Oscar Noboa

24-h ambulatory recording of aortic pulse wave velocity and central systolic augmentation: a feasibility study

We assessed the feasibility of ambulatory pulse wave analysis by comparing this approach with an established tonometric technique. We investigated 35 volunteers (45.6 years; 51.0% women) exclusively at rest (R study) and 83 volunteers (49.9 years; 61.4% women) at rest and during daytime (1000–2000 h) ambulatory monitoring (R+A study). We recorded central systolic (cSP), diastolic (cDP) and pulse (cPP) pressures, augmentation index (cAI) and pulse wave velocity (PWV) by brachial oscillometry (Mobil-O-Graph 24h PWA Monitor) and radial tonometry (SphygmoCor). We applied the Bland and Altman’s statistics. In the R study, tonometric and oscillometric estimates of cSP (105.6 vs. 106.9 mm Hg), cDP (74.6 vs. 74.7 mm Hg), cPP (31.0 vs. 32.1 mm Hg), cAI (21.1 vs. 20.6%) and PWV (7.3 vs. 7.0 m s−1) were similar (P⩾0.11). In the R+A study, tonometric vs. oscillometric assessment yielded similar values for cSP (115.4 vs. 113.9 mm Hg; P=0.19) and cAI (26.5 vs. 25.3%; P=0.54), but lower cDP (77.8 vs. 81.9 mm Hg; P<0.0001), so that cPP was higher (37.6 vs. 32.1 mm Hg; P<0.0001). PWV (7.9 vs. 7.4 m s−1) was higher (P=0.0002) on tonometric assessment. The differences between tonometric and oscillometric estimates increased (P⩽0.004) with cSP (r=0.37), cAI (r=0.39) and PWV (r=0.39), but not (P⩾0.17) with cDP (r=0.15) or cPP (r=0.13). Irrespective of measurement conditions, brachial oscillometry compared with an established tonometric method provided similar estimates for cSP and systolic augmentation, but slightly underestimated PWV. Pending further validation, ambulatory assessment of central hemodynamic variables is feasible.

Burden of disease: prevalence and incidence of ESRD in Latin America.

INTRODUCTION Chronic kidney disease (CKD) represents a major challenge for Latin America (LA), due to its epidemic proportions and high burden to the population affected and to public health systems. METHODS Our methods have been reported previously: This paper shows the data for the last 10 years until 2010, from the Latin American Dialysis and Renal Transplantation Registry (RLADTR). RESULTS 20 countries participated in the surveys, covering 99% of Latin America (LA). The prevalence of end-stage renal disease (ESRD) under renal replacement therapy (RRT) in LA increased from 119 patients per million population (pmp) in 1991 to 660 pmp in 2010 (hemodialysis (HD) 413 pmp, peritoneal dialysis (PD) 135 pmp, and LFG 111 pmp). HD proportionally increased more than PD and transplant and continues to be the treatment of choice in the region (75%). The kidney transplant rate increased from 3.7 pmp in 1987 to 6.9 pmp in 1991 and to 19.1 in 2010. The total number of transplants in 2010 was 10,397, with 58% being deceased donors. The total RRT prevalence correlated positively with gross national income (GNI) (r = 0.86; p < 0.05) and life expectancy at birth (r = 0.58; p < 0.05). The global incidence rate correlated significantly only with GNI (r = 0.56; p < 0.05). Diabetes remained the leading cause of ESRD. CONCLUSION The prevalence and incidence of RRT continues to increase. In countries with 100% public health or insurance coverage for RRT the rates are comparable to those displayed by developed countries with better GNI. PD is still an underutilized strategy for RRT in the region. Diagnostic and prevention programs for hypertension and diabetes, appropriate policies promoting the expansion of PD and organ procurement as well as transplantation as cost effective forms of RRT are needed in the region.

Delayed mTOR Inhibition with Low Dose of Everolimus Reduces TGFβ Expression, Attenuates Proteinuria and Renal Damage in the Renal Mass Reduction Model

Background The immunosuppressive mammalian target of rapamycin (mTOR) inhibitors are widely used in solid organ transplantation, but their effect on kidney disease progression is controversial. mTOR has emerged as one of the main pathways regulating cell growth, proliferation, differentiation, migration, and survival. The aim of this study was to analyze the effects of delayed inhibition of mTOR pathway with low dose of everolimus on progression of renal disease and TGFβ expression in the 5/6 nephrectomy model in Wistar rats. Methods This study evaluated the effects of everolimus (0.3 mg/k/day) introduced 15 days after surgical procedure on renal function, proteinuria, renal histology and mechanisms of fibrosis and proliferation. Results Everolimus treated group (EveG) showed significantly less proteinuria and albuminuria, less glomerular and tubulointerstitial damage and fibrosis, fibroblast activation cell proliferation, when compared with control group (CG), even though the EveG remained with high blood pressure. Treatment with everolimus also diminished glomerular hypertrophy. Everolimus effectively inhibited the increase of mTOR developed in 5/6 nephrectomy animals, without changes in AKT mRNA or protein abundance, but with an increase in the pAKT/AKT ratio. Associated with this inhibition, everolimus blunted the increased expression of TGFβ observed in the remnant kidney model. Conclusion Delayed mTOR inhibition with low dose of everolimus significantly prevented progressive renal damage and protected the remnant kidney. mTOR and TGFβ mRNA reduction can partially explain this anti fibrotic effect. mTOR can be a new target to attenuate the progression of chronic kidney disease even in those nephropathies of non-immunologic origin.

Estimation of Glomerular Filtration Rate Based on Serum Cystatin C versus Creatinine in a Uruguayan Population

Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans (54.5% women; 56.2 years (mean)), we used Bland and Altmans method and Cohens kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohens kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2.

Rust Urine after Intense Hand Drumming Is Caused by Extracorpuscular Hemolysis

BACKGROUND AND OBJECTIVES During Carnival, groups of > or =60 drummers go drumming with their hands and marching for periods of 2 to 4 h. The objective of this study was to determine the frequency and type of urinary abnormalities after candombe drumming and to evaluate possible pathogenic mechanisms. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS For analysis of pathogenic mechanisms, a group of individuals were prospectively evaluated before and after candombe drumming. METHODS Candombe drummers were recruited in January 2006, 1 wk before prolonged drumming. After clinical evaluation, urine and blood samples were obtained before and immediately after drumming. RESULTS Forty-five healthy individuals (four women and 41 men), median age 31 yr (14 to 56), were evaluated. Predrumming urine and plasma samples were obtained for 30 individuals. Nineteen (42%) of 45 had a previous history of rust urine emission temporally related with candombe drumming. After drumming, 18 of 26 showed urine abnormalities; six of 26 showed rust urine, eight of 26 had microhematuria, and seven of 26 had proteinuria >1 g/L. The candombe drummers who showed rust urine after heavy drumming presented significantly higher levels of lactate dehydrogenase and total bilirubin when compared with those without urine abnormalities. Haptoglobin was significantly lower in the rust urine group. Fragmented red cells were observed in the blood smear of individuals with rust urine. Rust urine after drumming was associated with previous episodes of rust urine and glucosuria. CONCLUSIONS Taken together, these data confirm that rust urine is caused by extracorpuscular hemolysis.

The Diurnal Profile of Central Hemodynamics in a General Uruguayan Population.

BACKGROUND No previous population study assessed the diurnal profile of central arterial properties. METHODS In 167 participants (mean age, 56.1 years; 63.5% women), randomly recruited in Montevideo, Uruguay, we used the oscillometric Mobil-O-Graph 24-h PWA monitor to measure peripheral and central systolic (SBP), diastolic (DBP), and pulse (PP) pressures and central hemodynamics standardized to a heart rate of 75 bpm, including aortic pulse wave velocity, systolic augmentation (first/second peak × 100), and pressure amplification (peripheral PP/central PP). RESULTS Over 24 hours, day and night, peripheral minus central differences in SBP/DBP and in PP averaged 12.2/-1.1, 14.0/-0.7, and 9.7/0.2mm Hg and 12.6, 14.7, and 9.5mm Hg, respectively (P < 0.001 except for nighttime DBP (P = 0.38)). The central-to-peripheral ratios of SBP, DBP, and PP were 0.89, 1.00, and 0.70 unadjusted, but after accounting for anthropometric characteristics decreased to 0.74, 0.97, and 0.63, respectively, with strong influence of height for SBP and DBP and of sex for PP. From day (10-20h) to nighttime (0-6h), peripheral (-10.4/-10.5 mm Hg) and central (-6.0/-11.3mm Hg) SBP/DBP, pulse wave velocity (-0.7 m/s) and pressure amplification (-0.05) decreased (P < 0.001), whereas central PP (+5.3mm Hg) and systolic augmentation (+2.3%) increased (P < 0.001). CONCLUSIONS The diurnal rhythm of central pressure runs in parallel with that of peripheral pressure, but the nocturnal fall in SBP is smaller centrally than peripherally. pulse wave velocity, systolic augmentation, and pressure amplification loop through the day with high pulse wave velocity and pressure amplification but low systolic augmentation in the evening and opposite trends in the morning.

Significance of white-coat and masked hypertension in chronic kidney disease and end-stage renal disease

Hypertension is a frequent and modifiable cardiovascular risk factor with a cyclic relationship with chronic kidney disease (CKD). The diagnosis, treatment, monitoring and control of high blood pressure are all mandatory not only in CKD but also in end-stage renal disease (ESRD). As demonstrated by studies using population and hypertensive patients, white-coat hypertension (WCHT) and masked hypertension (MHT) carry a particular degree of risk. The advantages of ambulatory techniques in the management and prognostic stratification of patients with CKD and ESRD have also been recognized. However, most of the evidence underlines the importance of nocturnal hypertension and neglects WCHT and MHT. The absence of specific reports involving untreated and treated patients hinders the ability to significantly discriminate WCHT from the white-coat effect and MHT from masked uncontrolled hypertension. The heterogeneous definitions that are used add additional difficulty in translating experimental evidence into clinical practice. Reaching a consensus in definitions is mandatory for designing future research. Cross-sectional studies underscore the frequency of misdiagnosis, potentially leading to undertreatment (MHT) and overtreatment (WCHT) in renal disease. The divergent prevalence of WCHT and MHT reported in CKD could be related to the diverse definitions of hypertension and the heterogeneity of the pathologies pooled under the CKD definition. Even in the absence of randomized clinical trials specifically addressing this issue, the scarce longitudinal studies confirm that WCHT carries a risk close to that of sustained normotension, whereas MHT is associated with a risk close or identical to that of sustained hypertension.

Reliable quantification of the potential for equations based on spot urine samples to estimate population salt intake: protocol for a systematic review and meta-analysis.

Background Methods based on spot urine samples (a single sample at one time-point) have been identified as a possible alternative approach to 24-hour urine samples for determining mean population salt intake. Objective The aim of this study is to identify a reliable method for estimating mean population salt intake from spot urine samples. This will be done by comparing the performance of existing equations against one other and against estimates derived from 24-hour urine samples. The effects of factors such as ethnicity, sex, age, body mass index, antihypertensive drug use, health status, and timing of spot urine collection will be explored. The capacity of spot urine samples to measure change in salt intake over time will also be determined. Finally, we aim to develop a novel equation (or equations) that performs better than existing equations to estimate mean population salt intake. Methods A systematic review and meta-analysis of individual participant data will be conducted. A search has been conducted to identify human studies that report salt (or sodium) excretion based upon 24-hour urine samples and spot urine samples. There were no restrictions on language, study sample size, or characteristics of the study population. MEDLINE via OvidSP (1946-present), Premedline via OvidSP, EMBASE, Global Health via OvidSP (1910-present), and the Cochrane Library were searched, and two reviewers identified eligible studies. The authors of these studies will be invited to contribute data according to a standard format. Individual participant records will be compiled and a series of analyses will be completed to: (1) compare existing equations for estimating 24-hour salt intake from spot urine samples with 24-hour urine samples, and assess the degree of bias according to key demographic and clinical characteristics; (2) assess the reliability of using spot urine samples to measure population changes in salt intake overtime; and (3) develop a novel equation that performs better than existing equations to estimate mean population salt intake. Results The search strategy identified 538 records; 100 records were obtained for review in full text and 73 have been confirmed as eligible. In addition, 68 abstracts were identified, some of which may contain data eligible for inclusion. Individual participant data will be requested from the authors of eligible studies. Conclusions Many equations for estimating salt intake from spot urine samples have been developed and validated, although most have been studied in very specific settings. This meta-analysis of individual participant data will enable a much broader understanding of the capacity for spot urine samples to estimate population salt intake.

Rabdomiólisis por hipopotasemia severa

Rhabdomyolysis results from acute necrosis of skeletal muscle fibers and consequent leakage of muscle constituents into the circulation. It ranges from an asymptomatic state to a severe condition associated with extreme elevations in creatine kinase and acute renal failure. Reported etiologies of rhabdomyolysis include alcohol abuse, drugs, muscle trauma and muscle overexertion. Less common causes include muscle enzyme deficiencies, electrolyte abnormalities, infectious causes, toxins and endocrine disorders. Hypokalemia is a rare cause of rhabdomyolysis. We report six patients aged 31 to 57 years (three women) with a severe hypokalemic rhabdomyolysis, secondary to chronic diarrhea in two patients, treatment with loop diuretics in one and Gitelman syndrome in three. Rhabdomyolysis may be underdiagnosed in the context of hypokalemia, because the neuromuscular symptoms can be attributed solely to the electrolyte disorder.

Lupus Nephritis in Males: Clinical Features, Course, and Prognostic Factors for End-Stage Renal Disease

Introduction Because of their rarity in men, systemic lupus erythematous and lupus nephritis (LN) are poorly understood in men. Our aim was to analyze the clinical presentation and course of histology-proven systemic lupus erythematous and LN in males and to determine the risk factors for progression to end-stage renal disease. Methods Fifty patients from 2 historical cohorts in Spain (Hospital 12 de Octubre) and Uruguay were retrospectively analyzed and compared with a female cohort matched for age and disease characteristics. Results The median age at the time of renal biopsy was 27 years (range, 8–79 years). The main forms of presentation were nephrotic syndrome in 26 of 50 patients (52%), and class IV LN in 34 of 50 (68%). After treatment, 21 patients (45.6%) achieved complete renal remission. During follow-up, 12 patients required renal replacement therapy, and 3 patients died of infectious causes. When patients who required renal replacement therapy were compared with those who did not require it, several parameters showed significant differences (P < 0.05) at the time of renal biopsy: estimated glomerular filtration rate < 60 ml/min, hypertension, hypoalbuminemia, and concomitant visceral involvement (neurologic, cardiovascular, and/or pulmonary). In the multivariate analysis, only estimated glomerular filtration rate < 60 ml/min persisted as a risk factor for progression to end-stage renal disease. When compared with a cohort of female patients with LN, there were no significant differences in remission or renal survival. Discussion LN in males usually presents as nephrotic syndrome, and type IV LN is the most frequent form. An estimated glomerular filtration rate < 60 ml/min at the time of renal biopsy is associated with poor renal outcomes. There were no differences in remission or progression of LN in males when compared with a cohort of female patients with LN.