P < .05). Also, DGF during the first week after operation and duration of hospital stay was less in Group I compared with Group II. Intermittent exposure of human living kidney donor to hyperoxic environment may improve renal function following kidney transplantation. The purpose of this human study was to investigate the effect of oxygen pretreatment in living kidney donors on early renal function of transplanted kidney. Sixty living kidney donor individuals were assigned to receive either 8–10 L/min oxygen (Group I) by a non-rebreather mask with reservoir bag intermittently for one hour at four times  or air (Group II). After kidney transplantation, urine output, blood urea nitrogen (BUN), serum creatinine, need to additional diuretics (NTADs) in the first 24 hours after transplantation, delayed graft function (DGF), the creatinine clearance (CrCL) on 10th day, and duration of hospital stay from the first posttransplant day till normalization of renal function was recorded and compared in two groups. Mean CrCL in posttransplant day 10, NTAD after 24 hours of transplantation, and urine output during 6 hours after operation were significantly better in Group I compared with Group II ( Preservation of renal function is an essential purpose in renal transplantation and in many other vascular and urological procedures where renal functional impairment follows ischemia-reperfusion (I-R) injury . IschemiDelayed graft function (DGF) was defined as hemodialysis requirement during the first week after renal transplantation. Reperfusion injury is a risk factor for development of DGF after transplantation . Therefore, protective maneuvers before transplantation could obviously profit the fate of the organ. Murry et al.  in 1986 Inducing brief episodes of ischemia and reperfusion in human appears fairly aggressive and not satisfactory by many surgeons . AccordiAmongst the most practical methods for induction of ischemic tolerance in tissues is short-period exposure to hyperoxia which has no significant adverse effects and occasionally appears to be beneficial . In animal models, the protective effects of oxygen pretreatment on subsequent ischemia-reperfusion injury have been confirmed in heart , 18, bra2) environment can decrease rat's renal ischemia-reperfusion damage.Wahhabaghai and colleagues  showed tSince free radical formation is the main cause of IR injury , the mecTo the best of our knowledge, there is no human study which indicates this effect of oxygen pretreatment on renal function of transplanted kidney. Therefore, the present study was undertaken to determine whether brief exposure to the hyperoxia in living donors could improve renal function measured throughout 10 days after kidney transplantation.From October 2007 to December 2009, sixty ASA (American society of Anesthesiology) III patients with end-stage renal disease who had undergone first kidney transplant from a living donor, aged 18–65 years old, with no history of previous transplantation, human immunodeficiency, and hepatitis B and C virus infection were recruited to participate in this randomized, double blind clinical trial study.The kidney donors were 18–55 years old healthy (ASA I) individuals who were evaluated for kidney donation by corresponding nephrologists and their own recipients were WBC cross match negative.The study protocol was approved by the medical ethics research committee of our university, and written informed consent was obtained from each kidney donor. Recipients with new onset of any major complications  after transplantation, female donors to male recipients, and donors who were noncompliant with study protocol and received maintenance anesthesia other than isoflurane were excluded from the study. At enrolment, living kidney donors were assigned by a computer-generated list of random numbers to receive either 8–10 L/min oxygen (Group I) by a non-rebreather mask with reservoir bag intermittently for one hour at four times  or air (Group II).aO2) and assessing the effectiveness of oxygen administration. In the first five donors in each group, an arterial blood gas (ABG) test was done with permission of the participants for measuring the oxygen arterial partial pressure , type of dialysis, serology to hepatitis C and B virus, and last panel-reactive antibodies), and donors  were recorded in both groups.2), electrocardiogram, noninvasive arterial blood pressure, and heart rate were recorded in the operating room. After 3–5 minutes preoxygenation with 100% oxygen, anesthesia was induced with thiopental 5 mg/kg and fentanyl 3 μg/kg followed by atracurium 0.6 mg/kg to facilitate tracheal intubation. Anaesthesia was maintained with isoflurane 1–1.2% and nitrous oxide 50% in oxygen, and patients were maintained under controlled ventilation to achieve end-tidal CO2 values of 32–35 mmHg. No anesthetic premedication was given to the recipients and donors. Peripheral oxygen saturation . All recipients received normal saline 0.9% 70 mL/kg and furosemide 3 mg/kg before completion of vascular anastomosis. Residual neuromuscular blockade was reversed by neostigmine 40 μg/kg and atropine 20 μg/ kg at the end of surgery.In recipients, fentanyl 1 2 at a rate of 2–4 L/min with nasal prongs and were transferred to the kidney transplant intensive care unit after stabilization. After emergence from anaesthesia, patients were cared in the postanaesthetic care unit (PACU). They received supplemental OIn donors, induction and maintenance of anesthesia were similar and so for recipient patients. In donors, patients received 30 mL/kg Ringer until just before open nephrectomy. After nephrectomy, the kidney was prepared in University of Wisconsin (UW) solution at 4°C temperature and immediately transplanted to recipients.After kidney transplantation, urine output was monitored closely for volume hourly for the first 24 hours and recorded for statistical analysis during 1, 6, and 24 hours. If the patients had urine output volume less than 200 mL per hour in spite of adequate fluid therapy, additional diuretics (furosemide 10 mg per hour) were administered. Also, blood urea nitrogen (BUN) and serum creatinine (sCr), serum sodium and potassium were tested and recorded daily for 10 days. Urine sodium and creatinine were measured, and the fractional excretion of sodium (FENa) was calculated on the days 2 and 4 after kidney transplant. Any patients' DGF was recorded.The creatinine clearance (CrCL) on 10th day and duration of hospital stay were also recorded in two groups. Duration of hospital stay was defined as days required for renal functions become stabilized after transplantation day. Acute rejection (AR) was defined based on clinical and/or paraclinical data . If any patient had AR, it was recorded and treated according to the standard protocols. Maintenance of immunosuppression was cyclosporine A 3-4 mg/kg q12 h and adjusted to maintain trough blood level 150–300 ng/mL, mycophenolate mofetil 500–1000 mg q12 h, and prednisolone 1 mg/kg. t-test for unpaired data, or chi-square analysis, was used as appropriate, to assess differences between two groups. A P value of less than .05 was considered statistically significant.All data were analyzed with SPSS 16 . Patient characteristics were described as means ± SDs for continuous variables and frequency for categorical variables. Student's Sixty patients completed the study criteria for randomization. Seven patients dropped out of the study  in the first five donor participants from group I and group II was 303 ± 7.8 and 85 ± 3.7 mmHg, respectively.There were no significant differences between the two study groups with respect to the data concerning recipients  and donors (age and gender) . Mean (±P < .05)  .P < .05) (Urine output during 6 hours after operation was significantly more in Group I compared to Group II (P < .05) . The incP < .05) .2 and FENa4 between the two groups (P < .05) (There was no significant difference in FENao groups . Mean crP < .05) . There wP < .05) .Mean BUN and sCr on posttransplant day 10 was less in Group I compared with Group II, but it was not significant statistically .P < .05)  .There was not any statistically significant difference between the rates of postoperative complications among the two groups .The major finding of our study was that the intermittent exposure of living human kidney donors to the hyperoxia improves early renal function measured in the first ten days after kidney transplantation. Mean serum BUN and creatinine throughout posttransplant day 1 to 10, creatinine clearance in day 10, need to additional diuretics in the first 24 hours after operation, urine output during 6 hours after operation, and also duration of hospital stay were significantly better in Group I who were pretreated with hyperoxia compared with Group II who had no such exposure.As our study showed that the incidence of DGF was insignificantly more in Group II (14.3%) compared with Group I (4%). Generally, the great majority of kidney transplants are carried out using kidneys from standard criteria donors with moderate DGF rates of 21–31% , 24.A number of factors have been documented to impact short-term graft survival. These consist of delayed allograft function, HLA antibodies, type of donor kidney, donor illness, medical center factors, and other factors.Allograft injury participates an important role in both short- and long-term graft function, as well as in the induction of renal allograft rejection . Such inIschemia and/or reperfusion injury is supposed to be a critical risk factor for both early delayed graft function and late allograft dysfunction. The major cause of delayed graft function is postischemic acute tubular necrosis (ATN) . A numbeIn Szostek and colleagues  study, tThe conditions surrounding organ removal, storage, and engraftment possibly will enhance graft immunogenicity –31. SuchOld and very young kidneys have moderately reduced numbers of functioning nephrons and stay alive less well once transplanted. Besides fewer nephrons other factors intrinsic to an older kidney may well impact whole allograft survival . Large sDifferences in the capacity to produce an efficient immune response versus the allograft as well as variations in primary factors influencing allograft fibrosis signify alloantigen-independent factors that may impinge on graft survival . The above-discussed factors are the main cause of graft survival that may influence 14.3% incidence of DGF in the Group II patients. One limitation of our study was that we did not investigate the role of each factor separately. The methods used in our study did not allow us to identify the mechanisms by which hyperoxic preconditioning protected the transplanted kidney. We hypothesized that increased oxygen volume dissolved in blood plasma resulted in enhanced oxygen supply to marginally perfused tissue. Higher plasma oxygen concentration possibly will be important because capillary blood flow during ischemia can mainly consist of plasma flow . Better On the other hand, several other mechanisms implicated in ischemia and reperfusion injury may be influenced by hyperoxia. Ahrens and colleagues  found a Thom et al.  and WarnFor the following reasons, oxygen-free radicals (OFRs) may present a common signal in ischemic tolerance (IT) induction: (1) the majority if not all of published tolerance inducing stimuli are associated with the production of OFR; (2) induction of antioxidant enzymes has been shown for many IT protocols; (3) OFR itself may induce IT .Hyperoxic oxygenation, the exposure of an organism to an environment of relatively pure oxygen, increases physiological OFR production in all organs, including the kidney –45.Rasoulian et al.  and WahhaO2 permits shunting of blood into the infarct from nearby normal brain [The mechanism of advantage of hyperoxemia might involve the vascular element with impaired autoregulation in the area of ischemia. Vasoconstriction caused by a high Pal brain .aO2 value more than 150 mmHg, was associated with improved graft survival even independently from the classification of the quality of early postoperative graft function. Donor hyperoxia might induce good early postoperative liver function by improving ATP hepatic content, increasing protein synthesis, and decreasing the proteolytic process in the liver. It was also proposed that donor hyperoxia could be valuable, as it has been demonstrated experimentally that hyperoxic pretreatment attenuates ischemic-reperfusion injury of the heart [Donor hyperoxia, defined as a Phe heart , 47, brahe heart , 48, spihe heart , liver [he heart , and kidhe heart , 22.We hypothesize that early hyperoxia treatment may prolong the short-time window for therapeutic interventions, a major management problem in ischemic stroke. Nevertheless, we caution against overinterpretation of our data because we did not study the effect of hyperoxia during reperfusion or in permanent focal ischemia. Future studies should address these issues and recognize the exact mechanisms and pathophysiologic targets of hyperoxia. Pure oxygen at atmospheric pressure is nontoxic if given for less than 6 hours, and 80% oxygen could be administered for 24 hours  far awayThe most important complication of short periods of oxygen administration is pulmonary atelectasis  and vomiIn conclusion, intermittent exposure of human living kidney donors to hyperoxic environment improves renal function in early period following kidney transplantation.


Hypertension secondary to chronic kidney disease prevails in earlier childhood and obesity-related primary hypertension in adolescence. Both are associated with a high risk of renal and cardiovascular morbidity. In children with chronic kidney disease, uncontrolled hypertension may accelerate progression to end-stage renal disease before adulthood is reached and increase a child’s risk of cardiac death a thousand-fold. Obesity-related hypertension is a slow and silent killer, and though early markers of renal damage are recognized during childhood, end-stage renal disease is a risk in later life. Renal damage will be a formidable multiplier of cardiovascular risk for adults in whom obesity and hypertension tracks from childhood. Management options to prevent renal damage will vary for these different target groups. This review provides a summary of the available renoprotective strategies in order to aid physicians involved in the care of this challenging group of children. Kidney damage is the second-most common complication of primary hypertension after cardiovascular events, and significantly contributes to the increasing number of adults with end-stage renal disease (ESRD) . In patiIn younger children, hypertension secondary to renal disease prevails, with primary hypertension becoming a major issue in adolescence , 4••, 5.A large proportion of children with hypertension have chronic kidney disease secondary to a multitude of different renal disorders. CAKUT constitute a major group within these, and renal hypodysplasia is the most common diagnosis. The prevalence of hypertension is notably high in hereditary glomerular, microangiopathic or cystic diseases  , 7. SeveThe aim of treatment in children with established chronic kidney disease is prevention of additional renal damage exerted by hypertension. The goal is to slow disease progression and delay the start of renal replacement therapy (RRT). A further, equally important aim is to decrease the well-documented burden of cardiovascular risk associated with declining renal function. Many adults actually die from CV complications before reaching ESRD . Though The last decade has witnessed an emerging shift in the epidemiology of childhood hypertension, parallel to the epidemic of childhood obesity. Primary hypertension has been increasingly recognized in the primary care setting and has become the leading cause of hypertension in adolescents ••. SimilIn children with CKD, once significant renal damage has occurred, progressive impairment of renal function ensues. The rate of deterioration is partially dependent upon the underlying renal disease, and children with renal hypodysplasia demonstrate a much slower progression than those with glomerulonephritis . Among tHypertension is highly prevalent in children with CKD, with rates ranging from 20 % to 80 %, depending upon the underlying disease and stage of renal dysfunction. The crucial pathophysiological pathways of hypertension in CKD are shown in Fig. The two most important strategies for slowing CKD progression that have emerged in the last years are adequate blood pressure control and minimization of proteinuria. There is less substantial data for the renoprotective effects of treating renal anemia, uremic dyslipidemia, and mineral metabolism disorders . TherefoBased on initial data from large adult trials, international guidelines unanimously recommended blood pressure values below 130/80 mmHg  . Though 2, or start of RRT. In the intensified blood pressure target group (MAP <50th percentile), only 29.9 % of patients reached the endpoint, which corresponded to a risk reduction of 35 %. The treatment was well tolerated. European Guidelines have accordingly recommended lowering BP in children with CKD to levels below the ambulatory 75th percentile and for patients with proteinuria below the ambulatory 50th percentile [The results of the ESCAPE trial, an international randomized clinical study, have clearly demonstrated a beneficial effect of intensified blood pressure control on renal function in the child CKD population ••. In thrcentile . In chilBlood pressure control in CKD patients exerts an additional beneficial antiproteinuric effect, as proteinuria has repeatedly been shown to be a strong independent predictor of renal progression in both adults and children –35. NeveThe ideal antihypertensive agent for renoprotection in children must be effective in decreasing blood pressure to target values and must target several mechanisms that induce renal injury, including RAAS activation. It must have a good pediatric safety profile and pediatric labelling, and it should need little modification with declining GFR. The various classes of available antihypertensive drugs are comparable in their ability to lower blood pressure and prevent cardiovascular events, but differ in their antiproteinuric and renoprotective effect •, 37. ThIn children, the ESCAPE trial demonstrated the antihypertensive and antiproteinuric efficacy of the ACE inhibitor ramipril in nearly 400 patients with CKD. However, the long-term efficacy of ACEI monotherapy was limited by a rebound of proteinuria following 24 months of treatment despite adequate blood pressure control. This so-called escape phenomenon may be due to compensatory up-regulation of ACE-independent angiotensin II production . PatientAlthough calcium channel blockers (CCBs) achieve adequate blood pressure goals in CKD patients, the more frequently used dihydropyridine agents  have not been shown to slow progression of CKD or reduce proteinuria. Their use is limited to combination therapy with RAAS antagonists.Beta-blockers are useful agents in reducing the overactivation of the sympathetic nervous system observed in CKD patients, resulting in reduction of cardiac output and afterload, pulse rate, and additional renal renin release. Although the renoprotective  and antiproteinuric effects  of this class of drugs has been demonstrated, they are most commonly used when combination therapy is necessary for adequate blood pressure control –45.Sympathetic activity has also been shown to normalize following bilateral nephrectomy, with a concomitant reduction in blood pressure . A recenMonotherapy with RAAS antagonists effectively lowers blood pressure in a subgroup of CKD children, although antiproteinuric effects may require higher doses than those registered for hypertensive treatment . RecommeAbnormal patterns of circadian BP rhythms in the form of nocturnal hypertension or non-dipping during sleep are common in the CKD population. This can be improved by administration of a nighttime dose of one of the prescribed antihypertensive medications .2) to achieve target blood pressure [When highest-approved dosage is not effective for reducing blood pressure, combination therapy is introduced. In some children, especially those with later stages of CKD, multidrug therapy is necessary. In the ESCAPE cohort, the intensive blood pressure group required an average 0.9 ± 1.1 additional drugs to high-dose ramipril  was recently implicated as a potential modifiable factor of CKD progression. Pilot studies suggest that lowering UA with allopurinol or febuxostat is associated with significant decrease of creatinine levels .According to European guidelines, non-pharmacological treatment is an essential component in the management of every hypertensive child, including CKD subjects . While tA recent publication on the nutritional status of the pediatric renal replacement population in Europe has shown that both overweight (20.8 %) and obesity (12.5 %) are highly prevalent . TherapeSleep apnea is present in up to 30 % of the adult CKD population, particularly in those with obesity or diabetes. Improved ECF volume control with nocturnal HD, nocturnal automated PD, and nasal continuous positive airway pressure improves sleep apnea , 61.Cross-sectional studies have found that there is a significant impact of obesity on the prevalence of childhood hypertension. A review of population studies in the United States reveals that hypertension prevalence has nearly doubled in recent decades, reaching 4 %. This has been attributed to the worldwide epidemic of obesity . The lonThe pathophysiology of obesity-related hypertension involves several interacting mechanisms, including sympathetic system activation, RAAS activation, vascular endothelial dysfunction, and reduced kidney blood flow ••, 65. AThe strong relationship between obesity, metabolic syndrome, and ESRD has become increasingly recognized , 70. TheChildren with obesity-related hypertension require a complex renoprotective strategy due to the multifactorial pathogenesis of kidney damage. According to current recommendations, obesity-associated hypertension requires non-pharmacological treatment including weight loss, lifestyle modifications, and salt restriction , 73. ThiDietary counseling is essential, and the DASH (Dietary Approach to Stop Hypertension) diet utilized in the United States may also be effective for adolescents . LowerinCurrent guidelines recommend 60 minutes of aerobic activity as part of a weight management strategy . PhysicaAccording to Endocrine Society guidelines, pharmacological therapy for obesity is considered if intensive lifestyle modifications fail to decrease weight or improve comorbidities . The twoPharmacological treatment of hypertension in obese children is indicated for severe stage 2 hypertension or in the presence of diabetes or target-organ damage. Therapy may also be necessary for those that do not respond to intensive non-pharmacological management. European treatment guidelines recommend lowering blood pressure below the 90th percentile for all hypertensive obese subjects . AmericaACE inhibitors have become the drug of choice for treating obesity-related hypertension in adults. In addition, both ACEIs and ARBs improve glucose tolerance, insulin levels, and visceral fat content, and reduce the risk of type 2 diabetes mellitus , 87. WhiAntihypertensive non-pharmacological interventions and pharmacological treatment will have a renoprotective effect only if blood pressure targets are lowered to the levels described above. Home and office blood pressure measurements are necessary to document the efficacy of treatment. When monotherapy is ineffective, additional drugs should be introduced. Adherence to salt reduction and other non-pharmacological strategies must be controlled in the case of resistant hypertension.2/day. RAAS antagonists are the first-line treatment for both hypertension and proteinuria, though many children will require multiple-drug therapy to achieve set goals.Renal damage is a recognized complication of hypertension in children. The two major pediatric groups at risk are those with existing chronic renal disease and obese patients. In children with CKD, renoprotective strategy is aimed at slowing the decline of renal function in order to postpone renal replacement therapy. The mainstay of treatment is intensive blood pressure control and minimization of proteinuria. Mean arterial blood pressure is targeted below the ambulatory 50th percentile values and proteinuria below 300 mg/mRenoprotection in children with obesity-related hypertension is aimed at conserving normal renal function. This can be achieved by reversing the metabolic consequences of obesity through weight loss. The mainstay of treatment is non-pharmacological measures modifying lifestyle and dietary habits, increasing physical activity, and reducing salt intake. There is a limited role for effective pharmacological reversal of the metabolic consequences of obesity, and bariatric surgery is controversial. Pharmacological therapy of hypertension is introduced if non-pharmacological measures fail to lower blood pressure or if diabetes or end-organ damage is present. First-line pharmacological antihypertensive drugs are RAAS antagonists. A further common goal of renoprotective strategies in children with either primary or secondary hypertension is prevention of the formidable cardiovascular morbidity associated with declining renal function.


Aims and Objectives. Metabolic dysregulation has failed to explain clinical variability of patients with diabetic nephropathy and hence a renewed interest emerged in haemodynamic factors as determinant of progression and development of diabetic nephropathy. We therefore studied for various factors which can correlate with raised renal vascular resistance in diabetic nephropathy. Material and Methods. Renal vascular resistance was measured in patients with established and incipient diabetic nephropathy and compared with controls using noninvasive color Doppler examinations of intrarenal vasculature. Results. Renal vascular resistance correlated with age, duration of disease, GFR, serum creatinine, and stage of retinopathy. Renal vascular resistance was significantly reduced in patients on treatment with RAAS inhibitors and insulin, than those on OHA and antihypertensives other than RAAS inhibitors. Conclusion. The study implies that renal vascular resistance may help identify diabetics at high risk of developing nephropathy, and these set of patients could be candidates for RAAS inhibition and early insulin therapy even in patients without albuminuria.  Diabetes and its complications pose an immense amount of social and economic burden on the health infrastructure and resources throughout the globe. Diabetic nephropathy is the single most common cause of end-stage renal disease (ESRD) throughout the globe accounting for a whooping 25–45% of all patients enrolled in ESRD programmes . DiabetiIn spite of several decades of research since 1940's when several studies linked diabetes to renal disease , there aOne of the intriguing controversies has been that which patients of diabetes (type 1/type 2) are predisposed and are likely to progress to diabetic nephropathy. Several studies have demonstrated that only about 40% of patients of Type 1 and Type 2 diabetes have renal involvement. These set of patients that progress to frank diabetic nephropathy have been labeled as “progressors” and the other set of patients that in spite of similar control of blood sugar and long-term poor glycemic control do not progress have been labeled as “nonprogressors” .There has been a paradigm shift in the understanding of factors held responsible for this discrepancy in the natural history of these two sets of patients with the balance tilting towards hemodynamic factors rather than towards metabolic factors . The othAnother area of active research has been finding suitable markers for predicting which patients will progress. Many studies addressed biochemical markers but none is specific or sensitive enough for clinical use –19.Of late researchers have tried to answer all these controversies by a single key and that is hemodynamic alterations  which inPrompted with above considerations, we designed our study to evaluate renal vascular resistance with noninvasive Doppler in 57 diabetic patients attending a tertiary care centre in India.This study was carried out in the Department of Medicine and Radiology, Sir Sunderlal Hospital, Institute of Medical sciences (IMS), Banaras Hindu University (BHU) from May 2008 to June 2010. The study protocol was approved by the research and ethical committee of the institute and written informed consent was taken from all patients.A total 31 patients of diabetic nephropathy with stable disease, and three groups of control subjects  were included in the study. Diabetes was diagnosed as per WHO guidelines . All of μg/dl. 24 hr urinary collection was done from 8 AM to 8 AM next day with morning urine of day of start of collection discarded and morning urine of next morning collected. Adequacy of collection was confirmed by 24 hr urinary creatinine estimation wherever necessary. Urine routine microscopy and urine cultures were done before estimation of 24 hr urinary protein to rule out urinary tract infection. Patients with diabetic foot, valvular heart disease, ischemic heart disease, glomerulonephritis, lupus nephritis, renal calculi, hydronephrosis, renal masses, cerebrovascular, cardiovascular, and peripheral vascular disease were excluded.Microalbuminuria defined as 24 hr urinary albumin 30–300 Pulsed Doppler study of interlobar and arcuate arteries was performed on bilateral kidneys.Peak systolic frequency shift—minimum diastolic frequency shift/Peak systolic frequency shift during whole cardiac cycle.Peak systolic frequency shift—minimum diastolic frequency shift/Mean frequency during the whole cardiac cycle.We used a Toshiba NEMIO-30 Doppler machine and recorded findings with the help of a curvilinear probe of 3.75 Mhz. The sonologist was unaware of the group to which the patient belonged. RI and PI readings 2 each per vessel (interlobar arteries) for both kidneys were recorded and average of all 4 readings was taken for study purposes. B mode ultrasound was also done to look for renal size length, breath, and thickness. Patients with anatomical renal artery stenosis of the renal artery (main) were excluded from the study. Wall filter was set to a minimum of 50 Hz and with a Doppler sample volume set at 2–4 mm, minimum pulse repetition frequencies that did not produce aliasing were used with readings noted from existing software in the machine and all readings done at minimum possible angle between ultrasound beam and the vessel. Patients were rested for 5 min before taking any Doppler reading and all readings made while subject was lying in supine position with the breath held in deep end inspiration. Subjects were required to hold their breath while readings were being taken to obtain adequate spectral waveforms. Readings of RI and PI were made after a minimum of 4 identical consecutive spectral waveforms were achieved. Reproducibility of Doppler readings was assessed by intraobserver and interobserver variance which was 3.9% and 5.0%, respectively.Many subjects could not cooperate in the study and could not hold breaths adequately and were removed from the study especially patients with morbid obesity, respiratory problems, and so forth. This may be the reason for a nonintentional lower mean BMI values in our study population.Blood pressure was recorded after a 5 min rest just before the Doppler examination in right arm supine position and a second reading was made 5 min after the Doppler examination was completed. Average values of both readings were recorded. Mean blood pressure was calculated for comparison purposes. A standard health questionnaire was completed which included type, duration of diabetes, treatment history, and other significant illness like hypertension and coronary artery disease were also enquired into.Patients with proteinuria had to have proteinuria on two occasions three months apart; they were put on adequate and necessary treatment in the first visit and most of them continued treatment till the next visit, therefore labeling a patient as “on insulin” or “on OHA” or “on ACE/ARB” meant they were on that treatment for at least 3 months. Other patient variables like age, 24 hour urinary protein/albumin, HbA1c% values, fundus examination, lipid profile, and anthropometric measurements were also recorded. Serum glucose level  was estimated by glucose oxidase/glucose peroxidase method and Serum lipid parameters  were quantified by commercially available Kits  using manufacturer's protocol using Autoanalyzer . HbA1c% was measured in venous sample after an overnight fast by D10 Bio-rad system automated machine using HPL-C technique of electrophoresis. All the biochemical tests were performed in hospital's central biochemical laboratory.Fundus examination was done by an ophthalmologist who did not know the group under which the patient felt. Staging of the disease was done according to International Clinical Diabetic Retinopathy Disease Severity Scale. We used the GAULT COCKROFT FORMULA to calculate GFR.t”-test between two groups. Chi square test was used for rates and proportions, however if >20% values were under 5, Fisher exact test was used. Mann Whitney test was used for nonparametric variables between two groups. P-value <.05 was ascribed as significant difference between groups. Data were analyzed by the sigma stat software version 3.5.All the data were reported as mean ± standard deviation if they were normally distributed and as median ± Inter Quartile Range (IQR) if they were not normally distributed. One way ANOVA was applied when comparing parametric variables (mean) between four groups. Kruskal-wallis one way Anova was used to compare median values between groups if data was not normally distributed. Pearson's correlation was used to see corelation of RI and PI with various variables. Multivariate linear and stepwise forward progression analysis was done using RI and PI as dependent variables and other variables as independent variables. Subgroup analysis was done using unpaired student's “The baseline characteristics showed that a significant difference between the groups existed in serum cholesterol, GFR, and treatment of hypertension. Patients with diabetic nephropathy and diabetics with microalbuminuria had higher levels of serum cholesterol than patients without microalbuminuria. GFR showed progressive decline from diabetes without albuminuria to diabetic nephropathy. Patients with diabetes without microalbuminuria although had mean values lower than control population but there were values above values in normal population signifying presence of hyperfiltration early in diabetes. Patients in diabetic nephropathy group had 9 patients receiving ACE/ARB, others were receiving other antihypertensive as either these patients had contraindications to use of this drug or could not tolerate the drug. Higher percentages of patients in diabetes with microalbuminuria group were on ACE inhibitors. Patients in this group who were not on ACE inhibitors were again those in whom it was contraindicated or not tolerated or patients who did not comply with the advised treatment. Duration of disease was not significantly different in the various groups signifying that in spite of long duration of diabetes many patients did not develop diabetic nephropathy and still remained in the group of diabetes without microalbuminuria, the median duration of disease in this group was 2.5 ± 19.25 yrs, which was nonsignificantly lower than other groups .P < .001) between each group except between group B and group C that is no significant difference was seen between subjects with microalbuminuria and subjects without microalbuminuria. This would imply that RI values start increasing in diabetic subjects even before appearance of microalbuminuria.The mean resistive index (RI) values of interlobar arteries showed a statistically significant difference (P < .001) but intragroup differences were significant only between subjects with diabetic nephropathy and diabetics without microalbuminuria  of interlobar arteries were also statistically significantly raised as compared to nondiabetics  (Spearman co relation coefficient). On multiple comparison tests there was significant difference between RI values of stage 4 versus normal and Stage 2 versus normal; PI also correlated with stage of fundal disease with higher values in higher retinal stage (P < .001). On multiple comparison tests there was significant difference between PI values of stage 4 versus normal, Stage 3 versus normal, stage 2 versus normal, and stage 2 versus stage 1.There was also significant co relation of stage of retinal disease with RI and PI values  .Our study did not show any co relation of RI or PI values with BMI, Sex, FBS, HbA1c, serum cholesterol, serum triglyceride, duration of disease, or mean blood pressure. Barring a few studies our results are in accordance with many similar studies on this topic. These findings suggest that there are factors other than the level of metabolic control that contribute to diabetic nephropathy and raised renal vascular resistance in these patients. Haemodynamic factors like blood pressure control could explain these variations but studies have shown conflicting results. Ishimura et al.  showed nOur study showed significant co relation of RI and PI values with serum creatinine and eGFR. GFR of subjects with microalbuminuria was significantly lower than subjects without proteinuria. This emphasizes the point that microalbuminuria is not a very good marker for early detection of diabetic nephropathy since fall in GFR has already set in once microalbuminuria develops, and hence the need to identify a more early marker. RI and PI values of all diabetics were 0.805 ± 0.187 and 1.63 ± 0.831, which was significantly higher than that of controls. Intragroup comparison showed significant differences between groups except between groups with and without microalbuminuria, that is, RI was raised even before microalbuminuria started. There were 2 patients with serum creatinine > 1.5, that is, with already set-in renal failure but still no microalbuminuria. No correlation of RI or PI was found with amount of proteinuria on univariate analysis. Kim et al.  cited a Another issue that has been addressed in various studies is that diabetic nephropathy has been demonstrated to have higher renal vascular resistance than other causes of CKD . This leIn our study we excluded patients with macrovascular complications and still found significant higher RI values. We also demonstrated a significant correlation of stage of retinal disease with RI & PI values which itself is a microvascular complication. There was significant difference between RI & PI values of stage 4 versus normal, stage 2 versus normal, and stage 2 versus stage 1. PI also corelated with stage of fundal disease with higher values in higher retinal stage. This suggests that raised renal vascular resistance starts due to diabetic microvascular pathophysiology and at a later date may get accelerated due to accompanying macro vascular complication.Therefore we from above findings conclude that RI and PI as an indices of renal vascular resistance are an early marker for recognition of diabetic nephropathy and also are predictive factorsof recognition of patients at risk for future development of diabetic nephropathy. However this exercise is useful only if we have measures to retard progression of these patients to diabetic nephropathy. One of the useful interventions is ACE/ARB, which in numerous studies have shown beneficial effect on prognosis of diabetic nephropathy. In our study diabetic patients on ACE/ARB had significantly lower PI values than patients not on ACE/ARB and nonsignificantly lower RI values; in spite of similar age, blood pressure, and glycemic control.Another important finding of our study was that patients on insulin had significantly lower RI and PI values, in spite of similar age, blood sugar and blood pressure control, and proteinuria. Several studies indicate that insulin deficiency per se contributes to the neovascularization, increased surface area and afferent arteriolar dilation in diabetes. Several studies show that physiological concentrations of insulin cause afferent arteriolar constriction and efferent arteriolar dilation. These observations strongly support the notion that insulin deficiency directly contributes, at least in part, to the glomerular hypertension in diabetes. Some studies have addressed differential class effect of antidiabetic drugs on renal vascular resistance. Of note is a study by Pistrosch et al. , which cHowever our study has certain limitations in the form of small sample size, a hospital-based sample, and cross-sectional nature of the study; hence large longitudinal population-based studies are required before any clinically meaningful outcomes can be derived from our observations.


The current study aimed to observe the value of B-type natriuretic peptide (BNP) in chronic heart failure (CHF) patients with and without diabetes mellitus (DM). The study consisted of 559 CHF patients, including 276 patients with coronary heart disease, 234 with hypertensive heart disease and 49 with dilated cardiomyopathy. The subjects were divided into non-DM and DM groups which included 384 and 175 patients, respectively. Their New York Heart Association (NYHA) cardiac function degree and BNP levels were detected following admission. Other blood parameters, including fasting blood glucose and serum creatinine, were also collected. Left ventricular ejection fraction (LVEF) and the average thickness of the left ventricular wall (LVW) were detected by echocardiography. The total score of the heart failure (HF)-related parameters was evaluated for each patient according to age, hypertension, LVEF, LVW and NYHA degree. Additionally, BNP-score relation curves were constructed. The levels of BNP were significantly higher in the DM group compared with the non-DM group . Positive BNP-score relation curves were obtained for the DM and non-DM groups, but the curve of the DM group was notably steeper. As the patients with DM have significantly higher BNP levels at a similar HF score, DM history and fasting blood glucose should be taken into consideration when evaluating the value of BNP in HF. Chronic heart failure (CHF) is an ongoing, progressive syndrome characterized by the impairment of cardiac function and an increase in neurohormonal activity . B-type It is well known that a high proportion of CHF patients have diabetes mellitus (DM), and the prognosis is worse for coronary heart disease patients who have DM than for those who do not ,6. The HThe aim of the current study was to accurately investigate the influence of DM on the level of BNP in CHF patients, using a scaling method based on parameters including age, hypertension, LVEF, LVW and NYHA degree.A total of 559 CHF inpatients from our hospital were enrolled in this study, including 276 patients with coronary heart disease, 234 with hypertensive heart disease and 49 with dilated cardiomyopathy diagnosed by coronary angiography. The study was conducted in accordance with the declaration of Helsinki and with approval from the Ethics Committee of Nanchang University. Written informed consent was obtained from all participants. The subjects were divided into a non-DM group and a DM group which included 384 and 175 patients, respectively. Blood samples for blood routine tests and biochemical tests of all subjects were drawn in the morning, following a 12 h fast. Plasma BNP was measured using a microplate luminometer reader  and a Shionoria BNP kit . As the minimum and maximum detectable concentrations were 0.1 and 4,000 ng/l respectively, BNP levels <0.1 ng/l were counted as 0.1 ng/l and BNP levels >4,000 ng/l were counted as 4,000 ng/l in this study. The above tests were performed in our clinical laboratory, and inter- and intra-batch coefficient of variations were controlled within 5.5 and 3.5%, respectively.The left ventricular ejection fraction (LVEF) and the average thickness of the septal and posterior walls of the left ventricle (LVW) were detected by echocardiography. The cardiac function grade was assessed according to the NYHA criterion. Body weight, body height and seated blood pressure were measured and body mass index (BMI) was calculated. History of smoking and aspirin use were recorded.Hypertension was divided into 3 grades based on blood pressure levels: grade 1 was systolic blood pressure (SBP) 140–159 mmHg and/or diastolic blood pressure (DBP) 99–90 mmHg; grade 2 was SBP 160–179 mmHg and/or DBP 100–109 mmHg; and grade 3 was SBP ≥180 mmHg and/or DBP ≥110 mmHg. Patients under DM treatment, or with fasting plasma glucose >7.0 mmol/l and/or 2 h postprandial plasma glucose >11.0 mol/l, were classified as having DM.Based on the recorded data, parameters relevant to BNP were collected to calculate the total score for each patient . The higStatistical analysis was performed using SPSS 13.0 software package. All data were expressed as the mean ± standard deviation (SD). We used an independent sample t-test between the two groups and linear correlation analysis was performed. A p-value of <0.05 was considered to indicate a statistically significant difference.Generally, the plasma BNP level was higher in the DM group than in the non-DM group . Based on the NYHA grade, the plasma BNP levels of the 3 DM subgroups were higher than those of the 3 non-DM subgroups. Statistical significance was observed with NYHA II  and III , but not with NYHA IV , but positive correlations between BNP level and NYHA , age  and LVW thickness .There was also a positive correlation between plasma BNP and fasting plasma glucose levels  compared with the non-DM group (r=0.436). The plasma BNP levels of the two patients with a total score of 14 points in the DM group were >4,000 ng/l .BNP is mainly secreted by ventricular muscle cells, and is directly related to ventricular volume change and ventricular wall tension. A number of studies have demonstrated that the level of plasma BNP may sensitively and specifically reflect the ventricular function and positively correlates with NYHA cardiac grades .However, various factors, including obesity and renal insufficiency, may affect the BNP level in CHF patients. Recently, some studies showed that the level of BNP in CHF patients with DM was higher than in CHF patients without DM; however, most of those studies were simple intergroup comparisons rather than strict control-based research ,13,15.In the current study, a total score of the HF-associated parameters was evaluated for each patient according to age, hypertension, LVEF, LVW and NYHA degree. The purpose of this score was to accurately explore the influence of DM on the level of BNP in CHF patients at the same HF degree.Our study not only demonstrated that the BNP level in CHF patients increased as the NYHA degree increased but also demonstrated that higher BNP levels were observed in the 3 NYHA subgroups with DM compared with the corresponding subgroups without DM. However, no significant difference was found in the NYHA IV subgroup. One reason for this may be the small number of subjects in that subgroup. Another possible reason is that the reported upper limit of BNP concentration was 4,000 ng/l, which underestimates the value of BNP in the DM subgroup, as there were more patients with BNP higher than 4,000 ng/l in the DM subgroup.In this study, a BNP-score curve was introduced for quantitative evaluation of the extent of HF. Positive correlations between the score and BNP levels were observed in the DM group and in the non-DM group. The two curves began to separate at 7 points, after which the curve of the DM group was persistently above that of the non-DM group. Among the subgroups with scores of between 9 and 13 points, the plasma BNP levels were significantly higher in the DM group than in the corresponding subgroups in the non-DM group. These results further demonstrate that DM is a promoting factor for higher plasma BNP levels in CHF patients. Research has shown that BNP levels of coronary heart disease patients with DM are significantly high compared with those of coronary heart disease patients without DM.The underlying mechanism for the higher BNP level in CHF patients with DM is not clear; however, it may involve an increase in BNP formation and a decrease in degradation .et al found that BNP levels in DM patients with renal failure were significantly higher than those in DM patients with normal renal function  levels in DM patients with an abnormal urinary albumin excretion rate (UAER >20 μg/min) was higher than in DM patients with a normal UAER  . In patifunction . Siebenhmal UAER . AlthougCertain studies suggest that atrial fibrillation (AF) may be a cause of the increased BNP level . Since tBased on the positive correlation between the fasting glucose and BNP levels in this study, it is reasonable to speculate that higher plasma glucose levels may accelerate BNP secretion. Higher levels of plasma glucose may induce a hypertonic state, causing cell dehydration and an increase in blood volume. All these changes might increase the ventricular tension and therefore raise the BNP level. Moreover, in patients with DM, symptoms were often accompanied by vascular lesions more frequently found in coronary heart disease patients. Coronary heart disease may not only cause myocardial ischemia, hypoxia, necrosis and fibrosis, but also increase ventricular wall tensions and promote BNP secretion . AdditioSince the plasma BNP level was significantly higher in the DM group than in the non-DM group at the same HF score, when plasma BNP level is used to evaluate HF in a clinical environment, the factor of DM should be taken into consideration.


Assessing asthma control using standardised questionnaires is recommended as good clinical practice but there is little evidence validating their use within primary care. There is however, strong empirical evidence to indicate that age, weight, gender, smoking, symptom pattern, medication use, health service resource use, geographical location, deprivation, and organisational issues, are factors strongly associated with asthma control. A good control measure is therefore one whose variation is most explained by these factors.Eight binary  models of asthma control were constructed from a large UK primary care dataset: the Royal College of Physicians 3-Questions (RCP-3Qs); the Jones Morbidity Index; three composite measures; three single component models. Accounting for practice clustering of patients, we investigated the effects of each model for assessing control. The binary models were assessed for goodness-of-fit statistics using Pseudo R-squared and Akaikes Information Criteria (AIC), and for performance using Area Under the Receiver Operator Characteristic (AUROC). In addition, an expanded RCP-3Q control scale (0-9) was derived and assessed with linear modelling. The analysis identified which model was best explained by the independent variables and thus could be considered a good model of control assessment.1,205 practices provided information on 64,929 patients aged 13+ years. The RCP-3Q model provided the best fit statistically, with a Pseudo R-squared of 18%, and an AUROC of 0.79. By contrast, the composite model based on the GINA definition of controlled asthma had a higher AIC, an AUROC of 0.72, and only 10% variability explained. In addition, although the Peak Expiratory Flow Rate (PEFR) model had the lowest AIC, it had an AUROC of 71% and only 6% of variability explained. However, compared with the RCP-3Qs binary model, the linear RCP-3Q Total Score Model , was found to be a more robust 'tool' for assessing asthma control with a lower AIC  and an R-squared of 33%.In the absence of a gold standard for assessing asthma control in primary care, the results indicate that the RCP-3Qs is an effective control assessment tool but, for maximum effect, the expanded scoring model should be used. The ability to identify poor control is a pre-requisite for improving asthma. To achieve the guideline standards for asthma there is a necessity for primary health care professionals to efficiently assess and monitor symptom control. To do this they must utilise questions and tools that are simple and brief to use, easy for the patient to understand, and have a scoring system meaningful to both practitioner and patient. Assessment of asthma control using a standardised tool is now considered good clinical practice ,2. ThereThe complexity and variability of asthma makes prediction of treatment response difficult . With suIn UK primary care, the tool most commonly used is the Royal College of Physicians 3 Questions(RCP-3Qs) . ConceivThe UK Quality Outcomes Framework(QOF) rewards practices for use of screening questionnaires in other chronic conditions but not for asthma, despite the availability of recommended measurement instruments. Therefore, the absence of a gold standard screening tool for asthma is a barrier to its inclusion as a QOF outcome measure. This may in turn impact on the consistency of asthma review appointments in the community.This paper adds to the limited knowledge available on asthma control screening tools by examining the appropriateness of a number of different models of asthma control assessment by:• Creating models of control from an existing UK data set• Using statistical modelling to identify the most appropriate model for assessing control.Currently there is no recommended gold standard for assessing asthma control in primary care. Consequently, there is no gold standard against which a measure of asthma control can be assessed. There is, however, strong empirical evidence to indicate those factors which are strongly associated and predictive of asthma control. These include: patient characteristics such as age, weight, presence of symptoms and symptom pattern, as well as factors related to healthcare resource use and organisation and provision of care. As a result, we would expect a good measure of control to be one whose variation was most explained by these factors, and a poor measure to be one which bears little relation to them. Therefore, utilising an extensive UK database, we used multiple regression techniques and statistical tests to examine a variety of current measures (assessing the derived models for fit and performance). We then identified which of them  was best explained by the independent variables.Between the beginning of January 2001 and the end of December 2005, over 1200 practices from throughout the UK participated in an electronic audit of asthma management. This provided cross-sectional observational review data for more than 78,000 patients from 0 to 99 years of age. The windows-based audit software was informed by the assessment recommendations of the British Thoracic Society (BTS) Guidelines for the management of Asthma and consisted of six data screens. Practice and patient personal details were completed prior to the consultation. The remaining screens, addressing symptoms, inhaler technique, use of self-management plans, compliance, health resource use, education, and therapeutic management, were completed during the consultation. The template acted as an aide memoir for conducting a thorough guideline-based asthma review. Based on previous audit experience ,14, pracFor the purpose of the original audit, practice clinical systems were searched for patients > 4 years of age receiving preventative asthma medication BTS treatment step 2 within the previous 12 month period. Systems were also searched for patients who were over-using their β2-agonist medication (more than 6 prescriptions for a short acting bronchodilator in the previous 12 months). Identified patients who met these inclusion criteria were then invited to the practice for a routine review of their asthma. The only exclusion criterion from the study was a co-morbidity of Chronic Obstructive Airways Disease(COPD). The review process was part of normal practice routine. Nurses were not expected to run special sessions in order to undertake the review but were instead required to fit it into their daily work schedule. Those patients who accepted the invitation for a review were asked for written consent for their consultation data to be downloaded anonymously on a monthly basis to a central database at the research centre. Practices signed up to a 12 month audit service and over the course of the year were sent quarterly reports comparing their asthma management with current BTS guidelines. For the purpose of this study data analysis was confined to the information from the first review consultation. In addition, due to the differences in guideline management of children under 13 years of age to adults with asthma , indicating a slightly higher number of urban or semi urban practices in the study cohort. However, over 30% of the practices were situated in rural or semi-rural areas  to very large   patients reported experiencing some degree of asthma related symptoms in the immediate 4 week period preceding the consultation: 13,438 (20.7%) on one or two days in the month; 17,451 (26.9%) patients one or two days a week; and 23,614 (36.4%) on a daily basis. Four out of five patients  were on preventative asthma medication (BTS treatment steps 2-5) prior to the review. Although, as one would expect, level of treatment step was significantly associated to symptom reporting  patients were reportedly overusing their reliever inhaler (more than 6 prescriptions for a short acting bronchodilator in the previous 12 months), with males statistically more likely than females to be using it more than once every day . Overuse increased with age, rising from 2,361(33.5%) of patients in the 13 to 19 year age band to 4,777(51%) of patients in the 70+ age range (p < 0.0001). It was also associated with weight being greatest in those with a BMI over 30  and lowest in those with a BMI of 18 to 25  (p < 0.0001). Reported overuse of inhaled reliever medication was also linked to level of preventive medication treatment step with patients on low or no preventative medication more likely to overuse .There was also a significant difference in the level of poor compliance between:• Gender-males being more likely than females to forget their inhaler .• Medication treatment step-patients on treatment step 0, 1 or 2 being more likely to forget to take their inhaler than patients on steps 3, 4 or 5 .• Age-teenagers and young adults being more likely to forget to take their preventer inhaler .• BMI-the more overweight a patient the less likely they were to forget their preventer inhaler ; 18- < 25: 7,606(30%); 25-30: 6,108(28%); 30+: 3,654(27%), (p < 0.0001).Of the eight binary control models investigated, the RCP-3 Questions provided the best fit statistically. It had the second lowest AIC, highest pseudo R-squared (amount of explained variability) of 18% and an AUROC of 0.79 Table . An AUROThe Royal College of Physicians 3 Question model was interrogated further to investigate whether expansion to include a score for the various symptom frequency levels within each of the three questions contributed to a more robust assessment tool. Compared with the RCP-3Q binary model the RCP-3Q expanded score model provided the best fit with a lower AIC 28,6163) and an R-squared of 33% . The Jones Morbidity Index on the other hand was less clear cut, the tool indicating three levels of morbidity , and a decision was made to use the medium morbidity level (1 Yes answer) to define poor control . A seconThe available evidence indicated that single component measures are not effective for identifying poor control ,37. The As we were looking at models that predicted control it was necessary to include patients with both poor and good control. The search criterion given to practices to assist them with the procedure for identifying patients for review was a pragmatic solution to facilitate organisation of the invitation process. However, the consequence of this guidance could have resulted in the over-inclusion of patients at high risk of having poorly controlled asthma, thus compromising the generalisability of the study findings. The inclusion of patients on all medication steps, and with a range of frequency and type of control issue, indicates that the study cohort transcended the range of asthma patients managed in primary care. The number of patients who reported control issues is, in fact, comparable with those reported by other studies -40.It is important for health professionals to accurately assess the level of asthma control experienced by their patients. Using a specific tool to aid this process not only increases their ability to identify sub-optimal control , but proThis work, along with Thomas et al. , is a tiPractical guidance on the best method to monitor and assess asthma control is required. The study underpinning this work was conducted on a large number of patients with a wide range of asthma severity and control, and from all levels of social strata across the UK. It supports the conclusions of Thomas et al.  that, alThe authors declare that they have no competing interests.GH managed the data collection, prepared the datasets, analysed the data, and wrote the first draft of the paper. PD, BW and CJ supervised and advised on the design of the project. In addition PD directed the statistical analysis; BW contributed to the focus of the analyses and interpretation of the data; and CJ advised on the clinical interpretation of the data. PN assisted with data preparation by geo-coding practice locations and linking them to primary care organisation geographies. He also obtained census data and adjusted these to Primary Care Organisation geographies and then calculated the deprivation scores and population densities which were used in analyses. All authors read and approved the final draft.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/12/105/prepub