Nitrous oxide-induced subacute combined degeneration of the cord: diagnosis and treatment.

Recreational use of nitrous oxide (N2O) has increased rapidly in recent years and is now the second most commonly used recreational drug among young people in the UK. There has been a corresponding rise in cases of nitrous oxide-induced subacute combined degeneration of the cord (N2O-SACD), a pattern of myeloneuropathy usually associated with severe vitamin B12 deficiency. This can cause serious and permanent disability in young people but, if recognised early, may be effectively treated. All neurologists should be aware of N2O-SACD and its treatment; however, there are currently no agreed guidelines. Based on our experience in East London, an area of high N2O use, we provide practical advice on its recognition, investigation and treatment.

Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea.

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: -100 ± 27 vs. -161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: -138 ± 27 vs. -206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

Activating mutations in STIM1 and ORAI1 cause overlapping syndromes of tubular myopathy and congenital miosis.

Signaling through the store-operated Ca(2+) release-activated Ca(2+) (CRAC) channel regulates critical cellular functions, including gene expression, cell growth and differentiation, and Ca(2+) homeostasis. Loss-of-function mutations in the CRAC channel pore-forming protein ORAI1 or the Ca(2+) sensing protein stromal interaction molecule 1 (STIM1) result in severe immune dysfunction and nonprogressive myopathy. Here, we identify gain-of-function mutations in the cytoplasmic domain of STIM1 (p.R304W) associated with thrombocytopenia, bleeding diathesis, miosis, and tubular myopathy in patients with Stormorken syndrome, and in ORAI1 (p.P245L), associated with a Stormorken-like syndrome of congenital miosis and tubular aggregate myopathy but without hematological abnormalities. Heterologous expression of STIM1 p.R304W results in constitutive activation of the CRAC channel in vitro, and spontaneous bleeding accompanied by reduced numbers of thrombocytes in zebrafish embryos, recapitulating key aspects of Stormorken syndrome. p.P245L in ORAI1 does not make a constitutively active CRAC channel, but suppresses the slow Ca(2+)-dependent inactivation of the CRAC channel, thus also functioning as a gain-of-function mutation. These data expand our understanding of the phenotypic spectrum of dysregulated CRAC channel signaling, advance our knowledge of the molecular function of the CRAC channel, and suggest new therapies aiming at attenuating store-operated Ca(2+) entry in the treatment of patients with Stormorken syndrome and related pathologic conditions.

Nocturnal hypoxemia severity and renin-angiotensin system activity in obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with chronic kidney disease and up-regulation of the renin-angiotensin system (RAS), which is deleterious to renal function. The extent to which the magnitude of RAS activation is influenced by the severity of nocturnal hypoxemia and comorbid obesity has not been determined. OBJECTIVES: To determine the association between the severity of nocturnal hypoxemia and RAS activity and whether this is independent of obesity in patients with OSA. METHODS: Effective renal plasma flow (ERPF) response to angiotensin II (AngII) challenge, a marker of renal RAS activity, was measured by paraaminohippurate clearance technique in 31 OSA subjects (respiratory disturbance index, 51 ± 25 h(-1)), stratified according to nocturnal hypoxemia status (mean nocturnal SaO2, ≥90% [moderate hypoxemia] or <90% [severe hypoxemia]) and 13 obese control subjects. MEASUREMENTS AND MAIN RESULTS: Compared with control subjects, OSA subjects demonstrated decreased renovascular sensitivity (ERPF, -153 ± 79 vs. -283 ± 31 ml/min; P = 0.004) (filtration fraction, 5.4 ± 3.8 vs. 7.1 ± 2.6%; P = 0.0025) in response to 60 minutes of AngII challenge (mean ± SD; all P values OSA vs. control). The fall in ERPF in response to AngII was less in patients with severe hypoxemia compared with those with moderate hypoxemia (P = 0.001) and obese control subjects after 30 minutes (P < 0.001) and 60 minutes (P < 0.001) of AngII challenge, reflecting more augmented renal RAS activity. Severity of hypoxemia was not associated with the blood pressure or the systemic circulating RAS component response to AngII. CONCLUSIONS: The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.

Clinical neurology: why this still matters in the 21st century.

This review argues that even with the tremendous advances in diagnostic neuroimaging that the clinical skills involved in clinical neurology (ie, history, examination, localisation and differential diagnosis) remain key. Yet a number of recent audits suggest that large numbers of patients are failing to be assessed properly with a risk of patient harm, costly, unnecessary or inappropriate investigations, or delayed diagnosis. We review some of the reasons why patients are not being assessed properly neurologically, in part as many doctors have limited neurological exposure and are hence neurophobic. We propose that a solution to these issues centres around ensuring that a core set of basic neurological skills is taught at an undergraduate level, whereas higher level skills, such as the use of heuristics, are taught at postgraduate level.

Evaluation of continuous positive airway pressure therapy on renin-angiotensin system activity in obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). OBJECTIVES: We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response to angiotensin II (AngII), which reflects RAS activity. METHODS: Twenty normotensive, nondiabetic, newly diagnosed OSA subjects (15 men, 5 women, 50 ± 2 yr, respiratory disturbance index [RDI] > 15 h(-1)) with nocturnal hypoxemia (SaO2 < 90% for >12% of the night) were studied in high-salt balance pre- and post-CPAP therapy (>4 h CPAP use/night for 1 mo). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) (a surrogate marker for intraglomerular pressure) were measured pre- and post-CPAP using inulin and para-aminohippurate clearance techniques at baseline and in response to graded AngII infusion (3 ng/kg/min × 30 min and 6 ng/kg/min × 30 min, respectively). MEASUREMENTS AND MAIN RESULTS: CPAP corrected OSA and hypoxemia (RDI: 42 ± 4 vs. 4 ± 1 h(-1), P < 0.001; duration SaO2 < 90%: 36% ± 5% vs. 6 ± 2%, P < 0.001). CPAP reduced GFR (124 ± 8 ml/min vs. 110 ± 6 ml/min, P = 0.014), increased RPF (692 ± 36 ml/min vs. 749 ± 40 ml/min, P = 0.059), and reduced baseline FF (18.9 ± 1.6% vs. 15.3 ± 1.0%, P = 0.004). Post-CPAP demonstrated a blunted GFR response (-9 ± 3 ml/min vs. -2 ± 2 ml/min, P = 0.033) and augmented RPF response (-182 ± 22 ml/min vs. -219 ± 25 ml/min, P = 0.024) to AngII. FF response was maintained (P = 0.4). CPAP reduced baseline mean arterial pressure (94 ± 2 vs. 89 ± 2 mm Hg, P = 0.002), plasma aldosterone (149 ± 18 vs. 109 ± 10 pmol/L, P = 0.003), and urinary protein excretion (61 [39-341] mg/day vs. 56 [22-204] mg/d, P = 0.003). CONCLUSIONS: CPAP therapy was associated with improved renal hemodynamics and down-regulation of renal RAS activity, suggesting a potential therapeutic benefit for kidney function.

Predictors of successful completion of diagnostic home sleep testing in patients with chronic kidney disease.

PURPOSE: Obstructive sleep apnea (OSA) is common among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Home sleep testing is used to diagnose OSA in many studies investigating sleep-disordered breathing in this population. However, failure to successfully complete the test is a significant source of participant exclusion from research studies and delayed diagnosis in clinical practice. The objective of the study was to identify potential factors impeding acceptance and successful completion of home sleep testing in patients with kidney disease. METHODS: Four hundred and nineteen patients were recruited from nephrology clinics and dialysis units. Following completion of a sleep and medical history questionnaire, all patients were invited to perform a single night, home sleep study. Acceptance or refusal of the test was noted, as well as the success of the sleep study, as determined by a review of the raw data by a sleep medicine physician. RESULTS: Male gender (OR = 1.61, CI = 1.02-2.53), hypertension (OR = 2.01, CI = 1.17-3.45), and snoring (OR = 1.75, CI = 1.11-2.77) were associated with sleep test acceptance. Older patients were less likely to accept the test (OR = 0.48, CI = 0.30-0.76). Diabetics were less likely to complete the sleep test successfully (OR = 0.28, CI = 0.12-0.66). CONCLUSIONS: Advanced age is an important factor in test refusal and complications of diabetes contributes to test failure. Symptom matching may be a source of selection bias, as patients with risk factors for OSA are more likely to accept the diagnostic test.

A genetic study of Wilson's disease in the United Kingdom.

Previous studies have failed to identify mutations in the Wilson's disease gene ATP7B in a significant number of clinically diagnosed cases. This has led to concerns about genetic heterogeneity for this condition but also suggested the presence of unusual mutational mechanisms. We now present our findings in 181 patients from the United Kingdom with clinically and biochemically confirmed Wilson's disease. A total of 116 different ATP7B mutations were detected, 32 of which are novel. The overall mutation detection frequency was 98%. The likelihood of mutations in genes other than ATP7B causing a Wilson's disease phenotype is therefore very low. We report the first cases with Wilson's disease due to segmental uniparental isodisomy as well as three patients with three ATP7B mutations and three families with Wilson's disease in two consecutive generations. We determined the genetic prevalence of Wilson's disease in the United Kingdom by sequencing the entire coding region and adjacent splice sites of ATP7B in 1000 control subjects. The frequency of all single nucleotide variants with in silico evidence of pathogenicity (Class 1 variant) was 0.056 or 0.040 if only those single nucleotide variants that had previously been reported as mutations in patients with Wilson's disease were included in the analysis (Class 2 variant). The frequency of heterozygote, putative or definite disease-associated ATP7B mutations was therefore considerably higher than the previously reported occurrence of 1:90 (or 0.011) for heterozygote ATP7B mutation carriers in the general population (P < 2.2 × 10(-16) for Class 1 variants or P < 5 × 10(-11) for Class 2 variants only). Subsequent exclusion of four Class 2 variants without additional in silico evidence of pathogenicity led to a further reduction of the mutation frequency to 0.024. Using this most conservative approach, the calculated frequency of individuals predicted to carry two mutant pathogenic ATP7B alleles is 1:7026 and thus still considerably higher than the typically reported prevalence of Wilson's disease of 1:30 000 (P = 0.00093). Our study provides strong evidence for monogenic inheritance of Wilson's disease. It also has major implications for ATP7B analysis in clinical practice, namely the need to consider unusual genetic mechanisms such as uniparental disomy or the possible presence of three ATP7B mutations. The marked discrepancy between the genetic prevalence and the number of clinically diagnosed cases of Wilson's disease may be due to both reduced penetrance of ATP7B mutations and failure to diagnose patients with this eminently treatable disorder.

25-Hydroxyvitamin D status, arterial stiffness and the renin-angiotensin system in healthy humans.

Vitamin D deficiency is associated with increased arterial stiffness. We sought to clarify the influence of vitamin D in modulating angiotensin II-dependent arterial stiffness. Thirty-six healthy subjects (33 ± 2 years, 67% female, mean 25-hydroxyvitamin D 69 ± 4 nmol/L) were studied in high salt balance. Arterial stiffness, expressed as brachial pulse wave velocity (bPWV) and aortic augmentation index (AIx), was measured by tonometry at baseline and in response to angiotensin II infusion (3 ng/kg/min × 30 min then 6 ng/kg/min × 30 min). The primary outcome was change in bPWV after an angiotensin II challenge. Results were analyzed according to plasma 25-hydroxyvitamin D status: deficient (<50 nmol/L) and sufficient (≥ 50 nmol/L). There were no differences in baseline arterial stiffness between vitamin D deficient (25-hydroxyvitamin D 40 ± 2 nmol/L) and sufficient (25-hydroxyvitamin D 80 ± 4 nmol/L) groups. Compared with sufficient vitamin D status, vitamin D deficiency was associated with a decreased arterial response to angiotensin II challenge (Δbrachial pulse wave velocity: 0.48 ± 0.44 m/s versus 1.95 ± 0.22 m/s, p=0.004; Δaortic augmentation index: 9.4 ± 3.4% versus 14.2 ± 2.7%, p=0.3), which persisted for brachial pulse wave velocity response after adjustment for covariates (p=0.03). Vitamin D deficiency is associated with increased arterial stiffness in healthy humans, possibly through an angiotensin II-dependent mechanism.

Sex differences in body fluid composition in humans with obstructive sleep apnea before and after CPAP therapy.

Obstructive sleep apnea (OSA) is common in heart and kidney disease, both conditions prone to fluid retention. Nocturnal rostral fluid shift contributes to the pathogenesis of OSA in men more than women, suggesting a potential role for sex differences in body fluid composition in the pathogenesis of OSA, with men having a predisposition to more severe OSA due to an underlying volume expanded state. Continuous positive airway pressure (CPAP) increases intraluminal pressure in the upper airway and mitigates the rostral fluid shift; this, in turn, may prevent fluid redistribution from other parts of the body to the upper airway. We sought to determine the impact of CPAP on sex differences in body fluid composition. Twenty-nine (10 women, 19 men) incident, sodium replete, otherwise healthy participants who were referred with symptomatic OSA (oxygen desaturation index >15/h) were studied pre- and post-CPAP (>4 h/night × 4 weeks) using bioimpedance analysis. Bioimpedance parameters including fat-free mass (FFM, %body mass), total body water (TBW, %FFM), extracellular and intracellular water (ECW and ICW, %TBW), and phase angle (°) were measured and evaluated for sex differences before and after CPAP. Pre-CPAP, despite TBW being similar between sexes (74.6 ± 0.4 vs. 74.3 ± 0.2%FFM, p = 0.14; all values women vs. men), ECW (49.7 ± 0.7 vs. 44.0 ± 0.9%TBW, p < 0.001) was increased, while ICW (49.7 ± 0.5 vs. 55.8 ± 0.9%TBW, p < 0.001) and phase angle (6.7 ± 0.3 vs. 8.0 ± 0.3°, p = 0.005) were reduced in women compared to men. There were no sex differences in response to CPAP (∆TBW -1.0 ± 0.8 vs. 0.7 ± 0.7%FFM, p = 0.14; ∆ECW -0.1 ± 0.8 vs. -0.3 ± 1.0%TBW, p = 0.3; ∆ICW 0.7 ± 0.4 vs. 0.5 ± 1.0%TBW, p = 0.2; ∆Phase Angle 0.2 ± 0.3 vs. 0.0 ± 0.1°, p = 0.7). Women with OSA had baseline parameters favoring volume expansion (increased ECW, reduced phase angle) compared to men. Changes in body fluid composition parameters in response to CPAP did not differ by sex.

Increased urinary protein excretion in the "normal" range is associated with increased renin-angiotensin system activity.

Increased levels of albuminuria and proteinuria, both linked to augmented renin-angiotensin system (RAS) activity, are associated with adverse kidney and cardiovascular events. However, the relationship between variations in urinary albumin excretion (UAE) and total protein excretion (UTPE) in the normal range and RAS activity is unclear. We examined the association between UAE and UTPE and the hemodynamic response to angiotensin II (ANG II) challenge, a well-accepted indirect measure of RAS activity, in healthy individuals with normal UAE and UTPE. Forty subjects (15 men, 25 women; age 38 ± 2 yr; UAE, 3.32 ± 0.55 mg/day; UTPE, 56.8 ± 3.6 mg/day) were studied in high-salt balance. Blood pressure (BP), arterial stiffness determined by applanation tonometry, and circulating RAS components were measured at baseline and in response to graded ANG II infusion. The primary outcome was the BP response to ANG II challenge at 30 and 60 min. UAE was associated with a blunted diastolic BP response to ANG II infusion (30 min, P = 0.005; 60 min, P = 0.17), a relationship which remained even after adjustment (30 min, P < 0.001; 60 min, P = 0.035). Similar results were observed with UTPE (30 min, P = 0.031; 60 min, P = 0.001), even after multivariate analysis (30 min, P = 0.008; 60 min, P = 0.001). Neither UAE nor UTPE was associated with systolic BP, circulating RAS components, or arterial stiffness responses to ANG II challenge. Among healthy individuals with UAE and UTPE in the normal range, increased levels of these measures were independently associated with a blunted diastolic BP response to ANG II, indicating increased vascular RAS activity, which is known to be deleterious to both renal and cardiac function.

Systematic review and UK-based study of PARK2 (parkin), PINK1, PARK7 (DJ-1) and LRRK2 in early-onset Parkinson's disease.

Approximately 3.6% of patients with Parkinson's disease develop symptoms before age 45. Early-onset Parkinson's disease (EOPD) patients have a higher familial recurrence risk than late-onset patients, and 3 main recessive EOPD genes have been described. We aimed to establish the prevalence of mutations in these genes in a UK cohort and in previous studies. We screened 136 EOPD probands from a high-ascertainment regional and community-based prevalence study for pathogenic mutations in PARK2 (parkin), PINK1, PARK7 (DJ-1), and exon 41 of LRRK2. We also carried out a systematic review, calculating the proportion of cases with pathogenic mutations in previously reported studies. We identified 5 patients with pathogenic PARK2, 1 patient with PINK1, and 1 with LRRK2 mutations. The rate of mutations overall was 5.1%. Mutations were more common in patients with age at onset (AAO) < 40 (9.5%), an affected first-degree relative (6.9%), an affected sibling (28.6%), or parental consanguinity (50%). In our study EOPD mutation carriers were more likely to present with rigidity and dystonia, and 6 of 7 mutation carriers had lower limb symptoms at onset. Our systematic review included information from >5800 unique cases. Overall, the weighted mean proportion of cases with PARK2 (parkin), PINK1, and PARK7 (DJ-1) mutations was 8.6%, 3.7%, and 0.4%, respectively. PINK1 mutations were more common in Asian subjects. The overall frequency of mutations in known EOPD genes was lower than previously estimated. Our study shows an increased likelihood of mutations in patients with lower AAO, family history, or parental consanguinity.

Nocturnal hypoxemia severity influences the effect of CPAP therapy on renal renin-angiotensin-aldosterone system activity in humans with obstructive sleep apnea.

STUDY OBJECTIVES: Nocturnal hypoxemia (NH) in obstructive sleep apnea (OSA) is associated with renal renin-angiotensin-aldosterone system (RAAS) up-regulation and loss of kidney function. Continuous positive airway pressure (CPAP) therapy is associated with RAAS down-regulation, though the impact of NH severity remains unknown. We sought to determine whether NH severity alters the effect of CPAP on renal hemodynamics and RAAS activity in humans. METHODS: Thirty sodium-replete, otherwise healthy, OSA participants (oxygen desaturation index ≥ 15 h-1) with NH (SpO2 < 90% ≥ 12%/night) were studied pre- and post-CPAP (>4 h/night∙4 weeks). NH severity was characterized as moderate (mean SpO2[MSpO2] ≥ 90%; N = 15) or severe (MSpO2 < 90%; N = 15). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) were measured at baseline and in response to angiotensin-II (3 ng/kg/min∙30 min, 6 ng/kg/min∙30 min), a marker of RAAS activity. RESULTS: Pre-CPAP, baseline renal hemodynamics did not differ by NH severity. Pre-CPAP, severe NH participants demonstrated blunted GFR (Δ30 min, -9 ± 4 vs 1 ± 3 mL/min, p = 0.021; Δ60 min, -5 ± 5 vs 8 ± 5 mL/min, p = 0.017) and RPF (Δ30 min, -165 ± 13 vs -93 ± 19 mL/min, p = 0.003; Δ60 min, -208 ± 18 vs -112 ± 22 mL/min, p = 0.001; moderate vs severe) responses to angiotensin-II. Post-CPAP, severe NH participants demonstrated maintained GFR (112 ± 5 vs 108 ± 3 mL/min, p = 0.9), increased RPF (664 ± 35 vs 745 ± 34 mL/min, p = 0.009), reduced FF (17.6 ± 1.4 vs 14.9 ± 0.6%, p = 0.009), and augmented RPF responses to Angiotensin-II (Δ30 min, -93 ± 19 vs -138 ± 16 mL/min, p = 0.009; Δ60 min, -112 ± 22 vs -175 ± 20 mL/min, p = 0.001; pre- vs post-CPAP), while moderate participants were unchanged. CONCLUSIONS: Correction of severe, but not moderate, NH with CPAP therapy was associated with improved renal hemodynamics and decreased renal RAAS activity in humans with OSA.

Comprehensive Immune Profiling of a Kidney Transplant Recipient With Peri-Operative SARS-CoV-2 Infection: A Case Report.

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection. We showed that continuation of basiliximab induction and maintenance of triple immunosuppression did not significantly impair the host's ability to mount a robust immune response against symptomatic COVID-19 infection diagnosed within the first week post-transplant.

Nosocomial spread of COVID-19: lessons learned from an audit on a stroke/neurology ward in a UK district general hospital.

We describe the details of a COVID-19 outbreak in a 25-bedded Birmingham neurology/stroke ward in the early phase of the pandemic (March to May 2020). Twenty-one of 133 admissions (16%) tested positive for COVID-19 and of those, 8 (6% of all admissions to the ward) were determined to be nosocomial. Thus 38% (8/21) of COVID-19 infections were hospital-acquired. Ten of the patients that contracted COVID-19 died; of these three were hospital-acquired cases. Five of the 21 patients had negative swabs prior to receiving a positive test result. This study highlights the importance of appropriate use of personal protective equipment (PPE) with high-risk patients (including those with stroke and complex brain injury with tracheostomies) and the difficulties of COVID-19 management in a high-risk patient population.

Urine biomarkers of renal renin-angiotensin system activity: Exploratory analysis in humans with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) may contribute to kidney injury by activation of the renin-angiotensin system (RAS), which is reduced by continuous positive airway pressure (CPAP) therapy. A biomarker in the urine that reflects renal RAS activity could identify patients at risk of kidney injury and monitor their response to CPAP therapy. Nine patients with OSA and six matched control subjects without OSA were recruited. Renal RAS activity was measured by the renovasoconstrictor response to Angiotensin II challenge, a validated marker of RAS activity, and urine samples were collected in all subjects at baseline and repeated in those with OSA following treatment with CPAP. A broad range (1,310) of urine analytes was measured including 26 associated with the RAS signaling pathway. The OSA group was a similar age and weight as the control group (48.7 ± 10.4 vs. 47.7 ± 9.3 yrs; BMI 36.9 ± 7.2 vs. 34.7 ± 2.5 kg/m2 ) and had severe sleep apnea (ODI 51.1 ± 26.8 vs. 4.3 ± 2/hour) and nocturnal hypoxemia (mean SaO2 87 ± 5.2 vs. 92.6 ± 1.1%). CPAP corrected OSA associated with a return of the renovasocontrictor response to Angiotensin II to control levels. Partial least squares (PLS) logistic regression analysis showed significant separation between pre- and post-CPAP levels (p < .002) when all analytes were used, and a strong trend when only RAS-associated analytes were used (p = .05). These findings support the concept that urine analytes may be used to identify OSA patients who are susceptible to kidney injury from OSA before renal function deteriorates and to monitor the impact of CPAP therapy on renal RAS activity.