nocturnal rostral fluid shift is associated with the severity of OSA in ESRD. Prospective evaluation of the effect of reducing fluid overload and severity of OSA in ESRD patients warrants further examination.

Relationship of pharyngeal water content and jugular volume with severity of obstructive sleep apnea in renal failure

BACKGROUND In patients with end-stage renal disease (ESRD), fluid overload may contribute to their high prevalence of obstructive sleep apnea (OSA) by increasing the amount of fluid displaced from the legs into the neck overnight, and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the amount of overnight rostral fluid displacement from the legs is related to the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI). We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the AHI. METHODS We studied 20 patients with ESRD on thrice weekly hemodialysis who had undergone diagnostic polysomnography (age 41.0 ± 12.3 years, with a body mass index (BMI) of 25.8 ± 6.3 kg/m(2) and an AHI of 20.2 ± 26.8). The leg fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were measured by UA magnetic resonance imaging (MRI). RESULTS The only significant independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC (r = 0.720, P = 0.0005) which together explained 72% of its variability. CONCLUSIONS These data suggest that fluid overload via increased IJVVol, and UA-MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings help us to explain the high prevalence of OSA in ESRD patients, and attenuation of OSA in association with nocturnal dialysis. They also suggest the need for randomized trials to determine whether more aggressive fluid removal in ESRD patients will alleviate OSA.

Contrasting Effects of Lower Body Positive Pressure on Upper Airways Resistance and Partial Pressure of Carbon Dioxide in Men With Heart Failure and Obstructive or Central Sleep Apnea

OBJECTIVES This study sought to test the effects of rostral fluid displacement from the legs on transpharyngeal resistance (Rph), minute volume of ventilation (Vmin), and partial pressure of carbon dioxide (PCO2) in men with heart failure (HF) and either obstructive (OSA) or central sleep apnea (CSA). BACKGROUND Overnight rostral fluid shift relates to severity of OSA and CSA in men with HF. Rostral fluid displacement may facilitate OSA if it shifts into the neck and increases Rph, because pharyngeal obstruction causes OSA. Rostral fluid displacement may also facilitate CSA if it shifts into the lungs and induces reflex augmentation of ventilation and reduces PCO2, because a decrease in PCO2 below the apnea threshold causes CSA. METHODS Men with HF were divided into those with mainly OSA (obstructive-dominant, n = 18) and those with mainly CSA (central-dominant, n = 10). While patients were supine, antishock trousers were deflated (control) or inflated for 15 min (lower body positive pressure [LBPP]) in random order. RESULTS LBPP reduced leg fluid volume and increased neck circumference in both obstructive- and central-dominant groups. However, in contrast to the obstructive-dominant group in whom LBPP induced an increase in Rph, a decrease in Vmin, and an increase in PCO2, in the central-dominant group, LBPP induced a reduction in Rph, an increase in Vmin, and a reduction in PCO2. CONCLUSIONS These findings suggest mechanisms by which rostral fluid shift contributes to the pathogenesis of OSA and CSA in men with HF. Rostral fluid shift could facilitate OSA if it induces pharyngeal obstruction, but could also facilitate CSA if it augments ventilation and lowers PCO2.

Differing Relationship of Nocturnal Fluid Shifts to Sleep Apnea in Men and Women with Heart Failure

Background—In men with heart failure, nocturnal rostral fluid shift is associated with an overnight increase in the neck circumference (NC) and with severity of obstructive sleep apnea. Because the prevalence of obstructive sleep apnea is lower in women than in men with heart failure, we hypothesized that less fluid would shift into the neck in association with less severe obstructive sleep apnea in women than in men with heart failure. Methods and Results—In 35 men and 30 women with heart failure, we assessed overnight changes in NC (&Dgr;NC) and leg fluid volume before and after polysomnography. The severity of obstructive sleep apnea was assessed by the apnea–hypopnea index. Although the changes in leg fluid volume did not differ significantly between men and women (−131 ± 90 versus −180 ± 132 mL, P=0.081), in women, &Dgr;NC was smaller (P<0.001) than in men. Furthermore, although in men, changes in leg fluid volume correlated inversely with &Dgr;NC (r=−0.755, P<0.001) and apnea–hypopnea index (r=−0.765, P<0.001), it did not in women. Conclusions—Despite no difference in overnight displacement of fluid from the legs compared with in men, in women, less of this fluid reached the neck, and unlike men, there was no relationship between changes in leg fluid volume and either &Dgr;NC or apnea–hypopnea index. These findings suggest a differing relationship between overnight fluid shift from the legs and severity of obstructive sleep apnea in women than in men with heart failure.

Effect of rostral fluid shift on pharyngeal resistance in men with and without obstructive sleep apnea

BACKGROUND Obstructive sleep apnea (OSA) relates to overnight rostral fluid shift, possibly because fluid accumulation around the pharynx increases pharyngeal resistance (Rph). We hypothesised that Rph will increase more in men with than without OSA in response to rostral fluid redistribution. METHODS Seventeen men with, and 12 without OSA were randomized to lower body positive pressure (LBPP) for 15min or control, then crossed over. Leg fluid volume (LFV) and Rph were measured before and after each period. RESULTS LBPP displaced similar amounts of fluid from the legs in both groups. However, compared to the non-OSA group, Rph increased significantly more during LBPP in the OSA group (-0.38±2.87 vs. 2.52±2.94cmH2O/l/s, p=0.016). Change in Rph during LBPP correlated directly with baseline Rph in the OSA group, but inversely in the non-OSA group. CONCLUSION OSA patients have increased susceptibility to pharyngeal obstruction in response to rostral fluid redistribution, which could predispose to pharyngeal collapse during sleep.

Renal complications of immune checkpoint blockade

Immune checkpoint inhibitors have been approved for a variety of cancer species. Renal complications in use of these agents are not very common compared with other immune-related adverse events (irAE). However, it is crucial for physicians to recognize and manage renal manifestations of irAE. In this review, we will summarize the up-to-date knowledge of the clinical presentation, pathologic features, and management of renal irAE. In addition, we will discuss the safety of immune checkpoint inhibitors in patients with chronic kidney disease as well as in kidney transplant recipients.

Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with Paraproteinemias

Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein-related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.

Influence of rostral fluid shift on upper airway size and mucosal water content.

STUDY OBJECTIVE Fluid displacement from the legs during recumbency while in bed might narrow the upper airway (UA) in association with nuchal fluid accumulation that may contribute to the pathogenesis of obstructive sleep apnea (OSA). The aim of this study was to test the hypothesis that rostral fluid displacement from the legs causes a greater decrease in UA cross-sectional area (UA-XSA) and a greater increase in UA mucosal water content (UA-MWC) and internal jugular venous volume (IJVVol) in subjects with OSA than in those without OSA. METHODS Subjects underwent baseline assessment of leg fluid volume (LFV) measured by bio-electrical impedance, as well as UA-XSA and UA-MWC by magnetic resonance imaging. They were then randomly assigned to a 20-min period either with or without application of lower body positive pressure (LBPP) of 40 mm Hg, followed by a 15-min washout period, after which they crossed over to the other arm of the study. Measurements of LFV, UA-MWC, and UA-XSA were repeated after each arm of the study. RESULTS In 12 subjects without sleep apnea, UA-XSA increased and UA-MWC decreased significantly, whereas in 12 subjects with OSA, UA-XSA decreased and UA-MWC increased significantly in response to LBPP. The changes in UA-XSA and UA-MWC in response to LBPP differed significantly between the 2 groups (p = 0.006 and p < 0.001, respectively), despite similar changes in LFV and IJVVol. CONCLUSIONS Our results suggest that rostral fluid shift may contribute to the pathogenesis of OSA at least partly through narrowing of the UA due to transudation of fluid into the UA mucosa.

Chronic Kidney Disease and Sleeping Disordered Breathing (SDB)

The outlines of the current manuscript are: 1. Re-establish the link between hypertension and SDB including prevalence, mechanism, and reversal of process (i.e. improvement in hypertension with improvement in SDB), why it is important-cardiovascular mortality with numbers. 2. Re-establish the link between hypertension and CKD including same points as above. Then ask if both CKD and SDB are combined, what happens to hypertension and cardiovascular mortality. 3. Lastly, talk about links between CKD and SDB on how each process feeds on the other and is a growing, common problem.