A central feature of CFS is orthostatic intolerance and abnormal autonomic cardiovascular control characterized by sympathetic predominance. We hypothesized that symptoms as well as the underlying pathophysiology might improve by treatment with the alphaA total of 176 adolescent CFS patients (12–18 years) were assessed for eligibility at a single referral center recruiting nation-wide. Patients were randomized 1:1 by a computer system and started treatment with clonidine capsules  or placebo capsules for 9 weeks. Double-blinding was provided. Data were collected from March 2010 until October 2012 as part of The Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL). Effect of clonidine intervention was assessed by general linear models in intention-to-treat analyses, including baseline values as covariates in the model.A total of 120 patients  were enrolled and started treatment. There were 14 drop-outs  during the intervention period. At 8 weeks, the clonidine group had lower plasma norepinephrine  and urine norepinephrine/creatinine ratio . During supine rest, the clonidine group had higher heart rate variability in the low-frequency range   as well as higher standard deviation of all RR-intervals (SDNN) ; during 20° head-up tilt there were no statistical differences in any cardiovascular variable. Symptoms of orthostatic intolerance did not change during the intervention period.Low-dose clonidine reduces catecholamine levels in adolescent CFS, but the effects on autonomic cardiovascular control are sparse. Clonidine does not improve symptoms of orthostatic intolerance.NCT01040429, date of registration 12/28/2009.Clinical Trials ID:  Chronic Fatigue Syndrome (CFS) is a disabling condition with unknown pathophysiology. In adolescents, prevalence has been estimated from 0.1 to 2.4 % depending on definition of CFS and method of estimation , no pharOrthostatic intolerance is common with a prevalence of more than 25 % in adults with CFS , and mor2A receptor, thereby attenuating sympathetic nervous activity and enhancing parasympathetic activity, even in low doses [2A receptor gene might possible modify the effect of clonidine treatment [Clonidine is a centrally acting agonist to the presynaptic alphaow doses –16. Thusow doses . Howeverreatment .NCT01040429, date of registration 12/28/2009).The aim of this study was to investigate the effects of low-dose clonidine on autonomic cardiovascular control in adolescent CFS. We hypothesized that clonidine would improve symptoms of orthostatic intolerance and normalize cardiovascular variables and indices of autonomic nervous activity at rest as well as during orthostatic challenges. The study is part of the NorCAPITAL-project  as well as primary care pediatricians and general practitioners were invited to refer patients aged 12 – 18 years to the national referral center for young CFS patients at Oslo University Hospital. The referring units were equipped with written information for distribution to potential study participants and their parents/next-of-kin. If consent was given, a standard form required the referral unit to confirm the result of clinical investigations considered compulsory to diagnose pediatric CFS according to national Norwegian recommendations . Also, the referring units were required to confirm that the patient a) was unable to follow normal school routines due to fatigue; b) was not permanently bedridden; c) did not have any concurrent medical or psychiatric disorder that might explain the fatigue; d) did not experience any concurrent demanding life event (such as parents’ divorce) that might explain the fatigue; e) did not use prescribed pharmaceuticals (including hormone contraceptives) regularly. A previous demanding life event was not an exclusion criterion. Completed forms were consecutively conveyed to the study center and carefully evaluated by either of two authors (DS or EF). Patients considered eligible to this study were invited to a clinical encounter at our study center after which a final decision on inclusion was made.All hospital pediatric departments in Norway ; 18 months disease duration (the median disease duration in a previous follow-up study ) served Clonidine dosages were 50 μg B.I.D for body weight >35 kg, and 25 μg B.I.D for body weight < 35 kg. Catapresan® 25 μg clonidine hydrochloride tablets  were enclosed in orange opaque, demolition-restraint lactose capsules . Identical capsules without Catapresan® were used as placebo comparator. Half the dose was given for the first 3 days of the intervention period in order to minimize adverse introductory effects. Blood samples for clonidine concentration analyses were taken approximately two weeks after start of the intervention, and at the second visit.NorCAPITAL was approved by the Norwegian National Committee for Ethics in Medical Research and the Norwegian Medicines Agency. Data were collected in the period March 2010 until October 2012. Written informed consent was obtained from all participants, and from parents/next-of-kin if required.A one-day in-hospital assessment included clinical examination, blood sampling , and 20° head-up tilt test (HUT), and always commenced between 7.30 and 9.30 a.m. Patients were instructed to fast overnight and abstain from tobacco products and caffeine for at least 48 h, to bring a morning spot urine sample in a sterile container, and to apply the local anesthetic lidocaine (Emla®) on the skin in the antecubital area one hour in advance. At week 8, CFS patients were told to postpone their prescribed morning study drug dose (clonidine/placebo) until after blood sampling and HUT. All procedures were undertaken in a quiet, warm room in a fixed sequence and by three researchers only . Blood samples were obtained in a fixed sequence from antecubital venous puncture after at least five minutes supine rest in calm surroundings. Samples of oral mucosa were collected for genetic analyses. Following the in-hospital assessment, a self-administered questionnaire was completed.The blood samples for plasma norepinephrine (NA) and epinephrine (A) analyses were obtained in vacutainer tubes treated with ethylene glycol tetraacetic acid (EGTA)–Glutathione. The samples were placed on ice for approximately 30 min; thereafter, plasma was separated by centrifugation  and frozen at – 80 °C until assayed. Samples were analyzed for plasma NA and A by high-performance liquid chromatography (HPLC) with a reversed-phase column and glassy carbon electrochemical detector  using a commercial kit  –24. All Urine samples for NA and A analyses were collected in 10 ml universal containers. Immediately after collection the urine was acidified to pH ≈ 2.5, thereafter, stored at 2–8 °C until assayed. Urine treated this way is stable at least 5 days. The analyses were performed consecutively. The same HPLC protocol as for plasma measurement was used for the measurement of urin NA/A. The intra- and interassay coefficient of variation (CV) for urine were 3.9 and 5.2 %, respectively.The blood samples for clonidine determinations were collected in 4 mL heparin tubes. After centrifugation for 12 min at 1000 g at room temperature, the plasma fraction was frozen at −20 °C until analysis. A slight modification of the method described by Müller et al.  was used2A receptor single nucleotide polymorphism (SNP) rs1800544 was carried out by predesigned TaqMan SNP genotyping assay , using the SDS 2.2 software (Applied Biosystems). As previously described, approximately 10 % of the samples were re-genotyped, and the concordance rate was 100 % [The genotyping of the alphaas 100 % . GenotypHead-up tilt-test (HUT) was performed using an electronically operated tilt table with foot-board support . Patients were connected to the Task Force Monitor (TFM) , a combined hardware and software device for noninvasive recording of cardiovascular variables. 5 min was used for supine recordings, after which the participants were head-up tilted to 20° for 15 min. Details of the HUT protocol have been described elsewhere . In partInstantaneous RR intervals (RRI) and heart rate (HR) were obtained from the electrocardiogram (ECG). Continuous arterial blood pressure was obtained noninvasively using photoplethysmography on the right middle finger. Mean arterial blood pressure (BP) was calculated by numerical integration of the recorded instantaneous BP. The recorded value was calibrated against conventional oscillometric measurements of arterial BP on the left arm every five minutes according to the TFM manufacturer’s recommendation. Impedance cardiography with electrodes placed on the neck and upper abdomen was used to obtain a continuous recording of the temporal derivative of the transthoracic impedance (dZ/dt). Beat-to-beat stroke volume was calculated from the impedance signal .Power spectral analysis (frequency-domain method) of HR variability and systolic blood pressure (SBP) variability was automatically provided by the TFM, using an adaptive autoregressive model . Power wHeart rate variability (HRV) is considered an index of autonomic cardiac modulation. In the frequency-domain, vagal (parasympathetic) activity is the main contributor to HF variability, whereas both vagal and sympathetic activity contributes to LF variability . The LF/Data from each HUT procedure was exported to Microsoft Excel for further calculations. Beat-to-beat stroke index (SI) was calculated dividing stroke volume by body surface area, and beat-to-beat total peripheral resistance index (TPRI) was calculated as mean BP divided by the product of SI and HR. For each participant, the following epochs of the recordings were chosen: Baseline (270 to 30 s before tilt up) and Early tilt (30 to 270 s after tilt). In each epoch we computed the median value for the conventional cardiovascular variables as well as the indices of HR and SBP variability; this procedure reduces the influence of erroneous outliers, such as ectopic heart beats. Thereafter, the delta values (Early Tilt – Baseline) which are considered indices of the cardiovascular response to orthostatic challenge were computed for each participant. This analytic approach has been proven feasible in several previous report from our group –11.The participants received a comprehensive questionnaire consisting of several validated inventories, as has been described in detail elsewhere .The Autonomic Symptom Profile (ASP) , which hThe questionnaire also included the CFS symptom inventory for adolescents , 35. Thi2A receptor single nucleotide polymorphism (SNP) rs1800544, and sex, were explored by including these variables as interaction terms. Dose–response relationships for patients allocated to clonidine were explored by linear regression analyses. Missing values were imputed as last observation carried forward from the pre-medication test. In order to obtain near-normally distributed variables, ln-transformation was carried out for supine values of LF-HRV, HF-HRV, Total Power-HRV, LF/HF ratio and LF-SBP. Square root transformation was carried out for 20° head-up tilt values of LF-HRV, HF-HRV and Total Power-HRV. Genotype frequency among patients and healthy controls were explored with chi-square analyses.Determination of sample size is described elsewhere . OutcomeSPSS statistical software  was applied for all statistical analyses, and all tests were carried out two-sided. A p-value ≤ 0.05 was considered statistically significant. Corrections for multiple comparisons were not applied.A total of 176 CFS patients were referred to the study, of which 151 were eligible for randomization  and urine norepinephrine/creatinine ratio (p = 0.002) as compared to the placebo group (Table p = 0.007) and as well as higher SDNN (p = 0.05)  Table . No otheB = −14.5, p = 0.004). TPRI supine , heart rate variability in the low-frequency band supine   and HRV-Total Power supine  were positively related to plasma clonidine concentration. No other dose response-relationships were found.Urine norepinephrine/creatinine ratio was negatively related to plasma clonidine concentration .Subgrouping according to the 1994 CFS case definition, genotype frequency of the alphaThis study shows that clonidine reduces catecholamine levels in adolescent CFS. However, the effects on cardiovascular autonomic control are sparse, and clonidine does not improve symptoms of orthostatic intolerance.Previous studies have documented that adult as well as adolescent CFS patients are characterized by enhanced sympathetic and attenuated parasympathetic nervous activity , 38, 39.Clonidine had limited impact on standard cardiovascular variables, both at rest and during orthostatic challenge. This finding was surprising. In previous studies of healthy individuals as well as hypertensive patients, clonidine dosages similar to those applied in this study have been shown to decrease both blood pressures and heart rate, and these alterations of hemodynamics were paralleled by a decrement of catecholamines , 44–47. 2A receptor protein, which is the ligand for clonidine. A single nucleotide polymorphism (SNP) (rs1800544) in the alpha2A receptor gene implies substitution of guanine (G) for cytosine (C) at position 1291, and has functional consequences [Taken together, the findings presented in this study suggest an alteration of clonidine pharmacodynamics in CFS. One possible explanation is genetically determined differences of the alpha (SNP) rs00544 in equences  as well equences .The possibility of increased long-term cardiovascular risk in CFS patients remains a concern . In addia priori-definition of the degree of school absenteeism necessary to fulfil the diagnostic criteria, which might have obscured results applying to a subgroup only. However, the study population corresponds closely to the population who is diagnosed as CFS by pediatricians; thus, we assume the external validity to be strong. Furthermore, subgrouping based upon the 1994 CFS case definition did not change the results. We have not done subgrouping based on caffeine use. Another limitation of this study is the 4 min epochs used for time-domain analyses of heart rate variability, as opposed to the 5 min epochs recommended [A possible limitation of this study is the wide inclusion criteria and no ommended . It is cLow-dose clonidine reduces catecholamine levels in adolescent CFS. However, the effects on cardiovascular autonomic control are sparse, and clonidine does not improve symptoms of orthostatic intolerance.


The year 2013 proved to be very exciting as far as landmark trials and new guidelines in the field of lipid disorders, blood pressure and kidney diseases. Among these are the International Atherosclerosis Society Global Recommendations for the Management of Dyslipidemia, European Society of Cardiology (ESC)/European Society of Hypertension Guidelines for the Management of Arterial Hypertension, American Diabetes Association Clinical Practice Recommendations, the Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease (CKD) Patients, the American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, the Joint National Committee Expert Panel (JNC 8) Evidence-Based Guideline for the Management of High Blood Pressure in Adults, the American Society of Hypertension/International Society of Hypertension Clinical Practice Guidelines for the Management of Hypertension in the Community, the American College of Physicians Clinical Practice Guideline on Screening, Monitoring, and Treatment of Stage 1–3 CKD and many important trials presented among others during the ESC Annual Congress in Amsterdam and the American Society of Nephrology Annual Meeting—Kidney Week in Atlanta, GA. The paper is an attempt to summarize the most important events and reports in the mentioned areas in the passing year. In patients with multiple cardiovascular (CV) risk factors, it is essential to effectively manage the overall risk, in order to prevent CV events . TraditiIt is worth emphasizing that the current European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines 2011) indicate LDL-C as an only target for lipid disorders therapy 011 indic. One of Later that month, the American College of Cardiology (ACC) and the American Heart Association (AHA) published very expected clinical practice guidelines for the treatment of cholesterol in those at high risk of atherosclerotic cardiovascular diseases (ASCVD) . CorollaThe large debate has started since the publishing of the new lipid guidelines. In the same month, the National Lipid Association (NLA) released a position statement expressing opposition to the former’s recommendation to remove LDL-C (and non-HDL-C) treatment targets . Also EuConsidering the complicated mechanisms and signals involved in atherosclerosis, research is now focused on novel lipid biomarkers that can be introduced as routine diagnostic tests. It is important to determine whether adding information on apolipoprotein B (apoB) and apolipoprotein A1 (apoA1), lipoprotein (a) or lipoprotein-associated phospholipase A2 to total cholesterol (TC), LDL-C and HDL-C improves cardiovascular disease (CVD) risk prediction –14. It iDifferent clinical conditions associated with inflammation, oxidation, advanced glycation and protein carbamylation, such as diabetes, coronary artery disease (CAD) or CKD can alter the functionality of HDL, converting normal HDL into so-called dysfunctional HDL which is no longer cardioprotective . FurtherHowever, we still need a direct method to measure dysfunctional HDL, as currently we use many indirect methods, including the ones concerning the analysis of subfractions/subpopulations of lipoproteins , 19. RecDespite well-established roles in primary and secondary prevention of CVD, due to their positive effects on the plasma lipid profile, statin use is associated with some side effects and residual risk . Beyond The first meta-analysis that revealed that statin therapy for a mean follow-up of 4 years was associated with a higher incidence (by 9 %) of NOD was published in 2010 . Then, tBecause diabetes is a risk equivalent condition for vascular diseases, recent findings create a paradox whereby needed statin therapy may be withheld to avoid excess risk of diabetes, while representing the strongest cardiovascular risk reduction tool in diabetics , 41. TheHypertension and hyperlipidemia often coexist and seem to be interrelated through common pathophysiological pathways . The rolCKD is associated with CVD even in the early stages, and a large number of patients die before developing advanced CKD , 55–58. The very recent position paper of International Atherosclerosis Society (IAS)—Global Recommendations for the Management of Dyslipidemia suggested that in CKD patients classified as moderately high risk, the optimal range of LDL-C should be <100 mg/dL (2.6 mmol/L) . The recInsights from randomized controlled trials in patients with heart failure, atrial fibrillation and CKD suggest that there are still some questions regarding the role of statins in these conditions . StatinsPCSK9 is able to induce degradation of the LDLR-related protein 1 (LRP-1), and although the latter is not an essential factor for LDLR regulation, the LDLR effectively competes with LRP-1 for PCSK9 activity. Identification of PCSK9 targets should allow a better understanding of the consequences of PCSK9 inhibition for lowering LDL-C . InhibitThe American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) 2011 expert consensus document on hypertension in the elderly developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists and European Society of Hypertension recommended that the BP should be lowered to less than 140/90 mmHg in adults with hypertension younger than 80 years at high risk of CV events . On the Dyslipidemia often coexists with hypertension, and statins should be always considered in hypertensive patients, especially with other CV risk factors and CAD (see above) , 89–92. In 2013, there have been several studies searching for new biomarkers that correlate with hypertension complications, such as cardiotrophin 1 (CT-1) and procollagen III N-terminal propeptide, which are early markers of left ventricular injury, as well as neutrophil gelatinase-associated lipocalin, which could be a sensitive marker of kidney function in elderly patients with hypertension , 94. In p < 0.001 for trend) [p < 0.001), especially in the Southern region of the United States [There have been also studies looking at improved control of hypertension, which remains as a large problem in both Europe and the US –98. The r trend) . The pred States .In recent years, there is also a large discussion on cardiometabolic risk at children. It has been recently showed that persons with persistently increased BP from childhood to adulthood had significantly increased risk of carotid atherosclerosis . This ri2013 is a year with new data on brain (cerebrovascular) damage in hypertensive patients. 3,020 patients (mean age 63 years) with a recent lacunar stroke were randomized in an open-label trial to a systolic blood pressure of 130–149 mmHg or of <130 mmHg; patients with a systolic blood pressure of 127 mmHg after 1 year had an insignificant 19 % reduction in all-stroke compared WITH patients with a systolic blood pressure of 138 mmHg after 1 year . FurtherThere were also some new guidelines published in 2013. The American Diabetes Association (ADA) 2013 guidelines recommend that diabetics with hypertension should have their systolic blood pressure reduced to less than 140 mmHg . A systoHowever, it is worth emphasizing that we have still had very limited data on optimal BP levels in the elderly –113. TheIn patients 60 years of age or older who do not have diabetes or CKD, the goal blood pressure level is <150/90 mmHg, whereas in patients 18–59 years of age without major comorbidities, and in patients 60 years of age or older who have diabetes, CKD or both, the goal blood pressure is <140/90 mmHg. In younger patients without major comorbidities, increased DBP is a more important CV risk factor than is increased SBP, whereas in patients 60 years of age and older SBP control remains the most important factor (as in JNC 7) ;First-line and later-line treatments are now be limited to four classes of medications namely: thiazide-type diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB). Second- and third-line agents include higher doses or combinations of ACE-I, ARB, thiazides and CCBs ;For black patients without CKD, initial choices of antihypertensives should include CCBs and thiazides instead of ACE-I. Use of ACE-I and ARB is recommended for all patients with CKD regardless of ethnic background, either as first-line therapy or in addition to first-line therapy ;p < 0.001), as was acute kidney injury . At a median follow-up of 2.2 years, there was no significant difference in the study’s primary endpoint of renal disease progression or death between the monotherapy and combination therapy groups . There was also no difference in cardiovascular events [ACE-I and ARB should not be used in the same patient simultaneously. This has been supported by three trials, namely the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) , the Alir events , 118.CCBs and thiazides should be used instead of ACE-I and ARB in patients over the age of 75 with impaired kidney function due to the risk of hyperkalemia, increased creatinine and further renal impairment .In December 2013, the Joint National Committee Expert Panel (JNC 8) published their Evidence-Based Guideline for the Management of High Blood Pressure in Adults . The mosThey recommended that the start treatment threshold of >150/90 mmHg applies to patients 80 years or older.They also suggested different antihypertensives for initial therapy, based on the patients’ race, age and blood pressure level. They recommended an ACE-I or ARB for non-black patients under age 60 years of age, and a CCB or thiazide-type diuretic for non-black patients over 60 years of age. For black patients, they recommended a CCB or thiazide-type diuretic. In patients with blood pressure of at least 160/100, they recommended starting with two drugs from the start and they also had separate drug recommendations for special populations.Later, the American Society of Hypertension (ASH) and the International Society of Hypertension (ISH) issued separate guidelines from JNC 8 , with soSeveral noteworthy trials on hypertension also deserve mention at this point. Over the past several years, renal angioplasty and stenting of atherosclerotic renal artery stenosis (RAS) became a common procedure. Recently, however, two randomized trials; the ASTRAL  and STARWith the burden of resistant hypertension, the concept of renal denervation has been introduced. This is based on the premise that in patients with resistant hypertension, there is overstimulation of the sympathetic nervous system, i.e., afferent signaling from the kidneys increases central sympathetic drive, while efferent signals to the kidneys increase renin release and sodium retention, while reducing renal blood flow. Catheter-based renal denervation cuts this communication between the kidneys and the sympathetic nervous system, and theoretically will result in lowering of blood pressure , 124. ThACP recommended against screening for CKD in asymptomatic adults without risk factors for CKD ;ACP recommended against testing for proteinuria in adults with or without diabetes who are currently taking an ACE-I or ARB ;ACP recommended that clinicians select pharmacologic therapy that includes either an ACE-I  or an ARB  in patients with hypertension and stage 1–3 CKD (grade: strong recommendation);ACP recommended that clinicians choose statin therapy to manage increased low-density lipoprotein in patients with stage 1–3 CKD  .In October 2013, the American College of Physicians (ACP) published guidelines  to preseWhile the American Society of Nephrology (ASN) agreed with most of the above recommendations from ACP as they did reflect current standard clinical practice, they expressed disagreement with the ACP’s recommendation against screening for CKD in asymptomatic adults without risk factors as well as the recommendation not to test for proteinuria in adults with or without diabetes who were already being treated with either an ACE-I or ARB . ASN PreA tendency toward phosphate retention begins early in renal disease, due to the reduction in the filtered phosphate load. Phosphate retention is intimately related to the common development of CVD risk in CKD, increased fibroblast growth factor (FGF)-23 levels and secondary hyperparathyroidism . The KidHowever, clinicians are becoming more cautious with the use of calcium-containing phosphate binders because of concerns about toxicity of calcium accumulation associated with vascular calcification or adynamic bone disease. The decision to use non-calcium-containing binders over calcium-containing binders was for many years a subject of debate. In a recent meta-analysis of 11 open-label trials  revealed a 22 percent decrease in all-cause mortality among patients with CKD randomly assigned to receive non-calcium-based phosphate binders . These rGiven that the current approach to management of hyperphosphatemia is not always optimal, a number of alternative therapies are undergoing evaluation. These include colestilan and iron-containing phosphate binders. Colestilan is an anion exchanger compound with some similarities to sevelamer, initially being approved for the treatment of hypercholesterolemia. Recently, it has been successfully used as a phosphate binder for patients on dialysis in a phase III study, with similar effects compared with sevelamer or calcium-containing phosphate binders  in conne,Iron-containing phosphate binders represent other new alternatives in the treatment of hyperphosphatemia. Two molecules are most promising: iron(III)-oxyhydroxide-based phosphate binder PA21) and ferric citrate, both being the subject of ongoing phase III studies. Even if appears that both products have similar efficiency with other phosphate binders with a lower pill burden, side effect profile and cost effectiveness remain to be evaluated , 134.1, and ferrThe administration of radiocontrast media can lead to a usually reversible form of acute kidney injury (AKI) that begins soon after the contrast is administered . Since tAn earlier randomized trial demonstrated that transient arm ischemia induced by intermittent blood pressure cuff inflation prior to contrast administration conferred protection against contrast nephropathy . A seconAdministration of intravenous fluids for volume expansion is very common in critically ill patients, particularly in the early stages of sepsis or during the perioperative period. A recent report of US Food and Drug Administration (FDA) indicates a higher risk of renal injury and mortality in critically ill patients treated with HES. The report recommends not using HES therapy in patients with preexisting renal dysfunction and to stop HES therapy at first sign of renal failure or coagulopathy. As HES fluids have higher associated costs than crystalloids, it seems reasonable to conclude that such fluids should not be used in critically ill patients .A recent paper  questionPeginesatide is a synthetic peptide, attached to polyethylene glycol (“PEGylated”)  which miTolvaptan is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia associated with congestive heart failure, cirrhosis and the syndrome of inappropriate antidiuretic hormone (SIADH). It was also demonstrated that it could be beneficial in the treatment for polycystic kidney disease by decreasing cAMP levels, inhibit cystogenesis . AccordiIn our days, dialysis is widely available determining the nephrologists to consider its application in every patient in whom it might be indicated. Furthermore, the proportion of aged patients entering dialysis is fasting increasing over time. Overall, the initiating of dialysis in patients older than 70 years is associated with a better outcome as noted in a recent large retrospective study. However, the survival benefit was not observed among patients older than 80 years or among those with significant comorbidities. In addition, dialyzed patients were more prone to be hospitalized compared with patients on conservative care, which could have a negative impact on quality of life .The human polyomaviruses BK are highly prevalent in humans but appear to cause clinical disease only in immunocompromised patients. BK virus primarily causes tubulointerstitial nephritis and ureteral stenosis in renal transplant with a medium reported prevalence of 5 % . Hirsch Quantitative nucleic acid amplification testing (QNAT) is preferred for diagnosis, decisions regarding preemptive therapy and monitoring response to therapy due to the ability to harmonize and standardize these tests . If QNAT is not available, antigenemia is an acceptable alternative; viral culture of blood or urine has a very limited role for the diagnosis of disease.Valganciclovir is increasingly used as the preferred agent for treatment. Additional specific recommendations on the use of IVIG with CMV treatment are included.Diagnostic resistance mutations have been updated, and the clinical management algorithm for ganciclovir-resistant CMV has been slightly modified to clarify decision-making criteria.In the pediatrics section, valganciclovir is included in the prevention and treatment of CMV due to new data detailing the pharmacokinetics of valganciclovir in pediatrics .Cytomegalovirus (CMV) remains one of the most common complications affecting organ transplant recipients, with significant morbidity, graft loss and occasional mortality . The Tra


P<0.001] and maximum P wave duration  were associated with progression to renal end points. Furthermore, increased P wave dispersion  and maximum P wave duration  were negatively associated with the eGFR slope. We demonstrated that increased P wave dispersion and maximum P wave duration were associated with progression to the renal end points of dialysis or death and faster renal function decline in CKD patients. Screening CKD patients on the basis of P wave dispersion and maximum P wave duration may help identify patients at high risk for worse renal outcomes.P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as a noninvasive tool to evaluate left atrial enlargement. This study was designed to assess whether P wave parameters were associated with renal outcomes in chronic kidney disease (CKD) patients. This longitudinal study enrolled 439 patients with CKD stages 3–5. Renal end points were defined as the commencement of dialysis or death. Change in renal function was measured using the estimated glomerular filtration rate (eGFR) slope. We measured two ECG P wave parameters corrected for heart rate, i.e., corrected P wave dispersion and corrected maximum P wave duration. The values of P wave dispersion and maximum P wave duration were 88.8±21.7 ms and 153.3±21.7 ms, respectively. During the follow-up period , 95 patients (21.6%) started hemodialysis and 30 deaths (6.8%) were recorded. Multivariate Cox regression analysis identified that increased P wave dispersion [hazard ratio (HR), 1.020; 95% confidence interval (CI), 1.009–1.032;  Both traditional risk factors, such as hypertension, diabetes, and dyslipidemia, and non-traditional risk factors, such as cardiovascular disease contribute to the risk of progressive renal function loss Echocardiographic measures of left ventricular function and structure as well as left atrial size have been reported to predict adverse renal outcomes The study protocol was approved by the Institutional Review Board of the Kaohsiung Medical University Hospital (KMUH-IRB-20130305). Informed consent was obtained in written form from patients and all clinical investigations were conducted according to the principles of the Declaration of Helsinki. The patients gave consent for the publication of the clinical details.2) of 30–59, 15–29, and <15 respectively. Patients with atrial fibrillation, significant mitral valve disease, and inadequate ECG image visualization were excluded. Twenty-seven patients with less than three eGFR measurements during the follow-up period were excluded. Those patients who died (n = 9) or entered dialysis therapy (n = 30) within 3 months after enrollment were also excluded to avoid incomplete observation of changes in renal function. Finally, 439 patients  were included in this study.The study was conducted in a regional hospital in southern Taiwan. From January 2007 to May 2010, we consecutively enrolled 505 pre-dialysis patients with CKD stages 3–5, according to the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines 1/2A standard 12-lead surface ECG  was performed in all study patients. An image analysis software system (Image Tool 3.0) was used to perform quantitative assessments. We assessed the correlation of two P wave parameters, corrected P wave dispersion and corrected maximum P wave duration, with progression to dialysis or death and decline in renal function. P wave dispersion was calculated as the difference between maximum and minimum P wave duration 1 and the R wave in lead V5 or V6 greater than 3.5 mV) LVH was defined as Sokolow-Lyon voltage criteria via 12-lead ECG (sum of the amplitude of the S wave in lead Vversus never), and comorbid conditions were obtained from medical records or patient interviews. The body mass index (BMI) was calculated as the ratio of weight in kilograms divided by square of height in meters. Laboratory data were measured from fasting blood samples using an autoanalyzer . Serum creatinine was measured by the compensated Jaffé  method in a Roche/Integra 400 Analyzer  using a calibrator traceable to isotope-dilution mass spectrometry Demographic and medical data including age, gender, smoking history  for triglycerides and number of serum creatinine measurements. The differences between groups were analyzed using the Chi-square test for categorical variables and using the independent t-test for continuous variables. Time to renal end points and covariates of risk factors were modeled using the Cox proportional hazards model. The survival curve for renal end points was derived using Kaplan–Meier analysis. Linear regression analysis was used to identify the factors associated with the eGFR slope. The association of P wave parameters with renal end points and the eGFR slope was assessed using a modified stepwise procedure in two modeling steps. The first model consisted of age and sex. In the second model, clinical and biochemical risk factors were added. A significant improvement in model prediction was found by calculating the improvement in –2 log likelihood or adjusted R square values. A difference was considered significant if the P value was less than 0.05.Statistical analysis was performed using SPSS version 17.0  for Windows. Data were expressed as percentages, mean ± standard deviation, mean ± standard error of the mean for the eGFR slope, or median (25th–75th percentile: 6–12). The values of P wave dispersion and maximum P wave duration were 88.8±21.7 ms and 153.3±21.7 ms, respectively. The eGFR slope for all patients was –1.60±0.15 mL/min/1.73 m2/year. The underlying etiology of CKD in our patients was diabetic kidney disease in 232 (52.8%), non-diabetic glomerular diseases in 128 (29.2%), tubulointerstitial diseases in 46 (10.5%), hypertension in 23 (5.2%), and other diseases in 10 (2.3%). The clinical characteristics of patients with and without renal end points are shown in Four hundred and thirty-nine non-dialyzed CKD patients were included. The mean age was 66.0±12.0 years and there were 274 males and 165 females. The average number of serum creatinine measurements during the follow-up period was eight (25P<0.001). The relationship remained significant after further adjustment for smoking, DM, hypertension, coronary artery disease, cerebrovascular disease, LVH, systolic and diastolic blood pressure, BMI, albumin, fasting glucose, log triglycerides, total cholesterol, hemoglobin, baseline eGFR, calcium-phosphorus product, uric acid, and proteinuria . In the second analysis, there was also a significant prognostic value of maximum P wave duration in relation to renal end points  in multivariate analysis after adjustment for demographic, clinical, and biochemical factors. In addition, the commencement of dialysis and death were competitive risks for composite end points in this study. We also performed competing risk analysis and found that P wave dispersion (P = 0.046) remained significantly associated with progression to dialysis after multivariate analysis, but maximum P wave duration did not (P = 0.14).The mean follow-up period was 25.2±12.7 months . During the follow-up period, ninety-five patients (21.6%) started hemodialysis and 30 deaths were recorded in the 439 patients. Causes of death included fatal cardiovascular events (n = 13), infectious disease (n = 13), and other (n = 4). Among the 13 fatal cardiovascular events, 4 were myocardial infarction, 3 were pulseless electrical activity, 3 were ventricular fibrillation and 3 were heart failure. The multivariate Cox proportional hazards regression analyses of P wave dispersion and maximum P wave duration for renal end points are shown in P<0.001). The unadjusted HR for tertile 2 versus tertile 1 was 1.834  and for tertile 3 versus tertile 1 was 2.842 . P = 0.003). The unadjusted HR for tertile 2 versus tertile 1 was 1.385  and for tertile 3 versus tertile 1 was 2.115 .P<0.001 and 6.335, P = 0.012, respectively).The addition of P wave dispersion and maximum P wave duration to a basic model  significantly improved the prediction value for renal end points  and maximum P wave duration  were significantly associated with progression to renal end points after multiple adjustments for demographic, clinical, and biochemical factors.Patients with CKD stage 5 (n = 131) were at an extremely high risk of reaching end-stage renal disease in a very short term. Therefore, we performed subgroup analysis after excluding those patients. The results were similar, i.e., patients with increased P wave dispersion  and, further adjustment for smoking, DM, hypertension, coronary artery disease, cerebrovascular disease, LVH, systolic and diastolic blood pressure, BMI, albumin, fasting glucose, log triglycerides, total cholesterol, hemoglobin, baseline eGFR, calcium-phosphorus product, uric acid, and proteinuria . In the second multivariate analysis, maximum P wave duration was also negatively associated with the eGFR slope  after adjustment for demographic, clinical, and biochemical factors.P = 0.037 and 0.009, P = 0.040, respectively).The addition of P wave dispersion and maximum P wave duration to a basic model  significantly improved the prediction value for renal function decline . In addition, maximum P wave duration had a significant positive correlation with DM, fasting glucose, log triglycerides, and proteinuria. In multivariate analysis, maximum P wave duration was independently correlated with DM .In univariate analysis, P wave dispersion had a significant positive correlation with DM  in the elderly. We recently reported that concentric LVH, increased left atrial diameter, and decreased left ventricular ejection fraction were associated with adverse renal outcomes 22.Paoletti et al. Diabetic nephropathy is one of the major complications of DM and one of the major causes of renal replacement therapy Our study had some limitations. The number and interval of serum creatinine measurements varied in each patient. We therefore excluded patients with less than three eGFR measurements during the follow-up period and those patients with a follow-up period of <3 months, in order to decrease the chance of not completely observing a change in renal function. In addition, P wave parameters cannot completely replace echocardiography because they do not provide a comprehensive examination of the heart. However, they can provide a simple and inexpensive method for detecting patients at risk of left atrial enlargement and left ventricular diastolic and systolic dysfunction.In conclusion, our results demonstrated that increases in P wave dispersion and maximum P wave duration were independently associated with progression to the renal end points of dialysis or death and faster renal function decline in patients with CKD stages 3–5. Beyond conventional clinical features, measurement of P wave dispersion and maximum P wave duration offers an extra benefit in predicting the renal end points of dialysis or death and faster renal function decline. Screening CKD patients on the basis of P wave dispersion and maximum P wave duration, measured by 12-lead ECG, may help identify patients at high risk for worse renal outcomes.


Ambulatory and/or home monitoring are recommended in the UK and the US for the diagnosis of hypertension but little is known about their acceptability.To determine the acceptability of different methods of measuring blood pressure to people from different minority ethnic groups.Cross-sectional study with focus groups in primary care in the West Midlands.People of different ethnicities with and without hypertension were assessed for acceptability of clinic, home, and ambulatory blood pressure measurement using completion rate, questionnaire, and focus groups.n = 300), South Asian (n = 241), and African Caribbean (n = 229). White British participants had significantly higher successful completion rates across all monitoring modalities compared with the other ethnic groups, especially for ambulatory monitoring: white British  versus South Asian  and African Caribbean , respectively. There were significantly lower acceptability scores for minority ethnic participants across all monitoring methods compared with white British participants. Focus group results highlighted self-monitoring as most acceptable and ambulatory monitoring least acceptable without consistent differences by ethnicity. Clinic monitoring was seen as inconvenient and anxiety provoking but with the advantage of immediate professional input.A total of 770 participants were included, who were white British (Reduced acceptability and completion rates among minority ethnic groups raise important questions for the implementation and interpretation of blood pressure monitoring. Selection of method of blood pressure monitoring should take into account clinical need, patient preference, and potential cultural barriers to monitoring. This may vary with both lifestyle and culture, hence the potential impact of ethnicity, which is also associated with cardiovascular prognosis.8–There have been few studies concerning the acceptability of different methods of blood pressure monitoring. Those that have been undertaken suggest that ABPM is associated with discomfort and sleep disturbance, although physicians may be able to make better treatment decisions as a result.10,14This work formed part of the Blood Pressure in Ethnic Groups Study (BP-Eth) for which detailed methods, including for the qualitative work, have been described previously.14,16,17Participants attended three research clinic appointments and had their blood pressure measured on each occasion. Between clinic visits their home blood pressure was measured for 1 week, and ambulatory blood pressure was measured for 24 hours.14Ambulatory and home blood pressure monitoring are now recommended in both the UK and the US but little is known about the acceptability of these methods, particularly among minority ethnic groups. This research has shown that home monitoring, and particularly ambulatory monitoring, are less likely to be completed by minority ethnic individuals, even in a research setting with multilingual facilitators. Acceptability of ambulatory monitoring as measured by questionnaire and in qualitative focus groups was lower than either home or clinic measurement. Clinicians’ decisions regarding method of blood pressure monitoring should take into account both clinical need and patient preference, particularly for those from minority ethnic populations.recording of clinic blood pressure at each of the three clinic appointments;12 home readings on at least 4 days in the measurement week; andat least 14 valid daytime ambulatory blood pressure readings.Completion rates for each method were defined using standard definitions as follows:Previously validated acceptability questionnaires were completed following each method (first occasion for clinic readings).11,A convenience sample of participants willing to take part in an embedded focus group study was purposefully chosen to represent males and females as well as the three ethnic groups .19completion rates for each method;acceptability using a previously validated questionnaire; and11a rank order of preference for each method. This included both doctor- and nurse-measured clinic blood pressure in order to be comparable with other studies using the same ranking system.Outcome data for the quantitative analysis comprised:A three-level hierarchical model was developed: level 1 acceptability score, level 2 patient, and level 3 general practice. The model had a pre-specified set of covariates: ethnicity, age, sex, marital status, Index of Multiple Deprivation (IMD 2007),The study was powered on the ability to detect differences in blood pressure between the different ethnic groups rather than acceptability, but retained the power of 80% at a 5% two-sided significance to detect a 10% difference in completion rates between ethnic groups assuming there were at least 219 participants in each group and that the rate was 80% on one group and 70% in the other.Focus group transcripts were analysed thematically then triangulated and coded.232.Data were available from 770 participants, (481 [63%] known to be hypertensive) from the three ethnic groups under consideration . One whin = 171, 71% [95% CI = 65% to 76%]) than either African Caribbean  or white British . Both minority ethnic groups were less likely to complete home monitoring than white British participants Participants from four out of six focus groups felt that a key benefit arising from office monitoring was the presence of a clinician while measurements were being made. This was due to a perceived improvement in the accuracy of readings resulting from a professional executing the process and their immediate interpretation of results, thus enabling any necessary action to be promptly taken:‘Well, I think the fact that you’re in the right place and that you’re not the expert … and if there are any issues … well, at least there is some experience and expertise around.’‘When I was taking it myself I was quite calm … but there’s something about coming up here that I don’t … I don’t cut it, I don’t like coming up to hospital and surgery so I get all wound up.’Every focus group apart from white British males mentioned anxiety caused by the office environment as an issue leading to falsely high readings. Some white British females found that the cuff that was used in the study for clinic readings sometimes caused bruising and members of the African Caribbean male group found attending the clinic inconvenient:‘The one you did yourself was much better, it saves you coming to the doctors … it’s much easier to do at home than coming in.’Home monitoring was popular and preferred by all three ethnic groups, particularly African Caribbean participants. Key positive themes emerging were the ease of home monitoring, its accuracy and/or efficiency, and increased patient involvement. Conversely, some expressed concern about the need for timing and discipline whereas others doubted their own competence in executing the method.‘I mean, taking it, is a doddle. It’s extremely easy to do when you know what you’re doing.’All six focus groups reported that home monitoring was straightforward both in terms of executing the process and fitting it around daily activities. The two South Asian groups in particular found it very convenient:‘I think that the GP should be able to decide better about the medication because I think that when you are at home you are more calm and relaxed, so your blood pressure reading should be alright.’Self-monitoring was also seen as offering improved efficiency over other methods due to the increased number of readings resulting from a relatively low input of time. This was considered to improve accuracy, as was the ‘relaxing’ nature of the home setting, which was felt to enable a better representation of blood pressure:‘I didn’t mind having it done, in fact I started to get more interested in my blood pressure.’Self-monitoring was considered to promote patient involvement in the management of blood pressure:‘Doctors don’t like people taking their blood pressure all the time … and I do think that there is resistance within doctors to people to keep on taking their own blood pressure … there is that idea that “leave it to the experts”.’However, the white British female group felt that they needed explicit ‘permission’ from their doctor to self-monitor:‘… at home because of the time limit that we were given, when we could take the morning and the evening, being a part-time worker, working shift work, I was very limited … to when I could do mine.’Remembering to home monitor was an issue raised by all ethnic groups, particularly for those doing shift work. This related to the guideline stipulation to take both morning and evening measurements between 6 and 12 o’clock:‘… the question when you’ve got your own monitor, is, is it as good as the one that the GP’s got? You think … well, am I doing it right?’There were concerns within all ethnic groups regarding accuracy of the equipment and lack of experience in executing the method:‘But when I got home and I thought, oh, you know, I’ve got to take my blood pressure I suddenly, I had a huge panic attack ... and then of course, when I took it, it was high ... I mean it was bound to be, wasn’t it?’Others felt that home monitoring was anxiety provoking due to the fear of a high reading and its associated health implications:‘The first one I had was 206 mmHg — I thought I was going to die.’ABPM was valued for its accuracy by all ethnic groups. However, this was tempered by its impact on daily activities and sleep, along with the embarrassment caused by others being aware of its presence.‘I think that coming to your GP etc. isn’t a problem: but they’re just random snapshots so I’m more convinced about the 24-hour one taking an average.’Ambulatory monitoring was widely seen to improve accuracy, thereby enabling better clinical decisions to be made about blood pressure:‘If we had to do it on a regular basis then I would find that really uncomfortable … but for the one day I didn’t mind.’However, although only a minority supported its use on multiple occasions, a number of participants said that they were happy to do it as a ‘one-off’:‘… but at the time I’d only just been made redundant so it was just a case of saying “this really isn’t a normal day” … so it would be interesting to see what the results would be (if I had been more active).’White British participants particularly commented that ABPM measurements depended on what they had been doing on the measurement day. If this was not typical of their usual routine then some thought that the resulting readings might not represent their ‘true’ blood pressure:‘I didn’t get much sleep (on the day of the ABPM) because as soon as it started it woke me up.’More than twice as many negative as positive comments were made regarding ambulatory monitoring. A key issue here was disruption to sleep and other activities due to discomfort. Such views were held regardless of ethnicity:‘If the design was a bit more discreet and a little bit more user-friendly then maybe we would have had a different experience but as it stands now, you know, it is intrusive.’The fact that monitoring occurred throughout the day and was obvious to others, hence resulting in potential embarrassment, were particular issues reported by South Asian and African Caribbean participants:‘… what I did mind was walking along the road and then I would get the warning and have to stop … and people were watching me … and it was so embarrassing.’‘… ‘cos I live with my in-laws I had to hide it from them ‘cos I didn’t want them to get worried that there was something wrong.’Both minority ethnic groups commented on the anxiety that ambulatory monitoring brought on and the impression given to others of having a medical problem:,This study has evaluated acceptability data from a large group of people drawn from white British and two major minority ethnic groups, and has shown that, although all methods of blood pressure monitoring were broadly acceptable to people from all three ethnic groups, ambulatory monitoring was less favoured. Furthermore, South Asian and African Caribbean participants found all types of monitoring significantly less acceptable than those from the white British group and this was reflected in lower completion rates, particularly for South Asian participants. Given UK and international guidelines on the use of ambulatory monitoring for the diagnosis of hypertension, a 20% difference in completion of such monitoring could have a significant impact on the quality of care across ethnic communities.6To the authors’ knowledge, this is the first study to gain detailed information on the acceptability and performance of different methods of blood pressure monitoring in a large multiethnic population. This is important because such monitoring is such a common aspect of clinical management, particularly in primary care. The results are strengthened by using a combination of methods.Participants were recruited from one area of the UK (the West Midlands), and homogeneity within ethnic groups has been assumed. This might potentially limit generalisability in that there may be differences within the ethnic categories used in this study. However, the uniformity of responses from multiple methods by those of different ethnic groups suggests that this is unlikely to have affected the headline results.Recruitment relied on purposive sampling of a pool of volunteers to ensure that all three minority ethnic groups were represented, as were those with and without a diagnosis of hypertension. Responders from minority ethnic groups were younger and this was taken into account in the statistical analysis.–In common with previous studies, this work has shown that ambulatory monitoring is less acceptable than other methods of blood pressure measurement.11Although relative preferences for modality of blood pressure monitoring were broadly consistent between ethnic groups, South Asian and African Caribbean participants rated all modalities of blood pressure monitoring less favourably than did their white British counterparts, albeit only approaching significance for the South Asian group for ABPM. This fits with data suggesting that minority ethnic groups rate various aspects of primary care less favourably than white British groups.27,Responders considered ABPM to be acceptable when there was a clear medical need, as it resulted in improved accuracy, reinforcing findings from the US and Greece.12,30,31The positive views on home monitoring expressed here reinforce similar findings from previous trials.28Around 20% fewer South Asian individuals completed the minimum acceptable number of ambulatory measurements than white British people, despite a multilingual research team, availability of translated research materials, and probably longer explanations than may occur in daily practice. This seems from the focus groups to have been at least in part because of issues of embarrassment compounded by questions from extended family that may be more relevant to those from minority ethnic groups. Serious consideration as to how this problem can be addressed is needed if the benefits of accurate monitoring and, particularly, diagnosis are to be extended to all. An important issue is the current often bulky and noisy ambulatory monitoring technology. New methods of indirect blood pressure monitoring that do not require inflating cuffs are under development and may address this.32,Greater use of home monitoring in the management of hypertension seems likely to be supported by people of all ethnicities. In the meantime, clinic monitoring currently retains a significant role in the management of hypertension despite its inaccuracy.5


Although several cross-sectional and intervention studies showed that sodium intake or excretion was associated with blood pressure levels, no prospective study has examined the long-term association between sodium excretion in spot urine and blood pressure changes.2) and overweight normotensives.We conducted a prospective study of 889 normotensive subjects  who underwent the baseline survey including spot urine test in 2005 and the follow-up survey in 2009 to 2011 (mean follow-up period: 5.8 years). We examined the association between sodium concentration in spot urine, a validated index of sodium excretion occurring over 24-h, and blood pressure changes between baseline and follow-up survey in all, non-overweight (body mass index(BMI) ≤ 25 kg/mP for difference = 0.021, P for trend = 0.040). After further adjustment of baseline blood pressure levels, the association was slightly weakened; the multivariable-adjusted mean values of the systolic blood pressure changes were +7.0 mmHg and +4.2 mmHg .For all subjects, sodium concentrations in spot urine were not associated with either systolic or diastolic blood pressure changes. When stratified by BMI at baseline survey, sodium concentrations were positively associated with systolic blood pressure changes in non-overweight subjects, but not in overweight subjects. After adjustment for age, sex, BMI, alcohol intake status, current smoking and estimated glomerular filtration rate, the multivariable-adjusted mean values of the systolic blood pressure change among non-overweight subjects was +7.3 mmHg in the highest quartiles of sodium concentrations, while it was +3.9 mmHg in the lowest quartile The online version of this article (doi:10.1186/s12872-016-0219-1) contains supplementary material, which is available to authorized users. The relationship between sodium intake and blood pressure has been investigated since the 1900s and the associations between sodium intake/excretion and blood pressure levels have been studied mainly by using cross-sectional designs . Further2 in men and 22.4 kg/m2 in women [2 in US men and 28.1 kg/m2 in US women [The prevalence of hypertension has been reported to be similar between the Japanese and American populations. According to national surveys, the prevalence of hypertension among 40 to 64-year-old Japanese men and women was 42 % , while tin women , while tUS women . AccordiUS women , while iUS women . TherefoA “gold standard” to evaluate sodium intake or excretion would be a urine sample collection repeated every 24 h, but it is not easy to conduct such an assay for general populations. Several studies have shown that spot urine is also a practical and useful method to evaluate sodium excretion –15. UsinThe subjects were residents of Kyowa, a rural district of Chikusei City, Ibaraki Prefecture, Japan. The population in the area was 16,778 , determined by census in 2005. The Kyowa community is a community-based part of the Circulatory Risk in the Community Study (CIRCS) [n = 8); they refused to take blood samples (n = 2); they had high-serum creatinine concentrations (≥ 1.4 mg/dl for men and ≥ 1.2 mg/dl for women) or had a history of renal disease (n = 18); extremely high sodium to creatinine ratio in spot urine (≥ 15) (n = 4) or non-validated height due to scoliosis (n = 3). Of the remaining 2,694 subjects, 1,516 subjects were normotensive and 1,178 subjects were hypertensive (systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure of ≥ 90 mm Hg and/or under antihypertensive medication). Of the normotensive 1,516 subjects, 971 subjects (64.1 %) participated in follow-up cardiovascular risk surveys in 2009 to 2011. We excluded 71 subjects who initiated antihypertensive medication at follow-up surveys. We also excluded 11 subjects because they measured their blood pressure only once (but not twice) at follow-up surveys.There were 2,729 participants  aged 40 to 75 years old in the 2005 baseline cardiovascular risk survey. We excluded 35 subjects because they refused to take urinalysis  for the analyses Fig. . If the rinri-1). According to the Japanese ethics guidelines, we provided the ethical information on our study at the survey sites and opt out opportunities.This study was approved by the Ethics Committee in University of Tsukuba , Osaka University  and Dokkyo Medical University (dmu-25004), and institutional review boards of the Osaka Center for Cancer and Cardiovascular Diseases Prevention   on the right arm twice. According to the validation study of TM-2655 series, the TM-2655 device achieved British Hypertension Society grade A for systolic and A for diastolic blood pressures, and the proportions of values agreeing to within 5 mmHg were 72.5 % for systolic blood pressure and 78.8 % for diastolic blood pressure . In addiThe validity of measurement of the components in spot urine was checked in a subsample of 225 subjects (85 men and 140 women) who underwent 24-h urine collection in 2005 . The conP<0.01; sodium excretion (g/day)= 0.032 x sodium concentration (mmol/l) -2.278 (women) + 9.130) , while it was 0.16 between the sodium to creatinine ratio in spot urine, and 24-h urinary sodium excretion. Therefore, we used the sodium concentrations in spot urine as an index of the level of sodium excretion. As for potassium and urea nitrogen, the Spearman correlation coefficients between their concentrations in spot urine and their levels of urinary excretion over 24-h were 0.01 and 0.31, respectively. The Spearman correlation coefficient between the potassium to creatinine ratio in spot urine and 24-h urinary potassium excretions was 0.20. That between of the urea nitrogen to creatinine ratio in spot urine and 24-h urinary urea nitrogen excretions was 0.11.The sodium to creatinine ratio in urine has frequently been used as a marker of sodium excretion during 24-h urine collections –15. In t2) according to the following formula, established by the working group of the Japanese Chronic Kidney Disease Initiative: eGFR (ml/min/1.73 m2) = 1.94 x (serum creatinine)-1.094 x (age)-0.287 for men and 1.94 x (serum creatinine)-1.094 x (age)-0.287 x 0.739 for women [We calculated estimated glomerular filtration rate (eGFR) (ml/min/1.73 mor women .P for interaction = 0.96 for systolic blood pressure and P for interaction = 0.36 for diastolic blood pressure). We performed the stratified analysis by the presence or absence of overweight (BMI ≥ 25 kg/m2) because sodium sensitivity can be enhanced in the overweight subjects [The analysis was performed for blood pressure changes according to quartiles of sodium concentrations in spot urine. We present the combined data for men and women, because we tested sex interaction for the each analysis and found no significant interactions  value: HbA1c (NGSP) = 1.02 × HbA1c(JDS) + 0.25 % . We defi2), drinking status , current smoking (yes or no) and eGFR (ml/min/1.73 m2). We also used the baseline value of systolic or diastolic blood pressure level as confounding variable.The confounding variables for adjustment included age (years), sex, BMI  were considered statistically significant.We used SAS version 9.3 software  for all analyses. The distribution of sodium concentration in spot urine among all subjects is illustrated in Additional file P = 0.060). The corresponding mean value was +6.8 mmHg in the highest quartile of sodium concentrations while it was +4.5 mmHg in the lowest quartile (P for difference = 0.078). For non-overweight subjects, the multivariable-adjusted mean of systolic blood pressure changes associated with 1-SD increment of sodium concentrations was +1.1 mmHg (P = 0.040). The corresponding mean value was +7.3 mmHg in the highest quartile of sodium concentrations, while it was +3.9 mmHg in the lowest quartile (P for difference = 0.021). After further adjustment for baseline blood pressure levels, these association were weakened slightly; the multivariable-adjusted mean of systolic blood pressure changes associated with 1-SD increment of sodium concentrations was +0.9 mmHg (P = 0.071). The corresponding mean value was +7.0 mmHg in the highest quartile of sodium concentrations, while it was +4.2 mmHg in the lowest quartile (P for difference = 0.047). For overweight subjects, no significant associations were observed between sodium concentrations and systolic blood pressure changes. For all categories, no significant changes were observed for diastolic blood pressure. We tested the interactions of sodium concentrations with body mass index, and found no significant interaction between them.Mean values in systolic and diastolic blood pressures at baseline and follow-up surveys among all subjects are illustrated in Additional file P = 0.187) and +0.1 mmHg (P = 0.728) for all subjects, respectively. We also examined the association between sodium/potassium ratio and blood pressure changes; however, the association was null. The multivariable-adjusted means of systolic and diastolic blood pressure changes associated with 1-SD increment of sodium/potassium ratio were −0.3 mmHg (P = 0.515) and 0.0 mmHg (P = 0.990) for all subjects, respectively. Those associations did not differ materially between non-overweight and overweight subjects.Additionally, we examined the association between sodium/creatinine ratio and blood pressure changes; however, the association was not statistically significant. The multivariable-adjusted means of systolic and diastolic blood pressure changes associated with 1-SD increment of sodium/creatinine ratio were −0.6 mmHg  was significantly associated with both systolic and diastolic blood pressure levels . The association was stronger in systolic blood pressure levels than in diastolic blood pressure levels .2 in the highest quartile, while it was 76.7 ml/min/1.73 m2 in the lowest quartile (P for difference = 0.038).Several mechanisms may be involved in the association between sodium excretion and increments in blood pressure levels. First, human kidneys cannot excrete excess sodium completely and thus accumulate water to decrease sodium concentrations in extracellular fluid . This leIn the present study, we found the significant association between sodium concentrations in spot urine and blood pressure changes in non-overweight but not overweight normotensives. The finding did not corroborate an implication that overweight or metabolic syndrome may enhance salt sensitivity , 21, makThe strength of the present study is that we conducted a prospective study of a community-based Japanese population sample. Prospective studies can show certain causal relationships and more relevant results compared with cross-sectional studies.P < 0.001). Because current smoking was not associated with blood pressure changes, such a selection bias unlikely affect our results. Fourth, we could not evaluate the changes of sodium intake between baseline and follow-up surveys because we did not measure sodium concentrations in spot urine repeatedly. Fifth, we have no information about education status, income and other social factors as potential confounding factors.The limitations of the present study warrant discussion. First, the correlation between sodium concentrations in spot urine and urine samples collected was very moderate. However, any errors concerning the misclassification were nondifferential and would have attenuated the association between sodium concentration and blood pressure changes. Second, we changed the device of blood pressure measurement from strandard mercury to automated sphygmomanometers in 2009 (the beginning of the follow-up study). However, the validation study allowed us to adjust the values of blood pressure between the two devices. Third, the follow-up rate of the present study was 64 %. However, there was no significant difference in baseline survey between subjects who participated in follow-up surveys and who did not, except for the proportion of current smoker. Subjects who participated in follow-up surveys showed the lower proportion of current smoker at baseline compared with subjects who did not (15 % vs. 21 %, High sodium concentrations in spot urine, an index of sodium excretion, was positively associated with future systolic blood pressure changes among non-overweight normotensive Japanese.


Retinal arterial narrowing is associated with higher office blood pressure (BP) and ambulatory blood pressure monitoring, and increased incidence of cardiovascular disease, but it is still unknown if the vessel caliber is associated with BP measured at the time of retinography acquisition.Retinal arteriolar and venular calibers were measured by the microdensitometric method in 448 patients with hypertension. Participants underwent 24-hours ambulatory blood pressure (24-h ABP) monitoring simultaneously with the retinography acquisition. Association between arteriolar and venular calibers with increase of 10 mmHg in the mean 24-hours, daily, and nightly BP, and with BP measured at the time of retinography, was evaluated by ANOVA and multivariate analyses.Mean 24-hours, daytime and nighttime systolic and diastolic BP were inversely associated with the arteriolar caliber, but not with the venular caliber. Arteriolar caliber decreased -0.8 (95% CI -1.4 to -0.2) μm per 10-mmHg increase in 24-hours mean systolic BP, adjusted for age, gender, fellow vessel, and duration of hypertension (P = 0.01). The corresponding decreasing in arteriolar caliber by 10 mmHg of increasing in mean diastolic BP was -1.1 μm . The decrease of arteriolar caliber by the same increasing of BP measured at the time of retinography was lower and not statistically significant, particularly for mean diastolic BP and outer arterioles calibers: -1.0 (-1.8 to -0.2) μm in the daytime BP average versus -0.3 (-0.9 to 0.3) at the moment of retinography acquisition.These findings suggest that the caliber of arteriolar retinal vessels in patients with uncontrolled hypertension are not significantly influenced by blood pressure measured at the time of retinography acquisition. The classical studies linking abnormalities in retinal vessels diameters and hypertension were based on direct examination of optic fundi and in office blood pressure measurement . The dirBlood pressure has been measured only at the office and not by 24-hour ambulatory blood pressure (24-h ABP) monitoring in epidemiological studies ,12. OverThis cross-sectional study was done with patients screened to participate in the MONITOR study  . This stAll individuals were submitted to 24-h ABP monitoring using the equipment Spacelabs 90207 . Readings were obtained automatically at intervals of 15 minutes during the day (07:00 AM to •23:00 PM) and 20 minutes at night (23:00 PM to 7:00 AM). Patients with less than eight measurements during the night or 16 during the day were excluded from further analysis [Fundus photography was acquired after pharmacologic pupil dilation (20 min after instillation of tropicamine) using Topcon TVR-50 retinal camera  in a 35- degree angle centered on the optic disc. The color slides were digitized in a 35-mm film scanner Hewlett Packard model Photo Smart 20S  with a resolution of 600 dots per inch. Images were stored in 24 bits (true color). Retinography was obtained during the day of ABP monitoring, usually between 11 AM and 2 PM. The capture of retinal image and blood pressure measurement were synchronized. The picture was taken just after a measurement of blood pressure by the device.Retinal vascular caliber was measured using an updated version of a semiautomatic computer-based program developed in our service  . BrieflyMeasurements of vessel calibers were performed in one eye, usually the right eye. When the right eye was not feasible, the assessment was carried out in the left eye. Previously to the study, we assessed differences among eyes by measuring the scale factor in both eyes and the mean scale factor was included as a constant in the software. The scale factor was determined measuring the distance between the center of macula to center of optic disc in a sample of digitized photographs containing the macula and the optic disc in the same field. Differences between right and left eyes among the same subjects were not clinically relevant or statistically significant and gave support for the use of a single eye vessel measurement in larger studies. In addition, we tested the association of blood pressure with vessel calibers estimated by the Hubbard-Parr method  revised All analyses were performed using SPSS . One-way ANOVA and linear regression models were used to explore the association between blood pressure and retinal vascular caliber, adjusting for age, gender, and duration of hypertension. We also controlled for anatomy and measurement errors, including the caliber of the vessel correlated in the analysis. This allows to take into account that arteriolar and venular calibers are correlated and people with narrower arterioles are more likely to have narrower venules. Systolic and diastolic blood pressures included in the analyses were the average of 24 hour, daytime, nighttime, and blood pressure measured at the time of retinography acquisition. Vascular calibers were summarized as mean arteriolar caliber, mean venular caliber, and mean AVR, for inner and outer zones, respectively, and were compared by 10 mmHg of incremental in blood pressure.Reproducibility of the microdensitometric method was tested by an ophthalmologist who assessed the same photographs twice and by an independent ophthalmologist who verified a subsample of 20% of the photos, to determine reliability intra and inter observer, respectively  Bland-Alpriori approval by the institution's human research committee of our Institution , which is accredited by the US Office of Human Research Protections as an Institutional Review Board.Patients provided free and written informed consent. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a Arteriolar and venular calibers estimated by the revised Parr-Hubbard method ,19 were This study showed that the increasing in BP measured by ABP monitoring was associated with narrowing of retinal arteriolar caliber. The association was present for almost all periods of ABP measurements for systolic and diastolic BP. There was no association between arteriolar calibers and blood pressure measured at the time of retinography acquisition. In addition, venular calibers were not associated with increasing of blood pressure at any period of assessment. These findings suggest that structural abnormalities in the wall of retinal arterioles are more important to determine their narrowing  than acuThis study is among few that demonstrated the association between blood pressure, assessed by 24-hours ABP monitoring and retinal arteriolar caliber, and it is unique to determine these parameters simultaneously. We have previously demonstrated that the diameter of the vessel measured by a microdensitometric method corresponds to the vessel lumen  and coulThis study confirmed the well-known inverse association between retinal arteriolar diameters and blood pressure –30, but In the last decade, efforts have been devoted to the evaluation of vessel calibers and AV ratio for the evaluation of hypertensive changes in the retina –38, someIn the analyses with the revised Parr-Hubbard method , the decDespite the sample size and the cross-sectional design, our findings strengthen the evidence from larger cohort studies ,30,42,43In conclusion, the association between arteriolar retinal vessels caliber and blood pressure is not importantly influenced by instantaneous variation of blood pressure and probably depends of histological damage of arteriolar wall secondary to sustained hypertension. The evaluation of retinal vessels abnormalities by microdensitometric methods may help the risk stratification of patients with high blood pressure.


Chronic kidney disease (CKD) is increasing being recognized as a global public health problem. However, there is dearth of information on the prevalence, determinants, and management of CKD from low- and middle-income countries. The objectives of the study were to determine the 1) prevalence of CKD; 2) socio-demographic and clinical factors associated with CKD; and 3) the existing management of these patients with regards to blood pressure control, and use of antihypertensive medications.2 estimated by CKD-EPI (CKD Epidemiology Collaboration) Pakistan equation (0.686 × CKD-EPI1.059) or urinary albumin to creatinine ratio ≥3 mg/mmol .We conducted a cross-sectional study on 2873 participants aged ≥40 years in 12 representative communities in Karachi, Pakistan. The primary outcome was clinically significant CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mThe overall prevalence (95% CI) of CKD was 12.5% (11.4 – 13.8%). The factors independently associated with CKD were older age, hypertension, diabetes, elevated systolic blood pressure, raised fasting plasma glucose, raised triglycerides, and history of stroke (p < 0.05 for each). About 267  adults with CKD had concomitant hypertension. Of these, 130  were on antihypertensive medications, and less than 20% had their BP controlled to conventional target of ≤140/90 mm Hg, and only 16.9% (12.6 – 21.9%) were on blockers of renin-angiotensin system alone or in combination with other drugs.Clinically significant CKD is common among Pakistani adults. The conventional risk factors for CKD and poor control of blood pressure among patients with CKD highlight the need to integrate CKD prevention and management in the primary care infrastructure in Pakistan, and possibly neighbouring countries. As demonstrated in a large meta-analysis of a large general-population cohort of 105,872 participants, albuminuria is an independent marker of increase CVD mortality [Chronic kidney disease (CKD) is increasing being recognized as a major public health problem globally . The adv2), and albuminuria stages (A1 (<3 mg/mmol), A2 (3 to 30 mg/mmol) and A3 (>30 mg/mmol)). The guidelines also recommend using locally validated CKD-EPI equation as preferred methods for estimating GFR where available [The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines 2012 for the Evaluation and Management of Chronic Kidney Disease classify CKD based on eGFR stages  prevalence of CKD stage G3, A2 or worse; 2) socio-demographic and clinical factors associated with CKD; and 3) the existing management of patients with CKD with regards to BP control, and use of antihypertensive medications among adults in Karachi, Pakistan.This was a cross-sectional study representative of urban city of Karachi, Pakistan, conducted as part of baseline within a factorial design cluster randomized controlled trial . In brieTrained research staff visited all households in each of the 12 clusters, and informed consent was obtained for screening from all eligible adults; who then underwent for measurement of BP three times. The study was conducted over one year during 2004 – 2005.A routine physical examination was performed and the following information collected: (i) smoking status, food frequency and physical activity , co-morbidities ; (ii) anthropometry ; (iii) BP was measured thrice with a calibrated automated device  in the sitting position after 5 minutes of rest. If BP was elevated (systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg) based on mean of last 2 of 3 readings, subjects were visited again after 1 – 4 weeks for re-measurement of BP to confirm hypertension status if BP were persistently elevated, and (iv) Blood specimens for glucose, creatinine and lipids profile were collected in the morning after an overnight fast of about 10 – 12 hours. For urine microalbumin and creatinine, first morning sample was collected. All samples were transported in about one hour to the clinical laboratory at the Aga Khan University Hospital where samples were processed and stored at 2 – 8°C for appropriate tests performed within 24 hours. Serum creatinine and fasting blood glucose were measured on Synchron Cx-7/Delta; Beckman Coulter, Fullerton, CA; the lipid profile was measured on Hitachi-912; Roche, Basel, Switzerland. Urine microalbumin and creatinine were measured using nephelometry by the Array Systems method on a Beckman Coulter and Synchron Cx-7/Delta. All tests were performed to a standard protocol that confirmed to the international standards for definitions and measurements.Serum creatinine measurements were calibrated at the Cleveland Clinic laboratory-reference laboratory, where serum creatinine levels were measured again using the Roche enzymatic creatinine assay (in duplicate) which is traceable to the National Institute of Standards and Technology creatinine reference measurement .PK) equation, a modified version of CKD-EPI creatinine equation with a correction factor (0.686 × CKD-EPI1.059) for South Asians (estimated GFR (eGFR) based on this equation denoted as eGFRCKD-EPI(PK)) [Glomerular Filtration Rate (GFR) was estimated using the CKD-EPI (CKD Epidemiology Collaboration) Pakistan (CKD-EPIEPI(PK)) .Hypertension was defined as persistent elevation of SBP ≥140 mm Hg or DBP ≥90 mm Hg on the basis of average of last two of three readings measured 5 minutes apart at each visit, on two separate occasions, or taking antihypertensive medications.Diabetes was defined as fasting blood glucose ≥7.0 mmol/L, or taking anti-diabetic medications.CKD-EPI(PK) < 60 mL/min/1.73 m2 (reduced eGFR) or urinary albumin to creatinine ratio (UACR) ≥3 mg/mmol  based on a single spot urine sample.CKD  was defined as eGFRth and 75th percentiles respectively using quantile regression. The crude and age-standardized prevalence (95% CI) of CKD was computed. The reference population for the latter was WHO  World Standard Population [The analyses were performed in IBM SPSS v20 and Stata release 12.1 statistical software. The descriptive statistics were performed on 2873 participants by CKD status. Differences in means and proportions were assessed by t-test and chi-square test respectively. The distribution of eGFR in men and women was assessed graphically by plotting median, 25The final sample size for multivariable models was 2823 because of missing information on hypertension status on 50 subjects  control of BP to levels ≤ 130/80 mm Hg, and ≤140 /90 mm Hg, and 2) use of anti-hypertensive medications by UACR status, i.e. UACR <3 mg/mmol and ≥3 mg/mmol, respectively. For these analyses, KDIGO 2012 Clinical Practice Guideline based disease-specific definition of hypertension in CKD  was used [A total of 3143 adults were aged 40 years or older in the 12 communities, and were invited for blood and urine tests; these measurements were available on 2873 (91.4%) individuals. The baseline characteristics of the population with and without CKD are shown in Table 2, p < 0.001), mean DBP  or proportion of hypertension  was higher among subjects with available CKD information compared to those with missing information. An additional 50 individuals did not have hypertension status confirmed. A comparison of the above-mentioned characteristics with the individuals with complete information  did not show any significant difference with respect to age, gender, SBP, DBP, or stroke.Information on serum creatinine and UACR measurements was missing in 261 (8.3%), and 253 (8.0%) participants respectively. The characteristics of subjects with (n = 270) and without missing information on CKD (n = 2873) (i.e. serum creatinine and/or UACR) did not differ by age , gender , SBP  or history of stroke . However, mean BMI (25.8 vs. 24.1 Kg/mCKD-EPI(PK) <60.0 mL/min/1.73 m2), albuminuria (UACR ≥3 mg/mmol), and CKD was 5.3% (4.5 – 6.2%), 9.4% (8.4 – 10.5%), and 12.5% (11.4 – 13.8%) respectively.The distribution of eGFR among adult men and women is illustrated in Figure CKD-EPI(PK) <60.0 mL/min/1.73 m2), albuminuria (UACR ≥3 mg/mmol), and CKD was 7.4% (6.2 – 8.6%), 11.1% (9.8 –12.4%), and 15.3% (13.7 – 16.9%) respectively.The prevalence of CKD and reduced eGFR was higher in women compared to men, and increased with age Figure . The ageAmong the 2873 adults, a total of 359 (12.5%) had CKD. These patients were significantly older, more likely to be less physically active, have concomitant hypertension, diabetes, coronary heart disease and stroke compared to those without CKD (p < 0.05 for each).Table Among 359 individuals with CKD, 267  had concomitant hypertension using CKD specific definition. About 48.7% (42.6 – 54.9%) of these patients were on antihypertensive medications, and less than 20% had their BP controlled to conventional target of ≤140/90 mm Hg (Table CKD-EPI(PK) <60 mL/min/1.73 m2, and/or albuminuria ≥3 mg/mmol or higher, among adults aged 40 years or older in Karachi, Pakistan. The prevalence of reduced eGFRCKD-EPI(PK) alone was 5.3% (4.5 – 6.2%). We found that CKD was independently associated with older age, hypertension, diabetes, elevated SBP, raised fasting plasma glucose, raised triglyceride levels, and history of stroke (p < 0.05 for each). Despite a high proportion of associated co-morbidities, CKD remains under-treated with less than 10% and 20% of patients had their BP controlled to targets of ≤130/80 mm Hg, and ≤140/90 mm Hg, respectively per KDIGO 2012 Clinical Practice guidelines [Our population based study is the first to report prevalence and factors associated with CKD from a South Asian country using a locally validated eGFR equation. Our findings indicate a high (12.5%) prevalence of CKD, defined using validated eGFRThe distribution of eGFR in this population illustrate an age related decline, Figure  albeit wThe high prevalence of CKD is not surprising given the high burden of major CKD risk factors in South Asia. Hypertension and diabetes, both established risk factors for end stage kidney disease, were independently associated with CKD in this population ,15. ResuWe observed that high triglyceride levels were independently associated with CKD. These findings are consistent with those in the Western population demonstrating raised triglycerides in individuals with CKD,  which inRecent trials data suggest benefit of lipid lowering on CVD morbidity and mortality among patients with CKD . This prWe found that BP control was grossly sub-optimal with less than 20% of patients having BP controlled to conventional target of ≤140/90 mm Hg. The recent 2012 KDIGO CKD Clinical Practice guidelines underscore BP target of 130/80 mm Hg or less if the patient has CKD with a higher degree of albuminuria (UACR ≥3 mg/mmol) [Evidence suggests benefit of antihypertensive therapy and blockers of renin-angiotensin system are especially protective in patients with CKD and albuminuria . StrikinOur study has limitations. First, the cross-sectional design of the study does not permit conclusions regarding causation, and reverse causal association of CKD with BP, lipids, and other factors remains a possibility. However, evidence on the importance of controlling raised BP and glucose levels for slowing progression of CKD is well established. Second, since the study was conducted in Karachi, some variation in findings would be expected in other urban and rural areas of Pakistan. However, national survey indicates a high prevalence of hypertension and diabetes across urban and rural Pakistan . MoreoveThe study has several strengths. This is the first report of prevalence of CKD using a validated eGFR equation with a correction developed in the local South Asian population. Moreover, IDMS (Isotope Dilution Mass Spectrophotometry)-traceable serum creatinine, door to door survey and representative population based on census data of Karachi, and high response rate are the main strength of this study. Thus, our findings would be generalizable to the general population.PK estimating equation (eGFRCKD-EPI(PK) <60 mL/min/1.73 m2), or albuminuria (UACR ≥3 mg/mmol). We found that a high prevalence of CKD affecting 12.5% of adults aged 40 years or older. CKD was independently associated with older age, hypertension, diabetes, raised systolic BP, raised plasma fasting glucose, raised triglycerides, and history of stroke. Less than 20% of patients with CKD had BP controlled to conventional levels of ≤140/90 mm Hg. Our findings underscore the urgent need for integrating CKD prevention efforts in the primary care infrastructure in Pakistan, and possibly neighbouring countries with high burden of CKD.In summary, our findings are the first report of prevalence of CKD in Pakistan using a validated CKD-EPIPK: CKD-EPI Pakistan; eGFR: Estimated GFR; eGFRCKD-EPI(PK): eGFR estimated by CKD-EPI Pakistan; UACR: Urinary albumin to creatinine ratio; BMI: Body mass index; HDL: High density lipoprotein cholesterol; LDL: Low density lipoprotein cholesterol; KDIGO: ; IDMS: Isotope Dilution Mass Spectrophotometry.CKD: Chronic kidney disease; CVD: Cardiovascular disease; BP: Blood pressure; IPAQ: International physical activity questionnaire; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; GFR: Glomerular Filtration Rate; CKD-EPI: CKD Epidemiology Collaboration; CKD-EPIThe authors declare that they have no competing interests.THJ conceptualized the analytic plan for the study. SJ analyzed the data along with RB and prepared the first draft with advice from THJ. All authors critically reviewed the manuscript and provided input to the interpretation of findings. All authors have read and approved the final manuscript. THJ is the guarantor.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/15/90/prepubhttp://www.kmc.gos.pk/Contents.aspx?id=94.Map of Karachi city with randomized study areas. This map showing the randomized study areas marked as (X) has been adapted from town maps published by the “Master Plan Group of Offices, City District Government, Karachi, Year 2002” publically available on URL: Click here for fileFlow diagram of study participants aged ≥ 40 years.Click here for fileTable S2. Socio-demographic and clinical characteristics of individuals with and without albuminuria.Socio-demographic and clinical characteristics of individuals according to levels of estimated glomerular filtration rate. Click here for file