New Oligonucleotide 2'-O-Alkyl N3'→P5' (Thio)-Phosphoramidates as Potent Antisense Agents: Physicochemical Properties and Biological Activity.

We describe here the design, synthesis, physicochemical properties, and hepatitis B antiviral activity of new 2'-O-alkyl ribonucleotide N3'→P5' phosphoramidate (2'-O-alkyl-NPO) and (thio)-phosphoramidite (2'-O-alkyl-NPS) oligonucleotide analogs. Oligonucleotides with different 2'-O-alkyl modifications such as 2'-O-methyl, -O-ethyl, -O-allyl, and -O-methoxyethyl combined with 3'-amino sugar-phosphate backbone were synthesized and evaluated. These molecules form stable duplexes with complementary DNA and RNA strands. They show an increase in duplex melting temperatures of up to 2.5°C and 4°C per linkage, respectively, compared to unmodified DNA. The results agree with predominantly C3'-endo sugar pucker conformation. Moreover, 2'-O-alkyl phosphoramidites demonstrate higher hydrolytic stability at pH 5.5 than 2'-deoxy NPOs. In addition, the relative lipophilicity of the 2'-O-alkyl-NPO and NPS oligonucleotides is higher than that of their 3'-O- counterparts. The 2'-O-alkyl-NPS oligonucleotides were evaluated as antisense (ASO) compounds in vitro and in vivo using Hepatitis B virus as a model system. Subcutaneous delivery of GalNAc conjugated 2'-O-MOE-NPS gapmers demonstrated higher activity than the 3'-O-containing 2'-O-MOE counterpart. The properties of 2'-O-alkyl-NPS constructs make them attractive candidates as ASO suitable for further evaluation and development.

Targeting TLR9 agonists to secondary lymphoid organs induces potent immune responses against HBV infection.

Despite the existence of a prophylactic vaccine against hepatitis B virus (HBV), chronic hepatitis B virus (CHB) infection remains the leading cause of cirrhosis and liver cancer in developing countries. Because HBV persistence is associated with insufficient host immune responses to the infection, development of an immunomodulator as a component of therapeutic vaccination may become an important strategy for treatment CHB. In the present study, we aimed to design a novel immunomodulator with the capacity to subvert immune tolerance to HBV. We developed a lymphoid organ-targeting immunomodulator by conjugating a naturally occurring, lipophilic molecule, α-tocopherol, to a potent CpG oligonucleotide adjuvant pharmacophore. This approach resulted in preferential trafficking of the α-tocopherol-conjugated oligonucleotide to lymphoid organs where it was internalized by antigen-presenting cells (APCs). Moreover, we show that conjugation of the oligonucleotides to α-tocopherol results in micelle-like structure formation, which improved cellular internalization and enhanced immunomodulatory properties of the conjugates. In a mouse model of chronic HBV infection, targeting CpG oligonucleotide to lymphoid organs induced strong cellular and humoral immune responses that resulted in sustained control of the virus. Given the potency and tolerability of an α-tocopherol-conjugated CpG oligonucleotide, this modality could potentially be broadly applied for therapeutic vaccine development.

Mechanism of action of hepatitis B virus S antigen transport-inhibiting oligonucleotide polymer, STOPS, molecules.

A functional cure of chronic hepatitis B requires eliminating the hepatitis B virus (HBV)-encoded surface antigen (HBsAg), which can suppress immune responses. STOPS are phosphorothioated single-stranded oligonucleotides containing novel chemistries that significantly reduce HBsAgs produced by HBV-infected liver cells. The STOPS molecule ALG-10000 functions inside cells to reduce the levels of multiple HBV-encoded molecules. However, it does not bind HBV molecules. An affinity resin coupled with ALG-10000 was found to bind several proteins from liver cells harboring replicating HBV. Silencing RNAs targeting host factors SRSF1, HNRNPA2B1, GRP78 (HspA5), RPLP1, and RPLP2 reduced HBsAg levels and other HBV molecules that are concomitantly reduced by STOPS. Host proteins RPLP1/RPLP2 and GRP78 function in the translation of membrane proteins, protein folding, and degradation. ALG-10000 and the knockdowns of RPLP1/2 and GRP78 decreased the levels of HBsAg and increased their ubiquitination and proteasome degradation. GRP78, RPLP1, and RPLP2 affected HBsAg production only when HBsAg was expressed with HBV regulatory sequences, suggesting that HBV has evolved to engage with these STOPS-interacting molecules. The STOPS inhibition of HBsAg levels in HBV-infected cells occurs by sequestering cellular proteins needed for proper expression and folding of HBsAg.

Clinicopathological Spectrum of Henoch-Schönlein Purpura Vasculitis: An Experience from a Tertiary Care Center.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with multiorgan involvement. Renal involvement is the key factor predicting morbidity. We have aimed to analyze the clinicopathological spectrum of HSP vasculitis and HSP nephritis to assess the risk factors associated with kidney involvement. This retrospective study was performed in the department of pathology with collaboration of department of dermatology and department of nephrology of a tertiary care center. All clinical details along with biopsy findings were retrieved. Starting materials of the study were cases of leukocytoclastic vasculitis with only perivascular IgA deposit of more than ++ in the absence of other immunoglobulin and trace complements. To investigate the possible factors that are influential on the development of biopsy-proven HSP nephritis, we divided the whole study population in two groups -group 1: with and group 2: without biopsy-proven nephritis. One-way analysis of variance was carried out during comparative analysis between two groups using IBM SPSS statistics software, version 19 and MedCalc software, version 12.3.0.0. HSP vasculitis comprised 11.6% (n = 19) of total cutaneous vasculitis in 2 years (164 cases) with a mean age of 13.52 ± 8.10 (range: 4-33 years). Three cases developed de novo kidney disease (15.79%). A correlation analysis revealed that predictors were seasonal variation (P = 0.018), severe gastrointestinal involvement (P = 0.03), and subcutaneous edema (P = 0.005). Various clinical and laboratory parameters were associated with renal consequences. Occult nephritis was the most common presentation with crescent as a constant histopathological feature.

A tale of tripartite: An experience from a tertiary care center of Eastern India.

BACKGROUND: Crescentic glomerulonephritis (Cr GN) is pattern of glomerular injury resulting from wide range of diseases sharing a common pathogenesis. OBJECTIVES: The objective of our study was to analyze the clinicopathological spectrum and outcome of Cr GN with special reference to its immunopathological subtypes using a panel of immunofluorescence stains. MATERIALS AND METHODS: Native renal biopsies with crescentic pattern of injury were included. Detailed Clinical and laboratory variables were analyzed along with the treatment protocol and renal outcome, wherever available. Renal biopsy slides were evaluated for various glomerular and extraglomerular features. Both qualitative and quantitative data were analyzed. RESULTS: A total of 57 cases of Cr GN were included; majority (47.36%) of cases were pauci-immune in nature. Among clinical features, ranges of proteinuria and creatinine level were significantly different between subgroups. The various light microscopic parameters, including proportion of cellular crescents and capillary wall necrosis were different. Presence of arteriolar changes also showed association with unfavorable outcome. Three unusual associations, including IgA nephropathy, membranous glomerulonephritis and Hepatitis B infection were detected. Adequate follow-up information was available in 35 of the patients. Of these, 14 were dialysis-dependent at the last follow-up. CONCLUSIONS: Type III Cr GN (pauci-immune Cr GN) was the commonest cause of Cr GN in our population. Adult patients required renal replacement therapy more frequently than pediatric cases those are chiefly infection associated. Critical appraisal of clinical, histopathological and immunofluorescence finding help to identify individual subtypes as treatment and outcome varies accordingly.

Remote Ischemic Preconditioning for Prevention of Contrast-Induced Acute Kidney Injury in Patients of CKD Stage III and IV Undergoing Elective Coronary Angiography: A Randomized Controlled Trial.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is a serious complication of coronary angiography (CA). The aim of this randomized, parallel group, single blind, sham-controlled trial was to assess the safety and efficacy of the remote ischemic preconditioning on the prevention of CI-AKI. METHODS: Patients of 18-80 years of age with CKD 3 and 4, who were admitted for elective coronary angiography in a tertiary care hospital in eastern India were randomized in a 1:1 ratio to standard care with ischemic preconditioning (n = 45; intermittent arm ischemia through 4 cycles of 5-min inflation and 5-min deflation of a blood pressure cuff) or with standard care and sham ischemic preconditioning (n = 42). Overall, both study groups were at moderate risk of developing CI-AKI according to the Mehran risk score. The primary endpoint was the incidence of CI-AKI, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 h after contrast medium exposure. RESULTS: CI-AKI occurred in 8 patients (19.04%) in the control group and 2 (4.4%) in the remote ischemic preconditioning group (odds ratio, 0.198, 95% confidence interval, 0.087 to 0.452; P = 0.04). No major adverse events were related to remote ischemic preconditioning. CONCLUSIONS: This study indicates that remote ischemic preconditioning is a simple and well-tolerated procedure, which reduces the incidence of CI-AKI in CKD 3 and 4 patients undergoing coronary angiography.

Effect of Chronotherapy of Antihypertensives in Chronic Kidney Disease: A Randomized Control Trial.

INTRODUCTION: There is a higher prevalence of non-dipping pattern in hypertensive chronic kidney disease (CKD) patients. Nocturnal hypertension has been shown to predict cardiovascular mortality and morbidity and is often superior to daytime blood pressure. We studied the effect of shifting or adding antihypertensive to night time on blood pressure profile of CKD III-IV patients. METHODS: In this single-center, prospective, randomized controlled trial, eligible participants were adults from eastern India aged 18-65 years with CKD stages 3 and 4, with a non-dipping pattern on ambulatory blood pressure monitor (ABPM). The intervention group received all the antihypertensives in the night time whereas the standard care group continued to take the medication in the morning. Both groups were followed up for 1 year. The primary outcome was the number of patients changed from non-dippers to dippers in the standard care group and intervention group. Secondary outcomes included a change in estimated glomerular filtration rate (eGFR) and change in the cardiac structure. RESULTS: 39 patients in the intervention group and 36 patients in the standard care group were analyzed. 10 patients (26%) reverted to dipping pattern in the intervention group as compared to none in the standard care group. Mean changes in eGFR were -2.55 and -0.18 mL/min/1.73 m2 in the standard care and intervention group at the end of the study, respectively. Between-group difference in eGFR was significant at 1 year (5.22 [95% CI, 4.3-6.1] ml/min/1.73 m2); (P = 0.03). The cardiac structure showed no significant changes in either group. CONCLUSIONS: Bedtime administration of antihypertensives reverted non-dippers to dippers and slowed the decline in eGFR in CKD stages 3 and 4 compared to morning administration of antihypertensives.

INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.

The changing face of pregnancy-related acute kidney injury from eastern part of India: A hospital-based, prospective, observational study.

This study was initiated to look into the etiologies, prevalence, and outcome of pregnancy-related acute kidney injury (PRAKI) in a tertiary care hospital. Women admitted with PRAKI from January 2015 to December 2016 were included in the study. All patients were investigated and treated and followed up for the next six months.. For statistical analysis, Chi- square test and analysis of variance were performed to analyze the data. Multivariate analysis was applied to compare the risk of nonrecovery of renal function in different etiologies of PRAKI. During the study period, 81 patients were admitted with PRAKI, of whom 68 (84%) received hemodialysis (HD). A total of 449 patients including all cases of AKI underwent HD from January 2015 to June 2016. The incidence of dialysis requiring PRAKI was 68 out of the 449 patients (15%). Sixty-eight (84%) patients required dialysis support while the most common cause was sepsis (49%), with the second being pregnancy-associated atypical hemolytic-uremic syndrome (P-aHUS) (17%) followed by obstetric hemorrhages (16%). There was a significant reduction of first-trimester AKI (8.6%) compared to a previous study published from this institute (19.3%). The maternal mortality (25%) and fetal mortality (23.5%) were high. Nearly 39% of the patients had complete recovery of renal function. This study revealed significant PRAKI burden due to a largely preventable cause, puerperal sepsis. Renal survival was poor in P- aHUS. The gaps in the obstetric care may be identified for the improvement of fetomaternal outcome.

Non-diabetic Renal Diseases in Patients with Diabetes Mellitus Clinicopathological Correlation.

BACKGROUND AND AIMS: Non-diabetic renal diseases (NDRDs) form an important part of disease manifestations in patients with diabetes. METHODS: This hospital-based prospective study was conducted to analyze incidence and spectrum of NDRDs in patients with diabetes with or without diabetic nephropathy (DN), effect of early specific interventions on outcome, and renal-retinal relationship in type 1 and type 2 diabetes mellitus with nephropathy. 44 Patients with T2DM with the clinical suspicion of NDRD were subjected to renal biopsy Renal biopsies were performed by using an automated biopsy gun. Tissue was processed for Light microscopy-LM and Immunofluorescence-IF. Electron Microscopy was done as and when required by reprocessing the tissue embedded in paraffin for LM. Biopsies were reported by one experienced renal pathologist. RESULTS: Renal histopathology revealed that of 44 enrolled patients with clinically suspected NDRD, 61.4% had isolated NDRD, 13.6% had NDRD superimposed on DN, and 25% had isolated DN. The most common NDRDs were minimal change disease (19.2%) and DN + chronic pyelonephritis (33.3%) in patients with isolated NDRD, and NDRD superimposed on DN, respectively. In the DN group, no patient had proliferative diabetic retinopathy (PDR) or hypertensive retinopathy, 45.5% had nonproliferative diabetic retinopathy (NPDR) and 54.5% had no microangiopathy in retina. In the NDRD group, 9.1% each had PDR and hypertensive retinopathy, 36.4% had NPDR and 45.4% had no microangiopathy in retina. No patient in the DN group and 72.7% in the NDRD group received specific treatment. In hospital, dialysis support was provided to 27.3% and 21.2% of patients in the DN and NDRD groups, respectively. In the DN group, 72.7% of patients improved with conservative therapy, 18.2% were dependent on dialysis when discharged. One patient died during treatment. In the NDRD group, 78.8% showed recovery in the renal function and clinical improvement, 15.1% were dialysis dependent when discharged. Two patients died during treatment. CONCLUSION: Accurate diagnosis of underlying NDRD by kidney biopsy facilitates initiation of specific therapy, which may lead to clinical improvement in significant number of patients.

Correction to: Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

Following publication of the original article [1], the authors reported errors in the presentation of Tables 2, 4 and 5.

Pharyngeal-Cervical-Brachial Variant of Guillain-Barré Syndrome Following Dengue Infection: A Rare Syndrome with Rare Association.

Pharyngeal-cervical-brachial (PCB) variant is a rare localized variant of Guillain-Barré syndrome that presents with a rapidly progressive oropharyngeal and cervicopharyngeal weakness associated with areflexia in the upper limb. Here, we are describing a case of a 20-year-old female who had a preceding history of fever with thrombocytopenia that was found to be dengue ELISA positive. This was followed by rapidly progressive weakness of cervical, bulbar, and bilateral facial muscles along with areflexia of upper limb. Nerve conduction study showed a reduced compound muscle action potential amplitude in the upper limb, and the CSF examination showed albuminocytological dissociation. The patient was given intravenous immunoglobulin, and she started improving within 3 days of commencing the treatment.

Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial.

BACKGROUND: Darbepoetin alfa (DA-α) is a long-acting erythropoiesis-stimulating glycoprotein which has half-life three-fold longer than that of Erythropoietin alfa (EPO). The objective of this study was to compare the efficacy and safety of DA-α injection versus EPO for treating renal anemia amongst Indian patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Patients of either gender (aged 18-65 years) with ESRD undergoing dialysis who had hemoglobin (Hb) levels < 10 g/dL after receiving EPO were switched to DA-α (0.45 µg/kg) once weekly subcutaneously or EPO 50 IU/kg thrice weekly subcutaneously (centrally randomized 1:1) for 12-24 weeks (correction phase) followed by 12 weeks maintenance phase (for Hb levels ≥10 g/dL). The primary efficacy endpoint was mean change in Hb level from baseline to end of correction phase. RESULTS: In the intention-to-treat population (n = 126), the between group difference in mean Hb change was - 0.01 g/dL (95% CI - 0.68 to - 0.66, p = 0.97). After adjusting for covariates, the difference was - 0.2878 g/dL (95% CI -0.936 to0.360). The lower limit of the two-sided 95% CI of primary endpoint was above the pre-specified non-inferiority margin of - 1.0 g/dL. Similar trend of non-inferiority was observed for per-protocol population. Safety profile of DA-α and EPO were observed to be similar. CONCLUSION: Our study results demonstrated that for patients with ESRD undergoing dialysis, administering DA-α at lower dose frequency, is equally effective and well tolerated as EPO for treating renal anemia. TRIAL REGISTRATION: CTRI/2012/07/002835 [Registered on: 27/07/2012]; Trial Registered Prospectively.

Tacrolimus as the first-line agent in adult-onset minimal change disease: A randomized controlled study.

Steroids have been the cornerstone of first-line therapy in adult-onset minimal change disease (MCD). The period of exposure to high dose steroids may be longer in adult MCD patients and would result in higher rates of steroid-related side effects. Although tacrolimus (TAC) is known to be effective in steroid-dependent/resistant MCD as well as in nephrotic syndrome due to other causes, there are minimal data available for assessing the effectiveness of TAC as the first-line agent in adult MCD. This is a prospective, open-label, randomized controlled study conducted from April 2014 to March 2016. Patients were randomized into two groups A and B which received TAC for 12 months and oral steroids for six months, respectively. Primary outcomes were remission rates, drug resistance was measured at 6, 12,and 18 months in each group and secondary outcomes were relapse rates, sustained remission rates, dependency, and adverse effects were measured at 18 months in both groups. At six months, total response (TR, i.e., complete and partial remission) was achieved in 80% in the TAC group and 78.26% in the steroid group (P = 1.000). At 12 months, TR was 60% in the TAC group and 43.48% in the steroid group (P = 0.386). At 18 months, TR rate was 44% in the TAC group and 43.48% in the steroid group (P = 1.000). About 32% in the TAC group and 39.13% in steroid group had relapsed by 18 months. Serious adverse effects were similar in the two groups, but overall adverse effects were more in the steroid group. TAC as a primary agent is not inferior to steroids in inducing remission. TAC may be considered as an alternative agent to steroid in high-risk groups such as elderly patients, uncontrolled diabetes and young females as a primary agent in the management of adult MCD.

Spectrum of renal allograft biopsy: A five-year experience at a tertiary care center of Eastern India.

Renal allograft dysfunction (RAD) can have myriad causes and presentations. Allograft biopsy remains the gold standard for optimum management. This is a retrospective study carried out at a tertiary care institute from August 2011 to March 2016. Details of the renal allograft biopsy requisitions were recorded and analyzed. Two hundred and two patients had undergone kidney transplantation (KT) during the study period. One hundred and twenty-six had undergone renal biopsy for RAD. The acute asymptomatic rise of serum creatinine was the most common clinical presentation (47.61%) followed by chronic RAD (CRAD) (19.84%), proteinuria (15.87%), immediate graft dysfunction (10.31%), and persistent active urinary sediments (6.34%) in that order. The incidence of delayed graft function was 1.98%. The overall incidence of biopsy-proven rejection was 8.41% within oneyear and 8.91% beyond oneyear of transplant. Acute cellular rejection (ACR) [with or without antibody-mediated rejection (AMR)] was found in 65%; AMR was found in 40% and 15% had both ACR and AMR. Borderline acute cell-mediated rejection was found in 22.5% of biopsies. CRAD was due to chronic rejection and chronic calcineurin inhibitor toxicity in only about one-fourth of the cases. Incidence of glomerulo-nephritis was 10.89% and most of these occurred two years after KT. Renal allograft biopsy was associated with minor complications in 3.17% of cases. Clinical presentations do not reliably distinguish the various causes of RAD. Allograft biopsy is a mainstay in the diagnosis of RAD and is safe. Results of live donor first transplantation using complement-dependent cytotoxi-city crossmatch are comparable to those programs using newer methods like solid-phase assays. However, the direct comparison of these results with other studies may not be completely applicable.

A cross-sectional study on renal involvement among HIV-infected patients attending a tertiary care hospital in Kolkata.

Background and objectives: The HIV-associated renal diseases represent a spectrum. Indian data on this is sparse. This study was undertaken to find out the prevalence and clinicopathological spectrum of renal involvement in HIV among antiretroviral therapy (ART) naïve patients (Group 1) and among those on ART (Group 2). Methods: Systematic random sampling was undertaken to select 109 patients each from virology outpatient department (VOPD) and ART centre of a tertiary care hospital. They were screened and further investigated if renal involvement was found. Results: Renal involvement was present in 25/109 (22.94%) and 15/109 (13.76%) patients of Groups 1 and 2, respectively. Among patients of Groups 1 and 2, 9/24 (37.5%) and 2/13 (15.4%), respectively, had clinically significant proteinuria, but none in the nephrotic range. Statistically significant relationships of renal involvement were observed with CD4 count <100/µl and with low BMI. Of the patients of Group 2, 20% of those on a tenofovir-based regimen had renal involvement with tubular changes, while only 4.6% of those on other regimens had renal involvement. This difference was statistically significant (p<0.05; OR=5.25). Conclusion: Renal involvement was less common among those on ART. Low CD4 count and body mass index (BMI) were associated with renal dysfunction. Patients on a tenofovir-based regimen had more renal involvement compared with not on a tenofovir-based regimen.

A Cross-sectional Prospective Study of Asymptomatic Urinary Abnormalities, Blood Pressure, and Body Mass Index in Healthy School Children.

INTRODUCTION: Screening school children for urinary abnormalities is an inexpensive task but is not commonly undertaken in India. Although debated in western countries, its utility in early diagnosis of kidney disorders has been proved by studies from Asia. We examined the prevalence of asymptomatic urinary abnormalities (AUA), obesity, and hypertension in school children and analyzed data to identify potential risk factors among those detected with such abnormalities. METHODS: Children and adolescents 8 to 18 years of age of either gender, attending 14 public schools in West Bengal, were screened prospectively from July 2013 to July 2016 for detecting asymptomatic urinary abnormalities by a spot urine test using a dipstick. Sociodemographic profile, medical examination (weight, height, and blood pressure), and questionnaire-based data were recorded. RESULTS: A total of 11,000 children were screened. Of these, data from 9306 children were available for AUA, obesity, and hypertension. The prevalence rate was 7.44% (95% confidence interval [CI] = 6.91%-7.97%) for at least 1 AUA. Isolated hematuria was present in 5.2% (95% CI 4.75%-5.65%), whereas isolated proteinuria was present in 1.9% (95% CI = 1.62%-2.18%). The prevalence of prehypertension was 13.43% (95% CI = 12.74%-14.12%) and that of hypertension and abnormal body mass index was 4.05% (95% CI = 6.43%-7.47%) and 38.67 (95% CI = 37.68%-39.66%) respectively. DISCUSSION: The prevalence rates of AUA were comparable with those in some Asian countries but higher than in most developed countries. Of children and adolescents 8 to 18 years of age, those 13 to 18 years had significantly more high risk factors such as AUA, hypertension, and obesity.

Effects of 6 months yoga program on renal functions and quality of life in patients suffering from chronic kidney disease.

AIM: To study the effect of 6 months yoga program in patients suffering from chronic kidney disease (CKD). MATERIALS AND METHODS: Fifty-four patients with CKD were studied and divided into two groups (yoga group and control group) to see the effect of yoga in CKD. Patients in the yoga group were offered yoga therapy along with other conventional treatment modalities, while the control group was only on conventional treatment. Subjects in yoga group were trained to perform specific yogic asanas for at least 5 days a week for 40-60 min a day. Regular monitoring of blood pressure, renal function, requirement of a number of dialysis, and quality of life (QOL) indicators were done. Fifty patients (yoga - 25; control-25) completed 6 months follow-up. RESULTS: In yoga group, a significant reduction of systolic and diastolic blood pressure, significant reduction in blood urea and serum creatinine levels, and significant improvement in physical and psychological domain of the World Health Organization QOL (as assessed by BREF QOL scores) were seen after 6 months. In control group, rise of blood pressure, deterioration of renal function, and QOL were observed. Poststudy comparison between the two groups showed a statistically significant reduction of blood pressure, nonsignificant reduction in blood urea and serum creatinine, and significant improvement in physical and psychological domain of QOL in yoga group as compared to control group. For subjects in yoga group, the need for dialysis was less when compared to control group although this difference was statistically insignificant. Except for inability of some patients to perform certain yogic asanas no adverse effect was found in the study. CONCLUSION: Six months yoga program is safe and effective as an adjuvant therapy in improving renal functions and QOL of CKD patients.

Indian chronic kidney disease study: Design and methods.

AIM: The rate and factors that influence progression of chronic kidney disease (CKD) in developing countries like India are unknown. A pan-country prospective, observational cohort study is needed to address these knowledge gaps. METHODS: The Indian Chronic Kidney Disease (ICKD) study will be a cohort study of approximately 5000 patients with mild to moderate CKD presenting to centres that represent different geographical regions in India. Time to 50% decline in baseline estimated glomerular filtration rate, need of renal replacement therapy or any new cardiovascular disease (CVD) event or death from CVD are the primary end points. VALUE OF STUDY: This study will provide the opportunity to determine risk factors for CKD progression and development of CVD in Indian subjects and perform international comparisons to determine ethnic and geographical differences. A bio-repository will provide a chance to discover biomarkers and explore genetic risk factors.